Reproductive Risk Factors Research Articles

Reproductive Risk Factor Patterns in Caribbean Women With Breast Cancer Across 4 Generations

Breast cancer (BC) is commonly diagnosed among Caribbean women. Shifts in reproductive patterns modify the incidence of BC diagnosis and age at BC diagnosis in population-based studies; however, reproductive patterns in Caribbean women remain understudied. To describe the temporal trends in reproductive patterns and age at BC diagnosis in Caribbean-born women. A cross-sectional observational study-the Caribbean Women's Cancer Study-was conducted, with data on reproductive patterns known to affect BC risk collected in The Bahamas, Barbados, Cayman Islands, Dominica, Haiti, Jamaica, and Trinidad and Tobago. Participants were recruited prospectively. The sample included women born in Caribbean countries and diagnosed with invasive BC and/or ovarian cancer from June 1, 2010, to June 30, 2018, and was divided into 4 birth cohorts (born before 1950, 1950-1959, 1960-1969, and in or after 1970). Data were analyzed between August 1, 2023, and July 31, 2024. Receipt of a BC diagnosis and birth in a Caribbean country. Change in reproductive patterns between birth cohorts, including age at BC diagnosis, family history of cancer, age at first pregnancy, number of pregnancies, number of full-term pregnancies, number of siblings, age at menarche and menopause, estrogen receptor status, and germline pathogenic/likely pathogenic variants. Of 1015 participants diagnosed with BC and ovarian cancer, 995 women (mean [SD] age, 46.6 [10.8] years; 605 [81.8%] Afro-Caribbean, 98 [13.2%] East Indian, 22 [3.0%] White, and 12 [1.6%] >1 race) received a diagnosis of invasive BC. Comparison from older to younger birth cohorts (presented in the order of born before 1950, 1950-1959, 1960-1969 and in or after 1970) showed an increased proportion of women experiencing menarche at age 12 years or younger (33.0% vs 47.3% vs 45.5% vs 57.9%; P < .001), women with no pregnancies (6.8% vs 6.8% vs 10.5% vs 22.8%; P < .001), and nulliparous women (8.6% vs 9.2% vs 13.9% vs 27.6%; P < .001). Younger age at BC diagnosis was observed in women experiencing menarche at age 12 years or younger (mean [SD], 45.0 [10.5] years) vs 15 years or older (mean [SD], 49.1 [11.2] years) and in nulliparous women (mean [SD], 42.1 [11.2] years) vs 3 or more full-term pregnancies (mean [SD], 49.9 [10.6] years; P < .001). For every year of first pregnancy delay, women had a 4% increased chance of being diagnosed with estrogen receptor-positive tumors (odds ratio, 1.04; 95% CI, 1.01-1.08; P = .02). In this cross-sectional study, between each 10-year birth cohort, women diagnosed with BC had a lower age at menarche, number of pregnancies, and number of full-term pregnancies. These findings suggest that interventions targeting other BC risk factors need to be implemented.

Reproductive Factors and Thyroid Cancer Risk: The Multiethnic Cohort Study.

Background: Women are three times more likely to be diagnosed with thyroid cancer than men, with incidence rates per 100,000 in the United States of 20.2 for women and 7.4 for men. Several reproductive and hormonal factors have been proposed as possible contributors to thyroid cancer risk, including age at menarche, parity, age at menopause, oral contraceptive use, surgical menopause, and menopausal hormone therapy. Our study aimed to investigate potential reproductive/hormonal factors in a multiethnic population. Methods: Risk factors for thyroid cancer were evaluated among female participants (n = 118,344) of the Multiethnic Cohort Study. The cohort was linked to Surveillance, Epidemiology, and End Results cancer incidence and statewide death certificate files in Hawaii and California, with 373 incident papillary thyroid cancer cases identified. Exposures investigated include age at menarche, parity, first pregnancy outcome, birth control use, and menopausal status and type. Multivariable Cox proportional hazards models were used to obtain relative risk (RR) of papillary thyroid cancer and their 95% confidence intervals (CI). Covariates included age, race and ethnicity, reproductive history, body size, smoking, and alcohol consumption. Results: We observed a statistically significant increased risk of papillary thyroid cancer for oophorectomy (adjusted RR 1.58, 95% CI: 1.26, 1.99), hysterectomy (adjusted RR 1.65, 95% CI: 1.33, 2.04), and surgical menopause (adjusted RR 1.55, 95% CI: 1.22, 1.97), and decreased risk for first live birth at ≤20 years of age versus nulliparity (adjusted RR 0.66, 95% CI: 0.46, 0.93). These associations did not vary by race and ethnicity (p het > 0.44). Conclusion: The reproductive risk factors for papillary thyroid cancer reported in the literature were largely confirmed in all racial and ethnic groups in our multiethnic population, which validates uniform obstetric and gynecological practice.

