Breast Cancer

This transcript has been edited for clarity.

Vidyard Video

Hello. It’s Dr. Kathy Miller from Indiana University.

I have to admit that time has snuck up on me this year. It is already time for the American Society of Clinical Oncology Annual Meeting.

I found it hard to keep track of time this year with the pandemic. Many of the things that help mark the passage of time haven’t happened, have happened at different times of the year than is typical, or have happened in different ways that just haven’t had the same impact in my brain.

Just recently, I was taking a look through the breast cancer program at ASCO and there is a special clinical science symposium that I want to make sure you know about and tune into. It’s the sort of session that might not otherwise reach you.

This has been a year of incredible turmoil and critical thinking about issues of race, ethnicity, justice, and how we can make sure that the medical care we’re providing is inclusive and equitable. How we can make sure we are giving the best outcome to all of our patients.

This special clinical science symposium this year includes several presentations that will delve into how genetically determined ancestry and socially determined race might impact the outcome of our patients. This is a tangled web that is difficult to unpack and separate, but there are clear distinctions here: The genes we inherit do affect how we metabolize drugs, what side effects we might have from drugs, and what drugs might be the best choices for us.

Our socially determined race affects how the world interacts with us. Those biases, be they conscious or unconscious, can affect where we live, where we go to school, how people treat us, what opportunities we have, and how the medical system treats us. They’re related, but they’re not the same. Tune into that clinical science symposium to begin thinking about those differences and how we can make sure we give our patients the best care.

There are other high-profile presentations that you’re going to want to see as well, looking at how we can optimize therapy in patients with HER2-positive disease and beginning to think about who might not need chemotherapy to have an excellent outcome in early-stage disease.

Also, we will be thinking about those patients with triple-negative disease who have residual disease after neoadjuvant chemotherapy. We were all caught off guard with the results of the CREATE-X trial, quite frankly, several years ago.

This year we will hear the results of a postneoadjuvant trial coordinated by the Eastern Cooperative Oncology Group comparing platinum therapy with capecitabine. Tune in to think more about whether capecitabine really should be the standard of care in this population.

As always, I’m interested in your thoughts before or after ASCO. What stood out for you this year in breast cancer? Drop us a comment and let us know about these sessions and what else you found worthwhile.

Dr. Miller is associate director of clinical research and codirector of the breast cancer program at the Melvin and Bren Simon Cancer Center at Indiana University, Indianapolis. Her career has combined both laboratory and clinical research in breast cancer.

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

This transcript has been edited for clarity.

Vidyard Video

Hello. It’s Dr. Kathy Miller from Indiana University.

I have to admit that time has snuck up on me this year. It is already time for the American Society of Clinical Oncology Annual Meeting.

I found it hard to keep track of time this year with the pandemic. Many of the things that help mark the passage of time haven’t happened, have happened at different times of the year than is typical, or have happened in different ways that just haven’t had the same impact in my brain.

Just recently, I was taking a look through the breast cancer program at ASCO and there is a special clinical science symposium that I want to make sure you know about and tune into. It’s the sort of session that might not otherwise reach you.

This has been a year of incredible turmoil and critical thinking about issues of race, ethnicity, justice, and how we can make sure that the medical care we’re providing is inclusive and equitable. How we can make sure we are giving the best outcome to all of our patients.

This special clinical science symposium this year includes several presentations that will delve into how genetically determined ancestry and socially determined race might impact the outcome of our patients. This is a tangled web that is difficult to unpack and separate, but there are clear distinctions here: The genes we inherit do affect how we metabolize drugs, what side effects we might have from drugs, and what drugs might be the best choices for us.

Our socially determined race affects how the world interacts with us. Those biases, be they conscious or unconscious, can affect where we live, where we go to school, how people treat us, what opportunities we have, and how the medical system treats us. They’re related, but they’re not the same. Tune into that clinical science symposium to begin thinking about those differences and how we can make sure we give our patients the best care.

There are other high-profile presentations that you’re going to want to see as well, looking at how we can optimize therapy in patients with HER2-positive disease and beginning to think about who might not need chemotherapy to have an excellent outcome in early-stage disease.

Also, we will be thinking about those patients with triple-negative disease who have residual disease after neoadjuvant chemotherapy. We were all caught off guard with the results of the CREATE-X trial, quite frankly, several years ago.

This year we will hear the results of a postneoadjuvant trial coordinated by the Eastern Cooperative Oncology Group comparing platinum therapy with capecitabine. Tune in to think more about whether capecitabine really should be the standard of care in this population.

As always, I’m interested in your thoughts before or after ASCO. What stood out for you this year in breast cancer? Drop us a comment and let us know about these sessions and what else you found worthwhile.

Dr. Miller is associate director of clinical research and codirector of the breast cancer program at the Melvin and Bren Simon Cancer Center at Indiana University, Indianapolis. Her career has combined both laboratory and clinical research in breast cancer.

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

This transcript has been edited for clarity.

Vidyard Video

Hello. It’s Dr. Kathy Miller from Indiana University.

I have to admit that time has snuck up on me this year. It is already time for the American Society of Clinical Oncology Annual Meeting.

I found it hard to keep track of time this year with the pandemic. Many of the things that help mark the passage of time haven’t happened, have happened at different times of the year than is typical, or have happened in different ways that just haven’t had the same impact in my brain.

Just recently, I was taking a look through the breast cancer program at ASCO and there is a special clinical science symposium that I want to make sure you know about and tune into. It’s the sort of session that might not otherwise reach you.

This has been a year of incredible turmoil and critical thinking about issues of race, ethnicity, justice, and how we can make sure that the medical care we’re providing is inclusive and equitable. How we can make sure we are giving the best outcome to all of our patients.

This special clinical science symposium this year includes several presentations that will delve into how genetically determined ancestry and socially determined race might impact the outcome of our patients. This is a tangled web that is difficult to unpack and separate, but there are clear distinctions here: The genes we inherit do affect how we metabolize drugs, what side effects we might have from drugs, and what drugs might be the best choices for us.

Our socially determined race affects how the world interacts with us. Those biases, be they conscious or unconscious, can affect where we live, where we go to school, how people treat us, what opportunities we have, and how the medical system treats us. They’re related, but they’re not the same. Tune into that clinical science symposium to begin thinking about those differences and how we can make sure we give our patients the best care.

There are other high-profile presentations that you’re going to want to see as well, looking at how we can optimize therapy in patients with HER2-positive disease and beginning to think about who might not need chemotherapy to have an excellent outcome in early-stage disease.

Also, we will be thinking about those patients with triple-negative disease who have residual disease after neoadjuvant chemotherapy. We were all caught off guard with the results of the CREATE-X trial, quite frankly, several years ago.

This year we will hear the results of a postneoadjuvant trial coordinated by the Eastern Cooperative Oncology Group comparing platinum therapy with capecitabine. Tune in to think more about whether capecitabine really should be the standard of care in this population.

As always, I’m interested in your thoughts before or after ASCO. What stood out for you this year in breast cancer? Drop us a comment and let us know about these sessions and what else you found worthwhile.

Dr. Miller is associate director of clinical research and codirector of the breast cancer program at the Melvin and Bren Simon Cancer Center at Indiana University, Indianapolis. Her career has combined both laboratory and clinical research in breast cancer.

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

New clinical data show that the PARP inhibitor olaparib (Lynparza, AstraZeneca/Merck) also has a place in the treatment of early stage breast cancer with BRCA mutations, in addition to its already established role in the treatment of metastatic disease.

It’s a notable outcome given that at least 5% of all breast cancers are associated with BRCA1 or BRCA2 mutations, said first author Andrew Tutt, MBChB, PhD, head of the division of breast cancer research at the Institute of Cancer Research and Guy’s Hospital, King’s College London.

The new results come from the phase 3 OlympiA trial, which involved nearly 2,000 women and showed that 1 year of adjuvant treatment with olaparib improved invasive and distant disease-free survival when used following adjuvant or neoadjuvant chemotherapy in patients with germline BRCA-mutated (gBRCAm) high-risk HER2-negative early breast cancer.

