Established Breast Cancer Risk Factors by Clinically Important Tumour Characteristics

Breast cancer is a morphologically and clinically heterogeneous disease; however, it is less clear how risk factors relate to tumour features. We evaluated risk factors by tumour characteristics (histopathologic type, grade, size, and nodal status) in a population-based case-control of 2386 breast cancers and 2502 controls in Poland. Use of a novel extension of the polytomous logistic regression permitted simultaneous modelling of multiple tumour characteristics. Late age at first full-term birth was associated with increased risk of large (> 2 cm) tumours (odds ratios (95% confidence intervals) 1.19 (1.07-1.33) for a 5-year increase in age), but not smaller tumours (P for heterogeneity adjusting for other tumour features (Phet) = 0.007). On the other hand, multiparity was associated with reduced risk for small tumours (0.76 (0.68-0.86) per additional birth; Phet = 0.004). Consideration of all tumour characteristics simultaneously revealed that current or recent use of combined hormone replacement therapy was associated with risk of small (2.29 (1.66-3.15)) and grade 1 (3.36 (2.22-5.08)) tumours (Phet = 0.05 for size and 0.0008 for grade 1 vs 3), rather than specific histopathologic types (Phet = 0.63 for ductal vs lobular). Finally, elevated body mass index was associated with larger tumour size among both pre- and postmenopausal women (Phet = 0.05 and 0.0001, respectively). None of these relationships were explained by hormone receptor status of the tumours. In conclusion, these data support distinctive risk factor relationships by tumour characteristics of prognostic relevance. These findings might be useful in developing targeted prevention efforts.