Breast Cancer

SAN ANTONIO – Circulating tumor cells are a useful prognostic biomarker in early breast cancer patients treated with neoadjuvant chemotherapy, according to findings from an international meta-analysis of individual patient data.

The cells (CTCs), which can be measured using a Food and Drug Administration–approved assay, are known to seed distant metastases and to be prognostic before and during therapy for patients with metastatic breast cancer, and prognostic before adjuvant therapy for patients with nonmetastatic breast cancer.

However, findings in the neoadjuvant setting have been variable, Francois-Clement Bidard, MD, of Institut Curie, Paris, reported at the San Antonio Breast Cancer Symposium.

In the study (the international meta-analysis of circulating tumor cell detection in early breast cancer patients treated by neoadjuvant chemotherapy, or IMENEO), CTCs were useful, independent of pathologic complete response, for predicting overall survival and distant disease-free survival in the neoadjuvant setting. Further, IMENEO showed for the first time that CTCs also predict locoregional relapse-free survival,

Based on the analysis of data from 2,156 patients from 21 studies and 16 centers in 10 countries, the CTC positivity rates using thresholds of one or more, two or more, and five or more, respectively, were 25%, 13%, and 6% in 1,574 patients tested at baseline, 17%, 6%, and 3% in 290 tested after neoadjuvant chemotherapy, 15%, 5%, and 1% in 1,200 tested before surgery, and 11%, 4%, and 1% in 285 tested after surgery, Dr. Bidard said.

Prior to neoadjuvant chemotherapy, at least one CTC was found in 19%, 22%, 24%, 29% and 41% of cT1, T2, T3, T4a-c, and T4d breast cancers, respectively, and this was marginally associated with hormone receptor negativity, he said, noting that later CTC detection rates were not associated with any patient baseline characteristics.

Nearly one in four patients (24%) achieved pathologic complete response, but this was not associated at any time point with CTC count.

For the primary study endpoint of overall survival, a significant association was found with the presence of at least two CTCs at baseline (hazard ratio, 2.6 for two CTCs; 3.84 for three to four CTCs; and 6.25 for five or more CTCs). Similar associations were found for distant disease-free survival (hazard ratios, 2.4, 3.4, and 5.0, respectively) and for locoregional relapse-free interval with two CTCs and five or more CTCs (hazard ratios, 2.4 and 4.2, respectively).

Similar results were found using later time points, such as after the start of neoadjuvant chemotherapy or before surgery, he said.

On multivariate analysis, baseline CTC detection using any of the thresholds remained an independent predictor of overall and distant disease-free survival and locoregional relapse-free interval when considered together with pathologic complete response, cT, cN, and tumor subtype, suggesting that CTC measurement adds value to comprehensive prognostic models.

That is, they complement rather than duplicate usual prognostic factors and pathologic complete response rates to better predict outcomes in patients with early breast cancer in the neoadjuvant setting, Dr. Bidard said.

This study was supported by a research grant from Janssen Diagnostics. Dr. Bidard reported having no disclosures.

[email protected]

SAN ANTONIO – Circulating tumor cells are a useful prognostic biomarker in early breast cancer patients treated with neoadjuvant chemotherapy, according to findings from an international meta-analysis of individual patient data.

The cells (CTCs), which can be measured using a Food and Drug Administration–approved assay, are known to seed distant metastases and to be prognostic before and during therapy for patients with metastatic breast cancer, and prognostic before adjuvant therapy for patients with nonmetastatic breast cancer.

However, findings in the neoadjuvant setting have been variable, Francois-Clement Bidard, MD, of Institut Curie, Paris, reported at the San Antonio Breast Cancer Symposium.

In the study (the international meta-analysis of circulating tumor cell detection in early breast cancer patients treated by neoadjuvant chemotherapy, or IMENEO), CTCs were useful, independent of pathologic complete response, for predicting overall survival and distant disease-free survival in the neoadjuvant setting. Further, IMENEO showed for the first time that CTCs also predict locoregional relapse-free survival,

Based on the analysis of data from 2,156 patients from 21 studies and 16 centers in 10 countries, the CTC positivity rates using thresholds of one or more, two or more, and five or more, respectively, were 25%, 13%, and 6% in 1,574 patients tested at baseline, 17%, 6%, and 3% in 290 tested after neoadjuvant chemotherapy, 15%, 5%, and 1% in 1,200 tested before surgery, and 11%, 4%, and 1% in 285 tested after surgery, Dr. Bidard said.

Prior to neoadjuvant chemotherapy, at least one CTC was found in 19%, 22%, 24%, 29% and 41% of cT1, T2, T3, T4a-c, and T4d breast cancers, respectively, and this was marginally associated with hormone receptor negativity, he said, noting that later CTC detection rates were not associated with any patient baseline characteristics.

Nearly one in four patients (24%) achieved pathologic complete response, but this was not associated at any time point with CTC count.

For the primary study endpoint of overall survival, a significant association was found with the presence of at least two CTCs at baseline (hazard ratio, 2.6 for two CTCs; 3.84 for three to four CTCs; and 6.25 for five or more CTCs). Similar associations were found for distant disease-free survival (hazard ratios, 2.4, 3.4, and 5.0, respectively) and for locoregional relapse-free interval with two CTCs and five or more CTCs (hazard ratios, 2.4 and 4.2, respectively).

Similar results were found using later time points, such as after the start of neoadjuvant chemotherapy or before surgery, he said.

On multivariate analysis, baseline CTC detection using any of the thresholds remained an independent predictor of overall and distant disease-free survival and locoregional relapse-free interval when considered together with pathologic complete response, cT, cN, and tumor subtype, suggesting that CTC measurement adds value to comprehensive prognostic models.

That is, they complement rather than duplicate usual prognostic factors and pathologic complete response rates to better predict outcomes in patients with early breast cancer in the neoadjuvant setting, Dr. Bidard said.

This study was supported by a research grant from Janssen Diagnostics. Dr. Bidard reported having no disclosures.

[email protected]

SAN ANTONIO – Circulating tumor cells are a useful prognostic biomarker in early breast cancer patients treated with neoadjuvant chemotherapy, according to findings from an international meta-analysis of individual patient data.

The cells (CTCs), which can be measured using a Food and Drug Administration–approved assay, are known to seed distant metastases and to be prognostic before and during therapy for patients with metastatic breast cancer, and prognostic before adjuvant therapy for patients with nonmetastatic breast cancer.

However, findings in the neoadjuvant setting have been variable, Francois-Clement Bidard, MD, of Institut Curie, Paris, reported at the San Antonio Breast Cancer Symposium.

In the study (the international meta-analysis of circulating tumor cell detection in early breast cancer patients treated by neoadjuvant chemotherapy, or IMENEO), CTCs were useful, independent of pathologic complete response, for predicting overall survival and distant disease-free survival in the neoadjuvant setting. Further, IMENEO showed for the first time that CTCs also predict locoregional relapse-free survival,

Based on the analysis of data from 2,156 patients from 21 studies and 16 centers in 10 countries, the CTC positivity rates using thresholds of one or more, two or more, and five or more, respectively, were 25%, 13%, and 6% in 1,574 patients tested at baseline, 17%, 6%, and 3% in 290 tested after neoadjuvant chemotherapy, 15%, 5%, and 1% in 1,200 tested before surgery, and 11%, 4%, and 1% in 285 tested after surgery, Dr. Bidard said.

Prior to neoadjuvant chemotherapy, at least one CTC was found in 19%, 22%, 24%, 29% and 41% of cT1, T2, T3, T4a-c, and T4d breast cancers, respectively, and this was marginally associated with hormone receptor negativity, he said, noting that later CTC detection rates were not associated with any patient baseline characteristics.

Nearly one in four patients (24%) achieved pathologic complete response, but this was not associated at any time point with CTC count.

For the primary study endpoint of overall survival, a significant association was found with the presence of at least two CTCs at baseline (hazard ratio, 2.6 for two CTCs; 3.84 for three to four CTCs; and 6.25 for five or more CTCs). Similar associations were found for distant disease-free survival (hazard ratios, 2.4, 3.4, and 5.0, respectively) and for locoregional relapse-free interval with two CTCs and five or more CTCs (hazard ratios, 2.4 and 4.2, respectively).

Similar results were found using later time points, such as after the start of neoadjuvant chemotherapy or before surgery, he said.

