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 foods is increasing rapidly in this region.We evaluated the association of ultra-processed food intake to breast cancer risk in a case–control study including 525 cases (women aged 20–45 years) and 525 matched population-based controls from Chile, Colombia, Costa Rica and Mexico. The degree of processing of foods was classified according to the NOVA classification.Overall, the major contributors to ultra-processed food intake were ready-to-eat/heat foods (18.2%), cakes and desserts (16.7%), carbonated and industrial fruit juice beverages (16.7%), breakfast cereals (12.9%), sausages and reconstituted meat products (12.1%), industrial bread (6.1%), dairy products and derivatives (7.6%) and package savoury snacks (6.1%). Ultra-processed food intake was positively associated with the risk of breast cancer in adjusted models (OR T3-T1=1.93; 95% CI=1.11 to 3.35). Specifically, a higher risk was observed with oestrogen receptor positive breast cancer (ORT3-T1=2.44, (95% CI=1.01 to 5.90, P-trend=0.049), while no significant association was observed with oestrogen receptor negative breast cancer (ORT3-T1=1.87, 95% CI=0.43 to 8.13, P-trend=0.36).Our findings suggest that the consumption of ultra-processed foods might increase the risk of breast cancer in young women in Latin America. Further studies should confirm these findings and disentangle specific mechanisms relating ultra-processed food intake and carcinogenic processes in the breast.

The Effects of Endocrine Therapies on Lipid Profiles in Chinese Young Women With Early Breast Cancer

This study aimed to evaluate and compare the effects of various endocrine therapies on lipid profiles in young patients with breast cancer. A retrospective, single-center study was performed to investigate the effects of tamoxifen (TAM), tamoxifen plus ovarian function suppression (TAM+OFS), and aromatase inhibitors plus ovarian function suppression (AI+OFS) on lipid profiles during the 60 months of endocrine therapy in hormone receptor-positive patients aged <40 with early breast cancer. The primary endpoint was the cumulative incidence of lipid events, and the secondary endpoints were the changes in lipid profiles. A total of 230 young patients were included with the mean age of 35.7 years old. The patients in TAM group had significantly lower incidence of 5-year lipid events than those in TAM+OFS group (7.4% versus 21.3%; P=0.016) and AI+OFS group (7.4% versus 21.6%; P=0.009). The incidence of fatty liver was significantly higher in TAM+OFS group than TAM group (52.5%versus 30.9%; P=0.043). Lipid events were associated with younger age (odds ratio (OR)=0.865, 95% confidence interval (CI): 0.780-0960; P=0.006), higher baseline LDL-C (OR=14.959, 95% CI: 4.379-51.105; P<0.001), and use of OFS (OR=3.557, 95% CI: 1.151-10.989; P=0.027). Therefore, application of OFS, with younger age and higher baseline LDL-C, may increase the incidence of lipid events in premenopausal breast cancer. More care should be taken for lipid profiles during the endocrine therapy for young breast cancer patients.

Association between serum lipids and breast cancer risk in premenopausal women: systematic review and meta-analysis

Objective Associations between serum lipids and their individual components with premenopausal breast cancer risk are unclear. This meta-analysis summarized the literature on serum lipids and premenopausal breast cancer risk to elucidate their relationship. Methods Eligible studies were identified by searching the PubMed, Embase, China National Knowledge Infrastructure, and Wanfang databases until 31 December 2020. Standardized mean difference (SMD) scores with 95% confidence intervals (95%CIs) were used to assess the impact of serum lipids on premenopausal breast cancer risk. The I2 statistic was calculated to measure the percentage of heterogeneity, and Egger’s test was performed to measure publication bias. Results Thirteen studies were included. The SMD scores of triglycerides (TG) and low-density lipoprotein cholesterol (LDL-C) were 12.90 (95%CI: 7.19–18.61) and 31.43 (95%CI: 8.72–54.15), respectively. The SMD scores of total cholesterol (TC) and high-density lipoprotein cholesterol (HDL-C) were not significantly different between the groups. The included studies were highly heterogeneous. There were no publication biases found in TC, LDL-C, or HDL-C analyses, whereas publication bias was present in the TG analysis. Conclusions TG and LDL-C were higher in premenopausal breast cancer patients than in women without breast cancer. However, no significant differences were found in TC or HDL-C levels.

