BRCA serves as a DNA repair molecule throughout the body, fixing cellular processes that have malfunctioned for some reason, said Furth. But once BRCA is damaged or mutated, these repair processes are slowed or stalled, which can set off a chain reaction resulting in cancer, as demonstrated in their laboratory model.
The reason why BRCA mutations are so potent for causing breast cancer is because of the multiple actions it can cause, said Furth. Loss of BRCA function interferes with DNA repair and, as shown in this study, it appears to enhance to growth effects of estrogen.
The teams research might also reveal why pregnancy does not appear to be as protective against the development of breast cancer in this population as it does in women without genetic mutations. In non-inherited breast cancers, early pregnancy and multiple pregnancies appear to be protective against breast cancer development, explained Rosen.
But for women who have inherited BRCA1 mutations, the situation is the oppositeearly and multiple pregnancies seems to accelerate the development of breast cancer, he said. We can now speculate that the higher levels of estrogen and other hormones during pregnancy stimulate the early stages of cancer development.
The researchers intend to build upon their findings in future studies, investigating what is happening in the very early stages of cancer development and figuring out how tumor cells can become estrogen receptor negative. Furth and Peter Shields, MD, professor of oncology and medicine at Georgetown and the associate director for Cancer Control and Population Sciences at the Lombardi Comprehensive Cancer Center, recently received a two-year, $776,000 grant from the Department of Defense to study the role of another protein, transforming growth factor-beta (TGF-beta), believed to be invol
|Contact: Becky Wexler|
Georgetown University Medical Center