Breast Cancer

Amazon is working with the Fred Hutchinson Cancer Research Center to develop cancer vaccines in a new clinical trial.

The trial is aimed at finding “personalized vaccines” to treat breast cancer and melanoma. The phase 1 trial is recruiting 20 people over the age of 18 to study the safety of the vaccines, according to CNBC.

The Fred Hutchinson Cancer Research Center and University of Washington Cancer Consortium are listed as the researchers of the clinical trial, and Amazon is listed as a collaborator, according to a filing on the ClinicalTrials.gov database.

“Amazon is contributing scientific and machine learning expertise to a partnership with Fred Hutch to explore the development of a personalized treatment for certain forms of cancer,” an Amazon spokesperson told CNBC.

“It’s very early, but Fred Hutch recently received permission from the U.S. Food and Drug Administration to proceed with a phase 1 clinical trial, and it’s unclear whether it will be successful,” the spokesperson said. “This will be a long, multiyear process – should it progress, we would be open to working with other organizations in health care and life sciences that might also be interested in similar efforts.”

In recent years, Amazon has grown its presence in the health care industry, CNBC reported. The company launched an online pharmacy in 2020, developed a telehealth service called Amazon Care, and released its own COVID-19 test during the pandemic.

A research and development group inside Amazon, known as Grand Challenge, oversaw the company’s early cancer vaccine effort, according to Business Insider. It’s now under the purview of a cancer research team that reports to Robert Williams, the company’s vice president of devices.

The study was first posted on ClinicalTrials.gov in October 2021 and began recruiting patients on June 9, according to the filing. The phase 1 trial is expected to run through November 2023.

The phase 1 trial will study the safety of personalized vaccines to treat patients with late-stage melanoma or hormone receptor-positive HER2-negative breast cancer which has either spread to other parts of the body or doesn’t respond to treatment.

More information about the study can be found on ClinicalTrials.gov under the identifier NCT05098210.

A version of this article first appeared on WebMD.com.

Amazon is working with the Fred Hutchinson Cancer Research Center to develop cancer vaccines in a new clinical trial.

The trial is aimed at finding “personalized vaccines” to treat breast cancer and melanoma. The phase 1 trial is recruiting 20 people over the age of 18 to study the safety of the vaccines, according to CNBC.

The Fred Hutchinson Cancer Research Center and University of Washington Cancer Consortium are listed as the researchers of the clinical trial, and Amazon is listed as a collaborator, according to a filing on the ClinicalTrials.gov database.

“Amazon is contributing scientific and machine learning expertise to a partnership with Fred Hutch to explore the development of a personalized treatment for certain forms of cancer,” an Amazon spokesperson told CNBC.

“It’s very early, but Fred Hutch recently received permission from the U.S. Food and Drug Administration to proceed with a phase 1 clinical trial, and it’s unclear whether it will be successful,” the spokesperson said. “This will be a long, multiyear process – should it progress, we would be open to working with other organizations in health care and life sciences that might also be interested in similar efforts.”

In recent years, Amazon has grown its presence in the health care industry, CNBC reported. The company launched an online pharmacy in 2020, developed a telehealth service called Amazon Care, and released its own COVID-19 test during the pandemic.

A research and development group inside Amazon, known as Grand Challenge, oversaw the company’s early cancer vaccine effort, according to Business Insider. It’s now under the purview of a cancer research team that reports to Robert Williams, the company’s vice president of devices.

The study was first posted on ClinicalTrials.gov in October 2021 and began recruiting patients on June 9, according to the filing. The phase 1 trial is expected to run through November 2023.

The phase 1 trial will study the safety of personalized vaccines to treat patients with late-stage melanoma or hormone receptor-positive HER2-negative breast cancer which has either spread to other parts of the body or doesn’t respond to treatment.

More information about the study can be found on ClinicalTrials.gov under the identifier NCT05098210.

A version of this article first appeared on WebMD.com.

Amazon is working with the Fred Hutchinson Cancer Research Center to develop cancer vaccines in a new clinical trial.

The trial is aimed at finding “personalized vaccines” to treat breast cancer and melanoma. The phase 1 trial is recruiting 20 people over the age of 18 to study the safety of the vaccines, according to CNBC.

The Fred Hutchinson Cancer Research Center and University of Washington Cancer Consortium are listed as the researchers of the clinical trial, and Amazon is listed as a collaborator, according to a filing on the ClinicalTrials.gov database.

“Amazon is contributing scientific and machine learning expertise to a partnership with Fred Hutch to explore the development of a personalized treatment for certain forms of cancer,” an Amazon spokesperson told CNBC.

“It’s very early, but Fred Hutch recently received permission from the U.S. Food and Drug Administration to proceed with a phase 1 clinical trial, and it’s unclear whether it will be successful,” the spokesperson said. “This will be a long, multiyear process – should it progress, we would be open to working with other organizations in health care and life sciences that might also be interested in similar efforts.”

In recent years, Amazon has grown its presence in the health care industry, CNBC reported. The company launched an online pharmacy in 2020, developed a telehealth service called Amazon Care, and released its own COVID-19 test during the pandemic.

A research and development group inside Amazon, known as Grand Challenge, oversaw the company’s early cancer vaccine effort, according to Business Insider. It’s now under the purview of a cancer research team that reports to Robert Williams, the company’s vice president of devices.

The study was first posted on ClinicalTrials.gov in October 2021 and began recruiting patients on June 9, according to the filing. The phase 1 trial is expected to run through November 2023.

The phase 1 trial will study the safety of personalized vaccines to treat patients with late-stage melanoma or hormone receptor-positive HER2-negative breast cancer which has either spread to other parts of the body or doesn’t respond to treatment.

More information about the study can be found on ClinicalTrials.gov under the identifier NCT05098210.

A version of this article first appeared on WebMD.com.

Based on biomarker findings, some patients may be able to avoid radiation therapy following breast-conserving surgery, suggest results from the LUMINA trial.

The women in this trial who skipped radiotherapy, and were treated with breast-conserving surgery followed by endocrine therapy, had an overall survival rate of 97.2%. The local recurrence rate was 2.3%, which was the study’s primary endpoint.

“Women 55 and over, with low-grade luminal A-type breast cancer, following breast conserving surgery and treated with endocrine therapy alone, had a very low rate of local recurrence at 5 years,” commented lead author Timothy Joseph Whelan, MD.

“The prospective and multicenter nature of this study supports that these patients are candidates for the omission of radiotherapy,” said Dr. Whelan, oncology professor and Canada Research Chair in Breast Cancer Research at McMaster University and a radiation oncologist at the Juravinski Cancer Centre, both in Hamilton, Ont.

“Over 300,000 [people] are diagnosed with invasive breast cancer in North America annually, the majority in the United States,” said Dr. Whelan. “We estimate that these results could apply to 10%-15% of them, so about 30,000-40,000 women per year who could avoid the morbidity, the cost, and inconvenience of radiotherapy.”

The results were presented at the annual meeting of the American Society of Clinical Oncology.

Dr. Whelan explained that adjuvant radiation therapy is generally prescribed following breast conservation therapy to lower the risk of local recurrence, but the treatment is also associated with acute and late toxicity. In addition, it can incur high costs and inconvenience for the patient.

Previous studies have found that among women older than 60 with low-grade, luminal A-type breast cancer who received only breast-conserving surgery, there was a low rate of local recurrence. In women aged older than 70 years, the risk of local recurrence was about 4%-5%.

This latest study focused on patients with breast cancer with a luminal A subtype combined with clinical pathological factors (defined as estrogen receptor ≥ 1%, progesterone receptor > 20%, HER2 negative, and Ki67 ≤ 13.25%).

This was a prospective, multicenter cohort study that included 501 patients aged 55 years and older who had undergone breast-conserving surgery for grade 1-2 T1N0 cancer.

The median patient age was 67, with 442 (88%) older than 75 years. The median tumor size was 1.1 cm.

Median follow-up was 5 years. The cohort was followed every 6 months for the first 2 years and then annually.

The primary outcome was local recurrence defined as time from enrollment to any invasive or noninvasive cancer in the ipsilateral breast, and secondary endpoints included contralateral breast cancer, relapse-free survival based on any recurrence, disease free survival, second cancer or death, and overall survival.

At five years, there were 10 events of local recurrence, for a rate of 2.3%. For secondary outcomes, there were eight events of contralateral breast cancer (1.9%); 12 relapses for a recurrence-free survival rate of 97.3%; 47 disease progression (23 second nonbreast cancers) for a disease-free survival rate of 89.9%; and 13 deaths, including 1 from breast cancer, for an overall survival of 97.2%.
 

Confirms earlier data

Penny R. Anderson, MD, professor in the department of radiation oncology at Fox Chase Cancer Center, Philadelphia, commented that this was an “extremely well-designed and important study.

“It has identified a specific subset of patients to be appropriate candidates for consideration of omission of adjuvant breast radiation therapy after breast-conserving surgery,” she added.

Although previously published trials have helped identify certain patient groups who have a low risk of local recurrence – and therefore, for whom it may be appropriate to omit radiation – they have been based on the traditional clinical and pathologic factors of tumor size, margin status, receptor status, and patient age.

“This LUMINA trial utilizes the molecular-defined intrinsic subtype of luminal A breast cancer to provide additional prognostic information,” she said. “This finding certainly suggests that this group of patients are ideal candidates for the omission of radiation, and that this should be discussed with these patients as a potential option in their treatment management.”

Overall, this trial is a “significant addition and a very relevant contribution to the literature demonstrating that adjuvant breast radiation may safely be omitted in this particular subgroup of breast cancer patients,” she said.
 

Unanswered questions

Commenting on the study, Julie Gralow, MD, chief medical officer and executive vice president of ASCO, told this news organization that she thinks the take-home message is that there is “clearly a population of early-stage breast cancer [patients] who after lumpectomy do not benefit from radiation.”

“I think where there will be discussion will be what is the optimal way of identifying that group,” she said, noting that in this study the patients were screened for Ki67, a marker of proliferation. 

Testing for Ki67 is not the standard of care, Dr. Gralow pointed out, and there is also a problem with reproducibility since “every lab does it somewhat differently, because it is not a standard pathology approach.”

There are now many unanswered questions, she noted. “Do we need that central testing of Ki67? Do we need to develop guidelines for how to do this? Is this better than if you’ve already run an Oncotype or a MammaPrint test to see if the patient needs chemo, then would that suffice? That is where the discussion will be. We can reduce the number of patients who need radiation without an increase in local regional recurrence.”

In terms of clinical practice, Dr. Gralow explained that there are already some  data supporting the omission of radiation therapy in an older population with ER-positive small low-grade tumors, and this has become a standard clinical practice. “It’s not based on solid data, but based on an accumulation of retrospective analyses,” she said. “So we have already been doing it for an older population. This would bring down the age group, and it would better define it, and test it prospectively.”
 

Limitations to note

Also commenting on the study, Deborah Axelrod, MD, director of clinical breast surgery at New York University Langone’s Perlmutter Cancer Center, explained that, in the last decade, knowledge about the behavior of breast cancers based on molecular subtyping has greatly increased. “Results of studies such as this have given us information on which cancers need more treatment and for which cancers we can de-escalate treatment,” she said. “Refining this more, it’s about reducing the morbidity and improving quality of life without compromising the oncological outcome.”

She noted that a big strength of this LUMINA study is that it is prospective and multicenter. “It has been supported by other past studies as well and will define for which patients with newly treated breast cancers can we omit radiation, which has been the standard of care,” said Dr. Axelrod. “It is based on the age and biology of breast cancer in defining which patient can forgo radiation and showed a low risk of recurrence in a specific population of women with a favorable breast cancer profile”

There were limitations to the study. “There is a 5-year follow-up and local recurrence for ER-positive cancers continues to rise after 5 years, so longer-term follow-up will be important,” she said. Also, she pointed out that it is a single-arm study so there is no radiation therapy comparison arm.

Other limitations were that the patients were older with smaller tumors, and all were committed to 5 years of endocrine therapy, although compliance with that has not been reported. There may be some older patients who prefer radiation therapy, especially a week of accelerated partial breast irradiation, rather than commit to 5 years of endocrine therapy as mandated in this study.

“Overall, the takeaway message for patients is that the omission of radiation therapy should be considered an option for older women with localized breast cancer with favorable features who receive endocrine therapies,” said Dr. Axelrod.

LUMINA was sponsored by the Canadian Breast Cancer Foundation and the Canadian Cancer Society. Dr. Whelan has reported research funding from Exact Sciences (Inst). Dr. Axelrod and Dr. Anderson reported no disclosures. Dr. Gralow reported relationships with Genentech, AstraZeneca, Hexal, Puma BioTechnology, Roche, Novartis, Seagen, and Genomic Health.

A version of this article first appeared on Medscape.com.

Based on biomarker findings, some patients may be able to avoid radiation therapy following breast-conserving surgery, suggest results from the LUMINA trial.

The women in this trial who skipped radiotherapy, and were treated with breast-conserving surgery followed by endocrine therapy, had an overall survival rate of 97.2%. The local recurrence rate was 2.3%, which was the study’s primary endpoint.

“Women 55 and over, with low-grade luminal A-type breast cancer, following breast conserving surgery and treated with endocrine therapy alone, had a very low rate of local recurrence at 5 years,” commented lead author Timothy Joseph Whelan, MD.

“The prospective and multicenter nature of this study supports that these patients are candidates for the omission of radiotherapy,” said Dr. Whelan, oncology professor and Canada Research Chair in Breast Cancer Research at McMaster University and a radiation oncologist at the Juravinski Cancer Centre, both in Hamilton, Ont.

“Over 300,000 [people] are diagnosed with invasive breast cancer in North America annually, the majority in the United States,” said Dr. Whelan. “We estimate that these results could apply to 10%-15% of them, so about 30,000-40,000 women per year who could avoid the morbidity, the cost, and inconvenience of radiotherapy.”

The results were presented at the annual meeting of the American Society of Clinical Oncology.

Dr. Whelan explained that adjuvant radiation therapy is generally prescribed following breast conservation therapy to lower the risk of local recurrence, but the treatment is also associated with acute and late toxicity. In addition, it can incur high costs and inconvenience for the patient.

