Breast Cancer Risk and Management in the Endocrine Clinic: A Comprehensive Review.

Abstract

Objective: This review seeks to provide endocrine clinicians with a comprehensive analysis of breast cancer risk, diagnostic modalities and management strategies in women with endocrine disorders, with particular emphasis on the influence of metabolic factors such as diabetes and obesity, and the role of Menopausal Hormone Therapy (MHT).

Design: The review examines a spectrum of endocrine disorders commonly encountered in clinical practice, including Multiple Endocrine Neoplasia Types 1 (MEN1), 2 (MEN2) and 4 (MEN4), Von Hippel-Lindau syndrome (VHL), Pheochromocytoma and Paraganglioma (PPGL), Acromegaly, Hyperprolactinaemia, Polycystic Ovary Syndrome (PCOS), Congenital Adrenal Hyperplasia (CAH), Turner Syndrome, alongside metabolic conditions such as diabetes and obesity and the effects of MHT. The review critically appraises each disorder's association with breast cancer risk, screening implications and therapeutic management.

Patients: This analysis focuses on women with the aforementioned endocrine and metabolic disorders, assessing their specific breast cancer risk profiles, informed by the latest clinical evidence and molecular insights.

Measurements: The review comprehensively evaluates current evidence-based approaches to screening, diagnostic accuracy and treatment in this patient cohort. Emphasis is placed on the metabolic derangements, hormonal influences and genetic predispositions that modulate breast cancer risk, providing disorder-specific recommendations for individualised care.

Results: The findings indicate a significantly elevated breast cancer risk in patients with MEN1, necessitating early initiation of MRI screening by age 40. In MEN2, emerging evidence suggests that combining RET inhibitors with endocrine therapy may yield clinical benefits, although further research is needed to validate this approach. The breast cancer risk associated with MEN4 and VHL syndromes, while documented, remains less well-characterised, requiring further investigation. Diabetes and obesity are confirmed as major modifiable risk factors, particularly in postmenopausal women, where hyperinsulinemia and metabolic dysfunction contribute to increased incidence and poorer outcomes, notably in triple-negative breast cancer (TNBC). The role of MHT, particularly combined oestrogen-progestogen therapy, is strongly associated with increased breast cancer risk, particularly for hormone receptor-positive malignancies, necessitating cautious use and personalised treatment planning. In contrast, oestrogen-only MHT appears to confer a reduced risk in women post-hysterectomy. For patients with PCOS, CAH and Turner Syndrome, while definitive evidence of elevated breast cancer risk is lacking, individualised screening strategies and careful hormone therapy management remain essential due to the complex interplay of hormonal and metabolic factors.

Conclusions: The review highlights the need for personalised breast cancer screening and management protocols in women with endocrine and metabolic disorders. For high-risk groups such as MEN1 patients, early initiation of MRI screening is warranted. In women with diabetes and obesity, targeted interventions addressing hyperinsulinemia and metabolic dysfunction are critical to mitigating their increased cancer risk. The association between MHT and breast cancer underscores the importance of individualised risk stratification in hormone therapy administration, particularly in women with predisposing genetic or endocrine conditions. Enhanced surveillance tailored to the unique risk profiles of endocrine disorder patients will facilitate early detection and improve clinical outcomes. However, further large-scale studies are necessary to refine these associations and develop robust, evidence-based guidelines.