Neoadjuvant Chemotherapy for Breast Cancer and Risk for Local Metastases
A pathologic complete response to presurgical therapy occurs in between 40% and 50% of patients with HER2-positive and triple-negative breast cancer, raising the question of the need for surgery for all patients after neoadjuvant chemotherapy indicates a pathologic complete response in the breast. Now, a study investigating the risk for axillary metastases in patients who achieve a pathologic complete response in the breast following neoadjuvant chemotherapy has found that the risk for local metastasis is low. These findings, reported by Tadros et al in JAMA Surgery, provide the fundamental basis and rationale for management of the axilla in clinical trials of omission of cancer surgery when image-guided biopsy indicates a pathologic complete response.
Study Methodology
Researchers from The University of Texas MD Anderson Cancer Center in Houston enrolled 527 consecutive patients with initial clinical triple-negative (T1/T2, N0/N1) and HER2-positive subtypes treated with neoadjuvant chemotherapy followed by standard breast and nodal surgery from January 1, 2010, through December 31, 2014. Of the 527 patients included in the study (median age of 51 years), 263 had HER2-positive and 264 had triple-negative disease. Most of the tumors were grade III. In this cohort, 251 patients underwent segmental mastectomy and 276 underwent mastectomy.
Patients who achieved a pathologic complete response in the breast were compared with patients who did not, based on subtype, initial ultrasonographic findings, and documented pathologic nodal status.
The incidence of positive findings for nodal disease on final pathologic review was calculated for patients with and without pathologic complete response and compared using relative risk ratios with 95% confidence interval (CI).
Study Findings
The researchers found that among 290 patients with initial nodal ultrasonography showing N0 disease, 116 (40.4%) had a pathologic complete response and 100% had no evidence of axillary lymph node metastases after neoadjuvant chemotherapy. Among 237 patients with initial biopsy-proved N1 disease, 69 of 77 (89.6%) with and 68 of 160 (42.5%) without a pathologic complete response had no evidence of residual nodal disease (P < .01). Patients without a pathologic complete response had a relative risk for positive nodal metastases of 7.4 (95% CI, 3.7–14.8; P < .001) compared with those who achieved a pathologic complete response.
“Breast [pathologic complete response] is highly correlated with nodal status after [neoadjuvant chemotherapy], and the risk for missing nodal metastases without axillary surgery in this cohort is extremely low. These data provide the fundamental basis and rationale for management of the axilla in clinical trials of omission of cancer surgery when image-guide biopsy indicates a breast [pathologic complete response],” concluded the researchers.
Testing Whether Surgery Is Necessary
“In our study, patients achieving a breast [pathologic complete response] were more than seven times less likely to have residual nodal disease, with even more pronounced differences among patients presenting with N0 stage disease,” said Audree Tadros, MD, Fellow in Breast Surgical Oncology at The University of Texas MD Anderson Cancer Center, and lead author of this study, in a statement. “Based upon these findings, we anticipate women with initial node-negative disease may avoid breast and axillary surgery if they achieve a [pathologic complete response] after [neoadjuvant chemotherapy] and move on to standard radiotherapy.”
MD Anderson has now opened a phase II study with women with stage I and II HER2-positive and triple-negative breast cancer. The participants who achieve image-guided, biopsy-proved pathologic complete response after [neoadjuvant chemotherapy] will undergo whole-breast radiation, without surgery. In those patients with initial, ultrasound-proven node-negative disease, axillary surgery will be avoided.
Henry M. Kuerer, MD, PhD, of The University of Texas MD Anderson Cancer Center, is corresponding author of this study.
Funding for the study was provided by the PH and Fay Etta Robinson Distinguished Professorship in Cancer Research and the National Institutes of Health.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
