Abstract:
PURPOSE:We conducted an exploratory biomarker study from a phase II clinical trial of eribulin plus gemcitabine (EG) versus paclitaxel plus gemcitabine (PG) in HER2-negative metastatic breast cancer (BC) patients. METHODS:We performed targeted deep sequencing with a customized cancer gene panel and RNA expression assay. Tumor mutation burden (TMB) and mutation signatures were determined based on genetic alteration in targeted regions. Gene set variation analysis was performed with PanCancer Immune Profiling and PanCancer Pathway Panels. Statistical analyses were conducted to identify the associations between genetic alterations and clinical outcomes. RESULTS:Of 119 patients, 40 had available biomarker data. Among the 40 patients, 4 supported their post-treatment tissues. In targeted deep sequencing, FAT3 (48%) was the most frequently mutated gene, followed by PKHD1, TP53, GATA3, PARP4, and PIK3CA. In terms of gene expression, low expression of epithelial-mesenchymal transition (EMT) pathway genes was associated with prolonged progression-free survival (PFS) in the EG group, while high expression of the EMT pathway was associated with good prognosis in the PG group. Median TMB was 6.5 (range 2.44-46.34) and there was no relationship between TMB and patient prognosis. Analysis of mutation signatures showed that signatures 3, 20, and 26 were frequently observed in our cohort. Further survival analysis according to mutation signature showed that mutation signature 3, as a homologous recombinant deficiency-related signature, was highly associated with disease progression (hazard ratio (log2 scale) 8.21, 95% confidence interval 2.93-13.48, p = 0.002). Kaplan-Meier plot also showed that BCs with signature 3 had short PFS compared to those without these signatures (median PFS (months) for signature 3 (low vs. high): 17.2 vs. 8.1, p = 0.0026). CONCLUSIONS:Mutation signature 3, found in about 30% of MBCs regardless of hormone receptor status, was associated with short PFS for patients with cytotoxic chemotherapy. TRIAL REGISTRY:ClinicalTrials.gov number: NCT02263495.
journal_name
Breast Cancer Res Treatjournal_title
Breast cancer research and treatmentauthors
Kim JY,Lee E,Park K,Im SA,Sohn J,Lee KS,Chae YS,Kim JH,Kim TY,Jung KH,Park YH,Breast Cancer Committee of the Korean Cancer Study Group.doi
10.1007/s10549-019-05400-ysubject
Has Abstractpub_date
2019-11-01 00:00:00pages
367-377issue
2eissn
0167-6806issn
1573-7217pii
10.1007/s10549-019-05400-yjournal_volume
178pub_type
杂志文章abstract::There remains a high unmet need for effective treatments for metastatic breast cancer. In recent years there have been many advances in the understanding of biological basis of cancer. Several cellular pathways have been identified that play crucial roles in causing or maintaining the cancer phenotype. Many new agents...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章,评审
doi:10.1007/s10549-008-0268-y
更新日期:2009-07-01 00:00:00
abstract::Medroxyprogesterone acetate (MPA) is well recognized to have beneficial effects for the treatment of advanced breast cancer which are comparable to those achieved with other forms of endocrine therapy. Using mammary tumors induced in the rat by dimethylbenz(a)anthracene (DMBA) as a model, we have studied the possibili...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/BF00665803
更新日期:1993-01-01 00:00:00
abstract::The response to primary chemotherapy is an important prognostic factor in patients with non metastatic breast cancer. In this study we compared the assessment of response performed by clinical palpation to that performed by echography and mammography in 141 out of 157 consecutive breast cancer patients (T2-4, N0-1, M0...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1023/a:1012277325168
更新日期:2001-09-01 00:00:00
abstract::Women who have been treated for breast cancer are typically followed up with regular mammography and palpation, with the aim of detecting recurrences and contralateral breast cancer (CBC). This study aims to investigate if the diagnostic work-up of breast cancer patients has improved over the last 25 years and resulte...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-010-0748-8
更新日期:2010-08-01 00:00:00
abstract::Since our previous findings had indicated that the androgenic steroid medroxyprogesterone acetate (MPA) exerts potent inhibitory effects on 7,12-dimethylbenz(a)anthracene (DMBA)-induced tumor growth, we have studied the effect of low doses of MPA released from Depo-Provera and from 50:50 poly[DL-lactide-co-glycolide] ...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/BF01961245
更新日期:1992-01-01 00:00:00
abstract::Erratum to: Breast Cancer Res Treat (2013),138:369–381,DOI 10.1007/s10549-012-2389-6. In the original publication of the article, the Fig. 4c and d were published erroneously. The revised Fig. 4 is given in this erratum. ...
