Can cN0 and pCR limit axillary surgery in some breast cancer patients?

 

CHICAGO – Patients with clinically node-negative HER2-positive or triple-negative breast cancer (TNBC) who achieve a pathological complete response in the breast after neoadjuvant chemotherapy could benefit from clinical trials to evaluate the option of omitting axillary node surgery in this population, according to a retrospective analysis of more than 22,000 cases in the National Cancer Database reported at the Society of Surgical Oncology Annual Cancer Symposium.

“With advances in systemic treatment options and targeted therapy, we are seeing high pathological response rates in patients with breast cancer treated with neoadjuvant chemotherapy, especially in patients with HER2+ disease and patients with TNBC,” senior author Judy C. Boughey, MD, professor of surgery at Mayo Clinic in Rochester, Minn, said in an interview. “This is prompting the question of whether surgery on the breast and on the lymph nodes is always required and whether we can identify patients who have had an excellent response and could potentially avoid surgery.”

Alison U. Barron, MD, breast surgery oncology fellow at Mayo, presented the results. “In patients with HER2+ breast cancer and TNBC who are clinically node negative (cN0) and achieve a breast pathological complete response, this data supports omitting axillary surgery in clinical trials assessing no surgery after neoadjuvant chemotherapy (NAC),” she said. “In patients who present with clinically positive node [cN1] disease with a breast pathological complete response, surgical staging of the axilla is still recommended.”

The analysis involved 22,695 patients who had clinical T1 and T2 disease and had NAC followed by surgery from 2010 to 2014. The goal, she said, was to evaluate rates of nodal positivity (ypN+) in patients with and without a pathological complete response (pCR) following NAC by tumor subtype across both academic and community settings.

“Response rates to NAC have increased,” Dr. Barron said. She cited previous reports that showed response rates ranging from 9%-13% for anthracyclines to 19%-26% with the addition of taxanes, and to 60%-70% with the addition of trastuzumab and pertuzumab in HER2+ disease. “Furthermore, we know that tumor biology affects response rates, with TNBC and HER2+ disease having the highest rates of pathologic complete response,” she said.

“In the current era when we frequently operate on patients, we find no residual cancer in the tissue at the time of surgery,” Dr. Barron said. “The question arises as to whether we can limit surgery in patients with a pathological complete response.” While imaging has limited ability to reliably detect pCR with 100% specificity, she noted that recent trials have shown the potential of tumor-bed biopsy to identify pCR in patients after NAC (Ann Surg. Published online Oct. 23, 2017. doi: 10.1097/SLA.0000000000002573; JAMA Surg. 2017;152(7):665-70).

The National Cancer Database data the Mayo researchers analyzed yielded an overall breast pCR of 29%. “When broken down by tumor subtype, we saw significantly higher rates of breast pCR in patients with HER2+ disease (42%, n = 3,107) and TNBC (35%, n = 2,469), compared with patients with hormone-receptor positive (HR+)/HER2-negative disease (12%, n = 1,020),” she said.

 

When the analysis looked specifically at patients who were clinically node negative at presentation and had a pCR, the rates of positive lymph nodes at the time of surgery were 1.6% in HER2+ patients and 1.7% in TNBC disease, Dr. Barron said. “If there was residual disease in the breast, the nodal positivity rate was significantly higher, at 18% in HER2+ and 12% in TNBC,” she added. In those who were clinical N1, the breast pCR rates were similar – 41% in HER2+ and 35% in TNBC – but nodal positivity rates were significantly higher, at 13% and 14%, respectively.

The HR+/HER2- group had significantly lower rates of pCR: 12% in the cN0 and 13% in the cN1 subgroups. This subgroup also had higher nodal positivity rates – in the cN0 subgroup, 4% in those with a breast pCR and 34% in those with residual disease in the breast, and in the cN1 subgroup, 30% and 83%, respectively.

When the investigators looked at the extent of nodal burden in cN0 patients with breast pCR, they found the rate of N2 and N3 disease was near zero across all biologic subtypes. “In patients who were cN1 at presentation and achieved a breast pCR but had residual axillary disease, the majority had N1 disease with only 1.5%-4% having four or more positive lymph nodes,” Dr. Barron said.

