Impact of molecular subtypes on the prediction of distant recurrence in estrogen receptor (ER) positive, human epidermal growth factor receptor 2 (HER2) negative breast cancer upon five years of endocrine therapy.

ABSTRACT

BACKGROUND: Current evidence suggests that patients with Luminal A early breast cancer can skip chemotherapy or extended endocrine therapy, but immunohistochemistry-based biomarker analysis for St Gallen subtyping may not be reproducible. We asked whether RT-qPCR can be used instead to address this clinical question. METHODS: RNA was extracted from tumor material derived from ER+/HER2- patients receiving adjuvant endocrine treatment for low-risk cancers and was semi-quantified by RT-qPCR with the MammaTyper®. St Gallen subtypes were based on the mRNA expression of ERBB2/HER2, ESR1/ER, PGR/PR and MKI67/Ki67 after dichotomizing at predefined cut-offs. Differences in distant disease-free survival (DDFS) were assessed by Kaplan Meier analysis and Cox regression. RESULTS: With a median follow up of 7.8 years, there were ten events in the group of 195 Luminal A-like tumors (5.1%) and 18 events in the remaining 127 tumors (14.1%), consisting mostly of Luminal B-like cases (N = 119). Luminal A-like had significantly better DDFS over the entire follow-up period (HR 0.35, 95% CIs 0.16-0.76, p = 0.0078) with a trend towards reduced probability of recurrences also in the late phase (> 5 years) (HR 0.20, p = 0.052). The survival advantage spanning the entire follow-up period persisted in the pN0 or pN0-N1 subgroups or after correcting for clinicopathological parameters. MKI67 alone significantly predicted for worse DDFS (HR 2.62, 95% CIs 1.24-5.56, p = 0.0088). CONCLUSIONS: St Gallen Luminal A-like tumors identified by RT-qPCR display markedly low rates of distant recurrence at ten years follow-up. Patients with such tumors could be spared chemotherapy due to the obviously unfavourable benefit/toxicity ratio.