Previous studies have found that among women older than 60 with low-grade, luminal A-type breast cancer who received only breast-conserving surgery, there was a low rate of local recurrence. In women aged older than 70 years, the risk of local recurrence was about 4%-5%.

This latest study focused on patients with breast cancer with a luminal A subtype combined with clinical pathological factors (defined as estrogen receptor ≥ 1%, progesterone receptor > 20%, HER2 negative, and Ki67 ≤ 13.25%).

This was a prospective, multicenter cohort study that included 501 patients aged 55 years and older who had undergone breast-conserving surgery for grade 1-2 T1N0 cancer.

The median patient age was 67, with 442 (88%) older than 75 years. The median tumor size was 1.1 cm.

Median follow-up was 5 years. The cohort was followed every 6 months for the first 2 years and then annually.

The primary outcome was local recurrence defined as time from enrollment to any invasive or noninvasive cancer in the ipsilateral breast, and secondary endpoints included contralateral breast cancer, relapse-free survival based on any recurrence, disease free survival, second cancer or death, and overall survival.

At five years, there were 10 events of local recurrence, for a rate of 2.3%. For secondary outcomes, there were eight events of contralateral breast cancer (1.9%); 12 relapses for a recurrence-free survival rate of 97.3%; 47 disease progression (23 second nonbreast cancers) for a disease-free survival rate of 89.9%; and 13 deaths, including 1 from breast cancer, for an overall survival of 97.2%.
 

Confirms earlier data

Penny R. Anderson, MD, professor in the department of radiation oncology at Fox Chase Cancer Center, Philadelphia, commented that this was an “extremely well-designed and important study.

“It has identified a specific subset of patients to be appropriate candidates for consideration of omission of adjuvant breast radiation therapy after breast-conserving surgery,” she added.

Although previously published trials have helped identify certain patient groups who have a low risk of local recurrence – and therefore, for whom it may be appropriate to omit radiation – they have been based on the traditional clinical and pathologic factors of tumor size, margin status, receptor status, and patient age.

“This LUMINA trial utilizes the molecular-defined intrinsic subtype of luminal A breast cancer to provide additional prognostic information,” she said. “This finding certainly suggests that this group of patients are ideal candidates for the omission of radiation, and that this should be discussed with these patients as a potential option in their treatment management.”

Overall, this trial is a “significant addition and a very relevant contribution to the literature demonstrating that adjuvant breast radiation may safely be omitted in this particular subgroup of breast cancer patients,” she said.
 

Unanswered questions

Commenting on the study, Julie Gralow, MD, chief medical officer and executive vice president of ASCO, told this news organization that she thinks the take-home message is that there is “clearly a population of early-stage breast cancer [patients] who after lumpectomy do not benefit from radiation.”

“I think where there will be discussion will be what is the optimal way of identifying that group,” she said, noting that in this study the patients were screened for Ki67, a marker of proliferation. 

Testing for Ki67 is not the standard of care, Dr. Gralow pointed out, and there is also a problem with reproducibility since “every lab does it somewhat differently, because it is not a standard pathology approach.”

There are now many unanswered questions, she noted. “Do we need that central testing of Ki67? Do we need to develop guidelines for how to do this? Is this better than if you’ve already run an Oncotype or a MammaPrint test to see if the patient needs chemo, then would that suffice? That is where the discussion will be. We can reduce the number of patients who need radiation without an increase in local regional recurrence.”

In terms of clinical practice, Dr. Gralow explained that there are already some  data supporting the omission of radiation therapy in an older population with ER-positive small low-grade tumors, and this has become a standard clinical practice. “It’s not based on solid data, but based on an accumulation of retrospective analyses,” she said. “So we have already been doing it for an older population. This would bring down the age group, and it would better define it, and test it prospectively.”
 

Limitations to note

Also commenting on the study, Deborah Axelrod, MD, director of clinical breast surgery at New York University Langone’s Perlmutter Cancer Center, explained that, in the last decade, knowledge about the behavior of breast cancers based on molecular subtyping has greatly increased. “Results of studies such as this have given us information on which cancers need more treatment and for which cancers we can de-escalate treatment,” she said. “Refining this more, it’s about reducing the morbidity and improving quality of life without compromising the oncological outcome.”

She noted that a big strength of this LUMINA study is that it is prospective and multicenter. “It has been supported by other past studies as well and will define for which patients with newly treated breast cancers can we omit radiation, which has been the standard of care,” said Dr. Axelrod. “It is based on the age and biology of breast cancer in defining which patient can forgo radiation and showed a low risk of recurrence in a specific population of women with a favorable breast cancer profile”

There were limitations to the study. “There is a 5-year follow-up and local recurrence for ER-positive cancers continues to rise after 5 years, so longer-term follow-up will be important,” she said. Also, she pointed out that it is a single-arm study so there is no radiation therapy comparison arm.

Other limitations were that the patients were older with smaller tumors, and all were committed to 5 years of endocrine therapy, although compliance with that has not been reported. There may be some older patients who prefer radiation therapy, especially a week of accelerated partial breast irradiation, rather than commit to 5 years of endocrine therapy as mandated in this study.

“Overall, the takeaway message for patients is that the omission of radiation therapy should be considered an option for older women with localized breast cancer with favorable features who receive endocrine therapies,” said Dr. Axelrod.

LUMINA was sponsored by the Canadian Breast Cancer Foundation and the Canadian Cancer Society. Dr. Whelan has reported research funding from Exact Sciences (Inst). Dr. Axelrod and Dr. Anderson reported no disclosures. Dr. Gralow reported relationships with Genentech, AstraZeneca, Hexal, Puma BioTechnology, Roche, Novartis, Seagen, and Genomic Health.

A version of this article first appeared on Medscape.com.

Based on biomarker findings, some patients may be able to avoid radiation therapy following breast-conserving surgery, suggest results from the LUMINA trial.

The women in this trial who skipped radiotherapy, and were treated with breast-conserving surgery followed by endocrine therapy, had an overall survival rate of 97.2%. The local recurrence rate was 2.3%, which was the study’s primary endpoint.

“Women 55 and over, with low-grade luminal A-type breast cancer, following breast conserving surgery and treated with endocrine therapy alone, had a very low rate of local recurrence at 5 years,” commented lead author Timothy Joseph Whelan, MD.

“The prospective and multicenter nature of this study supports that these patients are candidates for the omission of radiotherapy,” said Dr. Whelan, oncology professor and Canada Research Chair in Breast Cancer Research at McMaster University and a radiation oncologist at the Juravinski Cancer Centre, both in Hamilton, Ont.

“Over 300,000 [people] are diagnosed with invasive breast cancer in North America annually, the majority in the United States,” said Dr. Whelan. “We estimate that these results could apply to 10%-15% of them, so about 30,000-40,000 women per year who could avoid the morbidity, the cost, and inconvenience of radiotherapy.”

The results were presented at the annual meeting of the American Society of Clinical Oncology.

Dr. Whelan explained that adjuvant radiation therapy is generally prescribed following breast conservation therapy to lower the risk of local recurrence, but the treatment is also associated with acute and late toxicity. In addition, it can incur high costs and inconvenience for the patient.

Previous studies have found that among women older than 60 with low-grade, luminal A-type breast cancer who received only breast-conserving surgery, there was a low rate of local recurrence. In women aged older than 70 years, the risk of local recurrence was about 4%-5%.

This latest study focused on patients with breast cancer with a luminal A subtype combined with clinical pathological factors (defined as estrogen receptor ≥ 1%, progesterone receptor > 20%, HER2 negative, and Ki67 ≤ 13.25%).

This was a prospective, multicenter cohort study that included 501 patients aged 55 years and older who had undergone breast-conserving surgery for grade 1-2 T1N0 cancer.

The median patient age was 67, with 442 (88%) older than 75 years. The median tumor size was 1.1 cm.

Median follow-up was 5 years. The cohort was followed every 6 months for the first 2 years and then annually.

The primary outcome was local recurrence defined as time from enrollment to any invasive or noninvasive cancer in the ipsilateral breast, and secondary endpoints included contralateral breast cancer, relapse-free survival based on any recurrence, disease free survival, second cancer or death, and overall survival.

At five years, there were 10 events of local recurrence, for a rate of 2.3%. For secondary outcomes, there were eight events of contralateral breast cancer (1.9%); 12 relapses for a recurrence-free survival rate of 97.3%; 47 disease progression (23 second nonbreast cancers) for a disease-free survival rate of 89.9%; and 13 deaths, including 1 from breast cancer, for an overall survival of 97.2%.
 

Confirms earlier data

Penny R. Anderson, MD, professor in the department of radiation oncology at Fox Chase Cancer Center, Philadelphia, commented that this was an “extremely well-designed and important study.

“It has identified a specific subset of patients to be appropriate candidates for consideration of omission of adjuvant breast radiation therapy after breast-conserving surgery,” she added.

Although previously published trials have helped identify certain patient groups who have a low risk of local recurrence – and therefore, for whom it may be appropriate to omit radiation – they have been based on the traditional clinical and pathologic factors of tumor size, margin status, receptor status, and patient age.

“This LUMINA trial utilizes the molecular-defined intrinsic subtype of luminal A breast cancer to provide additional prognostic information,” she said. “This finding certainly suggests that this group of patients are ideal candidates for the omission of radiation, and that this should be discussed with these patients as a potential option in their treatment management.”

Overall, this trial is a “significant addition and a very relevant contribution to the literature demonstrating that adjuvant breast radiation may safely be omitted in this particular subgroup of breast cancer patients,” she said.
 

Unanswered questions

Commenting on the study, Julie Gralow, MD, chief medical officer and executive vice president of ASCO, told this news organization that she thinks the take-home message is that there is “clearly a population of early-stage breast cancer [patients] who after lumpectomy do not benefit from radiation.”

“I think where there will be discussion will be what is the optimal way of identifying that group,” she said, noting that in this study the patients were screened for Ki67, a marker of proliferation. 

Testing for Ki67 is not the standard of care, Dr. Gralow pointed out, and there is also a problem with reproducibility since “every lab does it somewhat differently, because it is not a standard pathology approach.”

There are now many unanswered questions, she noted. “Do we need that central testing of Ki67? Do we need to develop guidelines for how to do this? Is this better than if you’ve already run an Oncotype or a MammaPrint test to see if the patient needs chemo, then would that suffice? That is where the discussion will be. We can reduce the number of patients who need radiation without an increase in local regional recurrence.”

In terms of clinical practice, Dr. Gralow explained that there are already some  data supporting the omission of radiation therapy in an older population with ER-positive small low-grade tumors, and this has become a standard clinical practice. “It’s not based on solid data, but based on an accumulation of retrospective analyses,” she said. “So we have already been doing it for an older population. This would bring down the age group, and it would better define it, and test it prospectively.”
 

Limitations to note

Also commenting on the study, Deborah Axelrod, MD, director of clinical breast surgery at New York University Langone’s Perlmutter Cancer Center, explained that, in the last decade, knowledge about the behavior of breast cancers based on molecular subtyping has greatly increased. “Results of studies such as this have given us information on which cancers need more treatment and for which cancers we can de-escalate treatment,” she said. “Refining this more, it’s about reducing the morbidity and improving quality of life without compromising the oncological outcome.”

She noted that a big strength of this LUMINA study is that it is prospective and multicenter. “It has been supported by other past studies as well and will define for which patients with newly treated breast cancers can we omit radiation, which has been the standard of care,” said Dr. Axelrod. “It is based on the age and biology of breast cancer in defining which patient can forgo radiation and showed a low risk of recurrence in a specific population of women with a favorable breast cancer profile”

There were limitations to the study. “There is a 5-year follow-up and local recurrence for ER-positive cancers continues to rise after 5 years, so longer-term follow-up will be important,” she said. Also, she pointed out that it is a single-arm study so there is no radiation therapy comparison arm.

Other limitations were that the patients were older with smaller tumors, and all were committed to 5 years of endocrine therapy, although compliance with that has not been reported. There may be some older patients who prefer radiation therapy, especially a week of accelerated partial breast irradiation, rather than commit to 5 years of endocrine therapy as mandated in this study.

“Overall, the takeaway message for patients is that the omission of radiation therapy should be considered an option for older women with localized breast cancer with favorable features who receive endocrine therapies,” said Dr. Axelrod.

LUMINA was sponsored by the Canadian Breast Cancer Foundation and the Canadian Cancer Society. Dr. Whelan has reported research funding from Exact Sciences (Inst). Dr. Axelrod and Dr. Anderson reported no disclosures. Dr. Gralow reported relationships with Genentech, AstraZeneca, Hexal, Puma BioTechnology, Roche, Novartis, Seagen, and Genomic Health.

A version of this article first appeared on Medscape.com.

A large case-control study finds the range of cancer types associated with pathogenic variants in BRCA1 and BRCA2 is broader than previously determined from prior analyses showing associations with breast, ovarian, prostate, and pancreatic cancers. The finding, published in JAMA Oncology suggests a possible broader clinical relevance for BRCA1 and BRCA2 genetic testing.

Pathogenic variants in BRCA1 were found to be associated with biliary tract cancer, in BRCA2 with esophageal cancer, and in BRCA1/2 with gastric cancer.

“The results suggest the range of cancer types associated with pathogenic variants in BRCA1 and BRCA2 is likely broader than that determined from previous analysis of largely European ancestry cohorts,” wrote authors who were led by Yukihide Momozawa, DVM, PhD, RIKEN Center for Integrative Medical Sciences, Japan.

“These risk association findings, together with our analysis of an association with family history of cancer and clinical phenotypes, are relevant for developing and adapting guidelines about genetic testing, treatment options, and treatability with PARP [poly adenosine diphosphate-ribose polymerase] inhibitors for each cancer type,” the authors wrote.

Dr. Momozawa and associates conducted a large-scale sequencing study across 14 common cancer types in 63,828 patients (mean age 64 years, 42% female) and 37,086 controls on data drawn from a Japanese nationwide biobank between April 2003 and March 2018. They estimated the risk of each cancer type and determined clinical characteristics associated with pathogenic variant carrier status, while also investigating the utility of family history in detecting patients with pathogenic variants.

