Case Report: Colonic metastasis from mixed breast carcinoma masquerading as abemaciclib-associated diarrhea.

Background: Invasive lobular carcinoma (ILC) demonstrates a distinctive propensity for gastrointestinal metastasis that differs from invasive ductal carcinoma (IDC). In mixed breast carcinomas, intratumoral heterogeneity poses challenges for disease surveillance and treatment assessment. Moreover, gastrointestinal adverse effects associated with CDK4/6 inhibitors, such as abemaciclib, may lead to diagnostic overshadowing, potentially delaying recognition of metastatic disease. Case description: A 68-year-old woman with mixed IDC and ILC underwent mastectomy following neoadjuvant chemotherapy. Histopathological evaluation revealed significant heterogeneity, with a luminal A IDC component and a triple-negative ILC component, the latter involving axillary lymph node metastases. During treatment with letrozole and abemaciclib, the patient developed progressive abdominal pain accompanied by rising carcinoembryonic antigen (CEA) levels, which were initially attributed to treatment-related toxicity. While bone metastases with a luminal phenotype remained radiographically stable, colonoscopy revealed an obstructing lesion in the descending colon. Biopsy confirmed metastatic carcinoma with a triple-negative profile (GATA3-positive, CDX2-negative), consistent with the primary ILC component and distinct from the bone metastases. Conclusions: This case highlights that persistent or evolving gastrointestinal symptoms during CDK4/6 inhibitor therapy warrant thorough evaluation for metastatic disease, particularly in patients with ILC. It also suggests that aggressive minor components in mixed tumors may have important clinical and prognostic implications. It emphasizes the importance of re-biopsy to identify phenotypic discordance and current therapeutic targets, informing timely and appropriate modifications to the treatment strategy.