The study was highlighted at a press briefing ahead of the American Society of Clinical Oncology (ASCO) Annual Meeting, where the data will be presented during a plenary session. The study will also be published simultaneously in The New England Journal of Medicine.

The “exciting findings” highlight the importance of genetic testing in appropriate patients to identify those who might benefit from this treatment, and could open the door to additional trials of adjuvant PARP inhibitor in other BRCA1- and BRCA2-associated cancers, ASCO President Lori J. Pierce, MD, said during the press briefing.

“I think the implications are ... one, it’s an early stage disease, and two, it’s a reminder that when you see a patient in clinic and you’re taking a history that you query them for family history,” Dr. Pierce said in an interview. “You try to find out which of these patients could have a mutation so we [can] refer them for testing, and if they have a mutation this will be a therapy that they would be able to get and will likely benefit from.”
 

Improved IDFS and DDFS

The double-blind OlympiA trial enrolled 1,836 patients with gBRCAm and HER2-negative stage II-III breast cancer, including triple-negative or hormone receptor–positive disease with high risk of recurrence after completion of primary local treatment and adjuvant or neoadjuvant chemotherapy. Patients were randomized 1:1 to receive 1 year of continuous oral olaparib at a dose of 300 mg twice daily or placebo.

“Compared with placebo, patients receiving olaparib had a 42% reduction in the risk of the following events: local recurrence of breast cancer, metastatic recurrence of breast cancer, other new cancers, or death due to any cause,” Dr. Tutt said, describing the factors comprising the study’s primary endpoint of invasive disease-free survival (IDSF).

The hazard ratio for IDSF with olaparib versus placebo at a median follow-up of 2.5 years was 0.58, prompting the independent data monitoring committee to recommend unblinding the study at the time of the interim analysis.

At 3 years, 85.9% of patients in the olaparib group and 77.1% in the placebo group were alive and free from invasive disease, for a difference of 8.8%, Dr. Tutt said.

For the secondary endpoint of distant disease-free survival (DDFS), defined as the absence of metastatic breast cancer, new cancer, and death due to any cause, a highly statistically significant 43% reduction was observed with olaparib versus placebo (hazard ratio [HR], 0.57). The survival curves separated early and remained separated, with 3-year DDFS of 87.5% and 80.4%, for a 7.1% difference between the treatment and placebo group, he said.

“The secondary endpoint of overall survival is inevitably immature,” he added, noting that fewer deaths were nonetheless reported with olaparib at 3 years (3-year overall survival 92.0% vs. 88.3%; HR, 0.68), although the difference did not reach statistical significance.

Adverse events observed in the trial were limited and manageable, and were consistent with known effects and product labeling, he said.

Grade 3 adverse events that occurred in more than 10% of patients receiving olaparib were anemia (8.7%), neutropenia (4.8%), leukopenia (3.0%), and fatigue (1.8%). Serious adverse events and adverse events of special interest, including myelodysplastic syndrome/acute myeloid leukemia, new primary malignancy, and pneumonitis, were not increased with olaparib; they occurred in 8.7% vs. 8.4% and 2.6% vs. 4.6% of patients in the treatment and placebo groups, respectively. 
 

Future implications

The findings have important implications for the future of breast cancer treatment, Dr. Tutt said.

Olaparib was already approved for use in the metastatic setting for gBRCAm HER2-negative breast cancer in 2018 on the basis of data from the pivotal OlympiAD trial, led by Mark E. Robson, MD, and colleagues.

In the high-risk early breast cancer setting, however, recurrence rates can be high even after chemotherapy, and novel adjuvant treatments have been lacking, Dr. Tutt said.

The latest findings from OlympiA appear to represent “a major advance for the subset of patients who have inherited BRCA1 and BRCA2 mutations,” Dr. Robson said in an interview.

“The absolute differences – even with relatively short follow-up – in invasive disease-free survival are impressive, and even though overall survival is not yet statistically significant, one surely would be hopeful that with further follow-up a difference would emerge,” he said.

There was some suggestion, even in the OlympiAD trial, that the earlier patients with metastatic disease were treated with PARP inhibition, the more benefit they received, so it’s not surprising that research has moved into the early stage disease setting, he noted.

Future directions may include looking at different drug combinations as investigators did with some success in the BROCADE3 trial of the PARP inhibitor veliparib plus carboplatin and paclitaxel in metastatic gBRCAmut HER2-negative breast cancer – particularly if concerns about worsening myelosuppression when combining a PARP inhibitor and chemotherapy are attenuated with newer PARP inhibitors, he said.

“But for now, using [olaparib] after completion of conventional chemotherapy is the approach that makes the most sense,” he added.

Dr. Robson also noted that some smaller studies show “fairly dramatic pathologic complete response rates” with preoperative PARP inhibitor therapy. He said that “the idea of giving therapy even before surgery, perhaps as a de-escalation approach, is something that would be worth studying in the future.”

For now, it will be important to keep a close eye on whether there is any worsening of rates of second malignancies, especially leukemia, over time in the OlympiA trial participants.

“That was not seen in either the OlympiAD or EMBRACA study [another phase 3 study looking at PARP inhibition in advanced gBRCAmut HER2-negative breast cancer] in the metastatic setting, but obviously [the early breast cancer] population will be at risk for a longer period of time and we will need to see what the data are,” he said. “So far the results are all very encouraging, and this could lead to a new paradigm where we’re basically testing all women with breast cancer at the time of diagnosis to figure out whether or not this is an appropriate adjuvant treatment for them.”

The OlympiA trial was funded by the National Cancer Institute and AstraZeneca. Dr. Tutt has reported multiple relationships with companies including Inbiomotion, Medscape, Prime Oncology, Artios, AstraZeneca, Merck Serono, Pfizer, Merck KGaA, Roche/Genentech, Breast Cancer Now Charity, and Cancer Research UK. Dr. Robson has reported being an investigator for clinical trials of PARP inhibitors and receiving research grants (to his institution) from AstraZeneca, Merck, and Pfizer.
 

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

New clinical data show that the PARP inhibitor olaparib (Lynparza, AstraZeneca/Merck) also has a place in the treatment of early stage breast cancer with BRCA mutations, in addition to its already established role in the treatment of metastatic disease.

It’s a notable outcome given that at least 5% of all breast cancers are associated with BRCA1 or BRCA2 mutations, said first author Andrew Tutt, MBChB, PhD, head of the division of breast cancer research at the Institute of Cancer Research and Guy’s Hospital, King’s College London.

The new results come from the phase 3 OlympiA trial, which involved nearly 2,000 women and showed that 1 year of adjuvant treatment with olaparib improved invasive and distant disease-free survival when used following adjuvant or neoadjuvant chemotherapy in patients with germline BRCA-mutated (gBRCAm) high-risk HER2-negative early breast cancer.

The study was highlighted at a press briefing ahead of the American Society of Clinical Oncology (ASCO) Annual Meeting, where the data will be presented during a plenary session. The study will also be published simultaneously in The New England Journal of Medicine.

The “exciting findings” highlight the importance of genetic testing in appropriate patients to identify those who might benefit from this treatment, and could open the door to additional trials of adjuvant PARP inhibitor in other BRCA1- and BRCA2-associated cancers, ASCO President Lori J. Pierce, MD, said during the press briefing.

“I think the implications are ... one, it’s an early stage disease, and two, it’s a reminder that when you see a patient in clinic and you’re taking a history that you query them for family history,” Dr. Pierce said in an interview. “You try to find out which of these patients could have a mutation so we [can] refer them for testing, and if they have a mutation this will be a therapy that they would be able to get and will likely benefit from.”
 

Improved IDFS and DDFS

The double-blind OlympiA trial enrolled 1,836 patients with gBRCAm and HER2-negative stage II-III breast cancer, including triple-negative or hormone receptor–positive disease with high risk of recurrence after completion of primary local treatment and adjuvant or neoadjuvant chemotherapy. Patients were randomized 1:1 to receive 1 year of continuous oral olaparib at a dose of 300 mg twice daily or placebo.

