Breast Cancer

Each year in the United States, approximately 1.7 million Americans are diagnosed with a potentially lethal malignancy. Typical therapies of choice include surgery, radiation, and occasionally, toxic chemotherapy (chemo) — approaches that eliminate the cancer in about 1,000,000 of these cases. The remaining 700,000 or so often proceed to chemotherapy either immediately or upon cancer recurrence, spread, or newly recognized metastases. “Cures” after that point are rare.

I’m speaking in generalities, understanding that each cancer and each patient is unique.
 

Chemotherapy

Chemotherapy alone can cure a small number of cancer types. When added to radiation or surgery, chemotherapy can help to cure a wider range of cancer types. As an add-on, chemotherapy can extend the length and quality of life for many patients with cancer. Since chemotherapy is by definition “toxic,” it can also shorten the duration or harm the quality of life and provide false hope. The Table summarizes what chemotherapy can and cannot achieve in selected cancer types.

• Lack of response (the tumor failed to shrink).
• Progression (the cancer may have grown or spread further).
• Adverse side effects were too severe to continue.

The drugs used in second-line chemo will typically be different from those used in first line, sometimes because cancer cells can develop resistance to chemotherapy drugs over time. Moreover, the goal of second-line chemo may differ from that of first-line therapy. Rather than chiefly aiming for a cure, second-line treatment might focus on slowing cancer growth, managing symptoms, or improving quality of life. Unfortunately, not every type of cancer has a readily available second-line option.

Third-line treatment. Third-line options come into play when both the initial course of chemo (first line) and the subsequent treatment (second line) have failed to achieve remission or control the cancer’s spread. Owing to the progressive nature of advanced cancers, patients might not be eligible or healthy enough for third-line therapy. Depending on cancer type, the patient’s general health, and response to previous treatments, third-line options could include:

• New or different chemotherapy drugs compared with prior lines.
• Surgery to debulk the tumor.
• Radiation for symptom control.
• Targeted therapy: drugs designed to target specific vulnerabilities in cancer cells.
• Immunotherapy: agents that help the body’s immune system fight cancer cells.
• Clinical trials testing new or investigational treatments, which may be applicable at any time, depending on the questions being addressed.

The goals of third-line therapy may shift from aiming for a cure to managing symptoms, improving quality of life, and potentially slowing cancer growth. The decision to pursue third-line therapy involves careful consideration by the doctor and patient, weighing the potential benefits and risks of treatment considering the individual’s overall health and specific situation.

It’s important to have realistic expectations about the potential outcomes of third-line therapy. Although remission may be unlikely, third-line therapy can still play a role in managing the disease.

Navigating advanced cancer treatment is very complex. The patient and physician must together consider detailed explanations and clarifications to set expectations and make informed decisions about care.
 

Interventions to Consider Earlier

In traditional clinical oncology practice, other interventions are possible, but these may not be offered until treatment has reached the third line:

• Molecular testing.
• Palliation.
• Clinical trials.
• Innovative testing to guide targeted therapy by ascertaining which agents are most likely (or not likely at all) to be effective.

I would argue that the patient’s interests are better served by considering and offering these other interventions much earlier, even before starting first-line chemotherapy.

Molecular testing. The best time for molecular testing of a new malignant tumor is typically at the time of diagnosis. Here’s why:

• Molecular testing helps identify specific genetic mutations in the cancer cells. This information can be crucial for selecting targeted therapies that are most effective against those specific mutations. Early detection allows for the most treatment options. For example, for non–small cell lung cancer, early is best because treatment and outcomes may well be changed by test results.
• Knowing the tumor’s molecular makeup can help determine whether a patient qualifies for clinical trials of new drugs designed for specific mutations.
• Some molecular markers can offer information about the tumor’s aggressiveness and potential for metastasis so that prognosis can be informed.

Molecular testing can be a valuable tool throughout a cancer patient’s journey. With genetically diverse tumors, the initial biopsy might not capture the full picture. Molecular testing of circulating tumor DNA can be used to monitor a patient’s response to treatment and detect potential mutations that might arise during treatment resistance. Retesting after metastasis can provide additional information that can aid in treatment decisions.

Palliative care. The ideal time to discuss palliative care with a patient with cancer is early in the diagnosis and treatment process. Palliative care is not the same as hospice care; it isn’t just about end-of-life. Palliative care focuses on improving a patient’s quality of life throughout cancer treatment. Palliative care specialists can address a wide range of symptoms a patient might experience from cancer or its treatment, including pain, fatigue, nausea, and anxiety.

Early discussions allow for a more comprehensive care plan. Open communication about all treatment options, including palliative care, empowers patients to make informed decisions about their care goals and preferences.

Specific situations where discussing palliative care might be appropriate are:

• Soon after a cancer diagnosis.
• If the patient experiences significant side effects from cancer treatment.
• When considering different treatment options, palliative care can complement those treatments.
• In advanced stages of cancer, to focus on comfort and quality of life.

Clinical trials. Participation in a clinical trial to explore new or investigational treatments should always be considered.

In theory, clinical trials should be an option at any time in the patient’s course. But the organized clinical trial experience may not be available or appropriate. Then, the individual becomes a de facto “clinical trial with an n of 1.” Read this brief open-access blog post at Cancer Commons to learn more about that circumstance.

Innovative testing. The best choice of chemotherapeutic or targeted therapies is often unclear. The clinician is likely to follow published guidelines, often from the National Comprehensive Cancer Network.

These are evidence based and driven by consensus of experts. But guideline-recommended therapy is not always effective, and weeks or months can pass before this ineffectiveness becomes apparent. Thus, many researchers and companies are seeking methods of testing each patient’s specific cancer to determine in advance, or very quickly, whether a particular drug is likely to be effective.

Read more about these leading innovations:

SAGE Oncotest: Entering the Next Generation of Tailored Cancer Treatment

Alibrex: A New Blood Test to Reveal Whether a Cancer Treatment is Working

PARIS Test Uses Lab-Grown Mini-Tumors to Find a Patient’s Best Treatment

Using Live Cells from Patients to Find the Right Cancer Drug

Other innovative therapies under investigation could even be agnostic to cancer type:

Treating Pancreatic Cancer: Could Metabolism — Not Genomics — Be the Key?

High-Energy Blue Light Powers a Promising New Treatment to Destroy Cancer Cells

All-Clear Follow-Up: Hydrogen Peroxide Appears to Treat Oral and Skin Lesions

Cancer is a tough nut to crack. Many people and organizations are trying very hard. So much is being learned. Some approaches will be effective. We can all hope.

Dr. Lundberg, editor in chief, Cancer Commons, has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

Each year in the United States, approximately 1.7 million Americans are diagnosed with a potentially lethal malignancy. Typical therapies of choice include surgery, radiation, and occasionally, toxic chemotherapy (chemo) — approaches that eliminate the cancer in about 1,000,000 of these cases. The remaining 700,000 or so often proceed to chemotherapy either immediately or upon cancer recurrence, spread, or newly recognized metastases. “Cures” after that point are rare.

I’m speaking in generalities, understanding that each cancer and each patient is unique.
 

Chemotherapy

Chemotherapy alone can cure a small number of cancer types. When added to radiation or surgery, chemotherapy can help to cure a wider range of cancer types. As an add-on, chemotherapy can extend the length and quality of life for many patients with cancer. Since chemotherapy is by definition “toxic,” it can also shorten the duration or harm the quality of life and provide false hope. The Table summarizes what chemotherapy can and cannot achieve in selected cancer types.

• Lack of response (the tumor failed to shrink).
• Progression (the cancer may have grown or spread further).
• Adverse side effects were too severe to continue.

The drugs used in second-line chemo will typically be different from those used in first line, sometimes because cancer cells can develop resistance to chemotherapy drugs over time. Moreover, the goal of second-line chemo may differ from that of first-line therapy. Rather than chiefly aiming for a cure, second-line treatment might focus on slowing cancer growth, managing symptoms, or improving quality of life. Unfortunately, not every type of cancer has a readily available second-line option.

Third-line treatment. Third-line options come into play when both the initial course of chemo (first line) and the subsequent treatment (second line) have failed to achieve remission or control the cancer’s spread. Owing to the progressive nature of advanced cancers, patients might not be eligible or healthy enough for third-line therapy. Depending on cancer type, the patient’s general health, and response to previous treatments, third-line options could include:

• New or different chemotherapy drugs compared with prior lines.
• Surgery to debulk the tumor.
• Radiation for symptom control.
• Targeted therapy: drugs designed to target specific vulnerabilities in cancer cells.
• Immunotherapy: agents that help the body’s immune system fight cancer cells.
• Clinical trials testing new or investigational treatments, which may be applicable at any time, depending on the questions being addressed.

The goals of third-line therapy may shift from aiming for a cure to managing symptoms, improving quality of life, and potentially slowing cancer growth. The decision to pursue third-line therapy involves careful consideration by the doctor and patient, weighing the potential benefits and risks of treatment considering the individual’s overall health and specific situation.

It’s important to have realistic expectations about the potential outcomes of third-line therapy. Although remission may be unlikely, third-line therapy can still play a role in managing the disease.

Navigating advanced cancer treatment is very complex. The patient and physician must together consider detailed explanations and clarifications to set expectations and make informed decisions about care.
 

Interventions to Consider Earlier

In traditional clinical oncology practice, other interventions are possible, but these may not be offered until treatment has reached the third line:

• Molecular testing.
• Palliation.
• Clinical trials.
• Innovative testing to guide targeted therapy by ascertaining which agents are most likely (or not likely at all) to be effective.

I would argue that the patient’s interests are better served by considering and offering these other interventions much earlier, even before starting first-line chemotherapy.

Molecular testing. The best time for molecular testing of a new malignant tumor is typically at the time of diagnosis. Here’s why:

• Molecular testing helps identify specific genetic mutations in the cancer cells. This information can be crucial for selecting targeted therapies that are most effective against those specific mutations. Early detection allows for the most treatment options. For example, for non–small cell lung cancer, early is best because treatment and outcomes may well be changed by test results.
• Knowing the tumor’s molecular makeup can help determine whether a patient qualifies for clinical trials of new drugs designed for specific mutations.
• Some molecular markers can offer information about the tumor’s aggressiveness and potential for metastasis so that prognosis can be informed.

Molecular testing can be a valuable tool throughout a cancer patient’s journey. With genetically diverse tumors, the initial biopsy might not capture the full picture. Molecular testing of circulating tumor DNA can be used to monitor a patient’s response to treatment and detect potential mutations that might arise during treatment resistance. Retesting after metastasis can provide additional information that can aid in treatment decisions.

Palliative care. The ideal time to discuss palliative care with a patient with cancer is early in the diagnosis and treatment process. Palliative care is not the same as hospice care; it isn’t just about end-of-life. Palliative care focuses on improving a patient’s quality of life throughout cancer treatment. Palliative care specialists can address a wide range of symptoms a patient might experience from cancer or its treatment, including pain, fatigue, nausea, and anxiety.

Early discussions allow for a more comprehensive care plan. Open communication about all treatment options, including palliative care, empowers patients to make informed decisions about their care goals and preferences.

Specific situations where discussing palliative care might be appropriate are:

• Soon after a cancer diagnosis.
• If the patient experiences significant side effects from cancer treatment.
• When considering different treatment options, palliative care can complement those treatments.
• In advanced stages of cancer, to focus on comfort and quality of life.

Clinical trials. Participation in a clinical trial to explore new or investigational treatments should always be considered.

In theory, clinical trials should be an option at any time in the patient’s course. But the organized clinical trial experience may not be available or appropriate. Then, the individual becomes a de facto “clinical trial with an n of 1.” Read this brief open-access blog post at Cancer Commons to learn more about that circumstance.

Innovative testing. The best choice of chemotherapeutic or targeted therapies is often unclear. The clinician is likely to follow published guidelines, often from the National Comprehensive Cancer Network.

These are evidence based and driven by consensus of experts. But guideline-recommended therapy is not always effective, and weeks or months can pass before this ineffectiveness becomes apparent. Thus, many researchers and companies are seeking methods of testing each patient’s specific cancer to determine in advance, or very quickly, whether a particular drug is likely to be effective.

Read more about these leading innovations:

SAGE Oncotest: Entering the Next Generation of Tailored Cancer Treatment

Alibrex: A New Blood Test to Reveal Whether a Cancer Treatment is Working

PARIS Test Uses Lab-Grown Mini-Tumors to Find a Patient’s Best Treatment

Using Live Cells from Patients to Find the Right Cancer Drug

Other innovative therapies under investigation could even be agnostic to cancer type:

Treating Pancreatic Cancer: Could Metabolism — Not Genomics — Be the Key?

