Risk Of Premenopausal Breast Cancer Research Articles

Breast cancer in women with previous gestational diabetes: a nationwide register-based cohort study

BackgroundGestational diabetes mellitus (GDM) is a common pregnancy complication characterized by insulin resistance. A link has been suggested between insulin resistance and breast cancer, which is the most common cancer in women. Hence, women with previous GDM may be at increased risk of developing breast cancer, yet, the existing evidence is conflicting. This study explored the association between GDM and incident breast cancer, including age at cancer diagnosis. Additionally, we investigated the potential impact of severity of insulin resistance during pregnancy and of subsequent diabetes development on the breast cancer risk.MethodsWe conducted a nationwide, register-based cohort study including all women giving birth in Denmark from 1997 to 2018. We defined GDM and breast cancer based on ICD-10 codes. Premenopausal and postmenopausal breast cancer was pragmatically defined as age at outcome < 50 years and ≥ 50 years, respectively. A proxy for severity of insulin resistance during pregnancy was based on insulin treatment; subsequent diabetes was defined as presence of ICD-10 codes and/or antidiabetic medication after pregnancy. The statistical analyses included Cox regression, logistic regression and t-test.ResultsOf 708,121 women, 3.4% had GDM. The median follow-up period was 11.9 years (range 0-21.9). The overall breast cancer risk was comparable in women with and without previous GDM (adjusted hazard ratio 0.96 [95% CI 0.83–1.12]). Premenopausal and postmenopausal breast cancer risk also did not differ; however, women with previous GDM had a breast cancer diagnosis at younger age (42.6 vs. 43.5 years, p-value 0.01). All-cause mortality was similar regardless of GDM history. Severity of insulin resistance during pregnancy and subsequent diabetes did not affect breast cancer risk.ConclusionsThis large, population-based cohort study showed no higher risk of incident breast cancer in women with previous GDM compared to women without previous GDM after a median of almost 12 years of follow-up. This was evident irrespective of menopausal state. The breast cancer risk was not influenced by the severity of insulin resistance during pregnancy and by subsequent diabetes development. Regardless of GDM history, attention towards prevention, early detection and treatment of breast cancer should be prioritized.

Urinary artificial sweeteners and breast cancer risk in women from the Moli-sani Study

Abstract Background Artificial sweeteners (AS) are chemical substances developed by the food industry to reduce sugar and calories while maintaining sweetness. Cohort studies suggested an increased risk of certain cancers, including breast cancer (BC), associated with AS intake, however evidence exclusively relied on self-reported dietary data rather than objectively measured AS. We examined the association of urinary biomarkers denoting AS intake with BC risk in women from the large Moli-sani Study. Methods Using a case-cohort design, a sample of 987 middle-aged women (mean age 55±12 y) was randomly selected as sub-cohort and compared with 273 women with incident BC (26 of them also belong to the sub-cohort). A total of 6 commonly used AS (i.e. aspartame, acesulfame, saccharine, sucralose, cyclamate, and steviol glycosides) were measured through liquid chromatography-mass spectrometry in urinary samples (creatinine-adjusted concentrations; µg/mg) collected at baseline (2005-2010). The multivariable hazard ratios (HRs) were estimated through Cox regression models using the Prentice method, where each AS was dichotomized as absence/presence, independent of concentrations. Results The main urinary AS was saccharine (E954), contributing to 71% of total AS, followed by steviol glycosides (E960;11%). During a median follow-up of 13.2 y we identified 38 premenopausal and 235 postmenopausal incident BC cases. In multivariable-adjusted Cox analyses, none of the individual AS was associated with overall BC risk, nor was the total urinary AS (HR = 0.93; 95%CI 0.63-1.37 for 1-unit increment). Compared to absence, presence of sucralose (E955) in urine was linked to premenopausal BC (HR = 4.23: 95%CI 1.23-14.51; p = 0.022). Conclusions Urinary artificial sweeteners were not associated with BC risk. However, sucralose presence in urine was linked to a higher risk of premenopausal BC. Prospective, dose-related studies with larger sample size are warranted to possibly confirm our findings. Key messages • The presence in the urine of commonly used artificial sweeteners was not associated with breast cancer risk. • Presence of urinary sucralose was linked to higher risk of premenopausal breast cancer.

Breast cancer risk and prevention in 2024: An overview from the Breast Cancer UK - Breast Cancer Prevention Conference.

