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BACKGROUND: Breast cancer constitutes a significant public health issue in most resource-constrained nations due to its high morbidity and mortality rates. There is a paucity of knowledge of the molecular subtypes of breast cancer in Nigeria primarily due to the lack of immunohistochemistry. This study aims to identify the molecular subtypes of histologically confirmed breast cancer cases at the University of Benin Teaching Hospital, Benin City, Nigeria, using ER, PR and HER2/neu as immunohistochemical biomarkers. MATERIALS AND METHOD: Breast cancer specimens received in the Histopathology department of the University of Benin Teaching Hospital between 2019 and 2021 were used for this study. Representative sections of paraffin-embedded blocks were recut for histological typing, tumour grading, and immunohistochemistry. RESULTS: A total of 330 cases were evaluated in this study. The average age was 49 years, with a M:F of 40.3:1. The most frequent histological type was invasive breast cancer (92.1%). Two hundred and forty-two (73.3%) cases were categorized as grade II tumours. The steroid hormone receptor positivity was 39.4%. Oestrogen and Progesterone receptor positivity were 39.4% and 22.1%, respectively. HER2/neu was positive in 16.4% of the cases. Triple-negative breast cancer (TNBC) was the most common molecular subtype, accounting for 49.4% of cases. Luminal A, Luminal B, and HER2/neu enriched subtypes were each found in 34.2%, 5.2%, and 11.2% of cases, respectively. CONCLUSION: Triple-negative breast cancers predominated among the study population and were more common in high-grade tumours with unfavourable histological types and among women who were younger than their Caucasian counterparts.

CONTEXTE: Le cancer du sein constitue un problème de santé publique majeur dans la plupart des nations aux ressources limitées en raison de son taux élevé de morbidité et de mortalité. Il existe une pénurie de connaissances sur les sous-types moléculaires du cancer du sein au Nigeria, principalement en raison du manque d'immunohistochimie. Cette étude vise à identifier les sous-types moléculaires des cas de cancer du sein confirmés histologiquement à l'Hôpital Universitaire de Benin, Benin City, Nigeria, en utilisant les biomarqueurs immunohistochimiques ER, PR et HER2/neu. MATÉRIAUX ET MÉTHODE: Les échantillons de cancer du sein reçus dans le département d'histopathologie de l'Hôpital Universitaire de Benin entre 2019 et 2021 ont été utilisés pour cette étude. Des sections représentatives de blocs inclus en paraffine ont été recoupées pour le typage histologique, le classement des tumeurs et l'immunohistochimie. RÉSULTATS: Un total de 330 cas ont été évalués dans cette étude. L'âge moyen était de 49 ans, avec un rapport H de 40,3:1. Le type histologique le plus fréquent était le cancer du sein invasif (92,1 %). Deux cent quarante-deux (73,3 %) cas ont été classés comme des tumeurs de grade II. La positivité des récepteurs hormonaux stéroïdiens était de 39,4 %. Les récepteurs des œstrogènes et de la progestérone étaient positifs dans 39,4 % et 22,1 % des cas, respectivement. HER2/neu était positif dans 16,4 % des cas. Le cancer du sein triple négatif (CSTN) était le sous-type moléculaire le plus courant, représentant 49,4 % des cas. Les sous-types Luminal A, Luminal B et enrichi en HER2/neu ont été trouvés dans 34,2 %, 5,2 % et 11,2 % des cas, respectivement. CONCLUSION: Les cancers du sein triple négatif prédominaient parmi la population étudiée et étaient plus fréquents dans les tumeurs de haut grade avec des types histologiques défavorables et chez les femmes plus jeunes que leurs homologues caucasiennes.

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BACKGROUND: Elevated mammographic density (MD) for a woman's age and body mass index (BMI) is an established breast cancer risk factor. The relationship of parity, age at first birth, and breastfeeding with MD is less clear. We examined the associations of these factors with MD within the International Consortium of Mammographic Density (ICMD). METHODS: ICMD is a consortium of 27 studies with pooled individual-level epidemiological and MD data from 11,755 women without breast cancer aged 35-85 years from 22 countries, capturing 40 country-& ethnicity-specific population groups. MD was measured using the area-based tool Cumulus. Meta-analyses across population groups and pooled analyses were used to examine linear regression associations of square-root (√) transformed MD measures (percent MD (PMD), dense area (DA), and non-dense area (NDA)) with parity, age at first birth, ever/never breastfed and lifetime breastfeeding duration. Models were adjusted for age at mammogram, age at menarche, BMI, menopausal status, use of hormone replacement therapy, calibration method, mammogram view and reader, and parity and age at first birth when not the association of interest. RESULTS: Among 10,988 women included in these analyses, 90.1% (n = 9,895) were parous, of whom 13% (n = 1,286) had ≥ five births. The mean age at first birth was 24.3 years (Standard deviation = 5.1). Increasing parity (per birth) was inversely associated with √PMD (ß: - 0.05, 95% confidence interval (CI): - 0.07, - 0.03) and √DA (ß: - 0.08, 95% CI: - 0.12, - 0.05) with this trend evident until at least nine births. Women who were older at first birth (per five-year increase) had higher √PMD (ß:0.06, 95% CI:0.03, 0.10) and √DA (ß:0.06, 95% CI:0.02, 0.10), and lower √NDA (ß: - 0.06, 95% CI: - 0.11, - 0.01). In stratified analyses, this association was only evident in women who were post-menopausal at MD assessment. Among parous women, no associations were found between ever/never breastfed or lifetime breastfeeding duration (per six-month increase) and √MD. CONCLUSIONS: Associations with higher parity and older age at first birth with √MD were consistent with the direction of their respective associations with breast cancer risk. Further research is needed to understand reproductive factor-related differences in the composition of breast tissue and their associations with breast cancer risk.

