PS5-06-22: Atypical recurrence of invasive lobular breast carcinoma with hormone receptor loss: a Case Report

Abstract Introduction: Invasive lobular carcinoma (ILC) is the second most common type of breast cancer and typically shows hormone receptor (HR) positivity. Unlike ductal carcinoma, it tends to metastasize later and to unusual sites such as the peritoneum, gastrointestinal tract, and ovaries. These atypical patterns can mimic primary tumors of other organs, complicating diagnosis. Late recurrences with loss of HR expression are rare and present additional challenges. We report a case of peritoneal recurrence of ILC, years after initial diagnosis, with loss of HR expression. Case Description: This report describes a 51-year-old premenopausal woman with no significant family history of cancer, diagnosed in 2019 with mixed invasive carcinoma of the right breast: invasive lobular carcinoma (ER 95%, PR 75%, HER2 2+ without ISH amplification, Ki67 10%) and invasive carcinoma of no special type (ER 10%, weak staining; PR 90%, HER2 0; Ki67 10%). The disease was staged as cT2N0M0. The patient underwent breast-conserving surgery and sentinel lymph node biopsy. Final pathology revealed pT2N2a disease, with 7 metastatic lymph nodes out of 12 examined. She subsequently underwent axillary lymph node dissection, confirming persistent HR positivity. Adjuvant treatment included chemotherapy with taxanes and anthracyclines, radiotherapy, and endocrine therapy planned for ten years—initially tamoxifen for 15 months, followed by an aromatase inhibitor after menopause onset. Long-term follow-up imaging remained negative for recurrence or metastasis. In 2023, the patient developed pelvic pain, prompting a pelvic MRI that revealed suspicious bone lesions in the left iliac and L5 vertebra, a solid hypogastric mass (30×28 mm), and moderate peritoneal effusion. However, subsequent imaging, including FDG PET-CT and lumbar spine MRI, showed no clear evidence of malignancy, and the patient remained under surveillance. In April 2025, a screening colonoscopy revealed a sigmoid lesion; biopsy showed poorly cohesive carcinoma cells, and immunohistochemistry (CK7+, GATA3++, ER-, HER2-, PD-L1-) favored metastasis from prior lobular breast carcinoma despite complete loss of ER expression. Pelvic MRI confirmed extensive pelvic-peritoneal disease involving the cervix, adnexa, and bilateral ureters, with associated hydronephrosis. Additional findings included suspected ovarian involvement and uterine leiomyomas. Tumor markers showed elevated CA 15.3 and CEA. A multidisciplinary tumor board concluded this was most consistent with metastatic recurrence of the original ILC. A PET-CT in June 2025 showed no FDG-avid disease but confirmed mass effect on the ureters. The patient was referred to urology, and first-line palliative chemotherapy with paclitaxel was proposed for HR-negative, HER2-negative, and PD-L1-negative disease. Discussion: This case shows a late recurrence of ILC with peritoneal involvement and loss of ER expression. Although this metastatic pattern is consistent with ILC, loss of HR expression is rare. This loss may result from clonal evolution due to long-term endocrine therapy, leading to resistance and poorer prognosis. Peritoneal carcinomatosis mimicking gynecologic cancer delayed diagnosis, highlighting the need for thorough histopathological and immunohistochemical evaluation. FDG PET-CT may miss low-metabolic lesions, emphasizing the role of biopsy in unclear cases. Conclusions: This case highlights the need for long-term vigilance in ILC patients and the consideration of metastasis years after treatment. It supports re-biopsy and pathological reassessment in atypical cases, especially when receptor status changes, underscoring the evolving biology of breast cancer and the importance of personalized management. Citation Format: R. Q. Ferreira, A. Montenegro, L. Fernandes, D. C. Simão. Atypical recurrence of invasive lobular breast carcinoma with hormone receptor loss: a Case Report abstract. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS5-06-22.