Systematic Review and Meta-Analysis of Lifestyle and Reproductive Factors Associated with Risk of Breast Cancer in Asian Women.

Assessing breast cancer risks from lifestyle and reproductive factors is critical for developing population-specific risk prediction tools. However, limited studies have evaluated these risks in recent Asian birth cohorts. We systematically reviewed articles published from January 2010 to December 2023, examining breast cancer risk factors in Asian women. Data were described narratively, estimates pooled, and prevalence and attributable proportions compared across Asian populations. Of the 128 studies reviewed, 103 reported adjusted effect sizes for meta-analysis. Lifestyle and reproductive factors were predictive of breast cancer risk in Asian women, with varying impacts on premenopausal and postmenopausal women. Relative risks were similar within Asian populations and in comparison to European populations, except for menarche, menopause, and hormone receptor therapy. However, risk factor distributions differed across populations. While alcohol intake (21%) and oral contraceptive use (20%) emerged as the most attributable modifiable risk factors in Europeans, passive smoking (24%) and higher BMI (17%, ≥24 kg/m2 among postmenopausal women) were predominant in Asians. Our study shows that while the effects of lifestyle and reproductive breast cancer risk factors are largely similar across different populations, their distributions vary. Our analysis underscores the importance of considering population-specific risk factor distributions when developing risk prediction tools for Asian populations.

Reproductive factors, genetic susceptibility and risk of type 2 diabetes: A prospective cohort study

AimTo explore the relationships of multiple reproductive factors with type 2 diabetes mellitus (T2DM) risk and the joint effects of reproductive factors and genetic susceptibility. MethodsWe included 262,368 women without prevalent T2DM from the UK biobank. Cox proportional hazards regression models were employed to estimate the relationships of reproductive factors with T2DM risk and the joint effects of reproductive factors and genetic susceptibility. ResultsDuring a mean follow-up of 12.2 years, 8,996 T2DM cases were identified. Early menarche (<12 years, hazard ratio (HR) 1.08 [95 % confidence interval (CI) 1.02;1.13]), late menarche (≥15 years, HR 1.11 [1.04;1.17]), early menopause (<45 years, HR 1.20 [1.12;1.29]), short reproductive lifespan (<30 years, HR 1.25 [1.16;1.35]), hysterectomy (1.31, HR [1.23;1.40]), oophorectomy (HR 1.28 [1.20;1.36]), high parity (≥4, HR 1.25 [1.17;1.34]), early age at first live birth (<20 years, HR 1.23 [1.16;1.31]), miscarriage (HR 1.13 [1.07;1.19]), stillbirth (HR 1.14 [1.03;1.27]), and ever used hormonal replacement therapy (HR 1.19 [1.14;1.24]) were related to a higher T2DM risk, while ever used oral contraceptives (HR 0.93 [0.89;0.98]) was related to a lower T2DM risk. Furthermore, women with reproductive risk factors and high genetic risk had the highest T2DM risk compared to those with low genetic risk and without reproductive risk factors. ConclusionOur findings show that multiple reproductive factors are related to T2DM risk, particularly in women with high genetic risk.

Incidence of peritoneal cancer after oophorectomy among BRCA1 and BRCA2 mutation carriers

Abstract Background To estimate the incidence of primary peritoneal cancer after preventive bilateral oophorectomy in women with a BRCA1 or BRCA2 mutation. Methods A total of 6310 women with a BRCA1 or BRCA2 mutation who underwent a preventive bilateral oophorectomy were followed for a mean of 7.8 years from oophorectomy. The 20-year cumulative incidence of peritoneal cancer post-oophorectomy was estimated using the Kaplan-Meier method. A left-truncated Cox proportional hazards analysis was used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) associated with the age at oophorectomy, year of oophorectomy, and family history of ovarian cancer as well as hormonal and reproductive risk factors. Results Fifty-five women developed primary peritoneal cancer (n = 45 in BRCA1, 8 in BRCA2, and 2 in women with a mutation in both genes). Their mean age at oophorectomy was 48.9 years. The annual risk of peritoneal cancer was 0.14% for women with a BRCA1 mutation and 0.06% for women with a BRCA2 mutation. The 20-year cumulative risk of peritoneal cancer from the date of oophorectomy was 2.7% for BRCA1 carriers and 0.9% for BRCA2 mutation carriers. There were no peritoneal cancers in BRCA1 carriers who had the operation before age 35 or in BRCA2 carriers who had the operation before age 45. Conclusions For BRCA1 mutation carriers, the annual risk of peritoneal cancer for 20 years post-oophorectomy is 0.14% per year. The risk is lower for BRCA2 carriers (0.06% per year).

