Extended Adjuvant Endocrine Therapy for Postmenopausal Women: Treating Many to Benefit a Few.
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ABSTRACT:
SUBMITTER: Pohlmann PR
PROVIDER: S-EPMC6279308 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundThe DATA study evaluated the use of two different durations of anastrozole in patients with hormone receptor-positive breast cancer who were disease-free after 2-3 years of tamoxifen. We hereby present the follow-up analysis, which was performed after all patients reached a minimum follow-up of 10 years beyond treatment divergence.MethodsThe open-label, randomised, phase 3 DATA study was performed in 79 hospitals in the Netherlands (ClinicalTrials.gov, number NCT00301457). Postmenopausal women with hormone receptor-positive breast cancer who were disease-free after 2-3 years of adjuvant tamoxifen treatment were assigned to either 3 or 6 years of anastrozole (1 mg orally once a day). Randomisation (1:1) was stratified by hormone receptor status, nodal status, HER2 status, and prior tamoxifen duration. The primary outcome was adapted disease-free survival, defined as disease-free survival from 3 years after randomisation onwards. Adapted overall survival was assessed as a secondary outcome. Analyses were performed according to the intention-to-treat design.FindingsBetween June 28, 2006, and August 10, 2009, 1912 patients were randomly assigned to 3 years (n = 955) or 6 years (n = 957) of anastrozole. Of these, 1660 patients were eligible and disease-free at 3 years after randomisation. The 10-year adapted disease-free survival was 69.2% (95% CI 55.8-72.3) in the 6-year group (n = 827) and 66.0% (95% CI 62.5-69.2) in the 3-year group (n = 833) (hazard ratio (HR) 0.86; 95% CI 0.72-1.01; p = 0.073). The 10-year adapted overall survival was 80.9% (95% CI 77.9-83.5) in the 6-year group and 79.2% (95% CI 76.2-81.9) in the 3-year group (HR 0.93; 95% CI 0.75-1.16; p = 0.53).InterpretationExtended aromatase inhibition beyond 5 years of sequential endocrine therapy did not improve the adapted disease-free survival and adapted overall survival of postmenopausal women with hormone receptor-positive breast cancer.FundingAstraZeneca.
| S-EPMC10041456 | biostudies-literature
Project description:Current adjuvant treatment modalities for breast cancer that express the estrogen receptor or progesterone receptor include adjuvant anti-estrogen therapies, and tamoxifen and aromatase inhibitors. Bone, including the jaw, is an endocrine-sensitive organ, as are other oral structures. This review examines the potential links between adjuvant anti-estrogen treatments in postmenopausal women with hormone receptor positive breast cancer and oral health. A search of PubMed, EMBASE, CENTRAL, and the Web of Knowledge was conducted using combinations of key terms "breast," "cancer," "neoplasm," "Tamoxifen," "Aromatase Inhibitor," "chemotherapy," "hormone therapy," "alveolar bone loss," "postmenopausal bone loss," "estrogen," "SERM," "hormone replacement therapy," and "quality of life." We selected articles published in peer-reviewed journals in the English. The authors found no studies reporting on periodontal diseases, alveolar bone loss, oral health, or oral health-related quality of life in association with anti-estrogen breast cancer treatments in postmenopausal women. Periodontal diseases, alveolar bone density, tooth loss, and conditions of the soft tissues of the mouth have all been associated with menopausal status supporting the hypothesis that the soft tissues and bone of the oral cavity could be negatively affected by anti-estrogen therapy. As a conclusion, the impact of adjuvant endocrine breast cancer therapy on the oral health of postmenopausal women is undefined. The structures of the oral cavity are influenced by estrogen; therefore, anti-estrogen therapies may carry the risk of oral toxicities. Oral health care for breast cancer patients is an important but understudied aspect of cancer survivorship.
| S-EPMC3529782 | biostudies-literature
Project description:Despite meaningful, incremental improvements in detection, local treatment and adjuvant systemic treatments for breast cancer, there remains a significant risk of late relapse in hormone receptor (HR)-positive disease. 5 years of tamoxifen or an aromatase inhibitor for all patients with HR-positive early breast cancer is considered standard; however, there are now data to support an extended approach using up to 10 years of treatment. This review will provide some historical background on endocrine therapy and summarize the key clinical trials that demonstrate the small absolute benefit of extended adjuvant therapy. We provide suggested treatment algorithms for both premenopausal and postmenopausal patients and an overview of ongoing adjuvant trials.