On multivariate analysis, baseline CTC detection using any of the thresholds remained an independent predictor of overall and distant disease-free survival and locoregional relapse-free interval when considered together with pathologic complete response, cT, cN, and tumor subtype, suggesting that CTC measurement adds value to comprehensive prognostic models.

That is, they complement rather than duplicate usual prognostic factors and pathologic complete response rates to better predict outcomes in patients with early breast cancer in the neoadjuvant setting, Dr. Bidard said.

This study was supported by a research grant from Janssen Diagnostics. Dr. Bidard reported having no disclosures.

[email protected]

Triage to chemotherapy using a Ki67-based Preoperative Endocrine Prognostic Index (PEPI), which also integrates residual disease burden, appears useful for deescalating adjuvant treatment after neoadjuvant aromatase inhibitor (AI) therapy for breast cancer, investigators report in the Journal of Clinical Oncology.

Only 4 of 109 patients (3.7%) in the American College of Surgeons Oncology Group Z1031B trial with a PEPI score of 0 relapsed after a median of 5.5 years (and were therefore unlikely to benefit from adjuvant chemotherapy), compared with 49 (14.4%) of 341 patients with a PEPI score greater than 0 (recurrence hazard ratio, 0.27), reported Matthew J. Ellis, MD, of Baylor College of Medicine, Houston, and his associates.

[email protected]

Triage to chemotherapy using a Ki67-based Preoperative Endocrine Prognostic Index (PEPI), which also integrates residual disease burden, appears useful for deescalating adjuvant treatment after neoadjuvant aromatase inhibitor (AI) therapy for breast cancer, investigators report in the Journal of Clinical Oncology.

Only 4 of 109 patients (3.7%) in the American College of Surgeons Oncology Group Z1031B trial with a PEPI score of 0 relapsed after a median of 5.5 years (and were therefore unlikely to benefit from adjuvant chemotherapy), compared with 49 (14.4%) of 341 patients with a PEPI score greater than 0 (recurrence hazard ratio, 0.27), reported Matthew J. Ellis, MD, of Baylor College of Medicine, Houston, and his associates.

[email protected]

Triage to chemotherapy using a Ki67-based Preoperative Endocrine Prognostic Index (PEPI), which also integrates residual disease burden, appears useful for deescalating adjuvant treatment after neoadjuvant aromatase inhibitor (AI) therapy for breast cancer, investigators report in the Journal of Clinical Oncology.

Only 4 of 109 patients (3.7%) in the American College of Surgeons Oncology Group Z1031B trial with a PEPI score of 0 relapsed after a median of 5.5 years (and were therefore unlikely to benefit from adjuvant chemotherapy), compared with 49 (14.4%) of 341 patients with a PEPI score greater than 0 (recurrence hazard ratio, 0.27), reported Matthew J. Ellis, MD, of Baylor College of Medicine, Houston, and his associates.

[email protected]

SAN ANTONIO – PARPi 7, BRCAness, and MammaPrint high1/(ultra)high2 signatures could help predict response to combination therapy with the poly ADP ribose polymerase (PARP) inhibitors veliparib and carboplatin among high-risk breast cancer patients and thereby improve patient care, according to findings from the I-SPY 2 clinical trial.

“I-SPY 2 is a phase II adaptively randomized neoadjuvant clinical trial with a shared control arm where patients receive standard neoadjuvant chemotherapy, and up to 4 simultaneous investigational arms. The primary endpoint of the trial is pathologic complete response, or pCR. The goal is to match therapies with the most responsive breast cancer subtypes,” Denise M. Wolf, PhD, of the University of California, San Francisco, explained at the San Antonio Breast Cancer Symposium.

The current analysis of I-Spy 2 data focuses on veliparib/carboplatin (VC), and the subtypes Dr. Wolf mentioned are defined by hormone receptor (HR) and HER2 expression, and by MammaPrint high1 or (ultra)high2 risk status, which, “roughly speaking, is a further stratification of the poor prognosis group into high- and extra-high-risk groups,” she said.

“This arm was open to HER2-negative patients, and graduated successfully in the triple-negative subset,” she noted, explaining that “agents or combinations graduate for efficacy if they reach 85% predicted probability of success in a subsequent phase III trial in the most responsive patient subset.”

The biomarker component of the trial aimed to evaluate biomarkers associated with the mechanisms of action of each investigational agent along with the predefined subsets.

Although the findings require verification in a larger trial, Dr. Wolf and her colleagues found that three biomarkers – the PARPi 7 gene signature, the 77-gene BRCAness signature (which both relate to DNA damage repair deficiency), and the MammaPrint high1 and (ultra)high2 risk categories – were each moderately correlated with treatment response in 72 patients receiving veliparib/carboplatin (VC), but not in 44 controls, and that the treatment-biomarker interactions retained statistical significance after adjusting for hormone receptor status.

“And so we asked the question, ‘Are these signatures identifying the same patients – and if not, might there be a way to combine them to identify a subset of patients who are especially likely to respond to VC?’” she said.

Further analysis showed that even though each of the biomarkers was a predictor of response, the biomarkers did not appear to identify exactly the same patients, therefore combining them might be of benefit.

“We did this using a simple voting scheme to combine pairs of biomarkers,” she said, adding that if the two paired biomarkers predicted resistance, the biomarker also predicted resistance. If only 1 predicted resistance, the combination predicted resistance, and only if both biomarkers predicted sensitivity did the combination predict sensitivity.

In the graduated triple-negative subset, for example, the 40% of patients who were PARPi 7–high and MammaPrint high2 (the two biomarkers most predictive of response) a dramatic separation was seen in the pCR probability curves, with an estimated pCR of 79% with VC treatment vs. 23% in the control arm.

“In contrast, triple-negative patients who were negative for one or more of the sensitivity markers had nearly overlapping probability response curves, from which we conclude that nearly all of the specific sensitivity to VC seen in the triple-negative patients is found in that subset who are positive for both sensitivity markers,” she said.

Additionally, although only 9% of HR-positive/HER2-negative patients were PARPi 7-high and MammaPrint high2, those patients also appeared to be more responsive to VC vs. the control arm (49% vs. 15%).

The results also demonstrate the value of an exploratory voting method for combining multiple biomarkers for the same treatment, Dr. Wolf noted.

However, the findings are limited by the small sample size and need to be evaluated in larger trials, and the biomarkers also need to be evaluated in carboplatin-only arms in order to “tease out whether the biomarkers are really specific to a PARP inhibitor with carboplatin or whether they might also apply to carboplatin alone.

“Our ongoing and future work is to develop predictive biomarkers for other I-Spy 2 agents,” she said.

Dr. Wolf reported having no disclosures.

[email protected]

SAN ANTONIO – PARPi 7, BRCAness, and MammaPrint high1/(ultra)high2 signatures could help predict response to combination therapy with the poly ADP ribose polymerase (PARP) inhibitors veliparib and carboplatin among high-risk breast cancer patients and thereby improve patient care, according to findings from the I-SPY 2 clinical trial.

“I-SPY 2 is a phase II adaptively randomized neoadjuvant clinical trial with a shared control arm where patients receive standard neoadjuvant chemotherapy, and up to 4 simultaneous investigational arms. The primary endpoint of the trial is pathologic complete response, or pCR. The goal is to match therapies with the most responsive breast cancer subtypes,” Denise M. Wolf, PhD, of the University of California, San Francisco, explained at the San Antonio Breast Cancer Symposium.

The current analysis of I-Spy 2 data focuses on veliparib/carboplatin (VC), and the subtypes Dr. Wolf mentioned are defined by hormone receptor (HR) and HER2 expression, and by MammaPrint high1 or (ultra)high2 risk status, which, “roughly speaking, is a further stratification of the poor prognosis group into high- and extra-high-risk groups,” she said.

“This arm was open to HER2-negative patients, and graduated successfully in the triple-negative subset,” she noted, explaining that “agents or combinations graduate for efficacy if they reach 85% predicted probability of success in a subsequent phase III trial in the most responsive patient subset.”

The biomarker component of the trial aimed to evaluate biomarkers associated with the mechanisms of action of each investigational agent along with the predefined subsets.

Although the findings require verification in a larger trial, Dr. Wolf and her colleagues found that three biomarkers – the PARPi 7 gene signature, the 77-gene BRCAness signature (which both relate to DNA damage repair deficiency), and the MammaPrint high1 and (ultra)high2 risk categories – were each moderately correlated with treatment response in 72 patients receiving veliparib/carboplatin (VC), but not in 44 controls, and that the treatment-biomarker interactions retained statistical significance after adjusting for hormone receptor status.