“Compared with placebo, patients receiving olaparib had a 42% reduction in the risk of the following events: local recurrence of breast cancer, metastatic recurrence of breast cancer, other new cancers, or death due to any cause,” Dr. Tutt said, describing the factors comprising the study’s primary endpoint of invasive disease-free survival (IDSF).

The hazard ratio for IDSF with olaparib versus placebo at a median follow-up of 2.5 years was 0.58, prompting the independent data monitoring committee to recommend unblinding the study at the time of the interim analysis.

At 3 years, 85.9% of patients in the olaparib group and 77.1% in the placebo group were alive and free from invasive disease, for a difference of 8.8%, Dr. Tutt said.

For the secondary endpoint of distant disease-free survival (DDFS), defined as the absence of metastatic breast cancer, new cancer, and death due to any cause, a highly statistically significant 43% reduction was observed with olaparib versus placebo (hazard ratio [HR], 0.57). The survival curves separated early and remained separated, with 3-year DDFS of 87.5% and 80.4%, for a 7.1% difference between the treatment and placebo group, he said.

“The secondary endpoint of overall survival is inevitably immature,” he added, noting that fewer deaths were nonetheless reported with olaparib at 3 years (3-year overall survival 92.0% vs. 88.3%; HR, 0.68), although the difference did not reach statistical significance.

Adverse events observed in the trial were limited and manageable, and were consistent with known effects and product labeling, he said.

Grade 3 adverse events that occurred in more than 10% of patients receiving olaparib were anemia (8.7%), neutropenia (4.8%), leukopenia (3.0%), and fatigue (1.8%). Serious adverse events and adverse events of special interest, including myelodysplastic syndrome/acute myeloid leukemia, new primary malignancy, and pneumonitis, were not increased with olaparib; they occurred in 8.7% vs. 8.4% and 2.6% vs. 4.6% of patients in the treatment and placebo groups, respectively. 
 

Future implications

The findings have important implications for the future of breast cancer treatment, Dr. Tutt said.

Olaparib was already approved for use in the metastatic setting for gBRCAm HER2-negative breast cancer in 2018 on the basis of data from the pivotal OlympiAD trial, led by Mark E. Robson, MD, and colleagues.

In the high-risk early breast cancer setting, however, recurrence rates can be high even after chemotherapy, and novel adjuvant treatments have been lacking, Dr. Tutt said.

The latest findings from OlympiA appear to represent “a major advance for the subset of patients who have inherited BRCA1 and BRCA2 mutations,” Dr. Robson said in an interview.

“The absolute differences – even with relatively short follow-up – in invasive disease-free survival are impressive, and even though overall survival is not yet statistically significant, one surely would be hopeful that with further follow-up a difference would emerge,” he said.

There was some suggestion, even in the OlympiAD trial, that the earlier patients with metastatic disease were treated with PARP inhibition, the more benefit they received, so it’s not surprising that research has moved into the early stage disease setting, he noted.

Future directions may include looking at different drug combinations as investigators did with some success in the BROCADE3 trial of the PARP inhibitor veliparib plus carboplatin and paclitaxel in metastatic gBRCAmut HER2-negative breast cancer – particularly if concerns about worsening myelosuppression when combining a PARP inhibitor and chemotherapy are attenuated with newer PARP inhibitors, he said.

“But for now, using [olaparib] after completion of conventional chemotherapy is the approach that makes the most sense,” he added.

Dr. Robson also noted that some smaller studies show “fairly dramatic pathologic complete response rates” with preoperative PARP inhibitor therapy. He said that “the idea of giving therapy even before surgery, perhaps as a de-escalation approach, is something that would be worth studying in the future.”

For now, it will be important to keep a close eye on whether there is any worsening of rates of second malignancies, especially leukemia, over time in the OlympiA trial participants.

“That was not seen in either the OlympiAD or EMBRACA study [another phase 3 study looking at PARP inhibition in advanced gBRCAmut HER2-negative breast cancer] in the metastatic setting, but obviously [the early breast cancer] population will be at risk for a longer period of time and we will need to see what the data are,” he said. “So far the results are all very encouraging, and this could lead to a new paradigm where we’re basically testing all women with breast cancer at the time of diagnosis to figure out whether or not this is an appropriate adjuvant treatment for them.”

The OlympiA trial was funded by the National Cancer Institute and AstraZeneca. Dr. Tutt has reported multiple relationships with companies including Inbiomotion, Medscape, Prime Oncology, Artios, AstraZeneca, Merck Serono, Pfizer, Merck KGaA, Roche/Genentech, Breast Cancer Now Charity, and Cancer Research UK. Dr. Robson has reported being an investigator for clinical trials of PARP inhibitors and receiving research grants (to his institution) from AstraZeneca, Merck, and Pfizer.
 

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

New clinical data show that the PARP inhibitor olaparib (Lynparza, AstraZeneca/Merck) also has a place in the treatment of early stage breast cancer with BRCA mutations, in addition to its already established role in the treatment of metastatic disease.

It’s a notable outcome given that at least 5% of all breast cancers are associated with BRCA1 or BRCA2 mutations, said first author Andrew Tutt, MBChB, PhD, head of the division of breast cancer research at the Institute of Cancer Research and Guy’s Hospital, King’s College London.

The new results come from the phase 3 OlympiA trial, which involved nearly 2,000 women and showed that 1 year of adjuvant treatment with olaparib improved invasive and distant disease-free survival when used following adjuvant or neoadjuvant chemotherapy in patients with germline BRCA-mutated (gBRCAm) high-risk HER2-negative early breast cancer.

The study was highlighted at a press briefing ahead of the American Society of Clinical Oncology (ASCO) Annual Meeting, where the data will be presented during a plenary session. The study will also be published simultaneously in The New England Journal of Medicine.

The “exciting findings” highlight the importance of genetic testing in appropriate patients to identify those who might benefit from this treatment, and could open the door to additional trials of adjuvant PARP inhibitor in other BRCA1- and BRCA2-associated cancers, ASCO President Lori J. Pierce, MD, said during the press briefing.

“I think the implications are ... one, it’s an early stage disease, and two, it’s a reminder that when you see a patient in clinic and you’re taking a history that you query them for family history,” Dr. Pierce said in an interview. “You try to find out which of these patients could have a mutation so we [can] refer them for testing, and if they have a mutation this will be a therapy that they would be able to get and will likely benefit from.”
 

Improved IDFS and DDFS

The double-blind OlympiA trial enrolled 1,836 patients with gBRCAm and HER2-negative stage II-III breast cancer, including triple-negative or hormone receptor–positive disease with high risk of recurrence after completion of primary local treatment and adjuvant or neoadjuvant chemotherapy. Patients were randomized 1:1 to receive 1 year of continuous oral olaparib at a dose of 300 mg twice daily or placebo.

“Compared with placebo, patients receiving olaparib had a 42% reduction in the risk of the following events: local recurrence of breast cancer, metastatic recurrence of breast cancer, other new cancers, or death due to any cause,” Dr. Tutt said, describing the factors comprising the study’s primary endpoint of invasive disease-free survival (IDSF).

The hazard ratio for IDSF with olaparib versus placebo at a median follow-up of 2.5 years was 0.58, prompting the independent data monitoring committee to recommend unblinding the study at the time of the interim analysis.

At 3 years, 85.9% of patients in the olaparib group and 77.1% in the placebo group were alive and free from invasive disease, for a difference of 8.8%, Dr. Tutt said.

For the secondary endpoint of distant disease-free survival (DDFS), defined as the absence of metastatic breast cancer, new cancer, and death due to any cause, a highly statistically significant 43% reduction was observed with olaparib versus placebo (hazard ratio [HR], 0.57). The survival curves separated early and remained separated, with 3-year DDFS of 87.5% and 80.4%, for a 7.1% difference between the treatment and placebo group, he said.