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/β 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/β 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.

Abstract PS10-09: Development of an absolute risk prediction model for premenopausal breast cancer in an international consortium

Abstract Risk prediction models that have been developed for overall breast cancer risk are based on a limited number of premenopausal cases in individual cohorts. As some risk factors differ in their associations with pre- versus postmenopausal breast cancer, a distinct risk prediction model is needed for premenopausal breast cancer. We developed a risk prediction model for premenopausal breast cancer using 779,601 participants and 9,665 incident cases from 18 prospective studies within the Premenopausal Breast Cancer Collaborative Group (PBCCG), across North America (N=9), Europe (N=6), Australia (N=1), and Asia (N=2). Data were split, within each cohort, into training (2/3) and testing (1/3) datasets. Individual risk was assessed in five-year intervals, using variables reported at the start of the time interval. Cox proportional hazards regression was used to model risk factors in a backwards-selection method, stratified by cohort: age at menarche, age at first birth, parity, breastfeeding (months), height (cm), BMI (kg/m2), BMI at age 18, recent weight change (kg), alcohol consumption (drinks/week), first-degree family history of breast cancer, and personal history of benign breast disease. To enable the use of information from all cohorts despite differences in missing variables by design, cohorts were grouped by available variables and risk models were fit for each group. In cohorts with incomplete data, model coefficients were adjusted based on the correlation of covariates with the missing variables in the complete case dataset. Coefficients were meta-analyzed with inverse variance weighting to obtain final coefficients. Discrimination was evaluated in the testing dataset by calculation of the c-index. Work is ongoing to calibrate the model based on five-year absolute risk using GLOBOCAN continent- and age-specific incidence rates to represent baseline risk. The final model included age at menarche, parity, height, BMI, BMI at age 18, first-degree family history of breast cancer, and history of benign breast disease. Young adulthood BMI and BMI (at start of the 5-year risk interval) were associated with a decreased risk (Hazard Ratio (HR) (95% confidence interval (CI)) per 5 kg/m2 = 0.87 (0.81-0.93) and 0.90 (0.86-0.95), respectively) as was parity (HR (95% CI) = 0.92 (0.90-0.94)). Height was associated with increased risk (HR (95% CI) per 10 cm = 1.14 (1.07-1.21)), while history of benign breast disease and family history were associated with larger increases in risk (HR (95% CI) = 1.64 (1.30-2.06) and 1.76 (1.63-1.90), respectively). Model discrimination was higher than that reported for women under 50 years in existing breast cancer risk prediction models considering clinical factors (AUC (95% CI) = 0.61 (0.59-0.62)). Calibration of absolute 5-year risk is ongoing. Several factors driving risk prediction of postmenopausal breast cancer have similar influence on risk of premenopausal breast cancer, while family history has a stronger influence on premenopausal breast cancer risk. Our model demonstrates acceptable discrimination and will enable individual 5-year absolute risk prediction for premenopausal breast cancer. Citation Format: Kristen Brantley, Michael Jones, Minouk Schoemaker, Hazel Nichols, Anthony Swerdlow, Robert MacInnis, Roger Milne, Tess Clenenden, Yu Chen, Xiao-Ou Shu, Wei Zheng, Woon-Puay Koh, Jian-Min Yuan, Cari Kitahara, Martha Linet, Dale Sandler, Bernard A Rosner, Peter Kraft, A. Heather Eliassen. Development of an absolute risk prediction model for premenopausal breast cancer in an international consortium [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 PS10-09.

Ambient polycyclic aromatic hydrocarbon exposure and breast cancer risk in a population-based Canadian case–control study

