In the first study, researchers tested 183 women with familial breast cancer for errors in the BRCA1 gene, which are associated with an increased risk for breast cancer. Forty patients, (22%) from 36 different families, had a detectable mutation. Tumors from BRCA1 carriers and non-carriers were then compared for several characteristics, including size and grade.

BRCA1 tumors were more advanced at the time of detection, and were larger in diameter. The proportion of tumors that had spread to the lymph nodes was 40% for BRCA1 carriers, versus 21% for the non-BRCA1 tumors. The tumors were also more often estrogen receptor-negative (ER-negative) and progesterone receptor-negative (PR-negative), meaning they can grow in the absence of these hormones and aren''t prevented by tamoxifen. Unfortunately, BRCA1 mutations were also associated with a poorer five-year survival rate for the patient (80% vs. 90%).

In a second study, Canadian researchers found that BRCA1/2 tumors tend to have low levels of a protein called p27^kip1, which is also associated with a poor outcome. They screened 202 Ashkenazi Jewish women with primary invasive breast cancer for the three BRCA1/2 mutations common to that population. Of these 202 samples, 32 were identified as BRCA1/2 carriers (16%).

The tumors from 27 of these BRCA1/2 carriers were then tested for levels of p27^kip1 protein. Eighty-five percent of BRCA1/2 tumors had low levels of the p27^kip1 protein, compared to 59% of the BRCA negative tumors. Low levels of this protein were associated with larger, higher-grade tumors that were likely to be ER-negative.

Patients with BRCA1/2 mutations or low p27^kip1 protein levels also had poorer outcomes. Five years after diagnosis and treatment, 58% of BRCA1/2 carriers were alive and cancer-free, compared to 82% of the non-carriers. The outcome for patients with low levels of p27^kip1 protein was similar – 68% of patients with low levels of the protein were alive and disease-free after five years, compared to 93% for those with high levels of the protein.

Heather Feigelson, PhD, an Epidemiologist at the American Cancer Society (ACS), says this study should be expanded to include larger numbers of patients. "The fact that both studies reached the same conclusion about reduced survival among women with breast cancer who carry a BRCA1 or BRCA2 mutation adds credibility to the findings, but these results really need to be confirmed in a larger study," says Feigelson.

Fortunately, BRCA1/2 mutations are very rare, accounting for only about 5% of all breast cancers. But outcome studies like this may prove beneficial to women who are BRCA1/2 carriers, since they may want more aggressive prevention and/or treatment options.

All women should do monthly self-breast exams. The ACS recommends that beginning at age 40, women should have regular screening, including mammograms, by a health care provider. "Women who think that they are at high risk should talk with their doctor about earlier and more frequent screening or other options like ultrasound or tamoxifen," says Feigelson. According to Herman Kattlove, MD, an Oncologist and Medical Editor for the ACS, "Tamoxifen might be a good choice. A recent study published in the December 2 issue of The Lancet reported that tamoxifen cut the rate of breast cancer in BRCA-positive women by 50%." He added "Some women just want to eliminate as much risk as possible and prefer to have prophylactic mastectomy."

• Breast Cancer