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Male, female breast cancers demonstrate biological differences
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Although overall histologic grade is significantly associated with outcome in female patients with breast cancer, this association did not persist among male patients with breast cancer, according to study results from the International Male Breast Cancer Program presented at The 10th European Breast Cancer Conference in Amsterdam.
However, mitotic activity index did appear significantly associated with OS in male patients with breast cancer, and men with fibrotic focus and a limited number of tumor infiltrating lymphocytes (TILs) were more likely to have unfavorable outcomes, results showed.
Overall, these data should better inform risk stratification and treatment decisions for male patients, according to Carolien van Deurzen, MD, a pathologist specializing in breast cancer at the Erasmus Medical Centre in Rotterdam, the Netherlands, and colleagues.
Although male breast cancer has important biological differences from female breast cancers, these differences had not been well studied and males have been excluded from many breast cancer clinical trials, according to the release.
To explore these differences, van Deurzen and colleagues evaluated 1,203 tumor samples from 1,483 male breast cancer patients from 23 centers in nine countries. The researchers assessed conventional tumor tissue characteristics, including tumor subtype and tumor grade, the development of fibrotic connective tissue and the density of tumor infiltrating lymphocytes.
Median follow-up for OS was 7.1 years.
Researchers classified 85% of carcinomas as ductal carcinomas, 50% of which were grade II.
Histologic grade was not significantly associated with OS (HR for grade II vs. I = 1.27; 95%CI, 0.95–1.7; and HR for grade III vs. grade I = 1.39; 95%CI, 1–1.93). This finding persisted in a subgroup analysis stratified by disease stage and chemotherapy and endocrine therapy administration.
The lack of an association between grading and outcome may be linked to the different distribution of disease subtypes in men compared with women, according to the researchers. For example, lobular tumors are rare in men but common in women. More men had luminal, or ER-positive tumors, whereas fewer had HER-2–positive or triple-negative disease.
“This subtyping of breast tumors does not seem to result in an optimal risk classification for male breast cancer patients,” van Deurzen said. “Additional tests that are well established in women, including gene-expression profiling, may result in the identification of more accurate prognostic and predictive markers. These could enable us to make better treatment choices, individualized for each patient, particularly in regard to the use of chemotherapy and new targeted agents.”
The researchers also found that a greater mitotic activity index — a component of grading — was associated with unfavorable OS among men (HR for 1-unit increase = 1.02; 95%CI, 1.01–1.03).
Further, the development of fibrotic connective tissue appeared associated with unfavorable OS (HR = 1.39; 95%CI, 1.11–1.74). Low density of TILs also increased risk for mortality (HR for moderate vs. minimal = 0.71; 95% CI, 0.49–1.03; HR for mild vs. minimal = 0.68; 95%CI, 0.53–0.87).
Van Deurzen and colleagues are planning a clinical trial that will evaluate an agent that blocks the androgen receptor in male breast cancer.
“This will only be possible with a worldwide collaboration, but it is also important that male breast cancer patients should take part in general breast cancer trials, since trials for them alone are difficult to run due to the rarity of the disease,” van Deurzen said. “In the meantime, we believe that our findings will help focus research in the field, since they indicate that we should be focusing on improving the management of luminal cancers as opposed to other subtypes in these patients.” – by Jennifer Southall
Reference: Vermeulen MA, et al. Abstract 7. Presented at: 10th European Breast Cancer Conference; March 9-11, 2016; Amsterdam.
Disclosure: The researchers report no relevant financial disclosures.