Three hundred fifteen pathogenic variants were identified. An odds ratios of greater than 4.0 (with P < 1 × 10−4 as the threshold of significance) for the pathogenic variants were found for biliary tract cancer (OR, 17.4; 95% confidence interval, 5.8-51.9) in BRCA1, esophageal cancer (OR, 5.6; 95% CI, 2.9-11.0) in BRCA2, and gastric cancer (OR, 5.2; 95% CI, 2.6-10.5) in BRCA1, and (OR, 4.7; 95% CI, 3.1-7.1) in BRCA2. Two other cancer types were found to be associated with BRCA1, and four other cancer types with BRCA2. Enrichment of carrier patients was shown in biliary tract, female breast, ovarian, and prostate cancers in accordance with increased numbers of reported cancer types in relatives.

Male patients with breast cancer had a very high carrier frequency of pathogenic variants in BRCA2 (18.9%), but not BRCA1 (1.89%). Patients with ovarian cancer showed the next highest proportion (BRCA1, 4.86%; BRCA2, 3.42%). Frequency exceeding 1% was seen for several other cancer types (two cancer types for BRCA1, four cancer types for BRCA2). More than one cancer types was identified in 4,128 patients (6.3%). Carrier frequency of pathogenic variants in BRCA1 was 0.44% with one cancer type, 0.85% with two cancer types, and 0.69% with three cancer types. It was 0.97%, 1.40%, and 1.74%, respectively, in BRCA2.

“The results of this large-scale registry-based case-control study suggest that pathogenic variants in BRCA1 and BRCA2 were associated with the risk of seven cancer types. These results indicate broader clinical relevance of BRCA1 and BRCA2 genetic testing,” the authors wrote.

PARP inhibitors were developed based on the mechanism in BRCA1 and BRCA2 of homologous recombination repair defects associated with pathogenic variants. PARP inhibitors have been found to have therapeutic efficacy also in pathogenic variants found to be enriched in prostate and pancreatic cancers. While risk for additional cancer types (for example, biliary tract cancer, cervical cancer, colorectal cancer, endometrial cancer, esophageal cancer, and stomach cancer) has been reported after analyzing family members for the presence of pathogenic variants and performing case-control analyses, evidence for an association with these cancer types has not been considered sufficient for them to be adopted into clinical management guidelines, the authors wrote.

In an interview, Dr. Momozawa said that BRCA1 and BRCA2 genetic testing should be expanded in Japan. “But further studies are needed to reveal how much. If a clinical trial of a PARP inhibitor for these three cancer types reveals its clinical utility, the importance of this expansion will increase.”

Dr. Momozawa and associates state that while their selection of controls without a family history of cancer affects the generalizability of the study results, the estimated cumulative risks were comparable with those based on prospective cohorts, suggesting the study design did not greatly affect the results.

A large case-control study finds the range of cancer types associated with pathogenic variants in BRCA1 and BRCA2 is broader than previously determined from prior analyses showing associations with breast, ovarian, prostate, and pancreatic cancers. The finding, published in JAMA Oncology suggests a possible broader clinical relevance for BRCA1 and BRCA2 genetic testing.

Pathogenic variants in BRCA1 were found to be associated with biliary tract cancer, in BRCA2 with esophageal cancer, and in BRCA1/2 with gastric cancer.

“The results suggest the range of cancer types associated with pathogenic variants in BRCA1 and BRCA2 is likely broader than that determined from previous analysis of largely European ancestry cohorts,” wrote authors who were led by Yukihide Momozawa, DVM, PhD, RIKEN Center for Integrative Medical Sciences, Japan.

“These risk association findings, together with our analysis of an association with family history of cancer and clinical phenotypes, are relevant for developing and adapting guidelines about genetic testing, treatment options, and treatability with PARP [poly adenosine diphosphate-ribose polymerase] inhibitors for each cancer type,” the authors wrote.

Dr. Momozawa and associates conducted a large-scale sequencing study across 14 common cancer types in 63,828 patients (mean age 64 years, 42% female) and 37,086 controls on data drawn from a Japanese nationwide biobank between April 2003 and March 2018. They estimated the risk of each cancer type and determined clinical characteristics associated with pathogenic variant carrier status, while also investigating the utility of family history in detecting patients with pathogenic variants.

Three hundred fifteen pathogenic variants were identified. An odds ratios of greater than 4.0 (with P < 1 × 10−4 as the threshold of significance) for the pathogenic variants were found for biliary tract cancer (OR, 17.4; 95% confidence interval, 5.8-51.9) in BRCA1, esophageal cancer (OR, 5.6; 95% CI, 2.9-11.0) in BRCA2, and gastric cancer (OR, 5.2; 95% CI, 2.6-10.5) in BRCA1, and (OR, 4.7; 95% CI, 3.1-7.1) in BRCA2. Two other cancer types were found to be associated with BRCA1, and four other cancer types with BRCA2. Enrichment of carrier patients was shown in biliary tract, female breast, ovarian, and prostate cancers in accordance with increased numbers of reported cancer types in relatives.

Male patients with breast cancer had a very high carrier frequency of pathogenic variants in BRCA2 (18.9%), but not BRCA1 (1.89%). Patients with ovarian cancer showed the next highest proportion (BRCA1, 4.86%; BRCA2, 3.42%). Frequency exceeding 1% was seen for several other cancer types (two cancer types for BRCA1, four cancer types for BRCA2). More than one cancer types was identified in 4,128 patients (6.3%). Carrier frequency of pathogenic variants in BRCA1 was 0.44% with one cancer type, 0.85% with two cancer types, and 0.69% with three cancer types. It was 0.97%, 1.40%, and 1.74%, respectively, in BRCA2.

“The results of this large-scale registry-based case-control study suggest that pathogenic variants in BRCA1 and BRCA2 were associated with the risk of seven cancer types. These results indicate broader clinical relevance of BRCA1 and BRCA2 genetic testing,” the authors wrote.

PARP inhibitors were developed based on the mechanism in BRCA1 and BRCA2 of homologous recombination repair defects associated with pathogenic variants. PARP inhibitors have been found to have therapeutic efficacy also in pathogenic variants found to be enriched in prostate and pancreatic cancers. While risk for additional cancer types (for example, biliary tract cancer, cervical cancer, colorectal cancer, endometrial cancer, esophageal cancer, and stomach cancer) has been reported after analyzing family members for the presence of pathogenic variants and performing case-control analyses, evidence for an association with these cancer types has not been considered sufficient for them to be adopted into clinical management guidelines, the authors wrote.

In an interview, Dr. Momozawa said that BRCA1 and BRCA2 genetic testing should be expanded in Japan. “But further studies are needed to reveal how much. If a clinical trial of a PARP inhibitor for these three cancer types reveals its clinical utility, the importance of this expansion will increase.”

Dr. Momozawa and associates state that while their selection of controls without a family history of cancer affects the generalizability of the study results, the estimated cumulative risks were comparable with those based on prospective cohorts, suggesting the study design did not greatly affect the results.

A large case-control study finds the range of cancer types associated with pathogenic variants in BRCA1 and BRCA2 is broader than previously determined from prior analyses showing associations with breast, ovarian, prostate, and pancreatic cancers. The finding, published in JAMA Oncology suggests a possible broader clinical relevance for BRCA1 and BRCA2 genetic testing.

Pathogenic variants in BRCA1 were found to be associated with biliary tract cancer, in BRCA2 with esophageal cancer, and in BRCA1/2 with gastric cancer.

“The results suggest the range of cancer types associated with pathogenic variants in BRCA1 and BRCA2 is likely broader than that determined from previous analysis of largely European ancestry cohorts,” wrote authors who were led by Yukihide Momozawa, DVM, PhD, RIKEN Center for Integrative Medical Sciences, Japan.

“These risk association findings, together with our analysis of an association with family history of cancer and clinical phenotypes, are relevant for developing and adapting guidelines about genetic testing, treatment options, and treatability with PARP [poly adenosine diphosphate-ribose polymerase] inhibitors for each cancer type,” the authors wrote.

Dr. Momozawa and associates conducted a large-scale sequencing study across 14 common cancer types in 63,828 patients (mean age 64 years, 42% female) and 37,086 controls on data drawn from a Japanese nationwide biobank between April 2003 and March 2018. They estimated the risk of each cancer type and determined clinical characteristics associated with pathogenic variant carrier status, while also investigating the utility of family history in detecting patients with pathogenic variants.

Three hundred fifteen pathogenic variants were identified. An odds ratios of greater than 4.0 (with P < 1 × 10−4 as the threshold of significance) for the pathogenic variants were found for biliary tract cancer (OR, 17.4; 95% confidence interval, 5.8-51.9) in BRCA1, esophageal cancer (OR, 5.6; 95% CI, 2.9-11.0) in BRCA2, and gastric cancer (OR, 5.2; 95% CI, 2.6-10.5) in BRCA1, and (OR, 4.7; 95% CI, 3.1-7.1) in BRCA2. Two other cancer types were found to be associated with BRCA1, and four other cancer types with BRCA2. Enrichment of carrier patients was shown in biliary tract, female breast, ovarian, and prostate cancers in accordance with increased numbers of reported cancer types in relatives.

Male patients with breast cancer had a very high carrier frequency of pathogenic variants in BRCA2 (18.9%), but not BRCA1 (1.89%). Patients with ovarian cancer showed the next highest proportion (BRCA1, 4.86%; BRCA2, 3.42%). Frequency exceeding 1% was seen for several other cancer types (two cancer types for BRCA1, four cancer types for BRCA2). More than one cancer types was identified in 4,128 patients (6.3%). Carrier frequency of pathogenic variants in BRCA1 was 0.44% with one cancer type, 0.85% with two cancer types, and 0.69% with three cancer types. It was 0.97%, 1.40%, and 1.74%, respectively, in BRCA2.

“The results of this large-scale registry-based case-control study suggest that pathogenic variants in BRCA1 and BRCA2 were associated with the risk of seven cancer types. These results indicate broader clinical relevance of BRCA1 and BRCA2 genetic testing,” the authors wrote.

PARP inhibitors were developed based on the mechanism in BRCA1 and BRCA2 of homologous recombination repair defects associated with pathogenic variants. PARP inhibitors have been found to have therapeutic efficacy also in pathogenic variants found to be enriched in prostate and pancreatic cancers. While risk for additional cancer types (for example, biliary tract cancer, cervical cancer, colorectal cancer, endometrial cancer, esophageal cancer, and stomach cancer) has been reported after analyzing family members for the presence of pathogenic variants and performing case-control analyses, evidence for an association with these cancer types has not been considered sufficient for them to be adopted into clinical management guidelines, the authors wrote.

In an interview, Dr. Momozawa said that BRCA1 and BRCA2 genetic testing should be expanded in Japan. “But further studies are needed to reveal how much. If a clinical trial of a PARP inhibitor for these three cancer types reveals its clinical utility, the importance of this expansion will increase.”

Dr. Momozawa and associates state that while their selection of controls without a family history of cancer affects the generalizability of the study results, the estimated cumulative risks were comparable with those based on prospective cohorts, suggesting the study design did not greatly affect the results.

Racial differences in cancer outcomes are widespread. Studies indicate that Black people face higher rates of mortality for most cancers than their White counterparts. To bridge this racial gap, researchers need to investigate the biological effects of structural racism and discrimination on cancer outcomes, experts say.

“As a physician, I always like to think that I can influence care in that if I just find the right drugs, help patients understand what their options are, it will help them,” said Ruth Carlos, MD, a radiologist with the University of Michigan Hospital, Ann Arbor. But these things alone are often not enough, because a large proportion of the variation in cancer outcomes is attributable to neighborhood social conditions and the physical environment. “It is incredibly important for us to start to understand just how the neighborhood exerts this effect.”

In a commentary published in the Journal of Clinical Oncology, Dr. Carlos and colleagues highlighted the limitations of previous studies aimed at identifying the causes of racial differences in cancer outcomes. They call upon researchers to turn instead to the long-underexamined biological effects of structural racism and discrimination that contribute to these differences.

In the past, studies on the role of race in health outcomes largely looked at race as a proxy for genetic predisposition. But such an interpretation is flawed, because no genes are specific for a racial or ethnic group, Dr. Carlos and coauthors wrote. Researchers have shown that the vast majority of genetic variation occurs within, rather than between groups.

In an analysis published in Science, researchers reported that within-group differences account for more than 90% of genetic variation.

“Using race in these analyses was not necessarily wrong, but the inferences may have been flawed or incomplete,” Dr. Carlos said. On one hand, looking at genetic predisposition has led to important insights, such as the link between mutations in the BRCA gene and increased risk for breast and ovarian cancer.

However, genetic variation alone is not enough to explain the disparities in cancer outcomes between racial and ethnic groups. The fact that breast cancer can be more aggressive in Black women raises several questions, Dr. Carlos said. Is the cancer worse because Black women have a specific genetic predisposition? Is it worse because Black women exist in a society that marginalizes them and exposes them to increased stress, which in turn produces bad outcomes? Or, could it be both?

Despite progress in the screening, diagnosis and treatment of breast cancer, Black women are 40% more likely to die from the disease than White women. At the time of diagnosis, Black women are more likely to have high-grade, more aggressive breast cancer molecular subtypes, and to have had their cancer spread to the lymph nodes. They also tend to be diagnosed at more advanced stages of breast cancer while at the same time, experience higher rates of false-positive screening results.

Although researchers have hypothesized that genetic differences related to African or European ancestry might contribute, studies have not turned up any differences in cancer susceptibility genes by race. Other factors, such as racial differences in the stage of presentation, molecular subtypes, and disparities in treatment, have also emerged as potential culprits.

In her commentary, Dr. Carlos and colleagues wrote that disparities in breast cancer outcomes previously attributed to race need to be examined from multiple angles. This means looking at both the complex interactions between social conditions and policies, which encompass racism both at the individual and structural level, and stressors such as the experience of discrimination in addition to potential biological and genetic contributions.

Many studies now provide evidence for the harmful effects of racism on health. For breast cancer, specifically, studies also suggest that factors such as racial segregation can influence the stage at which Black women get diagnosed and their likelihood of dying from the disease.

