Pathological Complete Response After Neoadjuvant Chemotherapy Predicts Improved Survival In All Major Subtypes Of Breast Cancer: Systematic Review And Meta-Analyses Of Over 18,000 Patients

Proceedings: AACR 107th Annual Meeting 2016; April 16-20, 2016; New Orleans, LAIntroduction:Several randomized clinical trials have shown that neoadjuvant chemotherapy has similar long-term survival outcomes as compared to adjuvant chemotherapy. However, the prognostic significance of pathological complete response (pCR) after neoadjuvant chemotherapy remains unclear, particularly for HR+ (Hormone Receptor positive) and HER2+ (Human Epidermal growth factor Receptor-2 positive) breast cancer where adjuvant therapy after surgery could also have an impact on survival. The primary objective of this study was to conduct a systematic review of published neoadjuvant chemotherapy studies to comprehensively evaluate the association between pCR with subsequent breast cancer recurrence (BCR) and mortality.Methods:Based on PRISMA guidelines, a librarian-led search of PubMed from inception until November 2015 was performed to identify potentially eligible studies. Inclusion criteria were clinical trials or retrospective studies with at least one arm featuring neoadjuvant chemotherapy that reported pCR results as well as recurrence and/or survival stratified by the presence or absence of pCR. A total of 1,171 citations with associated abstracts were reviewed. Pooled odds ratios (ORs), 95% confidence intervals (CI), and p values were estimated for endpoints using the fixed and random effects statistical model.Results:18,772 patients from 49 studies met inclusion criteria. The majority of studies featured patients with stage II-III breast cancer and defined pCR as no residual invasive cancer in breast or nodes with residual noninvasive breast cancer allowed (ypT0/is ypN0). The overall pCR rate was 21.5% (range: 5.7-62%), with the highest pCR rates seen in HER2+ (range: 16.7-76%) and triple negative tumors (range: 14.3-67%). Achievement of pCR, as compared to absence of pCR, was associated with significantly reduced BCR (OR 0.33, CI: 0.28-0.39, p = u003c .001) and mortality (OR 0.28, CI: 0.21-0.36, p = u003c .001) overall. Similar association of pCR with reduced mortality was seen in all major breast cancer subtypes. The highest survival differential between pCR and no pCR was seen among patients who did not receive subsequent adjuvant chemotherapy.Conclusions:Achieving pCR following neoadjuvant chemotherapy is associated with significantly improved disease recurrence and survival across the various breast cancer subtypes, including HR+ and HER2+ breast cancer. These results provide further support for using pCR as a surrogate marker for survival outcomes as newer targeted therapies are evaluated in the neoadjuvant setting and might provide an efficient model for drug development in early breast cancer, but impact of adjuvant therapy needs to be carefully weighed in the analytical interpretation.Citation Format: Laura Spring, Rachel Greenup, Kerry Reynolds, Barbara L. Smith, Beverly Moy, Aditya Bardia. Pathological complete response after neoadjuvant chemotherapy predicts improved survival in all major subtypes of breast cancer: systematic review and meta-analyses of over 18,000 patients. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1439.