The unique risk factor profile of triple negative breast cancer: a comprehensive meta-analysis.

BACKGROUND: Triple-negative breast cancer (TNBC) has a poor prognosis compared to other breast cancer subtypes. This systematic review and meta-analysis examines whether known risk factors for breast cancer are also associated with TNBC in adult females. METHODS: EMBASE, Medline, SCOPUS, and grey literature were queried with no limit on the date or language of publication. The exposures of interest included parity, breastfeeding, duration of breastfeeding, age at menarche, age at first live birth, oral contraceptive (OC) use, duration of OC use, use of menopausal hormone therapy (MHT), family history, body mass index (BMI), alcohol use, smoking and breast density. The main outcome of interest was TNBC. Study quality was determined using the Newcastle-Ottawa scale for case control studies and cohort studies. We estimated weighted odds ratios from random effects models to study the exposure-outcome associations. Protocol was registered under the number: PROSPERO 2021 CRD42021254594. RESULTS: Thirty-three studies were included. Family history, longer duration of oral contraceptive use, and higher breast density were significantly associated with increased risk for TNBC, whereas, later age at menarche, later age at first birth and breastfeeding were protective against TNBC. Parity, MHT, alcohol, smoking, and BMI were not significantly associated with TNBC overall, but higher parity was associated with higher risk among Black women. CONCLUSION: Our findings highlight that TNBC has a distinct risk-factor profile compared to overall breast cancer. This can be the foundational work in identification of actionable TNBC risk factors to improve prevention and early detection of these poor prognosis breast tumors.

Protocol for a pragmatic stepped wedge cluster randomized clinical trial testing behavioral economic implementation strategies to increase supplemental breast MRI screening among patients with extremely dense breasts.

BACKGROUND: Increased breast density augments breast cancer risk and reduces mammography sensitivity. Supplemental breast MRI screening can significantly increase cancer detection among women with dense breasts. However, few women undergo this exam, and screening is consistently lower among racially minoritized populations. Implementation strategies informed by behavioral economics ("nudges") can promote evidence-based practices by improving clinician decision-making under conditions of uncertainty. Nudges directed toward clinicians and patients may facilitate the implementation of supplemental breast MRI. METHODS: Approximately 1600 patients identified as having extremely dense breasts after non-actionable mammograms, along with about 1100 clinicians involved with their care at 32 primary care or OB/GYN clinics across a racially diverse academically based health system, will be enrolled. A 2 × 2 randomized pragmatic trial will test nudges to patients, clinicians, both, or neither to promote supplemental breast MRI screening. Before implementation, rapid cycle approaches informed by clinician and patient experiences and behavioral economics and health equity frameworks guided nudge design. Clinicians will be clustered into clinic groups based on existing administrative departments and care patterns, and these clinic groups will be randomized to have the nudge activated at different times per a stepped wedge design. Clinicians will receive nudges integrated into the routine mammographic report or sent through electronic health record (EHR) in-basket messaging once their clinic group (i.e., wedge) is randomized to receive the intervention. Independently, patients will be randomized to receive text message nudges or not. The primary outcome will be defined as ordering or scheduling supplemental breast MRI. Secondary outcomes include MRI completion, cancer detection rates, and false-positive rates. Patient sociodemographic information and clinic-level variables will be examined as moderators of nudge effectiveness. Qualitative interviews conducted at the trial's conclusion will examine barriers and facilitators to implementation. DISCUSSION: This study will add to the growing literature on the effectiveness of behavioral economics-informed implementation strategies to promote evidence-based interventions. The design will facilitate testing the relative effects of nudges to patients and clinicians and the effects of moderators of nudge effectiveness, including key indicators of health disparities. The results may inform the introduction of low-cost, scalable implementation strategies to promote early breast cancer detection. TRIAL REGISTRATION: ClinicalTrials.gov NCT05787249. Registered on March 28, 2023.

Genome-Wide Association Study of Breast Density among Women of African Ancestry.

