Postmenopausal Breast Cancer Research Articles

Abstract 4135985: Association of Plasma Cystatin-C with Cancer Risk in Individuals with and without Cardiovascular and Chronic Kidney Disease: An Atherosclerosis Risk in Communities (ARIC) Study

Background: While previous studies suggested a relationship between circulating Cystatin-C (Cys-C), a cysteine protease inhibitor involved in regulating tissue inflammation and a renal filtration marker, and both cancer and CVD, they often lacked long-term follow-up or did not account for the impact of CVD on the relationship between Cys-C and cancer. Methods: We included participants from the Atherosclerosis Risk in Communities (ARIC) study followed from visit 2 (1990-1992) through 2015. Plasma Cys-C level was measured by SomaScan. Other renal filtration markers beta-2 microglobulin (B2M) and beta-trace protein (BTP) were used to compare their cancer association with Cys-C. Incident cancer was ascertained by state cancer registry linkage supplemented with medical records. After adjusting for age, sex, race, and study center, adjusted hazard ratios (aHR) of total and site-specific cancers were estimated using Cox proportional hazards regression stratified by baseline chronic kidney disease (CKD) and CVD status. Results: Among 10,869 individuals (median age of 56.9 years, 55% female, 25% Black, 74% White), 3352 incident cancers were ascertained over a median follow-up of 22.9 years. Among 9585 individuals with no history of CKD or CVD, higher Cys-C was significantly associated with a higher risk of total (aHR 1.22, 95%CI 1.02-1.46), bladder, lung, colorectal, and hematologic malignancies. Among 1,050 individuals with CVD, but not CKD, Cys-C level was not associated with total cancer (aHR 1.22, 95%CI 0.74-2.01), but was significantly inversely associated with colorectal (aHR 0.19, 95%CI 0.05-0.76) and positively associated with post-menopausal breast (aHR 4.52, 95%CI 1.05-19.40) cancer risk. In individuals with CKD but not CVD, Cys-C was negatively associated with bladder (HR 0.08, 95%CI 0.0-0.77) and lung (0.23, 95%CI 0.06-0.82) cancers. Lastly, those with both CKD and CVD showed higher hematopoietic and lymphatic cancer with higher Cys-C (HR 4.68, 95%CI 1.32-16.60). Similar patterns were observed for B2M and BTP proteins. Conclusions: Our study highlights the intricate relationship between various renal filtration markers and cancer risk. It suggests that they may play a significant role in cancer development among the general population and CVD patients but not CKD patients. Further research should explore the biological mechanism underlying these associations with even more CKD cases to refine risk estimates. Funding: NHLBI, NCI, NPCR

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.

Menopausal hormone therapy and incidence, mortality, and survival of breast cancer subtypes: a prospective cohort study

BackgroundMenopausal hormone therapy (MHT) is associated with an increased risk of postmenopausal breast cancer, predominantly the luminal A-like subtype. The impact of MHT on deaths from breast cancer subtypes is less understood. This study aimed to explore associations between MHT use and the incidence, mortality, and survival of intrinsic-like breast cancer subtypes.MethodsData from 160,881 participants with self-reported MHT use from the prospective Norwegian Women and Cancer Study were analyzed. Among them, 7,844 incident breast cancer cases, and 721 breast cancer-specific deaths occurred. Cox proportional hazard regression was performed to calculate hazard ratios (HRs) with 95% confidence intervals (CIs) for the association between MHT use and the incidence, mortality, and survival of breast cancer subtypes.ResultsMHT use was associated with increased risk of overall, luminal A-like, and luminal B-like breast cancer, with respective HRs of 1.44 (95% CI 1.36–1.52), 1.41 (95% CI 1.31–1.52), and 1.23 (95% CI 1.09–1.40) among current estrogen-progestin therapy (EPT) users compared with never users. The risk increased by 4%, 4%, and 2% per year of EPT use for overall, luminal A-like, and luminal B-like breast cancers, respectively. MHT use was also associated with increased risk of overall and luminal A-like breast cancer mortality, with HRs 1.61% (95% CI 1.36–1.91) and 2.15% (95% CI 1.51–3.05) increased risk among current EPT users compared with non-users. Among patients with breast cancer, pre-diagnostic MHT use was not associated with worse survival from overall breast cancer but was inversely associated with survival from triple-negative breast cancer (TNBC; HR death 0.41; 95% CI 0.24–0.73 among current users). Results varied significantly according to tumor subtype (pheterogeneity = 0.02).ConclusionsOur study suggests that MHT use increases the risk of incident and fatal overall and luminal A-like, and incident luminal B-like breast cancer but does not decrease overall survival among patients with breast cancer. Further research is needed to elucidate the mechanisms underlying MHT use and breast cancer lethality, and to explore whether MHT use among patients with TNBC is indeed free from harm.