“And so we asked the question, ‘Are these signatures identifying the same patients – and if not, might there be a way to combine them to identify a subset of patients who are especially likely to respond to VC?’” she said.

Further analysis showed that even though each of the biomarkers was a predictor of response, the biomarkers did not appear to identify exactly the same patients, therefore combining them might be of benefit.

“We did this using a simple voting scheme to combine pairs of biomarkers,” she said, adding that if the two paired biomarkers predicted resistance, the biomarker also predicted resistance. If only 1 predicted resistance, the combination predicted resistance, and only if both biomarkers predicted sensitivity did the combination predict sensitivity.

In the graduated triple-negative subset, for example, the 40% of patients who were PARPi 7–high and MammaPrint high2 (the two biomarkers most predictive of response) a dramatic separation was seen in the pCR probability curves, with an estimated pCR of 79% with VC treatment vs. 23% in the control arm.

“In contrast, triple-negative patients who were negative for one or more of the sensitivity markers had nearly overlapping probability response curves, from which we conclude that nearly all of the specific sensitivity to VC seen in the triple-negative patients is found in that subset who are positive for both sensitivity markers,” she said.

Additionally, although only 9% of HR-positive/HER2-negative patients were PARPi 7-high and MammaPrint high2, those patients also appeared to be more responsive to VC vs. the control arm (49% vs. 15%).

The results also demonstrate the value of an exploratory voting method for combining multiple biomarkers for the same treatment, Dr. Wolf noted.

However, the findings are limited by the small sample size and need to be evaluated in larger trials, and the biomarkers also need to be evaluated in carboplatin-only arms in order to “tease out whether the biomarkers are really specific to a PARP inhibitor with carboplatin or whether they might also apply to carboplatin alone.

“Our ongoing and future work is to develop predictive biomarkers for other I-Spy 2 agents,” she said.

Dr. Wolf reported having no disclosures.

[email protected]

SAN ANTONIO – PARPi 7, BRCAness, and MammaPrint high1/(ultra)high2 signatures could help predict response to combination therapy with the poly ADP ribose polymerase (PARP) inhibitors veliparib and carboplatin among high-risk breast cancer patients and thereby improve patient care, according to findings from the I-SPY 2 clinical trial.

“I-SPY 2 is a phase II adaptively randomized neoadjuvant clinical trial with a shared control arm where patients receive standard neoadjuvant chemotherapy, and up to 4 simultaneous investigational arms. The primary endpoint of the trial is pathologic complete response, or pCR. The goal is to match therapies with the most responsive breast cancer subtypes,” Denise M. Wolf, PhD, of the University of California, San Francisco, explained at the San Antonio Breast Cancer Symposium.

The current analysis of I-Spy 2 data focuses on veliparib/carboplatin (VC), and the subtypes Dr. Wolf mentioned are defined by hormone receptor (HR) and HER2 expression, and by MammaPrint high1 or (ultra)high2 risk status, which, “roughly speaking, is a further stratification of the poor prognosis group into high- and extra-high-risk groups,” she said.

“This arm was open to HER2-negative patients, and graduated successfully in the triple-negative subset,” she noted, explaining that “agents or combinations graduate for efficacy if they reach 85% predicted probability of success in a subsequent phase III trial in the most responsive patient subset.”

The biomarker component of the trial aimed to evaluate biomarkers associated with the mechanisms of action of each investigational agent along with the predefined subsets.

Although the findings require verification in a larger trial, Dr. Wolf and her colleagues found that three biomarkers – the PARPi 7 gene signature, the 77-gene BRCAness signature (which both relate to DNA damage repair deficiency), and the MammaPrint high1 and (ultra)high2 risk categories – were each moderately correlated with treatment response in 72 patients receiving veliparib/carboplatin (VC), but not in 44 controls, and that the treatment-biomarker interactions retained statistical significance after adjusting for hormone receptor status.

“And so we asked the question, ‘Are these signatures identifying the same patients – and if not, might there be a way to combine them to identify a subset of patients who are especially likely to respond to VC?’” she said.

Further analysis showed that even though each of the biomarkers was a predictor of response, the biomarkers did not appear to identify exactly the same patients, therefore combining them might be of benefit.

“We did this using a simple voting scheme to combine pairs of biomarkers,” she said, adding that if the two paired biomarkers predicted resistance, the biomarker also predicted resistance. If only 1 predicted resistance, the combination predicted resistance, and only if both biomarkers predicted sensitivity did the combination predict sensitivity.

In the graduated triple-negative subset, for example, the 40% of patients who were PARPi 7–high and MammaPrint high2 (the two biomarkers most predictive of response) a dramatic separation was seen in the pCR probability curves, with an estimated pCR of 79% with VC treatment vs. 23% in the control arm.

“In contrast, triple-negative patients who were negative for one or more of the sensitivity markers had nearly overlapping probability response curves, from which we conclude that nearly all of the specific sensitivity to VC seen in the triple-negative patients is found in that subset who are positive for both sensitivity markers,” she said.

Additionally, although only 9% of HR-positive/HER2-negative patients were PARPi 7-high and MammaPrint high2, those patients also appeared to be more responsive to VC vs. the control arm (49% vs. 15%).

The results also demonstrate the value of an exploratory voting method for combining multiple biomarkers for the same treatment, Dr. Wolf noted.

However, the findings are limited by the small sample size and need to be evaluated in larger trials, and the biomarkers also need to be evaluated in carboplatin-only arms in order to “tease out whether the biomarkers are really specific to a PARP inhibitor with carboplatin or whether they might also apply to carboplatin alone.

“Our ongoing and future work is to develop predictive biomarkers for other I-Spy 2 agents,” she said.

Dr. Wolf reported having no disclosures.

[email protected]

Background The importance of social support for cancer patients has been established in previous studies. However, much of the existing research has identified associations between general measures of social support and various health indicators. Nevertheless, some research has begun to suggest the utility of more nuanced understandings of how patients receive and use social support.

Objective To examine the roles of nondirective (ie, support that accepts recipients’ feelings and is cooperative with their plans) and directive support (ie, support that prescribes “correct” choices and feelings) as well as social support needs and desires among patients with advanced breast cancer.

Methods We conducted semi-structured interviews (qualitative method) with 8 patients with stage IV breast cancer to collect qualitative information about the disease-related challenges they faced, the support they received from their families and medical teams, and the appropriateness of directive and nondirective support. In addition, we used the 14-item Hospital Anxiety and Depression Scale (HADS) to assess clinically relevant cut-offs for anxiety and depression and the 16-item Social Support Inventory to assess the provision of nondirective and directive social support to the patients (quantitative method).

Results Qualitative findings suggested that there was considerable variability among patients’ reports of social support provided by family, friends, and the medical team. From the qualitative data, patients reported directive support as more useful in times of acute need and emphasized the importance of supportive systems rather than supportive persons in providing emotional support. From the quantitative data, patients reported nondirective support as more typical of support received from both family and medical teams than directive support. On the HADS, 1 patient had a score of 9 on the anxiety subscale, above the score of 7 that is for mild anxiety. No patients scored above the criterion for mild depression, also a score of 7.

Limitations Very small sample limits the ability to generalize findings.

Conclusions The right type of support for patients with advanced breast cancer is contingent on a range of variables, which suggests that the key characteristic of support may not be any particular feature, but the nuanced adjustment of its content and style of delivery to the patient’s circumstances.

Funding Peers for Progress

Click on the PDF icon at the top of this introduction to read the full article.

Background The importance of social support for cancer patients has been established in previous studies. However, much of the existing research has identified associations between general measures of social support and various health indicators. Nevertheless, some research has begun to suggest the utility of more nuanced understandings of how patients receive and use social support.

Objective To examine the roles of nondirective (ie, support that accepts recipients’ feelings and is cooperative with their plans) and directive support (ie, support that prescribes “correct” choices and feelings) as well as social support needs and desires among patients with advanced breast cancer.

Methods We conducted semi-structured interviews (qualitative method) with 8 patients with stage IV breast cancer to collect qualitative information about the disease-related challenges they faced, the support they received from their families and medical teams, and the appropriateness of directive and nondirective support. In addition, we used the 14-item Hospital Anxiety and Depression Scale (HADS) to assess clinically relevant cut-offs for anxiety and depression and the 16-item Social Support Inventory to assess the provision of nondirective and directive social support to the patients (quantitative method).