Breast density, the amount of fibroglandular versus fatty tissue in the breast, is a strong breast cancer risk factor. Understanding genetic factors associated with breast density may help in clarifying mechanisms by which breast density increases cancer risk. To date, 50 genetic loci have been associated with breast density, however, these studies were performed among predominantly European ancestry populations. We utilized a cohort of women aged 40-85 years who underwent screening mammography and had genetic information available from the Penn Medicine BioBank to conduct a Genome-Wide Association Study (GWAS) of breast density among 1323 women of African ancestry. For each mammogram, the publicly available "LIBRA" software was used to quantify dense area and area percent density. We identified 34 significant loci associated with dense area and area percent density, with the strongest signals in GACAT3, CTNNA3, HSD17B6, UGDH, TAAR8, ARHGAP10, BOD1L2, and NR3C2. There was significant overlap between previously identified breast cancer SNPs and SNPs identified as associated with breast density. Our results highlight the importance of breast density GWAS among diverse populations, including African ancestry populations. They may provide novel insights into genetic factors associated with breast density and help in elucidating mechanisms by which density increases breast cancer risk.

Factors associated with shorter-interval cervical cancer screening for young women in three United States healthcare systems.

Frequently changing cervical cancer screening guidelines over the past two decades have been inconsistently adopted in the United States. Current guidelines set the recommended screening interval to three years for average-risk women aged 21-29 years. Few studies have evaluated how patient and provider factors are associated with implementation of cervical cancer screening intervals among younger women. This study evaluated multilevel factors associated with screening interval length among 69,939 women aged 21-29 years with an initial negative Pap screen between 2010 and 2015 across three large health systems in the U.S. Shorter-interval screening was defined as a second screening Pap within 2.5 years of an initial negative Pap. Mixed-effects logistic regression was performed for each site to identify provider and patient characteristics associated with shorter-interval screening. The odds of shorter-interval screening decreased over the study period across all sites, though the proportion of patients screened within 2.5 years remained between 7.5% and 20.7% across sites in 2014-2015. Patient factors including insurance, race/ethnicity, and pregnancy were associated with shorter-interval screening, though the patterns differed across sites. At one site, the variation in shorter-interval screening explained by the provider was 10.6%, whereas at the other two sites, the provider accounted for < 2% of the variation in shorter-interval screening. Our results highlight the heterogeneity in factors driving cervical cancer screening interval across health systems and point to the need for tailored approaches targeted to both providers and patients to improve guideline-concordant screening.

Breast density quantitative measures and breast cancer risk among screened Black women.

Mammographic density is a strong predictor of breast cancer but only slightly increased the discriminatory ability of existing risk prediction models in previous studies with limited racial diversity. We assessed discrimination and calibration of models consisting of the Breast Cancer Risk Assessment Tool (BCRAT), Breast Imaging-Reporting and Data System density and quantitative density measures. Patients were followed up from the date of first screening mammogram until invasive breast cancer diagnosis or 5-year follow-up. Areas under the curve for White women stayed consistently around 0.59 for all models, whereas the area under the curve increased slightly from 0.60 to 0.62 when adding dense area and area percent density to the BCRAT model for Black women. All women saw underprediction in all models, with Black women having less underprediction. Adding quantitative density to the BCRAT did not statistically significantly improve prediction for White or Black women. Future studies should evaluate whether volumetric breast density improves risk prediction.

Changes in mammographic density and risk of breast cancer among a diverse cohort of women undergoing mammography screening.