Long-term estrogen-deprived estrogen receptor α-positive breast cancer cell migration assisted by fatty acid 2-hydroxylase.

The risk of breast cancer (BC) recurrence is high in postmenopausal women, though the underlying molecular mechanisms are not yet fully understood. We developed a long-term estrogen-deprived (LTED) cell line from MCF-7 cells, which we used as an in vitro model for aromatase inhibitor (AI)-resistant estrogen receptor α (ERα)-positive postmenopausal BC. We also describe the involvement of fatty acid 2-hydroxylase (FA2H) in the modulation of LTED cell migration. Small interfering RNA specific to FA2H (siFA2H) could reduce cell migration, whereas the introduction of plasmid expressing FA2H, but not its inactive mutant, resulted in enhanced migration. Moreover, proliferation of the LTED cells was not affected by modulation of FA2H expression. Fulvestrant (FUL), a selective estrogen receptor degrader used to treat AI-resistant ERα-positive postmenopausal BC, was found to induce degradation of ERα together with a decrease in ER-mediated transcription; however, FA2H protein expression and migration remained unchanged. Overall, the findings of this study suggest that FA2H is one of the drivers of LTED cell migration, and that LTED cells resistant to FUL therapy may be involved in malignancy and metastatic mechanisms.

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.

Childhood-to-adulthood body size trajectory and cancer risk: a prospective cohort study

Abstract Background While excess weight in adulthood and childhood has been associated with increased cancer risk, the link between childhood-to-adulthood body size trajectories and cancer risk requires further investigation. Methods We used data from the UK Biobank, a prospective population-based cohort study. The main exposure was childhood-to-adulthood body size trajectory, constructed from self-reported body at age 10 (categories: thinner, average, and plumper than average) and measured body mass index (BMI) at recruitment (normal weight, overweight, and obese). Primary outcome was obesity-related cancer (13 different cancer types). Results During a median follow-up of 11.7 years, 21,289 participants developed obesity-related cancers. Having a larger body size at age 10 was strongly associated with being overweight or obese in adulthood. Compared to participants with average childhood to normal adulthood body size trajectory, all trajectories ending in overweight or obesity in adulthood were strongly associated with an increased risk of obesity-related cancers. The strength of the association was mostly determined by adulthood BMI, and similar patterns were observed for colorectal, endometrial, kidney, pancreatic and esophageal cancer. However, a larger body size in childhood was associated with a lower risk of postmenopausal breast cancer. Conclusions Although a larger body size in childhood predisposes to overweight and obesity in adulthood, it does not necessarily predispose to an increased obesity-related cancer risk if measures to maintain a healthy weight are taken in adulthood. Key messages • While larger body size in childhood predisposes individuals to overweight and obesity in adulthood, maintaining a healthy weight in adulthood may help mitigate the risk of obesity-related cancers. • Our findings highlight the importance of preventing and reducing overweight and obesity in adulthood for primary cancer prevention.

Comparison of Clinicopathological Features between Premenopausal and Postmenopausal Female Breast Cancer Patients in Kurdistan Region of Iraq: A Retrospective Single Institution Study of 671 Female Patients

