As a bodybuilder, you're typically more aware of your chest than most men. If you've ever taken prohormone supplements, you may also be more aware of your nipples than most men, since some prohormones can lead to gynecomastia--a condition where your nipples swell as a result of growing breast tissue. But as aware of your chest as you may be, did you know that men can get breast cancer? Every year in the United States, approximately 1,000 men develop carcinoma of the breast. While the average age at diagnosis is about 65 years, the problem can occur in younger men, too.

A recent study on male breast cancer was performed at Anderson Cancer Center in Houston. Using a National Cancer Institute database, the researchers identified more than 2,500 men who had the disease from 1973-1998. They also discovered that male breast-cancer rates went up from 0.86 cases per 100,000 Americans to 1.08 cases per 100,000 during the study period. The group concluded that this was a significant increase, though they're uncertain why it occurred.

Just as the causes of female breast cancer are still elusive, so are the precise causes of male breast cancer. Men have glandular breast tissue that is subject to hormonal influences; excess estrogen--especially around the time of puberty--and testosterone deficiency have been identified as possible factors. Men who work in steel mills, blast furnaces, rolling mills or other environments of intense heat have also been shown to have a slightly higher incidence of breast cancer. Genetic factors may play a role as well. If you've noticed a change in your nipples, see "Read the Signs" for information on symptoms to watch for.

RELATED ARTICLE: READ THE SIGNS

HERE ARE SOME SIGNS AND SYMPTOMS OF MALE BREAST CANCER:

* The most common symptom is a breast mass under the nipple.

* This mass usually is firm and not tender.

* The average tumor size is approximately 1 inch.

* Because of the short distance to the nipple, nipple retraction, ulceration or destruction are also common.

* Nipple discharge (bloody or serous) is distinctly abnormal in men and must be fully investigated.

* A prolonged rash or irritation of the nipple may indicate a special kind of breast cancer called Paget's disease, which specifically affects the nipple.

* Biopsy is required to make a proper diagnosis.

By impeding estrogen's cancer-promoting properties, the drug tamoxifen has enabled thousands of breast cancer patients to fend off recurrences. But taking tamoxifen increases the frequency of hot flashes, and many women use antidepressants to limit this side effect.

Researchers now report that popular antidepressants called selective serotonin reuptake inhibitors (SSRIs) might diminish the effectiveness of tamoxifen by limiting its conversion into medicinally important agents.

David A. Flockhart of the Indiana University School of Medicine in Indianapolis and his colleagues there and elsewhere measured one of these compounds, called endoxifen, which binds to estrogen receptors on cells and slows cancerous growth. In the Jan. 5 Journal of the National Cancer Institute, they report that women taking tamoxifen and an SSRI had lower blood concentrations of endoxifen than did similar women on tamoxifen who weren't using an SSRI.

The scientists also determined that a woman's genes can hinder her conversion of tamoxifen to endoxifen. Women with certain variant forms of a gene called CYP2D6 showed diminished endoxifen concentrations. Lab studies had shown that the enzyme encoded by CYP2D6 is one of the substances that break down tamoxifen to create endoxifen. About two-fifths of women have one of the enzyme-disabling variants of CYP2D6, says Flockhart. The findings could explain some of the variability in tamoxifen's effectiveness from patient to patient, he says.

Flockhart and his colleagues identified 80 women, average age 57, who had breast cancer and were just starting on tamoxifen. Some of the women were taking SSRIs, and some weren't; some in each group had a normal CYP2D6 gene, and some carried an enzyme-disabling variant. Over the following year, the scientists periodically recorded endoxifen concentrations in the women's blood.

The data showed that 48 of these 80 women had a normal CYP2D6 gene and thus probably made a full complement of its corresponding enzyme. After 4 months on tamoxifen, these women had nearly twice as much circulating endoxifen as did women who had inherited one of the enzyme-disabling variants of CYP2D6 from just one parent. Compared with women who had inherited variant forms from both parents, those with the normal gene had four times as much endoxifen in their blood.

Twelve of the 48 women with a normal CYP2D6 gene were also taking an antidepressant. Ten were on an SSRI--paroxetine (Paxil) or sertraline (Zoloff). The two others were getting venlafaxine (Effexor), which differs slightly from the SSRIs. Paroxetine and sertraline use coincided with significantly diminished endoxifen concentrations in blood, but venlafaxine didn't. The findings bolster test-tube studies in the 1990s that suggested that SSRIs could suppress the CYP2D6 enzyme.

