Clinicopathological predictors of long-term benefit in breast cancer treated with neoadjuvant chemotherapy

AIM To investigate the survival impact of clinicopathological factors, including pathological complete response(p CR) and tumor-infiltrating lymphocytes(s TIL) levels according to subtypes, in breast cancer(BC) patients who received neo-adjuvant chemotherapy(NAC).METHODS We evaluated 435 BC patients who presented and received NAC at the Instituto Nacional de Enfermedades Neoplasicas from 2003 to 2014. s TIL was analyzed as the proportion of tumor stroma occupied by lymphocytes, and was prospectively evaluated on hematoxylin and eosin-stained sections of the preN AC core biopsy. p CR was considered in the absence of infiltrating cancer cells in primary tumor and axillary lymph nodes. Analysis of statistical association between clinical pathological features, s TIL, p CR and survival were carried out using SPSSvs19.RESULTS Median age was 49 years(range 24-84 years) and the most frequent clinical stage was ⅢB(58.3%). Luminal A, Luminal B, HER2-enriched and(triple-negative) TN phenotype was found in 24.6%, 37.9%, 17.7% and 19.8%, respectively. p CR was observed in 11% and median percentage of s TIL was 40%(2%-95%) in the whole population. p CR was associated to Ct1-2(P = 0.045) and to high s TIL(P = 0.029) in the whole population. There was a slight trend towards significance for s TIL(P = 0.054) in Luminal A. s TIL was associated with grade Ⅲ(P < 0.001), no-Luminal A subtype(P < 0.001), RE-negative(P < 0.001), PgR-negative(P < 0.001), HER2-positive(P = 0.002) and p CR(P = 0.029) in the whole population. Longer disease-free survival was associated with grade Ⅰ-Ⅱ(P = 0.006), cN 0(P < 0.001), clinical stage Ⅱ(P = 0.004), ER-positive(P < 0.001), Pg R-positive(P < 0.001), luminal A(P < 0.001) and p CR(P = 0.002). Longer disease-free survival was associated with grade Ⅰ-Ⅱ in Luminal A(P < 0.001), N0-1 in Luminal A(P = 0.045) and TNBC(P = 0.01), clinical stage Ⅱ in Luminal A(P = 0.003) and TNBC(P = 0.038), and pC R in TNBC(P < 0.001). Longer overall survival was associated with grade Ⅰ-Ⅱ(P < 0.001), ER-positive(P < 0.001), PgR-positive(P < 0.001), Luminal A(P < 0.001), cN 0(P = 0.002) and p CR(P = 0.002) in the whole population. Overall survival was associated with clinical stage Ⅱ(P = 0.017) in Luminal A, older age(P = 0.042) in Luminal B, and pC R in TNBC(P = 0.005).CONCLUSION Predictive and prognostic values of clinicopathological features, like p CR and s TIL, differ depending on the evaluated molecular subtype.