Triple negative breast cancer (TNBC) is a heterogeneous disease with distinct
molecular subtypes that differentially respond to chemotherapy and targeted agents.
The purpose of this study is to explore the clinical relevance of Lehmann TNBC subtypes
by identifying any differences in response to neoadjuvant chemotherapy among
them. We determined Lehmann subtypes by gene expression profiling in paraffined
pre-treatment tumor biopsies from 125 TNBC patients treated with neoadjuvant
anthracyclines and/or taxanes +/- carboplatin. We explored the clinicopathological
characteristics of Lehmann subtypes and their association with the pathologic complete
response (pCR) to different treatments. The global pCR rate was 37%, and it was
unevenly distributed within Lehmann’s subtypes. Basal-like 1 (BL1) tumors exhibited
the highest pCR to carboplatin containing regimens (80% vs 23%, p=0.027) and were
the most proliferative (Ki-67>50% of 88.2% vs. 63.7%, p=0.02). Luminal-androgen
receptor (LAR) patients achieved the lowest pCR to all treatments (14.3% vs 42.7%,
p=0.045 when excluding mesenchymal stem-like (MSL) samples) and were the group
with the lowest proliferation (Ki-67≤50% of 71% vs 27%, p=0.002). In our cohort,
only tumors with LAR phenotype presented non-basal-like intrinsic subtypes (HER2-
enriched and luminal A). TNBC patients present tumors with a high genetic diversity
ranging from highly proliferative tumors, likely responsive to platinum-based therapies,
to a subset of chemoresistant tumors with low proliferation and luminal characteristics.
; Lluch, Ana; Chica Parrado, María del Rosario; Albanell, J.; Chacón, José Ignacio; Antolín, Silvia; Jerez-Aragonés, José Manuel
