SynthesisBreast cancer research : BCR2015
Assessment of variation in immunosuppressive pathway genes reveals TGFBR2 to be associated with prognosis of estrogen receptor-negative breast cancer after chemotherapy.
Synthesis in Breast cancer research : BCR, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 24 citations in OpenAlex.
- Association of germline genetic variants with breast cancer-specific survival in patient subgroups defined by clinic-pathological variables related to tumor biology and type of systemic treatment.Breast cancer research : BCR · 2021Article
- DAGM: A novel modelling framework to assess the risk of HER2-negative breast cancer based on germline rare coding mutations.EBioMedicine · 2021Article
- Genetic Influences in Breast Cancer Drug Resistance.Breast cancer (Dove Medical Press) · 2021Review
- Eight immune-related genes predict survival outcomes and immune characteristics in breast cancer.Aging · 2020Article
- Reciprocal fine-tuning of progesterone and prolactin-regulated gene expression in breast cancer cells.Molecular and cellular endocrinology · 2020Article
- Modeling and comparing data mining algorithms for prediction of recurrence of breast cancer.PloS one · 2020Article
- Tumor exome sequencing and copy number alterations reveal potential predictors of intrinsic resistance to multi-targeted tyrosine kinase inhibitors.Oncotarget · 2017Article
- Predicting radiotherapy response for patients with soft tissue sarcoma by developing a molecular signature.Oncology reports · 2017Article
- Breast tumor DNA methylation patterns associated with smoking in the Carolina Breast Cancer Study.Breast cancer research and treatment · 2017Article
- Expression ofOncology letters · 2017Article
- Association of multiple genetic variants with breast cancer susceptibility in the Han Chinese population.Oncotarget · 2016Article
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Authors and funding
91 authors at 20 institutions in 18 countries.
Funding
Abstract
introductionTumor 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).
methodsWe 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.
resultsThree independent SNPs in TGFBR2 and IL12B were associated with OS (P <10⁻³) solely in ER-negative patients after chemotherapy (267 events). Poorer OS associated with TGFBR2 rs1367610 (G > 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 <10-3). Two SNPs in IL12B (r² = 0.20) showed different associations with ER-negative disease after chemotherapy: rs2546892 (G > 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.
conclusionsTGFBR2 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.
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