Cover Story

Better understanding of disease biology triggers ‘revolution’ in male breast cancer

Breast cancer is the most common malignancy in the United States.

It also is the most highly funded, accounting for nearly one-sixth of NCI’s annual research budget.

The financial investment has yielded tremendous insights into breast cancer biology, the importance of tailoring treatment based on patients’ genetic make-up, and the potential value of screening.

However, experts contend one key aspect — the nature of the disease in men — remains woefully understudied.

“Male breast cancer is poorly understood, primarily because of the rarity of the disease,” Xiaoxian (Bill) Li, MD, PhD, assistant professor in the department of pathology and laboratory medicine at Emory University School of Medicine, told HemOnc Today. “We are unable to conduct large prospective clinical trials in men because of the small number of patients.”

Xiaoxian (Bill) Li, MD, PhD, and colleagues conducted a study that indicated this may not be true.
Researchers previously thought male breast cancer behaved the same way as female breast cancer, and that survival is comparable among men and women. Xiaoxian (Bill) Li, MD, PhD, and colleagues conducted a study that indicated this may not be true.

Photo by Donna M. Martin, director, pathology resources & development, department of pathology and laboratory medicine, Emory University

As with many other orphan diseases, research funding for male breast cancer is minimal. The lack of knowledge is compounded by the fact that an estimated two-thirds of breast cancer clinical trials exclude men.

“Most information on breast cancer in men has been collected from retrospective studies spanning several decades, and treatment recommendations have been extrapolated from results of trials in female patients,” Sharon H. Giordano, MD, MPH, chair of the department of health services research at The University of Texas MD Anderson Cancer Center, wrote in a review article published in The Oncologist. “[Although] breast cancer in men is similar to female breast cancer, there are distinct features that should be appreciated.”

HemOnc Today spoke with oncologists and investigators about the challenges associated with studying and treating male breast cancer, the insights recent studies have provided into disease biology, the need for expanded trial access and the potential that additional research could lead to tailored treatments for men.

Incidence, risk factors

Nearly 250,000 Americans will be diagnosed with invasive breast cancer this year, according to NCI estimates. Only 2,600 of them — approximately 1% — will be men.

Median age at diagnosis for men is 68 years, compared with 61 years for women.

“The most common age group is between 60 and 70 years,” Richard L. White, MD, FACS, chief of the division of surgical oncology and co-director of the breast and melanoma programs at Levine Cancer Institute at Carolinas HealthCare System, told HemOnc Today. “I am not sure that we know the answer as to why this appears to be a disease that occurs in older males.”

A population-based study by Giordano and colleagues showed male breast cancer cases in the United States increased by 25% between 1973 and 1998. During that time, incidence rose from 0.86 cases to 1.08 cases per 100,000 people (P < .001).

Researchers determined men had an older median age at diagnosis than women. Men also were more likely to have lymph node involvement and advanced disease stage at diagnosis (P < .001 for all). Multivariate analysis showed lymph node involvement and larger tumor size were associated with shortened survival.

Research into potential causes of breast cancer in men has been limited.

Risk factors include obesity, older age, prior radiation to the chest and presence of a BRCA2 mutation. The risk for breast cancer in a man with a BRCA2 mutation is about 7% to 8%, whereas woman have roughly a 50% risk, White said. The average man has a 0.1% risk, or one in 1,000.