Comprehensive profiles and diagnostic value of menopausal-specific gut microbiota in premenopausal breast cancer

In Western countries, breast cancer tends to occur in older postmenopausal women. However, in Asian countries, the proportion of younger premenopausal breast cancer patients is increasing. Increasing evidence suggests that the gut microbiota plays a critical role in breast cancer. However, studies on the gut microbiota in the context of breast cancer have mainly focused on postmenopausal breast cancer. Little is known about the gut microbiota in the context of premenopausal breast cancer. This study aimed to comprehensively explore the gut microbial profiles, diagnostic value, and functional pathways in premenopausal breast cancer patients. Here, we analyzed 267 breast cancer patients with different menopausal statuses and age-matched female controls. The α-diversity was significantly reduced in premenopausal breast cancer patients, and the β-diversity differed significantly between breast cancer patients and controls. By performing multiple analyses and classification, 14 microbial markers were identified in the different menopausal statuses of breast cancer. Bacteroides fragilis was specifically found in young women of premenopausal statuses and Klebsiella pneumoniae in older women of postmenopausal statuses. In addition, menopausal-specific microbial markers could exhibit excellent discriminatory ability in distinguishing breast cancer patients from controls. Finally, the functional pathways differed between breast cancer patients and controls. Our findings provide the first evidence that the gut microbiota in premenopausal breast cancer patients differs from that in postmenopausal breast cancer patients and shed light on menopausal-specific microbial markers for diagnosis and investigation, ultimately providing a noninvasive approach for breast cancer detection and a novel strategy for preventing premenopausal breast cancer.

IHC-based Ki67 as response biomarker to tamoxifen in breast cancer window trials enrolling premenopausal women

Window studies are gaining traction to assess (molecular) changes in short timeframes. Decreased tumor cell positivity for the proliferation marker Ki67 is often used as a proxy for treatment response. Immunohistochemistry (IHC)-based Ki67 on tissue from neo-adjuvant trials was previously reported to be predictive for long-term response to endocrine therapy for breast cancer in postmenopausal women, but none of these trials enrolled premenopausal women. Nonetheless, the marker is being used on this subpopulation. We compared pathologist assessed IHC-based Ki67 in samples from pre- and postmenopausal women in a neo-adjuvant, endocrine therapy focused trial (NCT00738777), randomized between tamoxifen, anastrozole, or fulvestrant. These results were compared with (1) IHC-based Ki67 scoring by AI, (2) mitotic figures, (3) mRNA-based Ki67, (4) five independent gene expression signatures capturing proliferation, and (5) blood levels for tamoxifen and its metabolites as well as estradiol. Upon tamoxifen, IHC-based Ki67 levels were decreased in both pre- and postmenopausal breast cancer patients, which was confirmed using mRNA-based cell proliferation markers. The magnitude of decrease of Ki67 IHC was smaller in pre- versus postmenopausal women. We found a direct relationship between post-treatment estradiol levels and the magnitude of the Ki67 decrease in tumors. These data suggest IHC-based Ki67 may be an appropriate biomarker for tamoxifen response in premenopausal breast cancer patients, but anti-proliferative effect size depends on estradiol levels.

Lipoprotein and metabolite associations to breast cancer risk in the HUNT2 study

Background: The aim of this study was to investigate if serum lipoprotein and metabolic profiles of healthy women can predict the risk of developing breast cancer in the future, and to gain a better understanding of the etiology of the disease. Methods: From a cohort of 70 000 participants within the Trondelag Health Study (HUNT study), we identified 1199 women who developed breast cancer within a 22 year follow-up period. Through a nested case-control study design, future breast cancer patients and matching controls (n = 2398) were analysed. Using nuclear magnetic resonance (NMR) spectroscopy, 28 metabolites and 112 lipoprotein subfractions were quantified from prediagnostic serum samples. Logistic regression was used to test metabolites and lipoprotein subfractions for associations with breast cancer risk and partial least-squares discriminant analysis (PLS-DA) models were built to predict future disease. Results: Among premenopausal women (554 cases) 14 lipoprotein subfractions were associated with long-term breast cancer risk. In specific, different subfractions of VLDL particles (in particular VLDL-2, VLDL-3 and VLDL-4) were inversely associated with breast cancer. For total VLDL: apolipoprotein B, cholesterol, free cholesterol and phospholipids were inversely associated with premenopausal breast cancer risk, and in addition total and HDL-4 triglycerides. No significant association was found in postmenopausal women. Conclusions: We identified several associations between lipoprotein subfractions and long-term risk of breast cancer in premenopausal women. Inverse associations between several VLDL subfractions and breast cancer risk were found, revealing an altered metabolism in the endogenous lipid pathway many years prior to a breast cancer diagnosis.

