Surgery for Breast Cancer Is Not Obsolete

Treatment for breast cancer has evolved over time and now consists of a multidisciplinary approach that includes surgery, radiation, and systemic therapy. The specific combination and sequence of therapies vary according to tumor biology and disease stage, but most patients will receive local therapy in conjunction with some form of systemic therapy. In the era of molecular characterization of tumors and improved targeted systemic therapy for breast cancer, could surgery be eliminated for certain subgroups of patients? This question, posed by Drs. Farr and Khan,[1] is thought-provoking but not realistic within the constraints of current practice.

As the authors detail, new developments in systemic therapy are showing increased efficacy, especially in the arena of human epidermal growth factor receptor 2 (HER2)-targeted therapy. Not all patients, however, will have complete eradication of their primary tumor or nodal disease with systemic therapy. Pathologic complete response (pCR) rates in HER2-positive cancers can approach 40% to 60% with dual-agent targeted therapy, but approximately 50% of patients will still have residual disease and require surgical resection. In addition, hormone-sensitive tumors-the majority of breast cancers-have far lower pCR rates.

Even if one could envision a future treatment paradigm in which certain subgroups of patients might be sufficiently treated with systemic therapy (chemotherapy, targeted therapy, or hormonal therapy) and radiation therapy, would long-term outcomes be similar if these patients did not undergo surgical resection? And how would we accurately identify which patients would not require surgery for the primary tumor in the breast or the involved axillary lymph nodes?

Experience with eliminating surgery is limited but suggests that outcomes are inferior. A retrospective study by Ring et al compared patients who attained a complete clinical response to neoadjuvant chemotherapy and underwent surgery vs those who attained a complete clinical response and only received radiation.[2] Although overall survival and disease-free survival were similar between the two groups, there was a 21% rate of locoregional recurrence at 5 years in the patients who did not undergo surgery vs a 10% rate in those patients who did. This study primarily assessed clinical response by physical examination; however, even modern-day imaging using MRI to assess treatment response is only 74% accurate in identifying the presence of residual disease. Moreover, the ability of MRI to predict residual disease appears to differ by tumor type, with enhanced negative predictive value in hormone-negative/HER2-positive and triple-negative tumors.[3]

Clinical and imaging responses to systemic treatment are not currently a surrogate for pathologic response. Farr and Khan astutely address the need for accurate assessment of treatment response if surgical pathologic evaluation will not be performed. In today’s practice, pCR is based on pathologic assessment of tissue removed at the time of definitive surgery. Advances in imaging techniques would be essential to accurately identify patients who have had a “complete” response to systemic therapy and radiation therapy.

Surgery is not obsolete in the management of breast cancer; it is an essential component for almost all patients in the present treatment paradigm. Future multidisciplinary treatment may stratify patients according to who will derive benefit from surgery and who could be adequately treated with systemic and radiation therapy. This is not possible currently, and it will only be possible in the future with enhanced rates of response to systemic therapy and improved imaging modalities to accurately identify patients with no residual disease.

Financial Disclosure:The authors have no significant financial interest in or other relationship with the manufacturer of any product or provider of any service mentioned in this article.

References:

1. Farr D, Khan SA. Local therapy for breast cancer in the molecular era: relevant or relic? Oncology (Williston Park). 2014;28:918-28.

2. Ring A, Webb A, Ashley S, et al. Is surgery necessary after complete clinical remission following neoadjuvant chemotherapy for early breast cancer? J Clin Oncol. 2003;21:4540-5.

3. De Los Santos JF, Cantor A, Amos KD. Magnetic resonance imaging as a predictor of pathologic response in patients treated with neoadjuvant systemic treatment for operable breast cancer. Translational Breast Cancer Research Consortium trial 017. Cancer. 2013;119:1776-83.