An Open-label, Randomized Study Comparing 3 Years Tamoxifen Versus 3 Years Letrozole as Continuation of Adjuvant Treatment of Postmenopausal Women with Estrogen Receptor (ER) Positive and/or Progesterone Receptor (PR) Positive Early Breast Cancer Who Already Completed 2 years Adjuvant Tamoxifen. A Large Thai Multicenter Study.

2012 ◽  
Author(s):  
Prasert Lertsaguansinchai
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Progesterone Receptor ◽  
Postmenopausal Women ◽  
Early Breast Cancer ◽  
Adjuvant Treatment ◽  
Multicenter Study ◽  
Randomized Study ◽  
Open Label ◽  
Er Positive

scholarly journals Economic evaluation of hormonal therapies for postmenopausal women with estrogen receptor–positive early breast cancer in Canada

2015 ◽  
Vol 22 (2) ◽  
pp. 84 ◽  
Author(s):  
S. Djalalov ◽  
J. Beca ◽  
E. Amir ◽  
M. Krahn ◽  
M.E. Trudeau ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Cost Effectiveness ◽  
Postmenopausal Women ◽  
Early Breast Cancer ◽  
Base Case ◽  
Parameter Uncertainties ◽  
System Perspective ◽  
Er Positive ◽  
The Cost

BackgroundAromatase inhibitor (ai) therapy has been subjected to numerous cost-effectiveness analyses. However, with most ais having reached the end of patent protection and with maturation of the clinical trials data, a re-analysis of ai cost-effectiveness and a consideration of ai use as part of sequential therapy is desirable. Our objective was to assess the cost-effectiveness of the 5-year upfront and sequential tamoxifen (tam) and ai hormonal strategies currently used for treating patients with estrogen receptor (er)–positive early breast cancer.Methods The cost-effectiveness analysis used a Markov model that took a Canadian health system perspective with a lifetime time horizon. The base case involved 65-year-old women with er-positive early breast cancer. Probabilistic sensitivity analyses were used to incorporate parameter uncertainties. An expected-value-of-perfect-information test was performed to identify future research directions. Outcomes were quality-adjusted life-years (qalys) and costs.Results The sequential tam–ai strategy was less costly than the other strategies, but less effective than upfront ai and more effective than upfront tam. Upfront ai was more effective and less costly than upfront tam because of less breast cancer recurrence and differences in adverse events. In an exploratory analysis that included a sequential ai–tam strategy, ai–tam dominated based on small numerical differences unlikely to be clinically significant; that strategy was thus not used in the base-case analysis.ConclusionsIn postmenopausal women with er-positive early breast cancer, strategies using ais appear to provide more benefit than strategies using tam alone. Among the ai-containing strategies, sequential strategies using tam and an ai appear to provide benefits similar to those provided by upfront ai, but at a lower cost.

Improved Overall Survival in Postmenopausal Women With Early Breast Cancer After Anastrozole Initiated After Treatment With Tamoxifen Compared With Continued Tamoxifen: The ARNO 95 Study

2007 ◽  
Vol 25 (19) ◽  
pp. 2664-2670 ◽  
Author(s):  
Manfred Kaufmann ◽  
Walter Jonat ◽  
Jörn Hilfrich ◽  
Holger Eidtmann ◽  
Günther Gademann ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Postmenopausal Women ◽  
Early Breast Cancer ◽  
Randomized Study ◽  
Disease Free Survival ◽  
Breast Cancer Surgery ◽  
Tamoxifen Treatment ◽  
Open Label ◽  
Serious Adverse Events