PurposePolycyclic aromatic hydrocarbons (PAHs) represent a class of ubiquitous pollutants recognized as established human carcinogens and endocrine-disrupting chemicals. PAHs have seldom been modeled at the population-level in epidemiological studies. Fluoranthene is a prevalent PAH in urban settings and correlates with the occurrence of other PAHs. The purpose of this study was to evaluate associations between long-term residential exposure to ambient PAHs and breast cancer risk, both pre- and post-menopausal, in Canada.MethodsUsing the National Enhanced Cancer Surveillance System (NECSS), a national-scale Canadian population-based case–control study, annual fluoranthene exposures were estimated using the GEM-MACH-PAH chemical transport model on the basis of geocoded residential histories throughout a 20-year exposure window. Odds ratios (ORs) and 95% confidence intervals (CIs) controlling for potential confounders were estimated using logistic regression. Separate analyses were conducted for Ontario and national samples given a finer-resolution exposure surface and additional risk factor information available for Ontario.ResultsPositive associations were observed between fluoranthene exposure and premenopausal breast cancer, with inconsistent findings for postmenopausal breast cancer. For premenopausal breast cancer, adjusted ORs of 2.48 (95% CI: 1.29, 4.77) and 1.59 (95% CI: 1.11, 2.29) were observed when comparing the second highest category of exposure to the lowest, among the Ontario and national samples, respectively. For postmenopausal breast cancer, adjusted ORs were 1.10 (95% CI: 0.67, 1.80) and 1.33 (95% CI: 1.02, 1.73). Associations for the highest level of exposure, across both samples and menopausal strata, were non-significant.ConclusionThis study provides support for the hypothesis that ambient PAH exposures increase the risk of premenopausal breast cancer.

Active and passive smoking and breast cancer in Japan: a pooled analysis of nine population-based cohort studies.

Epidemiological studies have shown inconsistent results regarding the link between smoking and breast cancer risk, despite the biological plausibility of a positive association. Participants were 166 611 women from nine prospective cohort studies in Japan which launched in 1984-1994 and followed for 8-22 years. Information on smoking and secondhand smoke was obtained through self-administered baseline questionnaires. Breast cancer was defined as code C50 according to the International Classification of Diseases for Oncology, 3rd Edition or the International Classification of Diseases, 10th Revision. After adjusting for several potential confounders, relative risks for breast cancer were calculated in the individual studies according to the current or previous status of active and passive smoking using Cox regression, followed by a summary estimate of hazard ratios using random-effects meta-analyses. Of the 60 441 participants who reported being premenopausal and 106 170 who reported being postmenopausal at baseline, 897 and 1168 developed breast cancer during follow-up, respectively. Compared with never smokers, current smokers had a higher risk of developing breast cancer before the age of 50 years. In addition, ever smokers who started smoking at 30 years of age or younger, or who started smoking before first childbirth, had a higher risk of developing breast cancer before the age of 50 years. No association between adulthood or childhood exposure to secondhand smoke and breast cancer was observed. Smoking may increase the risk of premenopausal breast cancer, and smoking earlier in life might be especially harmful. The impact of secondhand smoke needs further investigation.

CYP2C8 rs11572080 and CYP3A4 rs2740574 risk genotypes in paclitaxel-treated premenopausal breast cancer patients

Breast cancer (BC) is the most prevalent malignancy in women globally. At time of diagnosis, premenopausal BC is considered more aggressive and harder to treat than postmenopausal cases. Cytochrome P450 (CYP) enzymes are responsible for phase I of estrogen metabolism and thus, they are prominently involved in the pathogenesis of BC. Moreover, CYP subfamily 2C and 3A play a pivotal role in the metabolism of taxane anticancer agents. To understand genetic risk factors that may have a role in pre-menopausal BC we studied the genotypic variants of CYP2C8, rs11572080 and CYP3A4, rs2740574 in female BC patients on taxane-based therapy and their association with menopausal status. Our study comprised 105 female patients with histologically proven BC on paclitaxel-therapy. They were stratified into pre-menopausal (n = 52, 49.5%) and post-menopausal (n = 53, 50.5%) groups. Genotyping was done using TaqMan assays and employed on Quantstudio 12 K flex real-time platform. Significant increased frequencies of rs11572080 heterozygous CT genotype and variant T allele were established in pre-menopausal group compared to post-menopausal group (p = 0.023, 0.01, respectively). Moreover, logistic regression analysis revealed a significant association between rs11572080 CT genotype and premenopausal BC. However, regarding rs2740574, no significant differences in genotypes and allele frequencies between both groups were detected. We reported a significant association between CYP2C8 genotypic variants and premenopausal BC risk in Egyptian females. Further studies on larger sample sizes are still needed to evaluate its importance in early prediction of BC in young women and its effect on treatment outcome.

International Pooled Analysis of Leisure-Time Physical Activity and Premenopausal Breast Cancer in Women From 19 Cohorts.

