Breast Density, Race, and Intrinsic Subtypes of Breast Cancer

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

Impact of Missing Data for Body Mass Index in an Epidemiologic Study

To assess the potential impact of missing data on body mass index (BMI) on the association between prepregnancy obesity and specific birth defects

Association between mammographic density and basal-like and luminal A breast cancer subtypes

Abstract: Introduction: Mammographic density is a strong risk factor for breast cancer overall, but few studies have examined the association between mammographic density and specific subtypes of breast cancer, especially aggressive basal-like breast cancers. Because basal-like breast cancers are less frequently screen-detected, it is important to understand how mammographic density relates to risk of basal-like breast cancer. Methods: We estimated associations between mammographic density and breast cancer risk according to breast cancer subtype. Cases and controls were participants in the Carolina Breast Cancer Study (CBCS) who also had mammograms recorded in the Carolina Mammography Registry (CMR). A total of 491 cases had mammograms within five years prior to and one year after diagnosis and 528 controls had screening or diagnostic mammograms close to the dates of selection into CBCS. Mammographic density was reported to the CMR using Breast Imaging Reporting and Data System categories. The expression of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 1 and 2 (HER1 and HER2), and cytokeratin 5/6 (CK5/6) were assessed by immunohistochemistry and dichotomized as positive or negative, with ER+ and/or PR+, and HER2- tumors classified as luminal A and ER-, PR-, HER2-, HER1+ and/or CK5/6+ tumors classified as basal-like breast cancer. Triple negative tumors were defined as negative for ER, PR and HER2. Of the 491 cases 175 were missing information on subtypes; the remaining cases included 181 luminal A, 17 luminal B, 48 basal-like, 29 ER-/PR-/HER2+, and 41 unclassified subtypes. Odds ratios comparing each subtype to all controls and case-case odds ratios comparing mammographic density distributions in basal-like to luminal A breast cancers were estimated using logistic regression. Results: Mammographic density was associated with increased risk of both luminal A and basal-like breast cancers, although estimates were imprecise. The magnitude of the odds ratio associated with mammographic density was not substantially different between basal-like and luminal A cancers in case–control analyses and case-case analyses (case-case OR = 1.08 (95% confidence interval: 0.30, 3.84)). Conclusions: These results suggest that risk estimates associated with mammographic density are not distinct for separate breast cancer subtypes (basal-like/triple negative vs. luminal A breast cancers). Studies with a larger number of basal-like breast cancers are needed to confirm our findings

Mammographic density and breast cancer risk in White and African American Women

Mammographic density is a strong risk factor for breast cancer, but limited data are available in African American (AA) women. We examined the association between mammographic density and breast cancer risk in AA and white women. Cases (n = 491) and controls (n = 528) were from the Carolina Breast Cancer Study (CBCS) who also had mammograms recorded in the Carolina Mammography Registry (CMR). Mammographic density was reported to CMR using Breast Imaging Reporting and Data System (BI-RADS) categories. Increasing mammographic density was associated with increased breast cancer risk among all women. 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)]. The association was stronger in whites, with ~40 % higher risk among those with extremely dense breasts compared to those with scattered fibroglandular densities [1.39, (0.75, 2.55)]. In AA women, the same comparison suggested lower risk [0.75, (0.30, 1.91)]. Because age, obesity, and exogenous hormones have strong associations with breast cancer risk, mammographic density, and race in the CBCS, effect measure modification by these factors was considered. Consistent with previous literature, density-associated risk was greatest among those with BMI > 30 and current hormone users (P value = 0.02 and 0.01, respectively). In the CBCS, mammographic density is associated with increased breast cancer risk, with some suggestion of effect measure modification by race, although results were not statistically significant. However, exposures such as BMI and hormone therapy may be important modifiers of this association and merit further investigation

A review of African American-white differences in risk factors for cancer: prostate cancer

African American men have higher prostate cancer incidence rates than White men, for reasons not completely understood. This review summarizes the existing literature of race-specific associations between risk factors and prostate cancer in order to examine whether associations differ

PATTERNS OF PERSISTENT GENITAL HUMAN PAPILLOMAVIRUS INFECTION AMONG WOMEN WORLDWIDE: A LITERATURE REVIEW AND META-ANALYSIS