Purpose In postmenopausal women with estrogen receptor–positive early breast cancer, surgery is usually followed by a 5-year course of tamoxifen. This report presents results of a prospective, open-label, randomized study, designed to evaluate the benefits of switching to anastrozole after 2 years of tamoxifen treatment, compared with continuing on tamoxifen for 5 years. Patients and Methods After receiving tamoxifen treatment for 2 years, eligible patients (n = 979) were randomly assigned to switch to anastrozole (1 mg/d) or continue tamoxifen (20 or 30 mg/d) for an additional 3 years. Patients were monitored every 6 months during years 1 to 3 and annually thereafter. The primary efficacy variable was disease-free survival, including local or distant recurrence, new contralateral breast cancer, or death. Secondary variables were overall survival and assessment of safety. Results Switching to anastrozole resulted in a significant reduction in the risk of disease recurrence (hazard ratio [HR], 0.66; 95% CI, 0.44 to 1.00; P = .049), and improved overall survival (HR, 0.53; 95% CI, 0.28 to 0.99; P = .045) compared with continuing on tamoxifen. Fewer patients who switched to anastrozole reported serious adverse events (22.7% v 30.8%) compared with those who continued on tamoxifen, mainly due to more patients in the tamoxifen group with endometrial events. The overall safety profile for anastrozole was consistent with previous reports and no new safety issues were identified. Conclusion Postmenopausal women who have taken tamoxifen for 2 years as adjuvant therapy are less likely to experience a recurrence of breast cancer and have improved overall survival if they switch to anastrozole compared with continuing to receive tamoxifen.

Phase II Randomized Study of Neoadjuvant Everolimus Plus Letrozole Compared With Placebo Plus Letrozole in Patients With Estrogen Receptor–Positive Breast Cancer

2009 ◽  
Vol 27 (16) ◽  
pp. 2630-2637 ◽  
Author(s):  
José Baselga ◽  
Vladimir Semiglazov ◽  
Peter van Dam ◽  
Alexey Manikhas ◽  
Meritxell Bellet ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Progesterone Receptor ◽  
Cyclin D1 ◽  
Randomized Study ◽  
Mammalian Target Of Rapamycin ◽  
Neoadjuvant Treatment ◽  
Natural Logarithm ◽  
Er Positive ◽  
Positive Breast Cancer

PurposeCross-talk between the estrogen receptor (ER) and the phosphoinositide-3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathways is a mechanism of resistance to endocrine therapy, and blockade of both pathways enhances antitumor activity in preclinical models. This study explored whether sensitivity to letrozole was enhanced with the oral mTOR inhibitor, everolimus (RAD001).Patients and MethodsTwo hundred seventy postmenopausal women with operable ER-positive breast cancer were randomly assigned to receive 4 months of neoadjuvant treatment with letrozole (2.5 mg/day) and either everolimus (10 mg/day) or placebo. The primary end point was clinical response by palpation. Mandatory biopsies were obtained at baseline and after 2 weeks of treatment (ie, day 15). Samples were assessed for PI3K mutation status (PIK3CA) and for pharmacodynamic changes of Ki67, phospho-S6, cyclin D1, and progesterone receptor (PgR) by immunohistochemistry.ResultsResponse rate by clinical palpation in the everolimus arm was higher than that with letrozole alone (ie, placebo; 68.1% v 59.1%), which was statistically significant at the preplanned, one-sided, α = 0.1 level (P = .062). Marked reductions in progesterone receptor and cyclin D1 expression occurred in both treatment arms, and dramatic downregulation of phospho-S6 occurred only in the everolimus arm. An antiproliferative response, as defined by a reduction in Ki67 expression to natural logarithm of percentage positive Ki67 of less than 1 at day 15, occurred in 52 (57%) of 91 patients in the everolimus arm and in 25 (30%) of 82 patients in the placebo arm (P < .01). The safety profile was consistent with historical results of everolimus monotherapy; grades 3 to 4 adverse events occurred in 22.6% of patients who received everolimus and in 3.8% of patients who received placebo.ConclusionEverolimus significantly increased letrozole efficacy in neoadjuvant therapy of patients with ER-positive breast cancer.

scholarly journals Relationship Between Plasma Estradiol Levels and Estrogen-Responsive Gene Expression in Estrogen Receptor–Positive Breast Cancer in Postmenopausal Women

2010 ◽  
Vol 28 (7) ◽  
pp. 1161-1167 ◽  
Author(s):  
Anita K. Dunbier ◽  
Helen Anderson ◽  
Zara Ghazoui ◽  
Elizabeth J. Folkerd ◽  
Roger A'Hern ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Estrogen Receptor ◽  
Postmenopausal Women ◽  
Multivariable Analysis ◽  
Independent Set ◽  
Breast Cancers ◽  
Plasma Estradiol ◽  
Er Positive ◽  
Positive Breast Cancer

