Dataset Information

Clinical outcomes comparison of 10 years versus 5 years of adjuvant endocrine therapy in patients with early breast cancer.

ABSTRACT:

Background

Adjuvant endocrine therapy undoubtedly prolongs the time to recurrence for patients with hormone-positive early breast cancer. Extended endocrine therapy to 10 years or longer has been expected to bring a greater clinical advantage. However, the related research conclusions are controversial.

Methods

Tamoxifen (TAM), Aromatase Inhibitor (AI), Exemestane, letrozole (LET) and anastrozole were used as key words in the literature search. After the patients completed 5 years of adjuvant endocrine treatment, they were allocated to continue endocrine treatment for 5 years or receive placebo/observation for 5 years. Disease-free survival (DFS) and overall survival (OS) were the end points. Systematic assessment was performed using Stata 12.0.

Results

Twelve trials including 30,848 cases were involved. The overall analysis demonstrated that extended endocrine therapy to 10 years significantly prolonged DFS compared with 5 years of endocrine therapy [hazard ratio (HR)?=?0.84, 95% CI: 0.73-0.97]. Subgroup analysis showed that DFS was significant prolonged with TAM 5y - AI 5y treatment versus TAM 5y treatment and with (AI and/or TAM) 5y - LET 5y treatment versus (AI and/or TAM) 5y treatment [(HR?=?0.61, 95% CI: 0.50-0.76) and (HR?=?0.81, 95% CI: 0.71-0.93), respectively]. However, no significant difference was found in the DFS with TAM 5y - TAM 5y treatment versus TAM 5y treatment (HR?=?0.97, 95% CI: 0.81-1.17). Overall and subgroup analysis did not demonstrate an OS benefit of therapy extended to 10 years. A DFS benefit of extended endocrine therapy to 10 years was verified in the lymph node-positive subgroup, postmenopausal subgroup and ER+ and/or PR+ subgroup (HR?=?058, 95% CI: 0.45-0.75; HR?=?0.70, 95% CI: 0.58-0.80; HR?=?0.80, 95% CI: 0.67-0.96).

Conclusions

An extended 10 years of endocrine treatment yields a DFS benefit for patients with early breast cancer; (AI and/or TAM) 5y - AI 5y treatment is the optimal choice. ER+ and/or PR+, postmenopausal and lymph node-positive patients are the most suitable groups.

SUBMITTER: Li L

PROVIDER: S-EPMC6186070 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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Publications

Clinical outcomes comparison of 10 years versus 5 years of adjuvant endocrine therapy in patients with early breast cancer.

Li Li L Chang Bingmei B Jiang Xiaoyue X Fan Xueke X Li Yingrui Y Li Teng T Wu Shanshan S Zhang Jun J Zhang Jun J Kariminia Seyed S Li Qin Q

BMC cancer 20181012 1

<h4>Background</h4>Adjuvant endocrine therapy undoubtedly prolongs the time to recurrence for patients with hormone-positive early breast cancer. Extended endocrine therapy to 10 years or longer has been expected to bring a greater clinical advantage. However, the related research conclusions are controversial.<h4>Methods</h4>Tamoxifen (TAM), Aromatase Inhibitor (AI), Exemestane, letrozole (LET) and anastrozole were used as key words in the literature search. After the patients completed 5 years ...[more]

