The female preponderance of many autoimmune diseases suggests a possible hormonal etiology. Little research exists on systemic and organ‐specific autoimmune diseases and risk of breast cancer by ...tumor estrogen receptor (ER)‐ and progesterone receptor (PR)‐ status. Here, we evaluate associations between selected systemic and organ‐specific autoimmune diseases and breast cancer risk overall and by tumor ER‐ and PR‐status. We used linked Surveillance, Epidemiology and End Results (SEER)‐Medicare data, with first female breast cancer cases ages ≥66 years identified by SEER registries (years 1992–2011; N = 209,929). We selected female controls (N = 200,000) from a stratified 5% random sample of Medicare recipients who were alive and breast cancer‐free. We assessed exposures until 12 months before breast cancer diagnosis/selection using Medicare claims data. We estimated odds ratios (OR) and 99.9% confidence intervals (CI) using unconditional and multinomial logistic regression. We found reduced breast cancer risk among those with rheumatoid arthritis (OR = 0.84; 99.9% CI 0.79–0.89), systemic lupus erythematosus (OR = 0.82; 99.9% CI 0.70–0.97) and pernicious anemia (OR = 0.90; 99.9% CI 0.83–0.97) and increased risk among those with psoriasis (OR = 1.16; 99.9% CI 1.06–1.27). Statistically significant alterations in risk for rheumatoid arthritis were limited to ER‐positive (+) breast cancer, whereas those for the other three conditions were further limited to ER+/PR+ breast cancer. However, only differences for rheumatoid arthritis by ER‐status were statistically significant (p‐heterogeneity = 0.0001). The reasons for these associations need to be investigated in future studies accounting for host characteristics and autoimmune disease treatment.
What's new?
The female preponderance of many autoimmune diseases suggests a possible hormonal etiology. Therefore, it is of interest to examine associations of autoimmune diseases with breast cancer by the hormone‐receptor status of the tumors. This is the first study to examine associations of systemic and organ‐specific autoimmune diseases with breast cancer according to tumor estrogen receptor (ER)‐ and progesterone receptor (PR)‐status. The findings that statistically significant alterations in risk with rheumatoid arthritis, systemic lupus erythematosus, pernicious anemia and psoriasis varied according to tumor ER‐ and PR‐status offer important clues to the complex relationship between certain autoimmune diseases and breast cancer risk.
Myotonic dystrophy type I (DM1) is an autosomal dominant multisystem disorder characterized by myotonia and muscle weakness. Type 2 diabetes (T2D) and cancer have been shown to be part of the DM1 ...phenotype. Metformin, a well‐established agent for the management of T2D, is thought to have cancer‐preventive effects in the general population. In our study, we aimed to assess the association between T2D, metformin use and the risk of cancer in DM1 patients. We identified a cohort of 913 DM1 patients and an age‐, sex‐ and clinic‐matched cohort of 12,318 DM1‐free controls from the UK Clinical Practice Research Datalink, a large primary care records database. We used Cox regression models to assess cancer risk in T2D patients who were metformin users or nonusers compared to patients without T2D. Separate analyses were conducted for DM1 patients and controls. T2D was more prevalent in DM1 than in controls (8% vs. 3%, p < 0.0001). DM1 patients with T2D, compared to those without T2D, were more likely to develop cancer (hazard ratio HR = 3.60, 95% confidence interval CI = 1.18–10.97; p = 0.02), but not if they were treated with metformin (HR = 0.43, 95% CI = 0.06–3.35; p = 0.42). Among controls, we observed no significant associations between T2D and cancer risk in either users or nonusers of Metformin (HR = 1.28, 95% CI = 0.91–1.79; p = 0.16 and HR = 1.13, 95% CI = 0.72–1.79; p = 0.59, respectively). These results show an association between T2D and cancer risk in DM1 patients and may provide new insights into the possible benefits of Metformin use in DM1.
What's new?