Results Qualitative findings suggested that there was considerable variability among patients’ reports of social support provided by family, friends, and the medical team. From the qualitative data, patients reported directive support as more useful in times of acute need and emphasized the importance of supportive systems rather than supportive persons in providing emotional support. From the quantitative data, patients reported nondirective support as more typical of support received from both family and medical teams than directive support. On the HADS, 1 patient had a score of 9 on the anxiety subscale, above the score of 7 that is for mild anxiety. No patients scored above the criterion for mild depression, also a score of 7.

Limitations Very small sample limits the ability to generalize findings.

Conclusions The right type of support for patients with advanced breast cancer is contingent on a range of variables, which suggests that the key characteristic of support may not be any particular feature, but the nuanced adjustment of its content and style of delivery to the patient’s circumstances.

Funding Peers for Progress

Click on the PDF icon at the top of this introduction to read the full article.

Background The importance of social support for cancer patients has been established in previous studies. However, much of the existing research has identified associations between general measures of social support and various health indicators. Nevertheless, some research has begun to suggest the utility of more nuanced understandings of how patients receive and use social support.

Objective To examine the roles of nondirective (ie, support that accepts recipients’ feelings and is cooperative with their plans) and directive support (ie, support that prescribes “correct” choices and feelings) as well as social support needs and desires among patients with advanced breast cancer.

Methods We conducted semi-structured interviews (qualitative method) with 8 patients with stage IV breast cancer to collect qualitative information about the disease-related challenges they faced, the support they received from their families and medical teams, and the appropriateness of directive and nondirective support. In addition, we used the 14-item Hospital Anxiety and Depression Scale (HADS) to assess clinically relevant cut-offs for anxiety and depression and the 16-item Social Support Inventory to assess the provision of nondirective and directive social support to the patients (quantitative method).

Results Qualitative findings suggested that there was considerable variability among patients’ reports of social support provided by family, friends, and the medical team. From the qualitative data, patients reported directive support as more useful in times of acute need and emphasized the importance of supportive systems rather than supportive persons in providing emotional support. From the quantitative data, patients reported nondirective support as more typical of support received from both family and medical teams than directive support. On the HADS, 1 patient had a score of 9 on the anxiety subscale, above the score of 7 that is for mild anxiety. No patients scored above the criterion for mild depression, also a score of 7.

Limitations Very small sample limits the ability to generalize findings.

Conclusions The right type of support for patients with advanced breast cancer is contingent on a range of variables, which suggests that the key characteristic of support may not be any particular feature, but the nuanced adjustment of its content and style of delivery to the patient’s circumstances.

Funding Peers for Progress

Click on the PDF icon at the top of this introduction to read the full article.

Women with breast cancer are much less likely to opt for contralateral prophylactic mastectomies if they know it won’t prolong their lives, according to a survey of 2,402 women with unilateral stage 0-II breast cancer.

Contralateral prophylactic mastectomy (CPM) – removing the healthy breast along with the cancerous one – is on the rise for early-stage, unilateral breast cancer because of “celebrity exposure and publicity,” said investigators led by Reshma Jagsi, MD, of the University of Michigan, Ann Arbor (JAMA Surg. 2016 Dec 21. doi: 10.1001/jamasurg.2016.4749).

CPM might make sense for women at genetic risk for breast cancer, like actress Angelina Jolie – who made headlines in 2013 when she opted for double mastectomy – but the survey found that nearly one in five women with no genetic risks also opted for CPM when their surgeons made no recommendation either way.

When surgeons advised against the procedure, the number fell to about 2%. Meanwhile, many women said their surgeons stayed silent on the issue, which is a problem, according to the investigators.

Overall, about 44% of women in the survey considered CPM, but just 38% of them said they knew that CPM didn’t improve survival for all women with breast cancer.

“Some patients may pursue CPM for cosmetic symmetry or other reasons. However, it is not clear that average-risk patients who choose CPM truly understand that it will not improve their survival or alter recurrence risk,” the investigators noted.

Surgeons’ knowledge and communication practices could be targets for quality improvement interventions, the investigators wrote. “Our findings should motivate surgeons to broach these difficult conversations with their patients, to make their recommendations clear, and to promote patients’ peace of mind by emphasizing how other treatments complement surgery to reduce the risk of both tumor recurrence and subsequent cancer development,” they said.

Women in the study were identified through the Surveillance Epidemiology and End Results (SEER) registries of Los Angeles County and Georgia. They were 62 years old, on average. CPM was associated with younger age, white race, higher educational level, family history, and private insurance.

The National Institutes of Health supported the study. Dr. Jagsi reported having no disclosures. A coauthor reported research funding from Myriad Genetics, Invitae, Ambry Genetics, GeneDx, and Genomic Health.

[email protected]

Women with breast cancer are much less likely to opt for contralateral prophylactic mastectomies if they know it won’t prolong their lives, according to a survey of 2,402 women with unilateral stage 0-II breast cancer.

Contralateral prophylactic mastectomy (CPM) – removing the healthy breast along with the cancerous one – is on the rise for early-stage, unilateral breast cancer because of “celebrity exposure and publicity,” said investigators led by Reshma Jagsi, MD, of the University of Michigan, Ann Arbor (JAMA Surg. 2016 Dec 21. doi: 10.1001/jamasurg.2016.4749).

CPM might make sense for women at genetic risk for breast cancer, like actress Angelina Jolie – who made headlines in 2013 when she opted for double mastectomy – but the survey found that nearly one in five women with no genetic risks also opted for CPM when their surgeons made no recommendation either way.

When surgeons advised against the procedure, the number fell to about 2%. Meanwhile, many women said their surgeons stayed silent on the issue, which is a problem, according to the investigators.

Overall, about 44% of women in the survey considered CPM, but just 38% of them said they knew that CPM didn’t improve survival for all women with breast cancer.

“Some patients may pursue CPM for cosmetic symmetry or other reasons. However, it is not clear that average-risk patients who choose CPM truly understand that it will not improve their survival or alter recurrence risk,” the investigators noted.

Surgeons’ knowledge and communication practices could be targets for quality improvement interventions, the investigators wrote. “Our findings should motivate surgeons to broach these difficult conversations with their patients, to make their recommendations clear, and to promote patients’ peace of mind by emphasizing how other treatments complement surgery to reduce the risk of both tumor recurrence and subsequent cancer development,” they said.

Women in the study were identified through the Surveillance Epidemiology and End Results (SEER) registries of Los Angeles County and Georgia. They were 62 years old, on average. CPM was associated with younger age, white race, higher educational level, family history, and private insurance.

The National Institutes of Health supported the study. Dr. Jagsi reported having no disclosures. A coauthor reported research funding from Myriad Genetics, Invitae, Ambry Genetics, GeneDx, and Genomic Health.

[email protected]

Women with breast cancer are much less likely to opt for contralateral prophylactic mastectomies if they know it won’t prolong their lives, according to a survey of 2,402 women with unilateral stage 0-II breast cancer.

Contralateral prophylactic mastectomy (CPM) – removing the healthy breast along with the cancerous one – is on the rise for early-stage, unilateral breast cancer because of “celebrity exposure and publicity,” said investigators led by Reshma Jagsi, MD, of the University of Michigan, Ann Arbor (JAMA Surg. 2016 Dec 21. doi: 10.1001/jamasurg.2016.4749).

CPM might make sense for women at genetic risk for breast cancer, like actress Angelina Jolie – who made headlines in 2013 when she opted for double mastectomy – but the survey found that nearly one in five women with no genetic risks also opted for CPM when their surgeons made no recommendation either way.

When surgeons advised against the procedure, the number fell to about 2%. Meanwhile, many women said their surgeons stayed silent on the issue, which is a problem, according to the investigators.

Overall, about 44% of women in the survey considered CPM, but just 38% of them said they knew that CPM didn’t improve survival for all women with breast cancer.

“Some patients may pursue CPM for cosmetic symmetry or other reasons. However, it is not clear that average-risk patients who choose CPM truly understand that it will not improve their survival or alter recurrence risk,” the investigators noted.

