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June 6, 2006

Breast-sparing surgery an option for women with breast cancer gene mutation, U-M-led study finds

Hormonal treatments reduce risk of cancer returning, finds 10-year study

ANN ARBOR, MI – Women diagnosed with breast cancer who carry a certain genetic mutation can have breast-sparing surgery but should consider hormonal treatments to reduce their risk of cancer returning.

Lori J. Pierce, M.D.,Those are the findings of a 10-year study led by researchers at the University of Michigan Comprehensive Cancer Center. The study authors found that women with the genetic mutation who had their ovaries removed or took the anti-estrogen drug tamoxifen had lower rates of breast cancer recurrence or new breast cancers in the other breast.

Women who carry a mutation on the BRCA1 or BRCA2 gene are at an increased risk of breast cancer compared to women without the mutation. And once diagnosed with breast cancer, they face a higher rate of a second tumor occurring. Because of this, questions remain about whether these women should undergo breast-conserving surgery instead of mastectomy, which removes the entire breast.

In this study, published in the June 1 issue of the Journal of Clinical Oncology, researchers from 11 sites in the United States, Canada and Israel looked at 160 women with early breast cancer and the BRCA1 or BRCA2 gene mutations. The women were treated with lumpectomy, surgery to remove only the tumor, followed by radiation therapy. These women were compared to 445 similar women who were treated for breast cancer but did not carry the genetic mutations.

After 15 years, both groups of women had similar rates of the tumor reoccurring in the same breast. But among the women with the BRCA1 or BRCA2 mutations, those who were further treated by having their ovaries removed, a procedure called oophorectomy, were less likely to have a recurrence. Similarly, tamoxifen dropped the risk of same-breast recurrence for the mutation carriers by 58 percent.

Women with the genetic mutations had a significantly greater risk of developing breast cancer in the opposite breast than did the control group. After 15 years, 45 percent of the women with the mutation who had not undergone oopherectomy developed a second breast cancer in the other breast, compared to only 9 percent of those women without the genetic mutation.

Women with the mutation who took tamoxifen had a 69 percent reduction in breast cancer in the opposite breast. Among women who did not undergo oophorectomy, tamoxifen made a significant difference: 6 percent of those taking tamoxifen had a second cancer in the opposite breast after 15 years, compared to 54 percent of those who did not take tamoxifen.

“For women with early stage breast cancer who are BRCA1 or BRCA2 carriers, our 10-year data suggest that oophorectomy or tamoxifen in women treated with breast conservation and radiation therapy help to reduce the risk of recurrences and new primary cancers in the treated breast to levels comparable to those observed in women with early stage breast cancer who are not BRCA1 or BRCA2 carriers,” says lead study author Lori J. Pierce, M.D., professor of radiation oncology at the U-M Medical School.

“However, carriers must understand that the risk of breast cancer in the opposite breast still remained significantly greater than in women without a mutation. Thus, it is very important that women who choose breast preservation discuss with their doctors surveillance strategies not only of the involved breast but also in the opposite breast,” she says.

Oophorectomy is a common procedure for women with the BRCA1 or BRCA2 gene mutations because it reduces the risk of ovarian cancer, which is also higher in women with these mutations. Tamoxifen is commonly prescribed to treat breast cancer that is responsive to estrogen.

Many women with the genetic mutations will have both their breasts removed before cancer develops as a preventive strategy. After breast cancer develops, bilateral mastectomy reduces the risk of it recurring by at least 90 percent. But studies have shown approximately the same number of breast cancer patients with the mutations choose mastectomy and breast conservation, suggesting considerable interest in breast conservation among this group of women.

“We need to look to hormonal therapies that may lead to greater risk reductions than tamoxifen. For example, recent studies suggest comparable risk reductions with raloxifene and tamoxifen but fewer side effects with raloxifene. Studies are needed to assess the effect drugs such as raloxifene or aromatase inhibitors have in preventing second tumors in breast cancer mutation carriers,” Pierce says.

This year, 212,920 women will be diagnosed with breast cancer. About 1 in 300 people carry the BRCA1 or BRCA2 gene mutation. For information about breast cancer or genetic counseling, visit www.cancer.med.umich.edu/clinic/briskclinic.htm or call the Cancer AnswerLine at 800-865-1125.

In addition to Pierce, U-M study authors were Merav Ben-David, M.D., clinical lecturer in radiation oncology; Sofia Merajver, M.D., Ph.D., professor of internal medicine; Albert Levin, Ph.D.; and Sharon Kardia, Ph.D., associate professor of epidemiology. Other authors were Timothy Rebbeck, Lawrence Solin, Eleanor Harris, and Barbara Weber, all from the University of Pennsylvania; Eitan Friedman from the Sheba Medical Center in Israel; David Gaffney from the University of Utah; Bruce Haffty from Yale University; Laura Dawson, Steven Narod and Kelly Metcalfe, all from the University of Toronto; Ivo Olivotto from the British Columbia Cancer Agency; Andrea Eisen and Timothy Whelan from the Hamilton Regional Cancer Center in Ontario; Olufunmilayo Olopade from the University of Chicago; Claudine Isaacs from Georgetown University; and Julia Wong and Judy Garber from Dana Farber Cancer Institute.

Funding for the study was from the Breast Cancer Research Foundation, National Institutes of Health and National Cancer Institute.

Reference: Journal of Clinical Oncology, June 1, 2006, Vol. 24, No. 16, pp. 2437-2443.

Written by Nicole Fawcett

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