In the discussion, session moderator Carla Fisher, MD, of Indiana University, Indianapolis, said, “While we might not be ready for prime time to not evaluate the lymph nodes of these patients, this study does speak to the importance of establishing N0 and N1 prior to NAC.” In reply to her question about how Mayo routinely evaluates node status prior to NAC, Dr. Barron noted that Mayo performs routine axillary ultrasound. However, the NCDB data does not specify what imaging was done. This is thought to vary across the centers in the NCDB, Dr. Barron said.

Noted Dr. Boughey, “The findings from this study provide data that can be used moving forward for planning future clinical trials.” She also said that these findings do not alter the current standard of care; that still calls for breast and nodal surgery after NAC. However, the ongoing NRG-BR005 phase II clinical trial is assessing the accuracy of tumor-bed biopsy in these situations (ClinicalTrials.gov Identifier: NCT03188393). “The results from that trial will help inform future trials evaluating eliminating breast surgery in patients with an excellent response to NAC,” Dr. Boughey said. “Those patients could also potentially avoid axillary surgery based on the data we have now.”

Dr. Barron and Dr. Boughey and coauthors reported having no financial disclosures.

SOURCE: Barron AU et al. Society of Surgical Oncology Annual Cancer Symposium, Abstract 48.

 

CHICAGO – Patients with clinically node-negative HER2-positive or triple-negative breast cancer (TNBC) who achieve a pathological complete response in the breast after neoadjuvant chemotherapy could benefit from clinical trials to evaluate the option of omitting axillary node surgery in this population, according to a retrospective analysis of more than 22,000 cases in the National Cancer Database reported at the Society of Surgical Oncology Annual Cancer Symposium.

“With advances in systemic treatment options and targeted therapy, we are seeing high pathological response rates in patients with breast cancer treated with neoadjuvant chemotherapy, especially in patients with HER2+ disease and patients with TNBC,” senior author Judy C. Boughey, MD, professor of surgery at Mayo Clinic in Rochester, Minn, said in an interview. “This is prompting the question of whether surgery on the breast and on the lymph nodes is always required and whether we can identify patients who have had an excellent response and could potentially avoid surgery.”

Alison U. Barron, MD, breast surgery oncology fellow at Mayo, presented the results. “In patients with HER2+ breast cancer and TNBC who are clinically node negative (cN0) and achieve a breast pathological complete response, this data supports omitting axillary surgery in clinical trials assessing no surgery after neoadjuvant chemotherapy (NAC),” she said. “In patients who present with clinically positive node [cN1] disease with a breast pathological complete response, surgical staging of the axilla is still recommended.”

The analysis involved 22,695 patients who had clinical T1 and T2 disease and had NAC followed by surgery from 2010 to 2014. The goal, she said, was to evaluate rates of nodal positivity (ypN+) in patients with and without a pathological complete response (pCR) following NAC by tumor subtype across both academic and community settings.

“Response rates to NAC have increased,” Dr. Barron said. She cited previous reports that showed response rates ranging from 9%-13% for anthracyclines to 19%-26% with the addition of taxanes, and to 60%-70% with the addition of trastuzumab and pertuzumab in HER2+ disease. “Furthermore, we know that tumor biology affects response rates, with TNBC and HER2+ disease having the highest rates of pathologic complete response,” she said.

“In the current era when we frequently operate on patients, we find no residual cancer in the tissue at the time of surgery,” Dr. Barron said. “The question arises as to whether we can limit surgery in patients with a pathological complete response.” While imaging has limited ability to reliably detect pCR with 100% specificity, she noted that recent trials have shown the potential of tumor-bed biopsy to identify pCR in patients after NAC (Ann Surg. Published online Oct. 23, 2017. doi: 10.1097/SLA.0000000000002573; JAMA Surg. 2017;152(7):665-70).