Surgeons’ knowledge and communication practices could be targets for quality improvement interventions, the investigators wrote. “Our findings should motivate surgeons to broach these difficult conversations with their patients, to make their recommendations clear, and to promote patients’ peace of mind by emphasizing how other treatments complement surgery to reduce the risk of both tumor recurrence and subsequent cancer development,” they said.

Women in the study were identified through the Surveillance Epidemiology and End Results (SEER) registries of Los Angeles County and Georgia. They were 62 years old, on average. CPM was associated with younger age, white race, higher educational level, family history, and private insurance.

The National Institutes of Health supported the study. Dr. Jagsi reported having no disclosures. A coauthor reported research funding from Myriad Genetics, Invitae, Ambry Genetics, GeneDx, and Genomic Health.

[email protected]

SAN ANTONIO – Sentinel lymph node detection after neoadjuvant chemotherapy (NAC) is a safe and feasible strategy for preventing unnecessary systematic lymphadenectomy in patients with operable breast cancer and no clinical signs of cancer in the axillary lymph nodes prior to NAC, according to findings from the French prospective multicenter GANEA 2 trial.

However, further study is needed to assess the clinical impact of the 12% false negative rate associated with sentinel lymph node detection (SLND) in the current study, according to Jean-Marc Classe, MD, who reported the findings at the San Antonio Breast Cancer Symposium.

SLND was feasible in that it was achieved in 570 of 590 women (97%) with large operable breast tumors and negative findings on axillary sonography with fine needle cytology who were enrolled in the study, said Dr. Classe of Institut Cancerologie de l’Ouest Rene Gauducheau, Nantes, France.

Cancer cells were detected by SLND in 139 subjects after NAC and surgery, and all of those patients underwent axillary lymph node dissection. Another 418 had no sentinel node involvement after NAC and surgery, and had adequate follow-up; among those, overall 3-year survival was 97.8% and 3-year disease-free survival was 94.8%,

“In this group of patients ... we found only one axillary relapse,” he said.

These rates are comparable to historical survival rates among those without axillary involvement who undergo axillary lymph node dissection rather than sentinel lymph node detection, and the findings suggest that women with no clinical signs of axillary involvement could be spared systematic lymphadenectomy, he said.

“The standard surgical treatment after neoadjuvant chemotherapy is breast cancer surgery and lymphadenectomy level 1 and 2, but since the [National Surgical Adjuvant Breast and Bowel Project] B-27 trial, we all know that after neoadjuvant chemotherapy there are not any involved nodes in 50%-58% of patients,” he said, adding that about half of all lymphadenectomies in these patients are therefore unnecessary.

That percentage increases to more than 70% in “the very specific situation of patients treated for HER2+ breast cancer with cytologically proved axillary metastases after neoadjuvant chemotherapy,” he said.

“So we know that there is a place for sentinel lymph node biopsy after neoadjuvant chemotherapy in order to avoid unnecessary lymphadenectomy,” he said.

However, the high false negative rate associated with SLND in this and in prior studies, including the first GANEA trial, remains a concern. In fact, the most recent guidelines stated that the proof was too weak to strongly recommend sentinel lymph node biopsy after NAC, he noted.

The GANEA 2 trial was performed in response to a call in those guidelines for additional studies to assess the long-term risks of this strategy.

Study subjects included patients with FIGO stage T1-T3 infiltrating breast cancer who were enrolled from 15 French institutions between July 2010 and February 2014. Those with inflammatory cancer, local relapse, contraindications for NAC, or interrupted NAC due to progressive disease were excluded.

Follow-up included a medical visit with clinical assessment every 6 months and annual mammography.

The findings suggest that in patients with no proof of node involvement before treatment, SLND “seems to be safe within the limits of the short-term follow-up of this study,” Dr. Classe said, noting that given the concerns about the false negative rate and the uncertainty about the clinical impact of that, this approach “is not proved to be a safe procedure outside of trials.”

The strategy will be further evaluated, with a focus on eliminating false negative results, in the GANEA 3 trial, he said.

Dr. Classe reported having no disclosures.

[email protected]

SAN ANTONIO – Sentinel lymph node detection after neoadjuvant chemotherapy (NAC) is a safe and feasible strategy for preventing unnecessary systematic lymphadenectomy in patients with operable breast cancer and no clinical signs of cancer in the axillary lymph nodes prior to NAC, according to findings from the French prospective multicenter GANEA 2 trial.

However, further study is needed to assess the clinical impact of the 12% false negative rate associated with sentinel lymph node detection (SLND) in the current study, according to Jean-Marc Classe, MD, who reported the findings at the San Antonio Breast Cancer Symposium.

SLND was feasible in that it was achieved in 570 of 590 women (97%) with large operable breast tumors and negative findings on axillary sonography with fine needle cytology who were enrolled in the study, said Dr. Classe of Institut Cancerologie de l’Ouest Rene Gauducheau, Nantes, France.

Cancer cells were detected by SLND in 139 subjects after NAC and surgery, and all of those patients underwent axillary lymph node dissection. Another 418 had no sentinel node involvement after NAC and surgery, and had adequate follow-up; among those, overall 3-year survival was 97.8% and 3-year disease-free survival was 94.8%,

“In this group of patients ... we found only one axillary relapse,” he said.

These rates are comparable to historical survival rates among those without axillary involvement who undergo axillary lymph node dissection rather than sentinel lymph node detection, and the findings suggest that women with no clinical signs of axillary involvement could be spared systematic lymphadenectomy, he said.

“The standard surgical treatment after neoadjuvant chemotherapy is breast cancer surgery and lymphadenectomy level 1 and 2, but since the [National Surgical Adjuvant Breast and Bowel Project] B-27 trial, we all know that after neoadjuvant chemotherapy there are not any involved nodes in 50%-58% of patients,” he said, adding that about half of all lymphadenectomies in these patients are therefore unnecessary.

That percentage increases to more than 70% in “the very specific situation of patients treated for HER2+ breast cancer with cytologically proved axillary metastases after neoadjuvant chemotherapy,” he said.

“So we know that there is a place for sentinel lymph node biopsy after neoadjuvant chemotherapy in order to avoid unnecessary lymphadenectomy,” he said.

However, the high false negative rate associated with SLND in this and in prior studies, including the first GANEA trial, remains a concern. In fact, the most recent guidelines stated that the proof was too weak to strongly recommend sentinel lymph node biopsy after NAC, he noted.

The GANEA 2 trial was performed in response to a call in those guidelines for additional studies to assess the long-term risks of this strategy.

Study subjects included patients with FIGO stage T1-T3 infiltrating breast cancer who were enrolled from 15 French institutions between July 2010 and February 2014. Those with inflammatory cancer, local relapse, contraindications for NAC, or interrupted NAC due to progressive disease were excluded.

Follow-up included a medical visit with clinical assessment every 6 months and annual mammography.

The findings suggest that in patients with no proof of node involvement before treatment, SLND “seems to be safe within the limits of the short-term follow-up of this study,” Dr. Classe said, noting that given the concerns about the false negative rate and the uncertainty about the clinical impact of that, this approach “is not proved to be a safe procedure outside of trials.”

The strategy will be further evaluated, with a focus on eliminating false negative results, in the GANEA 3 trial, he said.

Dr. Classe reported having no disclosures.

[email protected]

SAN ANTONIO – Sentinel lymph node detection after neoadjuvant chemotherapy (NAC) is a safe and feasible strategy for preventing unnecessary systematic lymphadenectomy in patients with operable breast cancer and no clinical signs of cancer in the axillary lymph nodes prior to NAC, according to findings from the French prospective multicenter GANEA 2 trial.

However, further study is needed to assess the clinical impact of the 12% false negative rate associated with sentinel lymph node detection (SLND) in the current study, according to Jean-Marc Classe, MD, who reported the findings at the San Antonio Breast Cancer Symposium.

SLND was feasible in that it was achieved in 570 of 590 women (97%) with large operable breast tumors and negative findings on axillary sonography with fine needle cytology who were enrolled in the study, said Dr. Classe of Institut Cancerologie de l’Ouest Rene Gauducheau, Nantes, France.

Cancer cells were detected by SLND in 139 subjects after NAC and surgery, and all of those patients underwent axillary lymph node dissection. Another 418 had no sentinel node involvement after NAC and surgery, and had adequate follow-up; among those, overall 3-year survival was 97.8% and 3-year disease-free survival was 94.8%,

“In this group of patients ... we found only one axillary relapse,” he said.

