Background: There is growing evidence that tumors of the inner quadrants (especially the lower-inner quadrant) metastasize more often to the internal mammary chain (IMC). As these metastases are not investigated, patients with lower-inner quadrant tumors have an increased risk of being under-staged and under-treated and may therefore have a higher risk of death from breast cancer. Methods: We identified all 1522 women operated for stage I breast cancer between 1984 and 2002 recorded at the population-based Geneva Cancer Registry. We compared breast cancer mortality risk by tumor location with multivariate Cox regression analysis that accounted for all factors linked to tumor location and survival. Results: Ten-year disease-specific survival was 93% (95%CI: 91-94%). Patients with breast cancer of the lower-inner quadrant (n=118; 7.8%) had an importantly increased risk of dying of breast cancer compared to women with breast cancer of the upper-outer quadrant (multiadjusted Hazard Ratio: 2.3, 95%CI: 1.1-4.5, P=0.0206). The over-mortality associated with this quadrant was particularly evident for tumors >10 mm (multiadjusted HR: 3.6, 95%CI: 1.6-7.9, P=0.0016). There was no increased breast cancer mortality risk for tumors located in other quadrants. Conclusions: Tumor location in the lower-inner quadrant is an independent and important prognostic factor of stage I breast cancer. Further research is needed to evaluate if the over-mortality of patients with stage I cancer of the lower-inner quadrant is indeed a result of under-treatment due to undetected IMC metastases. If so, patients with stage I breast cancer of the lower-inner quadrant are good candidates for systematic IMC investigatio