High-Energy Blue Light Powers a Promising New Treatment to Destroy Cancer Cells

All-Clear Follow-Up: Hydrogen Peroxide Appears to Treat Oral and Skin Lesions

Cancer is a tough nut to crack. Many people and organizations are trying very hard. So much is being learned. Some approaches will be effective. We can all hope.

Dr. Lundberg, editor in chief, Cancer Commons, has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

Each year in the United States, approximately 1.7 million Americans are diagnosed with a potentially lethal malignancy. Typical therapies of choice include surgery, radiation, and occasionally, toxic chemotherapy (chemo) — approaches that eliminate the cancer in about 1,000,000 of these cases. The remaining 700,000 or so often proceed to chemotherapy either immediately or upon cancer recurrence, spread, or newly recognized metastases. “Cures” after that point are rare.

I’m speaking in generalities, understanding that each cancer and each patient is unique.
 

Chemotherapy

Chemotherapy alone can cure a small number of cancer types. When added to radiation or surgery, chemotherapy can help to cure a wider range of cancer types. As an add-on, chemotherapy can extend the length and quality of life for many patients with cancer. Since chemotherapy is by definition “toxic,” it can also shorten the duration or harm the quality of life and provide false hope. The Table summarizes what chemotherapy can and cannot achieve in selected cancer types.

• Lack of response (the tumor failed to shrink).
• Progression (the cancer may have grown or spread further).
• Adverse side effects were too severe to continue.

The drugs used in second-line chemo will typically be different from those used in first line, sometimes because cancer cells can develop resistance to chemotherapy drugs over time. Moreover, the goal of second-line chemo may differ from that of first-line therapy. Rather than chiefly aiming for a cure, second-line treatment might focus on slowing cancer growth, managing symptoms, or improving quality of life. Unfortunately, not every type of cancer has a readily available second-line option.

Third-line treatment. Third-line options come into play when both the initial course of chemo (first line) and the subsequent treatment (second line) have failed to achieve remission or control the cancer’s spread. Owing to the progressive nature of advanced cancers, patients might not be eligible or healthy enough for third-line therapy. Depending on cancer type, the patient’s general health, and response to previous treatments, third-line options could include:

• New or different chemotherapy drugs compared with prior lines.
• Surgery to debulk the tumor.
• Radiation for symptom control.
• Targeted therapy: drugs designed to target specific vulnerabilities in cancer cells.
• Immunotherapy: agents that help the body’s immune system fight cancer cells.
• Clinical trials testing new or investigational treatments, which may be applicable at any time, depending on the questions being addressed.

The goals of third-line therapy may shift from aiming for a cure to managing symptoms, improving quality of life, and potentially slowing cancer growth. The decision to pursue third-line therapy involves careful consideration by the doctor and patient, weighing the potential benefits and risks of treatment considering the individual’s overall health and specific situation.

It’s important to have realistic expectations about the potential outcomes of third-line therapy. Although remission may be unlikely, third-line therapy can still play a role in managing the disease.

Navigating advanced cancer treatment is very complex. The patient and physician must together consider detailed explanations and clarifications to set expectations and make informed decisions about care.
 

Interventions to Consider Earlier

In traditional clinical oncology practice, other interventions are possible, but these may not be offered until treatment has reached the third line:

• Molecular testing.
• Palliation.
• Clinical trials.
• Innovative testing to guide targeted therapy by ascertaining which agents are most likely (or not likely at all) to be effective.

I would argue that the patient’s interests are better served by considering and offering these other interventions much earlier, even before starting first-line chemotherapy.

Molecular testing. The best time for molecular testing of a new malignant tumor is typically at the time of diagnosis. Here’s why:

• Molecular testing helps identify specific genetic mutations in the cancer cells. This information can be crucial for selecting targeted therapies that are most effective against those specific mutations. Early detection allows for the most treatment options. For example, for non–small cell lung cancer, early is best because treatment and outcomes may well be changed by test results.
• Knowing the tumor’s molecular makeup can help determine whether a patient qualifies for clinical trials of new drugs designed for specific mutations.
• Some molecular markers can offer information about the tumor’s aggressiveness and potential for metastasis so that prognosis can be informed.

Molecular testing can be a valuable tool throughout a cancer patient’s journey. With genetically diverse tumors, the initial biopsy might not capture the full picture. Molecular testing of circulating tumor DNA can be used to monitor a patient’s response to treatment and detect potential mutations that might arise during treatment resistance. Retesting after metastasis can provide additional information that can aid in treatment decisions.

Palliative care. The ideal time to discuss palliative care with a patient with cancer is early in the diagnosis and treatment process. Palliative care is not the same as hospice care; it isn’t just about end-of-life. Palliative care focuses on improving a patient’s quality of life throughout cancer treatment. Palliative care specialists can address a wide range of symptoms a patient might experience from cancer or its treatment, including pain, fatigue, nausea, and anxiety.

Early discussions allow for a more comprehensive care plan. Open communication about all treatment options, including palliative care, empowers patients to make informed decisions about their care goals and preferences.

Specific situations where discussing palliative care might be appropriate are:

• Soon after a cancer diagnosis.
• If the patient experiences significant side effects from cancer treatment.
• When considering different treatment options, palliative care can complement those treatments.
• In advanced stages of cancer, to focus on comfort and quality of life.

Clinical trials. Participation in a clinical trial to explore new or investigational treatments should always be considered.

In theory, clinical trials should be an option at any time in the patient’s course. But the organized clinical trial experience may not be available or appropriate. Then, the individual becomes a de facto “clinical trial with an n of 1.” Read this brief open-access blog post at Cancer Commons to learn more about that circumstance.

Innovative testing. The best choice of chemotherapeutic or targeted therapies is often unclear. The clinician is likely to follow published guidelines, often from the National Comprehensive Cancer Network.

These are evidence based and driven by consensus of experts. But guideline-recommended therapy is not always effective, and weeks or months can pass before this ineffectiveness becomes apparent. Thus, many researchers and companies are seeking methods of testing each patient’s specific cancer to determine in advance, or very quickly, whether a particular drug is likely to be effective.

Read more about these leading innovations:

SAGE Oncotest: Entering the Next Generation of Tailored Cancer Treatment

Alibrex: A New Blood Test to Reveal Whether a Cancer Treatment is Working

PARIS Test Uses Lab-Grown Mini-Tumors to Find a Patient’s Best Treatment

Using Live Cells from Patients to Find the Right Cancer Drug

Other innovative therapies under investigation could even be agnostic to cancer type:

Treating Pancreatic Cancer: Could Metabolism — Not Genomics — Be the Key?

High-Energy Blue Light Powers a Promising New Treatment to Destroy Cancer Cells

All-Clear Follow-Up: Hydrogen Peroxide Appears to Treat Oral and Skin Lesions

Cancer is a tough nut to crack. Many people and organizations are trying very hard. So much is being learned. Some approaches will be effective. We can all hope.

Dr. Lundberg, editor in chief, Cancer Commons, has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

TOPLINE:

Stereotactic body radiotherapy (SBRT) is a safe treatment option for patients with oligometastatic cancer, with only 0.5% of patients experiencing severe acute toxicities within 6 months, according to a large real-world analysis.

METHODOLOGY:

• Advances in cancer imaging have helped identify more patients with oligometastatic disease. Although the standard treatment approach typically involves systemic therapy such as chemotherapy and immunotherapy, SBRT has increasingly become an option for these patients. However, the toxicities associated with SBRT remain less clear.
• OligoCare, a European, prospective, registry-based, single-arm observational study, aims to provide real-world outcomes among patients with oligometastatic cancer who received SBRT. In this analysis, the researchers evaluated early toxicities among 1468 patients with different primary cancers — non–small cell lung cancer (NSCLC; 19.7%), colorectal cancer (20%), breast cancer (15.5%), and prostate cancer (44.8%).
• The primary outcome was acute toxicities, including new malignancies and deaths, within 6 months of initiating SBRT.
• Overall, 527 (35.9%) patients received concomitant systemic treatment and 828 (56%) had de novo oligometastatic disease.

TAKEAWAY:

• Overall, though, only eight patients (0.5%) experienced acute SBRT-related toxicity of grade 3 and above within 6 months; two events, however, were fatal (pneumonitis and cerebral hemorrhage), and both occurred in patients with NSCLC.
• The other six grade 3 events included one instance of each of the following: empyema, pneumonia, radiation pneumonitis, radiation skin injury, decreased appetite, and bone pain. Two of these events occurred in patients with NSCLC, two in patients with breast cancer, one in patients with colorectal cancer, and one in patients with prostate cancer.
• New primary malignancies were reported in 13 (0.9%) patients, which included bladder cancer (n = 3), nonmelanoma skin cancer (n = 3), and leukemia (n = 1).
• Overall, 43 (2.9%) patients died within 6 months, most from their primary cancer (58.1%).

IN PRACTICE:

Low rates of early acute toxicities reported in this real-world study help confirm the safety of SBRT in the treatment of oligometastases, the authors concluded. However, “some anatomical sites might be associated with an increased risk of even severe or fatal toxicities.”

SOURCE:

The study, led by Filippo Alongi, Advanced Radiation Oncology Department, IRCCS Sacro Cuore Don Calabria Hospital, Cancer Care Center, Negrar di Valpolicella, Italy, and University of Brescia, also in Italy, was published online in Radiotherapy & Oncology .

LIMITATIONS:

Some limitations of the study include the nonrandomized design and potential variability in patient selection criteria, treatment doses, and schedules.

DISCLOSURES:

The study did not receive any funding support. Two authors declared receiving speaker or lecture honoraria or consultation fees from various sources.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Stereotactic body radiotherapy (SBRT) is a safe treatment option for patients with oligometastatic cancer, with only 0.5% of patients experiencing severe acute toxicities within 6 months, according to a large real-world analysis.

METHODOLOGY:

• Advances in cancer imaging have helped identify more patients with oligometastatic disease. Although the standard treatment approach typically involves systemic therapy such as chemotherapy and immunotherapy, SBRT has increasingly become an option for these patients. However, the toxicities associated with SBRT remain less clear.
• OligoCare, a European, prospective, registry-based, single-arm observational study, aims to provide real-world outcomes among patients with oligometastatic cancer who received SBRT. In this analysis, the researchers evaluated early toxicities among 1468 patients with different primary cancers — non–small cell lung cancer (NSCLC; 19.7%), colorectal cancer (20%), breast cancer (15.5%), and prostate cancer (44.8%).
• The primary outcome was acute toxicities, including new malignancies and deaths, within 6 months of initiating SBRT.
• Overall, 527 (35.9%) patients received concomitant systemic treatment and 828 (56%) had de novo oligometastatic disease.

TAKEAWAY:

• Overall, though, only eight patients (0.5%) experienced acute SBRT-related toxicity of grade 3 and above within 6 months; two events, however, were fatal (pneumonitis and cerebral hemorrhage), and both occurred in patients with NSCLC.
• The other six grade 3 events included one instance of each of the following: empyema, pneumonia, radiation pneumonitis, radiation skin injury, decreased appetite, and bone pain. Two of these events occurred in patients with NSCLC, two in patients with breast cancer, one in patients with colorectal cancer, and one in patients with prostate cancer.
• New primary malignancies were reported in 13 (0.9%) patients, which included bladder cancer (n = 3), nonmelanoma skin cancer (n = 3), and leukemia (n = 1).
• Overall, 43 (2.9%) patients died within 6 months, most from their primary cancer (58.1%).

IN PRACTICE:

Low rates of early acute toxicities reported in this real-world study help confirm the safety of SBRT in the treatment of oligometastases, the authors concluded. However, “some anatomical sites might be associated with an increased risk of even severe or fatal toxicities.”

SOURCE:

The study, led by Filippo Alongi, Advanced Radiation Oncology Department, IRCCS Sacro Cuore Don Calabria Hospital, Cancer Care Center, Negrar di Valpolicella, Italy, and University of Brescia, also in Italy, was published online in Radiotherapy & Oncology .

LIMITATIONS:

Some limitations of the study include the nonrandomized design and potential variability in patient selection criteria, treatment doses, and schedules.

DISCLOSURES:

The study did not receive any funding support. Two authors declared receiving speaker or lecture honoraria or consultation fees from various sources.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Stereotactic body radiotherapy (SBRT) is a safe treatment option for patients with oligometastatic cancer, with only 0.5% of patients experiencing severe acute toxicities within 6 months, according to a large real-world analysis.