PURPOSE: Mammographic density (MD) is a strong breast cancer risk factor. MD may change over time, with potential implications for breast cancer risk. Few studies have assessed associations between MD change and breast cancer in racially diverse populations. We investigated the relationships between MD and MD change over time and breast cancer risk in a large, diverse screening cohort. MATERIALS AND METHODS: We retrospectively analyzed data from 8462 women who underwent ≥ 2 screening mammograms from Sept. 2010 to Jan. 2015 (N = 20,766 exams); 185 breast cancers were diagnosed 1-7 years after screening. Breast percent density (PD) and dense area (DA) were estimated from raw digital mammograms (Hologic Inc.) using LIBRA (v1.0.4). For each MD measure, we modeled breast density change between two sequential visits as a function of demographic and risk covariates. We used Cox regression to examine whether varying degrees of breast density change were associated with breast cancer risk, accounting for multiple exams per woman. RESULTS: PD at any screen was significantly associated with breast cancer risk (hazard ratio (HR) for PD = 1.03 (95% CI [1.01, 1.05], p < 0.0005), but neither change in breast density nor more extreme than expected changes in breast density were associated with breast cancer risk. We found no evidence of differences in density change or breast cancer risk due to density change by race. Results using DA were essentially identical. CONCLUSIONS: Using a large racially diverse cohort, we found no evidence of association between short-term change in MD and risk of breast cancer, suggesting that short-term MD change is not a strong predictor for risk.

External Validation of a Mammography-Derived AI-Based Risk Model in a U.S. Breast Cancer Screening Cohort of White and Black Women.

Despite the demonstrated potential of artificial intelligence (AI) in breast cancer risk assessment for personalizing screening recommendations, further validation is required regarding AI model bias and generalizability. We performed external validation on a U.S. screening cohort of a mammography-derived AI breast cancer risk model originally developed for European screening cohorts. We retrospectively identified 176 breast cancers with exams 3 months to 2 years prior to cancer diagnosis and a random sample of 4963 controls from women with at least one-year negative follow-up. A risk score for each woman was calculated via the AI risk model. Age-adjusted areas under the ROC curves (AUCs) were estimated for the entire cohort and separately for White and Black women. The Gail 5-year risk model was also evaluated for comparison. The overall AUC was 0.68 (95% CIs 0.64−0.72) for all women, 0.67 (0.61−0.72) for White women, and 0.70 (0.65−0.76) for Black women. The AI risk model significantly outperformed the Gail risk model for all women p < 0.01 and for Black women p < 0.01, but not for White women p = 0.38. The performance of the mammography-derived AI risk model was comparable to previously reported European validation results; non-significantly different when comparing White and Black women; and overall, significantly higher than that of the Gail model.

Effect of core stabilization exercises in addition to conventional therapy in improving trunk mobility, function, ambulation and quality of life in stroke patients: a randomized controlled trial.

BACKGROUND: Stroke is a major cause of disability with mainly affecting trunk mobility and function. The purpose of this study is to determine the effectiveness of core stabilization exercises versus conventional therapy on trunk mobility, function, ambulation, and quality of life of stroke patients. DESIGN: Assessor blinded randomized control trial. SETTING: Ibrahim polyclinic-Shadman, Ch Muhammad Akram teaching hospital-Raiwind, Rasheed hospital-Defence. SUBJECTS: Chronic ischemic stroke patients. INTERVENTION: Control group (n = 21) underwent conventional treatment for stroke for 40 min/ day, 5 times/ week for 8 weeks. Experimental group (n = 20) received core stability training for additional 15 min along with conventional treatment. MAIN MEASURES: Main outcome measures were Trunk impairment scale (TIS), functional ambulation category (FAC), stroke specific quality of life (SSQOL) and trunk range of motion (ROM). RESULTS: The differences between the control group and experimental group post-treatment were statistically significant for trunk impairment, functional ambulation, quality of life, and frontal plane trunk motion (p-value < 0.05) with higher mean values for core stabilization training. The frontal plane trunk mobility and rotation showed non-significant differences post-treatment (p-value > 0.05). CONCLUSION: This study concluded that core stabilization training is better as compared to the conventional physical therapy treatment for improving trunk impairments, functional ambulation and quality of life among patients of stroke. The core stabilization training is also more effective in improving trunk mobility in sagittal plane. This study is registered in Iranian Registry of Clinical Trials IRCT20210614051578N1 and was approved by the local research ethics committee of Riphah International University.

