Although the molecular mechanisms to explain this loss of sensitivity are not yet clear, the researchers believe that the BRCA1 mutation is causing the estrogen signaling pathway to malfunction, ultimately making these tumors harder to treat.
The findings also explain why the small proportion of women who have had an oophorectomy and still develop breast cancer frequently have tumors that are unresponsive to anti-estrogens like Tamoxifen, said Furth.
Both breast and ovarian cancers are often stimulated by estrogen, so oncologists counsel women who are over the age of 35 and know they carry a BRCA mutation to remove their ovariesthe bodys major source of estrogento reduce their chances of developing breast cancer and virtually eliminate risk of ovarian cancer, she explained.
Women with a BRCA1 mutation develop breast cancers that are most often unresponsive to hormones and anti-hormonal therapies like Tamoxifen, said Furth, but doctors continue to see reduced incidence of breast cancer among high-risk women who have undergone the oophorectomy procedure.
The finding that estrogen is important in the development of BRCA1 mutant breast cancers is one of the strongest pieces of evidence to support removing the ovaries to reduce incidence of cancer in BRCA1 mutation carriers, said co-author Eliot Rosen, MD, PhD, professor of oncology, biochemistry & cell and molecular biology, and radiation medicine at Georgetown.
The research also explains why oophorectomy appears to be more effective for younger women than older women, he said. This study demonstrates that estrogen is important to the early development of cancer, said Rosen. Women who have lost BRCA1 function need estrogen to generat
|Contact: Becky Wexler|
Georgetown University Medical Center