These rates are comparable to historical survival rates among those without axillary involvement who undergo axillary lymph node dissection rather than sentinel lymph node detection, and the findings suggest that women with no clinical signs of axillary involvement could be spared systematic lymphadenectomy, he said.

“The standard surgical treatment after neoadjuvant chemotherapy is breast cancer surgery and lymphadenectomy level 1 and 2, but since the [National Surgical Adjuvant Breast and Bowel Project] B-27 trial, we all know that after neoadjuvant chemotherapy there are not any involved nodes in 50%-58% of patients,” he said, adding that about half of all lymphadenectomies in these patients are therefore unnecessary.

That percentage increases to more than 70% in “the very specific situation of patients treated for HER2+ breast cancer with cytologically proved axillary metastases after neoadjuvant chemotherapy,” he said.

“So we know that there is a place for sentinel lymph node biopsy after neoadjuvant chemotherapy in order to avoid unnecessary lymphadenectomy,” he said.

However, the high false negative rate associated with SLND in this and in prior studies, including the first GANEA trial, remains a concern. In fact, the most recent guidelines stated that the proof was too weak to strongly recommend sentinel lymph node biopsy after NAC, he noted.

The GANEA 2 trial was performed in response to a call in those guidelines for additional studies to assess the long-term risks of this strategy.

Study subjects included patients with FIGO stage T1-T3 infiltrating breast cancer who were enrolled from 15 French institutions between July 2010 and February 2014. Those with inflammatory cancer, local relapse, contraindications for NAC, or interrupted NAC due to progressive disease were excluded.

Follow-up included a medical visit with clinical assessment every 6 months and annual mammography.

The findings suggest that in patients with no proof of node involvement before treatment, SLND “seems to be safe within the limits of the short-term follow-up of this study,” Dr. Classe said, noting that given the concerns about the false negative rate and the uncertainty about the clinical impact of that, this approach “is not proved to be a safe procedure outside of trials.”

The strategy will be further evaluated, with a focus on eliminating false negative results, in the GANEA 3 trial, he said.

Dr. Classe reported having no disclosures.

[email protected]

SAN ANTONIO – Every day, practicing oncologists sort through mountains of data from treatment guidelines, clinical trials, protocols, and algorithms to make the best possible therapeutic decisions for their patients.

At Manipal Hospitals in Bangalore, India, those decisions are informed with the aid of Watson for Oncology (WFO), a software platform developed by IBM in concert with clinicians and investigators at Memorial Sloan Kettering Cancer Center in New York City.

In this video interview at the San Antonio Breast Cancer Symposium, S.P. Somashekhar, MBBS, MS, MCH, chairman of the Manipal Comprehensive Cancer Center, discusses how the system is used by the members of the center’s multidisciplinary tumor board to inform decision making. He also describes results of a study he presented at the symposium that shows a relatively high degree of concordance between clinician and WFO choices in the treatment of patients with local breast cancer but less agreement when it comes to the management of metastatic disease, for which there is no universal standard of care.

SAN ANTONIO – Every day, practicing oncologists sort through mountains of data from treatment guidelines, clinical trials, protocols, and algorithms to make the best possible therapeutic decisions for their patients.

At Manipal Hospitals in Bangalore, India, those decisions are informed with the aid of Watson for Oncology (WFO), a software platform developed by IBM in concert with clinicians and investigators at Memorial Sloan Kettering Cancer Center in New York City.

In this video interview at the San Antonio Breast Cancer Symposium, S.P. Somashekhar, MBBS, MS, MCH, chairman of the Manipal Comprehensive Cancer Center, discusses how the system is used by the members of the center’s multidisciplinary tumor board to inform decision making. He also describes results of a study he presented at the symposium that shows a relatively high degree of concordance between clinician and WFO choices in the treatment of patients with local breast cancer but less agreement when it comes to the management of metastatic disease, for which there is no universal standard of care.

SAN ANTONIO – Every day, practicing oncologists sort through mountains of data from treatment guidelines, clinical trials, protocols, and algorithms to make the best possible therapeutic decisions for their patients.

At Manipal Hospitals in Bangalore, India, those decisions are informed with the aid of Watson for Oncology (WFO), a software platform developed by IBM in concert with clinicians and investigators at Memorial Sloan Kettering Cancer Center in New York City.

In this video interview at the San Antonio Breast Cancer Symposium, S.P. Somashekhar, MBBS, MS, MCH, chairman of the Manipal Comprehensive Cancer Center, discusses how the system is used by the members of the center’s multidisciplinary tumor board to inform decision making. He also describes results of a study he presented at the symposium that shows a relatively high degree of concordance between clinician and WFO choices in the treatment of patients with local breast cancer but less agreement when it comes to the management of metastatic disease, for which there is no universal standard of care.

SAN ANTONIO – A combination of a PI3K inhibitor and selective estrogen receptor down-regulator (SERD) met its primary endpoint of 2.1 months better progression-free survival (PFS) in postmenopausal women with locally advanced or metastatic breast cancer who were quickly running out of other treatment options.

Yet the small gain in PFS came at a very high price in terms of toxicities, including mood disorders that may have led to patient suicide attempts, according to investigators.

The BELLE-3 trial looked at the combination of the SERD fulvestrant (Faslodex) and an experimental inhibitor of the PI3 kinase, buparlisib, in postmenopausal women with hormone receptor–positive, human epidermal growth factor receptor–2 (HER2)-negative breast cancer treated with an aromatase inhibitor (AI) who experienced disease progression either on or after receiving therapy with an inhibitor of the mammalian target of rapamycin complex 1 (mTORC1).

The combination of fulvestrant and buparlisib was associated with a median PFS of 3.9 months, compared with 1.8 months for fulvestrant and placebo (P less than .001), Angelo Di Leo, MD, of Ospedale Misericordia e Dolce in Prato, Italy, reported at the San Antonio Breast Cancer Symposium,

Objective response rates (ORR) were low, at 7.8% in the combination arm, and 2.1% in the fulvestrant-plus-placebo arm.

Although the PFS difference was statistically significant, “the higher rate of toxicity in patients receiving buparlisib and fulvestrant, including transaminase elevations and mood disorders, may represent a clinically relevant challenge for future development of this compound in this particular group of patients,” Dr. Di Leo said.
 

Blocks AKT pathway

The preclinical rationale for the use of a P13K inhibitor after disease progression on mTORC1 inhibitor is that current mTOR inhibitors such as everolimus have a feedback mechanism that activates the AKT pathway, and that the use of P13K inhibitors can “abrogate or attenuate this activation, potentially blocking that pathway,” explained coinvestigator Ruth O’Regan, MD, head of the division of hematology and oncology at the University of Wisconsin–Madison School of Medicine and Public Health. Dr. O’Regan discussed the BELLE-3 findings in a briefing prior to Dr. Di Leo’s presentation of the data in general session.

In BELLE-3, 432 postmenopausal women with HR+/HER2-, AI-pretreated, locally advanced or metastatic breast cancer that had progressed on or after treatment with an mTOR inhibitor as the last line of therapy were enrolled. The patients were stratified by the presence or absence of visceral disease and then randomized on a 2:1 basis to fulvestrant 500 mg daily plus either buparlisib 100 mg/day (289 patients), or placebo (143).

As noted, the primary endpoint of investigator-assessed PFS favored the addition of buparlisib, with a hazard ratio for progression of 0.67 (P less than .001). PFS results by independent central review were similar (HR 0.57, P less than .001).

The ORR for the buparlisib/fulvestrant combination, 7.6%, consisted of 0.3% complete responses, and 7.3% partial responses. The ORR for placebo/fulvestrant, 2.1%, was composed entirely of partial responses. The respective clinical benefit rates, defined as a combination of complete and partial responses and stable disease, were 24.6% and 15.4.

The benefit of buparlisib was evidently entirely among patients with visceral disease, with a PFS of 3.1 vs. 1.5 months. In contrast, PFS among patients with no visceral disease was 4.2 vs. 4.1 months, respectively, and was not significant.

In addition, the P13K inhibitor seemed to benefit patients with PIK3CA mutations detected in either the primary tumor or in circulating DNA samples, but not patients with wild-type PIK3CA.
 

Depression, anxiety with combination

Patients assigned to buparlisib/fulvestrant had substantially higher proportions of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) elevations compared with patients on placebo fulvestrant, as well as more reported depression and anxiety. Three patients in the buparlisib arm attempted suicide. There were no reported suicide attempts in the placebo arm.