Abstract PO3-09-11: Age Group Analysis of Breast Cancer Patterns in Brazil: Findings from Population-Based Registries

Abstract Background: The rising breast cancer (BC) incidence among young women is potentially influenced by modifiable genetic and reproductive risk factors, as well as the increased incidence among older women may be associated with lifestyle-related factors and screening programs. This study examines BC incidence and mortality rates across different age groups in Brazil, focusing on clinicopathological and sociodemographic variations. Patients and methods: By using data from 13 Brazilian Population-Based Cancer Registries spanning the period 2010-2015, this study analyzed incidence trends among women with BC. Crude incidence ratios (CIRs) and the annual average percent change (AAPC) were computed. Additionally, clinical and sociodemographic information from 348 Hospital-Based Cancer Registries covering 2000-2019 was incorporated. Mortality data for the years 2000-2020 were obtained from the National Mortality Information System. Comparative analyses were conducted across three predefined age groups: &amp;lt; 40, 40-69, and ≥ 70 years. Statistical significance was defined as a p-value &amp;lt; 0.05, while a threshold of more than 5% difference in proportional values was used as a criterion to identify clinically relevant differentials. Results: Between 2010 and 2015, a total of 205,966 newly diagnosed cases of BC were documented. The CIRs were 7.1/100,000 for the age group &amp;lt; 40, 156.5/100,000 for the age group 40-69, and 247.5/100,000 for the age group ≥ 70 years. Within the scope of the analyzed age groups, it was observed that solely the age group &amp;lt; 40 years exhibited a noteworthy and persistent increase in the rate of occurrence (AAPC +1.6; 95% CI: 1.0 to 2.2; p &amp;lt; 0.001). This age group also displayed a significantly higher proportion of black women (53%, p &amp;lt; 0.001), a higher prevalence of alcohol consumption (20.5%, p &amp;lt; 0.001), and a greater likelihood of receiving multiple treatment modalities (60.7%, p &amp;lt; 0.001). In contrast, the age group ≥ 70 years experienced a more extended time delay of &amp;gt; 60 days from diagnosis to treatment onset (54%, p &amp;lt; 0.001), while exhibiting a higher utilization rate of hormone therapy (45.3%, p &amp;lt; 0.01). The mortality rates witnessed a significant increase across all age categories, with the age group &amp;lt; 40 years manifesting the most substantial escalation (AAPC +1.8%; 95% CI: 1.6 to 2.1; p &amp;lt; 0.001). This rise was comparatively more than double the rate observed in the 40-69 age group (AAPC +0.7%; 95% CI: 0.5 to 0.8; p &amp;lt; 0.001) and exactly twice as high as the rate recorded in the age group &amp;gt; 70 years (AAPC +0.9%; 95% CI: 0.7 to 1.1 ; p &amp;lt; 0.001). Conclusion: This study reveals substantial disparities in BC incidence and mortality rates, as well as significant differences in clinicopathological and sociodemographic features, among women aged &amp;lt; 40 compared to those in the 40-69 and ≥ 70 years in Brazil. Keywords: Breast cancer; age groups; incidence; mortality. Citation Format: Jesse Lopes da Silva, Andreia Cristina De Melo, Lucas Zanetti de Albuquerque, Mariana Espirito Santo Rodrigues, Luiz Claudio Santos Thuler. Age Group Analysis of Breast Cancer Patterns in Brazil: Findings from Population-Based Registries [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-09-11.

Abstract PO3-08-01: Decision curve analysis to compare breast cancer risk predictions for a polygenic integrated clinical risk model with those of a gold standard

