Sex Disparity in Oncotype DX Breast Recurrence Scores

Sex Disparity in Oncotype DX Breast Recurrence Scores
Male patients may require lower Recurrence Score to inform therapies.

When considering the benefit of adjuvant chemotherapy for female patients with early-stage breast cancer, the Oncotype DX Breast Recurrence Score is a validated and recommended tool. The Recurrence Score helps predict whether a patient with estrogen receptor (ER)-positive and human epidermal growth factor 2 (HER2)-negative breast cancer might be treated effectively with hormone therapy alone or benefit from adjuvant chemotherapy.

For men with breast cancer, the prognostic value of the Recurrence Score has not been well investigated.

A new study by Vanderbilt-Ingram Cancer Center researchers published in Clinical Cancer Research found that the Recurrence Score is prognostic for mortality in male breast cancer patients, but at a lower threshold than that used for female patients.

“The score threshold that we developed based on women with breast cancer needs to be modified. It cannot be lifted and applied for men.

“That means that the score threshold that we developed based on women with breast cancer needs to be modified. It cannot be lifted and applied for men,” said Xiao-Ou Shu, M.D., lead investigator on the study and Ingram Professor of Cancer Research at Vanderbilt University Medical Center.

Oncotype DX Breast Recurrence Score

Several prospective clinical trials have validated the prognostic value of the Recurrence Score for women with breast cancer, including the National Surgical Adjuvant Breast and Bowel Project B-20 trial, Southwest Oncology Group 8814-trial, and Trial Assigning Individualized Options for Treatment (TAILORx).

In 2018, TAILORx investigators reported that women with Recurrence Scores between 11-25 benefit equally from endocrine therapy alone or in combination with chemotherapy. As such, the National Comprehensive Cancer Network established new guidelines increasing the cutoff of the recurrence risk for chemotherapy benefit to 26.

Evaluating the Disparity

Shu and colleagues analyzed a National Cancer Database cohort of 848 male and 110,898 female breast cancer patients diagnosed between 2010 and 2014 with ER-positive, HER2-negative, stage I or II invasive breast cancer. Patients were classified as low-, intermediate- or high-risk based on traditional cutoffs (0-17, 18-30 and 31-100) and TAILORx cutoffs (0-10, 11-25 26-100).

Shu explained that while the average Recurrence Score in men was comparable to women (16.6 versus 17.2, respectively), score distribution was different with males occupying the extremes. “The proportion of patients with low and high Recurrence Scores was higher in male patients compared to female patients.”

The association of the Recurrence Score with mortality was also different between men and women. In men, Recurrence Score was associated with increased mortality until a score of 21, after which risk plateaued. In comparison, in female patients, mortality risk only began to increase with a score of 23.

Traditional cutoffs for Recurrence Score were not significantly associated with mortality in male patients. However, TAILORx cutoffs were, with both the intermediate (11-25) and high-risk groups having elevated mortality risk compared to the low-risk (≤ 10) group. In line with new guidelines, the study found that only female patients with a score of greater than 26, but not scores between 11-25, had higher mortality risk compared to those with a score of ten or less.

Distinct Biology  

Accounting for roughly one percent of all breast cancers, male breast cancers are rare, generally understudied, and follow treatment recommendations based largely on evidence from female patients. 

Shu says the results from this study and others support the idea that male breast cancer may have distinct biology and different prognostic factors compared to female breast cancer.