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BACKGROUND: Despite known benefits of physical activity in reducing breast cancer risk, its impact on mammographic characteristics remain unclear and understudied. This study aimed to investigate associations between pre-diagnostic physical activity and mammographic features at breast cancer diagnosis, specifically mammographic breast density (MBD) and mammographic tumor appearance (MA), as well as mode of cancer detection (MoD). METHODS: Physical activity levels from study baseline (1991-1996) and mammographic information from the time of invasive breast cancer diagnosis (1991-2014) of 1116 women enrolled in the Malmö Diet and Cancer Study cohort were used. Duration and intensity of physical activity were assessed according to metabolic equivalent of task hours (MET-h) per week, or World Health Organization (WHO) guideline recommendations. MBD was dichotomized into low-moderate or high, MA into spiculated or non-spiculated tumors, and MoD into clinical or screening detection. Associations were investigated through logistic regression analyses providing odds ratios (OR) with 95% confidence intervals (CI) in crude and multivariable-adjusted models. RESULTS: In total, 32% of participants had high MBD at diagnosis, 37% had non-spiculated MA and 50% had clinical MoD. Overall, no association between physical activity and MBD was found with increasing MET-h/week or when comparing women who exceeded WHO guidelines to those subceeding recommendations (ORadj 1.24, 95% CI 0.78-1.98). Likewise, no differences in MA or MoD were observed across categories of physical activity. CONCLUSIONS: No associations were observed between pre-diagnostic physical activity and MBD, MA, or MoD at breast cancer diagnosis. While physical activity is an established breast cancer prevention strategy, it does not appear to modify mammographic characteristics or screening detection.

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Objective: To understand the current and integrated disease burden and economic burden caused by breast cancer in females in China. Methods: Based on six updated data sources, including the series of Chinese Cancer Registry Annual Report, China Death Cause Surveillance Datasets, China Health Statistical Yearbook, GLOBOCAN, Cancer Incidence in Five Continents, Global Burden of Disease Study (GBD), the information about incidence, mortality and disability adjusted life years (DALY) of breast cancer were extracted for the analysis on the current incidence and time trend of breast cancer and predicted disease burden of breast cancer in females in China. Software Joinpoint was used for time trend analysis. The data of economic burden were systematically updated and analyzed by literature review. Results: 1) GLOBOCAN 2022 estimated that the age-standardized incidence rate (ASIR) age-standardized mortality rate (ASMR) and one- year prevalence rate of breast cancer in females were 33.0/100 000, 6.1/100 000 and 40.1/100 000, respectively, in China in 2022. According to Chinese Cancer Registry Annual Report, the ASIR and ASMR were 28.4/100 000 and 5.8/100 000, respectively, in 2018. The China Death Cause Surveillance Datasets showed that the ASMR was 4.5/100 000 in 2021, and the urban to rural area mortality ratio was 1.2∶1. GBD reported that the DALYs of breast cancer were 2.921 million in China in 2021, accounting for 14.4% of the global total. 2) Chinese Cancer Registry Annual Report data showed that the ASIR and ASMR of breast cancer decreased by 2.1% and 11.4%, respectively, in China from 2009 to 2018, while increased by 43.9% and 8.2% in rural area, respectively. The Joinpoint analysis showed that the average annual percentage change (AAPC) of ASIR and ASMR in China were -0.2% (P>0.05) and -1.6% (P<0.05). The AAPC of ASIR and ASMR in rural area were 3.9% (P<0.05) and 0.6% (P>0.05), and -0.3% (P>0.05) and -1.2% (P<0.05) in urban area, respectively. China Health Statistical Yearbook data showed that the urban ASMR decreased by 12.3% from 2014 to 2021 with AAPC of -2.6% (P<0.05). 3) The GLOBOCAN 2022 predicted that, the breast cancer case count and death count in China would be 387 776 and 111 133 by 2050, an increase of 8.6% and 48.2%, respectively, compared with 2022, the increases would be more obvious in people over 65 years old, an increase of 80.8% and 124.9%, respectively. 4) Thirteen individual- based studies reported that the median medical expenditure per patient (M=21 000 to 39 000 Yuan) and length of hospital stay (M=11.0 to 30.5 days) for breast cancer treatment decreased from 2010 to 2019, while the average medical expenditure per visit (M=9 000 to 23 000 Yuan) showed an upward trend. There was only one national-level analysis, which showed that the treatment cost of breast cancer was 25.24 billion Yuan in China in 2018, accounting for 6.4% of the total cancer treatment cost. Conclusions: According to the above updated multi-source data, the incidence and mortality of female breast cancer in China were stable in the past ten years, but the increasing trend in rural area should be noted. The direct medical expenditure of breast cancer treatment per case might decrease, but the population-level economic burden would remain heavy due to population aging.