Relationship of established risk factors with breast cancer subtypes.

BACKGROUND: Breast 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. METHODS: Women 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. RESULTS: The 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. CONCLUSIONS: These 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.

Risk factors for breast cancer subtypes among Black women undergoing screening mammography.

PURPOSE: Black women are more likely than non-Hispanic White women to be diagnosed with triple negative breast cancer (TNBC), an aggressive subtype with limited treatment options. The study objective was to evaluate the associations of known breast cancer risk factors, including breast density, with TNBC among Black women. METHODS: This study included Black women who underwent screening mammography between the ages of 40-84 years at a University of Pennsylvania Health System between 2010 and 2015. Cox proportional hazard models using multiple imputation with chained equations were used to estimate hazard ratios and 95% confidence intervals for risk factors for ER/PR+/HER2- and TNBC. RESULTS: Among 25,013 Black women, there were 330 incident breast cancers (1.3%) during a mean follow-up of 5.8 years; 218 (66.1%) ER/PR+ HER- and 61 (18.1%) TNBC. Having dense breasts (heterogeneously dense or extremely dense) vs. non-dense breasts (almost entirely fatty or scattered areas of fibroglandular density) increased risk of ER/PR+/HER2- breast cancer almost 80% (HR 1.79, 95% CI 1.32-2.43) and TNBC more than twofold (HR 2.53, 1.45-4.44). Older age was associated with an increased risk for ER/PR+/HER2- (HR 1.04, 1.03-1.06) and TNBC (HR 1.03, 1.00-1.05). Having a BMI of > 30 kg/m2 was associated with an increased risk (HR 2.77, 1.05-7.30) for TNBC and an increased risk of ERPR+/HER2- breast cancer in postmenopausal but not pre-menopausal women (p-interaction = 0.016). CONCLUSION: Our results suggest that breast density and obesity are strong risk factors for TNBC among Black women. Understanding breast cancer subtype specific risk factors among Black women can help improve risk assessment.

Risk factors for an advanced breast cancer diagnosis within 2 years of a negative mammogram.

BACKGROUND: Identifying women at risk for advanced interval cancers would allow better targeting of mammography and supplemental screening. The authors assessed risk factors for advanced breast cancer within 2 years of a negative mammogram. METHODS: The authors included 293,520 negative mammograms performed from 2006 to 2015 among 74,736 women. Breast cancers were defined as advanced if they were >2 cm, were >1 cm and triple-negative or human epidermal growth factor receptor 2-positive, had positive lymph nodes, or were metastatic. Cox proportional hazards modeling was used to evaluate associations of age, breast density, menopause, mammogram type, prior breast biopsy, body mass index (BMI), and a family history of breast cancer with a cancer diagnosis within 2 years of a negative mammogram. Models were stratified by year since a negative mammogram. RESULTS: Among 1345 breast cancers, 357 were advanced (26.5%), and 988 (73.5%) were at an early stage. Breast density, prior biopsy, and family history were associated with an increased risk of both advanced and early-stage cancers. Overweight and obese women had a 40% higher risk of early-stage cancer only in year 2 (overweight hazard ratio [HR], 1.41; 95% confidence interval [CI], 1.19-1.67; P < .001; obese HR, 1.41; 95% CI, 1.17-1.70; P < .001). Obese women had a 90% increased risk of advanced cancer in year 1 (HR, 1.90; 95% CI, 1.14-3.18; P = .014), and both overweight and obese women had a 40% or greater increased risk in year 2 (overweight HR, 1.55; 95% CI, 1.14-2.07; P = .005; obese HR, 1.42; 95% CI, 1.00-2.01; P = .051). CONCLUSIONS: A higher BMI was associated with an advanced breast cancer diagnosis within 2 years of a negative mammogram. These results have important implications for risk assessment, screening intervals, and use of supplemental screening.

Upper extremity musculoskeletal disorders and exposure to Ergonomic risk factors among handicraft workers.