| S-EPMC5527163 | biostudies-literature
Project description:Opinion statementIn the past decade, several endocrine treatment regimens have been developed for the adjuvant treatment of postmenopausal women with hormone receptor-positive early breast cancer, including tamoxifen, aromatase inhibitors (AI), or a combination of these. The standard duration of adjuvant endocrine treatment has been 5 years for a long time. Nevertheless, the high number of recurrences occurring after 5 years suggested that extended endocrine therapy could further improve outcome, which led to the start of several randomized clinical trials investigating the effects of extended use of endocrine therapy. The extended duration of tamoxifen has been shown to improve disease-free survival and overall survival in the ATLAS and aTTom trials. However, in postmenopausal women, AIs have been shown to be more effective when compared with tamoxifen. Based hereon, it is recommended that adjuvant endocrine therapy in postmenopausal women with early breast cancer should include an AI. Recently, the DATA, IDEAL, and NSABP B42 trials showed that extended adjuvant endocrine therapy with AIs beyond 5 years in postmenopausal women with early breast cancer did reduce the occurrence of secondary breast tumors, but had no or only a small impact on distant metastasis free survival. Furthermore, toxicity of adjuvant AIs led to gradually decreasing compliance rates and long-term toxicities to non-breast cancer-related deaths. Therefore, we suggest considering extended adjuvant treatment only in women with high-risk early breast cancer who tolerate treatment well.
| S-EPMC5937869 | biostudies-literature
Project description:Simple Summary Five years of therapy remains the standard for adjuvant endocrine therapy in early breast cancer. However, the recurrence risk remains elevated beyond this time period. Estimating the risk of recurrence as well as the efficacy of therapy is important in the selection of patients who will benefit from the extension of adjuvant endocrine therapy. The aim of this review is to summarize the major studies investigating the optimal duration of adjuvant endocrine therapy as well as to elaborate the possible individual indications for the extension of this therapy. Abstract Seventy percent of all breast cancer subtypes are hormone receptor-positive. Adjuvant endocrine therapy in these patients plays a key role. Despite the traditional duration of a 5-year intake, the risk of relapse remains elevated in a substantial proportion of patients. Several trials report that the risk of late recurrence is reduced by the extension of adjuvant endocrine therapy beyond 5 years. However, the optimal duration of endocrine therapy is still a matter of debate. The newer data only show a marginal benefit resulting from extension beyond 7 to 10 years. Furthermore, extension may be associated with more side effects. Thus, the adequate selection of patients qualifying for an extended adjuvant therapy is of importance. Tools/genomic tests, which include the characteristics of the patient and the tumor, may help to better identify patients with a risk of a late relapse. Taken together, the magnitude of benefit for extended adjuvant endocrine therapy is based on the precise estimation of the risk of relapse after 5 years. This must be balanced against the long-term side effects of endocrine treatment and the competing risks. For patients with an intermediate risk, 7 years appears to be the optimal duration, and in those with high-risk features, endocrine therapy up to 10 years may be considered.
| S-EPMC10453164 | biostudies-literature
Project description:To compare the efficacy of chemoendocrine treatment with that of endocrine treatment (ET) alone for postmenopausal women with highly endocrine responsive breast cancer. In the International Breast Cancer Study Group (IBCSG) Trials VII and 12-93, postmenopausal women with node-positive, estrogen receptor (ER)-positive or ER-negative, operable breast cancer were randomized to receive either chemotherapy or endocrine therapy or combined chemoendocrine treatment. Results were analyzed overall in the cohort of 893 patients with endocrine-responsive disease, and according to prospectively defined categories of ER, age and nodal status. STEPP analyses assessed chemotherapy effect. The median follow-up was 13 years. Adding chemotherapy reduced the relative risk of a disease-free survival event by 19% (P = 0.02) compared with ET alone. STEPP analyses showed little effect of chemotherapy for tumors with high levels of ER expression (P = 0.07), or for the cohort with one positive node (P = 0.03). Chemotherapy significantly improves disease-free survival for postmenopausal women with endocrine-responsive breast cancer, but the magnitude of the effect is substantially attenuated if ER levels are high.
| S-EPMC3589110 | biostudies-literature
Project description:Extended adjuvant endocrine therapy (eET) improves outcomes in breast cancer survivors. Most studies however have been limited to postmenopausal women, and optimal eET for young survivors is uncertain. We report eET use among participants in the Young Women's Breast Cancer Study (YWS), a multicenter prospective cohort of women age ≤40 newly diagnosed with breast cancer enrolled between 2006-2016. Women with stage I-III hormone receptor-positive breast cancer, ≥6 years from diagnosis without recurrence were considered eET candidates. Use of eET was elicited from annual surveys sent years 6-8 after diagnosis, censoring for recurrence/death. 663 women were identified as eET candidates with 73.9% (490/663) having surveys eligible for analysis. Among eligible participants, mean age was 35.5 (±3.9), 85.9% were non-Hispanic white, and 59.6% reported eET use. Tamoxifen monotherapy was the most reported eET (77.4%), followed by aromatase inhibitor (AI) monotherapy (21.9%), AI-ovarian function suppression (AI-OFS) (6.8%) and tamoxifen-OFS (3.1%). In multivariable analysis, increasing age (per year odds ratio [OR]: 1.10, 95% confidence interval [CI]: 1.04-1.16), stage (II v. I: OR: 2.86, 95% CI: 1.81-4.51; III v. I: OR: 3.73, 95%CI: 1.87-7.44) and receipt of chemotherapy (OR: 3.66, 95% CI: 2.16-6.21) were significantly associated with eET use. Many young breast cancer survivors receive eET despite limited data regarding utility in this population. While some factors associated with eET use reflect appropriate risk-based care, potential sociodemographic disparities in uptake warrants further investigation in more diverse populations.