Introduction: Breast cancer is the most common cancer in women, and its incidence is increasing annually worldwide. It accounts for 24% of new cancer cases and 15% of cancer deaths in 2018, and according to the GLOBOCAN Cancer Tomorrow prediction tool, incident cases are expected to increase by more than 46% by 2040. Studies carried out thus far have shown that risk factors and histopathological features of breast malignancies may vary among different age groups. Menopausal status is an essential factor influencing clinicopathological characteristics of patients with breast cancer. Prognostic factors are used to estimate how aggressive the tumor may evolve and to decide on a treatment approach. In Iraq, breast cancer is most frequently seen in younger women in their fourth and fifth decades of life, who often show in advanced stages at the time of diagnosis, according to previous surveys. Objectives: The main objective of this study was to assess the clinicopathologic features between premenopausal and postmenopausal breast cancers to provide valuable insights into what may influence the age at diagnosis of breast cancer in the Kurdistan region of Iraq. Methods: This retrospective study included 671 non-metastatic breast cancer patients referred to Zhianawa Cancer Center between January 2015 and December 2017. Disease stage was determined using the American Joint Committee on Cancer and Union for International Cancer Control (UICC) (“Tumour,” “Nodes,” “Metastases”) TNM systems. The patients were divided into premenopausal and postmenopausal groups. The chi-square test was used to evaluate the association between the variables. Results: The mean age of the participants was 47.5 years. The most prevalent age group was 40-49, followed by the age group 50-59. Of the participants, 60.5% were premenopausal, and 39.4% were postmenopausal. Stage IIIA was the most common stage at diagnosis. At the same time, the most minor stage at diagnosis was stage 0. The second most common stage was IIB. There was a strong association between menopausal status with grade (P value 0.001) and LVI (P value 0.01); however, there was a non-significant correlation between menopausal status and stage at diagnosis (P value 0.529). Conclusion: Most patients included in this study had locally advanced disease stages. Menopausal status affected grade and LVI but not stage. Further professional efforts, endorsed by practical policy decisions, are recommended to down stage breast cancer through promoting evidence based protocol guidelines and adopting comprehensive well designed diagnostic, screening and cancer control strategies.

Pro-inflammatory cytokines increase temporarily after adjuvant treatment for breast cancer in postmenopausal women: a longitudinal study

BackgroundBreast cancer patients have an increased risk of cardiometabolic disease and for many patients, adjuvant therapy causes an altered lipid profile, insulin resistance and inflammation. Previous follow-up studies are inconclusive regarding the duration of therapy-induced inflammation. We examined the acute and persistent changes of adjuvant chemotherapy on inflammatory and metabolic health markers in breast cancer patients.MethodsPlasma levels of IL-6, IL-8, IL-10, IFN-γ, TNF-α, high-sensitivity C-reactive protein (hsCRP) and metabolic health parameters were analyzed before, shortly after and every six months up to two years after adjuvant chemotherapy treatment in 51 postmenopausal early breast cancer (EBC) patients, as well as in 41 healthy age- and BMI-matched controls. A target-specific multiplex assay was applied for cytokine measurements.ResultsBefore initiation of adjuvant therapy, plasma IL-8 levels were higher in EBC patients (31%, p = 0.0001). Also, a larger proportion of the patients had a hsCRP level above 2 mg/L (41%) compared to the controls (17%, Χ2 = 5.15, p = 0.023). Plasma levels of all five cytokines, but not hsCRP, were significantly increased after compared to before adjuvant chemotherapy (15–48% increase; all p ≤ 0.05). Already six months after ending chemotherapy treatment, all plasma cytokine levels were significantly reduced and close to pre-chemotherapy levels. Adjuvant chemotherapy caused a worsened lipid profile (increased triglycerides, lower HDL levels), insulin resistance and increased plasma insulin levels that remained high during the first year after chemotherapy.ConclusionPostmenopausal women with EBC have temporarily increased plasma levels of pro-inflammatory cytokines after adjuvant chemotherapy. Although transient, the therapy-induced increase in plasma cytokine levels, together with dyslipidemia and insulin resistance, may contribute to cardiometabolic risk in breast cancer patients treated with adjuvant chemotherapy.Trial registration The clinical trial (registration number NCT03784651) was registered on www.clinicaltrials.gov on 24 December 2018.

Physical activity, metabolites, and breast cancer associations.

