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Introduction
Breast cancer (BC) remains one of the most prevalent and clinically challenging malignancies worldwide, constituting a leading cause of cancer-related morbidity and mortality among women [1]. In 2020, the WHO reported nearly 2.3 million new diagnoses, making BC the most commonly diagnosed cancer globally. Furthermore, the disease is responsible for over 685,000 deaths annually. The epidemiology of BC shows significant geographic, ethnic, and temporal variation. In high-income nations, while incidence rates are higher, mortality has declined due to advances in early detection, treatment, and patient management [2]. In contrast, in lower-resource regions, BC often presents at more advanced stages, contributing to poorer survival outcomes. The risk factors for BC are complex, involving both modifiable and non-modifiable components. Age, genetic predisposition, and family history are well-established non-modifiable risks [3]. Genetic mutations, particularly in BRCA1 and BRCA2, markedly elevate the lifetime risk of developing BC. Additionally, lifestyle factors—such as sedentary behavior, poor diet, and obesity—have become increasingly linked to rising incidence, especially among postmenopausal women [4]. Historically, axillary lymph node metastasis has been a key prognostic biomarker for BC, but its predictive power is limited [5]. For example, a study showed that approximately 30% of untreated patients without nodal involvement developed metastatic disease within 10 years, while about 50% of patients with nodal involvement were cured with local treatment. Other established prognostic factors include tumor size and grade, though these also have notable limitations [6]. Tumor grading suffers from issues of reproducibility, and many tumors are ambiguously classified as grade 2, reflecting the inherent heterogeneity of the disease. In the era of personalized medicine, these traditional biomarkers are no longer sufficient for optimal management, particularly for early-stage BC [7]. Consequently, there has been growing interest in the identification and validation of molecular biomarkers that can more precisely predict prognosis and treatment response. Recent efforts have focused on multi-parameter, multi-analyte, and multi-gene approaches, offering more nuanced and individualized insights into BC prognosis and therapy.
Ferroptosis, a distinct form of iron-dependent cell death driven by lipid peroxidation, has garnered increasing attention for its pivotal role in cancer progression. Extensive research has underscored the significance of ferroptotic regulatory genes in shaping the oncogenic microenvironment, highlighting their potential as therapeutic targets [8]. The induction of ferroptosis has emerged as a...