Researchers Identify Gene Variants for Breast Cancer

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ER Productions / Corbis

A woman receives a breast exam.

Thanks to advances in genetic analysis, researchers are constantly getting better at identifying which genes increase the risk of cancer. Most of the known genetic links apply to the risk of breast cancer — for example, the genes BRCA1 and BRCA2 account for as many as one-third of breast cancer cases in the U.S. But scientists are striving to refine their understanding further by studying other — albeit less powerful — genes that influence breast cancer risk and may even help determine what type of tumor a woman develops.

French and English researchers led by Gillian Reeves at University of Oxford compared the genes of 10,000 breast cancer patients and 10,000 healthy volunteers and found a suite of 14 genetic variations that were correlated with the disease (many of these gene differences had been identified in previous studies). Women with the highest number of these variants were twice as likely to develop breast cancer as women with the fewest combinations of these genes, and the pattern was more predictive of breast tumors that were positive for estrogen than those that were estrogen-negative.

Overall, says Reeves, the effect of the genetic variants was not strong enough to justify using them as a predictor for breast cancer quite yet. The risk of cancer among women with the most strongly associated genetic variations was 8.8% up to age 70, for instance — about the same rate as in women with a family history of breast cancer. Further, the newly identified gene variants are common in the general population — as many as 20% to 30% of women may carry them — and their contribution to breast cancer may be very small. That makes it difficult to use these genes in the clinic as a screening tool for breast cancer. "Certainly, these are very strong scientific results," says Dr. Kenneth Offit, chief of the clinical genetics service at Memorial Sloan-Kettering Cancer Center. "Yet it really remains unclear what their usefulness is to the patient or health care provider at the moment."

Instead, the most immediate utility of the genes, say both Offit and Reeves, is in providing researchers new targets for interrupting the formation of tumors. "What we have to remember is these genes that are associated with breast cancer risk come from regions [in the genome] where there are no known genes, or from genes whose function we don't fully understand yet," says Reeves. "By studying these genes associated with breast cancer risk, we can throw light on what in the body leads to breast cancer development. If we understand what their functions are, it can help us to better understand what the mechanism is for the development of breast cancer."

Reeves and her team found that slightly different genetic variations are associated with different types of breast tumors, such as ductal tumors, which form in the milk ducts, versus lobular cancers, which emerge from the tissues where milk is produced. Where a tumor forms plays a role in how aggressive the cancer will be, so detailed genetic information about a patient's tumor may help doctors decide which treatment options are best. "These pathways are not ones we otherwise would have known about," says Offit. "They haven't emerged from studies of tumors and only emerge from these types of large scale genomic studies. It's entirely possible that over time we will be able to devise drugs that target these new pathways and prevent breast cancer." Until then, he says, it's prudent to exercise some clinical caution in the face of scientific excitement.