The effects of usual physical activity on physiology and disease prevention are not fully understood. We examined the associations between physical activity, metabolites, and breast cancer risk. Physical activity levels were assessed using doubly labeled water, accelerometers, and 24-hr recalls in the IDATA study (N = 707 participants, ages 50-74 years, 51% women), with 1-6 assessments over 12 months and two blood sample collections. Partial Spearman correlations were used to estimate associations between physical activity and 843 serum metabolites, corrected for multiple testing. Conditional logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) of metabolites with postmenopausal breast cancer in a nested case-control study (621 cases, 621 controls), all statistical tests were 2-sided. Physical activity was associated with 164 metabolites spanning numerous pathways, including amino acid and fatty acid metabolism. Twelve of these metabolites were also associated with breast cancer risk, ten of which supported a protective role of physical activity. Notably, higher physical activity was associated with lower 16alpha-hydroxy DHEA 3-sulfate (androgen) and adipoylcarnitine (fatty acid), both of which were associated with increased breast cancer risk (OR per 1 standard deviation (SD)=1.34, 95% CI = 1.16-1.55 and 1.26,1.11-1.42, respectively). Higher physical activity energy expenditure was also associated with lower sphingomyelin (d18:1/20:1, d18:2/20:0), which was associated with a reduced breast cancer risk (0.82,0.73-0.93). Physical activity is associated with a broad range of metabolites, many of which are consistent with a protective effect against breast cancer. Our findings highlight potential metabolic pathways for cancer prevention.

Burden of postmenopausal breast cancer attributable to excess body weight: comparative study of body mass index and CUN-BAE in MCC-Spain study

Background10% of postmenopausal breast cancer cases are attributed to a high body mass index (BMI). BMI underestimates body fat, particularly in older women, and therefore the cancer burden attributable to...

Trem2 deficiency attenuates breast cancer tumor growth in lean, but not obese or weight loss, mice and is associated with alterations of clonal T cell populations.

Obesity is an established risk factor for breast cancer development and worsened prognosis; however, the mechanisms for this association - and the potential benefits of weight loss - have not been fully explored. The adipose environment surrounding breast tumors, which is inflamed in obesity, has been implicated in tumor progression. An emerging therapeutic target for cancer is TREM2, a transmembrane receptor of the immunoglobulin superfamily that is expressed on macrophages in adipose tissue and tumors. We utilized genetic loss of function (Trem2 +,+ and Trem2 -/-) models and dietary (lean, obese, and weight loss) intervention approaches to examine impacts on postmenopausal breast cancer. Remarkably, Trem2 deficiency ameliorated tumor growth in lean, but not obese or weight loss mice. Single-cell RNA sequencing, in conjunction with VDJ sequencing of tumor and tumor-adjacent mammary adipose tissue (mATTum-adj) immune cells, revealed that tumors of lean Trem2 -/- mice exhibited a shift in clonal CD8+ T cells from an exhausted to an effector memory state, accompanied with increased clonality of CD4+ Th1 cells, that was not observed in any other diet-genotype group. Notably, identical T cell clonotypes were identified in the tumor and mATTum-adj of the same mouse. Finally, an immune checkpoint study demonstrated that αPD-1 therapy restricted tumor growth in lean and weight loss, but not obese mice. We conclude that weight history is relevant when considering potential efficacy of TREM2 inhibition in postmenopausal breast cancer. This work reveals immunological interactions between tumors and surrounding adipose tissue, highlighting significant differences under obese and weight loss conditions.

Circulating Estrogen Metabolites and Risk of Breast Cancer among Postmenopausal Women in the Nurses' Health Study.

Estradiol and estrone are well-established risk factors for postmenopausal breast cancer (BC). Experimental evidence suggests that specific estrogen metabolites, produced via irreversible hydroxylation of estrone and estradiol at the 2- or 16-position may independently influence carcinogenesis. We performed a nested case-control study of BC (328 BC cases; 639 controls) among postmenopausal women within the Nurses' Health Study (NHS)to examine the role of estrogens and estrogen metabolites (jointly referred to as EM). Plasma concentrations of each EM (unconjugated+conjugated forms) were measured by liquid chromatography-tandem mass spectrometry. Multivariable conditional logistic regression, adjusting for BC risk factors, estimated relative risks (RR) and 95% confidence intervals (CI) of BC across quintiles of individual EM, EM pathways, and pathway ratios. Associations by estrogen/progesterone receptor (ER/PR) status were analyzed by unconditional logistic regression. Estradiol and estrone were strongly associated with increased BC risk [estradiol: RRQ5v.Q1 (95% CI)=2.64 (1.64-4.26), estrone: 2.78 (1.74-4.45); both p-trends<0.001]. The 2-hydroxylation pathway was strongly associated with risk [RRQ5v.Q1=3.09 (1.81-5.27), p-trend<0.001], and remained so after adjusting for unconjugated estradiol [RRQ5v.Q1=2.23 (1.25-3.96), p-trend=0.01]. While the 16-hydroxylation pathway was modestly associated with risk [RRQ5v.Q1=1.62 (1.03-2.54), p-trend=0.01], the association was attenuated after unconjugated estradiol adjustment [RRQ5v.Q1=1.24 (0.77-1.99), p-trend=0.19]. Similar positive associations with the 2-pathway and 16-pathway were observed for ER+/PR+ and ER-/PR- tumors. In this cohort of postmenopausal women, 2-hydroxylation of estrone and estradiol was associated with increased BC risk, independent of unconjugated estradiol. These results highlight the need to revisit the role of estrogen metabolism in BC etiology and prevention.