There is strong evidence that leisure-time physical activity is protective against postmenopausal breast cancer risk but the association with premenopausal breast cancer is less clear. The purpose of this study was to examine the association of physical activity with the risk of developing premenopausal breast cancer. We pooled individual-level data on self-reported leisure-time physical activity across 19 cohort studies comprising 547,601 premenopausal women, with 10,231 incident cases of breast cancer. Multivariable Cox regression was used to estimate hazard ratios (HRs) and 95% CIs for associations of leisure-time physical activity with breast cancer incidence. HRs for high versus low levels of activity were based on a comparison of risk at the 90th versus 10th percentiles of activity. We assessed the linearity of the relationship and examined subtype-specific associations and effect modification across strata of breast cancer risk factors, including adiposity. Over a median 11.5 years of follow-up (IQR, 8.0-16.1 years), high versus low levels of leisure-time physical activity were associated with a 6% (HR, 0.94 [95% CI, 0.89 to 0.99]) and a 10% (HR, 0.90 [95% CI, 0.85 to 0.95]) reduction in breast cancer risk, before and after adjustment for BMI, respectively. Tests of nonlinearity suggested an approximately linear relationship (Pnonlinearity = .94). The inverse association was particularly strong for human epidermal growth factor receptor 2-enriched breast cancer (HR, 0.57 [95% CI, 0.39 to 0.84]; Phet = .07). Associations did not vary significantly across strata of breast cancer risk factors, including subgroups of adiposity. This large, pooled analysis of cohort studies adds to evidence that engagement in higher levels of leisure-time physical activity may lead to reduced premenopausal breast cancer risk.

Smoking history and breast cancer risk by pathological subtype: MCC-Spain study.

The role of cigarette smoking on breast cancer risk remains controversial, due to its dual carcinogenic-antiestrogenic action. In the population-based multi-case-control study (MCC-Spain), we collected epidemiological and clinical information for 1733 breast cancer cases and 1903 controls, including smoking exposure. The association with breast cancer, overall, by pathological subtype and menopausal status, was assessed using logistic and multinomial regression models. Smokers had higher risk of premenopausal breast cancer, particularly if they had smoked ≥30 years (AOR=1.75; 95% CI: 1.04-2.94), although most estimates did not achieve statistical significance. In contrast, among postmenopausal women, smoking was associated with lower risk of breast cancer, mainly in overweight and obese women. The strongest risk reductions were observed among postmenopausal women who had stopped smoking ≥10 years before cancer diagnosis, particularly for HER2+ tumors (AOR=0.28; 95% CI: 0.11-0.68); p for heterogeneity = 0.040). Also, those who had smoked <10 pack-years (AOR=0.68; 95% CI: 0.47-0.98) or 10-25 pack-years (AOR=0.62; 95% CI: 0.42-0.92) during their lifetime were at a reduced risk of all breast cancer subtypes (p for heterogeneity: 0.405 and 0.475, respectively); however, women who had smoked more than 25 pack-years showed no reduced risk. Menopausal status plays a key role in the relationship between tobacco and breast cancer for all cancer subtypes. While smoking seems to increase the risk in premenopausal woman, it might be associated to lower risk of breast cancer among postmenopausal women with excess weight.

Prediagnostic selenium status, selenoprotein gene variants and association with breast cancer risk in a European cohort study

Selenium (Se) may help prevent breast cancer (BC) development. Owing to limited observational evidence, we investigated whether prediagnostic Se status and/or variants in the selenoprotein genes are associated with BC risk in a large European cohort. Se status was assessed by plasma measures of Se and its major circulating proteins, selenoprotein P (SELENOP) and glutathione peroxidase 3 (GPX3), in matched BC case-control pairs (2208 for SELENOP; 1785 for GPX3 and Se) nested within the European Prospective Investigation into Cancer and Nutrition (EPIC). Single nucleotide polymorphisms (SNPs, n = 452) in 55 selenoprotein and Se metabolic pathway genes and an additional 18 variants previously associated with Se concentrations were extracted from existing genotyping data within EPIC for 1564 case-control pairs. Multivariable-adjusted logistic regression models were used to calculate the odds ratios (ORs) and 95 % confidence intervals (CIs) of the association between Se status markers, SNP variants and BC risk. Overall, there was no statistically significant association of Se status with BC risk. However, higher GPX3 activity was associated with lower risk of premenopausal BC (4th versus 1st quartile, OR = 0.54, 95 % CI: 0.30–0.98, Ptrend = 0.013). While none of the genetic variant associations (P ≤ 0.05) retained significance after multiple testing correction, rs1004243 in the SELENOM selenoprotein gene and two SNPs in the related antioxidant TXN2 gene (rs4821494 and rs5750261) were associated with respective lower and higher risks of BC at a significance threshold of P ≤ 0.01. Fourteen SNPs in twelve Se pathway genes (P ≤ 0.01) in interaction with Se status were also associated with BC risk. Higher Se status does not appear to be associated with BC risk, although activity of the selenoenzyme GPX3 may be inversely associated with premenopausal BC risk, and SNPs in the Se pathway alone or in combination with suboptimal Se status may influence BC risk.

