From OncoLog, April 2004, Vol. 49, No. 4
An Unexpected Finding: Male Breast Cancer Is Rare and Often Overlooked
by Katie Prout Matias
Richard Pitre was lying in bed one night talking with his wife when they discovered a hard knot behind one nipple—his nipple. Alarmed, they made an appointment with his physician, who ordered a fine-needle biopsy of the lump. When the results came back negative for cancer, the physician told Mr. Pitre that it was probably fatty tissue. But when Mr. Pitre returned five months later for follow-up mammography and ultrasonography, the results shocked him: breast cancer.
“That is the last thing I thought I would have,” said Mr. Pitre, 57.
In 2002, 1,500 men were diagnosed with breast cancer in the United States; 21 of them were treated at The University of Texas M. D. Anderson Cancer Center. Each year, approximately 400 men die of the disease.
Because breast cancer is so uncommon in men, no large, population-based studies have been conducted, and very little is known about the disease’s epidemiology, risk factors, pathology, and treatment in men. “There is a huge void in information that needs to be filled,” said Sharon Giordano, M.D., M.P.H., an assistant professor in the Department of Breast Medical Oncology who treats most of M. D. Anderson’s male patients with breast cancer. “All the men who come here are wondering, ‘Why did I get breast cancer?’ We can’t really answer that right now.”
To shed light on this and other unanswered questions, Dr. Giordano has led two retrospective studies. In “Breast Cancer in Men,” published in the Annals of Internal Medicine in October 2002, she reviewed 114 articles published between 1942 and 2000. In a report accepted for publication in Cancer, she analyzed data from 1973 to 1998 in the National Cancer Institute’s Surveillance, Epidemiology, and End Results database, a cancer registry that includes data from 14% of the U.S. population. In this study, 2,524 cases of male breast cancer were compared with 380,856 cases of female breast cancer.
“Most men do not even think they can get breast cancer,” said Dr. Giordano. Mr. Pitre speculates that many men ignore the signs and delay the doctor visit because they are embarrassed or in denial. Because of his quick action in going to the doctor (and scheduling his mastectomy for the first day available— a Friday the 13th), Mr. Pitre’s cancer was stage I when it was removed.
When men do seek medical attention for their symptoms, 85% of the time they report a painless subareolar mass. Often, this is mistakenly diagnosed as gynecomastia, a benign swelling of the breast tissue that up to a third of men experience in their lifetimes. Other symptoms at presentation include local pain and nipple ulceration, retraction, bleeding, or discharge. In men, the cancer tends to involve the nipple, the skin, and the muscles because there is less breast tissue to invade.
A family history of breast cancer appears to be a risk factor for men: 15% to 20% of men with breast cancer have a family history, compared with 7% of the general male population. Carrying the BRCA1 gene mutation does not seem to increase risk in men, but the BRCA2 gene defect confers significant risk. Many risk factors are related to abnormalities in estrogen and androgen balance; other risk factors include testicular defects or injury, infertility, Klinefelter syndrome, obesity, cirrhosis, benign breast conditions or breast trauma, increasing age, Jewish ancestry, and radiation and estrogen exposure.
Ironically, breast cancers in men are more likely to be estrogen receptor positive and progesterone receptor positive than those in women. “It’s counterintuitive because estrogen and progesterone are female hormones,” said Dr. Giordano. Most men’s breast tumors (90%) are invasive, and the predominant histologic subtype is infiltrating ductal carcinoma (80%).
Dr. Giordano is very interested in how breast cancers in men differ biologically from those in women. The literature review she published in 2002 showed that breast cancers in men and women express many of the same molecular markers—c-erbB-2, p53, cyclin D1, and epidermal growth factor receptor—to the same degrees. However, men may have higher rates of Bcl-2 overexpression.
Five- and 10-year disease-specific survival rates are similar in men and women, but the overall survival rate is lower in men. As with women, lymph node status, tumor size, histologic grade, and hormone receptor status are significant prognostic factors for men.
Because no large, population-based studies have been conducted, many of these findings have not been verified. Furthermore, no large clinical trials have studied breast cancer treatment for men; most men are treated based on the standard of care guidelines established for women, which often indicate a modified radical mastectomy, axillary lymph node biopsy, and adjuvant therapy. The high rates of hormone receptor–positive tumors in male breast cancer suggest that adjuvant hormonal therapy could be effective, and indeed, the recommendation for men with hormone receptor–positive tumors is daily tamoxifen for five years.
Mr. Pitre, whose cancer was estrogen receptor positive, had great reservations about taking tamoxifen because of the increased risk of blood clots and stroke. “All of the hormonal questions, the possible impact on sexual activity, none of those things bothered me because I knew that men produce estrogen. The only thing that bothered me was the fact that I didn’t want to be cured of breast cancer and die from a stroke or blood clot,” said Mr. Pitre, who decided after much inner debate to take the pills.
While Mr. Pitre initially had no side effects, he later began experiencing gastrointestinal and vision problems, adverse effects that have been reported by other patients. After six months of taking tamoxifen, he decided to discontinue its use and since then has been feeling much better.
Dr. Giordano is very interested in studying how hormonal therapies may affect men differently. She plans to set up a registry with a standardized treatment algorithm for men, looking at outcomes and toxicity and correlating side effects with prognosis. She also intends to build a tissue bank of breast tumors from men.
In addition to the lack of research or data, the greatest problem for men with breast cancer may be the stigma associated with having what is traditionally considered a woman’s disease.
“I am sure there is a psychological burden to it, just because a lot of breast cancer centers are called women’s centers. Everyone assumes that they are a woman,” said Dr. Giordano. “It is important to keep the public consciousness open. People should be aware that [breast cancer] can happen [to men].”
According to Mr. Pitre, preconceived ideas about what a man is are a problem for all men seeking medical care. “Real men don’t cry. Real men don’t show pain. It is ludicrous because those real men die,” said Mr. Pitre. “The [breast cancer] death rate among men is so high because most men ignore it and don’t do anything about it, and by the time they do anything about it, it is in an advanced stage. I can tell other people, and if they can discover it as early as I did or earlier, then lives can be saved.”
For more information on this topic or for questions about M. D. Anderson’s treatments, programs, or services, call askMDAnderson at (877) MDA-6789.
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