However, an important question that remains is what biological changes occur in women exposed to the kind of persistent low-level stress that is associated with structural racism and discrimination, Dr. Carlos said. “We don’t know what stress pathways actually manifest in the body and how they eventually produce the disease.” Studies to address this issue are important, “especially if you would like to develop interventions to prevent or mitigate disease.”

To address this issue, Dr. Carlos and colleagues called upon the research community to conduct both studies that delineate the underlying biology as well as those that test potential interventions – particularly those associated with breast cancer screening outcomes – to try to shed light on why Black women receive more false positives and diagnoses of more aggressive cancer.

Interventions that can target these specific biological pathways could potentially reduce the negative effects of structural racism and discrimination as well as the effects of other social factors that contribute to breast cancer outcomes, “to ultimately help enhance clinical outcomes and close persistent disparities gaps,” the authors wrote.

Racial differences in cancer outcomes are widespread. Studies indicate that Black people face higher rates of mortality for most cancers than their White counterparts. To bridge this racial gap, researchers need to investigate the biological effects of structural racism and discrimination on cancer outcomes, experts say.

“As a physician, I always like to think that I can influence care in that if I just find the right drugs, help patients understand what their options are, it will help them,” said Ruth Carlos, MD, a radiologist with the University of Michigan Hospital, Ann Arbor. But these things alone are often not enough, because a large proportion of the variation in cancer outcomes is attributable to neighborhood social conditions and the physical environment. “It is incredibly important for us to start to understand just how the neighborhood exerts this effect.”

In a commentary published in the Journal of Clinical Oncology, Dr. Carlos and colleagues highlighted the limitations of previous studies aimed at identifying the causes of racial differences in cancer outcomes. They call upon researchers to turn instead to the long-underexamined biological effects of structural racism and discrimination that contribute to these differences.

In the past, studies on the role of race in health outcomes largely looked at race as a proxy for genetic predisposition. But such an interpretation is flawed, because no genes are specific for a racial or ethnic group, Dr. Carlos and coauthors wrote. Researchers have shown that the vast majority of genetic variation occurs within, rather than between groups.

In an analysis published in Science, researchers reported that within-group differences account for more than 90% of genetic variation.

“Using race in these analyses was not necessarily wrong, but the inferences may have been flawed or incomplete,” Dr. Carlos said. On one hand, looking at genetic predisposition has led to important insights, such as the link between mutations in the BRCA gene and increased risk for breast and ovarian cancer.

However, genetic variation alone is not enough to explain the disparities in cancer outcomes between racial and ethnic groups. The fact that breast cancer can be more aggressive in Black women raises several questions, Dr. Carlos said. Is the cancer worse because Black women have a specific genetic predisposition? Is it worse because Black women exist in a society that marginalizes them and exposes them to increased stress, which in turn produces bad outcomes? Or, could it be both?

Despite progress in the screening, diagnosis and treatment of breast cancer, Black women are 40% more likely to die from the disease than White women. At the time of diagnosis, Black women are more likely to have high-grade, more aggressive breast cancer molecular subtypes, and to have had their cancer spread to the lymph nodes. They also tend to be diagnosed at more advanced stages of breast cancer while at the same time, experience higher rates of false-positive screening results.

Although researchers have hypothesized that genetic differences related to African or European ancestry might contribute, studies have not turned up any differences in cancer susceptibility genes by race. Other factors, such as racial differences in the stage of presentation, molecular subtypes, and disparities in treatment, have also emerged as potential culprits.

In her commentary, Dr. Carlos and colleagues wrote that disparities in breast cancer outcomes previously attributed to race need to be examined from multiple angles. This means looking at both the complex interactions between social conditions and policies, which encompass racism both at the individual and structural level, and stressors such as the experience of discrimination in addition to potential biological and genetic contributions.

Many studies now provide evidence for the harmful effects of racism on health. For breast cancer, specifically, studies also suggest that factors such as racial segregation can influence the stage at which Black women get diagnosed and their likelihood of dying from the disease.

However, an important question that remains is what biological changes occur in women exposed to the kind of persistent low-level stress that is associated with structural racism and discrimination, Dr. Carlos said. “We don’t know what stress pathways actually manifest in the body and how they eventually produce the disease.” Studies to address this issue are important, “especially if you would like to develop interventions to prevent or mitigate disease.”

To address this issue, Dr. Carlos and colleagues called upon the research community to conduct both studies that delineate the underlying biology as well as those that test potential interventions – particularly those associated with breast cancer screening outcomes – to try to shed light on why Black women receive more false positives and diagnoses of more aggressive cancer.

Interventions that can target these specific biological pathways could potentially reduce the negative effects of structural racism and discrimination as well as the effects of other social factors that contribute to breast cancer outcomes, “to ultimately help enhance clinical outcomes and close persistent disparities gaps,” the authors wrote.

Racial differences in cancer outcomes are widespread. Studies indicate that Black people face higher rates of mortality for most cancers than their White counterparts. To bridge this racial gap, researchers need to investigate the biological effects of structural racism and discrimination on cancer outcomes, experts say.

“As a physician, I always like to think that I can influence care in that if I just find the right drugs, help patients understand what their options are, it will help them,” said Ruth Carlos, MD, a radiologist with the University of Michigan Hospital, Ann Arbor. But these things alone are often not enough, because a large proportion of the variation in cancer outcomes is attributable to neighborhood social conditions and the physical environment. “It is incredibly important for us to start to understand just how the neighborhood exerts this effect.”

In a commentary published in the Journal of Clinical Oncology, Dr. Carlos and colleagues highlighted the limitations of previous studies aimed at identifying the causes of racial differences in cancer outcomes. They call upon researchers to turn instead to the long-underexamined biological effects of structural racism and discrimination that contribute to these differences.

In the past, studies on the role of race in health outcomes largely looked at race as a proxy for genetic predisposition. But such an interpretation is flawed, because no genes are specific for a racial or ethnic group, Dr. Carlos and coauthors wrote. Researchers have shown that the vast majority of genetic variation occurs within, rather than between groups.

In an analysis published in Science, researchers reported that within-group differences account for more than 90% of genetic variation.

“Using race in these analyses was not necessarily wrong, but the inferences may have been flawed or incomplete,” Dr. Carlos said. On one hand, looking at genetic predisposition has led to important insights, such as the link between mutations in the BRCA gene and increased risk for breast and ovarian cancer.

However, genetic variation alone is not enough to explain the disparities in cancer outcomes between racial and ethnic groups. The fact that breast cancer can be more aggressive in Black women raises several questions, Dr. Carlos said. Is the cancer worse because Black women have a specific genetic predisposition? Is it worse because Black women exist in a society that marginalizes them and exposes them to increased stress, which in turn produces bad outcomes? Or, could it be both?

Despite progress in the screening, diagnosis and treatment of breast cancer, Black women are 40% more likely to die from the disease than White women. At the time of diagnosis, Black women are more likely to have high-grade, more aggressive breast cancer molecular subtypes, and to have had their cancer spread to the lymph nodes. They also tend to be diagnosed at more advanced stages of breast cancer while at the same time, experience higher rates of false-positive screening results.

Although researchers have hypothesized that genetic differences related to African or European ancestry might contribute, studies have not turned up any differences in cancer susceptibility genes by race. Other factors, such as racial differences in the stage of presentation, molecular subtypes, and disparities in treatment, have also emerged as potential culprits.

In her commentary, Dr. Carlos and colleagues wrote that disparities in breast cancer outcomes previously attributed to race need to be examined from multiple angles. This means looking at both the complex interactions between social conditions and policies, which encompass racism both at the individual and structural level, and stressors such as the experience of discrimination in addition to potential biological and genetic contributions.

Many studies now provide evidence for the harmful effects of racism on health. For breast cancer, specifically, studies also suggest that factors such as racial segregation can influence the stage at which Black women get diagnosed and their likelihood of dying from the disease.

However, an important question that remains is what biological changes occur in women exposed to the kind of persistent low-level stress that is associated with structural racism and discrimination, Dr. Carlos said. “We don’t know what stress pathways actually manifest in the body and how they eventually produce the disease.” Studies to address this issue are important, “especially if you would like to develop interventions to prevent or mitigate disease.”

To address this issue, Dr. Carlos and colleagues called upon the research community to conduct both studies that delineate the underlying biology as well as those that test potential interventions – particularly those associated with breast cancer screening outcomes – to try to shed light on why Black women receive more false positives and diagnoses of more aggressive cancer.

Interventions that can target these specific biological pathways could potentially reduce the negative effects of structural racism and discrimination as well as the effects of other social factors that contribute to breast cancer outcomes, “to ultimately help enhance clinical outcomes and close persistent disparities gaps,” the authors wrote.

Only a small number of research clinical trials for cancer drugs actually show benefit in quality of life, according to a study published in JAMA Oncology.

The study found trials that failed to show improved quality of life often reported their quality of life outcomes more favorably. Non–immunotherapy-targeted drugs were found to lead to worse quality of life outcomes more often than did cytotoxic agents. And, while there is an association between quality of life benefit and overall survival, no such association was found with progression-free survival.

“In this study, we evaluated the outcomes of cancer drug trials with regard to patients’ quality of life and found that only a quarter of phase 3 cancer drug trials in the advanced-disease setting demonstrated improved quality of life,” wrote authors who were led by Bishal Gyawali, MD, PhD, of the Cancer Research Institute, Queen’s University, Kingston, Ont.

“Improved quality of life outcomes were associated with improved overall survival but not with improved progression-free survival. Importantly, almost half of the cancer drugs drug trials that showed improved progression-free survival showed no improved overall survival or quality of life (i.e., PFS-only benefit). Some reports included conclusions regarding quality of life (QOL) findings that were not directly supported by the trial data, particularly for inferior or non–statistically significant QOL outcomes, thereby framing the findings in a favorable light or downplaying detrimental effects of the study intervention on QOL. Furthermore, contrary to common perception, inferior QOL outcomes were more common with targeted drugs than cytotoxic drugs. Taken together, these findings have important policy implications,” the authors wrote.

These findings are based on the results of a cohort study of 45 phase 3 research clinical trials of 24,806 patients. Only a small percentage of patients showed QOL benefits. The study found that industry-funded clinical trial reports often framed QOL findings more favorably than was warranted by the data.

The study found improved QOL with experimental agents in 11 of 45 randomized controlled trials (24.4%). Studies that reported improved QOL were more likely to also show improved overall survival as compared with trials in which quality of life was not improved (7 of 11 [64%] versus 10 of 34 [29%] trials). For improved progression-free survival, however, there was no positive association (6 of 11 [55%] trials versus 17 of 34 [50%] trials without improved QOL). Among six trials reporting worsening QOL, three (50%) were trials of targeted drugs. Among 11 trials reporting improved QOL, 6 (55%) were trials of immunotherapy drugs. Among the 34 trials in which QOL was not improved compared with controls, the findings were framed favorably (versus neutrally or negatively) in the abstract or conclusions in 16 (47%), an observation that was statistically significantly associated with industry funding (chi-squared = 6.35; P = .01).

“It is important to clearly understand and communicate the effects of cancer drugs”

To fulfill the obligation to inform patients about proposed treatments, the authors wrote that it is important to clearly understand and communicate the effects of cancer drugs on patient quality of life alongside their effects on overall survival and intermediate end points such as progression-free survival. “Patients with advanced cancer expect treatment to help them live longer or have better lives,” the authors wrote. In that respect, in clinical trials of cancer medicines, overall survival and quality of life are the most important measures. Toxicity profiles and disease progression delays do not reliably predict quality of life, and studies have shown poor correlations between quality of life, overall survival, and progression-free survival. This raises the question of validity of progression-free survival as a surrogate endpoint. “Progression-free survival is meaningless without overall survival or quality of life gains,” Dr. Gyawali said in an interview.

Writing in The Lancet Oncology in March, Dr. Gyawali stated that, because progression free survival “does not directly measure how a patient feels or functions, or how long a patient lives, progression-free survival was not intended to inform clinical practice or establish whether a new therapy provides clinically meaningful benefits for patients. However, over the past 2 decades, it has become the most common primary endpoint in oncology clinical trials. We are deeply worried about how the term survival in this phrase can influence clinical practice and patient choices. We propose replacing the phrase progression-free survival with a less ambiguous term: progression-free interval.”

In JAMA Oncology, Dr. Gyawali aimed to elucidate relationships between QOL, overall survival, and progression-free survival, and to assess, as well, how QOL results are framed, especially in industry-sponsored research. When drug trials they analyzed showed no change in QOL but reported that QOL did not worsen or QOL was maintained rather than stating that QOL did not improve, or if there was downplaying of worse QOL outcomes, the study had favorable interpretation, Dr. Gyawali and associates wrote. The expectation of patients receiving cancer drugs would be improved QOL rather than “not worse” QOL, Dr. Gyawali said.

Regarding the finding that QOL outcomes were described as favorable in 47% of trials with unimproved QOL outcomes, Dr. Gyawali said, “the bias in reporting should be corrected by the reviewers and editors of journals. Also, quality of life reporting should be made mandatory. Without unbiased quality of life information, informed decision making on whether or not to use a certain drug is impossible. Patients and physicians need to know that information. Regulators can demand that this should be mandatory in all trials in noncurative settings.”

He remarked further on the worsening QOL in some targeted drug trials, “People tout chemo-free regimens as automatically having better quality of life, but that doesn’t seem to be the case. Targeted drugs can have a severe impact on quality of life, probably due to prolonged duration of side effects. Quality of life should be measured and reported for all drugs.”

Dr. Gyawali and associates noted the limitation in that several studies with negative QOL results are not published at all or are published after a considerable delay, so the present observations may understate the issues that have been raised.

Dr. Gyawali declared that he received no funding and disclosed no conflicts of interest for this study.

Only a small number of research clinical trials for cancer drugs actually show benefit in quality of life, according to a study published in JAMA Oncology.

The study found trials that failed to show improved quality of life often reported their quality of life outcomes more favorably. Non–immunotherapy-targeted drugs were found to lead to worse quality of life outcomes more often than did cytotoxic agents. And, while there is an association between quality of life benefit and overall survival, no such association was found with progression-free survival.

“In this study, we evaluated the outcomes of cancer drug trials with regard to patients’ quality of life and found that only a quarter of phase 3 cancer drug trials in the advanced-disease setting demonstrated improved quality of life,” wrote authors who were led by Bishal Gyawali, MD, PhD, of the Cancer Research Institute, Queen’s University, Kingston, Ont.

