Sequential versus concurrent use of chemotherapy and endocrine therapy in the adjuvant treatment of ER-positive breast cancer: A systematic review and Bayesian network meta-analysis.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e12040-e12040
Author(s):  
Tianfu Li ◽  
Zhen Shan ◽  
Liang Yu ◽  
Xiaying Kuang ◽  
Deyuan Zhang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Endocrine Therapy ◽  
Adjuvant Treatment ◽  
Randomized Clinical Trials ◽  
Statistical Significance ◽  
Disease Free Survival ◽  
Breast Cancer Patients ◽  
Concurrent Use ◽  
Er Positive ◽  
Positive Breast Cancer

e12040 Background: Chemotherapy followed by endocrine therapy is the standard adjuvant treatment strategy for estrogen receptor-positive breast cancer patients. However, no direct evidence so far demonstrated better efficacy of sequential use of chemotherapy and endocrine therapy over concurrent. Objective: To evaluate the efficacy between sequential and concurrent use of chemotherapy and endocrine therapy in the adjuvant treatment of ER positive breast cancer. Methods: Randomized clinical trials comparing chemotherapy and/or endocrine therapy in the adjuvant treatment of ER positive breast cancer were included. Hazard ratios (HRs) of disease-free survival (DFS) and overall survival (OS) were extracted and analyzed in Bayesian analysis. Patients were stratified by menopause status for subgroup analysis. Results: 37 trials were identified with 37225 patients enrolled in total, 37 trials with DFS results and 24 with OS. 3 comparisons were done between sequential and concurrent arms. In DFS analysis, no statistical significance was found in all 3 comparisons [CHE seq/con TAM (HR 1.01, 95%CI 0.8497 - 1.199); CHE seq/con OFS+TAM (HR 0.9119, 95%CI 0.5666 - 1.49); CHE seq/con OFS+AI (HR 1.032, 95%CI 0.6291 - 1.776)]. The same were seen in OS analysis [CHE seq/con TAM (HR 0.9512, 95%CI 0.8053 - 1.125); CHE seq/con OFS+TAM (HR 1.065, 95%CI 0.6344 - 1.789); CHE seq/con OFS+AI (HR 1.069, 95%CI 0.665 - 1.717)]. Rankings were done for preferable treatment recommendations. In DFS analyses, sequential arms ranked higher than concurrent arms [CHE seq/con OFS+AI (1 vs. 3); CHE seq/con OFS+TAM (6 vs. 7); CHE seq/con TAM (8 vs. 8)]. The same tendency was seen in OS analyses [CHE seq/con OFS+AI (1 vs. 2); CHE seq/con TAM (4 vs. 5)] except for CHE seq/con OFS+TAM (11 vs. 6-9). In subgroup ranking results, CHE seq/con OFS+AI and CHE seq/con OFS+TAM showed consistency among comparisons with concurrent arms ranked higher than sequential arms. However, CHE seq TAM ranked higher than CHE con TAM in all comparisons. Conclusions: The combination of chemotherapy and endocrine therapy in the adjuvant treatment of ER positive breast cancer demonstrated equal efficacy either used sequentially or concurrently. However, concurrent arms were recommended over sequential arms in premenopausal patients for better DFS and OS, except for the combination of chemotherapy and tamoxifen which was recommended to be used sequentially. Others: This study has been registered in PROSPERO (CRD42018104889).

scholarly journals ESR1-Stabilizing Long Noncoding RNA TMPO-AS1 Promotes Hormone-Refractory Breast Cancer Progression

2019 ◽  
Vol 39 (23) ◽  
Author(s):  
Yuichi Mitobe ◽  
Kazuhiro Ikeda ◽  
Takashi Suzuki ◽  
Kiyoshi Takagi ◽  
Hidetaka Kawabata ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Cancer Patients ◽  
Endocrine Therapy ◽  
Cancer Progression ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Breast Cancer Patients ◽  
Er Positive ◽  
Positive Breast Cancer