PMID: 30314452

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Project description:PurposeThere remain a lack of biomarkers for endocrine therapy resistance in patients with breast cancer (BC), which is proving to be a great challenge. In vitro experiments have shown that downregulation of PTEN expression leads to resistance to tamoxifen (TAM) in BC cells. We aimed to investigate the predictive role of tumor PTEN promoter methylation and PTEN expression in long-term survival after TAM adjuvant therapy in patients with early-stage BC.MethodsFrom 2001 to 2013, 105 patients with stage I-III BC who were treated with standardized adjuvant TAM for 5 years or until relapse in West China Hospital (WCH) were enrolled in this study. PTEN expression and DNA methylation of three specified sequences from the PTEN promoter in primary tumors were measured using immunohistochemistry and pyrosequencing. A cohort of 159 hormone receptor-positive patients receiving TAM treatment from The Cancer Genome Atlas (TCGA) database was used for verification.ResultsMedian follow-up time for the WCH cohort was 141.7 months. The low, moderate, and high PTEN expression groups had differing 10-year disease-free survival (DFS) (42.3%, 55%, 81%, respectively, P = 0.027) and overall survival (OS) rates (65%, 84.2%, 90.5%, respectively, P = 0.027). Higher methylation levels of the second sequence (- 819 to - 787 bp), rather than the first (- 1143 to - 1107 bp) or third sequence (- 663 to - 593 bp), independently increased the risk of disease recurrence (hazard ratio = 2.60) and death (hazard ratio = 3.79) in the WCH cohort, according to multivariate Cox regression analysis. Importantly, out of the five CpG islands located within this sequence, only high methylation of the - 796 CpG island predicted shorter DFS and OS. In TCGA validation cohort, there was also a trend of higher methylation of the - 796 CpG island correlating with shorter disease-free intervals, with borderline significance (P = 0.057).ConclusionLow PTEN expression and high methylation of its promoter (sequence - 819 to - 787 bp) in tissue predict poor DFS and OS in hormone receptor-positive early BC patients who received adjuvant TAM.

Project description:BackgroundTreatment with an aromatase inhibitor for 5 years as up-front monotherapy or after tamoxifen therapy is the treatment of choice for hormone-receptor-positive early breast cancer in postmenopausal women. Extending treatment with an aromatase inhibitor to 10 years may further reduce the risk of breast-cancer recurrence.MethodsWe conducted a double-blind, placebo-controlled trial to assess the effect of the extended use of letrozole for an additional 5 years. Our primary end point was disease-free survival.ResultsWe enrolled 1918 women. After a median follow-up of 6.3 years, there were 165 events involving disease recurrence or the occurrence of contralateral breast cancer (67 with letrozole and 98 with placebo) and 200 deaths (100 in each group). The 5-year disease-free survival rate was 95% (95% confidence interval [CI], 93 to 96) with letrozole and 91% (95% CI; 89 to 93) with placebo (hazard ratio for disease recurrence or the occurrence of contralateral breast cancer, 0.66; P=0.01 by a two-sided log-rank test stratified according to nodal status, prior adjuvant chemotherapy, the interval from the last dose of aromatase-inhibitor therapy, and the duration of treatment with tamoxifen). The rate of 5-year overall survival was 93% (95% CI, 92 to 95) with letrozole and 94% (95% CI, 92 to 95) with placebo (hazard ratio, 0.97; P=0.83). The annual incidence rate of contralateral breast cancer in the letrozole group was 0.21% (95% CI, 0.10 to 0.32), and the rate in the placebo group was 0.49% (95% CI, 0.32 to 0.67) (hazard ratio, 0.42; P=0.007). Bone-related toxic effects occurred more frequently among patients receiving letrozole than among those receiving placebo, including a higher incidence of bone pain, bone fractures, and new-onset osteoporosis. No significant differences between letrozole and placebo were observed in scores on most subscales measuring quality of life.ConclusionsThe extension of treatment with an adjuvant aromatase inhibitor to 10 years resulted in significantly higher rates of disease-free survival and a lower incidence of contralateral breast cancer than those with placebo, but the rate of overall survival was not higher with the aromatase inhibitor than with placebo. (Funded by the Canadian Cancer Society and others; ClinicalTrials.gov numbers, NCT00003140 and NCT00754845.).

