Long-held Assumption of Histologic Precursors of Breast Cancer Refuted

The largest longitudinal study to date in women with atypical hyperplasia has the potential to change clinical practice; its results have shown that atypical ductal hyperplasia (ADH) and atypical locular hyperplasia (ALH) “behave similarly in terms of later breast cancer endpoints.”¹

This finding refutes the long-held belief that the presence of ADH, considered a direct precursor to breast cancer, necessitates complete surgical excision, while ALH, serving as an indicator of heightened and equal risk of breast cancer across both breasts, does not need complete surgical removal.

What does this mean for the more than 100,000 American women annually who have a benign breast biopsy that reveals atypical hyperplasia, a premalignant lesion of the breast?

First, that ADH and ALH are equally important, with the affected breast “at especially high risk for breast cancer in the first 5 years after diagnosis of breast cancer, with risk remaining elevated in both breasts long term,” the Mayo Clinic study reported in Cancer Prevention Research. In the study, 23% of women developed breast cancer at 20 years and 29% at 25 years.¹

Second, “Both ADH and ALH portend risk for DCIS [ductal carcinoma in situ] and invasive breast cancers, predominantly ductal”; 69% were moderate or high-grade.¹

RELATED: Breast Cancer Resource Center

Finally, “the onus is on us to get as good as we can at biopsying only higher risk lesions, really relevant lesions,” Lynn C. Hartmann, MD, professor of oncology at the Mayo Clinic, Rochester, MN, and the study’s lead author, told ChemotherapyAdvisor.com.

Among the 698 women in the Mayo Benign Breast Disease Cohort with atypical hyperplasia who had biopsies performed from 1967 to 2001 with all atypias, 33 breast cancers were expected and 143 occurred (standardized incidence ratio [SIR], 4.34; 95% CI, 3.66-5.12). The women were followed for an average of 12.5 years.¹

Of the risk variables—age at atypia, type of atypia, number of atypical foci, extent of lobular involution, family history of breast cancer, and calcifications—the highest significant risk was found in women with three or more atypical foci (SIR, 7.61; 95% CI, 5.36-10.49; P<0.001) and no lobular involution (SIR, 7.66; 95% CI, 4.74-11.72; P<0.001). Age was also a risk factor, with those younger than age 45 years at atypia diagnosis having the highest risk (SIR, 5.45; 95% CI, 3.17-8.73; P=0.04).¹

Prior to 1981, when mammography use became routine, atypia was present in about 2% of benign biopsies of lumps found palpably compared with 10% today.

Although not addressed in the study, Dr. Hartmann said these findings support the use of antiestrogens for women with atypia who have been included in chemoprevention trials. However, “studies have found that women are reluctant to use those drugs due to side effects. The positive benefit-to-risk ratio in atypia specifically has not been appreciated.”

One likely outcome of this study is a simple model that would stratify women with atypical hyperplasia for high, moderate, and lower risk of breast cancer. She said a woman’s age, the number of foci or atypia, and the extent of involution would be included in this stratification with the goal of predicting risk of breast cancer in 5 years. The ultimate goal would be to include molecular features and use these biomarkers to determine when a woman should be screened next or whether she should take an antiestrogen or have an MRI.

“If a woman has a breast biopsy and if it shows atypia, it might be wise for her to be seen at a breast center for recommendations about surveillance and preventive therapy options,” she concluded. “We hope these data will further help clinicians make informed decisions for breast atypia management strategies.”

Reference

1. Hartmann LC, Radisky DC, Frost MH, et al. Understanding the premalignant potential of atypical hyperplasia through its natural history: a longitudinal cohort study. Cancer Prev Res. 2014;7(2):211-217.