Premenopausal Breast Cancer Risk Factors and Associations with Molecular Subtypes: A Case-Control Study

Background. Breast cancer (BC) is the most prevalent cancer in women and the leading cause of women’s cancer-related deaths and morbidity worldwide. In Rwanda, BC incidence is increasing with an unacceptably high mortality rate in premenopausal women. Objectives. The purpose was to identify modifiable BC risk factors and assess associations between common breast cancer risks factors and molecular subtypes in premenopausal women in Rwanda. Methods. This was a case-control study. Premenopausal women with histological confirmation of BC and frequency-matched for age controls were recruited. A preestablished questionnaire was administered to both cases and controls for sociodemographics, BC probable risk factors, and clinical and pathological characteristics. BC was classified into luminal A, luminal B, HER2-type, basal-like (triple negative), and unclassified molecular subtypes by immunohistochemistry (IHC). Odds ratio (OR) and 95% confidence interval (CI) were estimated using multivariate logistic regression analysis. Results. 340 participants were recruited into the study (170 cases vs. 170 controls). The median age was 39 years. The majority of cases presented at advanced stages of the disease (51.2% in stages III and IV) and had invasive ductal carcinoma (98.2%). 60.6% had subtypes of poor prognosis (HER2 enriched 14.7%, triple negative 12.9%, and unclassified 32.9%). Alcohol intake AOR = 3.73 , 95 % C I 2.19 − 6.32 , p < 0.001 , obesity/overweight in adolescence or early adulthood AOR = 10.86 , 95 % C I 4.82 − 24.4 , p < 0.001 , history of primary infertility AOR = 33.8 , 95 % C I 3.5 − 321.5 , p = 0.002 , nulliparity AOR = 3.75 , 95 % C I 1.61 − 8.75 , p = 0.002 , and a history of benign breast disease AOR = 6.06 , 95 % C I 1.19 − 30.73 , p = 0.03 were associated with the occurrence of premenopausal breast cancer. There was no significant difference between risk factor stratification per molecular subtype. Conclusion. Several reproductive, environmental, and lifestyle risk factors have been identified to be associated with premenopausal BC. Among them, alcohol intake and obesity/overweight during adolescence/early adulthood can be modified. Interventions targeting alcohol consumption and obesity/overweight in adolescents and young adults may decrease the incidence of premenopausal breast cancer.

Socioeconomic position and prognosis in premenopausal breast cancer: a population-based cohort study in Denmark

Background To investigate how socioeconomic position (SEP) influences the effectiveness of cancer-directed treatment in premenopausal breast cancer patients in terms of breast cancer recurrence and mortality. Methods We conducted a cohort study nested in the ProBeCaRe (Predictors of Breast Cancer Recurrence) cohort (n = 5959). We identified all premenopausal women aged 18–55 years diagnosed with non-metastatic breast cancer and prescribed docetaxel-based chemotherapy in Denmark during 2007–2011. Population-based administrative registries provided data on SEP: marital status (married including registered partnership or single including divorced or widowed), cohabitation (cohabiting or living alone), education (low, intermediate, or high), income (low, medium, or high), and employment status (employed, unemployed, or health-related absenteeism). For each SEP measure, we computed incidence rates, cumulative incidence proportions (CIPs), and used Poisson regression to compute incidence rate ratios (IRRs) and 95% confidence intervals (CIs) of recurrence and death. We stratified on estrogen receptor (ER) status/tamoxifen to evaluate interaction. Results Our study cohort included 2616 women; 286 (CIP 13%) experienced recurrence and 223 (CIP 11%) died during follow-up (median 6.6 and 7.2 years, respectively). Single women had both increased 5-year risks of recurrence (IRR 1.45, 95% CI 1.11–1.89) and mortality (IRR 1.83, 95% CI 1.32–2.52). Furthermore, we observed increased 5-year mortality in women with low education (IRR 1.49, 95% CI 0.95–2.33), low income (IRR 1.37, 95% CI 0.83–2.28), unemployment (IRR 1.61, 95% CI 0.83–3.13), or health-related work absenteeism (IRR 1.80, 95% CI 1.14–2.82), but smaller or no increased risk of recurrence. These findings were especially evident among women with ER+ tumors prescribed tamoxifen. Overall analyses (follow-up max. 10 years) provided similar results. Conclusions Low SEP in premenopausal women with non-metastatic breast cancer was associated with increased mortality, but not always recurrence. This suggests underdetection of recurrences in certain groups. Poor prognosis in women with low SEP, especially single women, may partly be explained by tamoxifen adherence.