“Improved quality of life outcomes were associated with improved overall survival but not with improved progression-free survival. Importantly, almost half of the cancer drugs drug trials that showed improved progression-free survival showed no improved overall survival or quality of life (i.e., PFS-only benefit). Some reports included conclusions regarding quality of life (QOL) findings that were not directly supported by the trial data, particularly for inferior or non–statistically significant QOL outcomes, thereby framing the findings in a favorable light or downplaying detrimental effects of the study intervention on QOL. Furthermore, contrary to common perception, inferior QOL outcomes were more common with targeted drugs than cytotoxic drugs. Taken together, these findings have important policy implications,” the authors wrote.

These findings are based on the results of a cohort study of 45 phase 3 research clinical trials of 24,806 patients. Only a small percentage of patients showed QOL benefits. The study found that industry-funded clinical trial reports often framed QOL findings more favorably than was warranted by the data.

The study found improved QOL with experimental agents in 11 of 45 randomized controlled trials (24.4%). Studies that reported improved QOL were more likely to also show improved overall survival as compared with trials in which quality of life was not improved (7 of 11 [64%] versus 10 of 34 [29%] trials). For improved progression-free survival, however, there was no positive association (6 of 11 [55%] trials versus 17 of 34 [50%] trials without improved QOL). Among six trials reporting worsening QOL, three (50%) were trials of targeted drugs. Among 11 trials reporting improved QOL, 6 (55%) were trials of immunotherapy drugs. Among the 34 trials in which QOL was not improved compared with controls, the findings were framed favorably (versus neutrally or negatively) in the abstract or conclusions in 16 (47%), an observation that was statistically significantly associated with industry funding (chi-squared = 6.35; P = .01).

“It is important to clearly understand and communicate the effects of cancer drugs”

To fulfill the obligation to inform patients about proposed treatments, the authors wrote that it is important to clearly understand and communicate the effects of cancer drugs on patient quality of life alongside their effects on overall survival and intermediate end points such as progression-free survival. “Patients with advanced cancer expect treatment to help them live longer or have better lives,” the authors wrote. In that respect, in clinical trials of cancer medicines, overall survival and quality of life are the most important measures. Toxicity profiles and disease progression delays do not reliably predict quality of life, and studies have shown poor correlations between quality of life, overall survival, and progression-free survival. This raises the question of validity of progression-free survival as a surrogate endpoint. “Progression-free survival is meaningless without overall survival or quality of life gains,” Dr. Gyawali said in an interview.

Writing in The Lancet Oncology in March, Dr. Gyawali stated that, because progression free survival “does not directly measure how a patient feels or functions, or how long a patient lives, progression-free survival was not intended to inform clinical practice or establish whether a new therapy provides clinically meaningful benefits for patients. However, over the past 2 decades, it has become the most common primary endpoint in oncology clinical trials. We are deeply worried about how the term survival in this phrase can influence clinical practice and patient choices. We propose replacing the phrase progression-free survival with a less ambiguous term: progression-free interval.”

In JAMA Oncology, Dr. Gyawali aimed to elucidate relationships between QOL, overall survival, and progression-free survival, and to assess, as well, how QOL results are framed, especially in industry-sponsored research. When drug trials they analyzed showed no change in QOL but reported that QOL did not worsen or QOL was maintained rather than stating that QOL did not improve, or if there was downplaying of worse QOL outcomes, the study had favorable interpretation, Dr. Gyawali and associates wrote. The expectation of patients receiving cancer drugs would be improved QOL rather than “not worse” QOL, Dr. Gyawali said.

Regarding the finding that QOL outcomes were described as favorable in 47% of trials with unimproved QOL outcomes, Dr. Gyawali said, “the bias in reporting should be corrected by the reviewers and editors of journals. Also, quality of life reporting should be made mandatory. Without unbiased quality of life information, informed decision making on whether or not to use a certain drug is impossible. Patients and physicians need to know that information. Regulators can demand that this should be mandatory in all trials in noncurative settings.”

He remarked further on the worsening QOL in some targeted drug trials, “People tout chemo-free regimens as automatically having better quality of life, but that doesn’t seem to be the case. Targeted drugs can have a severe impact on quality of life, probably due to prolonged duration of side effects. Quality of life should be measured and reported for all drugs.”

Dr. Gyawali and associates noted the limitation in that several studies with negative QOL results are not published at all or are published after a considerable delay, so the present observations may understate the issues that have been raised.

Dr. Gyawali declared that he received no funding and disclosed no conflicts of interest for this study.

Only a small number of research clinical trials for cancer drugs actually show benefit in quality of life, according to a study published in JAMA Oncology.

The study found trials that failed to show improved quality of life often reported their quality of life outcomes more favorably. Non–immunotherapy-targeted drugs were found to lead to worse quality of life outcomes more often than did cytotoxic agents. And, while there is an association between quality of life benefit and overall survival, no such association was found with progression-free survival.

“In this study, we evaluated the outcomes of cancer drug trials with regard to patients’ quality of life and found that only a quarter of phase 3 cancer drug trials in the advanced-disease setting demonstrated improved quality of life,” wrote authors who were led by Bishal Gyawali, MD, PhD, of the Cancer Research Institute, Queen’s University, Kingston, Ont.

“Improved quality of life outcomes were associated with improved overall survival but not with improved progression-free survival. Importantly, almost half of the cancer drugs drug trials that showed improved progression-free survival showed no improved overall survival or quality of life (i.e., PFS-only benefit). Some reports included conclusions regarding quality of life (QOL) findings that were not directly supported by the trial data, particularly for inferior or non–statistically significant QOL outcomes, thereby framing the findings in a favorable light or downplaying detrimental effects of the study intervention on QOL. Furthermore, contrary to common perception, inferior QOL outcomes were more common with targeted drugs than cytotoxic drugs. Taken together, these findings have important policy implications,” the authors wrote.

These findings are based on the results of a cohort study of 45 phase 3 research clinical trials of 24,806 patients. Only a small percentage of patients showed QOL benefits. The study found that industry-funded clinical trial reports often framed QOL findings more favorably than was warranted by the data.

The study found improved QOL with experimental agents in 11 of 45 randomized controlled trials (24.4%). Studies that reported improved QOL were more likely to also show improved overall survival as compared with trials in which quality of life was not improved (7 of 11 [64%] versus 10 of 34 [29%] trials). For improved progression-free survival, however, there was no positive association (6 of 11 [55%] trials versus 17 of 34 [50%] trials without improved QOL). Among six trials reporting worsening QOL, three (50%) were trials of targeted drugs. Among 11 trials reporting improved QOL, 6 (55%) were trials of immunotherapy drugs. Among the 34 trials in which QOL was not improved compared with controls, the findings were framed favorably (versus neutrally or negatively) in the abstract or conclusions in 16 (47%), an observation that was statistically significantly associated with industry funding (chi-squared = 6.35; P = .01).

“It is important to clearly understand and communicate the effects of cancer drugs”

To fulfill the obligation to inform patients about proposed treatments, the authors wrote that it is important to clearly understand and communicate the effects of cancer drugs on patient quality of life alongside their effects on overall survival and intermediate end points such as progression-free survival. “Patients with advanced cancer expect treatment to help them live longer or have better lives,” the authors wrote. In that respect, in clinical trials of cancer medicines, overall survival and quality of life are the most important measures. Toxicity profiles and disease progression delays do not reliably predict quality of life, and studies have shown poor correlations between quality of life, overall survival, and progression-free survival. This raises the question of validity of progression-free survival as a surrogate endpoint. “Progression-free survival is meaningless without overall survival or quality of life gains,” Dr. Gyawali said in an interview.

Writing in The Lancet Oncology in March, Dr. Gyawali stated that, because progression free survival “does not directly measure how a patient feels or functions, or how long a patient lives, progression-free survival was not intended to inform clinical practice or establish whether a new therapy provides clinically meaningful benefits for patients. However, over the past 2 decades, it has become the most common primary endpoint in oncology clinical trials. We are deeply worried about how the term survival in this phrase can influence clinical practice and patient choices. We propose replacing the phrase progression-free survival with a less ambiguous term: progression-free interval.”

In JAMA Oncology, Dr. Gyawali aimed to elucidate relationships between QOL, overall survival, and progression-free survival, and to assess, as well, how QOL results are framed, especially in industry-sponsored research. When drug trials they analyzed showed no change in QOL but reported that QOL did not worsen or QOL was maintained rather than stating that QOL did not improve, or if there was downplaying of worse QOL outcomes, the study had favorable interpretation, Dr. Gyawali and associates wrote. The expectation of patients receiving cancer drugs would be improved QOL rather than “not worse” QOL, Dr. Gyawali said.

Regarding the finding that QOL outcomes were described as favorable in 47% of trials with unimproved QOL outcomes, Dr. Gyawali said, “the bias in reporting should be corrected by the reviewers and editors of journals. Also, quality of life reporting should be made mandatory. Without unbiased quality of life information, informed decision making on whether or not to use a certain drug is impossible. Patients and physicians need to know that information. Regulators can demand that this should be mandatory in all trials in noncurative settings.”

He remarked further on the worsening QOL in some targeted drug trials, “People tout chemo-free regimens as automatically having better quality of life, but that doesn’t seem to be the case. Targeted drugs can have a severe impact on quality of life, probably due to prolonged duration of side effects. Quality of life should be measured and reported for all drugs.”

Dr. Gyawali and associates noted the limitation in that several studies with negative QOL results are not published at all or are published after a considerable delay, so the present observations may understate the issues that have been raised.

Dr. Gyawali declared that he received no funding and disclosed no conflicts of interest for this study.

The clinical benefit of fulvestrant as a second-line treatment after tumor progression with CDK4/6i-based therapy has been discouraging, highlighting an unmet need for a better SERD in this space.¹ Multiple oral SERD are currently in trials. The EMERALD trial is a phase 3 study that randomly assigned 477 patients with ER+/HER2- mBC in a 1:1 ratio to elacestrant, an oral SERD, vs standard of care (SOC) endocrine therapy (ET). Enrolled patients had received one to two prior ET and one or less chemotherapy treatments in the metastatic disease settings. All patients had prior treatment with a CDK4/6i. Fulvestrant-naive patients were required to have fulvestrant as the SOC ET. In contrast, patients previously treated with fulvestrant received an AI, the selection of which was based on prior AI therapy. Primary endpoints were progression-free survival (PFS) in all patients and in patients with detectable ESR1 mutation. The median PFS in the elacestrant arm was 2.8 months vs 1.9 months in the control arm [hazard ratio (HR) 0.70; 95% CI 0.55-0.88; P = .002]. The 6-month PFS was 34% vs 20% in all patients and 41% vs 19% in patients with detectable ESR1 mutation, favoring the elacestrant arm. In the subgroup analysis among patients who received fulvestrant in the control arm, the 6-month PFS was 34% vs 21% in all patients and 41% vs 19% in patients with ESR1 mutation. Grade 3 or 4 adverse events developed in 27% patients in the elacestrant arm compared with 20% in the SOC arm. More patients in the elacestrant arm developed nausea, vomiting, and liver function abnormalities compared with patients in the SOC arm.

This is the first phase 3 trial demonstrating statistically significant prolongation of PFS associated with an oral SERD compared with SOC ET in patients with ER+/HER2- mBC who had prior treatment with a CDK4/6i. A new drug application has been submitted to the US Food and Drug Administration based on this data. If approved, elacestrant may be favored over fulvestrant as the standard ET for ER+/HER2- mBC after progression on a CDK4/6i-based therapy.

Patients with breast cancer brain metastasis (BrM) have a poor prognosis. Systemic therapies with good central nervous system (CNS) permeability and strong activity against BrM are much needed. An exploratory subset of the phase 3 BEACON trial demonstrated improvement in overall survival (OS) with etirinotecan pegol, a long-acting polymer conjugate of irinotecan, compared with physicians' choice chemotherapy in patients with mBC with treated and stable BrMs.²

Based on this data, a large phase 3 study (the ATTAIN study) was conducted. Patients with mBC with treated and stable BrM (n = 178) were randomly assigned to receive etirinotecan pegol vs physicians' choice of chemotherapy (eribulin, ixabepilone, vinorelbine, gemcitabine, paclitaxel, docetaxel, or nab-paclitaxel). The primary endpoint of OS was similar in both groups (etirinotecan pegol 7.8 months; chemotherapy 7.5 months; HR 0.90; 95% CI 0.61-1.33; P = .60). Median PFS for mBC with CNS metastases (etirinotecan pegol vs chemotherapy) were 3.9 vs 3.3 months (HR 0.59; 95% CI 0.33-1.05; P = .07) and for non-CNS metastases were 2.8 vs 1.9 months (HR 0.72; 95% CI 0.45-1.16; P = .18). Adverse events were grade 3 or 4 in 57% patients receiving etirinotecan pegol compared with 64% receiving SOC chemotherapy.

This trial failed to meet its primary endpoint. The possible explanations proposed by the investigators are a protocol amendment that reduced the power of the trial to 80%, some key differences in the patient population in the ATTAIN trial compared with the BEACON trial, and the possibility of the BEACON trial exploratory analysis result being a false positive. The OS of around 7 months highlights the unmet need for better systemic therapy for patients with BrM breast cancer, especially those with HER2- breast cancer.

