Analysis Identifies Distinct Characteristics of Male Breast Cancer

Distinctive biologic features of breast cancer in men were determined in a recent analysis of clinical characteristics, gene expression, and 21-gene Breast Recurrence Score, which also suggested that that RS testing may have an important prognostic role for both men and women.

Suleiman Alfred Massarweh, MD

Distinctive biologic features of breast cancer in men were determined in a recent analysis of clinical characteristics, gene expression, and 21-gene Breast Recurrence Score (RS), which also suggested that that RS testing may have an important prognostic role for both men and women.

From June 2004 to January 2017, male and female patients with breast cancer specimens were identified and submitted for Genomic Health 21-gene RS testing in North America. Overall, 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) were included in the 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 for their outcomes analysis. 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, defined by both the SEER-reported ER and PR (positive or borderline) immunohistochemistry results and 21-gene assay quantitative ER and PR score.

Survival analysis was performed 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 the RS findings was then correlated with 5-year survival and overall survival (OS).

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

For women under the age of 50, quantitative ER expression was relatively low but increased with age. Investigators observed the reverse pattern with PR, with higher quantitative PR expression in those younger than age 50.

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

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

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

Although 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). The 5-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 among the women 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).

Also, 5-year BCSS was 81.0% (95% CI 53.3-93.2) for men with RS ≥31 versus 94.9% for women with RS ≥31 (95% CI, 93.9-95.7). While 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.