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Panels of single nucleotide polymorphisms (SNPs) stratify risk for breast cancer in women from the general population, but studies are needed assess their use in a fully comprehensive model including classical risk factors, mammographic density and more than 100 SNPs associated with breast cancer. A case–control study was designed (1,668 controls, 405 cases) in women aged 47–73 years attending routine screening in Manchester UK, and enrolled in a wider study to assess methods for risk assessment. Risk from classical questionnaire risk factors was assessed using the Tyrer–Cuzick model; mean percentage visual mammographic density was scored by two independent readers. DNA extracted from saliva was genotyped at selected SNPs using the OncoArray. A predefined polygenic risk score based on 143 SNPs was calculated (SNP143). The odds ratio (OR, and 95% confidence interval, CI) per interquartile range (IQ‐OR) of SNP143 was estimated unadjusted and adjusted for Tyrer–Cuzick and breast density. Secondary analysis assessed risk by oestrogen receptor (ER) status. The primary polygenic risk score was well calibrated (O/E OR 1.10, 95% CI 0.86–1.34) and accuracy was retained after adjustment for Tyrer–Cuzick risk and mammographic density (IQ‐OR unadjusted 2.12, 95% CI% 1.75–2.42; adjusted 2.06, 95% CI 1.75–2.42). SNP143 was a risk factor for ER+ and ER− breast cancer (adjusted IQ‐OR, ER+ 2.11, 95% CI 1.78–2.51; ER− 1.81, 95% CI 1.16–2.84). In conclusion, polygenic risk scores based on a large number of SNPs improve risk stratification in combination with classical risk factors and mammographic density, and SNP143 was similarly predictive for ER‐positive and ER‐negative disease., What's new? Panels of single nucleotide polymorphisms (SNPs) stratify risk for breast cancer in women from the general population, but studies are needed to assess their use in a fully‐comprehensive model including classical questionnaire risk factors, mammographic density, and more than 100 SNPs associated with breast cancer. In this study, the predictive ability of a predefined panel of 143 SNPs was assessed after adjustment for questionnaire risk factors and mammography density using women from a U.K. cohort. The panel showed substantial improvement in risk stratification in combination with classical risk factors and mammographic density, for both oestrogen receptor‐positive and negative breast cancer.

Purpose: Although most patients with estrogen receptor (ER)–positive breast cancer benefit from endocrine therapies, a significant proportion do not. Our aim was to identify inherited genetic variations that might predict survival among patients receiving adjuvant endocrine therapies. Experimental Design: We performed a meta-analysis of two genome-wide studies; Helsinki Breast Cancer Study, 805 patients, with 240 receiving endocrine therapy and Prospective study of Outcomes in Sporadic versus Hereditary breast cancer, 536 patients, with 155 endocrine therapy patients, evaluating 486,478 single-nucleotide polymorphisms (SNP). The top four associations from the endocrine treatment subgroup were further investigated in two independent datasets totaling 5,011 patients, with 3,485 receiving endocrine therapy. Results: A meta-analysis identified a common SNP rs8113308, mapped to 19q13.41, associating with reduced survival among endocrine-treated patients [hazard ratio (HR), 1.69; 95% confidence interval (CI), 1.37–2.07; P = 6.34 × 10−7] and improved survival among ER-negative patients, with a similar trend in ER-positive cases not receiving endocrine therapy. In a multivariate analysis adjusted for conventional prognostic factors, we found a significant interaction between the rs8113308 and endocrine treatment, indicating a predictive, treatment-specific effect of the SNP rs8113308 on breast cancer survival, with the per-allele HR for interaction 2.16 (95% CI, 1.30–3.60; Pinteraction = 0.003) and HR = 7.77 (95% CI, 0.93–64.71) for the homozygous genotype carriers. A biologic rationale is suggested by in silico functional analyses. Conclusions: Our findings suggest carrying the rs8113308 rare allele may identify patients who will not benefit from adjuvant endocrine treatment. Clin Cancer Res; 21(18); 4086–96. ©2015 AACR.