METHODOLOGY:

• Advances in cancer imaging have helped identify more patients with oligometastatic disease. Although the standard treatment approach typically involves systemic therapy such as chemotherapy and immunotherapy, SBRT has increasingly become an option for these patients. However, the toxicities associated with SBRT remain less clear.
• OligoCare, a European, prospective, registry-based, single-arm observational study, aims to provide real-world outcomes among patients with oligometastatic cancer who received SBRT. In this analysis, the researchers evaluated early toxicities among 1468 patients with different primary cancers — non–small cell lung cancer (NSCLC; 19.7%), colorectal cancer (20%), breast cancer (15.5%), and prostate cancer (44.8%).
• The primary outcome was acute toxicities, including new malignancies and deaths, within 6 months of initiating SBRT.
• Overall, 527 (35.9%) patients received concomitant systemic treatment and 828 (56%) had de novo oligometastatic disease.

TAKEAWAY:

• Overall, though, only eight patients (0.5%) experienced acute SBRT-related toxicity of grade 3 and above within 6 months; two events, however, were fatal (pneumonitis and cerebral hemorrhage), and both occurred in patients with NSCLC.
• The other six grade 3 events included one instance of each of the following: empyema, pneumonia, radiation pneumonitis, radiation skin injury, decreased appetite, and bone pain. Two of these events occurred in patients with NSCLC, two in patients with breast cancer, one in patients with colorectal cancer, and one in patients with prostate cancer.
• New primary malignancies were reported in 13 (0.9%) patients, which included bladder cancer (n = 3), nonmelanoma skin cancer (n = 3), and leukemia (n = 1).
• Overall, 43 (2.9%) patients died within 6 months, most from their primary cancer (58.1%).

IN PRACTICE:

Low rates of early acute toxicities reported in this real-world study help confirm the safety of SBRT in the treatment of oligometastases, the authors concluded. However, “some anatomical sites might be associated with an increased risk of even severe or fatal toxicities.”

SOURCE:

The study, led by Filippo Alongi, Advanced Radiation Oncology Department, IRCCS Sacro Cuore Don Calabria Hospital, Cancer Care Center, Negrar di Valpolicella, Italy, and University of Brescia, also in Italy, was published online in Radiotherapy & Oncology .

LIMITATIONS:

Some limitations of the study include the nonrandomized design and potential variability in patient selection criteria, treatment doses, and schedules.

DISCLOSURES:

The study did not receive any funding support. Two authors declared receiving speaker or lecture honoraria or consultation fees from various sources.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE: 

The Breast Cancer Index (BCI) can predict which premenopausal women with hormone receptor–positive breast cancer benefit from ovarian function suppression (OFS) therapy. Women with BCI HOXB13/IL17BR ratio (BCI[H/I])–low tumors showed significant benefit from OFS, whereas those with BCI(H/I)-high tumors did not.

METHODOLOGY:

• Researchers conducted a prospective-retrospective translational study using tumor tissue samples from 1,718 premenopausal women with hormone receptor–positive early-stage breast cancer.
• Participants were randomly assigned to receive 5 years of tamoxifen alone, tamoxifen plus OFS, or exemestane plus OFS.
• BCI testing was performed on RNA extracted from formalin-fixed paraffin-embedded tumor specimens, blinded to clinical data and outcomes.
• The primary endpoints were breast cancer–free interval (BCFI) and distant recurrence-free interval (DRFI), with a median follow-up time of 12 years.
• Settings spanned multiple centers internationally, and data were collected from December 2003 to April 2021, analyzed from May 2022 to October 2022.

TAKEAWAY:

• According to the authors, patients with BCI(H/I)-low tumors exhibited a 12-year absolute benefit in BCFI of 11.6% from exemestane plus OFS (hazard ratio [HR], 0.48; 95% CI, 0.33-0.71) and 7.3% from tamoxifen plus OFS (HR, 0.69; 95% CI, 0.48-0.97), relative to tamoxifen alone.
• Patients with BCI(H/I)-high tumors did not derive significant benefit from either exemestane plus OFS (absolute benefit, -0.4%; HR, 1.03; 95% CI, 0.70-1.53) or tamoxifen plus OFS (absolute benefit, -1.2%; HR, 1.05; 95% CI, 0.72-1.54), compared with tamoxifen alone.
• In the ERBB2-negative subgroup, patients with BCI(H/I)-low tumors experienced a 12-year absolute benefit of 13.2% in BCFI from exemestane plus OFS (HR, 0.39; 95% CI, 0.25-0.60) and 7.4% from tamoxifen plus OFS (HR, 0.64; 95% CI, 0.44-0.93), compared with tamoxifen alone.
• BCI continuous index was significantly prognostic in the subgroup for DRFI (n = 1110; P =.004), with 12-year DRFI of 95.9%, 90.8%, and 86.3% in BCI low-risk, intermediate-risk, and high-risk cases of cancer than had not spread to nearly lymph nodes (N0 cancers), respectively.

IN PRACTICE:

“This investigation suggests a potential clinical use of BCI(H/I) results, adding to their use to identify patients most likely to benefit from extended endocrine therapy, as proven in multiple studies, although in the extended endocrine validation studies, it was the BCI(H/I)-high group that derived the greatest benefit,” wrote the authors of the study.

SOURCE:

The study was led by Ruth M. O’Regan, MD, University of Rochester Department of Medicine in Rochester, New York. It was published online on August 15, in JAMA Oncology.

LIMITATIONS: 

The study’s retrospective nature may introduce biases despite the prospective statistical analysis plan. The sample size for certain clinical subgroups might be too small to definitively confirm the predictive value of BCI(H/I) for OFS benefit. The generalizability of the findings may be limited due to the specific population studied. Further validation in other patient cohorts is necessary to confirm these findings.

DISCLOSURES:

Dr. O’Regan disclosed receiving personal fees from Pfizer and Gilead DSMB, grants from Puma, and nonfinancial support from Novartis. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE: 

The Breast Cancer Index (BCI) can predict which premenopausal women with hormone receptor–positive breast cancer benefit from ovarian function suppression (OFS) therapy. Women with BCI HOXB13/IL17BR ratio (BCI[H/I])–low tumors showed significant benefit from OFS, whereas those with BCI(H/I)-high tumors did not.

METHODOLOGY:

• Researchers conducted a prospective-retrospective translational study using tumor tissue samples from 1,718 premenopausal women with hormone receptor–positive early-stage breast cancer.
• Participants were randomly assigned to receive 5 years of tamoxifen alone, tamoxifen plus OFS, or exemestane plus OFS.
• BCI testing was performed on RNA extracted from formalin-fixed paraffin-embedded tumor specimens, blinded to clinical data and outcomes.
• The primary endpoints were breast cancer–free interval (BCFI) and distant recurrence-free interval (DRFI), with a median follow-up time of 12 years.
• Settings spanned multiple centers internationally, and data were collected from December 2003 to April 2021, analyzed from May 2022 to October 2022.

TAKEAWAY:

• According to the authors, patients with BCI(H/I)-low tumors exhibited a 12-year absolute benefit in BCFI of 11.6% from exemestane plus OFS (hazard ratio [HR], 0.48; 95% CI, 0.33-0.71) and 7.3% from tamoxifen plus OFS (HR, 0.69; 95% CI, 0.48-0.97), relative to tamoxifen alone.
• Patients with BCI(H/I)-high tumors did not derive significant benefit from either exemestane plus OFS (absolute benefit, -0.4%; HR, 1.03; 95% CI, 0.70-1.53) or tamoxifen plus OFS (absolute benefit, -1.2%; HR, 1.05; 95% CI, 0.72-1.54), compared with tamoxifen alone.
• In the ERBB2-negative subgroup, patients with BCI(H/I)-low tumors experienced a 12-year absolute benefit of 13.2% in BCFI from exemestane plus OFS (HR, 0.39; 95% CI, 0.25-0.60) and 7.4% from tamoxifen plus OFS (HR, 0.64; 95% CI, 0.44-0.93), compared with tamoxifen alone.
• BCI continuous index was significantly prognostic in the subgroup for DRFI (n = 1110; P =.004), with 12-year DRFI of 95.9%, 90.8%, and 86.3% in BCI low-risk, intermediate-risk, and high-risk cases of cancer than had not spread to nearly lymph nodes (N0 cancers), respectively.

IN PRACTICE:

“This investigation suggests a potential clinical use of BCI(H/I) results, adding to their use to identify patients most likely to benefit from extended endocrine therapy, as proven in multiple studies, although in the extended endocrine validation studies, it was the BCI(H/I)-high group that derived the greatest benefit,” wrote the authors of the study.

SOURCE:

The study was led by Ruth M. O’Regan, MD, University of Rochester Department of Medicine in Rochester, New York. It was published online on August 15, in JAMA Oncology.

LIMITATIONS: 

The study’s retrospective nature may introduce biases despite the prospective statistical analysis plan. The sample size for certain clinical subgroups might be too small to definitively confirm the predictive value of BCI(H/I) for OFS benefit. The generalizability of the findings may be limited due to the specific population studied. Further validation in other patient cohorts is necessary to confirm these findings.

DISCLOSURES:

Dr. O’Regan disclosed receiving personal fees from Pfizer and Gilead DSMB, grants from Puma, and nonfinancial support from Novartis. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE: 

The Breast Cancer Index (BCI) can predict which premenopausal women with hormone receptor–positive breast cancer benefit from ovarian function suppression (OFS) therapy. Women with BCI HOXB13/IL17BR ratio (BCI[H/I])–low tumors showed significant benefit from OFS, whereas those with BCI(H/I)-high tumors did not.

METHODOLOGY:

• Researchers conducted a prospective-retrospective translational study using tumor tissue samples from 1,718 premenopausal women with hormone receptor–positive early-stage breast cancer.
• Participants were randomly assigned to receive 5 years of tamoxifen alone, tamoxifen plus OFS, or exemestane plus OFS.
• BCI testing was performed on RNA extracted from formalin-fixed paraffin-embedded tumor specimens, blinded to clinical data and outcomes.
• The primary endpoints were breast cancer–free interval (BCFI) and distant recurrence-free interval (DRFI), with a median follow-up time of 12 years.
• Settings spanned multiple centers internationally, and data were collected from December 2003 to April 2021, analyzed from May 2022 to October 2022.

TAKEAWAY:

• According to the authors, patients with BCI(H/I)-low tumors exhibited a 12-year absolute benefit in BCFI of 11.6% from exemestane plus OFS (hazard ratio [HR], 0.48; 95% CI, 0.33-0.71) and 7.3% from tamoxifen plus OFS (HR, 0.69; 95% CI, 0.48-0.97), relative to tamoxifen alone.
• Patients with BCI(H/I)-high tumors did not derive significant benefit from either exemestane plus OFS (absolute benefit, -0.4%; HR, 1.03; 95% CI, 0.70-1.53) or tamoxifen plus OFS (absolute benefit, -1.2%; HR, 1.05; 95% CI, 0.72-1.54), compared with tamoxifen alone.
• In the ERBB2-negative subgroup, patients with BCI(H/I)-low tumors experienced a 12-year absolute benefit of 13.2% in BCFI from exemestane plus OFS (HR, 0.39; 95% CI, 0.25-0.60) and 7.4% from tamoxifen plus OFS (HR, 0.64; 95% CI, 0.44-0.93), compared with tamoxifen alone.
• BCI continuous index was significantly prognostic in the subgroup for DRFI (n = 1110; P =.004), with 12-year DRFI of 95.9%, 90.8%, and 86.3% in BCI low-risk, intermediate-risk, and high-risk cases of cancer than had not spread to nearly lymph nodes (N0 cancers), respectively.

IN PRACTICE:

“This investigation suggests a potential clinical use of BCI(H/I) results, adding to their use to identify patients most likely to benefit from extended endocrine therapy, as proven in multiple studies, although in the extended endocrine validation studies, it was the BCI(H/I)-high group that derived the greatest benefit,” wrote the authors of the study.

SOURCE:

The study was led by Ruth M. O’Regan, MD, University of Rochester Department of Medicine in Rochester, New York. It was published online on August 15, in JAMA Oncology.

LIMITATIONS: 

The study’s retrospective nature may introduce biases despite the prospective statistical analysis plan. The sample size for certain clinical subgroups might be too small to definitively confirm the predictive value of BCI(H/I) for OFS benefit. The generalizability of the findings may be limited due to the specific population studied. Further validation in other patient cohorts is necessary to confirm these findings.

DISCLOSURES:

Dr. O’Regan disclosed receiving personal fees from Pfizer and Gilead DSMB, grants from Puma, and nonfinancial support from Novartis. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE: 

Despite experiencing higher rates of positive margins and pathologic node involvement, patients with early-stage breast cancer who undergo nipple-sparing mastectomy are less likely to receive adjuvant radiation therapy than are those who have breast-conserving surgery. 

