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Women With BRCA Mutations Get Cancer Diagnosis Earlier Than Before
Date:9/12/2011

By Kathleen Doheny
HealthDay Reporter

MONDAY, Sept. 12 (HealthDay News) -- Women with the genetic BRCA mutations, known to be at higher risk of developing breast and ovarian cancers, are being diagnosed with those cancers earlier than previous generations, researchers now report.

''We found with some mathematical modeling about a 7.9-year difference between older and newer [generations]," said Dr. Jennifer Litton, a breast medical oncologist at the University of Texas M.D. Anderson Cancer Center in Houston.

In the study, Litton analyzed the age at diagnosis of two generations of families in which there were BRCA-related cancers. Her research included 132 women diagnosed with a BRCA-positive breast cancer, 106 of whom had a family member of an earlier generation who had also been diagnosed with a BRCA-related breast or ovarian cancer.

In the analysis, the median age for the older generation at diagnosis was 48 (half older, half younger). The median age for the younger generation was 42. And, in a parametric model, the estimated change in the expected age at onset for the entire cohort was 7.9 years, the study showed.

A number of factors could explain the earlier onset, Litton said. Experts talk about a phenomenon in inherited diseases known as anticipation. It refers to diseases occurring at younger ages or with increased severity with each generation. This is due to DNA instability in which the genes actually evolve and change.

Other factors may also help explain the earlier onset, Litton added. Among them, better screening and finding cancers at earlier stages.

"It's important to continue to follow this [research] forward and validate it in bigger studies with more women involved," added Litton, whose research is published in the Sept. 12 online edition of the journal Cancer.

For now, the finding validates the recommendation of the National Comprehensive Cancer Network that screening begin at age 20 to 25 for women at risk of hereditary breast and ovarian cancer because of the BRCA gene mutations, or five to 10 years earlier than the youngest age of diagnosis in the family.

Another expert agreed that better screening and earlier diagnosis, among other factors, may well explain the earlier age at diagnosis.

"This may have nothing to do with genetic anticipation," said Dr. Jeffrey Weitzel, chief of the division of clinical cancer genetics at City of Hope Comprehensive Cancer Center in Duarte, Calif.

The factors explaining the earlier onset in the women with BRCA mutations could be the same ones that explain trends in the general population, Weitzel added. "But in high-risk women, it is magnified."

Genetic anticipation involves a process in which genes actually evolve and the underlying structure of the DNA changes, he said.

Environmental factors and reproductive factors may also play a role, he said. For instance, a woman whose menstrual periods started later -- which was often the case with older generations -- is at lower risk of breast cancer than a woman whose period started at a younger age.

The women in the study reporting the age at diagnosis of an older family member could also have reported incorrectly, he noted.

The results should inspire younger women with BRCA mutations to follow screening guidelines, which "have taken this observation [about earlier diagnosis] into account already," Weitzel said.

Women today, he added, "have access to what your grandmother didn't have. We have better screening technology."

The risk for women with a BRCA mutation developing breast cancer is as high as 80 percent, according to the American Cancer Society.

More information

To learn more about breast cancer and BRCA mutations, visit the American Cancer Society.

SOURCES: Jennifer Litton, M.D., breast medical oncologist, University of Texas M.D. Anderson Cancer Center, Houston; Jeffrey Weitzel, M.D., chief, division of clinical cancer genetics, and professor of oncology and population sciences, City of Hope Comprehensive Cancer Center, Duarte, Calif.; Sept. 12, 2011, Cancer, online


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