Background Self‐rated health ( SRH ) is a strong predictor of mortality in different populations. However, the associations between SRH measures and risk of ischemic heart disease ( IHD ) have not been extensively explored, especially in a Chinese population. Methods and Results More than 500 000 adults from 10 cities in China were followed from baseline (2004–2008) through December 31, 2013. Global and age‐comparative SRH were reported from baseline questionnaires. Incident IHD cases were identified through links to well‐established disease registry systems and the national health insurance system. During 3 423 542 person‐years of follow‐up, we identified 24 705 incident cases of IHD . In multivariable‐adjusted models, both global and age‐comparative SRH was significantly associated with incident IHD . Compared with excellent SRH , the hazard ratios for good, fair, and poor SRH were 1.02 (95% confidence interval [CI], 0.98–1.07), 1.32 (95% CI, 1.27–1.37), and 1.76 (95% CI, 1.68–1.85), respectively. Compared with better age‐comparative SRH , the hazard ratios for same and worse age‐comparative SRH were 1.23 (95% CI, 1.19–1.27) and 1.78 (95% CI, 1.70–1.86), respectively. The associations persisted in all subgroup analyses, although they were slightly modified by study location, education, and income levels. Conclusions A simple questionnaire for self‐assessment of health status was significantly associated with incident IHD in Chinese adults. Individuals and healthcare providers can use SRH measures as a convenient tool for assessing future IHD risk.

BACKGROUND: Adherence to a combination of healthy lifestyle factors has been related to a considerable reduction of cardiovascular risk in white populations; however, little is known whether such associations persist in nonwhite populations like the Asian population. OBJECTIVES: This study aimed to examine the associations of a combination of modifiable, healthy lifestyle factors with the risks of ischemic cardiovascular diseases and estimate the proportion of diseases that could potentially be prevented by adherence to these healthy lifestyle patterns. METHODS: This study examined the associations of 6 lifestyle factors with ischemic heart disease and ischemic stroke (IS) in the China Kadoorie Biobank of 461,211 participants 30 to 79 years of age who did not have cardiovascular diseases, cancer, or diabetes at baseline. Low-risk lifestyle factors were defined as nonsmoking status or having stopped smoking for reasons other than illness, alcohol consumption of

We have utilized a two-stage study design to search for SNPs associated with the survival of breast cancer patients treated with adjuvant chemotherapy. Our initial GWS data set consisted of 805 Finnish breast cancer cases (360 treated with adjuvant chemotherapy). The top 39 SNPs from this stage were analyzed in three independent data sets: iCOGS (n=6720 chemotherapy-treated cases), SUCCESS-A (n=3596), and POSH (n=518). Two SNPs were successfully validated: rs6500843 (any chemotherapy; per-allele HR 1.16, 95% C.I. 1.08-1.26, p=0.0001, p(adjusted)=0.0091), and rs11155012 (anthracycline therapy; per-allele HR 1.21, 95% C.I. 1.08-1.35, p=0.0010, p(adjusted)=0.0270). The SNP rs6500843 was found to specifically interact with adjuvant chemotherapy, independently of standard prognostic markers (p(interaction)=0.0009), with the rs6500843-GG genotype corresponding to the highest hazard among chemotherapy-treated cases (HR 1.47, 95% C.I. 1.20-1.80). Upon trans-eQTL analysis of public microarray data, the rs6500843 locus was found to associate with the expression of a group of genes involved in cell cycle control, notably AURKA, the expression of which also exhibited differential prognostic value between chemotherapy-treated and untreated cases in our analysis of microarray data. Based on previously published information, we propose that the eQTL genes may be connected to the rs6500843 locus via a RBFOX1-FOXM1 -mediated regulatory pathway. ispartof: Oncotarget vol:6 issue:10 pages:7390-407 ispartof: location:United States status: published

Large population-based registry studies have shown that breast cancer prognosis is inherited. Here we analyse single-nucleotide polymorphisms (SNPs) of genes implicated in human immunology and inflammation as candidates for prognostic markers of breast cancer survival involving 1,804 oestrogen receptor (ER)-negative patients treated with chemotherapy (279 events) from 14 European studies in a prior large-scale genotyping experiment, which is part of the Collaborative Oncological Gene-environment Study (COGS) initiative. We carry out replication using Asian COGS samples (n=522, 53 events) and the Prospective Study of Outcomes in Sporadic versus Hereditary breast cancer (POSH) study (n=315, 108 events). Rs4458204_A near CCL20 (2q36.3) is found to be associated with breast cancer-specific death at a genome-wide significant level (n=2,641, 440 events, combined allelic hazard ratio (HR)=1.81 (1.49–2.19); P for trend=1.90 × 10−9). Such survival-associated variants can represent ideal targets for tailored therapeutics, and may also enhance our current prognostic prediction capabilities., Studies have shown that breast cancer prognosis is hereditary. Here the authors show that a genetic variant in CCL20, a chemokine ligand involved in immune response, is significantly associated with breast cancer survival and may therefore represent an important therapeutic or prognostic target.