Trajectories in mammographic breast screening participation in middle-age overweight and obese women: A retrospective cohort study using linked data

ObjectivesDespite the established benefits and availability of mammographic breast screening, participation rates remain suboptimal. Women with higher BMIs may not screen regularly, despite being at increased risk of postmenopausal breast cancer and worse outcomes. This study investigated the association between prospective changes in BMI and longitudinal adherence to mammographic screening among women with overweight or obesity. MethodsRetrospective cohort study of women (N = 2822) participating in the Australian Longitudinal Study on Women's Health with an average follow-up of 20 years, with screening participation enumerated via BreastScreen NSW, Australia clinical records over the period 1996–2016. Association between BMI and subsequent adherence to screening was investigated in a series of marginal structural models, incorporating a time variant/invariant socio-demographic, clinical, and health behaviour confounders. Models were also stratified by a proxy measure of socio-economic status (education). ResultsParticipants with overweight/obesity were less adherent to mammography screening, compared to healthy/underweight participants (OR=1.29, 95 % CI=1.07, 1.55). The association between overweight/obesity and non-adherence was higher among those who ever had private health insurance (OR=1.30, 95 % CI=1.05, 1.61) compared to those who never had private health insurance and among those with lower educational background (OR=1.38, 95 % CI=1.08, 1.75) compared to those with higher educational background. ConclusionsLong-term impacts on screening participation exist among women with higher BMI, who are less likely to participate in routinely organised breast screening. Women with a higher BMI should be a focus of efforts to improve breast screening participation, particularly given their increased risk of breast cancer and association of higher BMI with worse breast cancer outcomes among older women.

Sex disparity in the association between metabolic-anthropometric phenotypes and risk of obesity-related cancer: a prospective cohort study

BackgroundSex disparity between metabolic-obesity (defined by body mass index, BMI) phenotypes and obesity-related cancer (ORC) remains unknown. Considering BMI reflecting overall obesity but not fat distribution, we aimed to systematically assess the association of our newly proposed metabolic-anthropometric phenotypes with risk of overall and site-specific ORC by sex.MethodsA total of 141,579 men (mean age: 56.37 years, mean follow-up time: 12.04 years) and 131,047 women (mean age: 56.22 years, mean follow up time: 11.82 years) from the UK Biobank was included, and designated as metabolic-anthropometric phenotypes based on metabolic status (metabolically healthy/unhealthy), BMI (non-obesity/obesity) and body shape (pear/slim/apple/wide). The sex-specific association of different phenotypes with overall and site-specific ORC was assessed by hazard ratios (HRs) and 95% confidence intervals (CIs) using Cox proportional hazards regression models.ResultsWe found metabolically unhealthy and/or obesity phenotypes conveyed a higher risk in men than in women for overall ORC and colorectal cancer compared with metabolically healthy non-obesity phenotype (Pinteraction < 0.05). Of note, metabolically healthy obesity phenotype contributed to increased risks of most ORC in men (HRs: 1.58 ~ 2.91), but only correlated with higher risks of endometrial (HR = 1.89, 95% CI: 1.54–2.32) and postmenopausal breast cancers (HR = 1.17, 95% CI: 1.05–1.31) in women. Similarly, even under metabolically healthy, men carrying apple and wide shapes phenotypes (metabolically healthy apple/wide and metabolically healthy non-obesity apple/wide) suffered an increased risk of ORC (mainly colorectal, liver, gastric cardia, and renal cancers, HRs: 1.20 ~ 3.81) in comparison with pear shape or non-obesity pear shape.ConclusionsThere was a significant sex disparity between metabolic-anthropometric phenotypes and ORC risk. We advised future ORC prevention and control worth taking body shape and sex disparity into account.

Association between body mass index combined with high-sensitivity C-reactive protein and the risk of postmenopausal breast cancer: A prospective cohort study.

