Breast Lesions of Uncertain Malignant Potential (B3) and the Risk of Breast Cancer Development: A Long-Term Follow-Up Study

Abstract

Breast lesions of uncertain malignant potential (B3) are frequently diagnosed in the era of breast cancer (BC) screening and their management is controversial. They are generally removed surgically, but some international organizations and guidelines for breast research suggest follow-up care alone or, more recently, propose vacuum-assisted excision (VAE). The risk of upgrade to BC is known, but very little data exist on its role as risk factor for future BC development. We analyzed 966 B3 lesions diagnosed at our institution, 731 of which had long-term follow-up available. Surgical removal was performed in 91%, VAE in 3.8%, and follow-up in 5.2% of cases. The B3 lesions included flat epithelial atypia (FEA), atypical ductal hyperplasia (ADH), lobular intraepithelial neoplasia (LIN), atypical papillary lesions (PLs), radial scars (RSs), and others. Overall, immediate upgrade to BC (invasive or in situ) was 22.7%. After long-term follow-up, 9.2% of the patients were diagnosed with BC in the same or contralateral breast. The highest risk was associated with ADH diagnosis, with 39.8% of patients upgraded and 13.6% with a future BC diagnosis (p < 0.0001). These data support the idea that B3 lesions should be removed and provide evidence to suggest annual screening mammography for women after a B3 diagnosis because their BC risk is considerably increased.

Keywords: B3 lesions; atypical ductal hyperplasia; atypical lobular hyperplasia; breast cancer risk; flat epithelial atypia; follow-up mammography; surgical excision.

Figure 1

Forty-nine-year-old patient with a cluster of microcalcifications at the upper outer quadrant of the left breast ((a) CC left view, with the white circle showing microcalcifications; (b) magnifications); the woman underwent vacuum-assisted excision and after three years developed a new cluster of microcalcifications ((c) CC left view, with the red circle showing microcalcifications; (d) magnifications) that, after biopsy, turned out to be ductal carcinoma in situ.

Figure 2

A 56-year-old patient with a cluster of microcalcifications at the upper outer quadrant of the right breast that was diagnosed as ADH after biopsy ((a) MLO bilateral view, with the red circle showing microcalcifications corresponding to a B3 lesion; the red square shows a magnification of this area); the woman underwent surgical excision and after five years developed an architectural distortion in the contralateral breast ((b) MLO bilateral view, with the red circle showing distortion; the red square shows a magnification of this area) that, after biopsy, turned out to be invasive ductal carcinoma.

Figure 3

Histologic picture (a, Magnification (×20)) and radiological presentation ((b) left CC view; (c) magnification) of flat epithelial atypia (white circle).

Figure 4

Histologic picture (a, Magnification (×20)) and radiological presentation ((b) right MLO view; (c) magnification) of atypical ductal hyperplasia (white circle).

Figure 5

Histologic picture (a, Magnification (×20)) and radiological presentation ((b) right CC view; (c) magnification) of lobular intraepithelial neoplasia (white circle).

Figure 6

Histologic picture (a, Magnification (×20)) and ultrasound presentation (b) of atypical papillary lesions.

Figure 7

Histologic picture (a, Magnification (×20)) and ultrasound presentation (b) of phyllodes tumors.

Figure 8

Histologic picture (a, Magnification (×10)) and radiological presentation ((b) right CC view; (c) magnification) of a radial scar (white circle).

Figure 9

Cumulative incidence of BC during follow-up according to the histotype of the original B3 lesion. Abbreviations: atypical ductal hyperplasia (ADH); lobular intraepithelial neoplasia (LIN); flat epithelial atypia (FEA); ‘Others’ included papillary lesions, phyllodes tumors, radial scars, and rare histotypes.