Recent evidence suggests that myotonic dystrophy type I (DM1), an inherited nucleotide repeat disorder, is a cancer predisposition syndrome. However, the underlying pathological mechanisms and cancer‐predisposing risk factors remain unknown. Here, type 2 diabetes (T2D) and metformin were investigated for potential associations with cancer risk in DM1 patients. T2D was found to be more prevalent in DM1 patients than controls. DM1 patients with T2D were at increased risk of developing cancer. By contrast, cancer risk was not elevated in DM1‐T2D patients taking metformin. Further investigation of metformin use and cancer in DM1 patients could yield important insights into DM1‐related cancer prevention.
Previous work in European ancestry populations has shown that adding a polygenic risk score (PRS) to breast cancer risk prediction models based on epidemiologic factors results in better ...discriminatory performance as measured by the AUC (area under the curve). Following publication of the first PRS to perform well in women of African ancestry (AA-PRS), we conducted an external validation of the AA-PRS and then evaluated the addition of the AA-PRS to a risk calculator for incident breast cancer in Black women based on epidemiologic factors (BWHS model).
Data from the Black Women's Health Study, an ongoing prospective cohort study of 59,000 US Black women followed by biennial questionnaire since 1995, were used to calculate AUCs and 95% confidence intervals (CIs) for discriminatory accuracy of the BWHS model, the AA-PRS alone, and a new model that combined them. Analyses were based on data from 922 women with invasive breast cancer and 1844 age-matched controls.
AUCs were 0.577 (95% CI 0.556-0.598) for the BWHS model and 0.584 (95% CI 0.563-0.605) for the AA-PRS. For a model that combined estimates from the questionnaire-based BWHS model with the PRS, the AUC increased to 0.623 (95% CI 0.603-0.644).
This combined model represents a step forward for personalized breast cancer preventive care for US Black women, as its performance metrics are similar to those from models in other populations. Use of this new model may mitigate exacerbation of breast cancer disparities if and when it becomes feasible to include a PRS in routine health care decision-making.
Hysterectomy is the most common nonobstetrical medical procedure performed in US women. Evaluating hysterectomy prevalence trends and determinants is important for estimating gynecologic cancer rates ...and management of uterine conditions.
This study aimed to assess hysterectomy prevalence trends and determinants using the Behavioral Risk Factor Surveillance System (2006–2016).
We estimated crude hysterectomy prevalences and multivariable-adjusted odds ratios and 95% confidence intervals for associations of race or ethnicity, age group (5-year), body mass index (categorical), smoking status, education, insurance, income, and US region with hysterectomy. Missing data were imputed. The number of women in each survey year ranged from 220,302 in 2006 to 275,631 in 2016.
Although overall hysterectomy prevalence changed little between 2006 and 2016 (21.4% and 21.1%, respectively), hysterectomy prevalence was lower in 2016 than in 2006 among women aged ≥40 years, particularly among non-Hispanic Black and Hispanic women. Current smoking (odds ratio, 1.38; 95% confidence interval, 1.35–1.41), increasing age (odds ratio, 1.40; 95% confidence interval, 1.39–1.40), living in the South compared with the Midwest (odds ratio, 1.36; 95% confidence interval, 1.34–1.39), higher body mass index (odds ratio, 1.26; 95% confidence interval, 1.25–1.27), Black race compared with White (odds ratio, 1.10; 95% confidence interval, 1.07–1.13), and having insurance compared with being uninsured (odds ratio, 1.26; 95% confidence interval, 1.22–1.30) were most strongly associated with increased prevalence. Hispanic ethnicity and living in the Northeast were most strongly associated with decreased prevalence (odds ratio, 0.73; 95% confidence interval, 0.70–0.76; odds ratio, 0.67; 95% confidence interval, 0.65–0.69).