Exosomes isolated from metabolically unhealthy normal weight and overweight phenotypes deteriorate the ER/PR positive breast cancer behavior.

Obesity has been linked to a higher risk of postmenopausal breast cancer Yet, research indicates an opposite correlation between obesity and premenopausal breast cancer risk. Various obesity phenotypes based on metabolic health could play a significant part. This study aims to assess how plasma exosomes taken from women with varying obesity phenotypes impact MCF-7 cell migration, matrix metalloproteinase-2 activity, and apoptosis. The characterization of isolated exosomes and their internalization into MCF-7 cells was evaluated. The treatment of MCF-7 cells with exosomes isolated from different groups was done. Migration, the activity of MMP-2, mRNA expression of Bax and Bcl-2, protein expression of p-53 and Thr55 p-p53, and apoptosis were assessed. Isolated exosomes from unhealthy obese individuals increase MCF-7 cell migration. Regarding MMP activities, unhealthy normal weight and overweight and healthy obese groups isolated exosomes increase the MMP-2 activity than the treated group with exosomes isolated from counterpart groups. Furthermore, unhealthy normal weight and overweight and healthy obese obtained exosomes decrease apoptosis compared to counterpart groups. Altogether, plasma exosomes derived from both unhealthy individuals with normal weight and overweight status, as well as those with unhealthy obesity, negatively impacted the behavior of estrogen/progesterone receptor-positive breast cancer cells. The online version contains supplementary material available at 10.1007/s40200-023-01295-1.

Association between vaginal bleeding in pregnancy that resulted in delivery and risk of cancer: A Danish registry-based cohort study.

Vaginal bleeding (VB) before 20 gestational weeks of a viable pregnancy is a manifestation of a threatened miscarriage. VB is associated with increased levels of pro-inflammatory cytokines such as interferon-gamma, tumour necrosis factor-alpha and interleukin-6. Increased levels of these cytokines and oxidative stress are risk factors for cancer. The risk of cancer following a VB-affected pregnancy that ended in childbirth is unknown. To investigate the associations between VB in pregnancy that resulted in delivery and risk of incident cancer. We conducted a cohort study (1995-2018) in Denmark using administrative and healthcare registries. We included 37,082 VB-affected deliveries, 1,363,614 VB-unaffected deliveries, 324,328 pregnancies ending in terminations, and 137,104 miscarriages. We computed the absolute risk of cancer and hazard ratios (HR) with 95% confidence intervals (CI) adjusted for age, calendar year, morbidities, and socio-economic factors using Cox proportional hazards regression. Multiple pregnancies to the same woman were accounted for in the analysis. The median (25th-75th percentile) follow-up in the study was 12.6 (6.9, 18.2) years. The prevalence of VB in the present study was 3%. At the end of the follow-up, there were 1320 cancer cases among the VB-affected delivery cohort, 40,420 among the VB-unaffected delivery cohort, 10,300 among the termination cohort and 4790 among the miscarriage cohort. HRs for any cancer among VB-affected deliveries were 1.03 (95% CI 0.97, 1.08) compared with VB-unaffected deliveries, 1.03 (95% CI 0.97, 1.09) compared with terminations and 0.90 (95% CI 0.84, 0.95) compared with miscarriages. There were no increased risks of premenopausal breast cancer, cervical cancer, ovary and fallopian tube cancer or uterine cancer following VB-affected deliveries vs. comparison cohorts. We found no evidence of an association between vaginal bleeding in pregnancy and an increased risk of cancer.