Purpose To determine whether plasma estradiol (E2) levels are related to gene expression in estrogen receptor (ER)–positive breast cancers in postmenopausal women. Materials and Methods Genome-wide RNA profiles were obtained from pretreatment core-cut tumor biopsies from 104 postmenopausal patients with primary ER-positive breast cancer treated with neoadjuvant anastrozole. Pretreatment plasma E2 levels were determined by highly sensitive radioimmunoassay. Genes were identified for which expression was correlated with pretreatment plasma E2 levels. Validation was performed in an independent set of 73 ER-positive breast cancers. Results The expression of many known estrogen-responsive genes and gene sets was highly significantly associated with plasma E2 levels (eg, TFF1/pS2, GREB1, PDZK1 and PGR; P < .005). Plasma E2 explained 27% of the average expression of these four average estrogen-responsive genes (ie, AvERG; r = 0.51; P < .0001), and a standardized mean of plasma E2 levels and ER transcript levels explained 37% (r, 0.61). These observations were validated in an independent set of 73 ER-positive tumors. Exploratory analysis suggested that addition of the nuclear coregulators in a multivariable analysis with ER and E2 levels might additionally improve the relationship with the AvERG. Plasma E2 and the standardized mean of E2 and ER were both significantly correlated with 2-week Ki67, a surrogate marker of clinical outcome (r = −0.179; P = .05; and r = −0.389; P = .0005, respectively). Conclusion Plasma E2 levels are significantly associated with gene expression of ER-positive breast cancers and should be considered in future genomic studies of ER-positive breast cancer. The AvERG is a new experimental tool for the study of putative estrogenic stimuli of breast cancer.

scholarly journals Ki-67 Expression is a Significant Prognostic Factor Only When Progesterone Receptor Expression is Low in Estrogen Receptor-Positive and HER2-Negative Early Breast Cancer

2019 ◽  
Vol 2019 ◽  
pp. 1-8
Author(s):  
Young-Joon Kang ◽  
Han-Byoel Lee ◽  
Yun Gyoung Kim ◽  
JaiHong Han ◽  
Yumi Kim ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Prognostic Factor ◽  
Progesterone Receptor ◽  
Cancer Patients ◽  
Early Breast Cancer ◽  
Receptor Expression ◽  
Breast Cancer Patients ◽  
Ki 67 ◽  
End Point

Objective. While the value of Ki-67 has been recognized in breast cancer, controversy also exists. The goal of this study is to show the prognostic value of Ki-67 according to progesterone receptor (PgR) expression in patients who have estrogen receptor- (ER-) positive, human epidermal growth factor receptor 2- (HER2-) negative early breast cancer. Methods. The records of nonmetastatic invasive breast cancer patients who underwent surgery at a single institution between 2009 and 2012 were reviewed. Primary end point was recurrence-free survival (RFS), and secondary end point was overall survival (OS). Ki-67 and PgR were assessed with immunohistochemistry for the tumor after surgery. Results. A total of 1848 patients were enrolled in this study. 223 (12%) patients had high (≥10%) Ki-67, and 1625 (88%) had low Ki-67 expression. Significantly worse RFS and OS were observed in the high vs. low Ki-67 expression only when the PgR was low (<20%) (p<0.001 and 0.005, respectively, for RFS and OS). There was no significant difference in RFS and OS according to Ki-67 when the PgR was high (p=0.120 and 0.076). RFS of four groups according to high/low Ki-67 and PgR expression was compared. The low PgR and high Ki-67 expression group showed worst outcome among them (p<0.001). In a multivariate analysis, high Ki-67 was an independent prognostic factor when the PgR was low (HR 3.05; 95% CI 1.50–6.19; p=0.002). Conclusions. Ki-67 had a value as a prognostic factor only under low PgR expression level in early breast cancer. PgR should be considered in evaluating the prognosis of breast cancer patients using Ki-67.

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