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PURPOSE: A breast cancer (BC) diagnosis may negatively affect health-related quality of life (HRQoL). However, there are few comparisons of HRQoL at several time points for women with BC, and particular when subdivided into invasive and in situ tumors. The purpose of this study was to investigate various aspects of HRQoL in women recently diagnosed with invasive BC or ductal carcinoma in situ (in situ) compared to age-matched BC free controls in a population-wide sample recruited through the Cancer Registry of Norway. METHODS: This cross-sectional study utilized HRQoL data collected in 2020-2022 from a digital survey including 4117 cases (3867 women with invasive BC and 430 with in situ) and 2911 controls. HRQoL was assessed ≥ 21 days after diagnosis, using EORTC QLQ-C30. This includes scores assessing global quality of life (gHRQoL) and HRQoL functions and symptoms. Multivariable regression analyses were used to compare HRQoL between cases and controls and to identify factors associated with gHRQoL and fatigue. Additionally, HRQoL 14 months after diagnosis was analyzed in 1989 of the included cases and in 1212 of the controls. Score differences of ≥ 10 points were considered clinically relevant and thus presented in the results. RESULTS: Invasive BC cases had lower gHRQoL, role- and social functioning in addition to more fatigue than controls. In situ cases had lower role-and social functioning than controls. Invasive BC cases scored worse than in situ on all domains, but the differences were not considered clinically relevant. Physical activity was associated with better gHRQoL and less fatigue in invasive BC, in situ and controls. Both invasive BC and in situ cases improved their role- and social functioning scores from diagnosis to 14 months follow-up, however no improvement was seen for fatigue. CONCLUSION: Women with invasive BC and in situ reported lower role- and social functioning scores than controls right after diagnosis with improvements 14 months after diagnosis. Physical activity was associated with better gHRQoL and less fatigue and should, whenever possible, play a key role in the care for BC patients.

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PURPOSE: Women with breast cancer (BC) are at high risk of developing cardiovascular disease (CVD). We examined adherence to CVD medications and their association with major CVD events over 14 years of follow-up in the Pathways Heart Study, a prospective study of 4,776 stage I-III BC patients diagnosed from 2005-2013. METHODS: Eligibility included being alive 6 months post-BC diagnosis, with dyslipidemia, hypertension, or diabetes at diagnosis along with ≥1 prior outpatient order or dispensing for a statin, anti-hypertensive, or diabetes medication, respectively, in the 30 months prior. Medication adherence was measured from pharmacy data to calculate cumulative average adherence (CAA). Incident heart failure (HF), ischemic heart disease (IHD), and stroke were determined via validated diagnosis and procedure codes. Working marginal structural models (MSM) fitted with inverse probability weighting evaluated the effect of adherence regimens on the hazards for each CVD event, while controlling for baseline and time-varying confounders. MSM parameterizations included: 1) CAA<100% versus CAA = 100% (ref), 2) CAA<80% versus CAA≥80% (ref) and 3) CAA<80% versus 80%≤CAA<100% versus CAA = 100%. RESULTS: Poor statin adherence (CAA<80%) was associated with higher risk of composite CVD (HR = 2.54; 95% CI: 1.09, 5.94) versus CAA≥80%. Poor statin adherence was also associated with a higher risk of stroke (HR = 8.13; 95% CI: 2.03, 32.51) but not risk of IHD and HF. Further, compared with perfect adherence (CAA = 100%), good adherence (80%≤CAA<100%) was associated with lower risk (HR = 0.35; 95% CI: 0.13, 0.92) while poor adherence (CAA<80%) was associated with higher risk of composite CVD (HR = 2.45; 95% CI: 1.05, 5.70). Levels of adherence to anti-hypertensives and diabetes medications had mixed or null associations with risk of CVD. CONCLUSIONS: Maintaining good adherence (≥80%) to statins after BC treatment is beneficial for cardiovascular health in patients with dyslipidemia. Future studies should determine factors associated with lower adherence to statins and ways to improve adherence.

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BACKGROUND: A few studies have examined the association between different types of dietary fiber as well as their sources and the risk of breast cancer (BC) and the present study aimed to investigate these associations in a case-control study among Iranian women. METHODS: A total of 464 women with pathologically confirmed breast cancer within the past year and 498 age-matched healthy controls were included. Dietary intakes were assessed using a 168-item food frequency questionnaire. The association between dietary soluble, insoluble, total dietary fiber, as well as, fiber from fruits, vegetables, legumes, cereals, and nuts intake with odds of breast cancer was assessed using multivariate logistic regression analysis. RESULTS: Mean total dietary fiber intake of patients with and without cancer were 33.1 ± 15.3 g per day (g/d) and 34.2 ± 16.5 (g/d), respectively. Dietary total fiber (OR = 0.65; 95%CI: 0.47-0.90, Ptrend = 0.01), insoluble fiber (OR = 0.68; 95%CI: 0.49-0.93, Ptrend = 0.01), fruits' fiber (OR = 0.68; 95%CI: 0.49-0.94, Ptrend = 0.02), and vegetables' fiber (OR = 0.66; 95%CI: 0.48-0.91, Ptrend = 0.01) were significantly associated with reduced likelihood of developing breast cancer in all participants. Furthermore, dietary total and insoluble fiber, as well as, fiber from fruits were significantly associated with lower odds of breast cancer in premenopausal women (P < 0.05). In contrast, cereals' fiber significantly increased the risk of breast cancer by 84% in premenopausal women (OR = 1.84; 95%CI: 1.18-2.86, Ptrend = 0.009). In postmenopausal women, cereals' fiber had a significant inverse association with odds of breast cancer (OR = 0.56; 95%CI: 0.31-1.03, Ptrend = 0.04). Also, fiber from vegetables was significantly associated with a lower risk of breast cancer in postmenopausal women (OR = 0.53; 95%CI: 0.30-0.94, Ptrend = 0.03). CONCLUSION: Dietary fiber intake and more specifically insoluble, fruits', and vegetables' fiber intake might be associated with a reduced breast cancer risk, particularly in premenopausal women. Future prospective investigations are needed to confirm these findings.

