Different biologic behaviors and risk profiles among B3 proliferative breast lesions

Background /Aim: despite risk tailoring ongoing research on the different B3 entities most cases progress to surgical intervention, with ongoing fluctuations in trends of treatment or perceived associations with malignancy. The aim of this study was to access the outcome of lesions diagnosed in this category in a large series of screen-detected cases to evaluate the upgrade rates for the different histological subtypes. Patients and methods: a total of 2986 CNB's were performed for screen detected breast lesions over a fifteen-year period (2003-2018). B3 diagnosis comprised 10.1% (300/2986), and was correlated with final excision histology. Positive predictive values (PPVs) for detection of malignancy were calculated for all B3 core cases and different subtypes to provide a complementary risk characterization according to clinicopathological features and morphological variables. Moreover, cumulative incidence curves of new primary/relapses of BC after CNB were estimated with a Kaplan-Meier analysis. Results: the B3 lesions comprised the following histopathological diagnoses: 105 (35%) atypical ductal hyperplasia (ADH), 50 (16.7%) flat epithelial atypia (FEA), 68 (22.7%) lobular neoplasia (LN), 27 (9%) papillary lesion (PL), 26 (8.6%) phylloides tumor (PT), and 24 (8%) radial scar (RS). Screen-detected calcifications showed no higher upgrade rate (15.9%; 17/107) when compared to mass lesions (13.7%, 19/139) or architectural deformities (16.7%, 9/54) (p = 0.828). Malignant lesions included 25 (8.3%) DCIS and 20 (6.7%) invasive cancers, giving an overall PPV of 15% (45/300) based on excision histology. Lesion specific positive predictive values (PPV) for a subsequent diagnosis of carcinoma were as follows: ADH 20% (21/105), FEA 12% (6/50), LN 16.2% (11/68), PL 18.5% (5/27), PT 3.8% (1/26) and RS 4.1% (1/24), demonstrating a higher but not statistically significant tendency toward lesion upgrade for the 3 major atypical areas (ADH, FEA, LN) (OR: 2.05; 95% confidence interval [CI]: 0.87-4.81; p = 0.092). Interestingly, the Chi-Squared test also revealed a growing risk of subsequent new primary BC among patients with previous LN diagnosis (n = 8/19, 42.1%), (OR: 2.679; 95% [CI]: 1.031-6.957; p = 0.037) during the study period. Conclusion: lesions of uncertain malignant potential of the breast (B3) are heterogeneous in respect to risk of malignancy and careful radiological-pathological correlation is the prerequisite for an optimal disease-tailored approach. Therefore it is becoming clear that these different borderline categories should be subjected to further investigation for updating quality assurance targets and moving forward to a more conservative approach in selected cases, as a part of the screening assessment.