Triple-negative (TN) breast cancer is an aggressive subtype of breast cancer associated with a unique set of epidemiologic and genetic risk factors. We conducted a two-stage genome-wide association study of TN breast cancer (stage 1: 1529 TN cases, 3399 controls; stage 2: 2148 cases, 1309 controls) to identify loci that influence TN breast cancer risk. Variants in the 19p13.1 and PTHLH loci showed genome-wide significant associations (P < 5 × 10(-) (8)) in stage 1 and 2 combined. Results also suggested a substantial enrichment of significantly associated variants among the single nucleotide polymorphisms (SNPs) analyzed in stage 2. Variants from 25 of 74 known breast cancer susceptibility loci were also associated with risk of TN breast cancer (P < 0.05). Associations with TN breast cancer were confirmed for 10 loci (LGR6, MDM4, CASP8, 2q35, 2p24.1, TERT-rs10069690, ESR1, TOX3, 19p13.1, RALY), and we identified associations with TN breast cancer for 15 additional breast cancer loci (P < 0.05: PEX14, 2q24.1, 2q31.1, ADAM29, EBF1, TCF7L2, 11q13.1, 11q24.3, 12p13.1, PTHLH, NTN4, 12q24, BRCA2, RAD51L1-rs2588809, MKL1). Further, two SNPs independent of previously reported signals in ESR1 [rs12525163 odds ratio (OR) = 1.15, P = 4.9 × 10(-) (4)] and 19p13.1 (rs1864112 OR = 0.84, P = 1.8 × 10(-) (9)) were associated with TN breast cancer. A polygenic risk score (PRS) for TN breast cancer based on known breast cancer risk variants showed a 4-fold difference in risk between the highest and lowest PRS quintiles (OR = 4.03, 95% confidence interval 3.46-4.70, P = 4.8 × 10(-) (69)). This translates to an absolute risk for TN breast cancer ranging from 0.8% to 3.4%, suggesting that genetic variation may be used for TN breast cancer risk prediction.

Two major breast cancer sub-types are defined by the expression of estrogen receptors on tumour cells. Cancers with large numbers of receptors are termed estrogen receptor positive and those with few are estrogen receptor negative. Using genome-wide single nucleotide polymorphism genotype data for a sample of early-onset breast cancer patients we developed a Support Vector Machine (SVM) classifier from 200 germline variants associated with estrogen receptor status (p

Genome-Wide Association Studies (GWAS) have begun to investigate associations between inherited genetic variations and breast cancer prognosis. Here, we report our findings from a GWAS conducted in 536 patients with early-onset breast cancer aged 40 or less at diagnosis and with a mean follow-up period of 4.1 years (SD = 1.96). Patients were selected from the Prospective Study of Outcomes in Sporadic versus Hereditary breast cancer. A Bonferroni correction for multiple testing determined that a P value of 1.0 × 10−7 was a statistically significant association signal. Following quality control, we identified 487,496 single nucleotide polymorphisms (SNP) for association tests in stage 1. In stage 2, 35 SNPs with the most significant associations were genotyped in 1,516 independent cases from the same early-onset cohort. In stage 2, 11 SNPs remained associated in the same direction (P ≤ 0.05). Fixed effects meta-analysis models identified one SNP associated at close to genome wide level of significance 556 kb upstream of the ARRDC3 locus [HR = 1.61; 95% confidence interval (CI), 1.33–1.96; P = 9.5 × 10−7]. Four further associations at or close to the PBX1, RORα, NTN1, and SYT6 loci also came close to genome-wide significance levels (P = 10−6). In the first ever GWAS for the identification of SNPs associated with prognosis in patients with early-onset breast cancer, we report a SNP upstream of the ARRDC3 locus as potentially associated with prognosis (median follow-up time for genotypes: CC = 4 years, CT = 3 years, and TT = 2.7 years; Wilcoxon rank-sum test CC vs. CT, P = 4 × 10−4 and CT vs. TT, P = 0.76). Four further loci may also be associated with prognosis. Cancer Res; 73(6); 1883–91. ©2012 AACR.