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BACKGROUND: Breast cancer (BC) is the most common cancer in women worldwide. Early diagnosis of BC could considerably improve outcomes. Since health literacy could influence preventive behaviors and women's ability to make decisions about breast care, therefore, this study aimed to explore breast cancer literacy in women. METHODS: This qualitative study was conducted in Iran using the directed content analysis. Data were collected through face-to-face interviews with a purposeful sample of women from April 2021 to June 2022 and continued until saturation was reached. Interviews were analyzed using the initial matrix developed based on the European health literacy framework. RESULTS: In all twelve women were interviewed. During data analysis, 612 primary codes grouped into four dimension of health literacy (access, understanding, appraise, and apply) of three health domain (health care, disease prevention, and health promotion). Many believed that it was difficult to access accurate information about BC. They used various sources to obtain information. The participants addressed some facilitators and barriers in understanding the information and for information appraisal they mentioned seeking help from health professionals. Through the acquired cognitive skills, the participants took some steps to apply BC information. Also, having information about BC and the involvement of relatives with cancer were indicated as triggers for decision-making on breast care, while poor financial conditions, not having enough information, fear, shame, and embarrassment, were pointed out as inhibiting factors. CONCLUSIONS: The findings suggest that barriers in access, and understanding of information on breast cancer exist among women. The findings also suggest that women's decision-making and preventive behaviors on breast care are much dependent on social and cultural factors.

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The Breast Cancer UK-Breast Cancer Prevention Conference addressed risk from environmental pollutants and health behaviour-related breast-cancer risk. Epidemiological studies examining individual chemicals and breast cancer risk have produced inconclusive results including endocrine disrupting chemicals (EDCs) Bisphenol A, per- and polyfluorinated alkyl substances as well as aluminium. However, laboratory studies have shown that multiple EDCs, can work together to exhibit effects, even when combined at levels that alone are ineffective. The TEXB-α/ß assay measures total estrogenic load, and studies have provided evidence of a link between multiple-chemical exposures and breast cancer. However, prospective studies using TEXB-α/ß are needed to establish a causative link. There is also a need to assess real-life exposure to environmental-chemical mixtures during pregnancy, and their potential involvement in programming adverse foetal health outcomes in later life. Higher rates of breast cancer have occurred alongside increases in potentially-modifiable risk factors such as obesity. Increasing body-mass index is associated with increased risk of developing postmenopausal breast cancer, but with decreased risk of premenopausal breast cancer. In contrast, lower rates of breast cancer in Asian compared to Western populations have been linked to soya/isoflavone consumption. Risk is decreased by breastfeeding, which is in addition to the decrease in risk observed for each birth and a young first-birth. Risk is lower in those with higher levels of self-reported physical activity. Current evidence suggests breast-cancer survivors should also avoid weight gain, be physically active, and eat a healthy diet for overall health. A broad scientific perspective on breast cancer risk requires focus on both environmental exposure to chemicals and health behaviour-related risk. Research into chemical exposure needs to focus on chemical mixtures and prospective epidemiological studies in order to test the effects on breast cancer risk. Behaviour-related research needs to focus on implementation as well as deeper understanding of the mechanisms of cancer prevention.

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BACKGROUND: Genetic testing for persons with a heightened likelihood of harboring a germline mutation permits early identification and appropriate management. This study aimed to identify the proportion of breast cancer (BC) patients who were offered genetic testing and the prevalence of BRCA mutations among them. Additionally, we assessed the demographic and clinical features of BC patients in the Eastern Region of Saudi Arabia. MATERIALS AND METHODS: Data from 2535 patients with BC were retrieved from the registry between 2017 and 2021. The data were analyzed and presented using univariate and bivariate statistics. Odds ratios and 95% confidence intervals using logistic regression analysis were computed to identify the predictors of BRCA testing. RESULTS: Patients with BC ranged in age from 18 to 103 years, and the mean age was 49.60 ± 12.14 years. BC was detected in men in 29 (1.1%) cases. Among diagnosed patients with BC, a total of 96 (3.7%) patients underwent testing for BRCA gene mutations. Of them, 36 (37.5%) patients had a BRCA gene mutation. The likelihood of undergoing BRCA testing was higher for those who were diagnosed with the condition before the age of 50, patients who were referred from private institutions, and patients with a history of previously diagnosed cancer. The likelihood of conducting BRCA testing was significantly lower among those with distant metastases. CONCLUSION: The proportion of BRCA testing among BC patients was found to be relatively low. The development of a cost-effective, locally developed risk assessment tool that incorporates genetic counseling and testing for those with a familial predisposition to BC is imperative.

