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Lower Cutoff Score for Oncotype DX Test May Be Needed for Male Breast Cancer Patients

NEW YORK – Recurrence scores from Genomic Health's Oncotype DX test might have a different meaning for men with breast cancer, suggesting a need for a lower cutoff score to predict mortality among male patients, a new study has found.

Oncotype DX, a 21-gene test, can help guide chemotherapy decisions for breast cancer patients by determining their risk of having a distant recurrence. In 2018, the TAILORx trial reported that women with an intermediate risk of breast cancer, as determined by Oncotype DX testing, were unlikely to benefit from chemotherapy following surgical treatment.

However, the test was developed and validated in female patients and its applicability to male breast cancer patients is unclear. Men make up a small portion, about 1 percent, of the breast cancer patient population.

In a new study, a Vanderbilt University Medical Center-led team of researchers examined the relationship between overall mortality among male and female breast cancer patients and their recurrence scores. They found that while higher recurrence scores were associated with increased mortality, the pattern of the association differed among male patients. This could mean that different cutoff values need to be established for male patients, the researchers said.

"Male breast cancer is relatively rare, and most treatment decisions are based on evidence derived from female breast cancer trials," Fei Wang, a visiting postdoctoral scholar at the Vanderbilt Epidemiology Center, said in a statement. "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."

Their analysis was published in Clinical Cancer Research.

Wang and colleagues conducted a registry study of patients from the National Cancer Database who were diagnosed with primary breast cancer and underwent Oncotype DX testing between 2010 and 2014. This cohort included 110,898 female breast cancer patients and 848 male breast cancer patients who had ER-positive, HER2-negative, stage 1 or stage 2 invasive breast cancer.

Both male and female breast cancer patients had similar average RS scores — 16.6 and 17.2, respectively — and similar portions of patients with scores under 26, the cutoff point above which indicated high-risk disease in the TAILORx trial. But the portion of men with scores below 10 or above 31 was higher than that of women, suggesting male breast cancer could have different biology.

When the researchers applied traditional Oncotype DX score cutoffs of low, intermediate, and high risk — scores of 17 and lower, between 18 and 30, and 31 and higher, respectively — to their male patients, they found that these cutoffs were not significantly associated with mortality.

But when they applied the TAILORx trial score cutoffs for low, intermediate, and high risk — scores of 10 and lower, between 11 and 25, and 26 and higher — to their male patients, they noted increased mortality among the intermediate and high groups, as compared to the low-risk group.

In particular, recurrence scores were associated with increased mortality among male breast cancer patients up to a score of 21, after which the risk plateaued. By contrast, in women, recurrence scores were linked with increased mortality beginning with a score of 23 and rising thereafter.

This indicated to the researchers that a lower cutoff score might be needed to predict mortality among male breast cancer patients. Because of this, the researchers argued that additional studies are needed to determine guidelines for recurrence score thresholds among male breast cancer patients.

"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," senior author Xiao-Ou Shu, professor of cancer research at the Vanderbilt Ingram Cancer Center, said in a statement.