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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.

SUBMITTER: Garcia-Closas M

PROVIDER: S-EPMC2360503 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundBreast cancer is a heterogeneous disease, divided into subtypes based on the expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). Subtypes have different biology and prognosis, with accumulating evidence of different risk factors. The purpose of this study was to compare breast cancer risk factors across tumor subtypes in a large, diverse mammography population.MethodsWomen aged 40-84 without a history of breast cancer with a screening mammogram at three United States health systems from 2006 to 2015 were included. Risk factor questionnaires were completed at mammogram visit, supplemented by electronic health records. Invasive tumor subtype was defined by immunohistochemistry as ER/PR+HER2-, ER/PR+HER2+, ER, and PR-HER2+, or triple-negative breast cancer (TNBC). Cox proportional hazards models were run for each subtype. Associations of race, reproductive history, prior breast problems, family history, breast density, and body mass index (BMI) were assessed. The association of tumor subtypes with screen detection and interval cancer was assessed using logistic regression among invasive cases.ResultsThe study population included 198,278 women with a median of 6.5 years of follow-up (IQR 4.2-9.0 years). There were 4002 invasive cancers, including 3077 (77%) ER/PR+HER2-, 300 (8%) TNBC, 342 (9%) ER/PR+HER2+, and 126 (3%) ER/PR-HER2+ subtype. In multivariate models, Black women had 2.7 times higher risk of TNBC than white women (HR = 2.67, 95% CI 1.99-3.58). Breast density was associated with increased risk of all subtypes. BMI was more strongly associated with ER/PR+HER2- and HER2+ subtypes among postmenopausal women than premenopausal women. Breast density was more strongly associated with ER/PR+HER2- and TNBC among premenopausal than postmenopausal women. TNBC was more likely to be interval cancer than other subtypes.ConclusionsThese results have implications for risk assessment and understanding of the etiology of breast cancer subtypes. More research is needed to determine what factors explain the higher risk of TNBC for Black women.

Project description:PurposeIn addition to impacting incidence, risk factors for breast cancer may also influence recurrence and survival from the disease. However, it is unclear how these factors affect combinatorial biomarkers for aiding treatment decision-making in breast cancer.MethodsPatients were 8179 women with histologically confirmed invasive breast cancer, diagnosed and treated in a large cancer hospital in Beijing, China. Individual clinicopathological (tumor size, grade, lymph nodes) and immunohistochemical (IHC: ER, PR, HER2, KI67) markers were used to define clinically relevant combinatorial prognostic biomarkers, including the Nottingham Prognostic Index (NPI: combining size, grade, nodes) and IHC4 score (combining ER, PR, HER2, KI67). Odds ratios (ORs) and 95% confidence intervals (CIs) for associations between breast cancer risk factors and quartiles (Q1-Q4) of NPI and IHC4 were assessed in multivariable polytomous logistic regression models.ResultsOverall, increasing parity (ORtrend(95% CI) = 1.20(1.05-1.37);Ptrend = 0.007), overweight (OR(95% CI)vs normal = 1.60(1.29-1.98)), and obesity (OR(95% CI) vs normal = 2.12(1.43-3.14)) were associated with higher likelihood of developing tumors with high (Q4) versus low (Q1) NPI score. Conversely, increasing age (ORtrend(95% CI) = 0.75(0.66-0.84);Ptrend < 0.001) and positive family history of breast cancer (FHBC) (OR(95% CI) = 0.66(0.45-0.95)) were inversely associated with NPI. Only body mass index (BMI) was associated with IHC4, with overweight (OR(95% CI) vs normal = 0.82(0.66-1.02)) and obese (OR(95% CI) vs normal = 0.52(0.36-0.76)) women less likely to develop high IHC4 tumors. Notably, elevated BMI was associated with higher NPI irrespective of hormone receptor-expression status.ConclusionsOur findings indicate that factors affecting breast cancer incidence, particularly age, parity, FHBC, and BMI, may impact clinically relevant prognostic biomarkers with implications for surveillance, prognostication, and counseling.

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Established breast cancer risk factors by clinically important tumour characteristics.

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