Clinicopathologic and genetic features of metaplastic breast cancer with osseous differentiation: a series of 6 cases

• Published in: Breast cancer (Tokyo, Japan) Vol. 28; no. 5; pp. 1100 - 1111
• Main Authors: Chao, Xue, Tan, Wanlin, Tsang, Julia Y., Tse, Gary M., Hu, Jintao, Li, Ping, Hou, Jinghui, Li, Mei, He, Jiehua, Sun, Peng
• Format: Journal Article
• Language: English
• Published: Singapore Springer Singapore 01.09.2021; Springer
• Subjects: Adult; Aged; Biomarkers, Tumor; Bone Neoplasms - pathology; Bone Neoplasms - secondary; Breast cancer; Breast Neoplasms - genetics; Breast Neoplasms - pathology; Cancer Research; Female; Genetic aspects; Genetic research; Humans; Mastectomy; Medicine; Medicine & Public Health; Middle Aged; Mutation; Oncology; Original Article; Surgery; Surgical Oncology; Tumor proteins; Genomic profile; Osseous differentiation; Metaplastic breast cancer
• ISSN: 1340-6868; 1880-4233
• DOI: 10.1007/s12282-021-01246-9

Aims Metaplastic breast cancer (MBC) comprises a heterogeneous group of tumors, of which MBC with osseous differentiation (MBC-OD) is extremely rare that only few cases have been reported. This study aimed to present the clinicopathologic and molecular features of MBC-OD. Methods We collected 6 cases of MBC-OD from five different centers and described its clinicopathologic and molecular characteristics based on the next-generation sequencing. Another 11 cases from the literature were also reviewed to better characterize the tumor. Results The tumor primarily showed an osteosarcoma-like appearance, which composed of high cellularity with spindle cells and osteoblast-like cells producing coarse lace-like neoplastic bone (4/6) or osteoid matrix (6/6). 55 somatic mutations including 39 missenses (70.9%), 9 frameshifts (16.4%), 3 splice sites (5.5%), 3 in-frame InDels (5.5%) and 1 nonsense (1.8%) were identified. TP53 was the most frequently mutated genes (5/6, 83.3%), followed by RB1 (3/6, 50.0%), BCOR (2/6, 33.3%), MED12 (2/6, 33.3%), PIK3CA (2/6, 33.3%), and TET2 (2/6, 33.3%). Genetic alterations suggesting therapies with clinical benefit, including mTOR inhibitors, tyrosine kinase inhibitors (TKI), and poly-ADP ribose polymerase inhibitor (PARPi), were observed in five cases. The median follow-up was 21 months (range, 3–80 months). Local recurrence was observed in two cases and three patients displayed distant metastasis. Two patients died of the disease at 3 months and 7 months, respectively. Conclusions Based on this series, MBC-OD is a highly aggressive breast tumor with osteosarcoma-like morphology and a high incidence of recurrent disease showing specific genetic profiles.