METHODOLOGY:

• Nipple-sparing mastectomy has become increasingly popular for treating early-stage breast cancer given the cosmetic and functional benefits of the procedure. However, appropriate use of adjuvant radiation therapy following nipple-sparing mastectomy has not been characterized.
• Researchers compared outcomes and appropriate uses of radiation therapy among 624,075 women diagnosed with cT1-3N0M0 invasive ductal or lobular breast cancer between 2004 and 2017 who underwent breast-conserving surgery (n = 611,907; median age, 63 years) or nipple-sparing mastectomy (n = 12,168; median age, 50 years).
• The researchers compared the rates of postoperative radiation therapy for two standard indications — positive margins and pathologic node involvement — in patients who had breast-conserving surgery or nipple-sparing mastectomy.
• The team also compared overall survival outcomes in patients with positive margins and node involvement.

TAKEAWAY: 

• Patients who had nipple-sparing surgery had higher rates of positive margins (4.5% vs 3.7%; P < .001) and, on multivariable analysis, a 15% higher risk for positive margins compared with those who had breast-conserving surgery (odds ratio [OR], 1.15; P = .005).
• Similarly, patients who had nipple-sparing surgery had significantly higher rates of node involvement compared with those who had breast-conserving surgery (22.5% vs 13.5%) and, on multivariable analysis, an 8% higher risk for node involvement (OR, 1.08; P < .001).
• Despite higher rates of positive margins and node involvement in the nipple-sparing surgery group, these patients were significantly less likely than those in the breast-conserving surgery group to receive adjuvant radiation therapy (OR, 0.07). Overall, only 17.2% of patients who underwent nipple-sparing mastectomy received postoperative radiation therapy compared with 83.3% of those undergoing breast-conserving surgery — an almost fivefold difference (P < .001).
• In the overall study sample, overall survival in the two surgical groups did not differ significantly among patients with positive margins (OR, 0.62; 95% CI, 0.30-1.31; P = .21) and those with node involvement (OR, 1.01; 95% CI, 0.80-1.28; P = .93).

IN PRACTICE:

The researchers emphasized that although overall survival outcomes were comparable in the two surgery groups, the “current standard indications and guidelines for post-mastectomy radiation are not being appropriately” used after nipple-sparing mastectomy.

SOURCE:

The study, led by Wesley J. Talcott, MD, MBA, Department of Radiation Medicine, Northwell Health, New York City, was published online in Advances in Radiation Oncology. 

LIMITATIONS: 

Data on locoregional recurrence, cause-specific mortality, and all pathologic details were not available. The relatively short median follow-up period might not capture differences in the long-term survival outcomes. 

DISCLOSURES:

The study did not receive any funding support. The authors disclosed no conflicts of interest. 

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE: 

Despite experiencing higher rates of positive margins and pathologic node involvement, patients with early-stage breast cancer who undergo nipple-sparing mastectomy are less likely to receive adjuvant radiation therapy than are those who have breast-conserving surgery. 

METHODOLOGY:

• Nipple-sparing mastectomy has become increasingly popular for treating early-stage breast cancer given the cosmetic and functional benefits of the procedure. However, appropriate use of adjuvant radiation therapy following nipple-sparing mastectomy has not been characterized.
• Researchers compared outcomes and appropriate uses of radiation therapy among 624,075 women diagnosed with cT1-3N0M0 invasive ductal or lobular breast cancer between 2004 and 2017 who underwent breast-conserving surgery (n = 611,907; median age, 63 years) or nipple-sparing mastectomy (n = 12,168; median age, 50 years).
• The researchers compared the rates of postoperative radiation therapy for two standard indications — positive margins and pathologic node involvement — in patients who had breast-conserving surgery or nipple-sparing mastectomy.
• The team also compared overall survival outcomes in patients with positive margins and node involvement.

TAKEAWAY: 

• Patients who had nipple-sparing surgery had higher rates of positive margins (4.5% vs 3.7%; P < .001) and, on multivariable analysis, a 15% higher risk for positive margins compared with those who had breast-conserving surgery (odds ratio [OR], 1.15; P = .005).
• Similarly, patients who had nipple-sparing surgery had significantly higher rates of node involvement compared with those who had breast-conserving surgery (22.5% vs 13.5%) and, on multivariable analysis, an 8% higher risk for node involvement (OR, 1.08; P < .001).
• Despite higher rates of positive margins and node involvement in the nipple-sparing surgery group, these patients were significantly less likely than those in the breast-conserving surgery group to receive adjuvant radiation therapy (OR, 0.07). Overall, only 17.2% of patients who underwent nipple-sparing mastectomy received postoperative radiation therapy compared with 83.3% of those undergoing breast-conserving surgery — an almost fivefold difference (P < .001).
• In the overall study sample, overall survival in the two surgical groups did not differ significantly among patients with positive margins (OR, 0.62; 95% CI, 0.30-1.31; P = .21) and those with node involvement (OR, 1.01; 95% CI, 0.80-1.28; P = .93).

IN PRACTICE:

The researchers emphasized that although overall survival outcomes were comparable in the two surgery groups, the “current standard indications and guidelines for post-mastectomy radiation are not being appropriately” used after nipple-sparing mastectomy.

SOURCE:

The study, led by Wesley J. Talcott, MD, MBA, Department of Radiation Medicine, Northwell Health, New York City, was published online in Advances in Radiation Oncology. 

LIMITATIONS: 

Data on locoregional recurrence, cause-specific mortality, and all pathologic details were not available. The relatively short median follow-up period might not capture differences in the long-term survival outcomes. 

DISCLOSURES:

The study did not receive any funding support. The authors disclosed no conflicts of interest. 

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE: 

Despite experiencing higher rates of positive margins and pathologic node involvement, patients with early-stage breast cancer who undergo nipple-sparing mastectomy are less likely to receive adjuvant radiation therapy than are those who have breast-conserving surgery. 

METHODOLOGY:

• Nipple-sparing mastectomy has become increasingly popular for treating early-stage breast cancer given the cosmetic and functional benefits of the procedure. However, appropriate use of adjuvant radiation therapy following nipple-sparing mastectomy has not been characterized.
• Researchers compared outcomes and appropriate uses of radiation therapy among 624,075 women diagnosed with cT1-3N0M0 invasive ductal or lobular breast cancer between 2004 and 2017 who underwent breast-conserving surgery (n = 611,907; median age, 63 years) or nipple-sparing mastectomy (n = 12,168; median age, 50 years).
• The researchers compared the rates of postoperative radiation therapy for two standard indications — positive margins and pathologic node involvement — in patients who had breast-conserving surgery or nipple-sparing mastectomy.
• The team also compared overall survival outcomes in patients with positive margins and node involvement.

TAKEAWAY: 

• Patients who had nipple-sparing surgery had higher rates of positive margins (4.5% vs 3.7%; P < .001) and, on multivariable analysis, a 15% higher risk for positive margins compared with those who had breast-conserving surgery (odds ratio [OR], 1.15; P = .005).
• Similarly, patients who had nipple-sparing surgery had significantly higher rates of node involvement compared with those who had breast-conserving surgery (22.5% vs 13.5%) and, on multivariable analysis, an 8% higher risk for node involvement (OR, 1.08; P < .001).
• Despite higher rates of positive margins and node involvement in the nipple-sparing surgery group, these patients were significantly less likely than those in the breast-conserving surgery group to receive adjuvant radiation therapy (OR, 0.07). Overall, only 17.2% of patients who underwent nipple-sparing mastectomy received postoperative radiation therapy compared with 83.3% of those undergoing breast-conserving surgery — an almost fivefold difference (P < .001).
• In the overall study sample, overall survival in the two surgical groups did not differ significantly among patients with positive margins (OR, 0.62; 95% CI, 0.30-1.31; P = .21) and those with node involvement (OR, 1.01; 95% CI, 0.80-1.28; P = .93).

IN PRACTICE:

The researchers emphasized that although overall survival outcomes were comparable in the two surgery groups, the “current standard indications and guidelines for post-mastectomy radiation are not being appropriately” used after nipple-sparing mastectomy.

SOURCE:

The study, led by Wesley J. Talcott, MD, MBA, Department of Radiation Medicine, Northwell Health, New York City, was published online in Advances in Radiation Oncology. 

LIMITATIONS: 

Data on locoregional recurrence, cause-specific mortality, and all pathologic details were not available. The relatively short median follow-up period might not capture differences in the long-term survival outcomes. 

DISCLOSURES:

The study did not receive any funding support. The authors disclosed no conflicts of interest. 

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

BRCA1 and BRCA2 pathogenic variants carry well-known associations with breast and ovarian cancers in women, which has led to robust clinical guidelines for early genetic testing and risk-reduction strategies. 

Male carriers of BRCA1/2 pathogenic variants also face an increased risk for cancer, particularly of the prostate, pancreas, and breast. 

However, men often fly under the radar. 

Although males represent half of BRCA1/2 pathogenic variant carriers, men are much less likely to receive genetic testing for BRCA mutations. “Most people (including their clinicians) are unaware of their carrier status,” Heather Cheng, MD, PhD, with University of Washington, Seattle, and colleagues explained in a comprehensive review on the subject, published in JAMA Oncology. Most are also unaware of “the associated cancer risks, and management recommendations” for BRCA carriers. 

The testing gap in males may exist, in part, because of a “general lack of awareness” that BRCA gene mutations can be passed down to children from both the mother and father, Elisa Port, MD, chief of breast surgery for the Mount Sinai Health System in New York City, told this news organization.

A daughter can inherit a mutated BRCA gene that puts her at risk for breast or ovarian cancer from her mother’s or father’s family and, similarly, a son can inherit a mutated BRCA gene from either side of the family that puts him at an increased risk for developing prostate and other cancers, explained Dr. Port, director of the Center of Excellence for Breast Cancer at The Tisch Cancer Institute at Mount Sinai. 

Considering family history and genetics on both sides of the family is important when assessing cancer risk in men and women, Dr. Port said. 
 

BRCA Mutations in Men: What’s the Risk? 

Although fewer than 1% of all breast cancers occur in men, when men do carry a BRCA mutation, their risk for breast cancer can increase considerably. The lifetime risk for breast cancer can be as high as 9% in male BRCA2 carriers and up to 1.2% in BRCA1 carriers. 

BRCA1/2 mutations also put men at increased risk for pancreatic and prostate cancers.

For pancreatic cancer, male BRCA1 carriers have a nearly twofold increased risk compared with the general population, with a lifetime risk of 3%. BRCA2 carriers have a three- to nearly eightfold increased risk, with a lifetime risk up to 7%.

Male BRCA1 carriers face a nearly fourfold increased risk of developing prostate cancer and an absolute lifetime risk of 15%-45%. Male BRCA2 carriers have a five- to ninefold increased risk for prostate cancer, with an absolute lifetime risk between 27% and 60%. 
 

When to Test, When to Screen?

Despite the increased risk for several cancers associated with BRCA mutations, many men are not offered genetic testing.

BRCA1/2 genetic testing in men is “ultra-important but underutilized and is an evolving unmet need that the field needs to address,” Kai Tsao, MD MS, medical director of the Medical Oncology Prostate Cancer Program at Mount Sinai in New York City, told this news organization. 

For men considering genetic testing, in Dr. Tsao’s experience, barriers may include fear that insurance may not cover the test and that a positive test may increase insurance premiums, as well as concerns about what the test result may mean for them and their family.

Even for confirmed BRCA carriers, cancer screening guidelines for men vary.

For breast screening in men, there’s limited data to inform guidelines. The National Cancer Center Network currently recommends breast awareness and teaching self-examination starting at age 35 and recommends men with BRCA variants consider yearly mammograms starting at age 50, or 10 years before the earliest male breast cancer diagnosis in the family. 

Data show that screening mammography in men at high-risk for breast cancer yields similar cancer detection rates in men and women, “suggesting mammography screening may be valuable in male BRCA carriers,” the review authors noted. And, in a recent study of men with BRCA1/2 pathogenic variants, most (71%) recommended for screening mammography completed their screening. 

The European Society for Medical Oncology (ESMO) has similar screening recommendations but focuses only on men with BRCA2 mutations and suggests breast ultrasonography as well as mammography as a screening option.

The larger “issue is the general population doesn’t think of breast cancer when they think of men, which may delay seeking medical attention,” said Melissa Fana, MD, of NYU Grossman Long Island School of Medicine and NYU Langone Health, who wasn’t involved in the review. 