“The secondary endpoint of overall survival is inevitably immature,” he added, noting that fewer deaths were nonetheless reported with olaparib at 3 years (3-year overall survival 92.0% vs. 88.3%; HR, 0.68), although the difference did not reach statistical significance.

Adverse events observed in the trial were limited and manageable, and were consistent with known effects and product labeling, he said.

Grade 3 adverse events that occurred in more than 10% of patients receiving olaparib were anemia (8.7%), neutropenia (4.8%), leukopenia (3.0%), and fatigue (1.8%). Serious adverse events and adverse events of special interest, including myelodysplastic syndrome/acute myeloid leukemia, new primary malignancy, and pneumonitis, were not increased with olaparib; they occurred in 8.7% vs. 8.4% and 2.6% vs. 4.6% of patients in the treatment and placebo groups, respectively. 
 

Future implications

The findings have important implications for the future of breast cancer treatment, Dr. Tutt said.

Olaparib was already approved for use in the metastatic setting for gBRCAm HER2-negative breast cancer in 2018 on the basis of data from the pivotal OlympiAD trial, led by Mark E. Robson, MD, and colleagues.

In the high-risk early breast cancer setting, however, recurrence rates can be high even after chemotherapy, and novel adjuvant treatments have been lacking, Dr. Tutt said.

The latest findings from OlympiA appear to represent “a major advance for the subset of patients who have inherited BRCA1 and BRCA2 mutations,” Dr. Robson said in an interview.

“The absolute differences – even with relatively short follow-up – in invasive disease-free survival are impressive, and even though overall survival is not yet statistically significant, one surely would be hopeful that with further follow-up a difference would emerge,” he said.

There was some suggestion, even in the OlympiAD trial, that the earlier patients with metastatic disease were treated with PARP inhibition, the more benefit they received, so it’s not surprising that research has moved into the early stage disease setting, he noted.

Future directions may include looking at different drug combinations as investigators did with some success in the BROCADE3 trial of the PARP inhibitor veliparib plus carboplatin and paclitaxel in metastatic gBRCAmut HER2-negative breast cancer – particularly if concerns about worsening myelosuppression when combining a PARP inhibitor and chemotherapy are attenuated with newer PARP inhibitors, he said.

“But for now, using [olaparib] after completion of conventional chemotherapy is the approach that makes the most sense,” he added.

Dr. Robson also noted that some smaller studies show “fairly dramatic pathologic complete response rates” with preoperative PARP inhibitor therapy. He said that “the idea of giving therapy even before surgery, perhaps as a de-escalation approach, is something that would be worth studying in the future.”

For now, it will be important to keep a close eye on whether there is any worsening of rates of second malignancies, especially leukemia, over time in the OlympiA trial participants.

“That was not seen in either the OlympiAD or EMBRACA study [another phase 3 study looking at PARP inhibition in advanced gBRCAmut HER2-negative breast cancer] in the metastatic setting, but obviously [the early breast cancer] population will be at risk for a longer period of time and we will need to see what the data are,” he said. “So far the results are all very encouraging, and this could lead to a new paradigm where we’re basically testing all women with breast cancer at the time of diagnosis to figure out whether or not this is an appropriate adjuvant treatment for them.”

The OlympiA trial was funded by the National Cancer Institute and AstraZeneca. Dr. Tutt has reported multiple relationships with companies including Inbiomotion, Medscape, Prime Oncology, Artios, AstraZeneca, Merck Serono, Pfizer, Merck KGaA, Roche/Genentech, Breast Cancer Now Charity, and Cancer Research UK. Dr. Robson has reported being an investigator for clinical trials of PARP inhibitors and receiving research grants (to his institution) from AstraZeneca, Merck, and Pfizer.
 

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

The inflammatory cytokine interleukin 6 may be a biomarker for distant recurrence of breast cancer among patients treated for stage II-III HER2-negative disease, investigators have found.

In a case-control study of 498 women with breast cancer treated with surgery and adjuvant chemotherapy, as well as endocrine therapy for women with estrogen receptor (ER)–positive tumors, those with higher serum levels of IL-6 at diagnosis had a significantly greater risk for disease recurrence than women with lower levels of the cytokine, Joseph A. Sparano, MD, from the Albert Einstein College of Medicine and Montefiore Medical Center, New York, and colleagues reported.

“This analysis provides level 1B evidence indicating that higher levels of the cytokine IL-6 at diagnosis are associated with a significantly higher distant recurrence risk in high-risk stage II-III breast cancer despite optimal adjuvant systemic therapy,” they wrote in a study presented in a poster discussion session at the American Society of Clinical Oncology Annual Meeting.(Abstract 520)

In an interview, Dr. Sparano said that their findings first need to be validated in a larger study.

“When validated, I think the other key issue is to try to understand what the best cut point for identifying high risk is, “ he said.

If further studies confirm that higher IL-6 levels are prognostic for worse outcomes, it might be possible to use levels of the cytokine as a biomarker to predict for therapies targeting the IL-6/Janus kinase/STAT3 pathway.

“There are trials ongoing testing IL-6 antibodies in combination chemotherapy, and this could be a rational biomarker to identify which patients would be more likely to benefit from that approach,” he said.
 

Systemic inflammation

Systemic inflammation is suspected as a contributing factor to cancer progression and disease recurrence, Dr. Sparano and colleagues noted.

To test their hypothesis that inflammatory cytokines and/or chemokines could be associated with distant recurrence, they conducted a case-control study with 249 matched pairs of patients enrolled in a phase 3 trial of adjuvant chemotherapy for lymph-node positive and high-risk lymph-node negative breast cancer (NCT00433511).

The patients all had surgery and adjuvant chemotherapy with doxorubicin, cyclophosphamide, and paclitaxel with or without bevacizumab, and endocrine therapy for patients whose tumors were ER positive.

They used propensity score matching to pair each patient with distant recurrence to one without, with covariates including post versus premenopausal or perimenopausal status, estrogen and/or progesterone receptor positivity, tumor size (less than 2 cm, greater than 2-5 cm, or greater than 5 cm) nodal status, and grade.

The only biomarker that met the prespecified boundary for statistical significance (P < .0014) was IL-6, with a hazard ratio for distant recurrence of 1.37 (P = .0006).

The median and mean values for IL-6 were 0.95 and 7.5 pg/mL, respectively

Other substances associated with distant recurrence (with a two-sided P value < .05) were macrophage-derived chemokine/CCL22 (HR, 1.90; P = .0098), IL-17A, a T-helper cell inflammatory cytokine (HR, 1.36; P = .0052), and the cytokine vascular endothelial growth factor A (VEGF-A, HR, 1.13; P = 0.037).

There was no statistical interaction between VEGF-A levels and the benefit of bevacizumab.
 

Prognostic value, not clinical utility

“This is a nice abstract. It looks at inflammatory cytokines and provides evidence that inflammatory cytokines, particularly IL-6, could have a prognostic role in predicting risk of recurrence in HER2-negative disease, and the team did a very nice job in multivariate analysis looking at different factors,” said Aditya Bardia, MD, MPH, from the Mass General Cancer Center in Boston, the invited discussant for the study.*

In an interview, Dr. Bardia said that the finding “provides prognostic value, but does not provide clinical utility. It’s unclear if we used this assay and it identified that a patient was at high risk of recurrence whether we could change that. Is there any intervention that could be done to potentially alter the course of disease, alter the natural history? That’s unknown.”

He agreed with Dr. Sparano and colleagues that validation of the finding was still needed, ideally in a prospective or retrospective cohort study.

The study was supported by grants from the National Cancer Institute, Komen Foundation, and Breast Cancer Research Foundation. Dr. Sparano disclosed relationships with multiple companies. Dr. Bardia disclosed a consulting or advisory role and research funding to his institution from multiple companies.

*Correction, 6/4/21: An earlier version of this article misstated Dr. Bardia's name.

The inflammatory cytokine interleukin 6 may be a biomarker for distant recurrence of breast cancer among patients treated for stage II-III HER2-negative disease, investigators have found.

