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Chemotherapy beneficial in BRCA1/2 carriers.

Stockholm -- Adjuvant chemotherapy appears critical to overcoming adverse prognostic factors for recurrence and survival in women with BRCAl or BRCA2 breast cancer, according to a large prospective study presented at the annual meeting of the European Society for Medical Oncology.

Although BRCAl and BRCA2 carriers presented at a younger age and with more advanced disease than patients with sporadic breast cancers, those who received adjuvant chemotherapy fared as well overall as comparable patients in the control group.

Hazard ratios for distant disease recurrence and for death were far worse in the absence of adjuvant chemotherapy, however: 1.69 and 1.97, respectively, in BRCAl carriers; 2.13 and 3.62 (P =.005), respectively, in BRCA2 carriers. That just one of these ratios is statistically significant owes to only a small number of carriers not receiving adjuvant chemotherapy, said study investigator Dr. Pamela J. Goodwin, Marvelle Koffler Chair in Breast Research and professor of medicine at the University of Toronto.

In all, 87% of BRCAl carriers and 79% of BRCA2 carriers had adjuvant chemotherapy. Those who did not have adjuvant therapy were likely treated 10-15 years ago, Dr. Goodwin suggested.

"The vast majority [of BRCAl carriers] receives chemotherapy, and what seems to be happening is the chemotherapy is overcoming the effect of the adverse prognostic factors," she said in an interview after her presentation.

Although adjuvant chemotherapy was slightly less frequent in BRCA2 carriers, the investigators saw a similar pattern. "It seems to overcome the adverse prognosis. ... Not getting chemotherapy is a major, major negative," she added.

Dr. Goodwin and her coinvestigators selected participants for the prospective study from population-based cancer registries in Ontario, Canada (1996-1998), Northern California (1995-2000), and Australia (1992-1999). DNA samples were required. The population compared in the analyses comprised 92 BRCAl carriers, 72 BRCA2 carriers, and 1,549 women with sporadic breast cancer.

Another 1,510 women were identified with other familial breast cancers. Although she did not discuss this population, Dr. Goodwin told her audience that "their results were virtually identical to the sporadic group." Analysis of the impact of adjuvant hormonal therapy is in progress, she added, and will be presented in December at the San Antonio Breast Cancer Symposium.

Compared with women with sporadic disease, the BRCAl carriers tended to be younger and have higher-grade disease with negative receptors, Dr. Goodwin reported. BRCA2 carriers presented with high-grade disease but had more nodal involvement.

Tumor characteristics such as T stage, nodal status, and grade appeared to have similar prognostic effects in carriers and patients with sporadic disease, Dr. Goodwin said, but "effects of grade were less apparent in carriers." Carrier status did not appear to have a significant effect on distant disease-free survival or overall status in BRCAl carriers.

The effect was significant with respect to both in univariate analysis for BRCA2 carriers, but disappeared after adjustment for age and tumor characteristics. The unadjusted prognosis is important when counseling individual patients, Dr. Goodwin advised. "They are more concerned about how they will fare as individuals than whether their outcomes are swayed by age or tumor characteristics," she said.

'Adjuvant chemotherapy appears to play a particularly important role in mutation carriers," Dr. Goodwin said, concluding, "Understanding the relative efficacy of different chemotherapeutic agents in the adjuvant setting in mutation carriers should be an important priority."


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Title Annotation:Women's Health
Author:MacNeil, Jane Salodof
Publication:Internal Medicine News
Article Type:Clinical report
Geographic Code:1USA
Date:Nov 1, 2008
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