Oncotype DX Breast Recurrence Score Reveals Sex-related Differences in Mortality Prediction in Patients With Early-stage ER-positive Breast Cancer

PHILADELPHIA — The associations of breast cancer recurrence scores (RS) with mortality measured using Oncotype DX, a commercial diagnostic test, were markedly different between male and female patients with early-stage estrogen receptor (ER)-positive breast cancer, with the threshold for RS score in predicting mortality in men being lower than the threshold for women, according to results published in Clinical Cancer Research, a journal of the American Association for Cancer Research.

“Male breast cancer is relatively rare, and most treatment decisions are based on evidence derived from female breast cancer trials,” said first author Fei Wang, MD, PhD, visiting postdoctoral scholar at the Vanderbilt Epidemiology Center in Nashville, Tennessee. “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.”

The 21-gene Oncotype DX test is recommended for patients with early-stage ER-positive, HER2-negative breast cancer to quantify the likelihood of distant recurrence (on a scale of 0-100), which may guide chemotherapy treatment decisions, explained senior author Xiao-Ou Shu, MD, PhD, professor of cancer research at the Vanderbilt Ingram Cancer Center. Additionally, this test may be predictive of breast cancer mortality in this patient population, she said. 

Because this test was developed and validated in female breast cancer patients, little is known about its performance in male breast cancer patients, Shu noted. “We set out to study if the Oncotype DX recurrence score had the same utility to predict mortality in men compared with women,” Shu said.

Using information from the National Cancer Database (NCDB), the Vanderbilt team analyzed data from patients with ER-positive, HER2-negative, stage 1 or stage 2 invasive breast cancer diagnosed between 2010 and 2014. The final analysis included 848 male and 110,898 female patients. All patients had received an Oncotype DX test.

The authors evaluated the relationship between RS and mortality in both male and female patients. They also evaluated the five-year overall survival across low-, intermediate-, and high-risk groups based on the RS categories as indicated by traditional categorization (17 or lower, 18-30, and 31 or greater), and by the TAILORx RS categorization, which was utilized in the TAILORx trial (10 or lower, 11-25, and 26 or greater).

The distribution of RS was markedly different between male and female patients; men had a significantly higher proportion of patients with an RS of 10 or less, as well as a significantly higher proportion of patients with an RS of 31 or greater, compared with women.

Among male patients, RS was associated with increased mortality risk up to a score of 21, beyond which the risk plateaued. However, among female patients, RS was associated with increased mortality risk only above a score of 23, beyond which the risk continued to increase.

“We found in our study that both the distribution and prognosis predictive utility of the Oncotype DX recurrence score differed between male and female breast cancer patients, suggesting a possible biological difference between male and female breast cancers, which requires further investigation,” Shu said.

The researchers found that the traditional RS categories of Oncotype DX, which were associated with mortality in female patients, were not significantly associated with mortality among male patients. However, the researchers observed that men with intermediate- and high-risk RS according to TAILORx cutoffs had significantly higher risks of mortality compared with men with a low-risk TAILORx RS.

“Even though the Oncotype DX test was not specifically designed for men, it still has some prognosis predictive utility in male patients with early-stage ER-positive/HER2-negative breast cancer,” said Shu. 

The primary outcome of the study was total mortality, not breast cancer-specific mortality, representing a major limitation of the study. Additionally, the researchers did not have access to detailed treatment information (including treatment compliance) or information about pre-existing health conditions or lifestyle habits, added Shu.

This study was supported by an Ingram Cancer Professorship fund to Shu, and Wang was supported by the China Scholarship Council. Wang and Shu declare no conflicts of interest.