ABSTRACT Acquired endocrine therapy resistance is a significant clinical problem for breast cancer patients. In recent years, increasing attention has been paid to long noncoding RNA (lncRNA) as a critical modulator for cancer progression. Based on RNA-sequencing data of breast invasive carcinomas in The Cancer Genome Atlas database, we identified thymopoietin antisense transcript 1 (TMPO-AS1) as a functional lncRNA that significantly correlates with proliferative biomarkers. TMPO-AS1 positivity analyzed by in situ hybridization significantly correlates with poor prognosis of breast cancer patients. TMPO-AS1 expression was upregulated in endocrine therapy-resistant MCF-7 cells compared with levels in parental cells and was estrogen inducible. Gain and loss of TMPO-AS1 experiments showed that TMPO-AS1 promotes the proliferation and viability of estrogen receptor (ER)-positive breast cancer cells in vitro and in vivo. Global expression analysis using a microarray demonstrated that TMPO-AS1 is closely associated with the estrogen signaling pathway. TMPO-AS1 could positively regulate estrogen receptor 1 (ESR1) mRNA expression by stabilizing ESR1 mRNA through interaction with ESR1 mRNA. Enhanced expression of ESR1 mRNA by TMPO-AS1 could play a critical role in the proliferation of ER-positive breast cancer. Our findings provide a new insight into the understanding of molecular mechanisms underlying hormone-dependent breast cancer progression and endocrine resistance.

scholarly journals Activated HER-receptors in predicting outcome of ER-positive breast cancer patients treated with adjuvant endocrine therapy

The Breast ◽  
2012 ◽  
Vol 21 (5) ◽  
pp. 662-668 ◽  
Author(s):  
Mathilde S. Larsen ◽  
Karsten Bjerre ◽  
Anne E. Lykkesfeldt ◽  
Anita Giobbie-Hurder ◽  
Anne-Vibeke Lænkholm ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Endocrine Therapy ◽  
Adjuvant Endocrine Therapy ◽  
Breast Cancer Patients ◽  
Er Positive ◽  
Predicting Outcome ◽  
Positive Breast Cancer

scholarly journals Identification of TACC1, NOV, and PTTG1 as new candidate genes associated with endocrine therapy resistance in breast cancer

2008 ◽  
Vol 42 (2) ◽  
pp. 87-103 ◽  
Author(s):  
Sandra E Ghayad ◽  
Julie A Vendrell ◽  
Ivan Bieche ◽  
Frédérique Spyratos ◽  
Charles Dumontet ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Candidate Genes ◽  
Endocrine Therapy ◽  
Cell Lines ◽  
Tamoxifen Treatment ◽  
Cross Resistance ◽  
Breast Cancer Patients ◽  
Er Positive ◽  
Positive Breast Cancer

Cross-resistance to molecules used in endocrine therapy is among the main challenges in the treatment of estrogen receptor-α (ERα) positive breast cancer. In this study, we used two different cell models of resistance to anti-estrogens: MVLN/CL6.7 cells and VP229/VP267 cells selected after exposure to tamoxifen respectively in vitro and in vivo to characterize a phenotype rarely observed, i.e. acquisition of cross-resistance to the pure ER antagonist fulvestrant. As MVLN/CL6.7 cells and VP229/VP267 cell lines are original and valuable models of cross-resistance to tamoxifen and fulvestrant, we examined candidate genes using a RTQ-PCR strategy to identify new biomarkers of endocrine resistance. Out of the 26 candidate genes tested, 19 displayed deregulation of expression at the basal level in at least one of the two resistant cell lines. Eight genes (TACC1, NOV, PTTG1, MAD2L1, BAK1, TGFB2, BIRC5, and CCNE2) were significantly overexpressed in samples from ER-positive breast cancer patients who relapsed after tamoxifen treatment (n=24) compared with samples from patients who did not (n=24). Five genes (TACC1, NOV, PTTG1, BAK1, and TGFB2) were correlated with significantly shorter relapse-free survival (univariate analysis). Finally, we identified TACC1 and a three-gene expression signature (TACC1, NOV, and PTTG1) as independent prognostic markers (multivariate analysis). Aberrant mRNA and protein levels of TACC1, NOV, and PTTG1 were also observed under tamoxifen and/or fulvestrant exposure in resistant CL6.7 cells compared with their respective control MVLN cells. In conclusion, our data identify TACC1, NOV, and PTTG1 as promising new markers that could be used in the clinical management of ER-positive breast cancer patients.

