Benign breast disease increases women's risk of developing breast cancer, especially if they have atypical lesions or a family history of breast cancer, a new study shows.

The researchers, led by Lynn Hartmann of the Division of Medical Oncology at the Mayo Clinic College of Medicine, Rochester, Minnesota, studied all women who received a diagnosis of benign breast disease at the Mayo Clinic between 1967 and 1991 to estimate the risk of their developing breast cancer and to find associations between the risk of cancer and various findings in benign disease (New England Journal of Medicine 2005;353: 229-37 and 297-9).

To estimate relative risks the researchers compared the number of women who developed breast cancer with the number of cases expected on the basis of rates of breast cancer in the population covered by the Iowa surveillance, epidemiology, and end results registry.

The researchers followed a total of 9087 women for a median of 15 years, looking at family history of breast cancer and the histological grade of the women's benign disease, among other factors.

In the group 6061 of the women (67%) had non-proliferative lesions, 2690 (30%) had proliferative lesions without atypia, and 336 (4%) had atypical hyperplasia.

A total of 707 cases of breast cancer developed in the group. The relative risk of breast cancer for the group was 1.56 (95% confidence interval 1.45 to 1.68), and this increased risk persisted for at least 25 years after biopsy.

However, the relative risk associated with atypical hyperplasia was 4.24 (3.26 to 5.41), whereas that for proliferative changes without atypia was 1.88 (1.66 to 2.12) and that for non-proliferative lesions was 1.27 (1.15 to 1.41).

Women with benign breast disease were 1.56 times more likely to develop breast cancer than women in the general population

Credit: CNRI/SPL

A major question concerns the possible interplay between atypia and a family history of breast cancer. An earlier study found that the risk of breast cancer in women with atypia and a family history was 11 times that in women with non-proliferative lesions and no family history (New England Journal of Medicine 1985;312: 146-51). However, two other major studies of benign breast disease found no significant interaction between atypia and family history (American Journal of Epidemiology 1988;128: 467-77 and JAMA 1992;267: 941-4).

The authors of the current study found that the strength of the family history of breast cancer, available for only 4808 women (53%) in the group, was a risk factor that was independent of histological findings.

Overall, the relative risk of developing breast cancer was 1.18 (1.01 to 1.37) in women with no known family history, 1.43 (1.15 to 1.75) in women with a weak family history, and 1.93 (1.58 to 2.32) in those with a strong family history.

In an accompanying editorial Joann Elmore, of the Department of Medicine at the University Of Washington School of Medicine in Seattle, and Gerd Gigerenzer, of the Max Planck Institute for Human Development in Berlin, write that the link between family history and histological findings was weakened by the fact that family history was available for only 53% of the women that the researchers followed.

However, they write that over-all “these data solidify what has long been known about the risk of breast cancer among women with benign breast disease and help stratify women with a benign lesion into high-risk and low-risk groups.”