Abstract: Background: Mechanisms linking occupational heat exposure with chronic diseases have been proposed. However, evidence on occupational heat exposure and cancer risk is limited. Methods: We evaluated occupational heat exposure and female breast cancer risk in a large Spanish case-control study. We enrolled 1,738 breast cancer cases and 1,910 frequency-matched population controls. A Spanish job-exposure matrix, MatEmEsp, was used to assign estimates of the proportion of workers exposed (P >= 25% for at least 1 year) and work time with heat stress (wet bulb globe temperature ISO 7243) for each occupation. We used three exposure indices: ever versus never exposed, lifetime cumulative exposure, and duration of exposure (years). We estimated ORs and 95% confidence intervals (CI), applying a lag period of 5 years and adjusting for potential confounders. Results: Ever occupational heat exposure was associated with a moderate but statistically significant higher risk of breast cancer (OR 1.22; 95% CI, 1.01-1.46), with significant trends across categories of lifetime cumulative exposure and duration (Ptrend = 0.01 and 0.03, respectively). Stronger associations were found for hormone receptor?positive disease (OR ever exposure = 1.38; 95% CI, 1.12-1.67). We found no confounding effects from multiple other common occupational exposures; however, results attenuated with adjustment for occupational detergent exposure. Conclusions: This study provides some evidence of an association between occupational heat exposure and female breast cancer risk. Impact: Our results contribute substantially to the scientific literature. Further investigations are needed considering multiple occupational exposures.

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