The formula that doctors use to calculate a woman’s risk of breast cancer underestimates the danger for black women most of the time and especially for those age 50 and older—the age when they are most likely to benefit from screening tests and protective drugs, according to the first major reassessment of the widely used tool.
“We’ve been concerned about the assumptions we had to make for African American women and other racial and ethnic groups for some time,” said Mitchell H. Gail, a biostatistician at the National Cancer Institute who led the reevaluation of the formula he himself developed. “It turns out that we have been underestimating the risk for African American women.”
The advance could have broad implications for many black women, prompting them to reconsider the danger they face from a disease that is women’s leading type of cancer and second-leading cancer killer. That could translate into more women undergoing mammograms and other examinations to detect the disease in its earliest, most treatable stages; taking drugs such as tamoxifen to reduce their risk; and signing up for studies to identify better warning signs or risk-reducing medicines.
The new findings, published online yesterday by the Journal of the National Cancer Institute, are the latest revelation about how breast cancer and other diseases can affect racial groups differently. A growing body of evidence suggests that breast cancer tends to be much more aggressive and deadly among black women, which could help explain why they are more likely to die from it even though fewer of them get it. More than 19,000 African American women are diagnosed with breast cancer each year, and nearly 6,000 die from it.
The research examined the Breast Cancer Risk Assessment Tool, more commonly known as the Gail model. Doctors use the model to calculate a woman’s risk by plugging in variables such as the age at which she started having her period or had her first child and whether a mother or sister has had the disease.
Because the model was based largely on data collected from about 240,000 white women, Gail and his colleagues decided to try to develop a more accurate alternative using data collected more recently on more than 3,200 black women, including more than 1,600 who had breast cancer.
The researchers then tested the new version and showed that it would have accurately predicted how many African American women in the federal government’s Women’s Health Initiative would have developed breast cancer. Next, the team compared the new model to the old one by using both to assess data collected from 20,278 African American women who were screened for eligibility for a landmark breast cancer-prevention trial: the Study of Tamoxifen and Raloxifene (STAR) trial, which compared tamoxifen to the newer drug raloxifene.
The accuracy of the two methods varied depending on each woman’s particular risk factors, and the old model slightly overestimated the risk for some younger women. But overall the old model underestimated the risk in at least 90 percent of all scenarios, particularly for older women, the team found.
For example, the old model calculated that a 50-year-old black woman who started having her period at age 14, had her first baby at age 32 and had a mother and sister who had breast cancer has a 1.53 percent risk of getting breast cancer within five years. The new model puts her risk at 2.26 percent, pushing her over the line into being eligible for the STAR trial.
“That doesn’t seem like a big difference, but even though those numbers look small, they can affect decisions,” Gail said.
There are many reasons for the discrepancy. Having a baby before age 30, for example, does not reduce the risk for black women as much as it does for white women.
Based on the findings, Gail and his colleagues recommended that doctors start using the new model for their African American patients. The National Cancer Institute plans to use the new model to update its calculator, which is online at http://www.cancer.gov/bcrisktool, he said. Gail also said he plans to try to develop similar alternative models for other groups, such as Hispanics and Asians.
The findings should also dispel long-standing myths about African Americans, some advocates said, noting that the lower risk assessments under the old model meant that many were not eligible for prevention trials.
“It’s always been thought that African American women were not interested in being part of clinical trials. In reality, they were denied access to those trials,” said Karen Jackson of Sisters Network Inc., the leading breast cancer group for black women. “Being in clinical trials gives you access to the latest and greatest treatments. This will allow all women who are interested in being involved to have equal access to take part in trials.”
[Editors Note: The abstract for “Projecting Individualized Absolute Invasive Breast Cancer Risk in African American Women,” by Mitchell Gail, et al., appears below. The full article can be accessed as a PDF document or in HTML format here. A subscription is required.]
Mitchell H. Gail, Joseph P. Costantino, David Pee, Melissa Bondy, Lisa Newman, Mano Selvan, Garnet L. Anderson, Kathleen E. Malone, Polly A. Marchbanks, Worta McCaskill-Stevens, Sandra A. Norman, Michael S. Simon, Robert Spirtas, Giske Ursin, Leslie Bernstein
Affiliations of authors: Division of Reproductive Health, Centers for Disease Control and Prevention, Atlanta, GA (PAM); Women’s Health Initiative Clinical Coordinating Center (GLA) and Division of Public Health Sciences (KEM), Fred Hutchinson Cancer Research Center, Seattle, WA; Information Management Services, Rockville, MD (DP); Division of Hematology and Oncology, Karmanos Cancer Institute at Wayne State University, Detroit, MI (MSS); University of Michigan Breast Care Center, University of Michigan, Ann Arbor, MI (LN); Division of Cancer Epidemiology and Genetics (MHG) and Division of Cancer Prevention (WMS), National Cancer Institute, Bethesda, MD; Contraception and Reproductive Branch, Center for Population Research, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD (RS); Center for Clinical Epidemiology and Biostatistics and Department of Biostatistics and Epidemiology, University of Pennsylvania School of Medicine, Philadelphia, PA (SAN); Graduate School of Public Health and Department of Biostatistics, University of Pittsburgh, Pittsburgh, PA (JPC); Department of Preventive Medicine, Keck School of Medicine and Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA (GU, LB); Department of Epidemiology (MB) and Department of Clinical Effectiveness (MS), The University of Texas M. D. Anderson Cancer Center, Houston, TX
Correspondence to: Mitchell H. Gail, MD, PhD, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Executive Plaza South Rm 8032, Bethesda, MD 20892-7244 (e-mail: [email protected]).
Background: The Breast Cancer Risk Assessment Tool of the National Cancer Institute (NCI) is widely used for counseling and determining eligibility for breast cancer prevention trials, although its validity for projecting risk in African American women is uncertain. We developed a model for projecting absolute risk of invasive breast cancer in African American women and compared its projections with those from the Breast Cancer Risk Assessment Tool.
Methods: Data from 1607 African American women with invasive breast cancer and 1647 African American control subjects in the Women’s Contraceptive and Reproductive Experiences (CARE) Study were used to compute relative and attributable risks that were based on age at menarche, number of affected mother or sisters, and number of previous benign biopsy examinations. Absolute risks were obtained by combining this information with data on invasive breast cancer incidence in African American women from the NCI’s Surveillance, Epidemiology and End Results Program and with national mortality data. Eligibility screening data from the Study of Tamoxifen and Raloxifene (STAR) trial were used to determine how the new model would affect eligibility, and independent data from the Women’s Health Initiative (WHI) were used to assess how well numbers of invasive breast cancers predicted by the new model agreed with observed cancers.
Results: Tables and graphs for estimating relative risks and projecting absolute invasive breast cancer risk with confidence intervals were developed for African American women. Relative risks for family history and number of biopsies and attributable risks estimated from the CARE population were lower than those from the Breast Cancer Risk Assessment Tool, as was the discriminatory accuracy (i.e., concordance). Using eligibility screening data from the STAR trial, we estimated that 30.3% of African American women would have had 5-year invasive breast cancer risks of at least 1.66% by use of the CARE model, compared with only 14.5% by use of the Breast Cancer Risk Assessment Tool. The numbers of cancers predicted by the CARE model agreed well with observed numbers of cancers (i.e., it was well calibrated) in data from the WHI, except that it underestimated risk in African American women with breast biopsy examinations.
Conclusions: The CARE model usually gave higher risk estimates for African American women than the Breast Cancer Risk Assessment Tool and is recommended for counseling African American women regarding their risk of breast cancer.