journal_title:Breast cancer research and treatment
pub_type: 已发布勘误
doi:10.1007/s10549-016-3752-9
更新日期:2016-04-01 00:00:00
abstract::Early and late effects of cancer treatment are of increasing concern with growing survivor populations, but relevant data are sparse. We sought to determine the prevalence and hazard ratio of such effects in breast cancer cases. Women with invasive breast cancer and women with no cancer history recruited for a cancer ...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-014-2928-4
更新日期:2014-05-01 00:00:00
abstract:BACKGROUND:The estrogen receptor alpha (ESR1) is a mediator of estrogen response in the breast. The most studied variants in this gene are the PvuII and XbaI polymorphisms, which have been associated to lower sensitivity to estrogen. We evaluated whether these polymorphisms were associated with breast cancer risk by me...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-007-9562-3
更新日期:2008-02-01 00:00:00
abstract:PURPOSE:To evaluate the loco-regional recurrence (LRR) rate after breast-conserving surgery without postoperative radiotherapy (RT) for ductal carcinoma in situ (DCIS) of the breast. METHODS:Between 2000 and 2010, 311 DCIS patients from 9 institutions were analyzed retrospectively. The median age was 47 (range, 20-82)...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章,多中心研究
doi:10.1007/s10549-017-4111-1
更新日期:2017-02-01 00:00:00
abstract:PURPOSE:Among patients diagnosed with breast cancer (BC), women also living with HIV (WLWH) have worse survival than women without HIV. Chronic HIV infection may interfere with the effectiveness of BC treatment, contributing to this disparity. We attempted to determine the impact of HIV infection on response to neoadju...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-020-05889-8
更新日期:2020-12-01 00:00:00
abstract:PURPOSE:In rodents, a single exercise bout performed 24 h prior to a single doxorubicin treatment provides cardio-protection. This study investigated whether performing this intervention prior to every doxorubicin treatment for breast cancer reduced subclinical cardiotoxicity and treatment symptoms. METHODS:Twenty-fou...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章,随机对照试验
doi:10.1007/s10549-017-4554-4
更新日期:2018-02-01 00:00:00
abstract::Breast cancer is the most common cancer in women worldwide, accounting for just over 1 million new cases annually. Population-based statistics show that globally, when compared to whites, women of African ancestry (AA) tend to have more aggressive breast cancers that present more frequently as estrogen receptor negati...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章,评审
doi:10.1007/s10549-010-0827-x
更新日期:2010-06-01 00:00:00
abstract::Inheritance is believed to play a major role in 5-10% of breast cancer. The breast cancer susceptibility genes BRCA1 and BRCA2 are estimated to account for more than half of these cases. Recent studies have suggested that breast cancers associated with BRCA1 germline mutations are of higher grade than sporadic cases. ...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1023/a:1005853022804
更新日期:1998-01-01 00:00:00
abstract:PURPOSE:Little is known about racial variations in the financial impact of cancer care. Using data from a national survey of racially diverse patients with metastatic breast cancer, we examined racial/ethnic patterns in employment and cost-management (i.e., financial coping) behaviors. METHODS:We conducted an online s...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-019-05449-9
更新日期:2020-01-01 00:00:00
abstract:PURPOSE:Previous work found that lower BMI is associated with a pathologic complete response (pCR) following neoadjuvant chemotherapy for breast cancer. Relative dose intensity (RDI) of chemotherapy is an important marker of treatment tolerability. We hypothesized that patients with low BMI would have higher RDI than p...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-020-05994-8
更新日期:2020-10-30 00:00:00
abstract::The aim of this study is to identify and validate copy number aberrations in early-stage primary breast tumors associated with bone or non-bone metastasis. Whole-genome molecular inversion probe arrays were used to evaluate copy number imbalances (CNIs) in breast tumors from 960 early-stage patients with information a...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-013-2796-3
更新日期:2014-01-01 00:00:00
abstract::Growth, progression, and metastasis of breast cancer, as well as of most of the other tumors, are angiogenesis-dependent processes. Several pro-angiogenic growth factors and endogenous inhibitors of angiogenesis have been identified and sequenced, and experimental studies suggest that angiogenic activity of a tumor ma...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章,评审
doi:10.1023/a:1006175504673
更新日期:1998-01-01 00:00:00
abstract::The article Reducing chemotherapy use in clinically high-risk, genomically low-risk pN0 and pN1 early breast cancer patients: five-year data from the prospective, randomised phase 3 West German Study Group (WSG) PlanB trial, written by Ulrike Nitz, Oleg Gluz, Matthias Christgen, Ronald E. Kates, Michael Clemens, Wolfr...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章,已发布勘误
doi:10.1007/s10549-018-05105-8
更新日期:2019-05-01 00:00:00
abstract::The concept of cancer cells being hierarchically organized and arising from their own progenitor stem cells will have important implications on cancer therapy. If this hypothesis were to be true then the paucity of estrogen receptors in stem cells as well as their inherent drug resistance mechanisms pose a challenge t...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-009-0619-3
更新日期:2010-08-01 00:00:00
abstract::To date, three molecular markers (ER, PR, and CYP2D6) have been used in clinical setting to predict the benefit of the anti-estrogen tamoxifen therapy. Our aim was to validate new biomarker candidates predicting response to tamoxifen treatment in breast cancer by evaluating these in a meta-analysis of available transc...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章,meta分析
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更新日期:2013-07-01 00:00:00
abstract::We have measured the levels of tamoxifen and three of its metabolites in the blood of patients receiving tamoxifen alone or combination therapy with tamoxifen and medroxyprogesterone acetate. Our results indicate that addition of the progestogen significantly alters the metabolism of tamoxifen over a six-month period....