| S-EPMC10130172 | biostudies-literature
Project description:PurposeEndoPredict (EPclin) is a prognostic test validated to inform decisions on adjuvant chemotherapy to endocrine therapy alone for patients with oestrogen receptor-positive, HER2-negative breast cancer. Here, we determine the performance of EPclin for estimating 10-year distant recurrence-free interval (DRFI) rates for those who received adjuvant endocrine therapy (ET) alone compared to those with chemotherapy plus endocrine therapy (ET + C).MethodsA total of 3746 women were included in this joint analysis. 2630 patients received 5 years of ET alone (ABCSG-6/8, TransATAC) and 1116 patients received ET + C (GEICAM 2003-02/9906). The primary objective was to evaluate the ability of EPclin to provide an estimate of the 10-year DR rate as a continuous function of EPclin separately for ET alone and ET + C. Cox proportional hazard models were used for these analyses.ResultsEPclin was highly prognostic for DR in women who received ET alone (HR 2.79 (2.49-3.13), P < 0.0001) as well as in those who received ET + C (HR 2.27 (1.99-2.59), P < 0.0001). Women who received ET + C had significantly smaller increases in 10-year DR rates with the increasing EPclin score than those receiving ET alone (EPclin = 5; 12% ET + C vs. 20% ET alone). We observed a significant positive interaction between EPclin and treatment groups (P-interaction = 0.022).ConclusionsIn this comparative non-randomised analysis, the rate of increase in DR with EPclin score was significantly reduced in women who received ET + C versus ET alone. Our indirect comparisons suggest that a high EPclin score can predict chemotherapy benefit in women with ER-positive, HER2-negative disease.
| S-EPMC6555778 | biostudies-literature
Project description:Mitochondrial disease is maternally inherited and refractory to treatment, but assisted reproduction methods can result in unaffected pregnancies. The authors provide estimates of the number of affected pregnancies per year in the United Kingdom and the United States.
| S-EPMC4481295 | biostudies-literature
Project description:BACKGROUND:Extending the duration of adjuvant endocrine therapy reduces the risk of recurrence in a subset of women with early-stage hormone receptor-positive (HR+) breast cancer. Validated predictive biomarkers of endocrine response could significantly improve patient selection for extended therapy. Breast cancer index (BCI) [HOXB13/IL17BR ratio (H/I)] was evaluated for its ability to predict benefit from extended endocrine therapy in patients previously randomized in the Adjuvant Tamoxifen-To Offer More? (aTTom) trial. PATIENTS AND METHODS:Trans-aTTom is a multi-institutional, prospective-retrospective study in patients with available formalin-fixed paraffin-embedded primary tumor blocks. BCI testing and central determination of estrogen receptor (ER) and progesterone receptor (PR) status by immunohistochemistry were carried out blinded to clinical outcome. Survival endpoints were evaluated using Kaplan-Meier analysis and Cox regression with recurrence-free interval (RFI) as the primary endpoint. Interaction between extended endocrine therapy and BCI (H/I) was assessed using the likelihood ratio test. RESULTS:Of 583 HR+, N+ patients analyzed, 49% classified as BCI (H/I)-High derived a significant benefit from 10 versus 5?years of tamoxifen treatment [hazard ratio (HR): 0.35; 95% confidence interval (CI) 0.15-0.86; 10.2% absolute risk reduction based on RFI, P?=?0.027]. BCI (H/I)-low patients showed no significant benefit from extended endocrine therapy (HR: 1.07; 95% CI 0.69-1.65; -0.2% absolute risk reduction; P?=?0.768). Continuous BCI (H/I) levels predicted the magnitude of benefit from extended tamoxifen, whereas centralized ER and PR did not. Interaction between extended tamoxifen treatment and BCI (H/I) was statistically significant (P?=?0.012), adjusting for clinicopathological factors. CONCLUSION:BCI by high H/I expression was predictive of endocrine response and identified a subset of HR+, N+ patients with significant benefit from 10 versus 5?years of tamoxifen therapy. These data provide further validation, consistent with previous MA.17 data, establishing level 1B evidence for BCI as a predictive biomarker of benefit from extended endocrine therapy. TRIAL REGISTRATION:ISRCTN17222211; NCT00003678.
| S-EPMC6927322 | biostudies-literature