Rare overlap of subtype and phenotype: HER2-positive pleomorphic invasive lobular carcinoma presenting with an inflammatory breast cancer phenotype: a case report and targeted treatment strategy.

Pleomorphic invasive lobular carcinoma (PLC) is a rare and aggressive subtype of invasive lobular carcinoma. When it presents with an inflammatory breast cancer (IBC) phenotype, due to its rarity, this can lead to substantial diagnostic and therapeutic challenges. Herein, we report the case of a 53-year-old woman presenting with a rapidly enlarging left breast mass, diffuse edema, erythema, and pain; these symptoms have affected the entire breast over the course of one month. Imaging revealed diffuse parenchymal abnormalities and nodal involvement, while biopsy indicated PLC, histologic grade III, with HER2 amplification and complete absence of hormone receptors. Clinical and radiological assessment demonstrated nodal involvement (supraclavicular, cervical, and bilateral axillary) and distant osseous metastases, consistent with stage cT4N3M1 disease. The patient received first-line docetaxel, trastuzumab, and pyrotinib (PyroHT) and achieved a partial response; however, progression was observed after ten cycles. Following multidisciplinary review, her treatment was changed to trastuzumab deruxtecan (T-DXd), resulting in significant symptom relief and radiologic regression of the breast lesions. This case highlights the importance of early biopsy in rapidly progressive breast disease and that treatment for rare histologic subtypes, such as PLC, should be guided by molecular profiling rather than histology alone. Sequential HER2-targeted therapy provided meaningful clinical benefit, though resistance ultimately developed. We present the case of a 53-year-old woman with HER2-positive advanced PLC presenting with an IBC phenotype, providing insight into the diagnostic process and treatment course in this rare clinical scenario.