In a case-control study of 498 women with breast cancer treated with surgery and adjuvant chemotherapy, as well as endocrine therapy for women with estrogen receptor (ER)–positive tumors, those with higher serum levels of IL-6 at diagnosis had a significantly greater risk for disease recurrence than women with lower levels of the cytokine, Joseph A. Sparano, MD, from the Albert Einstein College of Medicine and Montefiore Medical Center, New York, and colleagues reported.

“This analysis provides level 1B evidence indicating that higher levels of the cytokine IL-6 at diagnosis are associated with a significantly higher distant recurrence risk in high-risk stage II-III breast cancer despite optimal adjuvant systemic therapy,” they wrote in a study presented in a poster discussion session at the American Society of Clinical Oncology Annual Meeting.(Abstract 520)

In an interview, Dr. Sparano said that their findings first need to be validated in a larger study.

“When validated, I think the other key issue is to try to understand what the best cut point for identifying high risk is, “ he said.

If further studies confirm that higher IL-6 levels are prognostic for worse outcomes, it might be possible to use levels of the cytokine as a biomarker to predict for therapies targeting the IL-6/Janus kinase/STAT3 pathway.

“There are trials ongoing testing IL-6 antibodies in combination chemotherapy, and this could be a rational biomarker to identify which patients would be more likely to benefit from that approach,” he said.
 

Systemic inflammation

Systemic inflammation is suspected as a contributing factor to cancer progression and disease recurrence, Dr. Sparano and colleagues noted.

To test their hypothesis that inflammatory cytokines and/or chemokines could be associated with distant recurrence, they conducted a case-control study with 249 matched pairs of patients enrolled in a phase 3 trial of adjuvant chemotherapy for lymph-node positive and high-risk lymph-node negative breast cancer (NCT00433511).

The patients all had surgery and adjuvant chemotherapy with doxorubicin, cyclophosphamide, and paclitaxel with or without bevacizumab, and endocrine therapy for patients whose tumors were ER positive.

They used propensity score matching to pair each patient with distant recurrence to one without, with covariates including post versus premenopausal or perimenopausal status, estrogen and/or progesterone receptor positivity, tumor size (less than 2 cm, greater than 2-5 cm, or greater than 5 cm) nodal status, and grade.

The only biomarker that met the prespecified boundary for statistical significance (P < .0014) was IL-6, with a hazard ratio for distant recurrence of 1.37 (P = .0006).

The median and mean values for IL-6 were 0.95 and 7.5 pg/mL, respectively

Other substances associated with distant recurrence (with a two-sided P value < .05) were macrophage-derived chemokine/CCL22 (HR, 1.90; P = .0098), IL-17A, a T-helper cell inflammatory cytokine (HR, 1.36; P = .0052), and the cytokine vascular endothelial growth factor A (VEGF-A, HR, 1.13; P = 0.037).

There was no statistical interaction between VEGF-A levels and the benefit of bevacizumab.
 

Prognostic value, not clinical utility

“This is a nice abstract. It looks at inflammatory cytokines and provides evidence that inflammatory cytokines, particularly IL-6, could have a prognostic role in predicting risk of recurrence in HER2-negative disease, and the team did a very nice job in multivariate analysis looking at different factors,” said Aditya Bardia, MD, MPH, from the Mass General Cancer Center in Boston, the invited discussant for the study.*

In an interview, Dr. Bardia said that the finding “provides prognostic value, but does not provide clinical utility. It’s unclear if we used this assay and it identified that a patient was at high risk of recurrence whether we could change that. Is there any intervention that could be done to potentially alter the course of disease, alter the natural history? That’s unknown.”

He agreed with Dr. Sparano and colleagues that validation of the finding was still needed, ideally in a prospective or retrospective cohort study.

The study was supported by grants from the National Cancer Institute, Komen Foundation, and Breast Cancer Research Foundation. Dr. Sparano disclosed relationships with multiple companies. Dr. Bardia disclosed a consulting or advisory role and research funding to his institution from multiple companies.

*Correction, 6/4/21: An earlier version of this article misstated Dr. Bardia's name.

The inflammatory cytokine interleukin 6 may be a biomarker for distant recurrence of breast cancer among patients treated for stage II-III HER2-negative disease, investigators have found.

In a case-control study of 498 women with breast cancer treated with surgery and adjuvant chemotherapy, as well as endocrine therapy for women with estrogen receptor (ER)–positive tumors, those with higher serum levels of IL-6 at diagnosis had a significantly greater risk for disease recurrence than women with lower levels of the cytokine, Joseph A. Sparano, MD, from the Albert Einstein College of Medicine and Montefiore Medical Center, New York, and colleagues reported.

“This analysis provides level 1B evidence indicating that higher levels of the cytokine IL-6 at diagnosis are associated with a significantly higher distant recurrence risk in high-risk stage II-III breast cancer despite optimal adjuvant systemic therapy,” they wrote in a study presented in a poster discussion session at the American Society of Clinical Oncology Annual Meeting.(Abstract 520)

In an interview, Dr. Sparano said that their findings first need to be validated in a larger study.

“When validated, I think the other key issue is to try to understand what the best cut point for identifying high risk is, “ he said.

If further studies confirm that higher IL-6 levels are prognostic for worse outcomes, it might be possible to use levels of the cytokine as a biomarker to predict for therapies targeting the IL-6/Janus kinase/STAT3 pathway.

“There are trials ongoing testing IL-6 antibodies in combination chemotherapy, and this could be a rational biomarker to identify which patients would be more likely to benefit from that approach,” he said.
 

Systemic inflammation

Systemic inflammation is suspected as a contributing factor to cancer progression and disease recurrence, Dr. Sparano and colleagues noted.

To test their hypothesis that inflammatory cytokines and/or chemokines could be associated with distant recurrence, they conducted a case-control study with 249 matched pairs of patients enrolled in a phase 3 trial of adjuvant chemotherapy for lymph-node positive and high-risk lymph-node negative breast cancer (NCT00433511).

The patients all had surgery and adjuvant chemotherapy with doxorubicin, cyclophosphamide, and paclitaxel with or without bevacizumab, and endocrine therapy for patients whose tumors were ER positive.

They used propensity score matching to pair each patient with distant recurrence to one without, with covariates including post versus premenopausal or perimenopausal status, estrogen and/or progesterone receptor positivity, tumor size (less than 2 cm, greater than 2-5 cm, or greater than 5 cm) nodal status, and grade.

The only biomarker that met the prespecified boundary for statistical significance (P < .0014) was IL-6, with a hazard ratio for distant recurrence of 1.37 (P = .0006).

The median and mean values for IL-6 were 0.95 and 7.5 pg/mL, respectively

Other substances associated with distant recurrence (with a two-sided P value < .05) were macrophage-derived chemokine/CCL22 (HR, 1.90; P = .0098), IL-17A, a T-helper cell inflammatory cytokine (HR, 1.36; P = .0052), and the cytokine vascular endothelial growth factor A (VEGF-A, HR, 1.13; P = 0.037).

There was no statistical interaction between VEGF-A levels and the benefit of bevacizumab.
 

Prognostic value, not clinical utility

“This is a nice abstract. It looks at inflammatory cytokines and provides evidence that inflammatory cytokines, particularly IL-6, could have a prognostic role in predicting risk of recurrence in HER2-negative disease, and the team did a very nice job in multivariate analysis looking at different factors,” said Aditya Bardia, MD, MPH, from the Mass General Cancer Center in Boston, the invited discussant for the study.*

In an interview, Dr. Bardia said that the finding “provides prognostic value, but does not provide clinical utility. It’s unclear if we used this assay and it identified that a patient was at high risk of recurrence whether we could change that. Is there any intervention that could be done to potentially alter the course of disease, alter the natural history? That’s unknown.”

He agreed with Dr. Sparano and colleagues that validation of the finding was still needed, ideally in a prospective or retrospective cohort study.

The study was supported by grants from the National Cancer Institute, Komen Foundation, and Breast Cancer Research Foundation. Dr. Sparano disclosed relationships with multiple companies. Dr. Bardia disclosed a consulting or advisory role and research funding to his institution from multiple companies.

