Risk Of Premenopausal Breast Cancer Research Articles

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.

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.

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.

A metabolomic analysis of adiposity measures and pre- and postmenopausal breast cancer risk in the Nurses' Health Studies.

Adiposity is consistently positively associated with postmenopausal breast cancer and inversely associated with premenopausal breast cancer risk, though the reasons for this difference remain unclear. In this nested case-control study of 1649 breast cancer cases and 1649 matched controls from the Nurses' Health Study (NHS) and the NHSII, we selected lipid and polar metabolites correlated with BMI, waist circumference, weight change since age 18, or derived fat mass, and developed a metabolomic score for each measure using LASSO regression. Logistic regression was used to investigate the association between this score and breast cancer risk, adjusted for risk factors and stratified by menopausal status at blood draw and diagnosis. Metabolite scores developed among only premenopausal or postmenopausal women were highly correlated with scores developed in all women (r = 0.93-0.96). Higher metabolomic adiposity scores were generally inversely related to breast cancer risk among premenopausal women. Among postmenopausal women, significant positive trends with risk were observed (e.g., metabolomic waist circumference score OR Q4 vs. Q1 = 1.47, 95% CI = 1.03-2.08, P-trend = 0.01). Though the same metabolites represented adiposity in pre- and postmenopausal women, breast cancer risk associations differed suggesting that metabolic dysregulation may have a differential association with pre- vs. postmenopausal breast cancer.

Abstract 2249: A metabolomic analysis of adiposity measures and pre- and postmenopausal breast cancer risk in the Nurses’ Health Studies

Abstract Adiposity is consistently positively associated with postmenopausal breast cancer and inversely associated with premenopausal breast cancer risk. In this nested case-control study of 1651 breast cancer cases and 1651 matched controls from the Nurses’ Health Study (NHS) and the Nurses’ Health Study II (NHSII), we selected lipids and polar metabolites correlated with BMI, waist circumference, weight change since age 18, or derived fat mass, developed a metabolomic score for each measure using LASSO regression, and used logistic regression to investigate the association between this score and breast cancer risk adjusted for risk factors. Analyses were stratified by menopausal status at blood draw and diagnosis. We further explored risk of ER+ and ER- breast cancer.Metabolite correlations were similar across adiposity measures. Metabolite scores developed among only premenopausal or postmenopausal women were highly correlated with scores developed in all women (r=0.94-0.96). Higher metabolomic adiposity scores were generally inversely related to breast cancer risk among premenopausal women. Among postmenopausal women, significant positive trends with risk were observed for higher metabolomic adiposity scores (e.g., metabolomic waist circumference score OR Q4 v. Q1=1.55, 95% CI=1.08-2.22, p-trend=0.01). Metabolites associated with adiposity and breast cancer risk, glycerophosphocholines and branched-chain amino acids, are also associated with metabolic dysregulation. The same metabolites represented adiposity in pre- and postmenopausal women, though breast cancer risk associations still differed by menopausal status. Thus, metabolic dysregulation may have a differential association with pre- vs. postmenopausal breast cancer. Investigation of these metabolites and their role in adiposity-related breast cancer risk should be further explored. Citation Format: Kristen D. Brantley, Oana A. Zeleznik, Barbra A. Dickerman, Raji Balasubramanian, Clary B. Clish, Julian Avila-Pacheco, Bernard Rosner, Rulla M. Tamimi, A. Heather Eliassen. A metabolomic analysis of adiposity measures and pre- and postmenopausal breast cancer risk in the Nurses’ Health Studies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2249.

Consumption of industrial processed foods and risk of premenopausal breast cancer among Latin American women: the PRECAMA study

Ultra-processed food intake has been linked to an increased risk of breast cancer in Western populations. No data are available in the Latin American population although the consumption of ultra-processed...

Birth weight and the risk of overall breast cancer, premenopausal and postmenopausal breast cancer in adulthood: a dose-response meta-analysis of observational studies.

