A study comparing the prognostic value of the Oncotype DX Breast Recurrence Score in male and female patients with early-stage estrogen receptor (ER)-positive breast cancer has found that the score is associated with mortality in male patients at a much lower threshold than female patients. The findings—published by Wang et al in Clinical Cancer Research—highlight the need to develop a recurrence score categorization specifically for male patients with breast cancer.

“Our results highlight the fact that male and female breast cancers may not be identical, and that additional research is needed to elucidate the best treatment options for men with breast cancer.”

— Fei Wang, MD, PhD

Tweet this quote

The recurrence score, a 21-gene marker based on the expression of 16 tumor-associated genes and five reference genes, was initially developed to quantify the likelihood of distant recurrence in women with ER-positive and node-negative breast cancer, with a high score indicating a higher risk of distant recurrence. However, the prognostic value of using the recurrence score in male patients with breast cancer has not been well studied. Breast cancer in men is a rare disease, with an incidence rate of less than 1% compared to women with breast cancer, but diagnostic and treatment approaches for male patients are largely based on evidence generated from female patients.

Study Methodology

The researchers used information from the National Cancer Database to identify patients diagnosed with ER-positive, HER2-negative stage I or II invasive breast cancer between 2010 and 2014. A total of 848 male and 110,898 female patients were included in the analysis. All the patients had undergone Oncotype DX testing.

The researchers evaluated the relationship between recurrence score and mortality in both male and female patients. They also evaluated the 5-year overall survival across low-, intermediate-, and high-risk groups based on the recurrence score categories as indicated by traditional categorization (17 or lower, 18–30, and 31 or greater), as well as by the TAILORx trial recurrence score categorization (10 or lower, 11–25, and 26 or greater). They estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for overall mortality associated with recurrence score using Cox regression models.

Study Results

The researchers found that the distribution of recurrence scores was markedly different between the male and female patients. Recurrence score was positively associated with mortality in male patients (HR = 1.13, 95% CI = 1.02–1.26 per unit of recurrence score increment) up to scores greater than 21, after which the risk plateaued. Among female patients, mortality began to increase with recurrence score only when the score was greater than 23 (HR = 1.02, 95% CI =1.01–1.02 per unit of recurrence score increment). The intermediate-risk (HR = 5.37, 95% CI = 1.79–16.11), and high-risk groups (HR = 4.28, 95% CI = 1.22–14.97) defined by TAILORx but not traditional cutoffs established for female patients were associated with elevated mortality risk in men even after adjustment for demographic, clinical characteristics, and treatments (except chemotherapy).

“[Recurrence score] is associated with mortality in male patients with breast cancer at a much lower threshold than that for female patients. Studies are needed to establish specific guidelines for [recurrence score] thresholds for male patients with breast cancer,” concluded the study researchers.

Translational Relevance

This research shows that in routine oncology practice settings, recurrence score predicts total mortality in both men and women with breast cancer, but it follows distinct patterns. The findings also highlight the need to develop score categorizations specifically for men with breast cancer.

“Male breast cancer is relatively rare, and most treatment decisions are based on evidence derived from female breast cancer trials,” said first study author Fei Wang, MD, PhD, visiting postdoctoral scholar at Vanderbilt Epidemiology Center at Vanderbilt University Medical Center, in an American Association for Cancer Research press release. “Our results highlight the fact that male and female breast cancers may not be identical, and that additional research is needed to elucidate the best treatment options for men with breast cancer.”

Xiao-Ou Shu, MD, PhD, of Vanderbilt-Ingram Cancer Center, is the corresponding author for the Clinical Cancer Research study.

Disclosure: For full disclosures of the study authors, visit clincancerres.aacrjournals.org.