Abstract
BACKGROUND: Acromegaly is a rare endocrine disorder characterized by chronic excess growth hormone (GH) and elevated insulin-like growth factor-1 (IGF-1), which are known to have mitogenic and anti-apoptotic effects on breast tissue. While an increased risk of several malignancies has been observed in patients with acromegaly, the relationship between acromegaly and breast cancer remains unclear. OBJECTIVE: To systematically evaluate the incidence and prevalence of breast cancer in patients with acromegaly and assess whether a consistent oncologic risk exists in this population. METHODS: We systematically searched PubMed, EMBASE, and Web of Science from inception through early 2025 for studies reporting breast cancer in acromegaly. Citation tracking identified additional reports. After screening, 24 studies (>17,000 patients) were included, with data on cancer frequency, timing, and GH/IGF-1 levels extracted for analysis. From a subset of these studies reporting standardized incidence ratios (SIR) with 95% confidence intervals (CIs), a random-effects meta-analysis was performed to generate a pooled SIR, accounting for between-study heterogeneity. RESULTS: This systematic review of 24 studies with diverse designs, encompassing 17,413 patients with acromegaly, found breast cancer prevalence ranging from 0.42% to 5.85%. Several studies reported elevated GH and IGF-1 levels at any cancer diagnosis, but methodological heterogeneity limited conclusions on dose-response or temporal associations. Ten studies reported SIRs with 95% CIs and were included in the pooled analysis. The pooled SIR for breast cancer among patients with acromegaly was 1.20 (95% CI: 0.94-1.54), with moderate heterogeneity (I² = 58%). CONCLUSION: Although there is a strong biological rationale for a link between GH/IGF-1 excess and breast cancer, current clinical studies have not shown a clear or consistently increased risk in patients with acromegaly. The mixed results likely reflect issues such as surveillance bias, differences in study designs, and limited adjustment for confounders. For now, breast cancer screening in this population should generally follow the same guidelines as the general population, with perhaps closer attention in patients who have poorly controlled disease. Moving forward, well-designed prospective studies that track cancer outcomes in relation to biochemical disease activity and control will be key to answering this question.