Benign Breast Disease and the Risk of Breast Cancer

Division of Medical Oncology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
New England Journal of Medicine (Impact Factor: 55.87). 08/2005; 353(3):229-37. DOI: 10.1056/NEJMoa044383
Source: PubMed


Benign breast disease is an important risk factor for breast cancer. We studied a large group of women with benign breast disease to obtain reliable estimates of this risk.
We identified all women who received a diagnosis of benign breast disease at the Mayo Clinic between 1967 and 1991. Breast-cancer events were obtained from medical records and questionnaires. To estimate relative risks, we compared the number of observed breast cancers with the number expected on the basis of the rates of breast cancer in the Iowa Surveillance, Epidemiology, and End Results registry.
We followed 9087 women for a median of 15 years. The histologic findings were nonproliferative lesions in 67 percent of women, proliferative lesions without atypia in 30 percent, and atypical hyperplasia in 4 percent. To date, 707 breast cancers have developed. The relative risk of breast cancer for the cohort was 1.56 (95 percent confidence interval, 1.45 to 1.68), and this increased risk persisted for at least 25 years after biopsy. The relative risk associated with atypia was 4.24 (95 percent confidence interval, 3.26 to 5.41), as compared with a relative risk of 1.88 (95 percent confidence interval, 1.66 to 2.12) for proliferative changes without atypia and of 1.27 (95 percent confidence interval, 1.15 to 1.41) for nonproliferative lesions. The strength of the family history of breast cancer, available for 4808 women, was a risk factor that was independent of histologic findings. No increased risk was found among women with no family history and nonproliferative findings. In the first 10 years after the initial biopsy, an excess of cancers occurred in the same breast, especially in women with atypia.
Risk factors for breast cancer after the diagnosis of benign breast disease include the histologic classification of a benign breast lesion and a family history of breast cancer.

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    • "This classification is commonly applied to examine the association between benign breast disease and breast cancer. Women with PDWA and with AH are at 1.5- to 2-fold, and 4- to 5-fold increased risk to develop breast cancer, respectively, compared to nonproliferative lesions [2]–[5]. However, the breast cancer risk of specific histologic features such as radial scar has not been well established [6]. "
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    • "We have previously identified histologic features of premalignant and normal breast tissue that are associated with increased breast cancer risk [18, 19]. We have found that age-related lobular involution of breast lobules (the natural regression of breast epithelium over time, distinct from post-lactational involution) is associated with decreased breast cancer risk [20, 21]. "
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    • "The specimens came from a total of 154 women: 24 healthy patients undergoing reduction mammoplasty; 14 patients with benign lesions; 25 patients with proliferative lesions (10 without atypia, 15 with atypia without co-existing IBC); and 32 patients with IBC whose histologically normal cells adjacent to tumor (‘malignant-adjacent’ normal) were analyzed; and 59 IBC patients whose malignant cells were analyzed. Among these lesions, normal, non-proliferative benign and proliferative lesions without atypia are considered as low-risk lesions (relative risk of 1–1.88 [34]) and patients with these lesions are not treated; while proliferative lesions with atypia has a significantly increased risk for breast cancer (relative risk of 4.24) and patients with this lesion are typically treated by both surgery and chemopreventive drug. The malignant-adjacent normal cells are no longer “normal”, because although these cells appear microscopically “normal” to pathologists, malignant tumor is already present in adjacent locations. "
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