Understanding the Rare Breast Cancer Subtypes With Variations in Histopathology, Molecular Profiling, Clinical Outcomes and Therapeutic Approaches.

Background Breast cancer is a heterogeneous disease with significant variation in clinical behaviour, pathological morphology and molecular patterns. While most of the breast cancer cases follow common histological and clinical patterns, but a few rare subtypes behave differently with a difference in prognosis and response to therapy. Recognizing these subtypes of breast cancer is important for accurate diagnosis and treatment planning. Aims and objectives This study aimed to evaluate the clinical features, pathological criteria, and outcomes of patients with these rare breast cancer subtypes treated at King Fahad Specialist Hospital (KFSH-D), a biggest regional tertiary care center.  Patients and methods This is a retrospective, observational, descriptive study analyzing 30 patients diagnosed with rare breast cancer subtypes and treated at KFSH-D between January 2019 and December 2024. Results We included 30 patients with rare pathological breast cancer subtypes. Among them, eight patients (27%) had apocrine carcinoma. The mean age at diagnosis for this group was between 55 and 60 years and a mean tumor size was greater than 2 cm. Additionally, 14 (46%) patients had metaplastic carcinoma, with a mean age at diagnosis of 45-60 years and tumor sizes ranging between 3 and 5 cm. Five (17%) patients were diagnosed with mucinous adenocarcinoma. Their mean age at diagnosis was 70 years, with tumors larger than 2 cm. All of these patients had stage N0-N1 disease and were positive for estrogen receptor (ER), progesterone receptor (PR), and negative for Her-2/neu on immunohistochemistry (IHC). One (3%) patient had lymphoepithelioma-like carcinoma. She was diagnosed at 51 years of age, with a tumor size of 2.2x3.2 cm. She underwent simple mastectomy and sentinel lymph node biopsy (SLNB). The tumor was histologic grade III with no lymphovascular invasion or intraductal component. We also identified two (7%) patients with invasive ductal carcinoma (IDC) showing neuroendocrine differentiation. Both were positive for chromogranin A and synaptophysin on IHC. Their ages at diagnosis were 55-65 years, and tumor sizes ranged from 4 to 6 cm. These tumors were histologic grade III, hormone receptor-positive, and Her-2/neu negative. Survival outcomes varied across groups, with mucinous carcinoma showing the most favorable prognosis. Conclusion Rare subtypes of invasive breast cancers have distinct clinical and pathological behaviours with different outcomes. Recognition of these tumors will help in patient-tailored treatment strategies and will contribute to better patient management.