*Correction, 6/4/21: An earlier version of this article misstated Dr. Bardia's name.

Key clinical point: Higher sugar-sweetened beverages (SSB) consumption after a breast cancer diagnosis was associated with greater breast cancer-specific and all-cause mortality.

Major finding: Compared with no consumption, the risk for breast cancer-specific and all-cause mortality increased with increasing consumption of SSB (P_trend= .001 and .0001, respectively). The consumption of artificially sweetened beverages was not associated with higher breast cancer-specific or all-cause mortality.

Study details: A prospective cohort of 8,863 women with stages I-III breast cancer who completed a validated food frequency questionnaire every 4 years.

Disclosure: This study was supported by the National Institutes of Health, the American Institute for Cancer Research, and the Breast Cancer Research Foundation. Dr. Holmes received grants, personal fees, and nonfinancial support from various sources outside this work. The remaining authors made no disclosures.

Source: Farvid MS et al. Cancer. 2021 May 4. doi: 10.1002/cncr.33461.

Key clinical point: Higher sugar-sweetened beverages (SSB) consumption after a breast cancer diagnosis was associated with greater breast cancer-specific and all-cause mortality.

Major finding: Compared with no consumption, the risk for breast cancer-specific and all-cause mortality increased with increasing consumption of SSB (P_trend= .001 and .0001, respectively). The consumption of artificially sweetened beverages was not associated with higher breast cancer-specific or all-cause mortality.

Study details: A prospective cohort of 8,863 women with stages I-III breast cancer who completed a validated food frequency questionnaire every 4 years.

Disclosure: This study was supported by the National Institutes of Health, the American Institute for Cancer Research, and the Breast Cancer Research Foundation. Dr. Holmes received grants, personal fees, and nonfinancial support from various sources outside this work. The remaining authors made no disclosures.

Source: Farvid MS et al. Cancer. 2021 May 4. doi: 10.1002/cncr.33461.

Key clinical point: Higher sugar-sweetened beverages (SSB) consumption after a breast cancer diagnosis was associated with greater breast cancer-specific and all-cause mortality.

Major finding: Compared with no consumption, the risk for breast cancer-specific and all-cause mortality increased with increasing consumption of SSB (P_trend= .001 and .0001, respectively). The consumption of artificially sweetened beverages was not associated with higher breast cancer-specific or all-cause mortality.

Study details: A prospective cohort of 8,863 women with stages I-III breast cancer who completed a validated food frequency questionnaire every 4 years.

Disclosure: This study was supported by the National Institutes of Health, the American Institute for Cancer Research, and the Breast Cancer Research Foundation. Dr. Holmes received grants, personal fees, and nonfinancial support from various sources outside this work. The remaining authors made no disclosures.

Source: Farvid MS et al. Cancer. 2021 May 4. doi: 10.1002/cncr.33461.

Key clinical point: In older women with stage I hormone receptor (HR)-positive breast cancer, radiation without endocrine therapy does not increase the risk for second breast cancer events (SBCE).

Major finding: Compared with endocrine therapy plus radiotherapy, radiotherapy alone was not associated with a higher risk for SBCE (P = .137), whereas no therapy (standardized hazard ratio [SHR], 3.7; P less than .001) or endocrine therapy (SHR, 2.2; P = .008) alone was associated with higher risk for SBCE.

Study details: A retrospective study of 13,321 women aged 66 years and older with stage I HR-positive breast cancer who underwent breast-conserving surgery between 2007 and 2012.

Disclosures: The study received funding from the Department of Radiation Oncology, NYU School of Medicine. Dr. Deb received personal fees from the NYU School of Medicine. The other authors did not disclose any conflicts of interest.

Source: Gerber NK et al. Int J Radiat Oncol Biol Phys. 2021 May 8. doi: 10.1016/j.ijrobp.2021.04.030.

Key clinical point: In older women with stage I hormone receptor (HR)-positive breast cancer, radiation without endocrine therapy does not increase the risk for second breast cancer events (SBCE).

Major finding: Compared with endocrine therapy plus radiotherapy, radiotherapy alone was not associated with a higher risk for SBCE (P = .137), whereas no therapy (standardized hazard ratio [SHR], 3.7; P less than .001) or endocrine therapy (SHR, 2.2; P = .008) alone was associated with higher risk for SBCE.

Study details: A retrospective study of 13,321 women aged 66 years and older with stage I HR-positive breast cancer who underwent breast-conserving surgery between 2007 and 2012.

Disclosures: The study received funding from the Department of Radiation Oncology, NYU School of Medicine. Dr. Deb received personal fees from the NYU School of Medicine. The other authors did not disclose any conflicts of interest.

Source: Gerber NK et al. Int J Radiat Oncol Biol Phys. 2021 May 8. doi: 10.1016/j.ijrobp.2021.04.030.

Key clinical point: In older women with stage I hormone receptor (HR)-positive breast cancer, radiation without endocrine therapy does not increase the risk for second breast cancer events (SBCE).

Major finding: Compared with endocrine therapy plus radiotherapy, radiotherapy alone was not associated with a higher risk for SBCE (P = .137), whereas no therapy (standardized hazard ratio [SHR], 3.7; P less than .001) or endocrine therapy (SHR, 2.2; P = .008) alone was associated with higher risk for SBCE.

Study details: A retrospective study of 13,321 women aged 66 years and older with stage I HR-positive breast cancer who underwent breast-conserving surgery between 2007 and 2012.

Disclosures: The study received funding from the Department of Radiation Oncology, NYU School of Medicine. Dr. Deb received personal fees from the NYU School of Medicine. The other authors did not disclose any conflicts of interest.

Source: Gerber NK et al. Int J Radiat Oncol Biol Phys. 2021 May 8. doi: 10.1016/j.ijrobp.2021.04.030.

Key clinical point: In patients with locally advanced or metastatic human epidermal growth factor receptor 2 (HER2)-negative, BRCA germline-mutated breast cancer, poly (ADP-ribose) polymerase (PARP) inhibitors improve progression-free survival (PFS), overall survival (OS), and tumor response rate.

Major findings: A PARP-containing regimen showed a small advantage in OS (hazard ratio, 0.87; 95% confidence interval, 0.76-1.00) vs. non-PARP regimen. PARP inhibitors improved PFS (hazard ratio, 0.63; P less than .00001) and tumor response rate (66.9% vs. 48.9%). The rate of grade 3 or higher adverse events was not significantly different in the PARP-containing vs. non-PARP regimen.

Study details: A meta-analysis of 5 randomized controlled trials comparing PARP-containing and non-PARP regimens in patients with locally advanced or metastatic breast cancer.

Disclosures: The funding source for this meta-analysis was not identified. Some of the authors received honoraria, research funding, compensation, financial support, consulting fees, and/or grants outside this work. Dr. Redfern is the Principal Investigator on the Brightness trial and served on the advisory board of AstraZeneca and Pfizer.

Source: Taylor AM. Cochrane Database Syst Rev. 2021 Apr 22. doi: 10.1002/14651858.CD011395.pub2.

Key clinical point: In patients with locally advanced or metastatic human epidermal growth factor receptor 2 (HER2)-negative, BRCA germline-mutated breast cancer, poly (ADP-ribose) polymerase (PARP) inhibitors improve progression-free survival (PFS), overall survival (OS), and tumor response rate.

Major findings: A PARP-containing regimen showed a small advantage in OS (hazard ratio, 0.87; 95% confidence interval, 0.76-1.00) vs. non-PARP regimen. PARP inhibitors improved PFS (hazard ratio, 0.63; P less than .00001) and tumor response rate (66.9% vs. 48.9%). The rate of grade 3 or higher adverse events was not significantly different in the PARP-containing vs. non-PARP regimen.

Study details: A meta-analysis of 5 randomized controlled trials comparing PARP-containing and non-PARP regimens in patients with locally advanced or metastatic breast cancer.

