Treatment and pathologic considerations
All of the patients received a complete course of neoadjuvant chemotherapy consisting of taxane, anthracycline, or both, and trastuzumab was given to patients with HER2+ breast cancer. After neoadjuvant chemotherapy, all patients underwent breast conserving surgery, axillary staging surgery with sentinel lymph node biopsy (SLNB) and/or axillary lymph node dissection (ALND), and irradiation therapy. When performing lumpectomy (BCS) after NAC, we remove the tumor with approximate 1 cm grossly negative margin. After completion of this lumpectomy, margins were evaluated by shaving the walls of the lumpectomy cavity, which was described previously by Chen K et al14. An intraoperatively frozen section analysis was performed to evaluate whether the tumor was involved in the cavity margins, and if the tumor was involved in the cavity margins, then additional excision of the involved margins for approximate 1cm width (not the whole circle of the cavity wall) was performed until free margins were obtained, AH but no tumor at the margin was also defined as a negative margin. Postoperative paraffin-embedded hematoxylin and eosin (H&E) staining was used to confirm the pathology diagnosis in the cavity margin specimens. AH at the margin was reviewed by two dedicated pathologists to verify the diagnosis in the tumor-free margin specimens. Additional adjuvant chemotherapy, targeted therapy (trastuzumab), and endocrine therapy were given when necessary according to the NCCN guidelines. There are two types of atypical hyperplasia, atypical ductal hyperplasia(ADH) and atypical lobular hyperplasia(ALH), which are based on their microscopic appearance, and ADH and ALH occur with equal frequency and confer a similar risk of breast cancer7. Therefore, in this study, we analyzed these two pathological features together as “atypical hyperplasia” (AH). ADH and ALH were diagnosed according to the criteria established by Page et al15. In atypical ductal hyperplasia, the involved ducts are filled and distended by monotonous epithelial cells forming architecturally complex patterns, including cribriform-like secondary lumens or micropapillary formations. Atypical lobular hyperplasia is characterized by expanded lobular acini filled with small, monotonous, round or polygonal cells, including a lack of cohesion and a loss of acinar lumens7.