Persistent high-risk human papillomavirus (HR-HPV) infection is the strongest risk factor for high-grade cervical precancer. We performed a systematic review and meta-analysis of HPV persistence patterns worldwide. Medline and ISI Web of Science were searched through January 1, 2010 for articles estimating HPV persistence or duration of detection. Descriptive and meta-regression techniques were used to summarize variability and the influence of study definitions and characteristics on duration and persistence of cervical HPV infections in women. Among 86 studies providing data on over 100,000 women, 73% defined persistence as HPV positivity at a minimum of two time points. Persistence varied notably across studies and was largely mediated by study region and HPV type, with HPV-16, 31, 33 and 52 being most persistent. Weighted median duration of any-HPV detection was 9.8 months. HR-HPV (9.3 months) persisted longer than low-risk HPV (8.4 months), and HPV-16 (12.4 months) persisted longer than HPV-18 (9.8 months). Among populations of HPV positive women with normal cytology, the median duration of any-HPV detection was 11.5 and HR-HPV detection was10.9 months. In conclusion, we estimated that approximately half of HPV infections persist past 6–12 months. Repeat HPV testing at 12 month intervals could identify women at increased risk of high-grade cervical precancer due to persistent HPV infections

Factors Associated with High Hospital Resource Use in a Population-based Study of Children with Orofacial Clefts

Background: Little is known about population-based maternal, child, and system characteristics associated with high hospital resource use for children with orofacial clefts (OFC) in the US. Methods: This was a statewide, population-based, retrospective observational study of children with OFC born between 1998 and 2006, identified by the Florida Birth Defects Registry whose records were linked with longitudinal hospital discharge records. We stratified the descriptive results by cleft type [cleft lip with cleft palate, cleft lip, and cleft palate] and by isolated versus nonisolated OFC (accompanied by other coded major birth defects). We used Poisson regression to analyze associations between selected characteristics and high hospital resource use (≥90th percentile of estimated hospitalized days and inpatient costs) for birth, postbirth, and total hospitalizations initiated before age 2 years. Results: Our analysis included 2,129 children with OFC. Infants who were born low birth weight (\u3c2500 \u3egrams) were significantly more likely to have high birth hospitalization costs for CLP (adjusted prevalence ratio: 1.6 [95% confidence interval: 1.0–2.7]), CL (adjusted prevalence ratio: 3.0 [95% confidence interval: 1.1–8.1]), and CP (adjusted prevalence ratio: 2.3 [95% confidence interval: 1.3–4.0]). Presence of multiple birth defects was significantly associated with a three- to eleven-fold and a three- to nine-fold increase in the prevalence of high costs and number of hospitalized days, respectively; at birth, postbirth before age 2 years Conclusion: Children with cleft palate had the greatest hospital resources use. Additionally, the presence of multiple birth defects contributed to greater inpatient days and costs for children with OFC. Birth Defects Research (Part A) 103:127–143, 2015 © 2015 Wiley Periodicals, Inc

Describing the Prevalence of Neural Tube Defects Worldwide: A Systematic Literature Review

<div><p>Background</p><p>Folate-sensitive neural tube defects (NTDs) are an important, preventable cause of morbidity and mortality worldwide. There is a need to describe the current global burden of NTDs and identify gaps in available NTD data.</p><p>Methods and Findings</p><p>We conducted a systematic review and searched multiple databases for NTD prevalence estimates and abstracted data from peer-reviewed literature, birth defects surveillance registries, and reports published between January 1990 and July 2014 that had greater than 5,000 births and were not solely based on mortality data. We classified countries according to World Health Organization (WHO) regions and World Bank income classifications. The initial search yielded 11,614 results; after systematic review we identified 160 full text manuscripts and reports that met the inclusion criteria. Data came from 75 countries. Coverage by WHO region varied in completeness (i.e., % of countries reporting) as follows: African (17%), Eastern Mediterranean (57%), European (49%), Americas (43%), South-East Asian (36%), and Western Pacific (33%). The reported NTD prevalence ranges and medians for each region were: African (5.2–75.4; 11.7 per 10,000 births), Eastern Mediterranean (2.1–124.1; 21.9 per 10,000 births), European (1.3–35.9; 9.0 per 10,000 births), Americas (3.3–27.9; 11.5 per 10,000 births), South-East Asian (1.9–66.2; 15.8 per 10,000 births), and Western Pacific (0.3–199.4; 6.9 per 10,000 births). The presence of a registry or surveillance system for NTDs increased with country income level: low income (0%), lower-middle income (25%), upper-middle income (70%), and high income (91%).</p><p>Conclusions</p><p>Many WHO member states (120/194) did not have any data on NTD prevalence. Where data are collected, prevalence estimates vary widely. These findings highlight the need for greater NTD surveillance efforts, especially in lower-income countries. NTDs are an important public health problem that can be prevented with folic acid supplementation and fortification of staple foods.</p></div