Disclosures: The funding source for this meta-analysis was not identified. Some of the authors received honoraria, research funding, compensation, financial support, consulting fees, and/or grants outside this work. Dr. Redfern is the Principal Investigator on the Brightness trial and served on the advisory board of AstraZeneca and Pfizer.

Source: Taylor AM. Cochrane Database Syst Rev. 2021 Apr 22. doi: 10.1002/14651858.CD011395.pub2.

Key clinical point: In patients with locally advanced or metastatic human epidermal growth factor receptor 2 (HER2)-negative, BRCA germline-mutated breast cancer, poly (ADP-ribose) polymerase (PARP) inhibitors improve progression-free survival (PFS), overall survival (OS), and tumor response rate.

Major findings: A PARP-containing regimen showed a small advantage in OS (hazard ratio, 0.87; 95% confidence interval, 0.76-1.00) vs. non-PARP regimen. PARP inhibitors improved PFS (hazard ratio, 0.63; P less than .00001) and tumor response rate (66.9% vs. 48.9%). The rate of grade 3 or higher adverse events was not significantly different in the PARP-containing vs. non-PARP regimen.

Study details: A meta-analysis of 5 randomized controlled trials comparing PARP-containing and non-PARP regimens in patients with locally advanced or metastatic breast cancer.

Disclosures: The funding source for this meta-analysis was not identified. Some of the authors received honoraria, research funding, compensation, financial support, consulting fees, and/or grants outside this work. Dr. Redfern is the Principal Investigator on the Brightness trial and served on the advisory board of AstraZeneca and Pfizer.

Source: Taylor AM. Cochrane Database Syst Rev. 2021 Apr 22. doi: 10.1002/14651858.CD011395.pub2.

Key clinical point: Fertility concerns affect adjuvant endocrine therapy (ET) decisions in one-third of young breast cancer survivors.

Major finding: Within 2 years after diagnosis, fertility concerns affected ET decisions in 33.12% of women. Parity at diagnosis showed a significant association with fertility concerns. The women who reported that fertility concerns affected their ET decisions showed a higher rate of noninitiation/nonpersistence with ET vs. those without fertility concerns (40% vs. 20%; P less than .0001).

Study details: An analysis of 643 hormone receptor-positive women (mean age, 36 years) who completed a survey from the Young Women’s Breast Cancer Study.

Disclosures: This study was funded by Susan G. Komen and the Breast Cancer Research Foundation. Dr. Rosenberg received a grant from the Agency for Healthcare Research and Quality. Dr. Sella was supported by the Pinchas Borenstein Talpiot Medical Leadership Program at Sheba Medical Center and the American Physicians Fellowship for Medicine in Israel. The authors reported receiving honorarium/research funding/consultancy fees/personal fees outside this study work. Dr. Peppercorn reported employment by/stocks in GlaxoSmithKline.

Source: Sella T. Cancer. 2021 Apr 22. doi: 10.1002/cncr.33596.

Key clinical point: Fertility concerns affect adjuvant endocrine therapy (ET) decisions in one-third of young breast cancer survivors.

Major finding: Within 2 years after diagnosis, fertility concerns affected ET decisions in 33.12% of women. Parity at diagnosis showed a significant association with fertility concerns. The women who reported that fertility concerns affected their ET decisions showed a higher rate of noninitiation/nonpersistence with ET vs. those without fertility concerns (40% vs. 20%; P less than .0001).

Study details: An analysis of 643 hormone receptor-positive women (mean age, 36 years) who completed a survey from the Young Women’s Breast Cancer Study.

Disclosures: This study was funded by Susan G. Komen and the Breast Cancer Research Foundation. Dr. Rosenberg received a grant from the Agency for Healthcare Research and Quality. Dr. Sella was supported by the Pinchas Borenstein Talpiot Medical Leadership Program at Sheba Medical Center and the American Physicians Fellowship for Medicine in Israel. The authors reported receiving honorarium/research funding/consultancy fees/personal fees outside this study work. Dr. Peppercorn reported employment by/stocks in GlaxoSmithKline.

Source: Sella T. Cancer. 2021 Apr 22. doi: 10.1002/cncr.33596.

Key clinical point: Fertility concerns affect adjuvant endocrine therapy (ET) decisions in one-third of young breast cancer survivors.

Major finding: Within 2 years after diagnosis, fertility concerns affected ET decisions in 33.12% of women. Parity at diagnosis showed a significant association with fertility concerns. The women who reported that fertility concerns affected their ET decisions showed a higher rate of noninitiation/nonpersistence with ET vs. those without fertility concerns (40% vs. 20%; P less than .0001).

Study details: An analysis of 643 hormone receptor-positive women (mean age, 36 years) who completed a survey from the Young Women’s Breast Cancer Study.

Disclosures: This study was funded by Susan G. Komen and the Breast Cancer Research Foundation. Dr. Rosenberg received a grant from the Agency for Healthcare Research and Quality. Dr. Sella was supported by the Pinchas Borenstein Talpiot Medical Leadership Program at Sheba Medical Center and the American Physicians Fellowship for Medicine in Israel. The authors reported receiving honorarium/research funding/consultancy fees/personal fees outside this study work. Dr. Peppercorn reported employment by/stocks in GlaxoSmithKline.

Source: Sella T. Cancer. 2021 Apr 22. doi: 10.1002/cncr.33596.

Key clinical point: The risk for breast cancer-specific mortality (BCSM) remains high beyond 5 years. The BCSM rate is significantly higher in hormone receptor (HR)-positive vs. HR-negative women.

Major finding: The overall BCSM rate was 14.9%. Of all BCSM, 54.2% of deaths occurred after 5 years and were significantly higher in HR-positive vs. HR-negative patients (P less than .001). Among patients with HR-positive and HR-negative breast cancer, independent risk factors for BCSM conditional on having survived 5 years were tumor size, nodal status, age, and year of diagnosis. Among patients with HR-positive status, tumor grade, marital status, and race were also independently associated with the risk for BCSM.

Study details: An observational study of 202,080 women with breast cancer with known HR status diagnosed between 1990 and 2005.

Disclosures: The study did not receive any funding. Some authors received research funding and/or advisory/consulting fees from various sources.

Source: Leone JP. Breast Cancer Res Treat. 2021 Apr 24. doi: 10.1007/s10549-021-06233-4.

Key clinical point: The risk for breast cancer-specific mortality (BCSM) remains high beyond 5 years. The BCSM rate is significantly higher in hormone receptor (HR)-positive vs. HR-negative women.

Major finding: The overall BCSM rate was 14.9%. Of all BCSM, 54.2% of deaths occurred after 5 years and were significantly higher in HR-positive vs. HR-negative patients (P less than .001). Among patients with HR-positive and HR-negative breast cancer, independent risk factors for BCSM conditional on having survived 5 years were tumor size, nodal status, age, and year of diagnosis. Among patients with HR-positive status, tumor grade, marital status, and race were also independently associated with the risk for BCSM.

Study details: An observational study of 202,080 women with breast cancer with known HR status diagnosed between 1990 and 2005.

Disclosures: The study did not receive any funding. Some authors received research funding and/or advisory/consulting fees from various sources.

Source: Leone JP. Breast Cancer Res Treat. 2021 Apr 24. doi: 10.1007/s10549-021-06233-4.

Key clinical point: The risk for breast cancer-specific mortality (BCSM) remains high beyond 5 years. The BCSM rate is significantly higher in hormone receptor (HR)-positive vs. HR-negative women.

Major finding: The overall BCSM rate was 14.9%. Of all BCSM, 54.2% of deaths occurred after 5 years and were significantly higher in HR-positive vs. HR-negative patients (P less than .001). Among patients with HR-positive and HR-negative breast cancer, independent risk factors for BCSM conditional on having survived 5 years were tumor size, nodal status, age, and year of diagnosis. Among patients with HR-positive status, tumor grade, marital status, and race were also independently associated with the risk for BCSM.

Study details: An observational study of 202,080 women with breast cancer with known HR status diagnosed between 1990 and 2005.

Disclosures: The study did not receive any funding. Some authors received research funding and/or advisory/consulting fees from various sources.