Associations of height, body mass index, and weight gain with breast cancer risk in carriers of a pathogenic variant in BRCA1 or BRCA2: the BRCA1 and BRCA2 Cohort Consortium

IntroductionHeight, body mass index (BMI), and weight gain are associated with breast cancer risk in the general population. It is unclear whether these associations also exist for carriers of pathogenic variants in the BRCA1 or BRCA2 genes.Patients and methodsAn international pooled cohort of 8091 BRCA1/2 variant carriers was used for retrospective and prospective analyses separately for premenopausal and postmenopausal women. Cox regression was used to estimate breast cancer risk associations with height, BMI, and weight change.ResultsIn the retrospective analysis, taller height was associated with risk of premenopausal breast cancer for BRCA2 variant carriers (HR 1.20 per 10 cm increase, 95% CI 1.04–1.38). Higher young-adult BMI was associated with lower premenopausal breast cancer risk for both BRCA1 (HR 0.75 per 5 kg/m2, 95% CI 0.66–0.84) and BRCA2 (HR 0.76, 95% CI 0.65–0.89) variant carriers in the retrospective analysis, with consistent, though not statistically significant, findings from the prospective analysis. In the prospective analysis, higher BMI and adult weight gain were associated with higher postmenopausal breast cancer risk for BRCA1 carriers (HR 1.20 per 5 kg/m2, 95% CI 1.02–1.42; and HR 1.10 per 5 kg weight gain, 95% CI 1.01–1.19, respectively).ConclusionAnthropometric measures are associated with breast cancer risk for BRCA1 and BRCA2 variant carriers, with relative risk estimates that are generally consistent with those for women from the general population.

Hypertensive conditions of pregnancy, preterm birth, and premenopausal breast cancer risk: a premenopausal breast cancer collaborative group analysis.

Women with preeclampsia are more likely to deliver preterm. Reports of inverse associations between preeclampsia and breast cancer risk, and positive associations between preterm birth and breast cancer risk are difficult to reconcile. We investigated the co-occurrence of preeclampsia/gestational hypertension with preterm birth and breast cancer risk using data from the Premenopausal Breast Cancer Collaborative Group. Across 6 cohorts, 3096 premenopausal breast cancers were diagnosed among 184,866 parous women. We estimated multivariable hazard ratios (HR) and 95% confidence intervals (CI) for premenopausal breast cancer risk using Cox proportional hazards regression. Overall, preterm birth was not associated (HR 1.02, 95% CI 0.92, 1.14), and preeclampsia was inversely associated (HR 0.86, 95% CI 0.76, 0.99), with premenopausal breast cancer risk. In stratified analyses using data from 3 cohorts, preterm birth associations with breast cancer risk were modified by hypertensive conditions in first pregnancies (P-interaction = 0.09). Preterm birth was positively associated with premenopausal breast cancer in strata of women with preeclampsia or gestational hypertension (HR 1.52, 95% CI: 1.06, 2.18), but not among women with normotensive pregnancy (HR = 1.09, 95% CI: 0.93, 1.28). When stratified by preterm birth, the inverse association with preeclampsia was more apparent, but not statistically different (P-interaction = 0.2), among women who did not deliver preterm (HR = 0.82, 95% CI 0.68, 1.00) than those who did (HR = 1.07, 95% CI 0.73, 1.56). Findings support an overall inverse association of preeclampsia history with premenopausal breast cancer risk. Estimates for preterm birth and breast cancer may vary according to other conditions of pregnancy.

Abstract 4215: Air pollution exposure during pregnancy and risk of premenopausal breast cancer among women with a family history of cancer

Abstract Background: Having a family history of breast or ovarian cancer is an important risk factor for premenopausal breast cancer. One reason for this could be that women with an underlying genetic susceptibility are more sensitive to environmental exposures due to gene-environment interactions. This might be especially important if the exposure occur during windows of susceptibility, such as pregnancy. Aim: The aim of this project is to determine if exposure to air pollution during pregnancy is associated with premenopausal breast cancer in a population with a known family history of breast or ovarian cancer. Methods: The project is based on nation-wide data from Sweden’s national registers and utilizes a cohort study design. The original cohort consists of women who gave birth to their first child between 1992 and 2015 (n=1 074 925), from this cohort we will select women with at least one first degree relative with breast or ovarian cancer (confirmed through register linkage). The primary outcome is primary breast cancer diagnosed before 50 years of age, and the exposure is levels of air pollution (PM10, PM2.5 and NO2) at the participant’s home address during each pregnancy. Cox proportional hazards regression will be used to determine hazard ratios using age as the time-scale. Results: The registry based linkage makes it possible to distinguish between both relational context (mother or sister), number of afflicted first degree relatives and type of cancer (breast or ovarian). All included women also have at least one recorded pregnancy (prior to any cancer diagnosis). Conclusion: This large scale study will be able to provide important information about the impact of air pollution exposure during pregnancy on breast cancer risk in a population with a documented family history of breast or ovarian cancer. Citation Format: Anna Hettinger, Jessica Edlund, Malin Gustafsson, Jenny Lindén, Wendy Yi-Ying Wu, Anna Oudin, Sophia Harlid. Air pollution exposure during pregnancy and risk of premenopausal breast cancer among women with a family history of cancer. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4215.