For pancreatic cancer, guidelines suggest BRCA1/2 carriers be screened for pancreatic cancer starting at age 50, or 10 years before the earliest known pancreatic cancer in the family, although the guidelines vary on the role family history should play.

And for prostate cancer, current guidelines recommend male BRCA carriers begin prostate-specific antigen screening between age 40 and 45 years, although recommendations on screening intervals and start age vary. ESMO recommendations are similar but only apply to BRCA2 carriers.

A male patient with a BRCA1/2 variant is typically referred for genetic counseling as well, Dr. Tsao explained. But “the challenge is that we don’t have a very good healthcare infrastructure right now” to follow through with that, he added. “Oftentimes a patient will wait many months or even more than a year for a genetic counseling appointment.”

To help improve these issues, Mount Sinai recently launched a comprehensive BRCA program for men and women that offers genetic testing and counseling for patients and family members.

Overall, identifying more male BRCA1/2 carriers will “maximize opportunities for cancer early detection, targeted risk management, and cancer treatment for males, along with facilitating opportunities for risk reduction and prevention in their family members, thereby decreasing the burden of hereditary cancer,” Dr. Cheng and colleagues concluded.

Support for the review was provided in part by BRCA Research and Cure Alliance and the Men & BRCA Program at the Basser Center for BRCA. Cheng reported grants from Promontory Pharmaceutics, Medivation, Sanofi, Janssen, royalties from UpToDate, nonfinancial support from Color Health, personal fees from AstraZeneca, BRCA Research and Cure Alliance (CureBRCA) outside the submitted work. Dr. Port, Dr. Tsao, and Dr. Fana had no conflicts of interest.
 

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

BRCA1 and BRCA2 pathogenic variants carry well-known associations with breast and ovarian cancers in women, which has led to robust clinical guidelines for early genetic testing and risk-reduction strategies. 

Male carriers of BRCA1/2 pathogenic variants also face an increased risk for cancer, particularly of the prostate, pancreas, and breast. 

However, men often fly under the radar. 

Although males represent half of BRCA1/2 pathogenic variant carriers, men are much less likely to receive genetic testing for BRCA mutations. “Most people (including their clinicians) are unaware of their carrier status,” Heather Cheng, MD, PhD, with University of Washington, Seattle, and colleagues explained in a comprehensive review on the subject, published in JAMA Oncology. Most are also unaware of “the associated cancer risks, and management recommendations” for BRCA carriers. 

The testing gap in males may exist, in part, because of a “general lack of awareness” that BRCA gene mutations can be passed down to children from both the mother and father, Elisa Port, MD, chief of breast surgery for the Mount Sinai Health System in New York City, told this news organization.

A daughter can inherit a mutated BRCA gene that puts her at risk for breast or ovarian cancer from her mother’s or father’s family and, similarly, a son can inherit a mutated BRCA gene from either side of the family that puts him at an increased risk for developing prostate and other cancers, explained Dr. Port, director of the Center of Excellence for Breast Cancer at The Tisch Cancer Institute at Mount Sinai. 

Considering family history and genetics on both sides of the family is important when assessing cancer risk in men and women, Dr. Port said. 
 

BRCA Mutations in Men: What’s the Risk? 

Although fewer than 1% of all breast cancers occur in men, when men do carry a BRCA mutation, their risk for breast cancer can increase considerably. The lifetime risk for breast cancer can be as high as 9% in male BRCA2 carriers and up to 1.2% in BRCA1 carriers. 

BRCA1/2 mutations also put men at increased risk for pancreatic and prostate cancers.

For pancreatic cancer, male BRCA1 carriers have a nearly twofold increased risk compared with the general population, with a lifetime risk of 3%. BRCA2 carriers have a three- to nearly eightfold increased risk, with a lifetime risk up to 7%.

Male BRCA1 carriers face a nearly fourfold increased risk of developing prostate cancer and an absolute lifetime risk of 15%-45%. Male BRCA2 carriers have a five- to ninefold increased risk for prostate cancer, with an absolute lifetime risk between 27% and 60%. 
 

When to Test, When to Screen?

Despite the increased risk for several cancers associated with BRCA mutations, many men are not offered genetic testing.

BRCA1/2 genetic testing in men is “ultra-important but underutilized and is an evolving unmet need that the field needs to address,” Kai Tsao, MD MS, medical director of the Medical Oncology Prostate Cancer Program at Mount Sinai in New York City, told this news organization. 

For men considering genetic testing, in Dr. Tsao’s experience, barriers may include fear that insurance may not cover the test and that a positive test may increase insurance premiums, as well as concerns about what the test result may mean for them and their family.

Even for confirmed BRCA carriers, cancer screening guidelines for men vary.

For breast screening in men, there’s limited data to inform guidelines. The National Cancer Center Network currently recommends breast awareness and teaching self-examination starting at age 35 and recommends men with BRCA variants consider yearly mammograms starting at age 50, or 10 years before the earliest male breast cancer diagnosis in the family. 

Data show that screening mammography in men at high-risk for breast cancer yields similar cancer detection rates in men and women, “suggesting mammography screening may be valuable in male BRCA carriers,” the review authors noted. And, in a recent study of men with BRCA1/2 pathogenic variants, most (71%) recommended for screening mammography completed their screening. 

The European Society for Medical Oncology (ESMO) has similar screening recommendations but focuses only on men with BRCA2 mutations and suggests breast ultrasonography as well as mammography as a screening option.

The larger “issue is the general population doesn’t think of breast cancer when they think of men, which may delay seeking medical attention,” said Melissa Fana, MD, of NYU Grossman Long Island School of Medicine and NYU Langone Health, who wasn’t involved in the review. 

For pancreatic cancer, guidelines suggest BRCA1/2 carriers be screened for pancreatic cancer starting at age 50, or 10 years before the earliest known pancreatic cancer in the family, although the guidelines vary on the role family history should play.

And for prostate cancer, current guidelines recommend male BRCA carriers begin prostate-specific antigen screening between age 40 and 45 years, although recommendations on screening intervals and start age vary. ESMO recommendations are similar but only apply to BRCA2 carriers.

A male patient with a BRCA1/2 variant is typically referred for genetic counseling as well, Dr. Tsao explained. But “the challenge is that we don’t have a very good healthcare infrastructure right now” to follow through with that, he added. “Oftentimes a patient will wait many months or even more than a year for a genetic counseling appointment.”

To help improve these issues, Mount Sinai recently launched a comprehensive BRCA program for men and women that offers genetic testing and counseling for patients and family members.

Overall, identifying more male BRCA1/2 carriers will “maximize opportunities for cancer early detection, targeted risk management, and cancer treatment for males, along with facilitating opportunities for risk reduction and prevention in their family members, thereby decreasing the burden of hereditary cancer,” Dr. Cheng and colleagues concluded.

Support for the review was provided in part by BRCA Research and Cure Alliance and the Men & BRCA Program at the Basser Center for BRCA. Cheng reported grants from Promontory Pharmaceutics, Medivation, Sanofi, Janssen, royalties from UpToDate, nonfinancial support from Color Health, personal fees from AstraZeneca, BRCA Research and Cure Alliance (CureBRCA) outside the submitted work. Dr. Port, Dr. Tsao, and Dr. Fana had no conflicts of interest.
 

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

BRCA1 and BRCA2 pathogenic variants carry well-known associations with breast and ovarian cancers in women, which has led to robust clinical guidelines for early genetic testing and risk-reduction strategies. 

Male carriers of BRCA1/2 pathogenic variants also face an increased risk for cancer, particularly of the prostate, pancreas, and breast. 

However, men often fly under the radar. 

Although males represent half of BRCA1/2 pathogenic variant carriers, men are much less likely to receive genetic testing for BRCA mutations. “Most people (including their clinicians) are unaware of their carrier status,” Heather Cheng, MD, PhD, with University of Washington, Seattle, and colleagues explained in a comprehensive review on the subject, published in JAMA Oncology. Most are also unaware of “the associated cancer risks, and management recommendations” for BRCA carriers. 

The testing gap in males may exist, in part, because of a “general lack of awareness” that BRCA gene mutations can be passed down to children from both the mother and father, Elisa Port, MD, chief of breast surgery for the Mount Sinai Health System in New York City, told this news organization.

A daughter can inherit a mutated BRCA gene that puts her at risk for breast or ovarian cancer from her mother’s or father’s family and, similarly, a son can inherit a mutated BRCA gene from either side of the family that puts him at an increased risk for developing prostate and other cancers, explained Dr. Port, director of the Center of Excellence for Breast Cancer at The Tisch Cancer Institute at Mount Sinai. 

Considering family history and genetics on both sides of the family is important when assessing cancer risk in men and women, Dr. Port said. 
 

BRCA Mutations in Men: What’s the Risk? 

Although fewer than 1% of all breast cancers occur in men, when men do carry a BRCA mutation, their risk for breast cancer can increase considerably. The lifetime risk for breast cancer can be as high as 9% in male BRCA2 carriers and up to 1.2% in BRCA1 carriers. 

BRCA1/2 mutations also put men at increased risk for pancreatic and prostate cancers.

For pancreatic cancer, male BRCA1 carriers have a nearly twofold increased risk compared with the general population, with a lifetime risk of 3%. BRCA2 carriers have a three- to nearly eightfold increased risk, with a lifetime risk up to 7%.

Male BRCA1 carriers face a nearly fourfold increased risk of developing prostate cancer and an absolute lifetime risk of 15%-45%. Male BRCA2 carriers have a five- to ninefold increased risk for prostate cancer, with an absolute lifetime risk between 27% and 60%. 
 

When to Test, When to Screen?

Despite the increased risk for several cancers associated with BRCA mutations, many men are not offered genetic testing.

BRCA1/2 genetic testing in men is “ultra-important but underutilized and is an evolving unmet need that the field needs to address,” Kai Tsao, MD MS, medical director of the Medical Oncology Prostate Cancer Program at Mount Sinai in New York City, told this news organization. 

For men considering genetic testing, in Dr. Tsao’s experience, barriers may include fear that insurance may not cover the test and that a positive test may increase insurance premiums, as well as concerns about what the test result may mean for them and their family.

Even for confirmed BRCA carriers, cancer screening guidelines for men vary.

For breast screening in men, there’s limited data to inform guidelines. The National Cancer Center Network currently recommends breast awareness and teaching self-examination starting at age 35 and recommends men with BRCA variants consider yearly mammograms starting at age 50, or 10 years before the earliest male breast cancer diagnosis in the family. 

Data show that screening mammography in men at high-risk for breast cancer yields similar cancer detection rates in men and women, “suggesting mammography screening may be valuable in male BRCA carriers,” the review authors noted. And, in a recent study of men with BRCA1/2 pathogenic variants, most (71%) recommended for screening mammography completed their screening. 

The European Society for Medical Oncology (ESMO) has similar screening recommendations but focuses only on men with BRCA2 mutations and suggests breast ultrasonography as well as mammography as a screening option.

The larger “issue is the general population doesn’t think of breast cancer when they think of men, which may delay seeking medical attention,” said Melissa Fana, MD, of NYU Grossman Long Island School of Medicine and NYU Langone Health, who wasn’t involved in the review. 

For pancreatic cancer, guidelines suggest BRCA1/2 carriers be screened for pancreatic cancer starting at age 50, or 10 years before the earliest known pancreatic cancer in the family, although the guidelines vary on the role family history should play.

And for prostate cancer, current guidelines recommend male BRCA carriers begin prostate-specific antigen screening between age 40 and 45 years, although recommendations on screening intervals and start age vary. ESMO recommendations are similar but only apply to BRCA2 carriers.

A male patient with a BRCA1/2 variant is typically referred for genetic counseling as well, Dr. Tsao explained. But “the challenge is that we don’t have a very good healthcare infrastructure right now” to follow through with that, he added. “Oftentimes a patient will wait many months or even more than a year for a genetic counseling appointment.”

To help improve these issues, Mount Sinai recently launched a comprehensive BRCA program for men and women that offers genetic testing and counseling for patients and family members.

Overall, identifying more male BRCA1/2 carriers will “maximize opportunities for cancer early detection, targeted risk management, and cancer treatment for males, along with facilitating opportunities for risk reduction and prevention in their family members, thereby decreasing the burden of hereditary cancer,” Dr. Cheng and colleagues concluded.

Support for the review was provided in part by BRCA Research and Cure Alliance and the Men & BRCA Program at the Basser Center for BRCA. Cheng reported grants from Promontory Pharmaceutics, Medivation, Sanofi, Janssen, royalties from UpToDate, nonfinancial support from Color Health, personal fees from AstraZeneca, BRCA Research and Cure Alliance (CureBRCA) outside the submitted work. Dr. Port, Dr. Tsao, and Dr. Fana had no conflicts of interest.
 

