Distinctive Features of Male Breast Cancer Identified

An analysis of clinical characteristics, gene expression, and 21-gene Breast Recurrence Score results identified distinctive biologic features of breast cancer in men.

Suleiman Alfred Massarweh, MD

An analysis of clinical characteristics, gene expression, and 21-gene Breast Recurrence Score (RS) results identified distinctive biologic features of breast cancer in men, and also suggested that that RS testing may have an important prognostic role for both men and women.

Investigators identified male and female patients with breast cancer specimens submitted for Genomic Health 21-gene RS testing in North America from June 2004 to January 2017. The data set included 3806 men and 571,115 women with ER- and/or PR-positive, HER2-negative disease with negative nodal involvement, micrometastases only, and involvement of 1 to 3 lymph nodes (1-3LN).

For outcomes analysis, researchers linked the National Cancer Institute’s SEER population of patients diagnosed with breast cancer from 2004 to 2012 to the 21-gene RS results from the Genomic Health Laboratory. The SEER study population included 322 men and 55,842 women from all the individual registries with ER- and/or PR-positive invasive breast cancer as defined by both the SEER-reported ER and PR (positive or borderline) immunohistochemistry results and 21-gene assay quantitative ER and PR score.

Investigators performed survival analysis on eligible patients and stratified by the 21-gene RS cut points—RS <18, RS 18-30, or RS ≥31—and by lymph node status. Distribution of RS results was then correlated with 5-year survival and overall survival (OS).

Men were older at the time of diagnosis (mean age, 64.2 vs 59.1 years; P <.001). Most patients (men, 58.0%; women, 58.2%) had RS <18. However, RS ≥31 was more frequent in men (12.4% vs 7.4%; P <.001), as were scores RS <11 (33.8% vs 22.1%; P <.001). Mean quantitative gene expression was higher in men for the ER, proliferation, and for stromelysin in the invasion gene groups.

In women younger than 50 years of age, quantitative ER expression was relatively low but increased with age. The reverse pattern was observed with PR, with higher quantitative PR expression in those younger than age 50.

Compared with older men, ER and PR were slightly lower in men younger than 50 years of age, but the finding was limited by the smaller numbers and greater variance in the youngest (<40 years) and oldest (>80 years) age groups

With the survival data from SEER for the 322 men and 55,842 women, the investigators found a wide range of RS results in both genders. Men had a higher proportion of larger tumors and grade 3 tumors.

The 5-year OS rates for men with RS <18 and RS 18 to 30 were 92.6% and 86.0%, respectively. In men with RS ≥31, the 5-year OS rate was 69.9%.

Although the number of events in men with breast cancer was relatively small, estimates for breast cancer—specific survival (BCSS) differed significantly across risk groups, regardless of nodal status (P = .003 in the overall group). Five-year BCSS was 99.0% (95% CI, 99.3-99.9) in men with RS <18 and 95.9% (95% CI, 87.6-98.7) in men with RS 18 to 30.

Five-year BCSS was similar in the RS <18 (99.5%; 95% CI, 99.4-99.6) and RS 18 to 30 groups (98.6%; 95% CI, 98.4-98.8) among women.

Five-year BCSS was 81.0% (95% CI 53.3-93.2) for men with RS ≥31 compared with 94.9% for women with RS ≥31 (95% CI, 93.9-95.7). Though the numbers in men are small, investigators concluded that women in the RS ≥31 group appear to have better survival than men.

“In addition to the biologic distinctions observed for breast cancer in men versus women, our study shows that both men and women with lower RS results have low mortality from ER-positive breast cancer, and many can be spared the risks associated with overtreatment, particularly from chemotherapy,” first author Suleiman Alfred Massarweh, MD, associate professor of medicine-oncology at the Stanford University Medical Center, and colleagues wrote. “Although there are limitations to our study, it may be appropriate to limit the use of chemotherapy in appropriately selected patients with RS 0-30, including those with 1-3LN.”

Massarweh SA, Sledge GW, Miller DP, et al. Molecular characterization and mortality from breast cancer in men [published online March 27, 2018]. J Clin Oncol. doi: 10.1200/JCO.2017.76.8861.