Source: Leone JP. Breast Cancer Res Treat. 2021 Apr 24. doi: 10.1007/s10549-021-06233-4.

Key clinical point: In patients with human epidermal growth factor 2 (HER2)-positive early breast cancer, trastuzumab emtansine vs. trastuzumab is associated with longer invasive disease-free survival (DFS) regardless of the type of neoadjuvant chemotherapy (NACT) received.

Major finding: Trastuzumab emtansine was associated with longer invasive DFS vs. trastuzumab in high-risk patients (hazard ratio [HR], 0.50; 95% confidence interval [CI], 0.39-0.64), in patients who received anthracycline-based NACT (HR, 0.51; 95% CI, 0.38-0.67), and in those who received nonanthracycline-based NACT (HR, 0.43; 95% CI, 0.22-0.82).

Study details: This is a subgroup analysis of the KATHERINE trial comparing trastuzumab emtansine with trastuzumab in 1,486 HER2-positive patients with early breast cancer.

Disclosure: This study was funded by F. Hoffmann-La Roche Ltd. The authors received consulting fees, speaker bureau fees, honoraria, educational support, research funding, travel expenses, royalties from, and/or owned stocks in various organizations outside this work. Dr. Boulet was an employee of Parexel International GmbH contracted by F. Hoffmann-La Roche Ltd. Dr. Liu, Dr. Tesarowski, Dr. Lam, Dr. Song, and Dr. Smitt were/are employees of Genetech and/or owned stocks in Roche. All other authors declared no conflicts of interest.

Source: Mamounas EP et al. Ann Oncol. 2021 Apr 28. doi: 10.1016/j.annonc.2021.04.011.

Key clinical point: In patients with human epidermal growth factor 2 (HER2)-positive early breast cancer, trastuzumab emtansine vs. trastuzumab is associated with longer invasive disease-free survival (DFS) regardless of the type of neoadjuvant chemotherapy (NACT) received.

Major finding: Trastuzumab emtansine was associated with longer invasive DFS vs. trastuzumab in high-risk patients (hazard ratio [HR], 0.50; 95% confidence interval [CI], 0.39-0.64), in patients who received anthracycline-based NACT (HR, 0.51; 95% CI, 0.38-0.67), and in those who received nonanthracycline-based NACT (HR, 0.43; 95% CI, 0.22-0.82).

Study details: This is a subgroup analysis of the KATHERINE trial comparing trastuzumab emtansine with trastuzumab in 1,486 HER2-positive patients with early breast cancer.

Disclosure: This study was funded by F. Hoffmann-La Roche Ltd. The authors received consulting fees, speaker bureau fees, honoraria, educational support, research funding, travel expenses, royalties from, and/or owned stocks in various organizations outside this work. Dr. Boulet was an employee of Parexel International GmbH contracted by F. Hoffmann-La Roche Ltd. Dr. Liu, Dr. Tesarowski, Dr. Lam, Dr. Song, and Dr. Smitt were/are employees of Genetech and/or owned stocks in Roche. All other authors declared no conflicts of interest.

Source: Mamounas EP et al. Ann Oncol. 2021 Apr 28. doi: 10.1016/j.annonc.2021.04.011.

Key clinical point: In patients with human epidermal growth factor 2 (HER2)-positive early breast cancer, trastuzumab emtansine vs. trastuzumab is associated with longer invasive disease-free survival (DFS) regardless of the type of neoadjuvant chemotherapy (NACT) received.

Major finding: Trastuzumab emtansine was associated with longer invasive DFS vs. trastuzumab in high-risk patients (hazard ratio [HR], 0.50; 95% confidence interval [CI], 0.39-0.64), in patients who received anthracycline-based NACT (HR, 0.51; 95% CI, 0.38-0.67), and in those who received nonanthracycline-based NACT (HR, 0.43; 95% CI, 0.22-0.82).

Study details: This is a subgroup analysis of the KATHERINE trial comparing trastuzumab emtansine with trastuzumab in 1,486 HER2-positive patients with early breast cancer.

Disclosure: This study was funded by F. Hoffmann-La Roche Ltd. The authors received consulting fees, speaker bureau fees, honoraria, educational support, research funding, travel expenses, royalties from, and/or owned stocks in various organizations outside this work. Dr. Boulet was an employee of Parexel International GmbH contracted by F. Hoffmann-La Roche Ltd. Dr. Liu, Dr. Tesarowski, Dr. Lam, Dr. Song, and Dr. Smitt were/are employees of Genetech and/or owned stocks in Roche. All other authors declared no conflicts of interest.

Source: Mamounas EP et al. Ann Oncol. 2021 Apr 28. doi: 10.1016/j.annonc.2021.04.011.

Key clinical point: In patients with human epidermal growth factor 2 (HER2)-positive metastatic breast cancer and progressive brain metastases despite radiotherapy, pertuzumab in combination with high-dose trastuzumab shows modest central nervous system (CNS) response and good clinical benefit.

Major finding: The confirmed CNS objective response rate was 11% with all partial responses. The clinical benefit rate at 4 months was 68% and at 6 months was 51%. The grade 3-4 adverse event rate was 44%. There were no new safety signals.

Study details: A phase 2 PATRICIA study evaluated pertuzumab in combination with high-dose trastuzumab in 39 patients with HER2-positive metastatic breast cancer and progressive brain metastases despite radiotherapy.

Disclosures: The study was sponsored by F. Hoffmann-La Roche/ Genentech. The authors received consulting/advisory fees, research funding, royalties, and travel/accommodation expenses from various sources. Dr. Fung, Dr. Cheng, and Dr. Kirschbrown reported employment by, stocks, and other ownership interests in Genentech/Roche.

Source: Lin NU et al. J Clin Oncol. 2021 May 4. doi: 10.1200/JCO.20.02822.

Key clinical point: In patients with human epidermal growth factor 2 (HER2)-positive metastatic breast cancer and progressive brain metastases despite radiotherapy, pertuzumab in combination with high-dose trastuzumab shows modest central nervous system (CNS) response and good clinical benefit.

Major finding: The confirmed CNS objective response rate was 11% with all partial responses. The clinical benefit rate at 4 months was 68% and at 6 months was 51%. The grade 3-4 adverse event rate was 44%. There were no new safety signals.

Study details: A phase 2 PATRICIA study evaluated pertuzumab in combination with high-dose trastuzumab in 39 patients with HER2-positive metastatic breast cancer and progressive brain metastases despite radiotherapy.

Disclosures: The study was sponsored by F. Hoffmann-La Roche/ Genentech. The authors received consulting/advisory fees, research funding, royalties, and travel/accommodation expenses from various sources. Dr. Fung, Dr. Cheng, and Dr. Kirschbrown reported employment by, stocks, and other ownership interests in Genentech/Roche.

Source: Lin NU et al. J Clin Oncol. 2021 May 4. doi: 10.1200/JCO.20.02822.

Key clinical point: In patients with human epidermal growth factor 2 (HER2)-positive metastatic breast cancer and progressive brain metastases despite radiotherapy, pertuzumab in combination with high-dose trastuzumab shows modest central nervous system (CNS) response and good clinical benefit.

Major finding: The confirmed CNS objective response rate was 11% with all partial responses. The clinical benefit rate at 4 months was 68% and at 6 months was 51%. The grade 3-4 adverse event rate was 44%. There were no new safety signals.

Study details: A phase 2 PATRICIA study evaluated pertuzumab in combination with high-dose trastuzumab in 39 patients with HER2-positive metastatic breast cancer and progressive brain metastases despite radiotherapy.

Disclosures: The study was sponsored by F. Hoffmann-La Roche/ Genentech. The authors received consulting/advisory fees, research funding, royalties, and travel/accommodation expenses from various sources. Dr. Fung, Dr. Cheng, and Dr. Kirschbrown reported employment by, stocks, and other ownership interests in Genentech/Roche.

Source: Lin NU et al. J Clin Oncol. 2021 May 4. doi: 10.1200/JCO.20.02822.