MOLECULAR SUBTYPES, RISK FACTORS, DIAGNOSTIC APPROACHES, AND THERAPEUTIC STRATEGIES IN BREAST CANCER: A COMPREHENSIVE REVIEW WITH CLINICAL IMPLICATIONS
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Abstract
Breast cancer (BC) is the most prevalent malignancy among women worldwide and the leading cause of cancer-related mortality in the female population, representing a critical global public health challenge. This comprehensive study aimed to analyze the epidemiological burden, molecular classification, risk factor profiles, diagnostic modalities, and contemporary therapeutic strategies of breast cancer, as well as to evaluate outcomes across molecular subtypes in a cohort of 320 histologically confirmed breast cancer patients. Patients were enrolled from the oncology department of a tertiary referral hospital between January 2020 and December 2023. Comprehensive clinicopathological data were collected including tumor characteristics, hormonal receptor status, HER2 expression, Ki-67 proliferative index, lymph node involvement, and treatment responses. Molecular subtype distribution revealed that Luminal A constituted the largest subgroup (38.4%), followed by Luminal B (26.9%), HER2-enriched (16.6%), and Triple-Negative Breast Cancer (TNBC) (18.1%). The mean age at diagnosis was 52.4 ± 11.8 years, with 73.4% of patients presenting at stages II and III. The five-year overall survival rates differed significantly among subtypes: Luminal A demonstrated the most favorable prognosis (89.2%), followed by Luminal B (76.4%), HER2-enriched (71.8%), and TNBC (58.6%) (p<0.001). Analysis of risk factors identified significant associations with family history of breast or ovarian cancer (OR 3.42, 95% CI 2.18–5.36, p<0.001), nulliparity (OR 2.17, 95% CI 1.54–3.06, p<0.001), hormone replacement therapy use >5 years (OR 1.94, 95% CI 1.28–2.94, p=0.002), obesity [BMI ≥30 kg/m²] (OR 1.76, 95% CI 1.22–2.54, p=0.002), and late age at first full-term pregnancy ≥30 years (OR 1.65, 95% CI 1.14–2.38, p=0.008). Sensitivity and specificity of combined digital mammography and ultrasound examination reached 91.3% and 87.6% respectively, while MRI demonstrated 96.8% sensitivity for dense breast tissue. Pathological complete response (pCR) to neoadjuvant chemotherapy was highest in TNBC (45.7%) and HER2-enriched (52.3%) subtypes. These findings underscore the heterogeneous nature of breast cancer, emphasizing the importance of molecular subtyping for individualized treatment planning, the critical role of early detection, and the need for continued development of targeted therapeutic strategies to improve survival across all disease subtypes.
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