journal_title:Breast cancer research and treatment
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1007/BF01833345
更新日期:1992-01-01 00:00:00
abstract:INTRODUCTION:To examine the trends in the prevalence of breast cancer risk factors in relation to breast cancer incidence trends and to explore whether the changes in risk factors differed by ethnicity in Hawaii over a 25-year period. METHODS:We pooled 17 population-based epidemiological studies conducted in Hawaii be...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-005-9129-0
更新日期:2006-07-01 00:00:00
abstract::Breast cancer is the most common malignant tumor-affecting women during the child bearing period. With the rising trend in delaying pregnancy later in life, the issue of subsequent pregnancy and lactation following breast cancer diagnosis has been more frequently encountered. In this context, data is scarce particular...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章,评审
doi:10.1007/s10549-008-9983-7
更新日期:2009-03-01 00:00:00
abstract::The uptake and retention of a radiolabeled synthetic progestin ORG 2058 by the mammary glands were examined in the baboon. Four estrogen-primed baboons were injected intravenously with 2.5 micrograms/kg body weight of 3H-ORG 2058. One animal received an additional injection of 2.5 mg/kg body weight of unlabeled proges...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/BF01806397
更新日期:1984-01-01 00:00:00
abstract::The aim of this study was to compare the effects on health-related quality of life (HRQOL) of two treatment regimens in the TEX trial during 9 month from random assignment, with emphasis on the 2- and 9-months assessments. A total of 287 patients were randomized to treatment in 3-week cycles with either epirubicin plu...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章,多中心研究,随机对照试验
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更新日期:2010-10-01 00:00:00
abstract::A class distribution of plasma cells associated with the stroma in twenty-eight cases of medullary carcinoma of the breast was investigated by an unlabeled immunoperoxidase method. The stroma of the medullary carcinomas tested was found to contain predominantly IgG plasma cells except in two cases. Stroma of the other...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/BF01806794
更新日期:1986-01-01 00:00:00
abstract::The biological and clinical significance of circulating tumor cells (CTC) in the peripheral blood of breast cancer patients is not known. To study this question, we used a direct visualization assay to correlate the number of CTC with disease stage and progression. The CTC were enriched from the nucleated cell fractio...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1023/B:BREA.0000036897.92513.72
更新日期:2004-08-01 00:00:00
abstract:PURPOSE:The purpose of the study was to assess self-reported taste and smell perception after chemotherapy in breast cancer patients compared with women without cancer, and to assess whether taste and smell perception is associated with quality of life after the end of chemotherapy. METHODS:We included 135 newly diagn...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-018-4720-3
更新日期:2018-07-01 00:00:00
abstract::We report a series of breast cancer patients with invasive skin and nail infections with Staphylococcus species that we attribute to the addition of pertuzumab to trastuzumab-based therapy. With the suspicion of an increased incidence of cutaneous infection in patients treated with pertuzumab and trastuzumab-based che...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章,随机对照试验
doi:10.1007/s10549-014-3190-5
更新日期:2014-12-01 00:00:00
abstract::Bone metastasis is a common and serious complication in advanced cancers such as breast cancer, prostate cancer, and multiple myeloma. Agents that prevent bone loss could be used to develop an alternative therapy for bone metastasis. RANKL, a member of the tumor necrosis factor superfamily, has been shown to play a si...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-014-2844-7
更新日期:2014-02-01 00:00:00