Abstract Risk-based guidelines have been developed to provide advice on options that are available to women who are at increased risk of breast cancer. We and others are focused on improving risk prediction models for general population use. For breast cancer, polygenic risk has been identified as important for risk prediction, especially when combined with clinical risk factors such as family history, anthropometric measures, breast imaging measures, and hormonal and reproductive risk factors. When comparing the performance of risk prediction models, the AUC is most often used but it focuses on performance in terms of distinguishing between affected and unaffected individuals and does not take into account differences in the specificity (true negative rate) and sensitivity (true positive rate) of the models being compared. In contrast, decision curve analysis takes sensitivity and specificity into account and enables the comparison of the net benefit of risk prediction tools at the clinical risk thresholds that are used to guide clinical management decisions. Herein, we use decision curve analysis to compare breast cancer risk prediction guidelines for BRISK and the Breast Cancer Risk Assessment Tool (BCRAT) in the UK Biobank, and for BRISK and IBIS version 7 in the Nurses’ Health Study. We evaluated the net benefit at the 5-year risk thresholds (1.67% and 3%) that are used to guide clinical management decisions around risk-reducing medication and at the remaining lifetime risk of 20% that is used to guide supplemental MRI surveillance. In the UK Biobank, BRISK showed a net benefit over BCRAT at the 5-year risk thresholds of 1.67% and 3.0%. The AUCs were 0.649 (95% CI = 0.640, 0.695) for BRISK and 0.567 (95% CI = 0.556, 0.577) for BCRAT and showed that, overall, BRISK discriminated between affected and unaffected women better than BCRAT (P &amp;lt; 0.001). In the Nurses’ Health Study, BRISK showed a net benefit over IBIS at the remaining lifetime risk threshold of 20%. The AUCs were 0.647; 95% CI = 0.627, 0.668 for BRISK and 0.571; 95% CI = 0.546, 0.595 for IBIS, a statistically significant improvement for BRISK over IBIS (P &amp;lt; 0.0001). We also looked at sensitivity, specificity, positive predictive value and negative predictive value even though these risk models are one-step removed from breast cancer diagnosis by screening/risk-reduction options. The positive predictive values are higher for the BRISK (27.1%) model compared to BCRAT (5.5%) in the UK Biobank dataset and higher for BRISK (15.4%) compared to IBISv7 (14.0%) in the Nurses’ dataset. We have shown the application of a statistical tool that can be used to directly compare risk models at clinically relevant thresholds. We have shown that BRISK, which comprises polygenic risk and clinical risk factors, shows higher net benefit at both 1.67% and 3% thresholds compared to BCRAT and at 20% remaining lifetime risk for IBIS version 7. In breast cancer risk prediction, a tool with high specificity (and therefore a necessary trade-off for low sensitivity) is preferred because we do not want to incorrectly classify women as not being at high risk and deny them the opportunity for intervention in the form of more frequent screening, alternative modes of screening or risk-reducing medication. This improvement in general population risk stratification that BRISK can provide has the potential to have a clinically significant effect on women’s health. Citation Format: Erika Spaeth, Bernard A Rosner, Gill Dite. Decision curve analysis to compare breast cancer risk predictions for a polygenic integrated clinical risk model with those of a gold standard [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-08-01.

Women's reproductive risk score and healthy lifestyle modification in cardiovascular disease: Findings from the UK Biobank

Background and aimsReproductive risk factors are associated with increased risk of cardiovascular disease (CVD) in women. However, the combined effects of the composite reproductive risk factors on CVD are unknown. This study was performed to construct a reproductive risk score (RRS) to measure reproductive status, examine the association between RRS and CVD, and explore the modification effect of healthy lifestyle on the association in women in the UK Biobank cohort. MethodsThe RRS was constructed in 74,141 female participants with data about the items derived for the RRS in the UK Biobank. The RRS was derived from 17 baseline variables, all of which indicated women's reproductive health status. We defined four categories of RRS status: low-risk group (score 0–1); low-intermediate group (score 2–3); high-intermediate group (score 4–5); and high-risk group (score 6–13). We also constructed a healthy lifestyle score (HLS) with five related factors, and categorized into unhealthy lifestyle group (score: 0–1), intermediate lifestyle group (score: 2–3) and healthy lifestyle group (score: 4–5). ResultsEach point increase in the RRS was associated with a 22 % higher risk of CVD (adjusted hazard ratio (aHR): 1.22; 95 % confidence interval (CI): 1.16 to 1.28), 23 % higher risk of IHD (1.23; 1.17 to 1.31) and 19 % higher risk of stroke (1.19; 1.07 to 1.32). The percentage population-attribution risks (PAR%) were 16 % (95 % CI: 8 to 24) for CVD, 15 % (95 % CI: 6 to 24) for IHD and 18 % (95 % CI: 1 to 33) for stroke. A healthy lifestyle significantly attenuated RRS associations with the incidence of CVD and IHD. The attributable proportions due to additive interaction (p < 0.001) between RRS and HLS were 0.14 (95 % CI: 0.07 to 0.22) for CVD and 0.15 (95 % CI: 0.09 to 0.23) for IHD, respectively. ConclusionsHigh RRS was associated with increased risks of CVD, IHD and stroke in female participants in the UK Biobank. The early-stage identification of women with reproductive risk using synthesised indicators and appropriate healthy lifestyle interventions could be useful for the prevention of early CVD and the extension of healthy active life expectancy.

Assisted reproductive technology-associated risk factors for placenta accreta spectrum after vaginal delivery

This study aimed to investigate assisted reproductive technology (ART) factors associated with placenta accreta spectrum (PAS) after vaginal delivery. This was a registry-based retrospective cohort study using the Japanese national ART registry. Cases of live singleton infants born via vaginal delivery after single embryo transfer (ET) between 2007 and 2020 were included (n = 224,043). PAS was diagnosed in 1412 cases (0.63% of deliveries), including 1360 cases (96.3%) derived from frozen-thawed ET cycles and 52 (3.7%) following fresh ET. Among fresh ET cycles, assisted hatching (AH) (adjusted odds ratio [aOR], 2.5; 95% confidence interval [CI] 1.4–4.7) and blastocyst embryo transfer (aOR, 2.2; 95% CI 1.3–3.9) were associated with a significantly increased risk of PAS. For frozen-thawed ET cycles, hormone replacement cycles (HRCs) constituted the greatest risk factor (aOR, 11.4; 95% CI 8.7–15.0), with PAS occurring in 1.4% of all vaginal deliveries following HRC (1258/91,418 deliveries) compared with only 0.11% following natural cycles (55/47,936). AH was also associated with a significantly increased risk of PAS in frozen-thawed cycles (aOR, 1.2; 95% CI 1.02–1.3). Our findings indicate the need for additional care in the management of patients undergoing vaginal delivery following ART with HRC and AH.

