Acute Estrogen Withdrawal Increases Breast Cancer Risk in Women with KRAS-Variant Mutation

UCLA researchers have discovered that for women with a relatively common inherited genetic mutation, known as the KRAS-variant, an abrupt lowering of estrogen in the body may increase the risk for breast cancer and impact the biology of their breast cancer. Scientists also found that women with the KRAS-variant are more likely to develop a second primary breast cancer, independent of a first breast cancer. The two-year study, led by Dr. Joanne Weidhaas (photo), a Professor of Radiation Oncology at the UCLA Jonsson Comprehensive Cancer Center and Director of Translational Research at the David Geffen School of Medicine, analyzed data from more than 1,700 women with breast cancer who submitted DNA samples to be tested for the inherited KRAS-variant. The study also included a group of women with the KRAS-variant who were cancer-free, as well as biological models to scientifically confirm the clinical findings. Dr. Weidhaas’ team found that acute estrogen withdrawal, as experienced after removal of the ovaries or when hormone replacement therapy was discontinued, and/or a low estrogen state, were associated with breast cancer in women with the KRAS-variant. Acute estrogen withdrawal also triggered breast cancer formation in KRAS-variant biological models used in the study. In addition, up to 45 percent of breast cancer patients with the KRAS-variant eventually developed a second independent breast cancer — representing a 12-fold greater risk than women with breast cancer who did not have the KRAS-variant. “Although we had evidence that the KRAS-variant was a stronger predictor of cancer risk for women than men, we did not previously have a scientific explanation for this observation,” Dr. Weidhaas said.
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