Mammostrat as an immunohistochemical multigene assay for prediction of early relapse risk in the TEAM pathology study.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 516-516
Author(s):  
John M. S. Bartlett ◽  
Kenneth J. Bloom ◽  
Tammy Robson ◽  
Thomas J. Lawton ◽  
Cornelis J. H. Van De Velde ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Adjuvant Chemotherapy ◽  
Endocrine Therapy ◽  
Disease Free Survival ◽  
Postmenopausal Breast Cancer ◽  
Nodal Status ◽  
Endocrine Treatment ◽  
Breast Cancer Patients ◽  
Additional Information ◽  
Er Positive

516 Background: Some postmenopausal patients with hormone sensitive early breast cancer remain at high risk of relapse despite endocrine therapy, and might benefit additionally from adjuvant chemotherapy. The challenge is to prospectively identify such patients. The Mammostrat test uses five immunohistochemical markers to stratify patients regarding recurrence risk, and may inform treatment decisions. We tested the efficacy of this panel in the TEAM trial. Methods: Pathology blocks from 4598 TEAM patients were collected and TMAs constructed. The cohort was 47% node positive and 36% were also treated with adjuvant chemotherapy. Triplicate 0.6mm2 TMA cores were stained and positivity for p53, HTF9C, CEACAM5, NDRG1, SLC7A5 assessed. Cases were assigned a Mammostrat risk score, and distant relapse free (DRFS) and disease free survival (DFS) analysed. Results: In multivariate regression analyses, corrected for conventional clinicopathological markers, Mammostrat provided significant additional information on DRFS after endocrine therapy in ER positive node negative patients (N=1226) not receiving chemotherapy (p=0.004). Further analyses in all patients not exposed to chemotherapy, irrespective of nodal status (N=2559) and in the entire cohort (N=3837) showed Mammostrat scores provide additional information on DRFS in these groups (p=0.001 and p<0.0001 respectively; multivariate analyses). No differences were seen between the two endocrine treatment regimens. Conclusions: The Mammostrat score predicts DRFS for both exemestane and tamoxifen-exemestane treated patients irrespective of nodal status and chemotherapy. The ability of this test to provide additional outcome data following treatment provides further evidence for its’ utility in risk stratification of ER positive postmenopausal breast cancer patients.

Comparing outcomes of neoadjuvant endocrine therapy versus chemotherapy in ER-positive breast cancer: Results from a prospective institutional database.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 581-581 ◽  
Author(s):  
Nathalie LeVasseur ◽  
Walter Yip ◽  
Huaqi Li ◽  
Kaylie Willems ◽  
Caroline Illmann ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Endocrine Therapy ◽  
Clinical Stage ◽  
Breast Cancer Patients ◽  
Long Term Outcomes ◽  
Neoadjuvant Endocrine Therapy ◽  
Er Positive ◽  
Positive Breast Cancer

581 Background: While neoadjuvant chemotherapy (NACT) has been established as the standard of care for medically fit patients, there has been renewed interest in utilizing neoadjuvant endocrine therapy (NET) for the treatment of women with estrogen-receptor (ER) positive, HER-2 negative breast cancer. Rates of pCR are known to be low in this population, but there is inconsistent data regarding downstaging and long-term outcomes in a non-trial setting with NET vs NACT. Methods: A prospective institutional databaseof breast cancer patients treated with neoadjuvant therapy at the British Columbia Cancer Agency from 2012-2016 was analyzed to identify all medically fit patients with ER positive, HER2 negative breast cancer. Patients were then divided into two groups: those who received NET or NACT. Baseline characteristics were compared between groups. A matched analysis (age, stage and grade) was then performed to compare rates of downstaging, pCR and scores from a validated neoadjuvant therapy outcomes calculator (CPS+EG). Results: A total of 154 patients met eligibility criteria for this study. One hundred and six patients (69%) received NACT and 48 (31%) received NET. Women offered NACT were significantly younger (51 vs 64y, p < 0.001) than those offered endocrine therapy and presented with a higher clinical stage (LR 27.93, p = 0.002). According to multiple linear regression for downstaging, clinical stage followed by NACT were the most important predictors of downstaging. When matched for age, stage and grade, downstaging was significantly higher with NACT (31/48, 65%) as compared to NET (12/48, 25%), p < 0.001. Of these, 12.5% achieved pCR with NACT as compared to 2.1% with NET, LR 4.243, p = 0.039. No significant differences in CPS+EG scores were identified when comparing NACT to NET. Conclusions: Significantly higher rates of downstaging were achieved with NACT as compared to NET when patients were matched for age, stage and grade. Rates of pCR remain low for ER-positive breast cancer patients. Although not validated with the use of NET, CPS+EG scores predicting long-term outcomes were not significantly different with NET compared to NACT.