Global epidemiology of epithelial ovarian cancer.

Globally, ovarian cancer is the eighth most common cancer in women, accounting for an estimated 3.7% of cases and 4.7% of cancer deaths in 2020. Until the early 2000s, age-standardized incidence was highest in northern Europe and North America, but this trend has changed; incidence is now declining in these regions and increasing in parts of eastern Europe and Asia. Ovarian cancer is a very heterogeneous disease and, even among the most common type, namely epithelial ovarian cancer, five major clinically and genetically distinct histotypes exist. Most high-grade serous ovarian carcinomas are now recognized to originate in the fimbrial ends of the fallopian tube. This knowledge has led to more cancers being coded as fallopian tube in origin, which probably explains some of the apparent declines in ovarian cancer incidence, particularly in high-income countries; however, it also suggests that opportunistic salpingectomy offers an important opportunity for prevention. The five histotypes share several reproductive and hormonal risk factors, although differences also exist. In this Review, we summarize the epidemiology of this complex disease, comparing the different histotypes, and consider the potential for prevention. We also discuss how changes in the prevalence of risk and protective factors might have contributed to the observed changes in incidence and what this might mean for incidence in the future.

Abstract 798: Increasing breast cancer incidence across generation status in Mexican American women: The Multiethnic Cohort

Abstract Background: Breast cancer (BC) is the most commonly diagnosed cancer among Latino women in the US. Compared to foreign-born Latino women, US-born Latino women have a higher incidence of BC. While prior studies have suggested this difference in incidence may be explained by risk factors such as unhealthy lifestyle behaviors, reproductive history, and neighborhood socioeconomic status, it is unclear how the risk of BC has changed over generations among Latinos women. In this study, we investigated the association between generational status and BC incidence among Mexican American women within the Multiethnic Cohort (MEC). Methods: The study population included 15,303 self-reported Mexican Americans from the MEC. Generational status was categorized as: 1st generation (Mexico-born, n = 6,347), 2nd generation (US-born with one or two parents born in Mexico, n = 6,390), or 3rd generation (US-born with both parents born in the US, n = 2,566). Multivariable Cox models were used to calculate the hazard ratios (HR) and 95% confidence intervals (CI) of BC incidence by generational status. All models were adjusted for relevant risk factors including age, physical activity, smoking, alcohol intake, education, body mass index, diet, family history of BC, menopausal status, age at menarche, parity, mammography history, hormone use, neighborhood socioeconomic status, and Hispanic ethnic enclave. Results: During an average 21.5-year follow-up, 815 incident BC cases were identified. The age-adjusted incidence rate (per 100,000) of BC increased by generation (1st: 191.9; 2nd: 265.3; 3rd: 284.0). Third (70.4%) and 2nd (66.5%) generations had a larger proportion of localized disease at diagnosis compared to 1st generation women (59.7%). Compared to 1st generation Mexican Americans, 2nd (HR = 1.24; 95% CI: 1.03-1.49) and 3rd generation (HR = 1.28; 95% CI: 1.02-1.60) had elevated risks of BC (p-trend: 0.02) The positive association with generational status remained significant when restricting to women who reported mammogram use (HR 2nd vs. 1st = 1.27, 95% CI: 1.04-1.55; HR 3rd vs. 1st = 1.34, 95% CI: 1.06-1.70) (p-trend: 0.01). Conclusions: Our findings suggest that generational status among Mexican American women is associated with risk of BC, after adjusting for sociodemographic, lifestyle, neighborhood, and reproductive risk factors. Further studies are warranted to discover the potential factors that contribute to this increased risk and elucidate the underlying etiology. Citation Format: Xinman Zhang, Iona Cheng, Adelynn Paik, Brian Huang, Veronica Wendy Setiawan. Increasing breast cancer incidence across generation status in Mexican American women: The Multiethnic Cohort [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 798.

Associations of reproductive breast cancer risk factors with expression of stem cell markers in benign breast tissue.