Project description:BACKGROUND:In the Suppression of Ovarian Function Trial (SOFT) and the Tamoxifen and Exemestane Trial (TEXT), the 5-year rates of recurrence of breast cancer were significantly lower among premenopausal women who received the aromatase inhibitor exemestane plus ovarian suppression than among those who received tamoxifen plus ovarian suppression. The addition of ovarian suppression to tamoxifen did not result in significantly lower recurrence rates than those with tamoxifen alone. Here, we report the updated results from the two trials. METHODS:Premenopausal women were randomly assigned to receive 5 years of tamoxifen, tamoxifen plus ovarian suppression, or exemestane plus ovarian suppression in SOFT and to receive tamoxifen plus ovarian suppression or exemestane plus ovarian suppression in TEXT. Randomization was stratified according to the receipt of chemotherapy. RESULTS:In SOFT, the 8-year disease-free survival rate was 78.9% with tamoxifen alone, 83.2% with tamoxifen plus ovarian suppression, and 85.9% with exemestane plus ovarian suppression (P=0.009 for tamoxifen alone vs. tamoxifen plus ovarian suppression). The 8-year rate of overall survival was 91.5% with tamoxifen alone, 93.3% with tamoxifen plus ovarian suppression, and 92.1% with exemestane plus ovarian suppression (P=0.01 for tamoxifen alone vs. tamoxifen plus ovarian suppression); among the women who remained premenopausal after chemotherapy, the rates were 85.1%, 89.4%, and 87.2%, respectively. Among the women with cancers that were negative for HER2 who received chemotherapy, the 8-year rate of distant recurrence with exemestane plus ovarian suppression was lower than the rate with tamoxifen plus ovarian suppression (by 7.0 percentage points in SOFT and by 5.0 percentage points in TEXT). Grade 3 or higher adverse events were reported in 24.6% of the tamoxifen-alone group, 31.0% of the tamoxifen-ovarian suppression group, and 32.3% of the exemestane-ovarian suppression group. CONCLUSIONS:Among premenopausal women with breast cancer, the addition of ovarian suppression to tamoxifen resulted in significantly higher 8-year rates of both disease-free and overall survival than tamoxifen alone. The use of exemestane plus ovarian suppression resulted in even higher rates of freedom from recurrence. The frequency of adverse events was higher in the two groups that received ovarian suppression than in the tamoxifen-alone group. (Funded by Pfizer and others; SOFT and TEXT ClinicalTrials.gov numbers, NCT00066690 and NCT00066703 , respectively.).

Project description:Background and objectiveHormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) breast cancer (BC) is the most prevalent subtype of all BCs. The primary treatment modality is endocrine therapy (ET). Traditional adjuvant ET for early-stage breast cancer (EBC) has undergone extensive exploration and is relatively well-established. However, patients at high risk of recurrence may still experience early relapse, necessitating consideration of intensified adjuvant ET to reduce recurrence risk. The objective of this narrative review is to examine various strategies for intensifying adjuvant ET in EBC, thoroughly analyze key clinical studies, and summarize the most effective treatment approaches supported by current evidence-based medicine. Furthermore, it addresses unresolved challenges that necessitate further refinement and investigation.MethodsAs of March 2024, a comprehensive literature search, compilation, and analysis were conducted across PubMed, Baidu Scholar, ClinicalTrials.gov, and relevant academic conferences.Key content and findingsThere are numerous methods to intensify adjuvant ET: (I) combining ovarian function suppression (OFS) to reduce estrogen levels in the body and induce a state of artificial menopause to enhance the efficacy of ET; (II) individual extension of the duration of ET based on patients' varying risks of recurrence, with high-risk patients covering two peak recurrence periods; (III) the addition of cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) can significantly extend invasive disease-free survival and reduce the risk of recurrence, serving as the main intensive treatment for high-risk patients; (IV) combination with bone-modifying drugs (BMD) can significantly reduce rates of bone metastasis and slightly enhance prognosis but is not commonly used in adjuvant settings; (V) combined with poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitors, current studies only show a trend towards benefit in HR+ patients with germline BRCA1/2 mutations; more data are still needed to support its clinical benefit. This narrative review examines various strategies for intensifying adjuvant ET in EBC, critically evaluates key clinical studies, and summarizes the most effective treatment approaches supported by current evidence-based medicine. Furthermore, it addresses unresolved challenges that necessitate further refinement and investigation.ConclusionsIn the context where traditional adjuvant ET is relatively well-established, the emergence of novel ET has notably addressed issues of endocrine resistance more effectively. Various intensified adjuvant ET has shown potential in further reducing recurrence risk among high-risk patients. However, additional research and time are essential to determine the optimal approaches for intensified adjuvant ET.

Dataset Information

Clinical outcomes comparison of 10 years versus 5 years of adjuvant endocrine therapy in patients with early breast cancer.

Background

Methods

Results

Conclusions

Publications

Clinical outcomes comparison of 10 years versus 5 years of adjuvant endocrine therapy in patients with early breast cancer.

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