Family History Raises Breast Cancer Risk

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Family History Raises Breast Cancer Risk
Study Shows Increased Risk Even Without Gene Mutations Linked to Breast Cancer

Women with a strong family history of breast cancer who do not have genes associated with increased risk of the disease have a fourfold greater chance of developing it than the average woman, new research indicates.

The finding may help doctors detect breast cancer earlier in high-risk women and lead to more and earlier preventive treatments, says the University of Toronto's Steven Narod, MD, senior author of the study.

Women with several blood relatives who have breast cancer have been known for years to be at higher risk themselves, Narod tells WebMD.

"We've always considered two groups of women -- those with family history of breast cancer and those with BRCA1 and BRCA2 genes -- to be at higher risk," Narod says. "But no one has ever looked at those with high risk of cancer because of family history, but negative tests [for BRCA1 and BRCA2]. It was assumed that most of the risk could be explained by those mutations."

The findings suggest that additional genes, hormones, or other unknown factors, perhaps environmental, are also responsible for causing breast cancer, Narod says.

That seems apparent from the study's finding that women with a strong family history were still at higher risk for developing the disease even if they didn't have BRCA gene mutations, Narod says.

"Now when we see families such as this, we will be able to offer better advice about their actual risk," he says. "It is clear to me that the risk is high enough that we need to discuss options, such as breast MRI for screening and chemoprevention with tamoxifen or raloxifene. Our hope is to be able to prevent or pick up on breast cancer early enough to stop patients from dying."

Kelly Metcalfe, RN, PhD, also of the University of Toronto, tells WebMD that "only 5% of women with breast cancer have a BRCA mutation," and therefore "it has been difficult to counsel women without a mutation" about their breast cancer risk.

"For a woman in which we do find a mutation, she has an approximate 80% risk of developing breast cancer," Metcalfe says. "For women with a significant family history of breast cancer, without a BRCA1-2 mutation, we can now say that she has an approximate 40% risk of developing breast cancer. This can be compared to a 10% risk of breast cancer for a woman in the general population."

Options for Women With Family History of Breast Cancer
The "take-away" message from the research, in which 1,492 women with first-degree breast cancer relatives were studied, is this, Metcalfe says:

"Having a BRCA mutation is the greatest risk factor for developing breast cancer. However, we still need to be very aware of a woman's family history of breast cancer, even without a mutation."

Options for Women With Family History of Breast Cancer continued...
Narod adds, "Despite the negative test [for the BRCA mutations], women are not in the clear."

He says he recommends that women without the BRCA mutations who have three or more relatives with breast cancer should undergo MRI screenings and consider taking tamoxifen. The findings do not call for preventive surgery -- removal of the breasts -- but he says some women may wish to consider that option.

"I think we have to take tamoxifen more seriously as a society" as a preventive measure, Narod tells WebMD. "You can reduce the risk from 40% to 20% -- pretty dramatic figures. Any woman at 40% risk of breast cancer should seriously consider it."

But researchers say they aren't ready yet to recommend that all women with family histories of breast cancer get tested for the BRCA genes.

"It is a personal decision about whether or not to have genetic testing," Metcalfe says. "However, for women with a family history of breast cancer, genetic testing can offer information about their personal risk of developing breast and ovarian cancer. And if a woman is found to have [the BRCA genes], options are available to significantly reduce their risk of cancer."

Metcalfe says the Toronto study, presented at the American Association for Cancer Research's 7th annual International Frontiers in Cancer Prevention Research meeting in Washington, should make high-risk women more knowledgeable about their options.

"My opinion, if you're at high risk, take tamoxifen or raloxifene, go for an annual MRI screening, but more study is needed," Metcalfe says.

Debbie Saslow, PhD, director of breast and gynecologic cancer for the American Cancer Society, says it's important for women with a family history of breast cancer but no genetic markers to know they "are still at increased risk. That's significant."

She says the study suggests other genes, yet to be identified, put women at higher risk for breast cancer.

"If you have a family history, even if BRCA is not responsible, these women should still be considered at high risk and have preventive measures," Saslow tells WebMD. "Women with family history of breast cancer should start screening early, with MRI as well as mammography," she says. "We don't have a lot of data for women with a family history who test negative for BRCA."

She says women with family history of breast cancer should start screening at age 30 and make sure their doctors know they have relatives who've been diagnosed.

"Genetic testing is not for everybody," Saslow says. "But counseling can help a woman make an informed decision."

The American Cancer Society says many clinical studies have shown that tamoxifen and raloxifene may reduce the risk of breast cancer in high-risk women

By Bill Hendrick
WebMD
Nov. 17, 2008