Dataset Information

Association of ?H2AX at Diagnosis with Chemotherapy Outcome in Patients with Breast Cancer.

ABSTRACT: ?H2AX plays a role in DNA damage response signaling and facilitates the repair of DNA double strand breaks. However, it remains unknown whether constitutive tumor ?H2AX expression is associated with treatment outcome in patients. ?H2AX status was detected in primary tumors from 24% of 826 patients with stage I, II and III breast cancer by immunohistochemistry; overall survival was analyzed by Kaplan-Meier method. At median follow-up of 176 months (range 13 - 282 months), we found substantial survival heterogeneity in ?H2AX-positive patients (P=0.002) among uniform treatment groups including radiation or endocrine therapy alone and no-treatment, as well as chemotherapy alone (being worst), in contrast to ?H2AX-negative patients (P=0.2). In the chemotherapy group (n=118), median survival was 63 months (95% confidence interval [CI], 29 - 83) in patients with ?H2AX-positive tumors compared with 170 months (95% CI 94 - 235) in those with ?H2AX-negative tumors (P=0.0017). ?H2AX remained a poor prognosis factor in the group by multivariable analysis (adjusted hazard ratio 2.12, P=0.009). Our data demonstrate that constitutive ?H2AX positivity is significantly associated with survival heterogeneity in patients among uniform treatment groups, and its expression at diagnosis independently predicts poor chemotherapy outcome in breast cancer.

SUBMITTER: Yang SX

PROVIDER: S-EPMC5381256 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Association of γH2AX at Diagnosis with Chemotherapy Outcome in Patients with Breast Cancer.

Yang Sherry X SX Polley Eric C EC Nguyen Dat D

Theranostics 20170222 4

γH2AX plays a role in DNA damage response signaling and facilitates the repair of DNA double strand breaks. However, it remains unknown whether constitutive tumor γH2AX expression is associated with treatment outcome in patients. γH2AX status was detected in primary tumors from 24% of 826 patients with stage I, II and III breast cancer by immunohistochemistry; overall survival was analyzed by Kaplan-Meier method. At median follow-up of 176 months (range 13 - 282 months), we found substantial sur ...[more]

PMID: 28382166

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Project description:PurposeWe aimed to determine the rate of pathological complete response (pCR), clinicopathological factors associated with pCR, and clinical outcomes following neoadjuvant chemotherapy in locally advanced breast cancer.MethodsMedical records of patients who had undergone neoadjuvant chemotherapy for breast cancer between January 2007 and September 2011 were retrospectively reviewed, and the pCR rates were calculated according to three sets of criteria: the National Surgical Adjuvant Breast and Bowel Project (NSABP), the MD Anderson Cancer Center (MDACC), and the German Breast Group (GBG). Tumors were classified as luminal A like, luminal B like, human epidermal growth factor receptor 2 (HER2), or triple-negative. pCR and clinical outcome, including overall survival (OS) and disease-free survival (DFS) rates were analyzed at the median follow-up of 54.2 months.ResultsOf a total of 179 patients who had received neoadjuvant chemotherapy, 167 patients (93.3%) had locally advanced breast cancer and 12 patients (6.7%) had early-stage breast cancer. The majority of patients (152 patients, 89.4%) received anthracycline-based neoadjuvant chemotherapy. The objective clinical response rate was 61.5%, comprising clinical partial response in 5.5% and clinical complete response in 3.9% of patients. Twenty-one (11.7%), 20 (11.2%), and 17 patients (9.5%) achieved pCR according to NSABP, MDACC, and GBG definitions, respectively. pCR rates, as defined by NSABP, according to breast cancer subtype were 4.4%, 9.7%, 24.2%, and 19.2% in luminal A like, luminal B like, HER2, and triple-negative subtypes, respectively. Patients who achieved pCR had significantly better DFS (5-year DFS rates, 80% vs. 53%, p=0.030) and OS (5-year OS rates, 86% vs. 54%, p=0.042) than those who did not.ConclusionThe pCR rate following neoadjuvant chemotherapy for breast cancer in Thai women attending our institution was 11.7%; pCR was more frequently observed in HER2 and triple-negative breast tumor subtypes. Patients who achieved pCR had significantly improved survival.

