Response and survival of breast cancer intrinsic subtypes following multi-agent neoadjuvant chemotherapy

Abstract

BackgroundPredicting treatment benefit and/or outcome before any therapeutic intervention has taken place would be clinically very useful. Herein, we evaluate the ability of the intrinsic subtypes and the risk of relapse score at diagnosis to predict survival and response following neoadjuvant chemotherapy. In addition, we evaluated the ability of the Claudin-low and 7-TNBCtype classifications to predict response within triple-negative breast cancer (TNBC).MethodsGene expression and clinical-pathological data were evaluated in a combined dataset of 957 breast cancer patients, including 350 with TNBC, treated with sequential anthracycline and anti-microtubule-based neoadjuvant regimens. Intrinsic subtype, risk of relapse score based on subtype and proliferation (ROR-P), the Claudin-low subtype and the 7-TNBCtype subtype classification were evaluated. Logistic regression models for pathological complete response (pCR) and Cox models for distant relapse-free survival (DRFS) were used.ResultsBasal-like, Luminal A, Luminal B, and HER2-enriched subtypes represented 32.7 %, 30.6 %, 18.2 %, and 10.3 % of cases, respectively. Intrinsic subtype was independently associated with pCR in all patients, in hormone receptor-positive/HER2-negative disease, in HER2-positive disease, and in TNBC. The pCR rate of Basal-like disease was >35 % across all clinical cohorts. Neither the Claudin-low nor the 7-TNBCtype subtype classifications predicted pCR within TNBCs after accounting for intrinsic subtype. Finally, intrinsic subtype and ROR-P provided independent prognostic information beyond clinicopathological variables and type of pathological response. A 5-year DRFS of 97.5 % (92.8–100.0 %) was observed in these neoadjuvant-treated and clinically node-negative patients predicted to be low risk by ROR-P (i.e. 57.4 % of Luminal A tumors with clinically node-negative disease).ConclusionsIntrinsic subtyping at diagnosis provides prognostic and predictive information for patients receiving neoadjuvant chemotherapy. Although we could not exclude a survival benefit of neoadjuvant chemotherapy in patients with early breast cancer with clinically node-negative and ROR-low disease at diagnosis, the absolute benefit of cytotoxic therapy in this group might be rather small (if any).Electronic supplementary materialThe online version of this article (doi:10.1186/s12916-015-0540-z) contains supplementary material, which is available to authorized users.

Hormonal Modulation of Breast Cancer Gene Expression: Implications for Intrinsic Subtyping in Premenopausal Women

“…Patients with Luminal B breast cancer have poorer outcomes from endocrine therapy, however, have a better response to chemotherapy, achieving pathological complete response (pCR) to neoadjuvant chemotherapy in 16% of tumors compared to 6% in Luminal A tumors (67). From the immunohistochemical point of view, Luminal B tumors are characterized by a lower expression of ER and PR, and higher Ki67 index, and display a higher histological grade, compared to Luminal A tumors (66).…”

Neutrophil–Lymphocyte Ratio Predicts Response to Chemotherapy in Triple-Negative Breast Cancer

“…The prognosis of cancer patients and the chemoresponsiveness of t he t u mou r a re deter m i ned by patient-related factors as well as by intrinsic tumour characteristics 11,12 . Cancer-related inflammation plays a critical role in cancer development and progression, and could be responsible for treatment response.…”

Molecular Testing in Breast Cancer: A Guide to Current Practices

“…38 Luminal subtype is associated with benefit from tamoxifen treatment. 39 Nonluminal (HER2-enriched and basal-like) subtypes were associated with pathologic complete response to anthracycline and taxane chemotherapy 40 in a retrospective series. Subtype can also be correlated with genetic background: germ line breast cancer 1 (BRCA1)-mutated tumors are generally of basal-like subtype, 41 and sporadic basal-like tumors may have loss of BRCA1 function due to mutation, epigenetic events (promoter methylation), or other regulatory mechanisms.…”