We investigated the associations of reproductive factors known to influence breast cancer risk with the expression of breast stem cell markers CD44, CD24, and ALDH1A1 in benign breast biopsy samples. We included 439 cancer-free women with biopsy-confirmed benign breast disease within the Nurses' Health Study (NHS) and NHSII. The data on reproductive and other breast cancer risk factors were obtained from biennial questionnaires. Immunohistochemistry (IHC) was performed on tissue microarrays. For each core, the IHC expression was assessed using a semi-automated platform and expressed as % of cells that stained positive for a specific marker out of the total cell count. Generalized linear regression was used to examine the associations of reproductive factors with a log-transformed expression of each marker (in epithelium and stroma), adjusted for other breast cancer risk factors. In multivariate analysis, the time between menarche and age at first birth was inversely associated with CD44 in epithelium (β per 5 years = -0.38, 95% CI -0.69; -0.06). Age at first birth and the time between menarche and age at first birth were inversely associated with ALDH1A1 (stroma: β per 5 years = -0.43, 95% CI -0.76; -0.10 and β = -0.47, 95% CI -0.79; -0.15, respectively; epithelium: β = -0.15, 95% CI -0.30; -0.01 and β = -0.17, 95% CI -0.30; -0.03, respectively). Time since last pregnancy was inversely associated with stromal ALDH1A1 (β per 5 years = -0.55, 95% CI -0.98; -0.11). No associations were found for CD24. The observed associations were similar in premenopausal women. In postmenopausal women, lifetime duration of breastfeeding was inversely associated with stromal ALDH1A1 expression (β for ≥24 vs. 0 to <1 months = -2.24, 95% CI 3.96; -0.51, p-trend = 0.01). Early-life reproductive factors may influence CD44 and ALDH1A1 expression in benign breast tissue.

Breast Cancer Risk Factors among Women with Solid Breast Lesions.

Breast cancer is the most frequent malignancy in women worldwide and one of the most curable cancers if diagnosed at an early stage. Female patients presenting solid breast lesions are greatly predisposed to breast cancer development, and as such, effective screening of high-risk patients is valuable in early-stage breast cancer detection. The aim of our study was to identify the most relevant demographic, reproductive and lifestyle risk factors for breast cancer among women with solid breast lesions living in western Romania, namely the urban region consisting of Timisoara and the rural surrounding regions. From January 2017 to December 2021, 1161 patients with solid breast lesions, as detected by sonoelastography, were divided into two groups: patients with benign lesions (1019, 87.77%) and patients with malignant nodules (142, 12.23%). The malignancy group was confirmed by a histopathological result. Variables including age, BMI, menarche, menopause, years of exposure to estrogen, number of births, breastfeeding period, use of oral combined contraceptives, smoker status, family medical history and living area (rural-urban) were recorded. It was evidenced by our study that the main risk factors for malignancy were elevated age (OR = 1.07, 95% CI 1.05-1.08), BMI (OR = 1.06, 95% CI 1.02-1.10), living area (rural) (OR = 1.86, 95% CI 1.13-2.85) and family medical history (negative) (OR 3.13, 95% CI 1.43-8.29). The other proposed risk factors were not found to be statistically significant. Age and BMI were observed to be the most significant factors for breast cancer risk increase, followed by living in a rural area. A family history of breast cancer was shown to be inversely correlated with cancer risk increase.

Sociodemographic and reproductive risk factors associated with metabolic syndrome in a population of Brazilian women from the city of Ribeirão Preto: a cross-sectional study.

To identify sociodemographic and reproductive risk factors associated with MetS in women in their fourth decade of life. Cohort study conducted on women born from June 1978 to May 1979 in Ribeirão Preto, Brazil. Sociodemographic, clinical, and obstetric data were collected by interview and clinical evaluation. Univariable and multivariable binomial logistic regression models were constructed to identify the risk factors of metabolic syndrome and the adjusted relative risk (RR) was calculated. The cohort included 916 women, and 286 (31.2%) of them have metabolic syndrome. MetS was associated with lack of paid work (RR 1.49; 95% CI 1.14-1.95), marital status of without a partner (RR 1.33; 95% CI 1.03-1.72), low educational level (less than 8 years of schooling [RR 1.72; 95% CI 1.23-2.41], 8 to 12 years of schooling [RR 1.37; 95% CI 1.06-1.76], when compared with more than 12 years of schooling), and teenage pregnancy (RR 2.00; 95% CI 1.45-2.77). There was no association between MetS, and the other covariates studied. Metabolic syndrome in a population of women in the fourth decade of life was associated with lack of employment, lack of a partner, low educational level, and teenage pregnancy.

