## 4 Discussion  
B3 lesions comprise a wide range of findings considered non-obligate precursors of breast cancer; some of these lesions can evolve into DCIS or low-grade invasive tumors after surgical excision with an overall risk of malignancy of 10-35%. Their management varies greatly from country to country and from hospital to hospital although, currently, there is a trend toward a more conservative management instead of open surgery, such as vacuum-assisted excision [11]. BRCA1 and BRCA2 are the most common genetic mutations responsible for breast and ovarian cancer development. These patients have a 3% greater risk of developing breast cancer before the age of 30, and the risk over their lifetime increases to 50-80% by 70 years of age. In particular, some meta-analyses reported a breast cancer risk of 55-70% for BRCA1 carriers and 40-70% for BRCA2 carriers [12; 13; 14]. The natural history of ATM-related breast cancer is not well defined, although some studies report their tendency to be more aggressive, dedifferentiated and endocrine-positive with respect to the sporadic ones, and with a poor prognosis. Moreover, this mutation is also a contraindication for radiation therapy because it increases radiotherapy toxicity and the risk of developing a second tumor after RT [15]. To our knowledge, this is the first study evaluating the relationship between the type of mutation and the imaging and pathological findings of B3 lesions. Our results indicated that ADHs were the most commonly encountered lesion after breast biopsy (42.8%), followed by LNs (28.6%), FEA and RSs (14.3% for both). Their distribution among the three groups of mutations showed a significant difference, with a higher prevalence of ADH in the BRCA1 group. LNs and FEA showed a higher malignancy correlation, with a PPV of 83% and 100%, respectively; these results are quite different from those observed in general populations, showing a PPV of about 8-60% for LN and 13-67% for FEA [16]. These results highlight that in mutation carriers, these lesions should always be surgically excised. ADHs and RSs had a PPV of 66.7% and 33.3%, respectively. The PPV in the general population for ADH is about 60%, quite similar to our results, but still high enough to require surgical excision. The data regarding RSs were higher than that observed in non-mutation carrier patients (between 1.1 and 7%) [16; 17]. This fact led to open excision in all the cases, although the natural history of this finding is that of a benign lesions requiring therapeutic excision with VAE for those lesions visible at imaging, according to the second International Consensus Conference on B3 lesions, which indicates surgery only in presence of RSs associated with atypia. Nevertheless, our results were still too high to recommend VAE only. According to the malignancy rate in the three groups of mutations, there was no significant difference among them, although we observed that the majority of patients in the BRCA1 group developed a tumor. Patient age was a significant factor influencing the malignancy rate, with patients between 45 and 55 years having the worst outcome, with 52.4% developing a breast cancer after surgical excision. In the current study, the most common mammographic presentation of B3 lesions was microcalcification (36.8%) followed by distortion + microcalcification (15.8%), findings which were more representative in the BRCA1 group, with a significant difference with respect to the other groups. In particular, microcalcifications were more often associated with ADH, FEA and LN, and they were rare in radial scars. Some studies demonstrated that when calcification was the main radiological abnormality, the lesion diagnosed on breast biopsy was frequently epithelial or lobular neoplasia. Moreover, where microcalcifications were the main radiological abnormality, it was more likely to be associated with malignancy at surgery in 77.8% of the cases, compared to mass lesions or architectural distortions.