Breast Density, Race, and Intrinsic Subtypes of Breast Cancer

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  • March 22, 2019
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  • Razzaghi, Hilda
    • Affiliation: Gillings School of Global Public Health, Department of Epidemiology
Abstract
  • Breast density is among the strongest and most consistent risk factors for breast cancer. Mammographic breast density refers to the radiographically dense areas on a mammogram, and is a measure of fibroglandular tissue in the breast. It has been estimated that women with the highest mammographic density may be at a four- to six-fold increased risk of developing breast cancer compared with women with less dense tissue. Although the strongest risk factor, breast density is one of the least understood. Whether breast density and breast cancer risk differ by race is unclear and limited data exists on this association. Similarly, it is unknown whether breast density has different patterns of association depending upon molecular characteristics of the cancers. Basal-like and luminal breast cancers have shown distinct patterns of risk for other breast cancer risk factors, but their associations with breast density have not been estimated. Cases and controls were participants in the Carolina Breast Cancer Study (CBCS) Phase I or Phase II (1993 - 2001) who also had mammograms recorded in the Carolina Mammography Registry (CMR). After combining the two datasets, 491 cases with mammograms within 5 years prior to and 1 year post diagnosis and 528 controls with mammograms within 5 years prior to and 3 years post to selection date were identified. Mammographic density was reported to CMR using Breast Imaging Reporting and Data System (BI-RADS) categories. The expression status of ER, PR, HER2, HER1, and CK5/6 was assessed by immunohistochemistry. We considered ER+ and/or PR+, and HER2- tumors as Luminal A and ER-, PR-, HER2-, HER1+ and/or CK5/6+ tumors as Basal-like breast cancer. In Aim 1, mammographic density was evaluated in association with breast cancer risk among all women and according to race. After adjusting for potential confounders, a monotonically increasing risk of breast cancer was observed between the highest versus the lowest BI-RADS density categories [OR = 2.45, (95% confidence interval: 0.99, 6.09)]. However, when stratifying by race, the association was stronger in whites, with approximately 40% higher risk among those with extremely dense breasts compared to those with scattered fibroglandular densities. Covariates that are associated with race and breast density, such as age, body mass index (BMI) and hormone therapy were also considered as possible modifiers of the breast density-breast cancer association. In examining Aim 2, mammographic breast density was evaluated in association with specific breast cancer subtypes: Luminal A and Basal-like breast cancers. Using BI-RADS category 2 as the referent group, the case-control odds ratio estimates were not substantially different between Basal-like and Luminal A cancers [1.04, (0.34, 3.17) and 0.98 (0.50, 1.92), respectively]. Furthermore, case-case odds ratios confirmed no significant difference in risk between the two subtypes [1.08, (0.30, 3.84)]. In conclusion, mammographic density is associated with increased breast cancer risk in CBCS, with some suggestion of effect measure modification by race. However, exposures such as BMI and hormone therapy may be important modifiers of this association and merit further investigation. Breast density was associated with increased risk of both Basal-like and Luminal A breast cancers, with no strong evidence of etiologic heterogeneity according to breast cancer subtype. These data help to elucidate important patterns of breast density-associated risk of breast cancer and describe previously poorly understood patterns by race and breast cancer subtype. These patterns are important for informing breast cancer prevention strategies.
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  • ... in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the Department of Epidemiology, School of Public Health.
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  • Troester, Melissa
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