Assessing breast arterial calcification in mammograms and its implications for atherosclerotic cardiovascular disease risk

PurposeBreast arterial calcifications (BAC) are incidentally observed on mammograms, yet their implications remain unclear. We investigated lifestyle, reproductive, and cardiovascular determinants of BAC in women undergoing mammography screening. Further, we investigated the relationship between BAC, coronary arterial calcifications (CAC) and estimated 10-year atherosclerotic cardiovascular (ASCVD) risk. MethodsIn this cross-sectional study, we obtained reproductive history and CVD risk factors from 215 women aged 18 or older who underwent mammography and cardiac computed tomographic angiography (CCTA) within a 2-year period between 2007 and 2017 at hospital. BAC was categorized as binary (present/absent) and semi-quantitatively (mild, moderate, severe). CAC was determined using the Agatston method and recorded as binary (present/absent). Adjusted odds ratios (ORs) and 95 % confidence intervals (CIs) were calculated, accounting for age as a confounding factor. ASCVD risk over a 10-year period was calculated using the Pooled Cohort Risk Equations. ResultsOlder age, systolic and diastolic blood pressures, higher parity, and younger age at first birth (≤28 years) were significantly associated with greater odds of BAC. Women with both BAC and CAC had the highest estimated 10-year risk of ASCVD (13.30 %). Those with only BAC (8.80 %), only CAC (5.80 %), and no BAC or CAC (4.40 %) had lower estimated 10-year risks of ASCVD. No association was detected between presence of BAC and CAC. ConclusionsThese findings support the hypothesis that BAC on a screening mammogram may help to identify women at potentially increased risk of future cardiovascular disease without additional cost and radiation exposure.

Risk Factors for Ovarian Cancer by BRCA Status: A Collaborative Case-Only Analysis.

Women with an inherited pathogenic variant in BRCA1 or BRCA2 have a greatly increased risk of developing ovarian cancer, but the importance of behavioral factors is less clear. We used a case-only design to compare the magnitude of associations with established reproductive, hormonal, and lifestyle risk factors between BRCA mutation carriers and noncarriers. We pooled data from five studies from the Ovarian Cancer Association Consortium including 637 BRCA carriers and 4,289 noncarriers. Covariate-adjusted generalized linear mixed models were used to estimate interaction risk ratios (IRR) and 95% confidence intervals (CI), with BRCA (carrier vs. noncarrier) as the response variable. IRRs were above 1.0 for known protective factors including ever being pregnant (IRR = 1.29, 95% CI; 1.00-1.67) and ever using the oral contraceptive pill (1.30, 95% CI; 1.07-1.60), suggesting the protective effects of these factors may be reduced in carriers compared with noncarriers. Conversely, the IRRs for risk factors including endometriosis and menopausal hormone therapy were below 1.0, suggesting weaker positive associations among BRCA carriers. In contrast, associations with lifestyle factors including smoking, physical inactivity, body mass index, and aspirin use did not appear to differ by BRCA status. Our results suggest that associations with hormonal and reproductive factors are generally weaker for those with a pathogenic BRCA variant than those without, while associations with modifiable lifestyle factors are similar for carriers and noncarriers. Advice to maintain a healthy weight, be physically active, and refrain from smoking will therefore benefit BRCA carriers as well as noncarriers.

Differential patterns of reproductive and lifestyle risk factors for breast cancer according to birth cohorts among women in China, Japan and Korea.

The birth cohort effect has been suggested to influence the rate of breast cancer incidence and the trends of associated reproductive and lifestyle factors. We conducted a cohort study to determine whether a differential pattern of associations exists between certain factors and breast cancer risk based on birth cohorts. This was a cohort study using pooled data from 12 cohort studies. We analysed associations between reproductive (menarche age, menopause age, parity and age at first delivery) and lifestyle (smoking and alcohol consumption) factors and breast cancer risk. We obtained hazard ratios (HRs) with 95% confidence intervals (CIs) using the Cox proportional hazard regression analysis on the 1920s, 1930s, 1940s and 1950s birth cohorts. Parity was found to lower the risk of breast cancer in the older but not in the younger birth cohort, whereas lifestyle factors showed associations with breast cancer risk only among the participants born in the 1950s. In the younger birth cohort group, the effect size was lower for parous women compared to the other cohort groups (HR [95% CI] 0.86 [0.66-1.13] compared to 0.60 [0.49-0.73], 0.46 [0.38-0.56] and 0.62 [0.51-0.77]). Meanwhile, a higher effect size was found for smoking (1.45 [1.14-1.84] compared to 1.25 [0.99-1.58], 1.06 [0.85-1.32] and 0.86 [0.69-1.08]) and alcohol consumption (1.22 [1.01-1.48] compared to 1.10 [0.90-1.33], 1.15 [0.96-1.38], and 1.07 [0.91-1.26]). We observed different associations of parity, smoking and alcohol consumption with breast cancer risk across various birth cohorts.