OBJECTIVE: To determine the association of Upper extremity musculoskeletal disorders and Exposure to Ergonomic risk factors among handicraft workers. METHODS: This cross-sectional survey was conducted in a 12 weeks' duration i.e. from November 2018 till January 2019. Nordic musculoskeletal questionnaire was used to determine the frequency of upper limb musculoskeletal disorders. Postural analysis was done using Rapid Upper Limb Assessment (RULA). Data was collected from 100 Handicraft workers and the type of work included Art work (n=18), Ada Work (n=7), botanical arrangement (n=11), Textile, fashion designing and stitching (n=38), Fine arts (n=20), embroidery and knitting (n=6). RESULTS: The frequency distribution of Rapid upper limb assessment (RULA) score for exposure to risk factors showed that 47 participants were at a high risk and required implementation of change. Most of the participants (n=35) reported pain in neck and shoulder (n=29). The chi square test for association between pain in upper extremity and exposure to risk factors showed that only wrist pain had statistically significant association with overall RULA score (p-value<0.05). CONCLUSION: The study concluded that neck and shoulder are more frequently affected among handicraft workers. The frequency of workers who were at high ergonomic risk and required implementation of change in working conditions was high.

Validation of Breast Cancer Risk Models by Race/Ethnicity, Family History and Molecular Subtypes.

(1) Background: The purpose of this study is to compare the performance of four breast cancer risk prediction models by race, molecular subtype, family history of breast cancer, age, and BMI. (2) Methods: Using a cohort of women aged 40-84 without prior history of breast cancer who underwent screening mammography from 2006 to 2015, we generated breast cancer risk estimates using the Breast Cancer Risk Assessment tool (BCRAT), BRCAPRO, Breast Cancer Surveillance Consortium (BCSC) and combined BRCAPRO+BCRAT models. Model calibration and discrimination were compared using observed-to-expected ratios (O/E) and the area under the receiver operator curve (AUC) among patients with at least five years of follow-up. (3) Results: We observed comparable discrimination and calibration across models. There was no significant difference in model performance between Black and White women. Model discrimination was poorer for HER2+ and triple-negative subtypes compared with ER/PR+HER2-. The BRCAPRO+BCRAT model displayed improved calibration and discrimination compared to BRCAPRO among women with a family history of breast cancer. Across models, discriminatory accuracy was greater among obese than non-obese women. When defining high risk as a 5-year risk of 1.67% or greater, models demonstrated discordance in 2.9% to 19.7% of patients. (4) Conclusions: Our results can inform the implementation of risk assessment and risk-based screening among women undergoing screening mammography.

Frequency of neck and shoulder pain and use of adjustable computer workstation among bankers.

BACKGROUND & OBJECTIVE: Neck and shoulder are the most susceptible areas for developing musculoskeletal symptoms among computer users. The modifiable risk factors for these work related musculoskeletal disorders include physical office environment and psychosocial work related factors. Computer workstation layout had been shown to be an important physical aspect of work environment that influences the upper quadrant symptoms. Our objective was to find the frequency of neck and shoulder pain and use of adjustable computer workstation among bankers of Islamabad/Rawalpindi/Multan. METHODS: A cross sectional study was conducted and 120 participants were questioned. Purposive sampling technique was used in this study. Maastricht Upper Extremity Questionnaire (MUEQ) was remodeled and important questions were extracted from its detailed version. The tool was then validated by taking expert opinion. Frequencies and percentages were calculated for categorical variables. RESULTS: Pain in the neck during working hours was experienced by 71.67% of the respondents and 48.33% of the participants had experienced shoulder pain during working hours. Adjustable keyboards were used by 16.67% of respondents. Back care material was used by 40% bankers. Adjustable chairs were used by 95.83% of the participants. Only 3% of the bankers did not have chairs with adjustable heights. Chairs with adjustable armrests were used by 25% bankers. CONCLUSION: Neck and shoulder pain are common occurrences among bankers. Most of the components of workstations of bankers were adjustable but some of them still need attention.