BACKGROUND: Genome wide association studies (GWAS), mostly in Europeans have identified several common variants as associated with key lipid traits. Replication of these genetic effects in South Asian populations is important since it would suggest wider relevance for these findings. Given the rising prevalence of metabolic disorders and heart disease in the Indian sub-continent, these studies could be of future clinical relevance. METHODS: We studied seven common variants associated with a variety of lipid traits in previous GWASs. The study sample comprised of 3178 sib-pairs recruited as participants for the Indian Migration Study (IMS). Associations with various lipid parameters and quantitative traits were analyzed using the Fulker genetic association model. RESULTS: We replicated five of the 7 main effect associations with p-values ranging from 0.03 to 1.97x10(-7). We identified particularly strong association signals at rs662799 in APOA5 (beta=0.18 s.d, p=1.97 x 10(-7)), rs10503669 in LPL (beta =-0.18 s.d, p=1.0 x 10(-4)) and rs780094 in GCKR (beta=0.11 s.d, p=0.001) loci in relation to triglycerides. In addition, the GCKR variant was also associated with total cholesterol (beta=0.11 s.d, p=3.9x10(-4)). We also replicated the association of rs562338 in APOB (p=0.03) and rs4775041 in LIPC (p=0.007) with LDL-cholesterol and HDL-cholesterol respectively. CONCLUSIONS: We report associations of five loci with various lipid traits with the effect size consistent with the same reported in Europeans. These results indicate an overlap of genetic effects pertaining to lipid traits across the European and Indian populations.

BackgroundTo evaluate if, among children aged 3 to 15 years, influenza vaccination for multiple seasons affects the proportion sero-protected.Methodology/principal findingsParticipants were 131 healthy children aged 3-15 years. Participants were vaccinated with trivalent inactivated seasonal influenza vaccine (TIV) over the 2005-06, 2006-07 and 2007-8 seasons. Number of seasons vaccinated were categorized as one (2007-08); two (2007-08 and 2006-07 or 2007-08 and 2005-06) or three (2005-06, 2006-07, and 2007-08). Pre- and post-vaccination sera were collected four weeks apart. Antibody titres were determined by hemagglutination inhibition (HAI) assay using antigens to A/Solomon Islands/03/06 (H1N1), A/Wisconsin/67/05 (H3N2) and B/Malaysia/2506/04. The proportions sero-protected were compared by number of seasons vaccinated using cut-points for seroprotection of 1:40 vs. 1:320. The proportions of children sero-protected against H1N1 and H3N2 was high (>85%) regardless of number of seasons vaccinated and regardless of cut-point for seroprotection. For B Malaysia there was no change in proportions sero-protected by number of seasons vaccinated; however the proportions protected were lower than for H1N1 and H3N2, and there was a lower proportion sero-protected when the higher, compared to lower, cut-point was used for sero-protection.Conclusion/significanceThe proportion of children sero-protected is not affected by number of seasons vaccinated.

Background. Levels of the proinfl ammatory cytokine interleukin-18 (IL-18) are raised in old age and are associated with reduced physical functioning. Previous studies have indicated that the C allele of the rs5744256 polymorphism in the IL-18 gene is strongly associated with reduced circulating IL-18 levels. This variant has previously been associated with improved locomotor performance in old age, but the fi nding requires independent replication. Methods. We examined the association between the IL-18 polymorphism rs5744256 and physical functioning in three cohorts with a total of 4,107 participants aged 60 – 85 years: the English Longitudinal Study of Ageing, Caerphilly, and Boyd Orr. We meta-analyzed ( N = 6,141) the results with data from the original paper reporting this association: IowaEstablished Populations for Epidemiological Study of the Elderly and InCHIANTI cohorts. Physical functioning was assessed by timed walks or the get up and go test. As locomotor performance tests differed between the cohorts and the distributions of times to complete the test (in seconds) were positively skewed, we used the reciprocal transformation and computed study-specifi c z scores. Results. Based on the three new studies, the estimated linear regression coeffi cient per C allele was 0.011 (95% confi dence interval [95% CI]: � 0.04 to 0.06). A meta-analysis that pooled the data from all studies showed weak evidence of an effect, with a regression coeffi cient of 0.047 (95% CI: 0.010 to 0.083). Conclusions. We did not replicate an association between the IL-18 rs5744256 polymorphism and the physical function in people aged 60 – 85 years. However, pooling data from all studies suggested a weak association of the C allele of the rs5744256 single nucleotide polymorphism on improving walking times in old age .

