KI67 AS A PREDICTOR OF RESPONSE AND LONG TERM SURVIVAL IN HORMONE RECEPTOR POSITIVE/HER2 NEGATIVE BREAST CANCER PATIENTS TREATED WITH PREOPERATIVE CHEMOTHERAPY

Purpose: Breast cancer is a heterogeneous disease, and newer technologies have identified different molecular classes with distinct behaviour. In particular, hormone receptor positive tumors can be classified as luminal A or luminal B subtypes. Luminal A is a true endocrine dependent disease, generally characterized by high hormone receptor expression, low proliferation and HER2 negativity. Luminal B tumors show a more aggressive phenotype, expressed as a higher proliferation and/or HER2 positivity. It is known that hormone receptor positive tumors are less likely to achieve a pathologic complete response (pCR) after preoperative chemotherapy. Aim of the present analysis was to discriminate, on the basis of tumor proliferation as measured by Ki67, patients with hormone receptor positive/HER2 negative tumors with different probability of obtaining a pCR, and with different long term outcome. Patients and Methods: 274 consecutive stage II-III breast cancer patients treated with preoperative chemotherapy were evaluated. Patients were classified as having hormone receptor positive tumors in case of ER and/or PgR >/= 10%. On the basis of immunohistochemical characteristic, patients were classified as follows: Luminal A, in case of hormone receptor positivity, HER2 negativity, and Ki67<15% (16%); Ki67-Luminal B, in case of hormone receptor positivity, HER2 negativity and Ki67 >/= 15% (37%); HER2-Luminal B in case of hormone receptor positivity and HER2 positivity (19%); HER2, in case of hormone receptor negativity and HER2 positivity (8%); triple negative, in case of hormone receptor negativity and HER2 negativity (20%) Results: Patients characteristics were as follows: median age 50 yrs (range: 27-76); clinical stage: IIA 35.7%, IIB 42.3%, III 22%. After a median of 4 courses of preoperative chemotherapy, 46% of the patients underwent conservative surgery. A pCR, as defined as absence of infiltrating tumor in both breast and axillary lymph-nodes, was observed in 28 patients (10.2%). All hormone receptor positive patients received adjuvant hormonal therapy for 5 years after surgery. The probability of obtaining a pCR was significantly lower in patients with hormone receptor positive tumors: 6.8% vs 17.5% in hormone receptor negative, p=0.010. No pCR was observed in the 40 patients classified as having Luminal A tumor; two pCRs only were observed among the 89 patients classified as having Ki67-Luminal B tumors. Patients in the Ki67-Luminal B group had significantly shorter disease-free survival (DFS) as compared with Luminal A patients (5-yr DFS 63% vs 86%, p= 0.0061). The 5-yr overall survival in Ki67-Luminal B group was 88% versus 93% in the Luminal A group. However, with 14 events only, this difference was not statistically significant. Conclusions: In this analysis, patients with Ki67-Luminal B have a worse DFS as compared to patients with Luminal A disease. Due to the limited number of events, no differences in the probability of obtaining a pCR were observed between Luminal A and Ki67-Luminal B tumors.