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

TOPLINE:

Patients with pure mucinous breast cancer (PMBC) show superior recurrence-free interval (RFI), recurrence-free survival (RFS), and overall survival (OS), compared with patients with invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC). Patients with PMBC had a 5-year RFI of 96.1%, RFS of 94.9%, and OS of 98.1%.

METHODOLOGY:

• Researchers analyzed data from 23,102 women diagnosed with hormone receptor–positive HER2-negative stage I-III breast cancer, including 20,684 with IDC, 1475 with ILC, and 943 with PMBC.
• The multicenter cohort study included patients who underwent primary breast surgery at six academic institutions in Singapore, Taiwan, Korea, and Japan between January 2000 and December 2015.
• Current National Comprehensive Cancer Network Clinical Practice Guidelines “recommend consideration of adjuvant chemotherapy only for node-positive tumors,” whereas adjuvant endocrine therapy is recommended for estrogen receptor–positive and/or progesterone receptor–positive, node-positive tumors or tumors ≥ 3 cm. Previous studies have reported no significant association between adjuvant chemotherapy and breast cancer–specific survival or OS in patients with early-stage mucinous breast carcinoma.
• The study aimed to compare the recurrence and survival outcomes of PMBC against IDC and ILC, identify clinicopathologic prognostic factors of PMBC, and explore the association of adjuvant systemic therapy with outcomes across subgroups of PMBC.
• Extracted information included patient demographics, tumor characteristics, treatment administered, and staging according to the AJCC TNM classifications.

TAKEAWAY:

• Patients with PMBC had better RFI (hazard ratio [HR], 0.59; 95% CI, 0.43-0.80), RFS (HR, 0.70; 95% CI, 0.56-0.89), and OS (HR, 0.71; 95% CI, 0.53-0.96) than patients with IDC in multivariable Cox regression analyses.
• Fewer than half (48.7%) of the recurrences in patients with PMBC were distant, which was a lower rate than for patients with IDC (67.3%) and ILC (80.6%).
• Significant prognostic factors for RFI in PMBC included positive lymph node(s) (HR, 2.42; 95% CI, 1.08-5.40), radiotherapy (HR, 0.44; 95% CI, 0.23-0.85), and endocrine therapy (HR, 0.25; 95% CI, 0.09-0.70).
• No differential chemotherapy associations with outcomes were detected across PMBC subgroups by nodal stage, tumor size, and age.

IN PRACTICE:

“This international multicenter cohort study on PMBC evaluated one of the largest contemporary real-world datasets for clinical prognostic factors, which also includes valuable data on relapse events, associations of adjuvant systemic therapy, and a comparison with the SEER database,” wrote the authors of the study. “In our cohort, as anticipated, PMBC showed superior RFI, RFS, and OS compared with IDC and ILC, which both had comparatively similar survival outcomes.”

SOURCE:

Corresponding author, Yoon-Sim Yap, MBBS, PhD, of the National Cancer Centre Singapore in Singapore, designed the study. The paper was published online on May 14 in the Journal of the National Comprehensive Cancer Network.

LIMITATIONS:

The retrospective nature over a long period and lack of a central pathology review in this study are among its limitations. The high extent of missing values for tumor grade in PMBC in the multicenter cohort could impact the identified prognostic factors. The study’s findings may not be generalizable to all populations due to the specific geographic locations of the participating institutions.

DISCLOSURES:

Study author Yeon Hee Park, MD, PhD, disclosed serving on a data safety monitoring board and on an advisory board for AstraZeneca, Pfizer, Roche, Menarini, Novartis, and Daiichi Sankyo and serving as a consultant for AstraZeneca, Pfizer, Eli Lilly and Company, Gilead Sciences, Merck, Eisai, Roche, Daiichi Sankyo, Menarini, Everest Pharmaceuticals, and Novartis. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Patients with pure mucinous breast cancer (PMBC) show superior recurrence-free interval (RFI), recurrence-free survival (RFS), and overall survival (OS), compared with patients with invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC). Patients with PMBC had a 5-year RFI of 96.1%, RFS of 94.9%, and OS of 98.1%.

METHODOLOGY:

• Researchers analyzed data from 23,102 women diagnosed with hormone receptor–positive HER2-negative stage I-III breast cancer, including 20,684 with IDC, 1475 with ILC, and 943 with PMBC.
• The multicenter cohort study included patients who underwent primary breast surgery at six academic institutions in Singapore, Taiwan, Korea, and Japan between January 2000 and December 2015.
• Current National Comprehensive Cancer Network Clinical Practice Guidelines “recommend consideration of adjuvant chemotherapy only for node-positive tumors,” whereas adjuvant endocrine therapy is recommended for estrogen receptor–positive and/or progesterone receptor–positive, node-positive tumors or tumors ≥ 3 cm. Previous studies have reported no significant association between adjuvant chemotherapy and breast cancer–specific survival or OS in patients with early-stage mucinous breast carcinoma.
• The study aimed to compare the recurrence and survival outcomes of PMBC against IDC and ILC, identify clinicopathologic prognostic factors of PMBC, and explore the association of adjuvant systemic therapy with outcomes across subgroups of PMBC.
• Extracted information included patient demographics, tumor characteristics, treatment administered, and staging according to the AJCC TNM classifications.

TAKEAWAY:

• Patients with PMBC had better RFI (hazard ratio [HR], 0.59; 95% CI, 0.43-0.80), RFS (HR, 0.70; 95% CI, 0.56-0.89), and OS (HR, 0.71; 95% CI, 0.53-0.96) than patients with IDC in multivariable Cox regression analyses.
• Fewer than half (48.7%) of the recurrences in patients with PMBC were distant, which was a lower rate than for patients with IDC (67.3%) and ILC (80.6%).
• Significant prognostic factors for RFI in PMBC included positive lymph node(s) (HR, 2.42; 95% CI, 1.08-5.40), radiotherapy (HR, 0.44; 95% CI, 0.23-0.85), and endocrine therapy (HR, 0.25; 95% CI, 0.09-0.70).
• No differential chemotherapy associations with outcomes were detected across PMBC subgroups by nodal stage, tumor size, and age.

IN PRACTICE:

“This international multicenter cohort study on PMBC evaluated one of the largest contemporary real-world datasets for clinical prognostic factors, which also includes valuable data on relapse events, associations of adjuvant systemic therapy, and a comparison with the SEER database,” wrote the authors of the study. “In our cohort, as anticipated, PMBC showed superior RFI, RFS, and OS compared with IDC and ILC, which both had comparatively similar survival outcomes.”

SOURCE:

Corresponding author, Yoon-Sim Yap, MBBS, PhD, of the National Cancer Centre Singapore in Singapore, designed the study. The paper was published online on May 14 in the Journal of the National Comprehensive Cancer Network.

LIMITATIONS:

The retrospective nature over a long period and lack of a central pathology review in this study are among its limitations. The high extent of missing values for tumor grade in PMBC in the multicenter cohort could impact the identified prognostic factors. The study’s findings may not be generalizable to all populations due to the specific geographic locations of the participating institutions.

DISCLOSURES:

Study author Yeon Hee Park, MD, PhD, disclosed serving on a data safety monitoring board and on an advisory board for AstraZeneca, Pfizer, Roche, Menarini, Novartis, and Daiichi Sankyo and serving as a consultant for AstraZeneca, Pfizer, Eli Lilly and Company, Gilead Sciences, Merck, Eisai, Roche, Daiichi Sankyo, Menarini, Everest Pharmaceuticals, and Novartis. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Patients with pure mucinous breast cancer (PMBC) show superior recurrence-free interval (RFI), recurrence-free survival (RFS), and overall survival (OS), compared with patients with invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC). Patients with PMBC had a 5-year RFI of 96.1%, RFS of 94.9%, and OS of 98.1%.

METHODOLOGY:

• Researchers analyzed data from 23,102 women diagnosed with hormone receptor–positive HER2-negative stage I-III breast cancer, including 20,684 with IDC, 1475 with ILC, and 943 with PMBC.
• The multicenter cohort study included patients who underwent primary breast surgery at six academic institutions in Singapore, Taiwan, Korea, and Japan between January 2000 and December 2015.
• Current National Comprehensive Cancer Network Clinical Practice Guidelines “recommend consideration of adjuvant chemotherapy only for node-positive tumors,” whereas adjuvant endocrine therapy is recommended for estrogen receptor–positive and/or progesterone receptor–positive, node-positive tumors or tumors ≥ 3 cm. Previous studies have reported no significant association between adjuvant chemotherapy and breast cancer–specific survival or OS in patients with early-stage mucinous breast carcinoma.
• The study aimed to compare the recurrence and survival outcomes of PMBC against IDC and ILC, identify clinicopathologic prognostic factors of PMBC, and explore the association of adjuvant systemic therapy with outcomes across subgroups of PMBC.
• Extracted information included patient demographics, tumor characteristics, treatment administered, and staging according to the AJCC TNM classifications.

TAKEAWAY:

• Patients with PMBC had better RFI (hazard ratio [HR], 0.59; 95% CI, 0.43-0.80), RFS (HR, 0.70; 95% CI, 0.56-0.89), and OS (HR, 0.71; 95% CI, 0.53-0.96) than patients with IDC in multivariable Cox regression analyses.
• Fewer than half (48.7%) of the recurrences in patients with PMBC were distant, which was a lower rate than for patients with IDC (67.3%) and ILC (80.6%).
• Significant prognostic factors for RFI in PMBC included positive lymph node(s) (HR, 2.42; 95% CI, 1.08-5.40), radiotherapy (HR, 0.44; 95% CI, 0.23-0.85), and endocrine therapy (HR, 0.25; 95% CI, 0.09-0.70).
• No differential chemotherapy associations with outcomes were detected across PMBC subgroups by nodal stage, tumor size, and age.

IN PRACTICE:

“This international multicenter cohort study on PMBC evaluated one of the largest contemporary real-world datasets for clinical prognostic factors, which also includes valuable data on relapse events, associations of adjuvant systemic therapy, and a comparison with the SEER database,” wrote the authors of the study. “In our cohort, as anticipated, PMBC showed superior RFI, RFS, and OS compared with IDC and ILC, which both had comparatively similar survival outcomes.”

SOURCE:

Corresponding author, Yoon-Sim Yap, MBBS, PhD, of the National Cancer Centre Singapore in Singapore, designed the study. The paper was published online on May 14 in the Journal of the National Comprehensive Cancer Network.

LIMITATIONS:

The retrospective nature over a long period and lack of a central pathology review in this study are among its limitations. The high extent of missing values for tumor grade in PMBC in the multicenter cohort could impact the identified prognostic factors. The study’s findings may not be generalizable to all populations due to the specific geographic locations of the participating institutions.

DISCLOSURES:

Study author Yeon Hee Park, MD, PhD, disclosed serving on a data safety monitoring board and on an advisory board for AstraZeneca, Pfizer, Roche, Menarini, Novartis, and Daiichi Sankyo and serving as a consultant for AstraZeneca, Pfizer, Eli Lilly and Company, Gilead Sciences, Merck, Eisai, Roche, Daiichi Sankyo, Menarini, Everest Pharmaceuticals, and Novartis. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

Chemotherapy has fallen out of favor for treating cancer toward the end of life. The toxicity is too high, and the benefit, if any, is often too low.

Immunotherapy, however, has been taking its place. Checkpoint inhibitors are increasingly being initiated to treat metastatic cancer in patients approaching the end of life and have become the leading driver of end-of-life cancer spending.

This means “there are patients who are getting immunotherapy who shouldn’t,” said Yale University, New Haven, Connecticut, surgical oncologist Sajid Khan, MD, senior investigator on a recent study that highlighted the growing use of these agents in patients’ last month of life.

What’s driving this trend, and how can oncologists avoid overtreatment with immunotherapy at the end of life?
 

The N-of-1 Patient

With immunotherapy at the end of life, “each of us has had our N-of-1” where a patient bounces back with a remarkable and durable response, said Don Dizon, MD, a gynecologic oncologist at Brown University, Providence, Rhode Island.

He recalled a patient with sarcoma who did not respond to chemotherapy. But after Dr. Dizon started her on immunotherapy, everything turned around. She has now been in remission for 8 years and counting.

The possibility of an unexpected or remarkable responder is seductive. And the improved safety of immunotherapy over chemotherapy adds to the allure.

Meanwhile, patients are often desperate. It’s rare for someone to be ready to stop treatment, Dr. Dizon said. Everybody “hopes that they’re going to be the exceptional responder.”

At the end of the day, the question often becomes: “Why not try immunotherapy? What’s there to lose?”