Additional References

1. Lindeman GJ, Fernando TM, Bowen R, et al. VERONICA: Randomized phase II study of fulvestrant and venetoclax in ER-positive metastatic breast cancer post-CDK4/6 inhibitors – Efficacy, safety, and biomarker results. Clin Cancer Res. 2022 (June 21). Doi: 10.1158/1078-0432.CCR-21-3811
    
2. Cortés J, Rugo HS, Awada A, et al. Prolonged survival in patients with breast cancer and a history of brain metastases: Results of a preplanned subgroup analysis from the randomized phase III BEACON trial. Breast Cancer Res Treat. 2017;165:329-341. Doi: 10.1007/s10549-017-4304-7

The clinical benefit of fulvestrant as a second-line treatment after tumor progression with CDK4/6i-based therapy has been discouraging, highlighting an unmet need for a better SERD in this space.¹ Multiple oral SERD are currently in trials. The EMERALD trial is a phase 3 study that randomly assigned 477 patients with ER+/HER2- mBC in a 1:1 ratio to elacestrant, an oral SERD, vs standard of care (SOC) endocrine therapy (ET). Enrolled patients had received one to two prior ET and one or less chemotherapy treatments in the metastatic disease settings. All patients had prior treatment with a CDK4/6i. Fulvestrant-naive patients were required to have fulvestrant as the SOC ET. In contrast, patients previously treated with fulvestrant received an AI, the selection of which was based on prior AI therapy. Primary endpoints were progression-free survival (PFS) in all patients and in patients with detectable ESR1 mutation. The median PFS in the elacestrant arm was 2.8 months vs 1.9 months in the control arm [hazard ratio (HR) 0.70; 95% CI 0.55-0.88; P = .002]. The 6-month PFS was 34% vs 20% in all patients and 41% vs 19% in patients with detectable ESR1 mutation, favoring the elacestrant arm. In the subgroup analysis among patients who received fulvestrant in the control arm, the 6-month PFS was 34% vs 21% in all patients and 41% vs 19% in patients with ESR1 mutation. Grade 3 or 4 adverse events developed in 27% patients in the elacestrant arm compared with 20% in the SOC arm. More patients in the elacestrant arm developed nausea, vomiting, and liver function abnormalities compared with patients in the SOC arm.

This is the first phase 3 trial demonstrating statistically significant prolongation of PFS associated with an oral SERD compared with SOC ET in patients with ER+/HER2- mBC who had prior treatment with a CDK4/6i. A new drug application has been submitted to the US Food and Drug Administration based on this data. If approved, elacestrant may be favored over fulvestrant as the standard ET for ER+/HER2- mBC after progression on a CDK4/6i-based therapy.

Patients with breast cancer brain metastasis (BrM) have a poor prognosis. Systemic therapies with good central nervous system (CNS) permeability and strong activity against BrM are much needed. An exploratory subset of the phase 3 BEACON trial demonstrated improvement in overall survival (OS) with etirinotecan pegol, a long-acting polymer conjugate of irinotecan, compared with physicians' choice chemotherapy in patients with mBC with treated and stable BrMs.²

Based on this data, a large phase 3 study (the ATTAIN study) was conducted. Patients with mBC with treated and stable BrM (n = 178) were randomly assigned to receive etirinotecan pegol vs physicians' choice of chemotherapy (eribulin, ixabepilone, vinorelbine, gemcitabine, paclitaxel, docetaxel, or nab-paclitaxel). The primary endpoint of OS was similar in both groups (etirinotecan pegol 7.8 months; chemotherapy 7.5 months; HR 0.90; 95% CI 0.61-1.33; P = .60). Median PFS for mBC with CNS metastases (etirinotecan pegol vs chemotherapy) were 3.9 vs 3.3 months (HR 0.59; 95% CI 0.33-1.05; P = .07) and for non-CNS metastases were 2.8 vs 1.9 months (HR 0.72; 95% CI 0.45-1.16; P = .18). Adverse events were grade 3 or 4 in 57% patients receiving etirinotecan pegol compared with 64% receiving SOC chemotherapy.

This trial failed to meet its primary endpoint. The possible explanations proposed by the investigators are a protocol amendment that reduced the power of the trial to 80%, some key differences in the patient population in the ATTAIN trial compared with the BEACON trial, and the possibility of the BEACON trial exploratory analysis result being a false positive. The OS of around 7 months highlights the unmet need for better systemic therapy for patients with BrM breast cancer, especially those with HER2- breast cancer.

Additional References

1. Lindeman GJ, Fernando TM, Bowen R, et al. VERONICA: Randomized phase II study of fulvestrant and venetoclax in ER-positive metastatic breast cancer post-CDK4/6 inhibitors – Efficacy, safety, and biomarker results. Clin Cancer Res. 2022 (June 21). Doi: 10.1158/1078-0432.CCR-21-3811
    
2. Cortés J, Rugo HS, Awada A, et al. Prolonged survival in patients with breast cancer and a history of brain metastases: Results of a preplanned subgroup analysis from the randomized phase III BEACON trial. Breast Cancer Res Treat. 2017;165:329-341. Doi: 10.1007/s10549-017-4304-7

The clinical benefit of fulvestrant as a second-line treatment after tumor progression with CDK4/6i-based therapy has been discouraging, highlighting an unmet need for a better SERD in this space.¹ Multiple oral SERD are currently in trials. The EMERALD trial is a phase 3 study that randomly assigned 477 patients with ER+/HER2- mBC in a 1:1 ratio to elacestrant, an oral SERD, vs standard of care (SOC) endocrine therapy (ET). Enrolled patients had received one to two prior ET and one or less chemotherapy treatments in the metastatic disease settings. All patients had prior treatment with a CDK4/6i. Fulvestrant-naive patients were required to have fulvestrant as the SOC ET. In contrast, patients previously treated with fulvestrant received an AI, the selection of which was based on prior AI therapy. Primary endpoints were progression-free survival (PFS) in all patients and in patients with detectable ESR1 mutation. The median PFS in the elacestrant arm was 2.8 months vs 1.9 months in the control arm [hazard ratio (HR) 0.70; 95% CI 0.55-0.88; P = .002]. The 6-month PFS was 34% vs 20% in all patients and 41% vs 19% in patients with detectable ESR1 mutation, favoring the elacestrant arm. In the subgroup analysis among patients who received fulvestrant in the control arm, the 6-month PFS was 34% vs 21% in all patients and 41% vs 19% in patients with ESR1 mutation. Grade 3 or 4 adverse events developed in 27% patients in the elacestrant arm compared with 20% in the SOC arm. More patients in the elacestrant arm developed nausea, vomiting, and liver function abnormalities compared with patients in the SOC arm.

This is the first phase 3 trial demonstrating statistically significant prolongation of PFS associated with an oral SERD compared with SOC ET in patients with ER+/HER2- mBC who had prior treatment with a CDK4/6i. A new drug application has been submitted to the US Food and Drug Administration based on this data. If approved, elacestrant may be favored over fulvestrant as the standard ET for ER+/HER2- mBC after progression on a CDK4/6i-based therapy.

Patients with breast cancer brain metastasis (BrM) have a poor prognosis. Systemic therapies with good central nervous system (CNS) permeability and strong activity against BrM are much needed. An exploratory subset of the phase 3 BEACON trial demonstrated improvement in overall survival (OS) with etirinotecan pegol, a long-acting polymer conjugate of irinotecan, compared with physicians' choice chemotherapy in patients with mBC with treated and stable BrMs.²

Based on this data, a large phase 3 study (the ATTAIN study) was conducted. Patients with mBC with treated and stable BrM (n = 178) were randomly assigned to receive etirinotecan pegol vs physicians' choice of chemotherapy (eribulin, ixabepilone, vinorelbine, gemcitabine, paclitaxel, docetaxel, or nab-paclitaxel). The primary endpoint of OS was similar in both groups (etirinotecan pegol 7.8 months; chemotherapy 7.5 months; HR 0.90; 95% CI 0.61-1.33; P = .60). Median PFS for mBC with CNS metastases (etirinotecan pegol vs chemotherapy) were 3.9 vs 3.3 months (HR 0.59; 95% CI 0.33-1.05; P = .07) and for non-CNS metastases were 2.8 vs 1.9 months (HR 0.72; 95% CI 0.45-1.16; P = .18). Adverse events were grade 3 or 4 in 57% patients receiving etirinotecan pegol compared with 64% receiving SOC chemotherapy.

This trial failed to meet its primary endpoint. The possible explanations proposed by the investigators are a protocol amendment that reduced the power of the trial to 80%, some key differences in the patient population in the ATTAIN trial compared with the BEACON trial, and the possibility of the BEACON trial exploratory analysis result being a false positive. The OS of around 7 months highlights the unmet need for better systemic therapy for patients with BrM breast cancer, especially those with HER2- breast cancer.

Additional References

1. Lindeman GJ, Fernando TM, Bowen R, et al. VERONICA: Randomized phase II study of fulvestrant and venetoclax in ER-positive metastatic breast cancer post-CDK4/6 inhibitors – Efficacy, safety, and biomarker results. Clin Cancer Res. 2022 (June 21). Doi: 10.1158/1078-0432.CCR-21-3811
    
2. Cortés J, Rugo HS, Awada A, et al. Prolonged survival in patients with breast cancer and a history of brain metastases: Results of a preplanned subgroup analysis from the randomized phase III BEACON trial. Breast Cancer Res Treat. 2017;165:329-341. Doi: 10.1007/s10549-017-4304-7

A large Danish study has found that cancer increases the risk of new-onset type 2 diabetes, especially certain types of cancer, most notably pancreatic malignancies.

“Our study demonstrates that there is an elevated risk of developing diabetes if a person is affected by lung, pancreatic, breast, brain, urinary tract, or uterine cancers,” said Lykke Sylow, PhD, associate professor in the Molecular Metabolism in Cancer and Ageing Group at the University of Copenhagen, in a statement.

“It is great to see such a large, well-designed study confirm the findings of previous smaller studies and observations,” said Elias S. Siraj, MD, the David L. Bernd Distinguished Chair for EVMS-Sentara Cardiovascular Diabetes Program at Eastern Virginia Medical School in Norfolk, when asked for comment by this news organization. Dr. Siraj also noted that “in clinical care we do observe that many patients develop diabetes after being diagnosed with cancer although one needs a well-designed study to confirm that observation.”
 

Diabetes risk highest with pancreatic cancer

Type 2 diabetes at the time of cancer diagnosis is known to increase cancer-specific and all-cause mortality, but not much is known about whether cancer is a risk factor for type 2 diabetes, the researchers state in their study, published in Diabetes Care.

Dr. Sylow and colleagues from the Steno Diabetes Center Copenhagen, Rigshospitalet, analyzed a database consisting of 112 million blood samples from 1.3 million Danes from 2000 to 2015. They looked at cancer cases with an incidence of more than 1,000 and excluded individuals with diabetes prior to cancer diagnosis. 

They found an increased risk of new-onset type 2 diabetes for all cancers (hazard ratio, 1.09; 95% confidence interval, 1.03-1.14). For pancreatic cancer, the hazard ratio rose to 5.0 (95% CI, 3.62-6.90), for brain and nervous system cancers the hazard ratio was 1.54 (95% CI, 1.22-1.95), and for uterine cancer the hazard ratio was 1.41 (95% CI, 1.10-1.84).

The link with pancreatic cancer was not surprising, said Dr. Sylow.

Dr. Siraj agreed, noting that a few studies have shown a strong association. “It has also been observed for years that many patients with pancreatic cancer may present with new-onset diabetes,” he said. “The mechanism is not clearly understood but could include a direct damage of the beta cells by the pancreatic cancer or could be due to a paraneoplastic secretion of special factors by the cancer that can affect beta-cell function or insulin resistance,” said Dr. Siraj, who is also professor and chief of endocrinology and director of the Strelitz Diabetes Center at Eastern Virginia Medical School.

The higher diabetes risk associated with brain and nervous system cancers has not been previously described and is “an intriguing finding,” he said.

In their statement, the Danish investigators said there is nothing in their research to suggest why some cancers are associated with a higher risk of new-onset type 2 diabetes, but they offered some theories, including that chemotherapeutics and perhaps the cancer, itself, may contribute.

“We know that cancer cells are able to secrete substances that can affect organs and possibility contribute to an increased incidence of diabetes,” said Dr. Sylow in the statement.
 

Increased mortality risk in those with cancer and type 2 diabetes

Dr. Sylow and colleagues also analyzed mortality in a subset of 28,308 patients with cancer who were still alive 2 years after diagnosis. They documented a 21% higher rate of all-cause mortality in these patients compared with those who did not have new-onset type 2 diabetes.

“We do not know enough about the patients who were diagnosed with type 2 diabetes, but we think our findings illustrate a potential new area of intervention in the cancer clinic,” Dr. Sylow said. However, the findings still require replication before drawing any definite conclusions, she added.

Christoffer Johansen, MD, PhD, DMSc, of Rigshospitalet, said in the statement that it might be prudent to screen patients with lung, breast, brain, uterine, and urinary tract cancers for diabetes. “Early intervention could have an impact on certain cancer patients,” said Dr. Johansen.

Dr. Siraj said he would urge oncologists to routinely monitor blood glucose levels during cancer treatment and as part of long-term surveillance, and to consider the potential risk of new-onset diabetes when choosing a cancer therapy. If diabetes is diagnosed, clinicians should be sure that it’s managed by a primary care physician or endocrinologist, “as proper treatment may contribute to better outcomes of the cancer,” said Dr. Siraj.

Endocrinologists should consider the possibility of pancreatic cancer if someone with few risk factors for type 2 diabetes has a new-onset diagnosis, he said. And they should aim for good glycemic control in those with new-onset type 2 diabetes, as it may lead to better cancer outcomes, he said.

Dr. Sylow has reported grant support from the Novo Nordisk Foundation and Independent Research Fund Denmark. Dr. Johansen has reported serving as an educator for Janssen and Pfizer. Coauthors have received grant support from the Danish Cancer Society and served as consultants, on advisory boards, or as educators for Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Incyte, GSK, MSD, Mundipharma, Novartis, Novo Nordisk, Pfizer, and Sanofi.

A version of this article first appeared on Medscape.com.

A large Danish study has found that cancer increases the risk of new-onset type 2 diabetes, especially certain types of cancer, most notably pancreatic malignancies.

“Our study demonstrates that there is an elevated risk of developing diabetes if a person is affected by lung, pancreatic, breast, brain, urinary tract, or uterine cancers,” said Lykke Sylow, PhD, associate professor in the Molecular Metabolism in Cancer and Ageing Group at the University of Copenhagen, in a statement.

“It is great to see such a large, well-designed study confirm the findings of previous smaller studies and observations,” said Elias S. Siraj, MD, the David L. Bernd Distinguished Chair for EVMS-Sentara Cardiovascular Diabetes Program at Eastern Virginia Medical School in Norfolk, when asked for comment by this news organization. Dr. Siraj also noted that “in clinical care we do observe that many patients develop diabetes after being diagnosed with cancer although one needs a well-designed study to confirm that observation.”
 