Dr. O’Regan said at the briefing that mood disorders are known adverse events associated with buparlisib, and that patients with psychiatric disorders were excluded from the trial.

Carlos Arteaga, MD, co-leader of the Breast Cancer Research Program at Vanderbilt-Ingram Cancer Center in Nashville, Tenn., who moderated the briefing, said in an interview that PI kinase mutations do not appear to be a good target, and that a pan-PIK3 inhibitor such as buparlisib may be hitting too many targets at once.

Inhibiting all of the PIK3 isoforms – alpha, beta, gamma, and delta – “may be a little too tough,” he said.

The trial should serve as impetus for developing agents that inhibit only the alpha isoform of PIK3 which mutates and appears to be the driver of some types of breast cancer, he said.

Following Dr. Di Leo’s presentation, perennial SABCS gadfly Steven Vogl, MD, New York, told the speaker that “you presented this very nicely, it’s very interesting biology. I don’t think you’d want to do this again to a human, right? Three month prolongation in PFS, miserable, with diarrhea, depression – you don’t want to do this again, is that correct?”

“I think buparlisib is probably not the best compound to be used in this particular setting of patients,” Dr. Di Leo said, but added that a better-tolerated PI3K inhibitor might be more effective.

“Actually, the study is raising an important question: Should we use the PI3K inhibitor in place of the mTOR inhibitor, or perhaps, as the study suggests, should we use the P13K inhibitors sequentially, after the mTOR inhibitor. This is an open question,” he replied.

Novartis sponsored the study. Dr. Di Leo disclosed consulting and lecture fees from the company, and Dr. O’Regan disclosed contracted research support. Dr. Arteaga reported no disclosures relevant to the study.

[email protected]

SAN ANTONIO – A combination of a PI3K inhibitor and selective estrogen receptor down-regulator (SERD) met its primary endpoint of 2.1 months better progression-free survival (PFS) in postmenopausal women with locally advanced or metastatic breast cancer who were quickly running out of other treatment options.

Yet the small gain in PFS came at a very high price in terms of toxicities, including mood disorders that may have led to patient suicide attempts, according to investigators.

The BELLE-3 trial looked at the combination of the SERD fulvestrant (Faslodex) and an experimental inhibitor of the PI3 kinase, buparlisib, in postmenopausal women with hormone receptor–positive, human epidermal growth factor receptor–2 (HER2)-negative breast cancer treated with an aromatase inhibitor (AI) who experienced disease progression either on or after receiving therapy with an inhibitor of the mammalian target of rapamycin complex 1 (mTORC1).

The combination of fulvestrant and buparlisib was associated with a median PFS of 3.9 months, compared with 1.8 months for fulvestrant and placebo (P less than .001), Angelo Di Leo, MD, of Ospedale Misericordia e Dolce in Prato, Italy, reported at the San Antonio Breast Cancer Symposium,

Objective response rates (ORR) were low, at 7.8% in the combination arm, and 2.1% in the fulvestrant-plus-placebo arm.

Although the PFS difference was statistically significant, “the higher rate of toxicity in patients receiving buparlisib and fulvestrant, including transaminase elevations and mood disorders, may represent a clinically relevant challenge for future development of this compound in this particular group of patients,” Dr. Di Leo said.
 

Blocks AKT pathway

The preclinical rationale for the use of a P13K inhibitor after disease progression on mTORC1 inhibitor is that current mTOR inhibitors such as everolimus have a feedback mechanism that activates the AKT pathway, and that the use of P13K inhibitors can “abrogate or attenuate this activation, potentially blocking that pathway,” explained coinvestigator Ruth O’Regan, MD, head of the division of hematology and oncology at the University of Wisconsin–Madison School of Medicine and Public Health. Dr. O’Regan discussed the BELLE-3 findings in a briefing prior to Dr. Di Leo’s presentation of the data in general session.

In BELLE-3, 432 postmenopausal women with HR+/HER2-, AI-pretreated, locally advanced or metastatic breast cancer that had progressed on or after treatment with an mTOR inhibitor as the last line of therapy were enrolled. The patients were stratified by the presence or absence of visceral disease and then randomized on a 2:1 basis to fulvestrant 500 mg daily plus either buparlisib 100 mg/day (289 patients), or placebo (143).

As noted, the primary endpoint of investigator-assessed PFS favored the addition of buparlisib, with a hazard ratio for progression of 0.67 (P less than .001). PFS results by independent central review were similar (HR 0.57, P less than .001).

The ORR for the buparlisib/fulvestrant combination, 7.6%, consisted of 0.3% complete responses, and 7.3% partial responses. The ORR for placebo/fulvestrant, 2.1%, was composed entirely of partial responses. The respective clinical benefit rates, defined as a combination of complete and partial responses and stable disease, were 24.6% and 15.4.

The benefit of buparlisib was evidently entirely among patients with visceral disease, with a PFS of 3.1 vs. 1.5 months. In contrast, PFS among patients with no visceral disease was 4.2 vs. 4.1 months, respectively, and was not significant.

In addition, the P13K inhibitor seemed to benefit patients with PIK3CA mutations detected in either the primary tumor or in circulating DNA samples, but not patients with wild-type PIK3CA.
 

Depression, anxiety with combination

Patients assigned to buparlisib/fulvestrant had substantially higher proportions of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) elevations compared with patients on placebo fulvestrant, as well as more reported depression and anxiety. Three patients in the buparlisib arm attempted suicide. There were no reported suicide attempts in the placebo arm.

Dr. O’Regan said at the briefing that mood disorders are known adverse events associated with buparlisib, and that patients with psychiatric disorders were excluded from the trial.

Carlos Arteaga, MD, co-leader of the Breast Cancer Research Program at Vanderbilt-Ingram Cancer Center in Nashville, Tenn., who moderated the briefing, said in an interview that PI kinase mutations do not appear to be a good target, and that a pan-PIK3 inhibitor such as buparlisib may be hitting too many targets at once.

Inhibiting all of the PIK3 isoforms – alpha, beta, gamma, and delta – “may be a little too tough,” he said.

The trial should serve as impetus for developing agents that inhibit only the alpha isoform of PIK3 which mutates and appears to be the driver of some types of breast cancer, he said.

Following Dr. Di Leo’s presentation, perennial SABCS gadfly Steven Vogl, MD, New York, told the speaker that “you presented this very nicely, it’s very interesting biology. I don’t think you’d want to do this again to a human, right? Three month prolongation in PFS, miserable, with diarrhea, depression – you don’t want to do this again, is that correct?”

“I think buparlisib is probably not the best compound to be used in this particular setting of patients,” Dr. Di Leo said, but added that a better-tolerated PI3K inhibitor might be more effective.

“Actually, the study is raising an important question: Should we use the PI3K inhibitor in place of the mTOR inhibitor, or perhaps, as the study suggests, should we use the P13K inhibitors sequentially, after the mTOR inhibitor. This is an open question,” he replied.

Novartis sponsored the study. Dr. Di Leo disclosed consulting and lecture fees from the company, and Dr. O’Regan disclosed contracted research support. Dr. Arteaga reported no disclosures relevant to the study.

[email protected]

SAN ANTONIO – A combination of a PI3K inhibitor and selective estrogen receptor down-regulator (SERD) met its primary endpoint of 2.1 months better progression-free survival (PFS) in postmenopausal women with locally advanced or metastatic breast cancer who were quickly running out of other treatment options.

Yet the small gain in PFS came at a very high price in terms of toxicities, including mood disorders that may have led to patient suicide attempts, according to investigators.

The BELLE-3 trial looked at the combination of the SERD fulvestrant (Faslodex) and an experimental inhibitor of the PI3 kinase, buparlisib, in postmenopausal women with hormone receptor–positive, human epidermal growth factor receptor–2 (HER2)-negative breast cancer treated with an aromatase inhibitor (AI) who experienced disease progression either on or after receiving therapy with an inhibitor of the mammalian target of rapamycin complex 1 (mTORC1).

The combination of fulvestrant and buparlisib was associated with a median PFS of 3.9 months, compared with 1.8 months for fulvestrant and placebo (P less than .001), Angelo Di Leo, MD, of Ospedale Misericordia e Dolce in Prato, Italy, reported at the San Antonio Breast Cancer Symposium,

Objective response rates (ORR) were low, at 7.8% in the combination arm, and 2.1% in the fulvestrant-plus-placebo arm.

