Sex Disparity in Recurrence Score Among Patients with Early Stage ER-Positive Breast Cancer

Oncotype DX® Breast Recurrence Scores from the National Cancer Database indicated that a lower threshold is needed for male patients with early stage ER-positive breast cancer to predict mortality.

A study by Vanderbilt-Ingram Cancer Center (VICC) suggests that Oncotype DX® Breast Recurrence Score (RS) is associated with mortality in male patients with early stage estrogen-receptor (ER)-positive breast cancer at a much lower threshold than that for female patients.1

Researchers indicated that studies are needed to establish specific guidelines for recurrence scores for male breast cancer patients. “To the best of our knowledge, the prognostic and predictive values of RS in male patients with breast cancer have not been well evaluated,” the researchers wrote.

In this cohort of 848 male and 110,898 female patients with breast cancer identified from the National Cancer Database, RS was positively associated with mortality in male patients (HR = 1.13; 95% CI, 1.02-1.26 per unit RS increment) up to RS > 21, after which the risk plateaued. Mortality began to increase among female patients with RS only when RS > 23 (HR = 1.02; 95% CI, 1.01-1.02 per unit of RS increment).

“The observed differences in RS distribution between men and women suggest that male breast cancer may have distinct biology and different prognostic factors compared with female patients,” the researchers wrote.

A TAILORx study published in 2018 investigated the Oncotype DX® Breast Recurrence Score test to predict the (female) patient population who will substantially benefit from chemotherapy. The results of the trial indicated that chemotherapy after surgery provided little advantage in overall survival (OS) for women with early stage ER-positive breast cancer.2

Little benefit from chemotherapy was observed for those with intermediate-risk male patients, defined either by TAILORx or traditional cutoffs, although this group, overall, was at high mortality risk.

The association for the high-risk group was only modestly attenuated after additional adjustment for chemotherapy, and chemotherapy was not significantly associated with mortality among male patients with RS 11-25 or those with RS 18-30. This may suggest that RS may only be associated with total mortality but not robustly predict the benefit of adjuvant chemotherapy for male patients with breast cancer.

However, according to the researchers, “the sample size for the analysis related to chemotherapy is small. In addition, our study was not equipped to investigate the predictive value of Oncotype DX® due to the lack of detailed treatment information and compliance data in the NCDB.”

Currently, RS is recommended in clinical practice to guide decisions on adjuvant systemic therapy for women with early-stage invasive breast cancer, especially for those who present with ER-positive, human epidermal growth factor receptor 2(HER2)-negative, and node-negative disease.

Previous studies have suggested that pathogenic mutations and epigenetic alterations involved in male breast carcinogenesis do not exactly overlap with those of women. However, treatment for male breast cancer, including those based on the RS categorization, is currently primarily based on the knowledge gained from clinical trials conducted in female patients.

According to the National Breast Cancer Foundation, less than 1% of all breast cancer cases develop in men and only one in a thousand men will ever be diagnosed with breast cancer.3

A clinical trial sponsored by the European Organisation for Research and Treatment of Cancer (EORTC) aims to provide important information regarding male patients’ with breast cancer biology and clinical evolution.

1. Wang F, Reid S, Zheng W, et al. Sex Disparity Observed for Oncotype DX Breast Recurrence Score in Predicting Mortality Among Patients with Early Stage ER-Positive Breast Cancer. Clin Cancer Res. doi:10.1158/1078-0432.CCR-19-2424
2. Sparano JA, Gray JR, Makower DF, et al. Adjuvant Chemotherapy Guided by a 21-Gene Expression Assay in Breast Cancer. N Engl J Med. doi:10.1056/NEJMoal1804710
3. National Breast Cancer Foundation, Inc. Male Breast Cancer. National Breast Cancer Foundation website. Published 2019. Accessed November 20, 2019.