Diabetes risk highest with pancreatic cancer

Type 2 diabetes at the time of cancer diagnosis is known to increase cancer-specific and all-cause mortality, but not much is known about whether cancer is a risk factor for type 2 diabetes, the researchers state in their study, published in Diabetes Care.

Dr. Sylow and colleagues from the Steno Diabetes Center Copenhagen, Rigshospitalet, analyzed a database consisting of 112 million blood samples from 1.3 million Danes from 2000 to 2015. They looked at cancer cases with an incidence of more than 1,000 and excluded individuals with diabetes prior to cancer diagnosis. 

They found an increased risk of new-onset type 2 diabetes for all cancers (hazard ratio, 1.09; 95% confidence interval, 1.03-1.14). For pancreatic cancer, the hazard ratio rose to 5.0 (95% CI, 3.62-6.90), for brain and nervous system cancers the hazard ratio was 1.54 (95% CI, 1.22-1.95), and for uterine cancer the hazard ratio was 1.41 (95% CI, 1.10-1.84).

The link with pancreatic cancer was not surprising, said Dr. Sylow.

Dr. Siraj agreed, noting that a few studies have shown a strong association. “It has also been observed for years that many patients with pancreatic cancer may present with new-onset diabetes,” he said. “The mechanism is not clearly understood but could include a direct damage of the beta cells by the pancreatic cancer or could be due to a paraneoplastic secretion of special factors by the cancer that can affect beta-cell function or insulin resistance,” said Dr. Siraj, who is also professor and chief of endocrinology and director of the Strelitz Diabetes Center at Eastern Virginia Medical School.

The higher diabetes risk associated with brain and nervous system cancers has not been previously described and is “an intriguing finding,” he said.

In their statement, the Danish investigators said there is nothing in their research to suggest why some cancers are associated with a higher risk of new-onset type 2 diabetes, but they offered some theories, including that chemotherapeutics and perhaps the cancer, itself, may contribute.

“We know that cancer cells are able to secrete substances that can affect organs and possibility contribute to an increased incidence of diabetes,” said Dr. Sylow in the statement.
 

Increased mortality risk in those with cancer and type 2 diabetes

Dr. Sylow and colleagues also analyzed mortality in a subset of 28,308 patients with cancer who were still alive 2 years after diagnosis. They documented a 21% higher rate of all-cause mortality in these patients compared with those who did not have new-onset type 2 diabetes.

“We do not know enough about the patients who were diagnosed with type 2 diabetes, but we think our findings illustrate a potential new area of intervention in the cancer clinic,” Dr. Sylow said. However, the findings still require replication before drawing any definite conclusions, she added.

Christoffer Johansen, MD, PhD, DMSc, of Rigshospitalet, said in the statement that it might be prudent to screen patients with lung, breast, brain, uterine, and urinary tract cancers for diabetes. “Early intervention could have an impact on certain cancer patients,” said Dr. Johansen.

Dr. Siraj said he would urge oncologists to routinely monitor blood glucose levels during cancer treatment and as part of long-term surveillance, and to consider the potential risk of new-onset diabetes when choosing a cancer therapy. If diabetes is diagnosed, clinicians should be sure that it’s managed by a primary care physician or endocrinologist, “as proper treatment may contribute to better outcomes of the cancer,” said Dr. Siraj.

Endocrinologists should consider the possibility of pancreatic cancer if someone with few risk factors for type 2 diabetes has a new-onset diagnosis, he said. And they should aim for good glycemic control in those with new-onset type 2 diabetes, as it may lead to better cancer outcomes, he said.

Dr. Sylow has reported grant support from the Novo Nordisk Foundation and Independent Research Fund Denmark. Dr. Johansen has reported serving as an educator for Janssen and Pfizer. Coauthors have received grant support from the Danish Cancer Society and served as consultants, on advisory boards, or as educators for Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Incyte, GSK, MSD, Mundipharma, Novartis, Novo Nordisk, Pfizer, and Sanofi.

A version of this article first appeared on Medscape.com.

A large Danish study has found that cancer increases the risk of new-onset type 2 diabetes, especially certain types of cancer, most notably pancreatic malignancies.

“Our study demonstrates that there is an elevated risk of developing diabetes if a person is affected by lung, pancreatic, breast, brain, urinary tract, or uterine cancers,” said Lykke Sylow, PhD, associate professor in the Molecular Metabolism in Cancer and Ageing Group at the University of Copenhagen, in a statement.

“It is great to see such a large, well-designed study confirm the findings of previous smaller studies and observations,” said Elias S. Siraj, MD, the David L. Bernd Distinguished Chair for EVMS-Sentara Cardiovascular Diabetes Program at Eastern Virginia Medical School in Norfolk, when asked for comment by this news organization. Dr. Siraj also noted that “in clinical care we do observe that many patients develop diabetes after being diagnosed with cancer although one needs a well-designed study to confirm that observation.”
 

Diabetes risk highest with pancreatic cancer

Type 2 diabetes at the time of cancer diagnosis is known to increase cancer-specific and all-cause mortality, but not much is known about whether cancer is a risk factor for type 2 diabetes, the researchers state in their study, published in Diabetes Care.

Dr. Sylow and colleagues from the Steno Diabetes Center Copenhagen, Rigshospitalet, analyzed a database consisting of 112 million blood samples from 1.3 million Danes from 2000 to 2015. They looked at cancer cases with an incidence of more than 1,000 and excluded individuals with diabetes prior to cancer diagnosis. 

They found an increased risk of new-onset type 2 diabetes for all cancers (hazard ratio, 1.09; 95% confidence interval, 1.03-1.14). For pancreatic cancer, the hazard ratio rose to 5.0 (95% CI, 3.62-6.90), for brain and nervous system cancers the hazard ratio was 1.54 (95% CI, 1.22-1.95), and for uterine cancer the hazard ratio was 1.41 (95% CI, 1.10-1.84).

The link with pancreatic cancer was not surprising, said Dr. Sylow.

Dr. Siraj agreed, noting that a few studies have shown a strong association. “It has also been observed for years that many patients with pancreatic cancer may present with new-onset diabetes,” he said. “The mechanism is not clearly understood but could include a direct damage of the beta cells by the pancreatic cancer or could be due to a paraneoplastic secretion of special factors by the cancer that can affect beta-cell function or insulin resistance,” said Dr. Siraj, who is also professor and chief of endocrinology and director of the Strelitz Diabetes Center at Eastern Virginia Medical School.

The higher diabetes risk associated with brain and nervous system cancers has not been previously described and is “an intriguing finding,” he said.

In their statement, the Danish investigators said there is nothing in their research to suggest why some cancers are associated with a higher risk of new-onset type 2 diabetes, but they offered some theories, including that chemotherapeutics and perhaps the cancer, itself, may contribute.

“We know that cancer cells are able to secrete substances that can affect organs and possibility contribute to an increased incidence of diabetes,” said Dr. Sylow in the statement.
 

Increased mortality risk in those with cancer and type 2 diabetes

Dr. Sylow and colleagues also analyzed mortality in a subset of 28,308 patients with cancer who were still alive 2 years after diagnosis. They documented a 21% higher rate of all-cause mortality in these patients compared with those who did not have new-onset type 2 diabetes.

“We do not know enough about the patients who were diagnosed with type 2 diabetes, but we think our findings illustrate a potential new area of intervention in the cancer clinic,” Dr. Sylow said. However, the findings still require replication before drawing any definite conclusions, she added.

Christoffer Johansen, MD, PhD, DMSc, of Rigshospitalet, said in the statement that it might be prudent to screen patients with lung, breast, brain, uterine, and urinary tract cancers for diabetes. “Early intervention could have an impact on certain cancer patients,” said Dr. Johansen.

Dr. Siraj said he would urge oncologists to routinely monitor blood glucose levels during cancer treatment and as part of long-term surveillance, and to consider the potential risk of new-onset diabetes when choosing a cancer therapy. If diabetes is diagnosed, clinicians should be sure that it’s managed by a primary care physician or endocrinologist, “as proper treatment may contribute to better outcomes of the cancer,” said Dr. Siraj.

Endocrinologists should consider the possibility of pancreatic cancer if someone with few risk factors for type 2 diabetes has a new-onset diagnosis, he said. And they should aim for good glycemic control in those with new-onset type 2 diabetes, as it may lead to better cancer outcomes, he said.

Dr. Sylow has reported grant support from the Novo Nordisk Foundation and Independent Research Fund Denmark. Dr. Johansen has reported serving as an educator for Janssen and Pfizer. Coauthors have received grant support from the Danish Cancer Society and served as consultants, on advisory boards, or as educators for Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Incyte, GSK, MSD, Mundipharma, Novartis, Novo Nordisk, Pfizer, and Sanofi.

A version of this article first appeared on Medscape.com.

Dr Ann Partridge from the Dana-Farber Cancer Institute in Boston, Massachusetts, highlights important new data in early breast cancer presented at American Society of Clinical Oncology (ASCO) 2022. 

Dr Partridge begins with promising results from the NeoSTAR study, which looked at the use of the novel antibody-drug conjugate (ADC) sacituzumab govitecan in the neoadjuvant setting. This is the first trial of an ADC in patients with triple-negative breast cancer (TNBC) and demonstrated single-agent efficacy in localized TNBC. 

Next, Dr Partridge discusses the 8-year post-trial follow-up of the ASTRRA study, which randomly assigned patients to 5 years of tamoxifen or 5 years of tamoxifen plus 2 years of ovarian suppression. The findings demonstrated consistent survival advantage and suggest that adding ovarian function suppression to tamoxifen should be considered for those who remain in a premenopausal state or resume ovarian function after chemotherapy. 

Looking to potential new biomarkers for risk recurrence, Dr Partridge reports on provocative data from the CHiRP study. The investigators looked at the use of circulating tumor DNA to identify minimal residual disease and predict clinical outcomes in high-risk, early-stage HR+ breast cancer. Although additional research is needed, Dr Partridge is encouraged that in the near future, the use of circulating DNA technology will help guide therapeutic decisions in early breast cancer. 

--

Ann H. Partridge, MD, MPH, Professor of Medicine; Vice Chair of Medical Oncology, Department of Breast Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 

Ann H. Partridge, MD, MPH, has disclosed no relevant financial relationships. 

Dr Ann Partridge from the Dana-Farber Cancer Institute in Boston, Massachusetts, highlights important new data in early breast cancer presented at American Society of Clinical Oncology (ASCO) 2022. 

Dr Partridge begins with promising results from the NeoSTAR study, which looked at the use of the novel antibody-drug conjugate (ADC) sacituzumab govitecan in the neoadjuvant setting. This is the first trial of an ADC in patients with triple-negative breast cancer (TNBC) and demonstrated single-agent efficacy in localized TNBC. 

Next, Dr Partridge discusses the 8-year post-trial follow-up of the ASTRRA study, which randomly assigned patients to 5 years of tamoxifen or 5 years of tamoxifen plus 2 years of ovarian suppression. The findings demonstrated consistent survival advantage and suggest that adding ovarian function suppression to tamoxifen should be considered for those who remain in a premenopausal state or resume ovarian function after chemotherapy. 

Looking to potential new biomarkers for risk recurrence, Dr Partridge reports on provocative data from the CHiRP study. The investigators looked at the use of circulating tumor DNA to identify minimal residual disease and predict clinical outcomes in high-risk, early-stage HR+ breast cancer. Although additional research is needed, Dr Partridge is encouraged that in the near future, the use of circulating DNA technology will help guide therapeutic decisions in early breast cancer. 

--

Ann H. Partridge, MD, MPH, Professor of Medicine; Vice Chair of Medical Oncology, Department of Breast Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 

Ann H. Partridge, MD, MPH, has disclosed no relevant financial relationships. 

Dr Ann Partridge from the Dana-Farber Cancer Institute in Boston, Massachusetts, highlights important new data in early breast cancer presented at American Society of Clinical Oncology (ASCO) 2022. 

Dr Partridge begins with promising results from the NeoSTAR study, which looked at the use of the novel antibody-drug conjugate (ADC) sacituzumab govitecan in the neoadjuvant setting. This is the first trial of an ADC in patients with triple-negative breast cancer (TNBC) and demonstrated single-agent efficacy in localized TNBC. 

Next, Dr Partridge discusses the 8-year post-trial follow-up of the ASTRRA study, which randomly assigned patients to 5 years of tamoxifen or 5 years of tamoxifen plus 2 years of ovarian suppression. The findings demonstrated consistent survival advantage and suggest that adding ovarian function suppression to tamoxifen should be considered for those who remain in a premenopausal state or resume ovarian function after chemotherapy. 

Looking to potential new biomarkers for risk recurrence, Dr Partridge reports on provocative data from the CHiRP study. The investigators looked at the use of circulating tumor DNA to identify minimal residual disease and predict clinical outcomes in high-risk, early-stage HR+ breast cancer. Although additional research is needed, Dr Partridge is encouraged that in the near future, the use of circulating DNA technology will help guide therapeutic decisions in early breast cancer. 

--

Ann H. Partridge, MD, MPH, Professor of Medicine; Vice Chair of Medical Oncology, Department of Breast Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 

Ann H. Partridge, MD, MPH, has disclosed no relevant financial relationships. 

Dr Harold J. Burstein, from the Dana-Farber Cancer Institute in Boston, Massachusetts, reports on important abstracts in the management of metastatic breast cancer from the 2022 American Society of Clinical Oncology (ASCO) annual meeting. 

Dr Burstein first highlights results from the NRG-BR002 trial, a randomized phase 2 study comparing standard therapy vs standard therapy in combination with focal stereotactic radiation treatment for oligometastatic disease in up to four sites. Investigators reported no impact on progression-free or overall survival.  

Exciting results from the DESTINY-Breast04 trial were a "showstopper," according to Dr Burstein. Investigators reported prolonged progression-free survival and overall survival in patients with HER2-low unresectable and/or metastatic disease with the use of the antibody-drug conjugate trastuzumab deruxtecan compared with physicians' choice of standard single-agent chemotherapy, advancing a new treatment option for the large subset of patients with HER2-low disease. 