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OBJECTIVE: To provide a comprehensive assessment of various fractionation schemes in radiation therapy for breast cancer, with a focus on side effects, cosmesis, quality of life, risks of recurrence, and survival outcomes. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Ovid MEDLINE, Embase, and Cochrane Central Register of Controlled Trials (from inception to 23 October 2023). STUDY SELECTION: Included studies were randomised controlled trials focusing on conventional fractionation (CF; daily fractions of 1.8-2 Gy, reaching a total dose of 50-50.4 Gy over 5-6 weeks), moderate hypofractionation (MHF; fraction sizes of 2.65-3.3 Gy for 13-16 fractions over 3-5 weeks), and/or ultra-hypofractionation (UHF; schedule of only 5 fractions). DATA EXTRACTION: Two independent investigators screened studies and extracted data. Risk of bias and quality of evidence were assessed using the Cochrane Collaboration's tool and the GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) approach, respectively. DATA SYNTHESIS: Pooled risk ratios (RRs) and hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated using a random effects model. Heterogeneity was analysed using Cochran's Q test and I2 statistic. Network meta-analysis was used to integrate all available evidence. MAIN OUTCOME MEASURES: The pre-specified primary outcome was grade ≥2 acute radiation dermatitis and late radiation therapy related side effects; secondary outcomes included cosmesis, quality of life, recurrence, and survival metrics. RESULTS: From 1754 studies, 59 articles representing 35 trials (20 237 patients) were assessed; 21.6% of outcomes showed low risk of bias, whereas 78.4% had some concerns or high risk, particularly in outcome measurement (47.4%). The RR for grade ≥2 acute radiation dermatitis for MHF compared with CF was 0.54 (95% CI 0.49 to 0.61; P<0.001) and 0.68 (0.49 to 0.93; P=0.02) following breast conserving therapy and mastectomy, respectively. Hyperpigmentation and grade ≥2 breast shrinkage were less frequent after MHF than after CF, with RRs of 0.77 (0.62 to 0.95; P=0.02) and 0.92 (0.85 to 0.99; P=0.03), respectively, in the combined breast conserving therapy and mastectomy population. However, in the breast conserving therapy only trials, these differences in hyperpigmentation (RR 0.79, 0.60 to 1.03; P=0.08) and breast shrinkage (0.94, 0.83 to 1.07; P=0.35) were not statistically significant. The RR for grade ≥2 acute radiation dermatitis for UHF compared with MHF was 0.85 (0.47 to 1.55; P=0.60) for breast conserving therapy and mastectomy patients combined. MHF was associated with improved cosmesis and quality of life compared with CF, whereas data on UHF were less conclusive. Survival and recurrence outcomes were similar between UHF, MHF, and CF. CONCLUSIONS: MHF shows improved safety profile, cosmesis, and quality of life compared with CF while maintaining equivalent oncological outcomes. Fewer randomised controlled trials have compared UHF with other fractionation schedules, but its safety and oncological effectiveness seem to be similar with short term follow-up. Given the advantages of reduced treatment time, enhanced convenience for patients, and potential cost effectiveness, MHF and UHF should be considered as preferred options over CF in appropriate clinical settings, with further research needed to solidify these findings. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42023460249.

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OBJECTIVE: This paper aims to evaluate the literature on the prevalence of psychological distress and its associated factors in patients with breast cancer. DESIGN: Systematic review and meta-analysis. DATA SOURCES: PubMed, Web of Science, Embase, the Cochrane Library, China National Knowledge Infrastructure and Wanfang were searched from inception to 11 June 2024. ELIGIBILITY CRITERIA: Studies reported data on the prevalence and correlates of psychological distress were included. Review, letter, conference abstracts and articles not available in English and Chinese were excluded. DATA EXTRACTION AND SYNTHESIS: Two researchers independently conducted literature screening, data extraction and bias risk assessment. Meta-analysis was employed to estimate the prevalence and correlates of psychological distress in patients with breast cancer. The Agency for Healthcare Research and Quality and the Newcastle-Ottawa Scale were used for quality assessment. Meta-analysis was performed by using the R V.4.1.1 software. RESULTS: In total, 34 studies representing 13 828 patients with breast cancer were included in the study. Most of the studies were cross-sectional study (n=25, 73.53%%). The pooled prevalence of psychological distress was 50% (95% CI 42% to 58%, I2=98%). Results showed that psychological distress was positively correlated with younger age (z=0.13, 95% CI 0.07 to 0.20), having children (z=0.39, 95% CI 0.11 to 0.61), poor financial situation (z=0.12, 95% CI -0.03 to 0.26), short time since diagnosis (z=0.19, 95% CI 0.01 to 0.36), previous treatment (z=0.15, 95% CI 0.03 to 0.27), distant metastasis (z=0.31, 95% CI 0.07 to 0.52), chemotherapy (z=0.22, 95% CI 0.05 to 0.38), prior emotional status (z=0.40, 95% CI 0.29 to 0.50), body image damaged (z=0.10, 95% CI -0.01 to 0.21), negative coping (z=0.12, 95% CI -0.11 to 0.34), communication avoidance (z=0.32, 95% CI 0.24 to 0.39) and negatively correlated with married (z=-0.25, 95% CI 0.45 to -0.02), high education level (z=-0.19, 95% CI -0.40 to 0.05), having insured (z=-0.04, 95% CI -0.15 to 0.08), full employment (z=-0.40, 95% CI -0.61 to -0.14), time of completion of treatment (z=-0.12, 95% CI -0.30 to -0.06), surgery (z=-0.05, 95% CI -0.53 to 0.45), social support (z=-0.18, 95% CI -0.29 to -0.06), post-traumatic growth (z=-0.19, 95% CI -0.34 to -0.03), good physical conditions (z=-0.17, 95% CI -0.29 to -0.04), positive coping (z=-0.22, 95% CI -0.53 to 0.15). CONCLUSION: Our findings indicated that the prevalence of psychological distress in patients with breast cancers was 50% and 21 correlates of psychological distress. Screening and evidence-based interventions are urgent and essential to address this public concern and promote the health of patients with breast cancer. PROSPERO REGISTRATION NUMBER: CRD42023397109.