The National Cancer Database data the Mayo researchers analyzed yielded an overall breast pCR of 29%. “When broken down by tumor subtype, we saw significantly higher rates of breast pCR in patients with HER2+ disease (42%, n = 3,107) and TNBC (35%, n = 2,469), compared with patients with hormone-receptor positive (HR+)/HER2-negative disease (12%, n = 1,020),” she said.

 

When the analysis looked specifically at patients who were clinically node negative at presentation and had a pCR, the rates of positive lymph nodes at the time of surgery were 1.6% in HER2+ patients and 1.7% in TNBC disease, Dr. Barron said. “If there was residual disease in the breast, the nodal positivity rate was significantly higher, at 18% in HER2+ and 12% in TNBC,” she added. In those who were clinical N1, the breast pCR rates were similar – 41% in HER2+ and 35% in TNBC – but nodal positivity rates were significantly higher, at 13% and 14%, respectively.

The HR+/HER2- group had significantly lower rates of pCR: 12% in the cN0 and 13% in the cN1 subgroups. This subgroup also had higher nodal positivity rates – in the cN0 subgroup, 4% in those with a breast pCR and 34% in those with residual disease in the breast, and in the cN1 subgroup, 30% and 83%, respectively.

When the investigators looked at the extent of nodal burden in cN0 patients with breast pCR, they found the rate of N2 and N3 disease was near zero across all biologic subtypes. “In patients who were cN1 at presentation and achieved a breast pCR but had residual axillary disease, the majority had N1 disease with only 1.5%-4% having four or more positive lymph nodes,” Dr. Barron said.

In the discussion, session moderator Carla Fisher, MD, of Indiana University, Indianapolis, said, “While we might not be ready for prime time to not evaluate the lymph nodes of these patients, this study does speak to the importance of establishing N0 and N1 prior to NAC.” In reply to her question about how Mayo routinely evaluates node status prior to NAC, Dr. Barron noted that Mayo performs routine axillary ultrasound. However, the NCDB data does not specify what imaging was done. This is thought to vary across the centers in the NCDB, Dr. Barron said.

Noted Dr. Boughey, “The findings from this study provide data that can be used moving forward for planning future clinical trials.” She also said that these findings do not alter the current standard of care; that still calls for breast and nodal surgery after NAC. However, the ongoing NRG-BR005 phase II clinical trial is assessing the accuracy of tumor-bed biopsy in these situations (ClinicalTrials.gov Identifier: NCT03188393). “The results from that trial will help inform future trials evaluating eliminating breast surgery in patients with an excellent response to NAC,” Dr. Boughey said. “Those patients could also potentially avoid axillary surgery based on the data we have now.”

Dr. Barron and Dr. Boughey and coauthors reported having no financial disclosures.

SOURCE: Barron AU et al. Society of Surgical Oncology Annual Cancer Symposium, Abstract 48.

 

CHICAGO – Patients with clinically node-negative HER2-positive or triple-negative breast cancer (TNBC) who achieve a pathological complete response in the breast after neoadjuvant chemotherapy could benefit from clinical trials to evaluate the option of omitting axillary node surgery in this population, according to a retrospective analysis of more than 22,000 cases in the National Cancer Database reported at the Society of Surgical Oncology Annual Cancer Symposium.

“With advances in systemic treatment options and targeted therapy, we are seeing high pathological response rates in patients with breast cancer treated with neoadjuvant chemotherapy, especially in patients with HER2+ disease and patients with TNBC,” senior author Judy C. Boughey, MD, professor of surgery at Mayo Clinic in Rochester, Minn, said in an interview. “This is prompting the question of whether surgery on the breast and on the lymph nodes is always required and whether we can identify patients who have had an excellent response and could potentially avoid surgery.”

Alison U. Barron, MD, breast surgery oncology fellow at Mayo, presented the results. “In patients with HER2+ breast cancer and TNBC who are clinically node negative (cN0) and achieve a breast pathological complete response, this data supports omitting axillary surgery in clinical trials assessing no surgery after neoadjuvant chemotherapy (NAC),” she said. “In patients who present with clinically positive node [cN1] disease with a breast pathological complete response, surgical staging of the axilla is still recommended.”