Genetic contribution of reproductive traits to risk of uterine leiomyomata: a large-scale, genome-wide, cross-trait analysis

BackgroundWhile phenotypic associations between female reproductive characteristics and uterine leiomyomata have long been observed in epidemiological investigations, the shared genetic architecture underlying these complex phenotypes remains unclear. ObjectiveWe aimed to investigate the shared genetic basis, pleiotropic effects, and potential causal relationships underlying reproductive traits (age at menarche, age at natural menopause, and age at first birth) and uterine leiomyomata . Study designUtilizing large-scale genome-wide association studies conducted in women of European ancestry for age at menarche (N = 329,345), age at natural menopause (N = 201,323), age at first birth (N = 418,758), and uterine leiomyomata (Ncases/Ncontrols = 35,474/267,505), we performed a comprehensive genome-wide cross-trait analysis to examine systematically the common genetic influences between reproductive traits and UL. ResultsSignificant global genetic correlations were identified for uterine leiomyomata with age at menarche (rg = –0.17, P = 3.65 × 10–10), age at natural menopause (rg = 0.23, P = 3.26 × 10–07), and age at first birth (rg = –0.16, P = 1.96 × 10–06). Thirteen genomic regions were further revealed as contributing significant local correlations to age at natural menopause and uterine leiomyomata. Cross-trait meta-analysis identified 23 shared loci, three of which were novel. Transcriptome-wide association study found 15 shared genes, targeting tissues of the digestive, exo-/endocrine, nervous, and cardiovascular systems. Mendelian randomization suggested causal relationships of genetically predicted later age at menarche (OR = 0.88, 95% CI = 0.85-0.92, P = 1.50 × 10–10) or later age at first birth (OR = 0.95, 95% CI = 0.90-0.99, P = 0.02) with a reduced risk of uterine leiomyomata, and a causal relationship of genetically predicted later age at natural menopause with an increased risk of uterine leiomyomata (OR = 1.08, 95% CI = 1.06-1.09, P = 2.30 × 10–27). No causal association in the reverse direction was found. ConclusionsOur work highlights substantial shared genetic influences as well as significant causal links underlying reproductive traits and uterine leiomyomata. Findings suggest that early identification of female reproductive risk factors may facilitate the initiation of strategies to modify potential uterine leiomyomata risk.

Risk factors for breast cancer among women in Freetown, Sierra Leone, 2017: a case-control study.

breast cancer is the most commonly diagnosed malignancy and an important cause of cancer death among females worldwide. The disease accounted for 25% (1.67 million) of new cancer cases and the fifth cause of cancer deaths. Incidence of all types of cancers is approximately 25% in Sierra Leone. However, there was no documented evidence on risk factors for breast cancer among women in the country. The main aim of this study was to assess risk factors associated with breast cancer among women screened for breast cancer in Freetown Sierra Leone. we conducted a case-control study on breast cancer involving 116 confirmed breast cancer cases and 116 controls. Questionnaire was designed to collect data on socio-demographic, reproductive and behavioral risk factors. Analysis was carried using logistic regression to assess the associations between breast cancer and the risk factors. in the final multiple logistic regression, had formal educational level, (aOR 0.1, 0.03-0.26, p= 0.001) physical activity for more than 30 minutes per week (aOR 0.5 (0.9- 0.7, p=0.001). Cigarette smoking (aOR 4.8, 1.2-18.5, p=0.023) and family history of breast cancer (aOR 9.9 cigarette smoking (OR 4.4, 1.2-18.5, p=0.023) and family history of breast cancer (OR 9.9, 2.7-36.45, p=0.040) were identified as the main risk factors for breast cancer. This study did not find any statistically significant associations between reproductive risk factors and breast cancer. risk factors for breast cancer among women in Sierra Leone include educational level, physical activity, cigarette smoking and family history of breast cancer. We recommended screening program for women above 40 years and had history of breast cancer. Also, to establish breast cancer registry.

Factors related to Morbidity and Mortality in cases of Maternal death of the Mexican Social Security Institute of Sinaloa for the year 2021- 2022

Introduction: obstetric morbidity runs parallel to maternal mortality rates, so it is a way to evaluate the quality of care provided. Behind every maternal death lies a personal tragedy that can be resolved. The objective is to relate the factors of Maternal Morbidity and Mortality in cases of maternal death in the Mexican Social Security Institute, Sinaloa from 2021 to 2022.Method: study population integrated into a sample of 116 pregnant women from the IMSS Sinaloa, identified through the “PAMM” database and institutional records, associating sociodemographic variables, reproductive and prenatal risk factors, comorbidities in the pregnant stage and action protocols, achieving the creation of a logistic regression model. Non-probabilistic convenience sampling. Observational, analytical, retrospective and transversal research design.Results: the variables of pregestational care, BMI, transfer, place of occurrence, APP of DM2 and SAH, complications in previous pregnancies and immunization of COVID and influenza, explain maternal mortality by 55,2 % according to the Cox and Snell R2 coefficient.Conclusion: addressing the differences of the health institution by ethnicity, gender, social territory, life cycles will give the possibility of making visible the true scenarios behind a maternal death: Preconception risk factors and Specific Action Protocols