This thinking may be prompting broader use of immunotherapy in late-stage disease, even in instances with no Food and Drug Administration indication and virtually no supportive data, such as for metastatic ovarian cancer, Dr. Dizon said.
 

Back to Earth

The problem with the hopeful approach is that end-of-life turnarounds with immunotherapy are rare, and there’s no way at the moment to predict who will have one, said Laura Petrillo, MD, a palliative care physician at Massachusetts General Hospital, Boston.

Even though immunotherapy generally comes with fewer adverse events than chemotherapy, catastrophic side effects are still possible.

Dr. Petrillo recalled a 95-year-old woman with metastatic cancer who was largely asymptomatic.

She had a qualifying mutation for a checkpoint inhibitor, so her oncologist started her on one. The patient never bounced back from the severe colitis the agent caused, and she died of complications in the hospital.

Although such reactions with immunotherapy are uncommon, less serious problems caused by the agents can still have a major impact on a person’s quality of life. Low-grade diarrhea, for instance, may not sound too bad, but in a patient’s daily life, it can translate to six or more episodes a day.

Even with no side effects, prescribing immunotherapy can mean that patients with limited time left spend a good portion of it at an infusion clinic instead of at home. These patients are also less likely to be referred to hospice and more likely to be admitted to and die in the hospital.

And with treatments that can cost $20,000 per dose, financial toxicity becomes a big concern.

In short, some of the reasons why chemotherapy is not recommended at the end of life also apply to immunotherapy, Dr. Petrillo said.
 

Prescribing Decisions

Recent research highlights the growing use of immunotherapy at the end of life.

Dr. Khan’s retrospective study found, for instance, that the percentage of patients starting immunotherapy in the last 30 days of life increased by about fourfold to fivefold over the study period for the three cancers analyzed — stage IV melanoma, lung, and kidney cancers.

Among the population that died within 30 days, the percentage receiving immunotherapy increased over the study periods — 0.8%-4.3% for melanoma, 0.9%-3.2% for NSCLC, and 0.5%-2.6% for kidney cell carcinoma — prompting the conclusion that immunotherapy prescriptions in the last month of life are on the rise.

Prescribing immunotherapy in patients who ultimately died within 1 month occurred more frequently at low-volume, nonacademic centers than at academic or high-volume centers, and outcomes varied by practice setting.

Patients had better survival outcomes overall when receiving immunotherapy at academic or high-volume centers — a finding Dr. Khan said is worth investigating further. Possible explanations include better management of severe immune-related side effects at larger centers and more caution when prescribing immunotherapy to “borderline” candidates, such as those with several comorbidities.

Importantly, given the retrospective design, Dr. Khan and colleagues already knew which patients prescribed immunotherapy died within 30 days of initiating treatment.

More specifically, 5192 of 71,204 patients who received immunotherapy (7.3%) died within a month of initiating therapy, while 66,012 (92.7%) lived beyond that point.

The study, however, did not assess how the remaining 92.7% who lived beyond 30 days fared on immunotherapy and the differences between those who lived less than 30 days and those who survived longer.

Knowing the outcome of patients at the outset of the analysis still leaves open the question of when immunotherapy can extend life and when it can’t for the patient in front of you.

To avoid overtreating at the end of life, it’s important to have “the same standard that you have for giving chemotherapy. You have to treat it with the same respect,” said Moshe Chasky, MD, a community medical oncologist with Alliance Cancer Specialists in Philadelphia, Pennsylvania. “You can’t just be throwing” immunotherapy around “at the end of life.”

While there are no clear predictors of risk and benefit, there are some factors to help guide decisions.

As with chemotherapy, Dr. Petrillo said performance status is key. Dr. Petrillo and colleagues found that median overall survival with immune checkpoint inhibitors for advanced non–small cell lung cancer was 14.3 months in patients with an Eastern Cooperative Oncology Group performance score of 0-1 but only 4.5 months with scores of ≥ 2.

Dr. Khan also found that immunotherapy survival is, unsurprisingly, worse in patients with high metastatic burdens and more comorbidities.

“You should still consider immunotherapy for metastatic melanoma, non–small cell lung cancer, and renal cell carcinoma,” Dr. Khan said. The message here is to “think twice before using” it, especially in comorbid patients with widespread metastases.

“Just because something can be done doesn’t always mean it should be done,” he said.

At Yale, when Dr. Khan works, immunotherapy decisions are considered by a multidisciplinary tumor board. At Mass General, immunotherapy has generally moved to the frontline setting, and the hospital no longer prescribes checkpoint inhibitors to hospitalized patients because the cost is too high relative to the potential benefit, Dr. Petrillo explained.

Still, with all the uncertainties about risk and benefit, counseling patients is a challenge. Dr. Dizon called it “the epitome of shared decision-making.”

Dr. Petrillo noted that it’s critical not to counsel patients based solely on the anecdotal patients who do surprisingly well.

“It’s hard to mention that and not have that be what somebody anchors on,” she said. But that speaks to “how desperate people can feel, how hopeful they can be.”

Dr. Khan, Dr. Petrillo, and Dr. Chasky all reported no relevant conflicts of interest.

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

Chemotherapy has fallen out of favor for treating cancer toward the end of life. The toxicity is too high, and the benefit, if any, is often too low.

Immunotherapy, however, has been taking its place. Checkpoint inhibitors are increasingly being initiated to treat metastatic cancer in patients approaching the end of life and have become the leading driver of end-of-life cancer spending.

This means “there are patients who are getting immunotherapy who shouldn’t,” said Yale University, New Haven, Connecticut, surgical oncologist Sajid Khan, MD, senior investigator on a recent study that highlighted the growing use of these agents in patients’ last month of life.

What’s driving this trend, and how can oncologists avoid overtreatment with immunotherapy at the end of life?
 

The N-of-1 Patient

With immunotherapy at the end of life, “each of us has had our N-of-1” where a patient bounces back with a remarkable and durable response, said Don Dizon, MD, a gynecologic oncologist at Brown University, Providence, Rhode Island.

He recalled a patient with sarcoma who did not respond to chemotherapy. But after Dr. Dizon started her on immunotherapy, everything turned around. She has now been in remission for 8 years and counting.

The possibility of an unexpected or remarkable responder is seductive. And the improved safety of immunotherapy over chemotherapy adds to the allure.

Meanwhile, patients are often desperate. It’s rare for someone to be ready to stop treatment, Dr. Dizon said. Everybody “hopes that they’re going to be the exceptional responder.”

At the end of the day, the question often becomes: “Why not try immunotherapy? What’s there to lose?”

This thinking may be prompting broader use of immunotherapy in late-stage disease, even in instances with no Food and Drug Administration indication and virtually no supportive data, such as for metastatic ovarian cancer, Dr. Dizon said.
 

Back to Earth

The problem with the hopeful approach is that end-of-life turnarounds with immunotherapy are rare, and there’s no way at the moment to predict who will have one, said Laura Petrillo, MD, a palliative care physician at Massachusetts General Hospital, Boston.

Even though immunotherapy generally comes with fewer adverse events than chemotherapy, catastrophic side effects are still possible.

Dr. Petrillo recalled a 95-year-old woman with metastatic cancer who was largely asymptomatic.

She had a qualifying mutation for a checkpoint inhibitor, so her oncologist started her on one. The patient never bounced back from the severe colitis the agent caused, and she died of complications in the hospital.

Although such reactions with immunotherapy are uncommon, less serious problems caused by the agents can still have a major impact on a person’s quality of life. Low-grade diarrhea, for instance, may not sound too bad, but in a patient’s daily life, it can translate to six or more episodes a day.

Even with no side effects, prescribing immunotherapy can mean that patients with limited time left spend a good portion of it at an infusion clinic instead of at home. These patients are also less likely to be referred to hospice and more likely to be admitted to and die in the hospital.

And with treatments that can cost $20,000 per dose, financial toxicity becomes a big concern.

In short, some of the reasons why chemotherapy is not recommended at the end of life also apply to immunotherapy, Dr. Petrillo said.
 

Prescribing Decisions

Recent research highlights the growing use of immunotherapy at the end of life.

Dr. Khan’s retrospective study found, for instance, that the percentage of patients starting immunotherapy in the last 30 days of life increased by about fourfold to fivefold over the study period for the three cancers analyzed — stage IV melanoma, lung, and kidney cancers.

Among the population that died within 30 days, the percentage receiving immunotherapy increased over the study periods — 0.8%-4.3% for melanoma, 0.9%-3.2% for NSCLC, and 0.5%-2.6% for kidney cell carcinoma — prompting the conclusion that immunotherapy prescriptions in the last month of life are on the rise.

Prescribing immunotherapy in patients who ultimately died within 1 month occurred more frequently at low-volume, nonacademic centers than at academic or high-volume centers, and outcomes varied by practice setting.

Patients had better survival outcomes overall when receiving immunotherapy at academic or high-volume centers — a finding Dr. Khan said is worth investigating further. Possible explanations include better management of severe immune-related side effects at larger centers and more caution when prescribing immunotherapy to “borderline” candidates, such as those with several comorbidities.

Importantly, given the retrospective design, Dr. Khan and colleagues already knew which patients prescribed immunotherapy died within 30 days of initiating treatment.

More specifically, 5192 of 71,204 patients who received immunotherapy (7.3%) died within a month of initiating therapy, while 66,012 (92.7%) lived beyond that point.

The study, however, did not assess how the remaining 92.7% who lived beyond 30 days fared on immunotherapy and the differences between those who lived less than 30 days and those who survived longer.

Knowing the outcome of patients at the outset of the analysis still leaves open the question of when immunotherapy can extend life and when it can’t for the patient in front of you.

To avoid overtreating at the end of life, it’s important to have “the same standard that you have for giving chemotherapy. You have to treat it with the same respect,” said Moshe Chasky, MD, a community medical oncologist with Alliance Cancer Specialists in Philadelphia, Pennsylvania. “You can’t just be throwing” immunotherapy around “at the end of life.”

While there are no clear predictors of risk and benefit, there are some factors to help guide decisions.

As with chemotherapy, Dr. Petrillo said performance status is key. Dr. Petrillo and colleagues found that median overall survival with immune checkpoint inhibitors for advanced non–small cell lung cancer was 14.3 months in patients with an Eastern Cooperative Oncology Group performance score of 0-1 but only 4.5 months with scores of ≥ 2.

Dr. Khan also found that immunotherapy survival is, unsurprisingly, worse in patients with high metastatic burdens and more comorbidities.

“You should still consider immunotherapy for metastatic melanoma, non–small cell lung cancer, and renal cell carcinoma,” Dr. Khan said. The message here is to “think twice before using” it, especially in comorbid patients with widespread metastases.

“Just because something can be done doesn’t always mean it should be done,” he said.

At Yale, when Dr. Khan works, immunotherapy decisions are considered by a multidisciplinary tumor board. At Mass General, immunotherapy has generally moved to the frontline setting, and the hospital no longer prescribes checkpoint inhibitors to hospitalized patients because the cost is too high relative to the potential benefit, Dr. Petrillo explained.

Still, with all the uncertainties about risk and benefit, counseling patients is a challenge. Dr. Dizon called it “the epitome of shared decision-making.”

Dr. Petrillo noted that it’s critical not to counsel patients based solely on the anecdotal patients who do surprisingly well.

“It’s hard to mention that and not have that be what somebody anchors on,” she said. But that speaks to “how desperate people can feel, how hopeful they can be.”

Dr. Khan, Dr. Petrillo, and Dr. Chasky all reported no relevant conflicts of interest.

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

Chemotherapy has fallen out of favor for treating cancer toward the end of life. The toxicity is too high, and the benefit, if any, is often too low.

Immunotherapy, however, has been taking its place. Checkpoint inhibitors are increasingly being initiated to treat metastatic cancer in patients approaching the end of life and have become the leading driver of end-of-life cancer spending.

This means “there are patients who are getting immunotherapy who shouldn’t,” said Yale University, New Haven, Connecticut, surgical oncologist Sajid Khan, MD, senior investigator on a recent study that highlighted the growing use of these agents in patients’ last month of life.

What’s driving this trend, and how can oncologists avoid overtreatment with immunotherapy at the end of life?
 

The N-of-1 Patient

With immunotherapy at the end of life, “each of us has had our N-of-1” where a patient bounces back with a remarkable and durable response, said Don Dizon, MD, a gynecologic oncologist at Brown University, Providence, Rhode Island.

He recalled a patient with sarcoma who did not respond to chemotherapy. But after Dr. Dizon started her on immunotherapy, everything turned around. She has now been in remission for 8 years and counting.

