Article

Breast Cancer Risk Prediction with Heterogeneous Risk Profiles According to Breast Cancer Tumor Markers

American journal of epidemiology (Impact Factor: 4.98). 05/2013; 178(2). DOI: 10.1093/aje/kws457
Source: PubMed

ABSTRACT Relationships between some risk factors and breast cancer incidence are known to vary by tumor subtype. However, breast tumors can be classified according to a number of markers, which may be correlated, making it difficult to identify heterogeneity of risk factors with specific tumor markers when using standard competing-risk survival analysis. In this paper, we propose a constrained competing-risk survival model that allows for assessment of heterogeneity of risk factor associations according to specific tumor markers while controlling for other markers. These methods are applied to Nurses' Health Study data from 1980-2006, during which 3,398 incident invasive breast cancers occurred over 1.4 million person-years of follow-up. Results suggested that when estrogen receptor (ER) and progesterone receptor (PR) status are mutually considered, some risk factors thought to be characteristic of "estrogen-positive tumors," such as high body mass index during postmenopause and increased height, are actually significantly associated with PR-positive tumors but not ER-positive tumors, while other risk factors thought to be characteristic of "estrogen-negative tumors," such as late age at first birth, are actually significantly associated with PR-negative rather than ER-negative breast cancer. This approach provides a strategy for evaluating heterogeneity of risk factor associations by tumor marker levels while controlling for additional tumor markers.

1 Follower
 · 
60 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Alcohol consumption is an established risk factor for breast cancer. Whether associations vary by specific tumor characteristics independent of other characteristics is unclear. We evaluated the association between alcohol consumption and breast cancer risk in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial cohort (54,562 women aged 55-74 years recruited at 10 US screening centers between 1993 and 2001; median follow-up, 8.9 years; 1,905 invasive breast cancer cases). Hazard ratios and 95% confidence intervals for subtypes defined by histological type and estrogen receptor (ER)/progesterone receptor (PR) status were calculated with standard Cox models. A novel 2-stage Cox model assessed heterogeneity in risk for individual tumor characteristics while adjusting for others. Significant trends across categories of alcohol consumption were observed, with hazard ratios for those consuming 7 or more drinks per week versus never drinkers as follows: for estrogen receptor-positive (ER+) cancer, 1.48 (95% confidence interval (CI): 1.19, 1.83); for progesterone receptor-positive (PR+) cancer, 1.64 (95% CI: 1.31, 2.06); for ER+/PR+ cancer, 1.63 (95% CI: 1.30, 2.05); and for mixed ductal/lobular cancer, 2.51 (95% CI: 1.20, 5.24). For ER+ and PR+ cancers, trends were significant for ductal and mixed ductal/lobular types. PR status explained the positive association with ER status (for ER status, Pheterogeneity = 0.70 after adjustment for PR status). Alcohol consumption was not associated with all breast cancer subtypes. Future work should emphasize large collaborative studies, precise definition of subtypes, and adjustment for correlated tumor characteristics.
    American Journal of Epidemiology 08/2014; 180(7). DOI:10.1093/aje/kwu189 · 4.98 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background: Few studies have assessed the association of body size with postmenopausal breast cancer (BC) risk in Hispanic women. Findings are inconsistent and appear to contradict those reported for non-Hispanic White (NHW) women. Methods: We pooled interview and anthropometric data for 2,023 Hispanic and 2,384 NHW women from two U.S. population-based case-control studies. Using logistic regression analysis, we examined associations of overall and abdominal adiposity with risk of postmenopausal BC defined by estrogen receptor (ER) and progesterone receptor (PR) status. Results: Weight gain was associated with increased risk of ER+PR+ BC in Hispanics not currently using menopausal hormone therapy (HT), but only among those with a low young-adult body mass index (BMI). In the subset of Hispanics with data on genetic ancestry, the association with weight gain was limited to women with lower Indigenous American ancestry. Young-adult BMI was inversely associated with both ER+PR+ and ER-PR- BC for both ethnicities combined, with similar, although non-significant, inverse trends in Hispanics and NHWs. Among all Hispanics, regardless of HT use, height was associated with risk of ER-PR- BC and hip circumference with risk of BC overall. Conclusions: Body size throughout adult life is associated with BC risk among postmenopausal Hispanic women, as has been reported for NHW women. Associations were specific for BC subtypes defined by hormone receptor status. Impact: Avoiding weight gain and maintaining a healthy weight are important strategies to reduce the risk of postmenopausal ER+PR+ BC, the most common BC subtype.
    Cancer Epidemiology Biomarkers & Prevention 10/2014; 24(1). DOI:10.1158/1055-9965.EPI-14-0560 · 4.32 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The frequencies of molecular breast cancer subtypes vary among different human populations. The Northeastern region of Brazil has a mixed population of African, Indigenous and European ancestry. This retrospective study investigated breast cancer subtypes and applied therapies in a public hospital of Northeastern Brazil.
    BMC Women's Health 09/2014; 14(1):110. DOI:10.1186/1472-6874-14-110 · 1.66 Impact Factor