Dr Kuerer on the Rationale for Eliminating Surgery in Select Patients With HER2+ or Triple-Negative Breast Cancer

"People may say a lumpectomy is not a big deal, so why even do this [evaluation of the omission of surgery]? It is because I don't believe that those patients without any residual disease [after neoadjuvant therapy] will benefit from surgery."

Henry M. Kuerer, MD, PhD, FACS, CMQ, a professor and executive director of the Breast Programs of MD Anderson Cancer Network in the Department of Breast Surgical Oncology at The University of Texas MD Anderson Cancer Center, discussed the clinical rationale for evaluating the selective elimination of breast surgery in patients with HER2-positive or triple-negative breast cancer who achieve a pathologic complete response (pCR) following neoadjuvant systemic therapy.

Five-year follow-up of a phase 2 trial (NCT02945579) investigating the omission of surgery in patients with early-stage triple-negative breast cancer (TNBC) or HER2-positive disease who achieved a complete response to neoadjuvant systemic therapy showed promising long-term outcomes. At a median follow-up of 55.4 months (IQR, 44.0-63.5), among 31 evaluable patients who did not undergo surgery, the ipsilateral breast tumor recurrence rate was 0%, and both 5-year disease-free survival (DFS) and overall survival (OS) were 100%.

This strategy was driven by the recognition that a substantial proportion of patients with early-stage TNBC or HER2-positive breast cancer now achieve high responses following neoadjuvant chemotherapy, Kuerer stated, adding that the pCR rates for these subtypes, even without the addition of immunotherapy, approach 60%. The rationale for evaluating the omission of surgery centers on the hypothesis that patients without residual disease may derive limited benefit from surgical intervention, including lumpectomy, he explained.

However, one of the primary challenges in identifying these patients lies in the limitations of imaging modalities—mammography, ultrasound, and breast MRI—which may inaccurately estimate the extent of residual disease, Kuerer said. To address this, the investigators developed a rigorous protocol involving strict eligibility criteria and a biopsy approach designed to optimize diagnostic accuracy, he stated. Specifically, they used image-guided vacuum-assisted core biopsy of the tumor bed following neoadjuvant therapy, which in prior analyses demonstrated an accuracy of approximately 98%, Kuerer noted.

This biopsy technique involves inserting a single device under image guidance to systematically sample around the tumor bed, he detailed. The group’s foundational research determined that approximately 12 tissue samples were needed to ensure adequate detection of residual disease, Kuerer shared. The investigators emphasized that inadequate sampling and loose selection criteria in other studies have contributed to higher false-negative rates, highlighting the importance of methodological precision in this surgical omission approach, he concluded.