Density, Risk Factors Predict Postmenopausal Breast Cancer

SAN FRANCISCO, March 10 (MedPage Today) -- All postmenopausal women should be screened for breast cancer risk by assessing breast density combined with other risk factors, researchers here said.

Physicians should also consider chemoprevention for those found to be at highest risk, Steven R. Cummings, M.D., of the California Pacific Medical Center Research Institute, and colleagues reported in the March 18 issue of the Journal of the National Cancer Institute.

"The evidence supports systematic assessment of women's risk of breast cancer and the recommendation that women at high risk consider chemoprevention to reduce that risk," the researchers said.

Increased use of mammography has resulted in decreased mortality from the disease, but it doesn't reduce the number of women who develop breast cancer, they said.

In 2002, guidelines from the American Society of Clinical Oncology recommended that tamoxifen could be offered to women with a five-year breast cancer risk of 1.66% or more in the absence of contraindications.

However, there's been no systematic attempt to identify women at high risk for the disease. So the researchers conducted a review of more than 40 studies of breast cancer risk published through June 2008.

They found that breast density was strongly associated with breast cancer, whether assessed through Breast Imaging Reporting and Data System (BI-RADS) or dense area percentages (RR 4.03, 95% CI 3.10 to 5.26 for category IV versus category I, and RR 4.20, 95% CI 3.61 to 4.89 for >75% versus <5% of dense area, respectively).

Combining breast density with risk factors such as age, race, ethnicity, and family history appeared to be the best approach to estimating risk, the researchers said.

Those found to be at high risk should start tamoxifen or raloxifene therapy, the researchers said, as both effectively reduced the risk of invasive breast cancer. They left the choice of agent to the physician, based on potential adverse effects, since the drugs have similar benefits.

To reduce breast cancer risk overall, they advised, physicians should recommend exercise, weight reduction, a low-fat diet, and reduced alcohol intake.

But they also noted that eating fruits and vegetables was not associated with a decreased risk.

They pointed out however "that evidence about lifestyle changes to reduce breast cancer risk is generally based on observational studies" and "the strength of associations between lifestyle changes and risk of breast cancer is modest. Nevertheless, because these lifestyle changes are safe, they can be recommended to all women regardless of breast cancer risk."

The researchers cautioned that measurements of the sex hormones estradiol and testosterone are not yet ready for routine clinical use in breast cancer screening. Common assessments are expensive, the researchers said, and only moderately correlated with risk -- although estradiol and testosterone levels are associated with risk of developing estrogen receptor-positive breast cancer.

"There is a need for standardized and inexpensive method for measuring sex hormone levels with established value for improving estimates of the risk of breast cancer based on assessments of risk factors and breast density," the researchers said.

Before systematic assessment for breast cancer risk can be implemented widely, physicians and patients must be educated about risk and how to reduce it, the researchers said. Genetic counseling for those who are tested for family history may also be warranted.

There were a few other limitations to the study. The findings can't be applied to premenopausal women, and they may not be applicable to clinical practice until other approaches to assessing other markers of breast cancer risk are developed.

Still, the researchers concluded that breast density combined with other risk factors is a viable assessment of risk.

They cautioned however that "although breast density is a strong risk factor for breast cancer, BI-RADS grading that could be widely used has only modest reproducibility and more reproducible quantitative approaches are not yet validated or feasible for clinical use; thus, our estimate of increased predictive accuracy may not be applicable to clinical practice at the current time."

The study was supported by the Daniel and Phyllis Da Costa Fund and a Breast Cancer Surveillance Consortium cooperative agreement.

Dr. Cummings has received research support and consulting fees from Eli Lilly. Co-authors reported receiving funds from Eli Lilly, AstraZeneca, Pfizer, and Novartis.

Primary source: Journal of the National Cancer Institute Source reference: Cummings SR, et al "Prevention of breast cancer in postmenopausal women: Approaches to estimating and reducing risk" J Nat Cancer Inst 2009; 101(6): 384-98.