Abstract 4214: Exposure to air pollution during pregnancy and risk of premenopausal breast cancer: A Swedish nation-wide cohort study including more than 1 million women

Abstract Background: Air pollution has been linked to an increased risk of breast cancer, but most previous studies have not considered if the exposure occurred during windows of susceptibility, such as pregnancy. Pregnancy is a period of rapid changes to both the breast tissue and the surrounding microenvironment. Exposures during this sensitive time-period could therefore result in erosion of the protective effect of pregnancy and make women more susceptible to external breast cancer risk factors. Aim: The aim of this study was to identify associations between air pollution exposure, occurring specifically during pregnancy, and risk of premenopausal breast cancer. Method: Using nation-wide data from Swedish registers we constructed a cohort consisting of all women in Sweden who gave birth to their first child between January 1st 1991 and December 31st 2015. Women with a cancer diagnosis prior to pregnancy were excluded. Data on air pollution (yearly averages of PM10, PM2.5 and NO2), was collected from the residence of women during, and to some extent between, pregnancies. Associations between air pollution and premenopausal breast cancer is evaluated using Cox proportional hazards regression to estimate hazard ratios (HR), using age as the time scale and including appropriate confounders such as socioeconomic variables, comorbidities and family history of breast or ovarian cancer. Results: The full cohort included 1 074 925 unique women and 2 302 256 pregnancies (the mean number of pregnancies for each woman was 1.75). During the study period, 13 292 (1.2 %) were diagnosed with breast cancer before they turned 50 years. Conclusion: Our working hypothesis is that women exposed to higher levels of air pollution during pregnancy will have a higher risk of breast cancer. This large-scale study will have enough statistical power to detect the effect of air pollution on breast cancer risk, taking into account exposure both during and between pregnancies. Citation Format: Jessica Lena Edlund, Malin Gustafsson, Jenny Linden, Wendy Yi-Ying Wu, Anna Oudin, Sophia Harlid. Exposure to air pollution during pregnancy and risk of premenopausal breast cancer: A Swedish nation-wide cohort study including more than 1 million women. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4214.

History of infertility and risk of breast cancer: a prospective cohort study.

Research on infertility and risk of breast cancer has been conflicting, potentially because many well-established breast cancer risk factors, such as pregnancy history, are strongly correlated with infertility. We followed participants in the Nurses' Health Study II from 1989 to 2015 (n = 103,080) for the development of invasive breast cancer and calculated Hazard Ratios (HR) and 95% confidence intervals (CI) using Cox regression. Participants with a self-reported history of infertility (12months of trying without conception) were compared to gravid women with no history of infertility. We classified breast cancer by menopausal status and investigated mediation by reproductive factors. Over 26years of follow-up, 26,208 (25.4%) women reported a history of infertility, and 3,201 women were newly diagnosed with invasive breast cancer. We observed no association between infertility history and risk of overall breast cancer (HR: 1.05, 95% CI: 0.97-1.14) or premenopausal breast cancer (RR: 0.93, 95% CI: 0.83-1.03). However, we observed a modest association between history of infertility and risk of postmenopausal breast cancer (HR: 1.13, 95% CI: 1.00-1.28), approximately 50% of which could be attributed to lower total parity and later age at first birth (95% CI: 8.2%-91.0%). Women with a history of infertility were at increased risk of postmenopausal breast cancer. Older age at first birth and lower total parity explained approximately half of the association between infertility and risk of postmenopausal breast cancer.

Associations of vitamin D receptor encoding gene variants with premenopausal breast cancer risk.