Nationwide hysterectomy prevalence decreased among women aged ≥40 years from 2006 to 2016, particularly among non-Hispanic Black and Hispanic women. Age, non-Hispanic Black race, having insurance, current smoking, and living in the South were associated with increased odds of hysterectomy, even after accounting for possible explanatory factors. Further research is needed to better understand associations of race and ethnicity and region with hysterectomy prevalence.
Abstract
Background
Emerging data indicate that variations in quantitative epithelial and stromal tissue composition and their relative abundance in benign breast biopsies independently impact risk ...of future invasive breast cancer. To gain further insights into breast cancer etiopathogenesis, we investigated associations between epidemiological factors and quantitative tissue composition metrics of the normal breast.
Methods
The study participants were 4108 healthy women ages 18–75 years who voluntarily donated breast tissue to the US-based Susan G. Komen Tissue Bank (KTB; 2008–2019). Using high-accuracy machine learning algorithms, we quantified the percentage of epithelial, stromal, adipose, and fibroglandular tissue, as well as the proportion of fibroglandular tissue that is epithelium relative to stroma (i.e., epithelium-to-stroma proportion, ESP) on digitized hematoxylin and eosin (H&E)-stained normal breast biopsy specimens. Data on epidemiological factors were obtained from participants using a detailed questionnaire administered at the time of tissue donation. Associations between epidemiological factors and square root transformed tissue metrics were investigated using multivariable linear regression models.
Results
With increasing age, the amount of stromal, epithelial, and fibroglandular tissue declined and adipose tissue increased, while that of ESP demonstrated a bimodal pattern. Several epidemiological factors were associated with individual tissue composition metrics, impacting ESP as a result. Compared with premenopausal women, postmenopausal women had lower ESP
β
(95% Confidence Interval (CI)) = −0.28 (− 0.43, − 0.13);
P
< 0.001 with ESP peaks at 30–40 years and 60–70 years among pre- and postmenopausal women, respectively. Pregnancy
β
(95%CI)
vs nulligravid
= 0.19 (0.08, 0.30);
P
< 0.001 and increasing number of live births (
P
-trend
< 0.001) were positively associated with ESP, while breastfeeding was inversely associated with ESP
β
(95%CI)
vs no breastfeeding
= −0.15 (− 0.29, − 0.01);
P
= 0.036. A positive family history of breast cancer (FHBC)
β
(95%CI)
vs no FHBC
= 0.14 (0.02–0.26);
P
= 0.02, being overweight or obese
β
(95%CI)
vs normal weight
= 0.18 (0.06–0.30);
P
= 0.004 and 0.32 (0.21–0.44);
P
< 0.001, respectively, and Black race
β
(95%CI)
vs White
= 0.12 (− 0.005, 0.25);
P
= 0.06 were positively associated with ESP.
Conclusion
Our findings revealed that cumulative exposure to etiological factors over the lifespan impacts normal breast tissue composition metrics, individually or jointly, to alter their dynamic equilibrium, with potential implications for breast cancer susceptibility and tumor etiologic heterogeneity.
Validation of risk prediction models in independent data provides a more rigorous assessment of model performance than internal assessment, for example, done by cross‐validation in the data used for ...model development. However, several differences between the populations that gave rise to the training and the validation data can lead to seemingly poor performance of a risk model. In this paper we formalize the notions of “similarity” or “relatedness” of the training and validation data, and define reproducibility and transportability. We address the impact of different distributions of model predictors and differences in verifying the disease status or outcome on measures of calibration, accuracy and discrimination of a model. When individual level information from both the training and validation data sets is available, we propose and study weighted versions of the validation metrics that adjust for differences in the risk factor distributions and in outcome verification between the training and validation data to provide a more comprehensive assessment of model performance. We provide conditions on the risk model and the populations that gave rise to the training and validation data that ensure a model's reproducibility or transportability, and show how to check these conditions using weighted and unweighted performance measures. We illustrate the method by developing and validating a model that predicts the risk of developing prostate cancer using data from two large prostate cancer screening trials.