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The incidence of prostate, breast, and thyroid cancers has increased in China over the past few decades. Whether and how much these increases can be attributed to overdiagnosis are less understood. This study aimed to estimate the proportion of overdiagnosis among these three cancers in China during 2004-2019. The age-specific cancer incidence, cancer mortality, and all-cause mortality in China were extracted from the Global Burden of Diseases 2019. The lifetime risk of developing and that of dying from each cancer were calculated using the life table method. The proportion of overdiagnosis of a cancer was estimated as the difference between the lifetime risk of developing the cancer and that of suffering from the cancer (including death, metastasis, and symptoms caused by the cancer), further divided by the lifetime risk of developing the cancer. The highest possible values of these parameters were adopted in the estimation so as to obtain the lower bounds of the proportions of overdiagnosis. Sensitivity analyses assuming different lag periods between the diagnosis of a cancer and death from the cancer were performed. The results showed that the lifetime risk of developing prostate, breast, and thyroid cancer increased dramatically from 2004 to 2019 in China, while the increase in the lifetime risk of dying from these cancers was less pronounced. The proportions of overdiagnosis among prostate, breast, and thyroid cancers were estimated to be 7.88%, 18.99%, and 24.92%, respectively, in 2004, and increased to 18.20%, 26.25%, and 29.24%, respectively, in 2019. The increasing trends were statistically significant for all three cancers (all p < 0.001). In sensitivity analyses, the proportions of overdiagnosis decreased, but upward trends over time remained for all three cancers. In conclusion, the overdiagnosis of prostate, breast, and thyroid cancers in China increased from 2004 to 2019, with the highest proportion seen in thyroid cancer and the most rapid increase seen in prostate cancer. Multifaceted efforts by policy makers, guideline developers, and clinicians are needed to tackle this problem.

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BACKGROUND: Chemicals emitted from industrial facilities include known or suspected mammary carcinogens and endocrine disruptors, but epidemiologic studies are limited. We evaluated associations between air emissions of multiple carcinogenic chemicals and postmenopausal breast cancer risk in a large prospective U.S. METHODS: We used the U.S. Environmental Protection Agency's Toxics Release Inventory to estimate historical airborne emissions (1987-1995) of 19 known and probable carcinogens for participants enrolled (1995-1996) in the NIH-AARP Diet and Health Study. Among 170,402 women, 15,124 breast cancers were diagnosed through 2018. We constructed inverse distance- and wind-weighted average emissions metrics within 1, 2, 5, and 10 km of the enrollment address for each chemical. We estimated multivariable adjusted HRs and 95 % CIs for categories (quartiles, tertiles, medians) of each chemical in association with breast cancer overall and separately by type (invasive, ductal carcinoma in situ) and estrogen receptor (ER) status. RESULTS: We observed an association between benzene emissions and breast cancer risk that was strongest at 1 km (HRQ4 vs. non-exposed = 2.06, 95 %CI: 1.34-3.17; p-trend = 0.001). The magnitude of the association weakened with increasing distance (2 km HRQ4 vs. non-exposed = 1.17, 95 %CI=0.92-1.49; p-trend = 0.19; 5 km HRQ4 vs. non-exposed = 1.05, 95 %CI=0.94-1.16; p-trend = 0.37; 10 km HRQ4 vs. non-exposed = 0.95, 95 %CI=0.89-1.02; p-trend = 0.19) and appeared to be most relevant for invasive rather than intraductal disease. Overall risk was also elevated for vinyl chloride at 5 km (HR≥median vs. non-exposed = 1.20, 95 %CI=1.01-1.43; p-trend = 0.04), but not 2 km or 10 km. We observed suggestive associations for asbestos, trichloroethylene, and styrene in different subgroup analyses, but risk patterns were not clear across distances. Associations with other chemicals were generally null, with limited evidence of heterogeneity by disease type or ER status. CONCLUSIONS: An increased risk of breast cancer associated with relatively high levels of industrial benzene emissions warrants additional study, particularly among participants with diverse sociodemographic characteristics that live in areas with higher density of industrial facilities.

