• 252 oesophageal cancers (488 matched controls) after breast cancer were analysed. • The excess odds-ratio of oesophageal cancer linearly increased with median dose. • At a fixed median dose, larger V30 increased the risk of squamous cell carcinoma. • Median dose and V30 could be relevant metrics in treatment plan optimization. • The study highlights the role of highest doses in oesophageal cancer risk. To investigate the relationship between oesophagus dose-volume distribution and long-term risk of oesophageal cancer after radiation therapy for breast cancer. In a case-control study nested within a cohort of 289,748 ≥5-year survivors of female breast cancer treated in 1943–2003 in five countries, doses to the second primary cancer (D SPC) and individual dose-volume histograms (DVH) to the entire oesophagus were reconstructed for 252 oesophageal cancer cases and 488 matched controls (median follow-up time: 13, range: 5–37 years). Using conditional logistic regression, we estimated excess odds ratios (EOR) of oesophageal cancer associated with DVH metrics. We also investigated whether DVH metrics confounded or modified D SPC -related -risk estimates. Among the DVH metrics evaluated, median dose (D median) to the entire oesophagus had the best statistical performance for estimating risk of all histological types combined (EOR/Gy = 0.071, 95% confidence interval [CI]: 0.018 to 0.206). For squamous cell carcinoma, the most common subtype, the EOR/Gy for D median increased by 31% (95% CI: 3% to 205%) for each increment of 10% of V30 (p = 0.02). Adjusting for DVH metrics did not materially change the EOR/Gy for D SPC , but there was a borderline significant positive interaction between D SPC and V30 (p = 0.07). This first study investigating the relationship between oesophagus dose-volume distribution and oesophageal cancer risk showed an increased risk per Gy for D median with larger volumes irradiated at high doses. While current techniques allows better oesophagus sparing, constraints applied to D median and V30 could potentially further reduce the risk of oesophageal cancer. [ABSTRACT FROM AUTHOR]