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07-04-2015 | Surgery | Article

Surgical issues in patients with breast cancer receiving neoadjuvant chemotherapy

Authors: Tari A. King, Monica Morrow

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Abstract

Early randomized trials of the addition of neoadjuvant chemotherapy (NACT) to the treatment regimen of patients with breast cancer failed to demonstrate an improvement in overall survival compared with conventional adjuvant therapy; nevertheless, the increased opportunities for breast conservation, owing to downstaging of the primary tumour, and enthusiasm regarding the potential to tailor systemic therapy based on responses observed in the neoadjuvant setting, resulted in the adoption of this approach as a useful clinical tool. That the effectiveness of NACT varies by molecular subtype is becoming increasingly clear, and although the potential of tailoring adjuvant systemic therapy based on treatment response before surgery remains to be realized, the increasing rates of pathological complete response following NACT have had a considerable impact on locoregional treatment considerations. For example, NACT reduces the need for mastectomy and axillary lymph-node dissection, thus decreasing the morbidity of surgery, without compromising outcomes. However, selection of the ideal candidates for preoperative chemotherapy remains critical, and personalizing local therapy based on the degree of response is the subject of ongoing clinical trials. This article reviews the current issues surrounding surgery of the breast and axilla in patients with breast cancer receiving NACT.

Nat Rev Clin Oncol 2015; 12: 335–343. doi:10.1038/nrclinonc.2015.63​​​​​​​

Subject terms: Breast cancer • Chemotherapy • Outcomes research • Surgical oncology

Preoperative or neoadjuvant chemotherapy (NACT) was initially used in the treatment of patients with locally advanced breast cancer (T4a–T4d disease), after historical series of patients with inflammatory breast carcinoma (T4d disease) and other T4 breast tumours who were treated with initial surgery demonstrated high rates of local recurrence and poor survival.1, 2 The demonstration in the 1970s that adjuvant chemotherapy improved both disease-free survival and overall survival of women with lymph-node-positive breast cancer3, 4 led to a number of studies examining the role of NACT in locally advanced breast cancer. The results of early studies of NACT indicated a prolongation of disease-free survival and overall survival compared with historical controls,5, 6 coupled with the observation that major reductions in tumour volume occurred in 60–80% of patients treated,7 providing the rationale for clinical trials of this approach in earlier-stage operable breast cancer. The primary aim of these studies was to determine if NACT, through prompt treatment of micrometastases, improved survival compared to chemotherapy given postoperatively. However, a meta-analysis of nine randomized studies, comprising a total of 3,946 patients, found no significant survival difference between patients who received NACT versus those who received adjuvant therapy, with a summary risk ratio of 1.0 (95% CI 0.90–1.12).8 Although this lack of a survival difference has persisted in more-recent studies,9 a number of benefits of NACT have nevertheless emerged, including increased opportunity to perform breast-conserving surgery (BCS) and a reduced need for axillary lymph-node dissection (ALND).10 Additionally, the achievement of pathological complete response (pCR) to NACT has emerged as a powerful prognostic factor.11 The acceptance by the FDA of pCR rate as a criterion supporting the approval of new drugs,12 together with the other benefits discussed, suggests that the use of NACT will continue to increase. This paradigm shift raises a number of important questions regarding appropriate approaches to local therapy for breast cancer, as the guiding principles for surgery and postoperative radiotherapy in use today were developed based on the findings of trials in which surgery was the initial treatment modality. This article will review current issues surrounding surgery of the breast and axilla in women receiving NACT for breast cancer.

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