Project description:BACKGROUND:The subtyping of breast cancer based on features of tumour biology such as hormonal receptor and HER2 status has led to increasingly patient-specific treatment and thus improved outcomes. However, such subgroups may not be sufficiently informed to best predict outcome and/or treatment response. The incorporation of multi-modal data may identify unexpected and actionable subgroups to enhance disease understanding and improve outcomes. METHODS:This retrospective cross-sectional study used the cancer registry Surveillance, Epidemiology and End Results (SEER), which represents 28% of the U.S. population. We included adult female patients diagnosed with breast cancer in 2010. Latent class analysis (LCA), a data-driven technique, was used to identify clinically homogeneous subgroups ("endophenotypes") of breast cancer from receptor status (hormonal receptor and HER2), clinical, and demographic data and each subgroup was explored using Bayesian networks. RESULTS:Included were 44,346 patients, 1257 (3%) of whom had distant organ metastases at diagnosis. Four endophenotypes were identified with LCA: 1) "Favourable biology" had entirely local disease with favourable biology, 2) "HGHR-" had the highest incidence of HR- receptor status and highest grade but few metastases and relatively good outcomes, 3) "HR+ bone" had isolated bone metastases and uniform receptor status (HR+/HER2-), and 4) "Distant organ spread" had high metastatic burden and poor survival. Bayesian networks revealed clinically intuitive interactions between patient and disease features. CONCLUSIONS:We have identified four distinct subgroups of breast cancer using LCA, including one unexpected group with good outcomes despite having the highest average histologic grade and rate of HR- tumours. Deeper understanding of subgroup characteristics can allow us to 1) identify actionable group properties relating to disease biology and patient features and 2) develop group-specific diagnostics and treatments.

Project description:INTRODUCTION: Chemotherapy-induced alopecia is one of the most common adverse events caused by conventional cytotoxic chemotherapy, yet there has been very little progress in the prevention or treatment of this side effect. Although this is not a life-threatening event, alopecia is very psychologically difficult for many women to manage. In order to improve the quality of life for these women, it is important to elucidate the molecular mechanisms of chemotherapy-induced alopecia and develop ways to effectively prevent and/or treat it. To identify the genetic risk factors associated with chemotherapy-induced alopecia, we conducted a genome-wide association study (GWAS) using DNA samples from breast cancer patients who were treated with chemotherapy. METHODS: We performed a case-control association study of 303 individuals who developed grade 2 alopecia, and compared them with 880 breast cancer patients who did not show hair loss after being treated with conventional chemotherapy. In addition, we separately analyzed a subset of patients who received specific combination therapies by GWASs and applied the weighted genetic risk scoring (wGRS) system to investigate the cumulative effects of the associated SNPs. RESULTS: We identified an SNP significantly associated with drug-induced grade 2 alopecia (rs3820706 in CACNB4 (calcium channel voltage-dependent subunit beta 4) on 2q23, P = 8.13 × 10(-9), OR = 3.71) and detected several SNPs that showed some suggestive associations by subgroup analyses. We also classified patients into four groups on the basis of wGRS analysis and found that patients who classified in the highest risk group showed 443 times higher risk of antimicrotubule agents-induced alopecia than the lowest risk group. CONCLUSIONS: Our study suggests several associated genes and should shed some light on the molecular mechanism of alopecia in chemotherapy-treated breast cancer patients and hopefully will contribute to development of interventions that will improve the quality of life (QOL) of cancer patients.

Dataset Information

Association of ?H2AX at Diagnosis with Chemotherapy Outcome in Patients with Breast Cancer.

Publications

Association of γH2AX at Diagnosis with Chemotherapy Outcome in Patients with Breast Cancer.

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