The effect of birth weight on breast cancer across different menopausal states remains unknown. The aim of this study was to systematically evaluate the association of birth weight with the risk of overall breast cancer (OBC) and premenopausal and postmenopausal breast cancer during adulthood. In parallel, the dose-response analyses were performed. Relevant studies were systematically searched from the PubMed, Embase, and the Cochrane Library databases from the inception to May 25, 2021, without language restrictions. All the results were pooled according to risk ratios (RRs). In total, 21 cohort studies comprising 1,139,032 participants were included. An increase in the birth weight was not associated with the risk of OBC and premenopausal and postmenopausal breast cancer. Compared with women having normal weight at birth, those with a high birth weight are likely to have an increased risk of invasive breast cancer (RR: 1.19, 95% confidence intervals: 1.03-1.38; I2: 28.6%). The dose-response analyses showed that the risk of premenopausal breast cancer increased significantly in unknown singleton status with birth weight over 2850 g (RR: 1.14 [1.02-1.30]). Similarly, postmenopausal breast cancer risk was increased in singleton births with birth weight over 3750 g (RR: 1.21 [1.00-1.47]). High weight at birth might be not significantly associated with the risk of OBC, premenopausal and postmenopausal breast cancer and ER+ and ER- breast cancer but is positively associated with the risk of invasive breast cancer, regardless of parity. Furthermore, with an increase in birth weight, the risk of postmenopausal breast cancer is likely to increase in the singleton births, whereas the risk of premenopausal breast cancer is likely to increase in unknown singleton status.

Menstrual cycle characteristics and incident cancer: a prospective cohort study.

Are menstrual cycle characteristics throughout the reproductive lifespan associated with cancer risk? Irregular and long menstrual cycles throughout the reproductive lifespan were associated with increased risk of total invasive cancer, especially obesity-related cancers. Long and irregular menstrual cycles have been associated with lower risk of pre-menopausal breast cancer and higher risk of endometrial cancer, but associations with other malignancies are less clear. Prospective cohort study. Prospective follow-up of 78 943 women participating in the Nurses' Health Study II between 1989 and 2015. We followed 78 943 pre-menopausal women without cancer history who reported the usual length and regularity of their menstrual cycles at different ages (14-17, 18-22 and 29-46 years). Cancer diagnosis was confirmed through medical record review and classified as obesity-related (colorectal, gallbladder, kidney, multiple myeloma, thyroid, pancreatic, esophageal, gastric, liver, endometrial, ovarian and post-menopausal breast) or non-obesity-related. We fitted Cox proportional hazards models to estimate hazard ratios (HRs) and 95% CIs of the association between menstrual cycle characteristics and cancer incidence. We documented 5794 incident cancer cases during 1 646 789 person-years of follow-up. After adjusting for BMI and other potential confounders, women reporting irregular cycles at age 29-46 years had an 11% (95% CI: 2-21%) higher risk of total invasive cancer than women reporting very regular cycles at the same age. This association was limited to obesity-related cancers, with a 23% (95% CI: 9-39%) higher risk and was strongest for endometrial cancer (HR = 1.39; 95% CI: 1.09-1.77). Findings were comparable for cycle characteristics earlier in life and for menstrual cycle length. Very irregular cycles at age 14-17 years were associated with significant increase in risk of colorectal cancer (HR = 1.36; 95% CI: 1.02-1.81). Our study might be subject to recall bias for findings pertaining to cycle characteristics in adolescence and early adulthood, as these were retrospectively reported. Generalizability to non-White women may be limited, as 96% of participants were White. Women with irregular or long menstrual cycles in mid-adulthood had a statistically significantly higher risk of developing cancer, especially obesity-related cancers. This association was not limited to gynecological cancers. Obesity-related cancers may need to be added to the spectrum of long-term health consequences of long or irregular cycles, possibly warranting targeted screening among women who experience long or irregular cycles in mid-adulthood. This work was supported by grants U01 CA176726, U01 HL145386 and R01 HD096033 from the National Institutes of Health. The authors have no conflicts of interest to declare. N/A.