Active surveillance of women diagnosed with atypical ductal hyperplasia on core needle biopsy may spare many women potentially unnecessary surgery, but at the risk of undertreatment for a minority: 10-year surgical outcomes of 114 consecutive cases from a single center

A needle core biopsy diagnosis of atypical ductal hyperplasia is an indication for open biopsy. The launch of randomized clinical trials of active surveillance for low-risk ductal carcinoma in situ leads to the paradoxical situation of women with low-grade ductal carcinoma in situ being observed, whereas those with atypical ductal hyperplasia have surgery. If the malignancies diagnosed after surgery for atypical ductal hyperplasia are dominated by low-risk ductal carcinoma in situ, women with atypical ductal hyperplasia may also be considered for surveillance. This 10-year prospective observational study includes women diagnosed with atypical ductal hyperplasia on core biopsy after screening mammography. We retrieved their clinical, imaging and histologic data and carried out a blind review of core biopsy histology, sub-classifying the atypical ductal hyperplasia along a spectrum from hyperplasia to ductal carcinoma in situ. Using the final surgical pathology data, we calculated: (1) The proportion and grades of ductal carcinoma in situ and invasive cancers diagnosed at open biopsy. (2) The histologic extent of the malignancy at surgery. (3) The biomarker profile and nodal status of any invasive cancers. (4) Ascertained any independent predictors of (i) any malignancy, (ii) high-risk malignancy, defined in this study as invasive cancer, or high-grade ductal carcinoma in situ, or intermediate grade ductal carcinoma in situ with any necrosis. (5) Extrapolated the above to simulate active surveillance for women with screen-detected atypical ductal hyperplasia. Between January 2005 and December 2014, 114 women, mean age 59 years (range 40-79 years) were included. Surgical pathology, available in 110 (97%), confirmed malignancy in 46 (40%). All 46 malignant cases had ductal carcinoma in situ, accompanied by invasive carcinoma in 9 (8%) women. Together, 21 (19%) women had either invasive cancer (9%), high-grade ductal carcinoma in situ (6%), or necrotizing, intermediate grade ductal carcinoma in situ (6%). Only one of nine invasive breast cancers was grade 1, 3 were multifocal, all were <= 8 mm, node negative, and ER positive but two were HER2 amplified. The mean extent of the ductal carcinoma in situ in any one specimen was 19.8 mm, median 13 mm, range 2-110 mm. Overall 32 women, 29% of the whole cohort and 70% of those 46 with malignancy, required further surgery, including mastectomy in 12 (11%). A multivariable model for predicting the likelihood of any malignancy showed a statistically significant association only with the post review subtype of atypical ductal hyperplasia, adjusting for lesion size. Independent predictors of high-risk malignancy (invasive cancer or non-low-grade ductal carcinoma in situ) were not identified. If active surveillance is adopted for screen-detected atypical ductal hyperplasia diagnosed on core biopsy, 60% of women will avoid unnecessary surgery and a further 24% would meet eligibility criteria for ductal carcinoma in situ surveillance trials. However, 18% of women will have undiagnosed invasive breast cancer or non-low-risk ductal carcinoma in situ. These women with high-risk lesions are not reliably identified pre-operatively.