Prognostic factors associated with pathological complete response in early breast cancer patients undergoing neoadjuvant chemotherapy: The importance of Ki-67 and molecular subtype

Abstract

Background: Ki-67 immunohistochemical determination is a widely used biomarker of cell proliferation in patients (pts) undergoing endocrine treatment for breast BC. The role of Ki-67 in pts undergoing neoadjuvant chemotherapy (NAC) for early BC remains controversial. Method(s): We analyzed retrospectively data on 137 patients undergoing taxane and/or anthracycline, transtuzumab based NAC. Luminal A was documented in 6 pts, Luminal B in 29 pts, Her-2 positive in 30 pts and triple negative breast cancers (TNBC) in 72 pts. Pathological complete response (pCR) was defined as the complete disappearance of the invasive cancer in the breast and absence of tumor in the axillary lymph nodes examined by axillary clearance. Result(s): The pCR rate of the entire cohort was 41.6%. At 2 years 92% of pts who attained a pCR were disease free compared to 80% of pts who did not attain a pCR (log rank test p<0.0147). On univariate analysis factors associated with higher pCR included primary tumor size (T1 68% vs. T2 41% vs. T3 or T4 0%, Chi2=20.05, p<0.00017), nodal disease (N0 49% vs. N1 39% vs. N2 8%, p<0.02948), ER receptor status (negative 59% vs. positive 14%, p<0.00000), PR receptor status (negative 53% vs. positive 17%, p<0.00002), molecular subtype (TNBC 53.4%, Her2=50% and Luminal A +B was 8.5%, p<0.00002), Ki67 (>40=55% vs. 15-39=34% vs.<15=0%, p<0.00060) and Stage (I=85% vs. IIA=49% vs. IIB=36% vs. III=5%, p<0.00006). Factors not associated with a higher pCR included age, menopausal status, extranodal spread and lympho-vascular invasion. In a logistic regression model Ki-67 as a continuous variable (p<0.01203) and molecular subtype (p<0.02228) retained its significance; while tumor size, stage of disease, nodal status, ER and PR loss significance. Conclusion(s): Ki67 and molecular subtype (Her-2 positive disease and TNBC) are independent prognostic factors of pCR in pts with early BC undergoing NAC.