Impact of Pathologic Complete Response following Neoadjuvant Chemotherapy ± Trastuzumab in Locally Advanced Breast Cancer.

Purpose: This study was designed to examine the relationship between breast cancer molecular subtypes and pathological response to neoadjuvant chemotherapy (NAC) ± trastuzumab, in locally advanced breast cancer (LABC).

Methods: Female patients with LABC (T2-T4, N0-N2, and M0) who received neoadjuvant chemotherapy + trastuzumab if HER2+ subtype, followed by surgery and radiotherapy ± hormonal therapy, were identified. The primary endpoint was pathologic complete response (pCR) in the breast and axilla (ypT0/ypN0), with final analysis on disease-free survival (DFS) and overall survival (OS).

Results: Six hundred eighty-one patients with a median age of 44 years, premenopausal: 70%, median tumour size: 7.0 cm (range 4-11 cm), stage II B: 27% and III A/III B: 73%, ER+/HER2-: 40.8%, ER-/HER2-: 23%, ER+/HER2+: 17.7%, and ER-/HER2+: 18.5%. Overall pCR (ypT0/ypN0) was 23%. The pCR rates based on molecular subtypes were ER+/HER2-: 9%; ER+/HER2+: 29%; ER-/HER2-: 31%; and ER-/HER2+: 37%. At median follow-up of 61 months, ER+/HER2+ and ER+/HER2- subtypes had the best 5-year DFS and OS; meanwhile, ER-/HER2+ and ER-/HER2- subtypes had the worst.

Conclusion: Women with ER+/HER2- disease are the least likely to achieve pCR, with the highest rates in HER2+ and triple-negative subgroups. Degree of response is associated with OS; despite the comparatively higher likelihood of achieving pCR in ER-/HER2+ and triple-negative, these subgroups experience a survival detriment. We are consistent with the published data that patients who attain the pathological complete response defined as ypT0/ypN0 have improved outcomes.