Stat5 expression predicts response to endocrine therapy and improves survival in estrogen receptor-positive breast cancer

2006 ◽  
Vol 13 (3) ◽  
pp. 885-893 ◽  
Author(s):  
H Yamashita ◽  
M Nishio ◽  
Y Ando ◽  
Z Zhang ◽  
M Hamaguchi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Epithelial Cell ◽  
Endocrine Therapy ◽  
Histological Grade ◽  
Metastatic Breast ◽  
Therapy Response ◽  
Breast Cancer Patients ◽  
Er Positive ◽  
Positive Breast Cancer

Constitutively activated signal transducers and activators of transcription (Stats), in particular Stat3 and Stat5, have been demonstrated to directly contribute to oncogenesis by stimulating cell proliferation and preventing apoptosis in various cancers. Stat3 is essential in mammary gland epithelial cell apoptosis and involution, whereas Stat5 is well established as a key factor in mammary epithelial cell growth and differentiation. Crosstalk between Stats and estrogen receptor (ER) has been demonstrated by several laboratories and we have focused on the role of Stat5 in ER-positive breast cancer. Using immunohistochemical techniques, we examined the expression of Stat3 and Stat5 in 517 human breast cancer tissues and analyzed their significance for prognosis and prediction of response to endocrine therapy. Stat5 expression was significantly correlated with histological grade (P < 0.0001), ER (P = 0.02), and progesterone receptor (P = 0.026) expression. There was no difference between Stat3 expression and clinicopathological factors. In 346 patients with ER-positive breast cancer, patients with Stat5 positive tumors had significantly increased overall survival (P = 0.0009) in multivariate analysis. There were 70 patients who received endocrine therapy as first-line treatment for metastatic breast cancer at relapse. The patients whose primary breast tumors were Stat5 positive, had significantly better response to endocrine therapy (P = 0.04), and longer survival after relapse (P = 0.0003), than those whose tumors were Stat5 negative. The present study demonstrates for the first time that Stat5 is a predictive factor for endocrine therapy response and a strong prognostic molecular marker in ER-positive breast cancer. Our data suggest that the expression of Stat5 is helpful in selecting patients who may benefit from endocrine therapy.

Effect of Molecular Disease Subsets on Disease-Free Survival in Randomized Adjuvant Chemotherapy Trials for Estrogen Receptor–Positive Breast Cancer

2008 ◽  
Vol 26 (28) ◽  
pp. 4679-4683 ◽  
Author(s):  
Lajos Pusztai ◽  
Kristine Broglio ◽  
Fabrice Andre ◽  
W. Fraser Symmans ◽  
Kenneth R. Hess ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Adjuvant Chemotherapy ◽  
Endocrine Therapy ◽  
Disease Free Survival ◽  
Molecular Diagnostic ◽  
Free Survival ◽  
Er Positive ◽  
Disease Free ◽  
Positive Breast Cancer

Purpose The majority of estrogen receptor (ER)–positive cancers are sensitive to endocrine therapy and may not derive much further benefit from chemotherapy, but a subset are potentially chemotherapy sensitive. Molecular diagnostic tests allow the identification of these various subsets with some accuracy. The goal of the current analysis was to examine how the proportion of cases in the various risk (recurrence score [RS]) categories of a commercially available multigene assay influences the power of randomized trials to show benefit from adjuvant chemotherapy. Methods We modeled 10-year disease-free survival (DFS) for hypothetical, two-arm clinical trials that randomly assigned patients with ER-positive breast cancer to endocrine therapy alone or endocrine therapy plus chemotherapy. We varied the proportion of patients in low, intermediate, and high RS categories and used DFS estimates for each risk group based on results from the Southwest Oncology Group 8814 study. Results The probability of observing significant improvement in DFS as a result of chemotherapy decreases as the proportion of patients in the low RS category increases. For example, if a trial is designed with 80% power and the actual proportion of low RS patients accrued to the study increases from 40% to 60%, the power drops to 63%. Conclusion Variable accrual of low RS patients into different randomized adjuvant chemotherapy trials may partly explain contradictory results in the literature. Studies can be underpowered to detect improvement with chemotherapy as a result of inclusion of too many patients with low RS. Future adjuvant studies for ER-positive breast cancer will need to consider stratifying patients by molecular subtype.

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