Although the PFS difference was statistically significant, “the higher rate of toxicity in patients receiving buparlisib and fulvestrant, including transaminase elevations and mood disorders, may represent a clinically relevant challenge for future development of this compound in this particular group of patients,” Dr. Di Leo said.
 

Blocks AKT pathway

The preclinical rationale for the use of a P13K inhibitor after disease progression on mTORC1 inhibitor is that current mTOR inhibitors such as everolimus have a feedback mechanism that activates the AKT pathway, and that the use of P13K inhibitors can “abrogate or attenuate this activation, potentially blocking that pathway,” explained coinvestigator Ruth O’Regan, MD, head of the division of hematology and oncology at the University of Wisconsin–Madison School of Medicine and Public Health. Dr. O’Regan discussed the BELLE-3 findings in a briefing prior to Dr. Di Leo’s presentation of the data in general session.

In BELLE-3, 432 postmenopausal women with HR+/HER2-, AI-pretreated, locally advanced or metastatic breast cancer that had progressed on or after treatment with an mTOR inhibitor as the last line of therapy were enrolled. The patients were stratified by the presence or absence of visceral disease and then randomized on a 2:1 basis to fulvestrant 500 mg daily plus either buparlisib 100 mg/day (289 patients), or placebo (143).

As noted, the primary endpoint of investigator-assessed PFS favored the addition of buparlisib, with a hazard ratio for progression of 0.67 (P less than .001). PFS results by independent central review were similar (HR 0.57, P less than .001).

The ORR for the buparlisib/fulvestrant combination, 7.6%, consisted of 0.3% complete responses, and 7.3% partial responses. The ORR for placebo/fulvestrant, 2.1%, was composed entirely of partial responses. The respective clinical benefit rates, defined as a combination of complete and partial responses and stable disease, were 24.6% and 15.4.

The benefit of buparlisib was evidently entirely among patients with visceral disease, with a PFS of 3.1 vs. 1.5 months. In contrast, PFS among patients with no visceral disease was 4.2 vs. 4.1 months, respectively, and was not significant.

In addition, the P13K inhibitor seemed to benefit patients with PIK3CA mutations detected in either the primary tumor or in circulating DNA samples, but not patients with wild-type PIK3CA.
 

Depression, anxiety with combination

Patients assigned to buparlisib/fulvestrant had substantially higher proportions of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) elevations compared with patients on placebo fulvestrant, as well as more reported depression and anxiety. Three patients in the buparlisib arm attempted suicide. There were no reported suicide attempts in the placebo arm.

Dr. O’Regan said at the briefing that mood disorders are known adverse events associated with buparlisib, and that patients with psychiatric disorders were excluded from the trial.

Carlos Arteaga, MD, co-leader of the Breast Cancer Research Program at Vanderbilt-Ingram Cancer Center in Nashville, Tenn., who moderated the briefing, said in an interview that PI kinase mutations do not appear to be a good target, and that a pan-PIK3 inhibitor such as buparlisib may be hitting too many targets at once.

Inhibiting all of the PIK3 isoforms – alpha, beta, gamma, and delta – “may be a little too tough,” he said.

The trial should serve as impetus for developing agents that inhibit only the alpha isoform of PIK3 which mutates and appears to be the driver of some types of breast cancer, he said.

Following Dr. Di Leo’s presentation, perennial SABCS gadfly Steven Vogl, MD, New York, told the speaker that “you presented this very nicely, it’s very interesting biology. I don’t think you’d want to do this again to a human, right? Three month prolongation in PFS, miserable, with diarrhea, depression – you don’t want to do this again, is that correct?”

“I think buparlisib is probably not the best compound to be used in this particular setting of patients,” Dr. Di Leo said, but added that a better-tolerated PI3K inhibitor might be more effective.

“Actually, the study is raising an important question: Should we use the PI3K inhibitor in place of the mTOR inhibitor, or perhaps, as the study suggests, should we use the P13K inhibitors sequentially, after the mTOR inhibitor. This is an open question,” he replied.

Novartis sponsored the study. Dr. Di Leo disclosed consulting and lecture fees from the company, and Dr. O’Regan disclosed contracted research support. Dr. Arteaga reported no disclosures relevant to the study.

[email protected]

SAN ANTONIO – About half of the women with stage 1 or 2 breast cancer who were treated using a scalp cooling device during chemotherapy retained their hair in the prospective, randomized Scalp Cooling Alopecia Prevention (SCALP) trial.

Of 229 women who were enrolled from seven U.S. sites between December 2013 and September 2016 and who planned to undergo at least four cycles of anthracycline- or taxane-based chemotherapy, 182 met eligibility criteria; 119 were randomized to undergo scalp cooling using the Orbis Paxman Hair Loss Prevention System (OPHLPS; Paxman Coolers) and 63 were assigned to a control group. Of those, 95 and 47, respectively, were evaluable and had completed four cycles of chemotherapy at the time of a preplanned interim analysis.

Baylor College of Medicine

[email protected]

SAN ANTONIO – About half of the women with stage 1 or 2 breast cancer who were treated using a scalp cooling device during chemotherapy retained their hair in the prospective, randomized Scalp Cooling Alopecia Prevention (SCALP) trial.

Of 229 women who were enrolled from seven U.S. sites between December 2013 and September 2016 and who planned to undergo at least four cycles of anthracycline- or taxane-based chemotherapy, 182 met eligibility criteria; 119 were randomized to undergo scalp cooling using the Orbis Paxman Hair Loss Prevention System (OPHLPS; Paxman Coolers) and 63 were assigned to a control group. Of those, 95 and 47, respectively, were evaluable and had completed four cycles of chemotherapy at the time of a preplanned interim analysis.

Baylor College of Medicine

[email protected]

SAN ANTONIO – About half of the women with stage 1 or 2 breast cancer who were treated using a scalp cooling device during chemotherapy retained their hair in the prospective, randomized Scalp Cooling Alopecia Prevention (SCALP) trial.

Of 229 women who were enrolled from seven U.S. sites between December 2013 and September 2016 and who planned to undergo at least four cycles of anthracycline- or taxane-based chemotherapy, 182 met eligibility criteria; 119 were randomized to undergo scalp cooling using the Orbis Paxman Hair Loss Prevention System (OPHLPS; Paxman Coolers) and 63 were assigned to a control group. Of those, 95 and 47, respectively, were evaluable and had completed four cycles of chemotherapy at the time of a preplanned interim analysis.

Baylor College of Medicine

[email protected]

SAN ANTONIO – Aromatase inhibitors (AIs) appear to be associated with declines in vascular endothelial function, which in turn have been associated with the development of cardiovascular disease, suggests a small study presented at the San Antonio Breast Cancer Symposium.

In this video interview, Anne Blaes, MD, from the Masonic Cancer Center at the University of Minnesota in Minneapolis, talks about the study, which compared endothelial function between postmenopausal women with hormone receptor–positive breast cancers treated with AIs and healthy postmenopausal controls.

Those treated with AIs, independent of the duration of therapy, had significantly worse endothelial function than healthy postmenopausal controls, as measured by the EndoPAT ratio.

SAN ANTONIO – Aromatase inhibitors (AIs) appear to be associated with declines in vascular endothelial function, which in turn have been associated with the development of cardiovascular disease, suggests a small study presented at the San Antonio Breast Cancer Symposium.

In this video interview, Anne Blaes, MD, from the Masonic Cancer Center at the University of Minnesota in Minneapolis, talks about the study, which compared endothelial function between postmenopausal women with hormone receptor–positive breast cancers treated with AIs and healthy postmenopausal controls.

Those treated with AIs, independent of the duration of therapy, had significantly worse endothelial function than healthy postmenopausal controls, as measured by the EndoPAT ratio.

SAN ANTONIO – Aromatase inhibitors (AIs) appear to be associated with declines in vascular endothelial function, which in turn have been associated with the development of cardiovascular disease, suggests a small study presented at the San Antonio Breast Cancer Symposium.

In this video interview, Anne Blaes, MD, from the Masonic Cancer Center at the University of Minnesota in Minneapolis, talks about the study, which compared endothelial function between postmenopausal women with hormone receptor–positive breast cancers treated with AIs and healthy postmenopausal controls.

Those treated with AIs, independent of the duration of therapy, had significantly worse endothelial function than healthy postmenopausal controls, as measured by the EndoPAT ratio.