Benign breast disease linked to increased breast cancer risk

Key takeaways:

• Women with benign breast disease had higher breast cancer risks than their peers.
• Greater risks were seen for invasive and ductal carcinoma breast cancers.

Women with benign breast disease diagnosed by percutaneous biopsies had an increased overall breast cancer risk compared with the general population, according to cohort study results published in JAMA Surgery.

“Since 2000, diagnostic methods shifted from film-based mammography and surgical biopsy to digital mammography and percutaneous biopsy, and the prevalence of several breast cancer risk factors changed, including increases in obesity and late age at first birth and a decline in use of menopausal hormone replacement,” Mark E. Sherman, MD, of the department of quantitative health sciences at Mayo Clinic in Jacksonville, Florida, and colleagues wrote. “However, the frequency of benign breast disease lesions and their associations with breast cancer risk have been largely unexamined in contemporary studies based on detailed histopathologic review.”

Sherman and colleagues conducted a retrospective cohort study with data from 4,819 women (median age, 51 years) with benign breast disease diagnosed at Mayo Clinic. All participants had benign breast disease biopsy specimens collected from 2002 to 2013. All women were followed from 6 months after biopsy collection until censoring, breast cancer diagnosis or December 2021. Researchers compared breast cancer risk for women with benign breast disease with the general population of female breast cancer incidence rates obtained from the Iowa Surveillance, Epidemiology, and End Results (SEER) program.

The primary outcome was overall breast cancer diagnoses as well as diagnoses stratified as ductal carcinoma in situ or invasive breast cancer.

Overall, 79.2% of women underwent core biopsy only, 10.2% underwent core biopsy and surgical excision and 10.6% underwent excisional biopsy only. Based on the most severe lesion identified, 50.8% of biopsy specimens were nonproliferative, 42% were proliferative disease without atypia and 7.2% were atypical hyperplasia.

Researchers observed a higher overall breast cancer risk among women with benign breast disease compared with the general population (standard incidence ratio [SIR] = 1.95; 95% CI, 1.76-2.17). The incidence ratios increased as benign breast disease severity increased for nonproliferative lesions (SIR = 1.42; 95% CI, 1.19-.171), proliferative disease without atypia (SIR = 2.19; 95% CI, 1.88-2.54) and atypical hyperplasia (SIR = 3.91; 95% CI, 2.97-5.14), which were all comparable with surgical cohorts with benign breast disease, according to the researchers.

Compared with the general population, women with benign breast disease had increased risks for invasive breast cancer (SIR = 1.56; 95% CI, 1.37-1.78) and ductal carcinoma in situ (SIR = 3.1; 95% CI, 2.54-3.77).

Breast cancer risk also increased as lesion multiplicity increased for three or more foci of nonproliferative lesions (SIR = 2.4; 95% CI, 2.06-2.79), proliferative disease without atypia (SIR = 3.72; 95% CI, 2.31-5.99) and atypical hyperplasia (SIR = 5.29; 95% CI, 3.37-8.29) compared with the general population.

In addition, the 10-year cumulative breast cancer incidence in the study was 4.3% for nonproliferative lesions, 6.6% for proliferative disease without atypia and 14.6% for atypical hyperplasia compared with the expected population cumulative incidence of 2.9%.

“Exhaustive benign breast disease analysis as performed in this study would be impractical in routine diagnostic practice, so our finding of higher risk associated with multiple benign breast disease lesions is not immediately actionable at this time,” the researchers wrote. “However, increased use of digital images with application of computational pathology approaches may enable more comprehensive future analysis of benign breast disease biopsy specimens and improve evaluation of breast cancer risk prediction.”