The possibility of an unexpected or remarkable responder is seductive. And the improved safety of immunotherapy over chemotherapy adds to the allure.

Meanwhile, patients are often desperate. It’s rare for someone to be ready to stop treatment, Dr. Dizon said. Everybody “hopes that they’re going to be the exceptional responder.”

At the end of the day, the question often becomes: “Why not try immunotherapy? What’s there to lose?”

This thinking may be prompting broader use of immunotherapy in late-stage disease, even in instances with no Food and Drug Administration indication and virtually no supportive data, such as for metastatic ovarian cancer, Dr. Dizon said.
 

Back to Earth

The problem with the hopeful approach is that end-of-life turnarounds with immunotherapy are rare, and there’s no way at the moment to predict who will have one, said Laura Petrillo, MD, a palliative care physician at Massachusetts General Hospital, Boston.

Even though immunotherapy generally comes with fewer adverse events than chemotherapy, catastrophic side effects are still possible.

Dr. Petrillo recalled a 95-year-old woman with metastatic cancer who was largely asymptomatic.

She had a qualifying mutation for a checkpoint inhibitor, so her oncologist started her on one. The patient never bounced back from the severe colitis the agent caused, and she died of complications in the hospital.

Although such reactions with immunotherapy are uncommon, less serious problems caused by the agents can still have a major impact on a person’s quality of life. Low-grade diarrhea, for instance, may not sound too bad, but in a patient’s daily life, it can translate to six or more episodes a day.

Even with no side effects, prescribing immunotherapy can mean that patients with limited time left spend a good portion of it at an infusion clinic instead of at home. These patients are also less likely to be referred to hospice and more likely to be admitted to and die in the hospital.

And with treatments that can cost $20,000 per dose, financial toxicity becomes a big concern.

In short, some of the reasons why chemotherapy is not recommended at the end of life also apply to immunotherapy, Dr. Petrillo said.
 

Prescribing Decisions

Recent research highlights the growing use of immunotherapy at the end of life.

Dr. Khan’s retrospective study found, for instance, that the percentage of patients starting immunotherapy in the last 30 days of life increased by about fourfold to fivefold over the study period for the three cancers analyzed — stage IV melanoma, lung, and kidney cancers.

Among the population that died within 30 days, the percentage receiving immunotherapy increased over the study periods — 0.8%-4.3% for melanoma, 0.9%-3.2% for NSCLC, and 0.5%-2.6% for kidney cell carcinoma — prompting the conclusion that immunotherapy prescriptions in the last month of life are on the rise.

Prescribing immunotherapy in patients who ultimately died within 1 month occurred more frequently at low-volume, nonacademic centers than at academic or high-volume centers, and outcomes varied by practice setting.

Patients had better survival outcomes overall when receiving immunotherapy at academic or high-volume centers — a finding Dr. Khan said is worth investigating further. Possible explanations include better management of severe immune-related side effects at larger centers and more caution when prescribing immunotherapy to “borderline” candidates, such as those with several comorbidities.

Importantly, given the retrospective design, Dr. Khan and colleagues already knew which patients prescribed immunotherapy died within 30 days of initiating treatment.

More specifically, 5192 of 71,204 patients who received immunotherapy (7.3%) died within a month of initiating therapy, while 66,012 (92.7%) lived beyond that point.

The study, however, did not assess how the remaining 92.7% who lived beyond 30 days fared on immunotherapy and the differences between those who lived less than 30 days and those who survived longer.

Knowing the outcome of patients at the outset of the analysis still leaves open the question of when immunotherapy can extend life and when it can’t for the patient in front of you.

To avoid overtreating at the end of life, it’s important to have “the same standard that you have for giving chemotherapy. You have to treat it with the same respect,” said Moshe Chasky, MD, a community medical oncologist with Alliance Cancer Specialists in Philadelphia, Pennsylvania. “You can’t just be throwing” immunotherapy around “at the end of life.”

While there are no clear predictors of risk and benefit, there are some factors to help guide decisions.

As with chemotherapy, Dr. Petrillo said performance status is key. Dr. Petrillo and colleagues found that median overall survival with immune checkpoint inhibitors for advanced non–small cell lung cancer was 14.3 months in patients with an Eastern Cooperative Oncology Group performance score of 0-1 but only 4.5 months with scores of ≥ 2.

Dr. Khan also found that immunotherapy survival is, unsurprisingly, worse in patients with high metastatic burdens and more comorbidities.

“You should still consider immunotherapy for metastatic melanoma, non–small cell lung cancer, and renal cell carcinoma,” Dr. Khan said. The message here is to “think twice before using” it, especially in comorbid patients with widespread metastases.

“Just because something can be done doesn’t always mean it should be done,” he said.

At Yale, when Dr. Khan works, immunotherapy decisions are considered by a multidisciplinary tumor board. At Mass General, immunotherapy has generally moved to the frontline setting, and the hospital no longer prescribes checkpoint inhibitors to hospitalized patients because the cost is too high relative to the potential benefit, Dr. Petrillo explained.

Still, with all the uncertainties about risk and benefit, counseling patients is a challenge. Dr. Dizon called it “the epitome of shared decision-making.”

Dr. Petrillo noted that it’s critical not to counsel patients based solely on the anecdotal patients who do surprisingly well.

“It’s hard to mention that and not have that be what somebody anchors on,” she said. But that speaks to “how desperate people can feel, how hopeful they can be.”

Dr. Khan, Dr. Petrillo, and Dr. Chasky all reported no relevant conflicts of interest.

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

TOPLINE:

Breast cancer immunotherapy trials yield modest clinical impact, with a quarter of trials failing to report their outcomes, particularly among single-center studies which are more likely to go unreported, and many phase 2 studies failing to translate into successful phase 3 trials.

METHODOLOGY:

• Few immunotherapy agents — only pembrolizumab in the United States, as of December 2023, and atezolizumab in Europe — have received approvals for use in patients with breast cancer, indicating low returns on the large number of breast cancer immunotherapy trials launched in the early 2010s.
• In this cross-sectional study, researchers evaluated 331 immunotherapy trials, initiated between January 2004 and April 2023, that enrolled 48,844 patients with breast cancer.
• Of these, 47 were phase 1 trials, 242 were phase 2 trials, and 42 were phase 3 trials.
• A trial was considered reported if the results were posted on ClinicalTrial.gov or reported as an abstract or a manuscript.
• Overall, 120 trials met their completion date up to November 2022; of these, 30 (25%) failed to report outcomes, which included two phase 3 trials.

TAKEAWAY:

• Phase 1 trials had the highest rate of nonreporting (31.8%), followed by phase 2 (23.6%) and phase 3 (22.2%) trials.
• Single-center studies were more likely to be unreported than multicenter studies (35.2% vs 15.0%; P = .02).
• Of 90 reported trials, 47 (52.2%) met their primary endpoints and 43 (47.8%) did not.
• The majority, 17 out of 19 (89.5%), of the reported randomized trials had negative results.

IN PRACTICE:

“The findings of this study suggest that the large number of immunotherapy trials being run have yielded modest clinical impact,” the authors wrote. “More selective initiation of phase 2 trials, grounded in preclinical and biomarker observations and with optimal statistical designs for early efficacy assessment, is needed to increase trial efficiency.” 

SOURCE:

The study, led by Marco Mariani, MD, Università Vita-Salute San Raffaele, Milan, Italy, was published online in JAMA Network Open. 

LIMITATIONS:

The study’s reliance on ClinicalTrials.gov as the primary source of trial data might have resulted in some trials being overlooked. In addition, manual data extraction could cause inaccuracies and potentially introduced biases in the interpretation of trial results. Primary study completion date cutoff of December 2022 could have excluded significant data from more recent trials.

DISCLOSURES:

This study received support via Susan Komen Leadership Grant and the Fondazione AIRC per la Ricerca sul Cancro. Several authors reported receiving grants and personal fees and having other ties with various sources.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Breast cancer immunotherapy trials yield modest clinical impact, with a quarter of trials failing to report their outcomes, particularly among single-center studies which are more likely to go unreported, and many phase 2 studies failing to translate into successful phase 3 trials.

METHODOLOGY:

• Few immunotherapy agents — only pembrolizumab in the United States, as of December 2023, and atezolizumab in Europe — have received approvals for use in patients with breast cancer, indicating low returns on the large number of breast cancer immunotherapy trials launched in the early 2010s.
• In this cross-sectional study, researchers evaluated 331 immunotherapy trials, initiated between January 2004 and April 2023, that enrolled 48,844 patients with breast cancer.
• Of these, 47 were phase 1 trials, 242 were phase 2 trials, and 42 were phase 3 trials.
• A trial was considered reported if the results were posted on ClinicalTrial.gov or reported as an abstract or a manuscript.
• Overall, 120 trials met their completion date up to November 2022; of these, 30 (25%) failed to report outcomes, which included two phase 3 trials.

TAKEAWAY:

• Phase 1 trials had the highest rate of nonreporting (31.8%), followed by phase 2 (23.6%) and phase 3 (22.2%) trials.
• Single-center studies were more likely to be unreported than multicenter studies (35.2% vs 15.0%; P = .02).
• Of 90 reported trials, 47 (52.2%) met their primary endpoints and 43 (47.8%) did not.
• The majority, 17 out of 19 (89.5%), of the reported randomized trials had negative results.

IN PRACTICE:

“The findings of this study suggest that the large number of immunotherapy trials being run have yielded modest clinical impact,” the authors wrote. “More selective initiation of phase 2 trials, grounded in preclinical and biomarker observations and with optimal statistical designs for early efficacy assessment, is needed to increase trial efficiency.” 

SOURCE:

The study, led by Marco Mariani, MD, Università Vita-Salute San Raffaele, Milan, Italy, was published online in JAMA Network Open. 

LIMITATIONS:

The study’s reliance on ClinicalTrials.gov as the primary source of trial data might have resulted in some trials being overlooked. In addition, manual data extraction could cause inaccuracies and potentially introduced biases in the interpretation of trial results. Primary study completion date cutoff of December 2022 could have excluded significant data from more recent trials.

DISCLOSURES:

This study received support via Susan Komen Leadership Grant and the Fondazione AIRC per la Ricerca sul Cancro. Several authors reported receiving grants and personal fees and having other ties with various sources.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Breast cancer immunotherapy trials yield modest clinical impact, with a quarter of trials failing to report their outcomes, particularly among single-center studies which are more likely to go unreported, and many phase 2 studies failing to translate into successful phase 3 trials.

METHODOLOGY:

• Few immunotherapy agents — only pembrolizumab in the United States, as of December 2023, and atezolizumab in Europe — have received approvals for use in patients with breast cancer, indicating low returns on the large number of breast cancer immunotherapy trials launched in the early 2010s.
• In this cross-sectional study, researchers evaluated 331 immunotherapy trials, initiated between January 2004 and April 2023, that enrolled 48,844 patients with breast cancer.
• Of these, 47 were phase 1 trials, 242 were phase 2 trials, and 42 were phase 3 trials.
• A trial was considered reported if the results were posted on ClinicalTrial.gov or reported as an abstract or a manuscript.
• Overall, 120 trials met their completion date up to November 2022; of these, 30 (25%) failed to report outcomes, which included two phase 3 trials.

TAKEAWAY:

• Phase 1 trials had the highest rate of nonreporting (31.8%), followed by phase 2 (23.6%) and phase 3 (22.2%) trials.
• Single-center studies were more likely to be unreported than multicenter studies (35.2% vs 15.0%; P = .02).
• Of 90 reported trials, 47 (52.2%) met their primary endpoints and 43 (47.8%) did not.
• The majority, 17 out of 19 (89.5%), of the reported randomized trials had negative results.

IN PRACTICE:

“The findings of this study suggest that the large number of immunotherapy trials being run have yielded modest clinical impact,” the authors wrote. “More selective initiation of phase 2 trials, grounded in preclinical and biomarker observations and with optimal statistical designs for early efficacy assessment, is needed to increase trial efficiency.” 

SOURCE:

The study, led by Marco Mariani, MD, Università Vita-Salute San Raffaele, Milan, Italy, was published online in JAMA Network Open. 

LIMITATIONS:

The study’s reliance on ClinicalTrials.gov as the primary source of trial data might have resulted in some trials being overlooked. In addition, manual data extraction could cause inaccuracies and potentially introduced biases in the interpretation of trial results. Primary study completion date cutoff of December 2022 could have excluded significant data from more recent trials.

DISCLOSURES:

This study received support via Susan Komen Leadership Grant and the Fondazione AIRC per la Ricerca sul Cancro. Several authors reported receiving grants and personal fees and having other ties with various sources.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.