Gastrointestinal Metastasis from Invasive Lobular Carcinoma with Acquired ESR1 Mutation: A Case Report

Background: Breast invasive lobular carcinoma (ILC) with multiple organ metastases at initial diagnosis is rare. This study reports a case of ILC presenting with bone marrow and bone metastases at first diagnosis, who developed gastrointestinal metastases (GIM) one year later, and reviews the relevant literature.

Case Description: Case Description: A 35-year-old female patient presented with a left breast mass accompanied by enlarged left axillary and cervical lymph nodes as well as thoracolumbar pain. Pathological biopsy confirmed the diagnosis of ER-positive, HER2-low ILC, with metastases to the left axillary and cervical lymph nodes, bone marrow, and bone. The patient achieved tumor remission following treatment with endocrine therapy combined with a CDK4/6 inhibitor. One year later, she developed gastrointestinal symptoms such as nausea and vomiting. Pathological biopsy confirmed GIM from ILC, and the metastatic tumors harbored an ESR1 mutation (ESR1M) at p.Y537N. After treatment with the anti-HER2 antibody-drug conjugate (ADC) trastuzumab deruxtecan (T-DXd), disease control was achieved.

Conclusion: Although ER-positive and HER2-low ILC can derive clinical benefit from endocrine therapy combined with a CDK4/6 inhibitor, the tumor may still undergo occult progression, such as ESR1M and GIM. This case highlights the importance of dynamic biomarker monitoring and repeat biopsy when occult progression is suspected. Anti-HER2 ADC therapy may provide disease control and clinical benefit in selected patients with HER2-low ILC after endocrine resistance.