Clinicopathologic features, treatment patterns, and survival outcomes of glycogen-rich clear cell carcinoma of the breast: A National Cancer Database Analysis.

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Background: Glycogen-rich clear cell carcinoma (GRCC) of the breast is rare subtype of invasive breast carcinoma, characterized by the presence of neoplastic cells with a glycogen-abundant clear cytoplasm. Due to the rarity of this disease, existing literature is limited to case reports and limited case series with conflicting data regarding clinicopathologic features, treatment patterns, and prognosis of this subtype. Methods: The National Cancer Database (NCDB) was queried for patients with invasive GRCC of the breast between 2004 to 2023. Baseline demographic, tumor, and treatment characteristics were summarized descriptively. Overall survival (OS) was assessed using Kaplan–Meier analysis and compared using log-rank tests. Multivariable Cox proportional hazards regression was performed to evaluate independent associations with OS. Statistical significance was defined as p<0.05. Results: A total of 132 patients with GRCC were identified. The median age at diagnosis was 61 years (interquartile range [IQR] 50–71), and the median tumor size was 2.0 cm (IQR 1.4–3.0). Patients were followed-up for a median duration of 85.0 months (IQR 48.9–137.9), during which 42 (31.8%) deaths occurred. Most patients presented with early-stage disease (48.8% Stage I, 41.0% Stage II, and 10.2% Stage III–IV disease), and 28.3% had node-positive disease. Surgical resection was performed in 90.9% of patients, and the most common surgical procedure was lumpectomy (40.9%). Chemotherapy, hormonal, and radiation therapy were administered in 63.6%, 56.8% and 56.1% of patients respectively. Of the 28 patients with available receptor data, tumors were predominantly estrogen receptor–positive (75.0%) and HER2-negative (92.9%). Surgical management (p<0.0001) and chemotherapy (p=0.004) were significantly associated with improved OS, whereas immunotherapy, hormone therapy, radiation therapy were not associated with OS. On multivariable analysis, increasing age (HR 1.04, 95% CI 1.01–1.08, p=0.020) and tumor size (HR 1.02, 95% CI 1.01–1.04, p=0.011) were significantly associated with worse OS. Surgical management remained independently associated with improved survival (HR 0.31, 95% CI 0.11–0.87, p=0.026), whereas chemotherapy was not independently associated with OS. Conclusions: In this largest study of GRCC to date, we characterize disease features, treatment patterns, and outcomes of this rare subtype. GRCC has a higher incidence in post-menopausal women, often presenting as a small primary tumor albeit with a higher likelihood of lymph node positivity and a higher mortality rate when compared to IDC as per our study. Age, tumor size, and surgical management were independently associated with OS. These findings provide valuable insight into this rare subtype that may inform management and future studies.