FEATURED , Neoadjuvant Treatment , Research , Surgery

Alan Stolier, MD/



One of the major benefits of neoadjuvant chemotherapy (NAC) is to reduce the size of large tumors to make them amendable to breast conserving surgery (BCS). The meta-analysis carried out by The Early Breast Cancer Trialist’ Collaborative Group in Lancet Oncology in 2018 evaluated almost 5000 patients in 10 randomized trials.The increase in local recurrence raised concerns about downstaging in patients undergoing NAC. Mamtani et al. from the Memorial Sloan Kettering Cancer Center has now reported on their series of patients who had been downstaged by NAC from May 2014 to December 2018 from a prospectively maintained database. This period allowed for a three or more-year follow-up. Eligible patients had cT1-3 invasive breast cancer. Patients with cT4 disease or multicentric disease were considered ineligible for this study.


From May 2014 to December 2018, 1136 consecutive patients with cT1-3 were treated with NAC; 374 patients were BCS ineligible or had unknown BCS eligibility after NAC. The study cohort, therefore, included 685 patients who are eligible for BCS. Of these, 282 patients were BCS ineligible before NAC and downstaged to BCS eligible after treatment. Of these patients, 160 would downstage to BCS suitable after chemotherapy but chose mastectomy. A majority of the patients received dose–dense doxorubicin, cyclophosphamide, and a taxane and 99% of HER2+ patients received dual-targeted HER2 therapy with trastuzumab and pertuzumab. Ninety-three percent of endocrine positive patients received adjuvant hormonal therapy. Radiation therapy was delivered to 96% of those patients having BCS.


NAC-LR1The median follow-up was 35 months. Of the 282 BCS ineligible patients who were downstaged and chose BCS, only 13 patients developed a local recurrence. A local recurrence occurred in 4 of the 160 patients who were BCS ineligible and downstaged and chose mastectomy. The Kaplan-Meier 4 year local recurrence rate was 3.8% overall and was similar between groups. The median time to local recurrence was approximately 14 months. The time and location of local recurrence were similar between groups.



The authors used a univariate analysis cohort of patients with a complete pathological response (pCR) and determined that only lymphovascular invasion (LVI) was associated with local recurrence. The researchers also noted that the clinical T stage and eligibility for BCS were not associated with local recurrence. In multivariate analysis, only LVI was independently associated with local recurrence.


Conclusions: In this large consecutive cohort of T1-3 patients receiving NAC, the rates of local recurrence are low even among those patients who initially were ineligible to undergo BCS and are downstaged with NAC. The authors concluded that “for many patients, this approach affords an opportunity for surgical de-escalation to minimize the burden of treatment without compromising oncologic outcomes.”

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