Clinical and molecular characterization of patients fulfilling Chompret criteria for Li-Fraumeni syndrome in Southern Brazil

Li-Fraumeni syndrome (LFS) is an autosomal dominant cancer predisposition syndrome caused by pathogenic germline variants in the TP53 gene, characterized by a predisposition to the development of a broad spectrum of tumors at an early age. The core tumors related to LFS are bone and soft tissue sarcomas, premenopausal breast cancer, brain tumors, adrenocortical carcinomas (ACC), and leukemias. The revised Chompret criteria has been widely used to establish clinical suspicion and support TP53 germline variant testing and LFS diagnosis. Information on TP53 germline pathogenic variant (PV) prevalence when using Chompret criteria in South America and especially in Brazil is scarce. Therefore, the aim of this study was to characterize patients that fulfilled these specific criteria in southern Brazil, a region known for its high population frequency of a founder TP53 variant c.1010G>A (p.Arg337His), as known as R337H. TP53 germline testing of 191 cancer-affected and independent probands with LFS phenotype identified a heterozygous pathogenic/likely pathogenic variant in 26 (13.6%) probands, both in the DNA binding domain (group A) and in the oligomerization domain (group B) of the gene. Of the 26 carriers, 18 (69.23%) were R337H heterozygotes. Median age at diagnosis of the first tumor in groups A and B differed significantly in this cohort: 22 and 2 years, respectively (P = 0.009). The present study shows the clinical heterogeneity of LFS, highlights particularities of the R337H variant and underscores the need for larger collaborative studies to better define LFS prevalence, clinical spectrum and penetrance of different germline TP53 pathogenic variants.

Age as an Independent Factor in the Permanent Chemotherapy-Induced Amenorrhea Incidence in Breast Cancer Patients at Dr. Moewardi Hospital, Surakarta, Indonesia

Background: Chemotherapy Induced Amenorrhea (CIA) is one common side effect of chemotherapy in breast cancer patients. Some who have CIA may experience menstruation return while others experience permanent CIA. Aim: to examines the factors that contribute to the incidence of persistent CIA in breast cancer patients. Methods: The population of this retrospective study was new breast cancer patients with premenopausal status when they started receiving chemotherapy at dr Moewardi Hospital Surakarta, Indonesia, from January 2019 to July 2021. To determine the relationship, the chi-square/Fisher’s exact test was performed. Risk factor analysis on the incidence of permanent CIA was carried out by using a bivariate logistic regression test, followed by multivariate analysis. Results: A number of 105 premenopausal breast cancer patients who received chemotherapy were found. Of these patients, 97 (93.38%) patients experienced CIA and 8 patients (6.62%) continued to menstruate. Of all the subjects having CIA, 49 patients (46.67%) menstruated again while the other 48 (45.71%) had persistent CIA. Age factor has a significant relationship with the incidence of permanent CIA (p =< 0.001), where patients aged > 45 years tend to have permanent CIA incidence with a proportion of 42 patients (87.5%) (p < 0.05). The multivariate analysis showed that age > 45 years (OR = 75.117; 95% CI = 12.671-445.311; p = < 0.001) was the most dominant risk factor associated with the incidence of permanent CIA, while other variables as risk factors for permanent CIA based on multivariate analysis were Stage III (R = 6.677; 95% CI = 1.370-32,545; p = 0.019) compared to stages I and II, and BMI in the normal category (OR = 5.485; 95% CI = 1.083-27.786; p = 0.040) compared to excess BMI. The other variables were not found to be associated with the incidence of permanent CIA. Conclusion: Age is a major factor associated with permanent CIA incidence. Other factors related to this study are staging and BMI. Keywords: Age, Permanent, Chemotherapy Induced Amenorrhea, Breast Cancer