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Importance: Most patients with pathogenic or likely pathogenic (P/LP) variants for breast cancer have not undergone genetic testing. Objective: To identify patients meeting family history criteria for genetic testing in the electronic health record (EHR). Design, Setting, and Participants: This study included both cross-sectional (observation date, February 1, 2024) and retrospective cohort (observation period, January 1, 2018, to February 1, 2024) analyses. Participants included patients aged 18 to 79 years enrolled in Renown Health, a large health system in Northern Nevada. Genotype was known for 38 003 patients enrolled in Healthy Nevada Project (HNP), a population genomics study. Exposure: An EHR indicating that a patient is positive for criteria according to the Seven-Question Family History Questionnaire (hereafter, FHS7 positive) assessing familial risk for hereditary breast and ovarian cancer (HBOC). Main Outcomes and Measures: The primary outcomes were the presence of P/LP variants in the ATM, BRCA1, BRCA2, CHEK2, or PALB2 genes (cross-sectional analysis) or a diagnosis of cancer (cohort analysis). Age-adjusted cancer incidence rates per 100 000 patients per year were calculated using the 2020 US population as the standard. Hazard ratios (HRs) for cancer attributable to FHS7-positive status were estimated using cause-specific hazard models. Results: Among 835 727 patients, 423 393 (50.7%) were female and 29 913 (3.6%) were FHS7 positive. Among those who were FHS7 positive, 24 535 (82.0%) had no evidence of prior genetic testing for HBOC in their EHR. Being FHS7 positive was associated with increased prevalence of P/LP variants in BRCA1/BRCA2 (odds ratio [OR], 3.34; 95% CI, 2.48-4.47), CHEK2 (OR, 1.62; 95% CI, 1.05-2.43), and PALB2 (OR, 2.84; 95% CI, 1.23-6.16) among HNP female individuals, and in BRCA1/BRCA2 (OR, 3.35; 95% CI, 1.93-5.56) among HNP male individuals. Being FHS7 positive was also associated with significantly increased risk of cancer among 131 622 non-HNP female individuals (HR, 1.44; 95% CI, 1.22-1.70) but not among 114 982 non-HNP male individuals (HR, 1.11; 95% CI, 0.87-1.42). Among 1527 HNP survey respondents, 352 of 383 EHR-FHS7 positive patients (91.9%) were survey-FHS7 positive, but only 352 of 883 survey-FHS7 positive patients (39.9%) were EHR-FHS7 positive. Of the 29 913 FHS7-positive patients, 19 764 (66.1%) were identified only after parsing free-text family history comments. Socioeconomic differences were also observed between EHR-FHS7-negative and EHR-FHS7-positive patients, suggesting disparities in recording family history. Conclusions and Relevance: In this cross-sectional study, EHR-derived FHS7 identified thousands of patients with familial risk for breast cancer, indicating a substantial gap in genetic testing. However, limitations in EHR family history data suggested that other identification methods, such as direct-to-patient questionnaires, are required to fully address this gap.

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The relationship between psoriasis and site-specific cancers remains unclear. Here, we aim to investigate whether psoriasis is causally associated with site-specific cancers. We use observational and genetic data from the UK Biobank, obtaining GWAS summary data, eQTL analysis data, TCGA data, and GTEx data from public datasets. We perform PheWAS, polygenic risk score analysis, and one-sample and two-sample Mendelian randomization analyses to investigate the potential causal associations between psoriasis and cancers. In the unselected PheWAS analysis, psoriasis is associated with higher risks of 16 types of cancer. Using one-sample Mendelian randomization analyses, it is found that genetically predicted psoriasis is associated with higher risks of anal canal cancer, breast cancer, follicular non-Hodgkin's lymphoma and nonmelanoma skin cancer in women; and lung cancer and kidney cancer in men. Our two-sample Mendelian randomization analysis indicates that psoriasis is causally associated with breast cancer and lung cancer. Gene annotation shows that psoriasis-related genes, such as ERAP1, are significantly different in lung and breast cancer tissues. Taken together, clinical attention to lung cancer and breast cancer may be warranted among patients with psoriasis.

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Polygenic risk scores (PRSs) hold promise in their potential translation into clinical settings to improve disease risk prediction. An important consideration in integrating PRSs into clinical settings is to gain an understanding of how to identify which subpopulations of individuals most benefit from PRSs for risk prediction. In this study, using the UK Biobank dataset, we trained logistic regression models to predict the 10 year incident risk of myocardial infarction, breast cancer, and schizophrenia using either just clinical features or clinical features combined with PRSs. For each disease, we identified the top 10% subgroup with the greatest magnitude of improvement in risk prediction accuracy attributed to PRSs in the multi-modal model. Using up to ~ 3.6 k demographic, lifestyle, diagnostic, lab, and physical measurement features from the UK Biobank dataset of ~ 500 k individuals, we characterized these subgroups based on various clinical, lifestyle, and demographic characteristics. The incident cases in the top 10% subgroup for each disease represent distinct phenotypes that differ from other cases and that are strongly correlated with genetic predisposition. Our findings provide insights into disease subtypes and can encourage future studies aimed at classifying these individuals to enhance the targeting of polygenic risk scoring in practice.

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OBJECTIVE: Breast cancer is one of the most common cancers in women worldwide. This study aims is to investigate the burden of breast cancer in Iran and its relationship with the Human Development Index (HDI) during 2009 to 2019. STUDY DESIGN: The present study is an observational study in Iran during the years 2009 to 2019. Data related to the incidence, mortality, Years of Life with Disability (YLD), Years of Life Lost (YLL) and Disability-Adjusted Life-Years (DALY) of breast cancer in Iran were extracted from the Global Burden of Disease 2019 (GBD-2019) website. Correlation tests are used to check the relationship between these indicators and the human development index. RESULTS: The highest incidence rate of breast cancer in 2019 is related to the provinces of Gilan (29 per 100,000) and Tehran (28.55 per 100,000) and the highest rate of death from breast cancer is related to the provinces of Gilan (10.71 per 100,000). and Semnan (9.97 in 100,000). The results showed that there is a positive and significant correlation between DALY (r = 0.626, P < 0.0001), YLL (r = 0.611, P < 0.0001) and, YLD (r = 0.773, P < 0.0001) breast cancer with HDI index. There is a positive and significant correlation between the incidence (r = 0.794, P < 0.0001) and mortality (r = 0.503, P = 0.003) of breast cancer with the HDI index. CONCLUSIONS: Considering that a positive correlation was observed between the incidence and burden of breast cancer and the human development index in the country, it is suggested to implement preventive measures such as public education programs to reduce the incidence and burden of breast cancer and the necessity of screening programs in areas with low human development index. It confirms the diagnosis of disease cases.