Next, Dr Burstein discusses results from the TROPiCS-02 trial, which compared another antibody-drug conjugate, sacituzumab govitecan, with standard chemotherapy in patients with ER+/HER- breast cancer. A statistically significant benefit was reported, although the progression-free survival at just 6 weeks was relatively modest. 

Finally, Dr Burstein reports on interesting data from the MAINTAIN study, a phase 2 randomized trial looking at maintenance CDK4/6 inhibition after progression on initial treatment. Results suggest that switching endocrine therapy and continuing treatment with CDK4/6 inhibitor ribociclib beyond progression may be of clinical value to patients.

--

Harold J. Burstein, MD, PhD, Professor, Department of Medicine, Harvard Medical School; Medical Oncologist, Dana-Farber Cancer Institute, Brigham & Women's Hospital, Boston, Massachusetts 

Harold J. Burstein, MD, PhD, has disclosed no relevant financial relationships. 

Dr Harold J. Burstein, from the Dana-Farber Cancer Institute in Boston, Massachusetts, reports on important abstracts in the management of metastatic breast cancer from the 2022 American Society of Clinical Oncology (ASCO) annual meeting. 

Dr Burstein first highlights results from the NRG-BR002 trial, a randomized phase 2 study comparing standard therapy vs standard therapy in combination with focal stereotactic radiation treatment for oligometastatic disease in up to four sites. Investigators reported no impact on progression-free or overall survival.  

Exciting results from the DESTINY-Breast04 trial were a "showstopper," according to Dr Burstein. Investigators reported prolonged progression-free survival and overall survival in patients with HER2-low unresectable and/or metastatic disease with the use of the antibody-drug conjugate trastuzumab deruxtecan compared with physicians' choice of standard single-agent chemotherapy, advancing a new treatment option for the large subset of patients with HER2-low disease. 

Next, Dr Burstein discusses results from the TROPiCS-02 trial, which compared another antibody-drug conjugate, sacituzumab govitecan, with standard chemotherapy in patients with ER+/HER- breast cancer. A statistically significant benefit was reported, although the progression-free survival at just 6 weeks was relatively modest. 

Finally, Dr Burstein reports on interesting data from the MAINTAIN study, a phase 2 randomized trial looking at maintenance CDK4/6 inhibition after progression on initial treatment. Results suggest that switching endocrine therapy and continuing treatment with CDK4/6 inhibitor ribociclib beyond progression may be of clinical value to patients.

--

Harold J. Burstein, MD, PhD, Professor, Department of Medicine, Harvard Medical School; Medical Oncologist, Dana-Farber Cancer Institute, Brigham & Women's Hospital, Boston, Massachusetts 

Harold J. Burstein, MD, PhD, has disclosed no relevant financial relationships. 

Dr Harold J. Burstein, from the Dana-Farber Cancer Institute in Boston, Massachusetts, reports on important abstracts in the management of metastatic breast cancer from the 2022 American Society of Clinical Oncology (ASCO) annual meeting. 

Dr Burstein first highlights results from the NRG-BR002 trial, a randomized phase 2 study comparing standard therapy vs standard therapy in combination with focal stereotactic radiation treatment for oligometastatic disease in up to four sites. Investigators reported no impact on progression-free or overall survival.  

Exciting results from the DESTINY-Breast04 trial were a "showstopper," according to Dr Burstein. Investigators reported prolonged progression-free survival and overall survival in patients with HER2-low unresectable and/or metastatic disease with the use of the antibody-drug conjugate trastuzumab deruxtecan compared with physicians' choice of standard single-agent chemotherapy, advancing a new treatment option for the large subset of patients with HER2-low disease. 

Next, Dr Burstein discusses results from the TROPiCS-02 trial, which compared another antibody-drug conjugate, sacituzumab govitecan, with standard chemotherapy in patients with ER+/HER- breast cancer. A statistically significant benefit was reported, although the progression-free survival at just 6 weeks was relatively modest. 

Finally, Dr Burstein reports on interesting data from the MAINTAIN study, a phase 2 randomized trial looking at maintenance CDK4/6 inhibition after progression on initial treatment. Results suggest that switching endocrine therapy and continuing treatment with CDK4/6 inhibitor ribociclib beyond progression may be of clinical value to patients.

--

Harold J. Burstein, MD, PhD, Professor, Department of Medicine, Harvard Medical School; Medical Oncologist, Dana-Farber Cancer Institute, Brigham & Women's Hospital, Boston, Massachusetts 

Harold J. Burstein, MD, PhD, has disclosed no relevant financial relationships. 

New research shows that the metastatic spread of breast cancer occurs predominantly during sleep, a discovery the investigators called “striking and unexpected.”

“This has not been shown before [and] we were surprised, indeed,” Nicola Aceto, PhD, professor of molecular oncology, Swiss Federal Institute of Technology Zürich, said in an interview.

The findings carry potential implications for the timing of biopsy and treatment of metastasis-prone cancers, the authors said.

The study was published online in Nature. 

Circulating tumor cells (CTCs) are generally believed to shed constantly or following particular events such as surgery or physical activity; however, the processes that regulate tumor cell metastasis and how circadian rhythms may play into tumorigenesis remain unclear.

To better understand these processes, Dr. Aceto and colleagues collected blood samples from 30 women with breast cancer at 4:00 a.m. and 10:00 a.m. – times representing the body’s resting and active phases, respectively.

The researchers observed that more than 78% of all CTCs obtained were from samples taken during the resting phase.

This finding is astounding, Harrison Ball, a PhD candidate, and Sunitha Nagrath, PhD, with the University of Michigan, Ann Arbor, wrote in Nature News & Views .

Dr. Aceto and colleagues also found that CTCs generated at night divide more quickly and therefore have a higher potential to metastasize, compared with those generated during the day, which “are devoid of metastatic ability,” according to the authors, who obtained similar results in a series of mouse models.

The team also observed that key circadian rhythm hormones (such as melatonin, testosterone, and glucocorticoids) regulate CTC generation, and insulin promotes tumor cell proliferation in a time-dependent manner, suggesting a “need for time-controlled approaches for the characterization and treatment of breast cancer,” the authors wrote.
 

Practice changing?

Dr. Ball and Dr. Nagrath said the time-dependent nature of CTC dynamics could very well transform how cancer patients are assessed and treated.

“The data pointing to CTC proliferation and release during the rest phase suggest that doctors might need to become more conscious of when to administer specific treatments,” they wrote.

Both cautioned, however, that large clinical trials would be needed before any consideration of circadian rhythms is incorporated into standard practice. It’s also unclear whether these results in breast cancer hold true for other tumor types.

Mariana G. Figueiro, PhD, who was not involved in the research, agreed that, if studies confirm more metastatic spread at night, “there is an opportunity to treat patients at strategic times.”

Dr. Figueiro, of the Icahn School of Medicine at Mount Sinai, New York, also saw a potential impact on the timing of blood draws. “I think tightening up on how people do biopsies and bloodwork based on circadian time is important.”

Marleen Meyers, MD, agreed that these findings could have many clinical implications.

“The most obvious is that the time of day [that] treatment is administered may influence efficacy,” said Dr. Meyers, clinical professor of medicine at New York University Langone’s Perlmutter Cancer Center.

But, Dr. Meyers noted, the benefits of treating someone at night would need to be weighed against the downsides of interrupting a person’s normal sleep-wake cycle. “If this finding is clinically important it will be a challenge incorporating this into clinical care,” she said.

The study had no funding reported. Dr. Aceto is a cofounder and member of the board of PAGE Therapeutics, listed as an inventor in patent applications related to circulating tumor cells, a paid consultant for several companies, and a Novartis shareholder. One coauthor is a cofounder of PAGE Therapeutics. All other authors declare no competing interests. Dr. Meyers and Dr. Figueiro reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

New research shows that the metastatic spread of breast cancer occurs predominantly during sleep, a discovery the investigators called “striking and unexpected.”

“This has not been shown before [and] we were surprised, indeed,” Nicola Aceto, PhD, professor of molecular oncology, Swiss Federal Institute of Technology Zürich, said in an interview.

The findings carry potential implications for the timing of biopsy and treatment of metastasis-prone cancers, the authors said.

The study was published online in Nature. 

Circulating tumor cells (CTCs) are generally believed to shed constantly or following particular events such as surgery or physical activity; however, the processes that regulate tumor cell metastasis and how circadian rhythms may play into tumorigenesis remain unclear.

To better understand these processes, Dr. Aceto and colleagues collected blood samples from 30 women with breast cancer at 4:00 a.m. and 10:00 a.m. – times representing the body’s resting and active phases, respectively.

The researchers observed that more than 78% of all CTCs obtained were from samples taken during the resting phase.

This finding is astounding, Harrison Ball, a PhD candidate, and Sunitha Nagrath, PhD, with the University of Michigan, Ann Arbor, wrote in Nature News & Views .

Dr. Aceto and colleagues also found that CTCs generated at night divide more quickly and therefore have a higher potential to metastasize, compared with those generated during the day, which “are devoid of metastatic ability,” according to the authors, who obtained similar results in a series of mouse models.

The team also observed that key circadian rhythm hormones (such as melatonin, testosterone, and glucocorticoids) regulate CTC generation, and insulin promotes tumor cell proliferation in a time-dependent manner, suggesting a “need for time-controlled approaches for the characterization and treatment of breast cancer,” the authors wrote.
 

Practice changing?

Dr. Ball and Dr. Nagrath said the time-dependent nature of CTC dynamics could very well transform how cancer patients are assessed and treated.

“The data pointing to CTC proliferation and release during the rest phase suggest that doctors might need to become more conscious of when to administer specific treatments,” they wrote.

Both cautioned, however, that large clinical trials would be needed before any consideration of circadian rhythms is incorporated into standard practice. It’s also unclear whether these results in breast cancer hold true for other tumor types.

Mariana G. Figueiro, PhD, who was not involved in the research, agreed that, if studies confirm more metastatic spread at night, “there is an opportunity to treat patients at strategic times.”

Dr. Figueiro, of the Icahn School of Medicine at Mount Sinai, New York, also saw a potential impact on the timing of blood draws. “I think tightening up on how people do biopsies and bloodwork based on circadian time is important.”

Marleen Meyers, MD, agreed that these findings could have many clinical implications.

“The most obvious is that the time of day [that] treatment is administered may influence efficacy,” said Dr. Meyers, clinical professor of medicine at New York University Langone’s Perlmutter Cancer Center.

But, Dr. Meyers noted, the benefits of treating someone at night would need to be weighed against the downsides of interrupting a person’s normal sleep-wake cycle. “If this finding is clinically important it will be a challenge incorporating this into clinical care,” she said.

The study had no funding reported. Dr. Aceto is a cofounder and member of the board of PAGE Therapeutics, listed as an inventor in patent applications related to circulating tumor cells, a paid consultant for several companies, and a Novartis shareholder. One coauthor is a cofounder of PAGE Therapeutics. All other authors declare no competing interests. Dr. Meyers and Dr. Figueiro reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

New research shows that the metastatic spread of breast cancer occurs predominantly during sleep, a discovery the investigators called “striking and unexpected.”

“This has not been shown before [and] we were surprised, indeed,” Nicola Aceto, PhD, professor of molecular oncology, Swiss Federal Institute of Technology Zürich, said in an interview.

The findings carry potential implications for the timing of biopsy and treatment of metastasis-prone cancers, the authors said.

The study was published online in Nature. 

Circulating tumor cells (CTCs) are generally believed to shed constantly or following particular events such as surgery or physical activity; however, the processes that regulate tumor cell metastasis and how circadian rhythms may play into tumorigenesis remain unclear.

To better understand these processes, Dr. Aceto and colleagues collected blood samples from 30 women with breast cancer at 4:00 a.m. and 10:00 a.m. – times representing the body’s resting and active phases, respectively.

The researchers observed that more than 78% of all CTCs obtained were from samples taken during the resting phase.

This finding is astounding, Harrison Ball, a PhD candidate, and Sunitha Nagrath, PhD, with the University of Michigan, Ann Arbor, wrote in Nature News & Views .

Dr. Aceto and colleagues also found that CTCs generated at night divide more quickly and therefore have a higher potential to metastasize, compared with those generated during the day, which “are devoid of metastatic ability,” according to the authors, who obtained similar results in a series of mouse models.

The team also observed that key circadian rhythm hormones (such as melatonin, testosterone, and glucocorticoids) regulate CTC generation, and insulin promotes tumor cell proliferation in a time-dependent manner, suggesting a “need for time-controlled approaches for the characterization and treatment of breast cancer,” the authors wrote.
 

Practice changing?

Dr. Ball and Dr. Nagrath said the time-dependent nature of CTC dynamics could very well transform how cancer patients are assessed and treated.

“The data pointing to CTC proliferation and release during the rest phase suggest that doctors might need to become more conscious of when to administer specific treatments,” they wrote.

Both cautioned, however, that large clinical trials would be needed before any consideration of circadian rhythms is incorporated into standard practice. It’s also unclear whether these results in breast cancer hold true for other tumor types.

Mariana G. Figueiro, PhD, who was not involved in the research, agreed that, if studies confirm more metastatic spread at night, “there is an opportunity to treat patients at strategic times.”

Dr. Figueiro, of the Icahn School of Medicine at Mount Sinai, New York, also saw a potential impact on the timing of blood draws. “I think tightening up on how people do biopsies and bloodwork based on circadian time is important.”

Marleen Meyers, MD, agreed that these findings could have many clinical implications.

“The most obvious is that the time of day [that] treatment is administered may influence efficacy,” said Dr. Meyers, clinical professor of medicine at New York University Langone’s Perlmutter Cancer Center.

But, Dr. Meyers noted, the benefits of treating someone at night would need to be weighed against the downsides of interrupting a person’s normal sleep-wake cycle. “If this finding is clinically important it will be a challenge incorporating this into clinical care,” she said.

The study had no funding reported. Dr. Aceto is a cofounder and member of the board of PAGE Therapeutics, listed as an inventor in patent applications related to circulating tumor cells, a paid consultant for several companies, and a Novartis shareholder. One coauthor is a cofounder of PAGE Therapeutics. All other authors declare no competing interests. Dr. Meyers and Dr. Figueiro reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.