Abstract SP023: State of the art treatment for neoadjuvant/adjuvant triple negative breast cancer
Authors: Carey LA 
Published: February 2021

Abstract
Systemic therapy for triple negative breast cancer (TNBC) is currently limited to chemotherapy, with the major questions being the nature and timing of the chemotherapy and optimizing locoregional management of the primary tumor. While TNBC carries the worst prognosis of the clinical subtypes, this prognosis has improved with modern treatment approaches (Cossetti RJ, JCO 2015), and there are subsets within TNBC that have excellent outcomes. Giving the chemotherapy neoadjuvantly has real clinical value. Cytoreduction can facilitate breast conserving surgery (BCS); 42-53% of patients considered ineligible convert to BCS-eligible after chemotherapy (Golshan M et al, Ann Surg 2015 and JAMA Surg 2020). A negative sentinel lymphadenectomy post-chemotherapy is reliable if dual tracer is used and at least three sentinel nodes are retrieved (Boughey J, JAMA 2013), and a high proportion of node-positive breast cancer can be converted to node-negative, allowing omission of axillary dissection and minimizing risk of lymphedema (Pilewskie M, Morrow M, JAMA Oncol 2017). Two ongoing trials in patients with up-front node-positive disease are examining omitting radiation in those converting to node-negative (NSABP B-51, NCT01872975), and axillary radiation instead of dissection in those that remain pathologically node-positive (A011202, NCT01901094). Pathologic complete response (pCR) to chemotherapy across all subtypes of breast cancer carries a markedly better prognosis compared with residual disease. In CALGB 40603, at over 5 years’ followup, 86% of pCR versus 57% of residual disease patients were event-free (Sikov W, SABCS 2019). CREATE-X enrolled approximately 900 patients with HER2-negative tumors and residual disease after chemotherapy, one-third TNBC, who were randomized to the addition of capecitabine versus standard adjuvant treatment. At 3.5 years’ followup, there was a benefit to adding capecitabine, driven by the TNBC subset in whom there was an absolute 14% difference in disease-free and 8.5% difference in overall survival (Masuda, NEJM 2017). For these two reasons (surgical optimization and risk stratification with treatment decisions driven by residual disease status), in TNBC patients appropriate for chemotherapy neoadjuvant timing is preferred. The nature of the regimens has evolved also during the modern era. The key improvements in chemotherapy includes the addition of taxanes to anthracyclines (Hayes DF, NEJM 2007), the use of dose dense schedules made possible through the development of growth factors (Citron M, JCO 2003), and efforts to minimize anthracycline use. The ABC Trials were a joint analysis of several trials examining anthracycline/taxane-based regimens (TAC or dose-dense AC-T) versus a similar duration (six cycles) of docetaxel plus cyclophosphamide (TC). While underpowered for subset analyses, in the 1300 TNBC patient cohort, anthracycline/taxane regimens outperformed TC, although the absolute benefits were modest in node-negative (2.5%) compared with node-positive (&gt;10%) (Blum J, JCO 2017). For this reason, the preferred regimen in TNBC remains anthracycline/taxane-based. A separate consideration is the incorporation of platinums. Several trials have demonstrated that adding carboplatin significantly increases the pCR rate. However the impact on relapse has been mixed (in underpowered trials); it is reasonable to add in high clinical risk where surgical optimization is desired but is not considered a standard addition to reduce risk of recurrence. Future advances include further surgical and radiation optimization, the potential for using clinical and biomarker analyses to identify low risk TNBC that need no chemotherapy at all, and the incorporation of immune checkpoint inhibitors, which in two neoadjuvant trials have demonstrated significantly increased pCR.
Citation Format: LA Carey. State of the art treatment for neoadjuvant/adjuvant triple negative breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr SP023.