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BACKGROUND: Breast cancer (BC) poses significant burdens on women globally. While past research suggests a potential link between bone mineral density (BMD) and BC risk, findings remain inconsistent. Our study aims to elucidate the causal relationship between BMD and BC in East Asians using bidirectional Mendelian randomization (MR). METHODS: Genetic association data for bone mineral density T-scores (BMD-T) and Z-scores (BMD-Z) (Sample size = 92,615) and BC from two different sources (Sample size1 = 98,283; Sample size2 = 79,550) were collected from publicly available genome-wide association studies (GWAS). Single-nucleotide polymorphisms (SNPs) associated with BMD-T and BMD-Z as phenotype-related instrumental variables (IVs) were used, with BC as the outcome. As the primary means of causal inference, the inverse variance weighted (IVW) approach was employed. Heterogeneity analysis was conducted using Cochran's Q test, while MR-Egger regression analysis was implemented to assess the pleiotropic effects of the IVs. Sensitivity analyses were performed using methods such as MR-Egger, weighted median, and weighted mode to analyze the robustness and reliability of the results. The MR-PRESSO method and the RadialMR were used to detect and remove outliers. The PhenoScanner V2 website was utilized to exclude confounding factors shared between BMD and BC. Besides, the Bonferroni correction was also used to adjust the significance threshold. Then, the meta-analysis method was applied to combine the MR analysis results from the two BC sources. Finally, a reverse MR analysis was conducted. RESULTS: The results of the IVW method were consolidated through meta-analysis, revealing a positive correlation between genetically predicted BMD-T ([Formula: see text], [Formula: see text], [Formula: see text]) and BMD-Z ([Formula: see text],[Formula: see text], [Formula: see text]) with increased BC risk. The Cochran's [Formula: see text] test and MR-Egger regression suggested that neither of these causal relationships was affected by heterogeneity or horizontal pleiotropy. The sensitivity analyses supported the IVW results, indicating the robustness of the findings. Reverse MR analysis showed no causal relationship between BC and BMD. CONCLUSION: Our MR study results provide evidence for the causal relationship between BMD and BC risk in East Asian populations, suggesting that BMD screening is of great significance in detecting and preventing BC.

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BACKGROUND: Mammographic breast density (MBD) is a strong risk factor and an intermediate phenotype for breast cancer, yet there are limited studies on how environmental pollutants are associated with MBD. OBJECTIVE: We investigated associations of perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), and perfluorohexane sulfonate (PFHxS) levels with measures of MBD and evaluated if early life factors modified any associations. METHODS: Metabolon performed metabolomics analysis using ultrahigh-performance liquid chromatography/tandem accurate mass spectrometry in fasting blood from 705 premenopausal women completing their annual screening mammogram in St. Louis, Missouri. We calculated least square means (LSM) of mammographic volumetric percent density (VPD), dense volume (DV), and nondense volume (NDV) by quartiles (Q) of PFOS, PFOA, and PFHxS from multivariable linear regression modeling overall and stratified by recruitment period, race, age at menarche, and body shape at age 10. Models were adjusted for age, age at menarche, body fat percentage, race, family history of breast cancer, oral contraceptive use, alcohol consumption, parity/age at first birth, and body shape at age 10. RESULTS: PFOS, PFOA, and PFHxS were not significantly associated with VPD or NDV. PFHxS was significantly positively associated with DV (Q1=67.64 cm3, Q2=69.91 cm3, Q3=69.06 cm3, Q4=75.79 cm3; p-trend=0.03). PFOS was positively associated with DV (Q1=65.45 cm3, Q2=70.74 cm3, Q3=73.31 cm3, Q4=73.52 cm3; p-trend=0.06) with DV being 8.1%, 12%, and 12.3% higher in Q2, Q3, and Q4 compared to Q1. Among women who were underweight/normal weight at age 10, PFOS was positively associated with VPD (Q1=9.02%, Q2=9.11%, Q3=9.48%, Q4=9.92%; p-trend=0.04) while there was an inverse association among women who were overweight/obese at age 10 (Q1=7.46%, Q2=6.94%, Q3=6.78%, Q4=5.47%; p-trend=0.005) (p-interaction=0.04). DISCUSSION: We report novel associations of PFHxS and PFOS with DV in premenopausal women. PFOS, PFOA, and PFHxS were not associated with VPD and NDV. In addition, body shape at age 10 may modify the associations of PFOS with MBD. Further studies are needed to validate our findings and to evaluate the associations of other per- and polyfluoroalkyl substances (PFAS), as well as mixtures of PFAS, with MBD. https://doi.org/10.1289/EHP14065.

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