January 14, 2003
Study aims to solve puzzle of ER-negative breast tumors
A puzzling pattern of risk
ER-negative cancers disproportionately strike younger, premenopausal women, African-Americans, women with a strong family history of breast cancer, and those who have inherited the mutant BRCA1 gene. Most tumors in women with the mutant BRCA2 gene, however, are ER-positive.
ER-positive tumors, on the other hand, are more likely to be diagnosed in women whose reproductive history has exposed them to more of their body's estrogen. This includes women who began menstruating early, had few children or had them late, or who concluded menopause after age 55. "It's thought, but not proven, that these hormonal factors play a small role, if any, in ER-negative breast cancer," says Dr. Brown.
Breast cancer patient Amy Osgood confers with Judy Garber, MD, MPH
They differ in other ways, too. ER-negative tumors are often more aggressive than the ER-positive type, making them harder to treat successfully. And some ER-negative cancer cells express another growth-factor receptor, called HER2/neu, which causes those tumors to grow faster and resist standard drugs. (In the past few years, a targeted treatment, Herceptin, which blocks the HER2/neu receptor, has been used along with conventional chemotherapy drugs to battle these cancers.)
Recent research suggests that ER-negative breast cancer may actually be several different subtypes of cancer, each stemming from a different abnormality in the cells. So the search for causes may lead in many directions, as if the researchers were pulling on different loose ends in a tangled ball of yarn.
Dr. Brown chose 20 individual investigators for the project because their research intersects with issues raised by ER-negative tumors. In addition, he enlisted the collaboration of epidemiologists Graham Colditz, MD, DPH, and Susan Hankinson, ScD, of Brigham and Women's Hospital to examine data from the nationwide Nurses' Health Study to clarify the risk factors in women's lifestyles and medical history that are specific to ER-positive, as opposed to ER-negative, cancer. The Nurses' Health Study has followed thousands of nurses since 1976 to observe the effects of diet, lifestyle, and other factors on women's health.
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