Impact of hormone receptor status and tumor subtypes of breast cancer in young BRCA carriers

Abstract

Early breast cancer; Hormone receptor status; Young patients

Cáncer de mama temprano; Estado del receptor hormonal; Pacientes jóvenes

Càncer de mama precoç; Estat del receptor hormonal; Pacients joves

Background Hormone receptor expression is a known positive prognostic and predictive factor in breast cancer; however, limited evidence exists on its prognostic impact on prognosis of young patients harboring a pathogenic variant (PV) in the BRCA1 and/or BRCA2 genes. Patients and methods This international, multicenter, retrospective cohort study included young patients (aged ≤40 years) diagnosed with invasive breast cancer and harboring germline PVs in BRCA genes. We investigated the impact of hormone receptor status on clinical behavior and outcomes of breast cancer. Outcomes of interest [disease-free survival (DFS), breast cancer-specific survival (BCSS), and overall survival (OS)] were first investigated according to hormone receptor expression (positive versus negative), and then according to breast cancer subtype [luminal A-like versus luminal B-like versus triple-negative versus human epidermal growth factor receptor 2 (HER2)-positive breast cancer]. Results From 78 centers worldwide, 4709 BRCA carriers were included, of whom 2143 (45.5%) had hormone receptor-positive and 2566 (54.5%) hormone receptor-negative breast cancer. Median follow-up was 7.9 years. The rate of distant recurrences was higher in patients with hormone receptor-positive disease (13.1% versus 9.6%, P < 0.001), while the rate of second primary breast cancer was lower (9.1% versus 14.7%, P < 0.001) compared to patients with hormone receptor-negative disease. The 8-year DFS was 65.8% and 63.4% in patients with hormone receptor-positive and negative disease, respectively. The hazard ratio of hormone receptor-positive versus negative disease changed over time for DFS, BCSS, and OS (P < 0.05 for interaction of hormone receptor status and survival time). Patients with luminal A-like breast cancer had the worst long-term prognosis in terms of DFS compared to all the other subgroups (8-year DFS: 60.8% in luminal A-like versus 63.5% in triple-negative versus 65.5% in HER2-positive and 69.7% in luminal B-like subtype). Conclusions In young BRCA carriers, differences in recurrence pattern and second primary breast cancer among hormone receptor-positive versus negative disease warrant consideration in counseling patients on treatment, follow-up, and risk-reducing surgery.

The study was partly supported by the Italian Association for Cancer Research (AIRC grant) [grant number MFAG 2020 ID 24698] ML received support from the European Society for Medical Oncology (ESMO) for a translational research fellowship at the Institut Jules Bordet in Brussels, Belgium, at the time this study was initiated. HJK received support from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health and Welfare, Republic of Korea [grant number HC20C0135]. KAP is an Australian National Health and Medical Research Council leadership fellow. Data collection for most Australian participants was through the kConFab Follow-Up Study with support from Cancer Australia and the National Breast Cancer Foundation [grant number PdCCRS 1100868], Cancer Australia [grant number 809195], the Australian National Breast Cancer Foundation (IF 17), the Australian National Health and Medical Research Council [grant numbers 454508, 288704, 145684], the US National Institutes of Health [grant number 1RO1CA159868], the Queensland Cancer Fund, the Cancer Councils of New South Wales, Victoria, Tasmania, and South Australia, and the Cancer Foundation of Western Australia. NIH R35CA253187, P50CA116201 SPORE in Breast Cancer, and Breast Cancer Research Foundation. AHP received support from the Breast Cancer Research Foundation and Susan G. Komen. FJC was supported by NIH grants R35CA253187 and P50CA115201 and the Breast Cancer research Foundation. The study supporters had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or decision to submit the manuscript for publication.