This study evaluates whether vitamin D receptor (VDR) gene variations are associated with premenopausal breast cancer in Pakistani cohorts. Genomic DNA was isolated from 228 breast cancer patients and 500 non-cancer controls. Six polymorphic variants (rs11568820, rs4516035, rs2228570, rs1544410, rs7975232, rs731236) of the VDR gene were genotyped using PCR-RFLP analysis. All statistical analysis was carried out on IBM-SPSS 23 at p-value <.05. Chi-square test and odds ratios (ORs) along with 95% confidence interval (CIs) were applied to evaluate the relationship between VDR gene polymorphisms and breast cancer. Results showed that the A/A genotype of EcoRV (OR=2.125, 95% CI=1.024 to 4.412) and the A/a genotype of Apa1 (OR=6.094, 95%CI=4.111 to 9.033) gene polymorphism had an increased risk of premenopausal breast cancer. No associations of the Bsm1 and Taq1 polymorphisms were observed in premenopausal women. Moreover, the Cdx2 GG (OR=0.34, 95%CI=0.192-0.602) genotype had a significant protective effect on breast cancer. However, strong LD was existed between Bsm1/Taq1 (D'=0.757, CI=0.67-0.82) and Apa1/Taq1 (D'=0.695, CI=0.6-0.77). Haplotype analysis showed no association between premenopausal breast cancer and VDR haplotypes. These analyses indicates that the VDR EcoRV A/A and Apa1 A/a genotypes may be risk factors for breast cancer development among premenopausal women.

Breast cancer: Risk factors and prevention strategies

Among the cancer diseases, breast cancer is becoming fast growing leading cause of oncologic mortality among women. It is hoped that, evaluation of different dimensions of breast cancer and its associated factors such as environmental and genetic factors, will increase the efforts of prevention. Current studies suggest that mutations in some genes play an crucial role in susceptibility of breast cancer. Thus, researchers aimed to isolate such breast cancer susceptible genes. Some epidemiologic studied also suggested that, moderate to vigorous exercise for 3-4 hours per week can lower the risk for breast cancer for 30%-40% in women than those of the sedentary women. Obese or overweight women have 50%-250% greater risk for breast cancer after menopause. Alcohol use also increases the risk of both postmenopausal and premenopausal breast cancer. Thus, these trends of sedentary lifestyle, decreasing physical activity and increasing obesity may lead to an increase in the incidence of breast cancer. Thus, adoption of healthy food habits, increasing physical activity and changes in sedentary lifestyle may have a great impact on the prevalence of this disease in future. The treatment strategies for breast cancer are broad-ranging depending on tumor’s biology; stages of the disease; tolerance, and acceptance of the patient. There is various treatment approaches of breast cancer such as radiology, surgery, and systematic therapy (chemotherapy, endocrine therapy and biological therapy) etc. In this article required information about risk factors and current breast cancer prevention strategies are collected through literature review.

Inflammatory biomarkers and risk of breast cancer among young women in Latin America: a case-control study

BackgroundBreast cancer incidence is increasing rapidly in Latin America, with a higher proportion of cases among young women than in developed countries. Studies have linked inflammation to breast cancer development, but data is limited in premenopausal women, especially in Latin America.MethodsWe investigated the associations between serum biomarkers of chronic inflammation (interleukin (IL)-6, IL-8, IL-10, tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), leptin, adiponectin) and risk of premenopausal breast cancer among 453 cases and 453 matched, population-based controls from Chile, Colombia, Costa Rica, and Mexico. Odds ratios (OR) were estimated using conditional logistic regression models. Analyses were stratified by size and hormonal receptor status of the tumors.ResultsIL-6 (ORper standard deviation (SD) = 1.33 (1.11–1.60)) and TNF-α (ORper SD = 1.32 (1.11–1.58)) were positively associated with breast cancer risk in fully adjusted models. Evidence of heterogeneity by estrogen receptor (ER) status was observed for IL-8 (P-homogeneity = 0.05), with a positive association in ER-negative tumors only. IL-8 (P-homogeneity = 0.06) and TNF-α (P-homogeneity = 0.003) were positively associated with risk in the largest tumors, while for leptin (P-homogeneity = 0.003) a positive association was observed for the smallest tumors only.ConclusionsThe results of this study support the implication of chronic inflammation in breast cancer risk in young women in Latin America. Largest studies of prospective design are needed to confirm these findings in premenopausal women.