HR(+)/HER2(-)乳腺癌多线治疗后组织学转化为化生性鳞癌1例报告OA

Breast cancer may undergo changes in receptor status and histological characteristics during multiple lines of treatment.In rare cases,metaplastic carcinoma may develop,posing challenges for subsequent management.Herein,we report a case of HR-positive/HER2-negative breast cancer that underwent histological transformation to metaplastic squamous cell carcinoma after multiple lines of therapy.A 50-year-old woman was initially diagnosed with grade Ⅱ invasive carcinoma of the right breast,classified as Luminal A and HER2-negative.She underwent surgery,chemotherapy,radiotherapy,and endocrine therapy combined with abemaciclib.Approximately 28 months after surgery,bone metastasis developed.Pathological examination of the sacral metastatic lesion revealed poorly differentiated adenocarcinoma,with 1％ER positivity,PR negativity,HER2(1+),and a programmed death ligand 1(PD-L1)combined positive score(CPS)of<1.During subsequent treatment,thoracic vertebral metastasis and spinal cord compression developed.Tumor resection and spinal canal decompression were performed,and postoperative pathology indicated metaplastic carcinoma,specifically poorly differentiated squamous cell carcinoma.The tumor was negative for ER,PR,androgen receptor,and HER2,with a Ki-67 positivity rate of approximately 90％;P40,P63,and CK5/6 were positive,and the PD-L1 CPS was approximately 20.The patient subsequently received capecitabine,trastuzumab deruxtecan,toripalimab combined with bevacizumab,and capivasertib combined with vinorelbine.Four multidisciplinary team(MDT)consultations were conducted based on disease progression,pathological findings,molecular testing,and treatment tolerance.Serial pathological assessments demonstrated a gradual change from invasive carcinoma in the primary tumor to poorly differentiated adenocarcinoma in the sacral metastatic lesion and finally to metaplastic carcinoma with squamous differentiation,accompanied by decreased ER and HER2 expression and increased PD-L1 expression.PIK3CA-and PTEN-related alterations were detected in both the primary tumor and the sacral metastatic lesion.The MDT integrated pathological,radiological,molecular,and clinical information to dynamically adjust the treatment strategy.During treatment with toripalimab combined with bevacizumab,imaging evaluation indicated stable disease;treatment was subsequently modified because of newly developed hepatic and splenic lesions.Advanced breast cancer may undergo dynamic changes in receptor status and histological characteristics during multiple lines of therapy.Timely re-biopsy of metastatic lesions and reassessment of pathological and molecular features may help identify tumor biological evolution and inform subsequent treatment decisions.Sequential MDT consultations may integrate multidisciplinary information and facilitate individualized management of complex advanced breast cancer.