There is considerable evidence that human genetic variation influences gene expression. Genome-wide studies have revealed that mRNA levels are associated with genetic variation in or close to the gene coding for those mRNA transcripts – cis effects, and elsewhere in the genome – trans effects. The role of genetic variation in determining protein levels has not been systematically assessed. Using a genome-wide association approach we show that common genetic variation influences levels of clinically relevant proteins in human serum and plasma. We evaluated the role of 496,032 polymorphisms on levels of 42 proteins measured in 1200 fasting individuals from the population based InCHIANTI study. Proteins included insulin, several interleukins, adipokines, chemokines, and liver function markers that are implicated in many common diseases including metabolic, inflammatory, and infectious conditions. We identified eight Cis effects, including variants in or near the IL6R (p = 1.8×10−57), CCL4L1 (p = 3.9×10−21), IL18 (p = 6.8×10−13), LPA (p = 4.4×10−10), GGT1 (p = 1.5×10−7), SHBG (p = 3.1×10−7), CRP (p = 6.4×10−6) and IL1RN (p = 7.3×10−6) genes, all associated with their respective protein products with effect sizes ranging from 0.19 to 0.69 standard deviations per allele. Mechanisms implicated include altered rates of cleavage of bound to unbound soluble receptor (IL6R), altered secretion rates of different sized proteins (LPA), variation in gene copy number (CCL4L1) and altered transcription (GGT1). We identified one novel trans effect that was an association between ABO blood group and tumour necrosis factor alpha (TNF-alpha) levels (p = 6.8×10−40), but this finding was not present when TNF-alpha was measured using a different assay , or in a second study, suggesting an assay-specific association. Our results show that protein levels share some of the features of the genetics of gene expression. These include the presence of strong genetic effects in cis locations. The identification of protein quantitative trait loci (pQTLs) may be a powerful complementary method of improving our understanding of disease pathways., Author Summary One of the central dogmas of molecular genetics is that DNA is transcribed to RNA which is translated to protein and alterations to proteins can influence human diseases. Genome-wide association studies have recently revealed many new DNA variants that influence human diseases. To complement these efforts, several genome-wide studies have established that DNA variation influences mRNA expression levels. Loci influencing mRNA levels have been termed “eQTLs”. In this study we have performed the first genome-wide association study of the third piece in this jigsaw – the role of DNA variation in relation to protein levels, or “pQTLs”. We analysed 42 proteins measured in blood fractions from the InCHIANTI study. We identified eight cis effects including common variants in or near the IL6R, CCL4, IL18, LPA, GGT1, SHBG, CRP and IL1RN genes, all associated with blood levels of their respective protein products. Mechanisms implicated included altered transcription (GGT1) but also rates of cleavage of bound to unbound soluble receptor (IL6R), altered secretion rates of different sized proteins (LPA) and variation in gene copy number (CCL4). Blood levels of many of these proteins are correlated with human diseases and the identification of “pQTLs” may in turn help our understanding of disease.

Interleukin-6 (IL-6) is a key inflammatory cytokine, signalling to most tissues by binding to a soluble IL-6 receptor (sIL-6r), making a complex with gp130. We used 1273 subjects (mean age 68 years) from the InCHIANTI Italian cohort to study common variation in the IL-6r locus and associations with interleukin 6 receptor (IL-6r), IL-6, gp130 and a battery of inflammatory markers. The rs4537545 single nucleotide polymorphism (SNP) tags the functional non-synonymous Asp358Ala variant (rs8192284) in IL-6r (r2 = 0.89, n = 343). Individuals homozygous for the rs4537545 SNP minor allele (frequency 40%) had a doubling of IL-6r levels (132.48 pg/ml, 95% CI 125.13–140.27) compared to the common allele homozygous group (68.31 pg/ml, 95% CI 65.35–71.41): in per allele regression models, the rs4537545 SNP accounted for 20% of the variance in sIL-6r, with P = 5.1 × 10−62. The minor allele of rs4537545 was also associated with higher circulating IL-6 levels (P = 1.9 × 10−4). There was no association of this variant with serum levels of gp130 or with any of the studied pro- and anti-inflammatory markers. A common variant of the IL-6r gene results in major changes in IL-6r and IL-6 serum levels, but with no apparent effect on gp130 levels or on inflammatory status in the general population.

