Women With BRCA Mutations at Greater Risk for Recurrence, New Breast Tumors

For many women under 40 years of age with breast cancer, surgery to remove the cancerous lump and accompanying radiation therapy seem to be the best option for eradicating the disease and preserving the natural breast. However, for women who carry a damaged version of the BRCA1 or BRCA2 gene, thus predisposing them to breast cancer, such treatment may be insufficient. Researchers at Jefferson Medical College have found that these women are at greater risk years later of either relapsing or developing new tumors than are similarly treated women who do not carry one of these genes.

As a result, women and physicians may want to rethink their treatment options said Bruce Turner, MD, PhD, who led the study and is assistant professor of radiation oncology at Thomas Jefferson University in Philadelphia and a member of Jefferson’s Kimmel Cancer Center.

Breast Conservation May Not Be Optimal Therapy for Mutation Carriers

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

“Our data suggest that breast-conserving therapy may not be 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 reported their findings in the October 1999 issue of the Journal of Clinical Oncology.

Of the 170,000 new breast cancer cases diagnosed annually in US women, about 10%—17,000 cases—occur in those under 40 years of age. Some 10% to 15% of these women (2,000) carry an altered BRCA1 or BRCA2 gene, and about 70% to 80% develop breast cancer.

Dr. Turner and his group wanted to determine whether women with a BRCA1 or BRCA2 mutation who are under 40 years of age and are likely to develop breast cancer are more appropriately treated with mastectomy or breast-conserving therapy.

The research team looked at the frequency of alterations in BRCA1 and BRCA2 in 52 breast cancer patients who were treated with breast-conserving lumpectomy and radiation between 1973 and 1994 and who subsequently developed a recurrent cancer in the same breast. They compared these women to 52 other women with localized breast cancer who were treated similarly but did not develop recurrent disease.

The researchers found that 8, or 15%, of the 52 women who had further breast cancer also carried a damaged BRCA1 or BRCA2 gene. In women 40 years of age or under with recurrent breast cancer, 6 of 15, or 40%, had a mutated BRCA1 or BRCA2 gene. In contrast, only 1 of 15 women in the comparison group who did not develop any recurrent cancers carried the damaged gene.

The scientists also found that it took longer—an average of about 8 years—for women with an altered BRCA1 or BRCA2 gene to relapse than it did for women without the damaged gene (slightly less than 5 years on average). They then carefully examined the tumors using molecular and histologic analysis, under the supposition that these were old cancers that had returned. Instead, they found that some of the tumors actually were completely new breast cancers. The new cancers took an average of 8.5 years to develop.

BRCA Testing May Be Reasonable to Determine Optimal Treatment

“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,” said Dr. Turner.

 He 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 9 years, 40% to 50% of patients like her are going to have a new breast cancer, and she may need a mastectomy, then you’d have to ask her, would you rather have the lumpectomy and 7 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 said that researchers now need to look at the frequency of chest wall relapse and metastatic disease in patients with BRCA1 or BRCA2 who have had a mastectomy. “It makes sense that by removing 90% to 95% 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.”