Density on mammography accounts for “a substantial proportion of cases of breast cancer, particularly in younger women”—to the extent that 26% of all breast cancers and 50% of all those detected within 1 year of a negative screen result occur in women whose mammograms show extensive breast density.
“The marked increase in the risk of breast cancer associated with extensive mammographic density … is probably due to cancers that were present at the time of screening but were not detected because of masking by dense breast tissue,” researchers reported in the New England Journal of Medicine.
Dr. Norman F. Boyd of the Ontario Cancer Institute, Toronto, and his associates assessed the relationship between mammographic density and the risk of breast cancer developing during follow-up.
The researchers used data from three large case-control studies: the Canadian National Breast Screening Study, the Screening Mammography Program of British Columbia, and the Ontario Breast Screening Program.
A total of 1,112 case-control pairs were followed for up to 8 years after baseline mammography. Mammographic density was determined by two independent methods, and results were similar in all three patient populations.
Women who developed breast cancer showed a higher percentage of dense tissue on baseline mammograms than did those who did not develop breast cancer, Dr. Boyd and his associates said (N. Engl. J. Med. 2007;356:227-36).
Women who had density in 75% or more of the mammogram had a rate of breast cancer that was nearly five times higher (odds ratio 4.7) than that for women who had density in less than 10% of the mammogram.
For the subgroup of women who were found to have cancer within 1 year of a negative screening result, those with density in 75% or more of the mammogram had a breast cancer rate nearly 18 times (odds ratio 17.8) higher than that of women with density in less than 10% of the mammogram.
These results indicate that masking, rather than rapid growth of tumors in dense breast tissue, is the most probable mechanism at work here, the investigators said. Thus, the best estimate of breast cancer incidence tied to mammographic density is “by combining cancers that were detected by screening with those that were diagnosed up to 12 months after a screening examination,” they wrote.
In an editorial comment accompanying this report, Dr. Karla Kerlikowske of the University of California, San Francisco, said that more frequent mammographic screenings probably would not improve cancer detection among women with extensive breast density, “because the tumors are not visible, because the tumors may grow quickly between examinations, or both.”
“The time has come to acknowledge breast density as a major risk factor for breast cancer and to determine, develop, and test the best ways to measure breast density in clinical practice and use this measurement to maximize primary and secondary prevention of breast cancer,” Dr. Kerlikowske commented (N. Engl. J. Med. 2007;356:297-300).