May 10, 2017
3 min read

Progressive epithelial proliferation on biopsy linked to breast cancer risk

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Women with benign breast biopsies that showed progressive epithelial proliferation had an increased risk for breast cancer compared with those whose biopsies showed less proliferation over time, according to a study published in Journal of the National Cancer Institute.

“These findings have important implications for optimization of clinical management for the approximately 100,000 women per year in the United States who have multiple, metachronous benign biopsies and provide insight into the natural history of benign breast disease and its role in breast carcinogenesis,” Daniel W. Visscher, MD, pathologist in the department of laboratory medicine and pathology at Mayo Clinic in Rochester, Minnesota, and colleagues wrote.

Between 1 million and 2 million women per year in the United States have a breast biopsy with benign findings and are classified as having benign breast disease. Women with benign breast disease have a greater risk for breast cancer, which can be stratified by the degree of histologic abnormality in the biopsy.

In the first study to systematically describe the histological features and outcomes of women with benign breast disease, researchers used the Mayo Clinic Benign Breast Disease Cohort to evaluate 13,466 women aged 18 to 85 years who underwent a benign breast biopsy for clinical indication from 1967 to 2001. Researchers considered patient family history and categorized women as having a strong family history if they had at least one first-degree relative with breast cancer when younger than age 50 years.

In total, 1,414 women (10.5%) had multiple metachronous benign biopsies. Women with multiple biopsies were younger (younger than 45 years, 48% vs. 31%; P < .001) and more likely to have a family history of breast cancer (49.3% vs. 37.9%, P = .001) than the rest of the cohort.

Median time between biopsies was 5.6 years. About half of the second biopsies occurred within 5 years of the initial biopsy, but 30% occurred more than 10 years later.

Of the women who had multiple nonsynchronous biopsies, 43.9% had histological classification change from initial to second breast biopsy. Those changes were twice as likely to involve progression to a higher-risk category.

Further, 41% of women with nonproliferative changes in their initial biopsy progressed to proliferative disease without atypia or atypical hyperplasia in their second sample.

Women with nonproliferative initial findings and subsequent proliferative findings had an increased risk for breast cancer compared with women with no change (HR = 1.77; 95% CI, 1.06-2.94; P = .03).


Among women with proliferative disease without atypia at initial biopsy, risk decreased if subsequent biopsy regressed to nonproliferative (HR = 0.49; 95% CI, 0.25-0.98) and increased if subsequent biopsy showed progression to atypical hyperplasia (HR = 1.49; 95% CI, 0.73-3.05).

“Most women with benign breast biopsies — about 65% across multiple studies — are diagnosed with nonproliferative lesions,” Visscher and colleagues wrote. “Our results imply that breast cancer risk status can evolve in many women with nonproliferative lesions and that breast cancer risk can increase for some of these women.”

Researchers note a potential limitation of their study is that a breast biopsy provides a small sample of any patient’s total breast tissue and small proliferative or atypical lesions may not be present in the biopsy.

The subset of women who had atypical hyperplasia in the first biopsy but had nonproliferative lesions or proliferative lesions without atypia in the subsequent biopsy are the most interesting subset in this analysis, Stuart J. Schnitt, MD, professor of pathology at Harvard Medical School, director of anatomic pathology at Beth Israel Deaconess Medical Center and breast cancer co-leader at Dana-Farber Cancer Center, and colleagues wrote in a related editorial.

“The data suggest that these women have a 43% reduction in breast cancer risk when compared with women who still have atypical hyperplasia in their second biopsy,” Schnitt and colleagues wrote. “However, this scenario appears to be extremely uncommon; 42 such women were identified in this study, representing only 3% of women with multiple biopsies and 0.3% of the entire Mayo Clinic Benign Breast Disease Cohort.

“Therefore, we believe that it would be premature to recommend altering the follow-up or management strategy for women who have atypical hyperplasia on a first biopsy but nonproliferative lesions or proliferative lesions without atypia on any subsequent biopsies,” they added. – by Chuck Gormley

Disclosure: Bankhead-Coley Foundation, Mayo Clinic and NCI funded this study. The researchers report no relevant financial disclosures. Schnitt and colleagues report no relevant financial disclosures.