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

• Published in: BMC cancer Vol. 19; no. 1; p. 694
• Main Authors: Laible, Mark, Hartmann, Kerstin, Gürtler, Claudia, Anzeneder, Tobias, Wirtz, Ralph, Weber, Stephan, Keller, Thomas, Sahin, Ugur, Rees, Martin, Ramaswamy, Annette
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 15.07.2019; BioMed Central; BMC
• Subjects: Adjuvant chemotherapy; Adult; Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal - therapeutic use; Biomarkers, Tumor - metabolism; Breast cancer; Breast Neoplasms - drug therapy; Breast Neoplasms - genetics; Breast Neoplasms - pathology; Breast Neoplasms - surgery; Cancer recurrence; Cancer treatment; Chemotherapy; Development and progression; Disease-Free Survival; Displays (Marketing); Distant recurrence; Epidermal growth factors; Estrogens; Female; Follow-Up Studies; Gene Expression; Hormone therapy; Humans; Immunohistochemistry; Kaplan-Meier Estimate; Ki-67 Antigen - genetics; Ki67; Luminal A-like; Messenger RNA; Middle Aged; MKI67; Molecular diagnostic techniques; Neoplasm Recurrence, Local; Patient outcomes; Phenols (Class of compounds); Proportional Hazards Models; Receptor, ErbB-2 - genetics; Receptors, Estrogen - genetics; Retrospective Studies; Risk factors; RNA; Triple negative breast cancer; Tumors; Germany; Breast cancer; Luminal A-like; Ki67; MKI67; Distant recurrence; ER
• ISSN: 1471-2407; 1471-2407
• DOI: 10.1186/s12885-019-5890-z

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. 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. 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). 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.