The study raises hard questions about prescribing SSRIs for breast cancer patients with hot flashes, says Charles L. Loprinzi of the Mayo Clinic in Rochester, Minn. But it's encouraging that venlafaxine appears to leave the CYP2D6 enzyme alone, he says.

At a recent meeting, Mayo Clinic researcher Matthew P. Goetz unveiled data showing that breast cancer patients taking tamoxifen survived longer if they had a normal CYP2D6 gene rather than an enzyme-disabling variant.

If scientists can conclusively connect tamoxifen's effect on breast cancer recurrences and deaths to variants of this gene, Flockhart says, doctors might better identify which patients would benefit most from the drug.

Clinical Question: Is ductal lavage effective in detecting breast cancer?

Setting: Inpatient (any location)

Study Design: Cross-sectional

Synopsis: In this study, 32 women (mean age: 50 years) undergoing prophylactic (n = eight) or therapeutic (n = 35) mastectomy received ductal lavage in the operating room before surgery. The women were enrolled consecutively. To confirm that ducts were lavaged successfully, the surgeon injected a colored dye for the pathologist to identify. The authors do not report whether the cytologists and pathologists were blinded to other test results.

This study emphasized the analysis of 42 breasts. Two of the women undergoing prophylactic mastectomy had occult malignancies. At least one duct was lavaged successfully in 36 breasts, but only 31 yielded adequate cellular fluid. Cytology detected cancer in only five cancerous breasts. The ability of ductal lavage to find cancer in a breast is limited. Lavage detected marked atypia only 42 percent of the time and was accurate only one half of the time. Lowering the threshold so that mild atypia also was defined as abnormal decreased the overall accuracy and detected only 20 percent of the cancers. Because this was an extremely high-risk population, the sensitivity, even among high-risk women, would be even lower. Bottom Line: In this small study, ductal lavage was insensitive for detecting breast cancer. (Level of Evidence: 2b)

Study Reference: Khan SA, et al. Ductal lavage findings in women with known breast cancer undergoing mastectomy. J Natl Cancer Inst October 20, 2004;96:1510-7.

Used with permission from Barry H. Ductal lavage ineffective in finding breast cancer. Accessed online November 24, 2004, at: http://www.InfoPOEMs.com.

In the largest, most comprehensive study on racial and ethnic disparities in breast-cancer diagnoses, Seattle's Fred Hutchinson Cancer Research Center found that Black women are 130 to 150 percent more likely than White women to be diagnosed with later-stage tumors and face a 50-percent greater risk of dying

CHICAGO -- Late breast cancer recurrence may be emerging as a new concern in patients participating in a study on tamoxifen versus tamoxifen plus radiotherapy treatment, according to a Canadian expert.

Researchers from Toronto's Princess Margaret Hospital recently showed that the 5-year breast cancer relapse rate was significantly lower in 386 women over age 50 who were treated with the combination of radiation and tamoxifen after lumpectomy, compared with 383 women who were treated with lumpectomy and tamoxifen alone (N. Engl. J. Med. 2004;351:963-70).

"But the 5-year results may not be the whole story," lead investigator Anthony W. Fyles, M.D., reported to colleagues at the annual meeting of the Radiological Society of North America.

A small cohort of the study subjects has been followed now for 8 years, and preliminary data from these 87 women suggest that late relapse rates may be creeping up in both treatment groups, said Dr. Fyles, professor of radiation oncology at the University of Toronto. "It's quite a small number of women, and we need to follow more of them for longer lengths of time, but we are concerned that we are starting to see quite a few more relapses," Dr. Fyles told this newspaper.

The published study showed that at 5 years, the relapse rate was 0.6% in the combination therapy group versus 7.7% in the tamoxifen-only group. But the 8-year data, although still showing a distinct advantage to the combination therapy, reveal increased relapse rates in both of the groups: 3.5% in the combination therapy group, compared with 18% in the tamoxifen-only group, he said.

Of concern in the 8-year follow-up are patients over age 70 with tumor sizes of 1-2 cm. In this group, women who received combination therapy had no relapses. But those who received tamoxifen alone had a relapse rate of 17.6%.

The study design involved treatment with tamoxifen for 5 years, and the sudden increase in relapses could be partly explained by the termination of tamoxifen therapy at the 5-year mark. Dr. Fyles said.

"Now what we do ... is often we add an aromatase inhibitor after patients stop the tamoxifen. We don't know yet whether this reduces the risk of relapse, but the available data on these agents suggest that they will lower the risk of late relapse," for breast cancer patients, Dr. Fyles said at the meeting.