Background—The proinflammatory cytokine interleukin-18 (IL-18) is associated with major disabling conditions, although whether as byproduct or driver is unclear. The role of common variation in the IL-18 gene on serum concentrations and functioning in old age is unknown. Methods—We used 1671 participants aged 65–80 years from two studies: the InCHIANTI study and wave 6 of the Iowa-Established Populations for Epidemiological Study of the Elderly (EPESE). We tested three common polymorphisms against IL-18 concentration and measures of functioning. Results—In the InCHIANTI study, a 1 standard deviation increase in serum IL-18 concentrations was associated with an increased chance of being in the 20% of slowest walkers (odds ratio 1.45; 95% confidence interval, 1.17–1.80; p = .0007) and 20% of those with poorest function based on the Short Physical Performance Battery Score (odds ratio 1.52; 95% confidence interval, 1.22–1.89; p =.00016) in age sex adjusted logistic regression models. There was no association with Activities of Daily Living (p = .26) or Mini-Mental State Examination score (p = .66). The C allele of the IL-18 polymorphism rs5744256 reduced serum concentrations of IL-18 by 39 pmol/mL per allele (p = . 00001). The rs5744256 single nucleotide polymorphism was also associated with shorter walk times in InCHIANTI (n =662, p =.016) and Iowa-EPESE (n =995, p =.026). In pooled ranked models rs5744256 was also associated with higher SPPB scores (n =1671, p = .019). Instead of adjusting for confounders in the IL-18 walk time association, we used rs5744256 in a Mendelian randomization analysis: The association remained in instrumental variable models (p = .021). Conclusion—IL-18 concentrations are associated with physical function in 65- to 80-year-olds. A polymorphism in the IL-18 gene alters IL-18 concentrations and is associated with an improvement in walk speed. IL-18 may play an active role in age-related functional impairment, but these findings need independent replication.

Introduction Tumor lymphocyte infiltration is associated with clinical response to chemotherapy in estrogen receptor (ER) negative breast cancer. To identify variants in immunosuppressive pathway genes associated with prognosis after adjuvant chemotherapy for ER-negative patients, we studied stage I-III invasive breast cancer patients of European ancestry, including 9,334 ER-positive (3,151 treated with chemotherapy) and 2,334 ER-negative patients (1,499 treated with chemotherapy). Methods We pooled data from sixteen studies from the Breast Cancer Association Consortium (BCAC), and employed two independent studies for replications. Overall 3,610 single nucleotide polymorphisms (SNPs) in 133 genes were genotyped as part of the Collaborative Oncological Gene-environment Study, in which phenotype and clinical data were collected and harmonized. Multivariable Cox proportional hazard regression was used to assess genetic associations with overall survival (OS) and breast cancer-specific survival (BCSS). Heterogeneity according to chemotherapy or ER status was evaluated with the log-likelihood ratio test. Results Three independent SNPs in TGFBR2 and IL12B were associated with OS (P C) (per allele hazard ratio (HR) 1.54 (95% confidence interval (CI) 1.22 to 1.95), P = 3.08 × 10−4) was not found in ER-negative patients without chemotherapy or ER-positive patients with chemotherapy (P for interaction A) with poorer OS (HR 1.50 (95% CI 1.21 to 1.86), P = 1.81 × 10−4), and rs2853694 (A > C) with improved OS (HR 0.73 (95% CI 0.61 to 0.87), P = 3.67 × 10−4). Similar associations were observed with BCSS. Association with TGFBR2 rs1367610 but not IL12B variants replicated using BCAC Asian samples and the independent Prospective Study of Outcomes in Sporadic versus Hereditary Breast Cancer Study and yielded a combined HR of 1.57 ((95% CI 1.28 to 1.94), P = 2.05 × 10−5) without study heterogeneity. Conclusions TGFBR2 variants may have prognostic and predictive value in ER-negative breast cancer patients treated with adjuvant chemotherapy. Our findings provide further insights into the development of immunotherapeutic targets for ER-negative breast cancer.