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

A case report of histological transformation from HR-positive/HER2-negative breast cancer to metaplastic squamous cell carcinoma after multiple lines of therapy

摘要:

乳腺癌在多线治疗过程中可发生受体状态及组织学类型改变，少数患者可出现化生性癌，给后续治疗带来挑战。本文报告1例HR（+）/HER2（-）乳腺癌多线治疗后转化为化生性鳞癌的病例。患者为50岁女性，初诊为右乳浸润性癌，组织学Ⅱ级，分子分型为Luminal A型［HER2（-）］，接受手术、化疗、放疗及内分泌联合阿贝西利治疗。术后约28个月出现骨转移，骶骨转移灶病理提示低分化腺癌，雌激素受体（ER）1%阳性、孕激素受体（PR）阴性、HER2（1+）、PD-L1联合阳性分数（CPS）<1。后续治疗过程中出现胸椎转移及脊髓压迫，行肿瘤切除及椎管减压术，术后病理提示化生性癌（低分化鳞癌），ER、PR、雄激素受体及HER2均阴性，Ki-67约90%阳性，P40、P63及CK5/6阳性，PD-L1 CPS约20。患者先后接受卡培他滨、德曲妥珠单抗、特瑞普利单抗联合贝伐珠单抗，以及卡匹色替联合长春瑞滨等治疗，并根据病情进展、病理结果、分子检测及治疗耐受性接受4次多学科诊疗（MDT）评估。连续病理评估显示，肿瘤由原发灶浸润性癌逐渐表现为转移灶低分化腺癌，最终呈现具有鳞状分化特征的化生性癌，并伴随ER、HER2表达下降及PD-L1表达升高。原发灶与骶骨转移灶均检测到PIK3CA及PTEN相关变异。MDT结合病理、影像学、分子检测及患者治疗耐受性，动态调整治疗方案；特瑞普利单抗联合贝伐珠单抗治疗期间影像学评估为疾病稳定，后因出现肝、脾新发病灶而再次调整治疗。晚期乳腺癌在多线治疗过程中可能发生受体状态及组织学类型的动态变化，适时开展转移灶再活检及病理、分子特征评估，有助于识别肿瘤生物学演变并为后续治疗决策提供依据。连续MDT可整合多学科信息，促进复杂晚期乳腺癌的个体化诊疗。

Abstract:

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.