The present study aimed to assess the risk of postmenopausal breast cancer in women based on a combination of body mass index (BMI) and high-sensitivity C-reactive protein (hs-CRP) levels. A total of 20,400 participants were investigated as part of the 'Kailuan Study' clinical trial. Participants were classified into four groups based on BMI (BMI ≥24 or <24 kg/m2) and hs-CRP level (hs-CRP ≥3 or <3 mg/l). Cox proportional hazards models were used to evaluate the association between the combination of BMI and hs-CRP and the risk of postmenopausal breast cancer. A total of 19,540 participants met the inclusion criteria. The median follow-up time was 14.97 years, with a cumulative follow-up period of 283,599.43 person-years. Among the participants, 269 individuals were diagnosed with postmenopausal breast cancer. Individuals with a high BMI (BMI ≥24 kg/m2) and a high hs-CRP level (hs-CRP ≥3 mg/) had a greater risk of postmenopausal breast cancer compared with individuals with a low BMI (BMI <24 kg/m2) and a low hs-CRP level (<3 mg/l) (hazard ratio, 1.75; 95% confidence interval, 1.25-2.47). The sensitivity analysis showed findings consistent with the primary results. In conclusion, the combination of high BMI and high hs-CRP level is associated with an increased risk of postmenopausal breast cancer. The present study is part of the Kailuan Study. Trial registration number: ChiCTRTNCR11001489 (Chinese Clinical Trial Registry, https://www.chictr.org.cn/showproj.html?proj=8050). Date of registration: 19/07/2015.

301P Changes in lipid-levels following aromatase inhibitor treatment in early postmenopausal breast cancer

301P Changes in lipid-levels following aromatase inhibitor treatment in early postmenopausal 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.

Preoperative plasma fibrinogen level is a risk factor for the long-term survival of postmenopausal women after surgery for breast cancer

BackgroundStudies have indicated an association between fibrinogen levels and the prognosis of breast cancer patients. However, fibrinogen levels are notably susceptible to fluctuations due to the menstrual cycle. This study explored the relationship between preoperative plasma fibrinogen levels and the prognosis of postmenopausal breast cancer women after surgery. Method855 patients with postmenopausal breast cancer were monitored for 10 years. Cox proportional hazards regression models were used to perform univariate and multivariate analyses to identify factors that are of substantial prognostic value. ResultsThe median follow-up was 77 months (51–105 months), and the maximum 142 months. Over the follow-up period, 65 deaths (7.6 %) were recorded. Multivariate Cox regression results show that preoperative plasma fibrinogen level (hazard ratio [HR] =1.615, 95 % confidence interval [CI]: 1.233–2.115) and age (HR = 1.626, 95%CI: 1.250–2.116) were independent risk factors for 10-year overall survival after surgery in postmenopausal breast cancer patients, while endocrine therapy (HR = 0.414, 95%CI: 0.202–0.846) was an independent protective factor. Multivariate Cox regression results also show preoperative plasma fibrinogen level was an independent risk factor for 10-year disease-free survival (HR = 1.398, 95 % CI: 1.137–1.719) and 10-year distant metastasis-free survival (HR = 1.436, 95%CI: 1.153–1.787). ConclusionElevated pretreatment plasma fibrinogen levels are associated with a poorer long-term prognosis in postmenopausal breast cancer patients following surgical treatment.

Assessing the Factor Structure and Measurement Invariance of the Pittsburgh Sleep Quality Index Between Postmenopausal Breast Cancer Survivors and Controls.

Background and Purpose: This study evaluates the Pittsburgh Sleep Quality Index (PSQI) in terms of factor structure and measurement invariance (MI). The sample included postmenopausal breast cancer (BC) survivors (n = 101) and matched healthy controls (n = 60). Methods: Exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) were performed on PSQI's seven component scores. MI was tested between groups and across time using Bayes factor (BF). Results: Two factors were identified: sleep efficiency and perceived sleep quality. MI is evidenced between groups (BF < 0.007) and over time (BF > 150). Conclusions: PSQI scores with two subscales are comparable between postmenopausal BC survivors and controls over a 1-year period, providing some validation of PSQI for researching sleep quality in this population.

Carcinogenic industrial air pollution and postmenopausal breast cancer risk in the National Institutes of Health AARP Diet and Health Study

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