The analysis involved 22,695 patients who had clinical T1 and T2 disease and had NAC followed by surgery from 2010 to 2014. The goal, she said, was to evaluate rates of nodal positivity (ypN+) in patients with and without a pathological complete response (pCR) following NAC by tumor subtype across both academic and community settings.

“Response rates to NAC have increased,” Dr. Barron said. She cited previous reports that showed response rates ranging from 9%-13% for anthracyclines to 19%-26% with the addition of taxanes, and to 60%-70% with the addition of trastuzumab and pertuzumab in HER2+ disease. “Furthermore, we know that tumor biology affects response rates, with TNBC and HER2+ disease having the highest rates of pathologic complete response,” she said.

“In the current era when we frequently operate on patients, we find no residual cancer in the tissue at the time of surgery,” Dr. Barron said. “The question arises as to whether we can limit surgery in patients with a pathological complete response.” While imaging has limited ability to reliably detect pCR with 100% specificity, she noted that recent trials have shown the potential of tumor-bed biopsy to identify pCR in patients after NAC (Ann Surg. Published online Oct. 23, 2017. doi: 10.1097/SLA.0000000000002573; JAMA Surg. 2017;152(7):665-70).

The National Cancer Database data the Mayo researchers analyzed yielded an overall breast pCR of 29%. “When broken down by tumor subtype, we saw significantly higher rates of breast pCR in patients with HER2+ disease (42%, n = 3,107) and TNBC (35%, n = 2,469), compared with patients with hormone-receptor positive (HR+)/HER2-negative disease (12%, n = 1,020),” she said.

 

When the analysis looked specifically at patients who were clinically node negative at presentation and had a pCR, the rates of positive lymph nodes at the time of surgery were 1.6% in HER2+ patients and 1.7% in TNBC disease, Dr. Barron said. “If there was residual disease in the breast, the nodal positivity rate was significantly higher, at 18% in HER2+ and 12% in TNBC,” she added. In those who were clinical N1, the breast pCR rates were similar – 41% in HER2+ and 35% in TNBC – but nodal positivity rates were significantly higher, at 13% and 14%, respectively.

The HR+/HER2- group had significantly lower rates of pCR: 12% in the cN0 and 13% in the cN1 subgroups. This subgroup also had higher nodal positivity rates – in the cN0 subgroup, 4% in those with a breast pCR and 34% in those with residual disease in the breast, and in the cN1 subgroup, 30% and 83%, respectively.

When the investigators looked at the extent of nodal burden in cN0 patients with breast pCR, they found the rate of N2 and N3 disease was near zero across all biologic subtypes. “In patients who were cN1 at presentation and achieved a breast pCR but had residual axillary disease, the majority had N1 disease with only 1.5%-4% having four or more positive lymph nodes,” Dr. Barron said.

In the discussion, session moderator Carla Fisher, MD, of Indiana University, Indianapolis, said, “While we might not be ready for prime time to not evaluate the lymph nodes of these patients, this study does speak to the importance of establishing N0 and N1 prior to NAC.” In reply to her question about how Mayo routinely evaluates node status prior to NAC, Dr. Barron noted that Mayo performs routine axillary ultrasound. However, the NCDB data does not specify what imaging was done. This is thought to vary across the centers in the NCDB, Dr. Barron said.

Noted Dr. Boughey, “The findings from this study provide data that can be used moving forward for planning future clinical trials.” She also said that these findings do not alter the current standard of care; that still calls for breast and nodal surgery after NAC. However, the ongoing NRG-BR005 phase II clinical trial is assessing the accuracy of tumor-bed biopsy in these situations (ClinicalTrials.gov Identifier: NCT03188393). “The results from that trial will help inform future trials evaluating eliminating breast surgery in patients with an excellent response to NAC,” Dr. Boughey said. “Those patients could also potentially avoid axillary surgery based on the data we have now.”

Dr. Barron and Dr. Boughey and coauthors reported having no financial disclosures.

SOURCE: Barron AU et al. Society of Surgical Oncology Annual Cancer Symposium, Abstract 48.