Jefferson study shows women with inherited breast cancer gene at greater risk for recurrence and new tumors

September 29, 1999



The results pose new questions regarding treatment options for women


For many women under 40 with breast cancer, surgery to remove the cancerous lump and accompanying radiation seem the best way to get rid of the disease and preserve the natural breast. But for women who carry a damaged version of BRCA1 or BRCA2, genes predisposing them to breast cancer, such treatment may not be enough. Researchers at Jefferson Medical College have found that such women have a greater risk of either relapsing or developing new tumors years later than those women who receive a lumpectomy and radiation therapy but don't carry one of these genes.

As a result, says Bruce Turner, M.D., Ph.D., assistant professor of radiation oncology at Thomas Jefferson University in Philadelphia and a member of Jefferson's Kimmel Cancer Center, who led the work, women and physicians may want to rethink their treatment options.

"These findings suggest that a woman who has a mutation in BRCA1 or BRCA2 who is treated with breast-conserving therapy not only has a high risk of local recurrence--40 percent according to our study--but also a high risk of developing breast cancer in the other breast as well," Dr. Turner says.

"Our data suggest that breast-conserving therapy may not be the most optimal treatment for breast cancer patients with BRCA1 or BRCA2 mutations who want to reduce the risk of locally recurrent breast cancer."

Dr. Turner and colleagues at Yale University and Myriad Genetics report their findings in the October issue of the Journal of Clinical Oncology.

Of 170,000 new breast cancer cases a year in U.S. women, about 10 percent--17,000 women--are under 40. Some 10 to 15 percent of those women (2,000) carry an altered BRCA1 or BRCA2 gene, and about 70 to 80 percent develop breast cancer.

Dr. Turner and his group wanted to examine the question of whether those women with a BRCA1 or BRCA2 mutation under 40 who are likely to develop breast cancer are more appropriately treated with mastectomy or breast conserving therapy.

Dr. Turner and his co-workers looked at the frequency of alterations in BRCA1 and BRCA2 in 52 breast cancer patients who, between 1973 and 1994, were treated with breast-conserving lumpectomy and radiation, and who subsequently developed a recurrent cancer in the same breast. They compared these women to 52 other women who had localized breast cancer and were treated similarly but did not experience recurrent disease.

The researchers found that eight, or 15 percent, of the 52 women who had further breast cancer also carried a damaged BRCA1 or BRCA2 gene. In women 40 or under with recurrent breast cancer, six of 15, or 40 percent, had a damaged inherited BRCA1 or BRCA2 gene. In contrast, only one of 15 women in the comparison group who did not have any recurrent cancers carried the bad gene.

The scientists also found that it took longer--an average of about eight years--for women with an altered BRCA1 or BRCA2 gene to relapse than it did women without the damaged gene (slightly less than five years on average). They then carefully examined the tumors using molecular and histologic analysis, thinking these were old cancers that had returned. Instead, they found that some of the tumors were actually completely new breast cancers. The new cancers took an average of 8.5 years to develop.

"If this study is validated with a larger prospective study, it may suggest that BRCA1 or BRCA2 testing may be reasonable to determine optimal breast cancer treatment--either breast-conserving therapy or mastectomy for younger women with family histories of breast or ovarian cancer," Dr. Turner says.

Dr. Turner believes that the study results may present women and their physicians with some difficult decisions regarding appropriate treatments.

"If you told a woman with a damaged BRCA1 or BRCA2 gene that in nine years, 40 to 50 percent of patients like you are going to have a new breast cancer, and you may need a mastectomy, then you'd have to ask her, would you rather have the lumpectomy and seven weeks of radiation or would you rather have the mastectomy now and reduce the risk of recurrent disease?"

One problem with recurring cancer is the threat that the disease may spread. While breast-conserving therapy may be curative for many women, some women who develop recurrent breast cancer also develop metastatic disease.

Dr. Turner says that researchers now need to "look at patients with BRCA1 or BRCA2 who have had a mastectomy and look at the frequency of chest-wall relapse and metastatic disease.

"It makes sense that by removing 90 to 95 percent of the breast cancer cells by mastectomy, the future risk of breast cancer is significantly reduced. But more definitive data is needed before we can justify this recommendation."
-end-


Thomas Jefferson University

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