Established breast cancer risk factors by clinically important tumour characteristics

Abstract

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.

Figures

Figure 1

Predictors of invasive breast cancer risk in the Polish Breast Cancer Study by histological subtypes. Odds ratios (95% CI) for ductal carcinomas, NOS (N=1,251) are shown in black, for lobular carcinomas (N=342) in blue, for tubular carcinomas (N=119) in red, and for mixed carcinoma (N=252) in green. Numbers in brackets denote statistically significant heterogeneity of ORs for lobular, tubular, and mixed compared to ductal carcinomas, NOS, respectively, based on standard polytomous logistic regression among cases: (1) 0.13, 0.002, and 0.98. Analyses are adjusted for age, study site, menopausal status, education level, family history, prior benign breast biopsy, screening mammogram, and all other factors shown in the figure. Comparison groups are 5-year increases for ages at menarche, first full-term birth, and menopause; each additional birth for number of full-term births; never HRT users for current or recent use of combined HRT; 5 unit increases for BMI.

Figure 2

Predictors of invasive breast cancer (ductal carcinomas, NOS, tubular, lobular, and mixed types) in the Polish Breast Cancer Study by tumour grade, size, and nodal status. Odds ratio (95% CI) for grade 1 (N=333), small (⩽2 cm, N=988), or node negative (N=1084) tumours are shown in black; for grade 2 (N=979), large (>2 cm, N=796), or node positive (N=708) are shown in blue; and for grade 3 (N=500) are shown in red. Numbers in brackets denote statistically significant heterogeneity of ORs based on standard polytomous logistic regression among cases: (1) 0.001 and 0.00008 for grades 2 and 3 compared to grade 1 tumours, respectively; (2) 0.02, (3) 0.0019, (4) 0.001, (5) 0.0006, and (6) 0.0005 for small (⩽2 cm) compared to large (>2 cm) tumours; and (7) 0.02, (8) 0.006, (9) 0.002, and (10) 0.02 for node positive compared to node negative tumours. Analyses are adjusted for age, study site, menopausal status, education level, family history, prior benign breast biopsy, screening mammogram, and all other factors shown in the figure. Comparison groups are 5-year increases for ages at menarche, first full-term birth, menopause; each additional birth for number of full-term births; never HRT users for current or recent use of combined HRT; 5 unit increases for BMI.