Elevated mammographic breast density is a strong breast cancer risk factor with poorly understood etiology. Increased deposition of collagen, one of the main fibrous proteins present in breast ...stroma, has been associated with increased mammographic density. Collagen fiber architecture has been linked to poor outcomes in breast cancer. However, relationships of quantitative collagen fiber features assessed in diagnostic biopsies with mammographic density and lesion severity are not well-established.
Clinically indicated breast biopsies from 65 in situ or invasive breast cancer cases and 73 frequency matched-controls with a benign biopsy result were used to measure collagen fiber features (length, straightness, width, alignment, orientation and density (fibers/µm
)) using second harmonic generation microscopy in up to three regions of interest (ROIs) per biopsy: normal, benign breast disease, and cancer. Local and global mammographic density volumes were quantified in the ipsilateral breast in pre-biopsy full-field digital mammograms. Associations of fibrillar collagen features with mammographic density and severity of biopsy diagnosis were evaluated using generalized estimating equation models with an independent correlation structure to account for multiple ROIs within each biopsy section.
Collagen fiber density was positively associated with the proportion of stroma on the biopsy slide (p < 0.001) and with local percent mammographic density volume at both the biopsy target (p = 0.035) and within a 2 mm perilesional ring (p = 0.02), but not with global mammographic density measures. As severity of the breast biopsy diagnosis increased at the ROI level, collagen fibers tended to be less dense, shorter, straighter, thinner, and more aligned with one another (p < 0.05).
Collagen fiber density was positively associated with local, but not global, mammographic density, suggesting that collagen microarchitecture may not translate into macroscopic mammographic features. However, collagen fiber features may be markers of cancer risk and/or progression among women referred for biopsy based on abnormal breast imaging.
Abstract
Treatment of screen-detected anal high-grade squamous intraepithelial lesions has been shown to effectively reduce the incidence of invasive anal cancer in people with HIV. We provide ...population-based estimates of cumulative incidence of anal cancer by risk group and age at HIV or AIDS diagnosis. The 0- to 10-year cumulative incidence of anal cancer for men who have sex with men and are younger than 30 years of age at HIV diagnosis was 0.17% (95% confidence interval CI = 0.13% to 0.20%) compared with 0.04% (95% CI = 0.02% to 0.06%) in other men and 0.03% (95% CI = 0.01% to 0.04%) in women. For men who have sex with men and have a diagnosis of AIDS and are younger than 30 years of age, the 0- to 10-year cumulative incidence was 0.35% (95% CI = 0.28% to 0.41%). Among people with HIV, men who have sex with men are at the greatest risk of anal cancer, and those with a diagnosis of AIDS had higher risk than those without AIDS. These estimates may inform recommendations for priority populations that could benefit most from anal cancer screening and treatment.
Patients with multiple myeloma are at an increased risk of venous thromboembolism and arterial thrombosis. We assessed the impact of venous and arterial thrombosis on survival in a population-based ...study of 9,399 multiple myeloma patients diagnosed in Sweden from 1987 to 2005. We found multiple myeloma patients with venous thromboembolism to have a higher mortality at 1-, 5-, and 10-years of follow up compared with those without, with hazard ratios of 2.9 (95% confidence interval (CI) 2.4-3.5), 1.6 (95% CI: 1.5-1.8), and 1.6 (95% CI: 1.4-1.7), respectively. There was an increase in risk of death among multiple myeloma patients with arterial thrombosis, with hazard ratios of 3.4 (95% CI: 3.0-3.8), 2.2 (95% CI: 2.0-2.3), and 2.1 (95% CI: 1.9-2.1), respectively. In landmark analyses at six months, early arterial but not venous thromboembolism was associated with a higher risk of death. Thus, in contrast to prior smaller studies, we found the development of thrombosis to be associated with significantly poorer survival. The prevention of thrombosis in multiple myeloma is an important goal in the management of these patients.
PDF
