Extended Adjuvant Endocrine Therapy in Hormone Receptor-Positive Early Breast Cancer.
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ABSTRACT:
SUBMITTER: Bracken-Clarke DB
PROVIDER: S-EPMC5527163 | biostudies-literature | 2017 Jul
REPOSITORIES: biostudies-literature
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Extended Adjuvant Endocrine Therapy in Hormone Receptor-Positive Early Breast Cancer.
Bracken-Clarke Dara B DB Lucas Mairi W MW Higgins Michaela J MJ
Breast care (Basel, Switzerland) 20170628 3
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 endocr ...[more]
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Project description:Importance:Although adjuvant endocrine therapy confers a survival benefit among females with hormone receptor (HR)-positive breast cancer, the effectiveness of this treatment among males with HR-positive breast cancer has not been rigorously investigated. Objective:To investigate trends, patterns of use, and effectiveness of adjuvant endocrine therapy among men with HR-positive breast cancer. Design, Setting, and Participants:This retrospective cohort study identified patients in the National Cancer Database with breast cancer who had received treatment from 2004 through 2014. Inclusion criteria for the primary study cohort were males at least 18 years old with nonmetastatic HR-positive invasive breast cancer who underwent surgery with or without adjuvant endocrine therapy. A cohort of female patients was also identified using the same inclusion criteria for comparative analyses by sex. Data analysis was conducted from October 1, 2017, to December 15, 2017. Exposures:Receipt of adjuvant endocrine therapy. Main Outcomes and Measures:Patterns of adjuvant endocrine therapy use were assessed using multivariable logistic regression analyses. Association between adjuvant endocrine therapy use and overall survival was assessed using propensity score-weighted multivariable Cox regression models. Results:The primary study cohort comprised 10?173 men with HR-positive breast cancer (mean [interquartile range] age, 66 [57-75] years). The comparative cohort comprised 961?676 women with HR-positive breast cancer (mean [interquartile range] age, 62 [52-72] years). The median follow-up for the male cohort was 49.6 months (range, 0.1-142.5 months). Men presented more frequently than women with HR-positive disease (94.0% vs 84.3%, P?<?.001). However, eligible men were less likely than women to receive adjuvant endocrine therapy (67.3% vs 79.0%; OR, 0.61; 95% CI, 0.58-0.63; P?<?.001). Treatment at academic facilities (odds ratio, 1.13; 95% CI, 1.02-1.25; P?=?.02) and receipt of adjuvant radiotherapy (odds ratio, 2.83; 95% CI, 2.55-3.15; P?<?.001) or chemotherapy (odds ratio, 1.20; 95% CI, 1.07-1.34; P?<?.001) were statistically significantly associated with adjuvant endocrine therapy use in men. A propensity score-weighted analysis indicated that relative to no use, adjuvant endocrine therapy use in men was associated with improved overall survival (hazard ratio, 0.70; 95% CI, 0.63-0.77; P?<?.001). Conclusions and Relevance:There is a sex disparate underuse of adjuvant endocrine therapy among men with HR-positive breast cancer despite the use of this treatment being associated with improved overall survival. Further research and interventions may be warranted to bridge gaps in care in this population.
| S-EPMC6233775 | biostudies-literature
Project description:Systemic therapy for premenopausal women with hormone receptor-positive breast cancer has evolved in the last 5 years, but critical questions remain. Recent randomized trials have demonstrated a benefit for the addition of ovarian suppression to endocrine therapy in patients with breast cancers considered to be at high risk for recurrence, whereas those with lower-risk cancers seem to have a favorable outcome with tamoxifen alone. Two large randomized trials have demonstrated a benefit for extending adjuvant tamoxifen beyond 5 years. Currently the choice of systemic therapy is selected empirically but molecular profiling may, in the near future, provide a more conclusive means of selecting an endocrine therapeutic approach for premenopausal patients. Given that a significant subset of hormone receptor-positive cancers are intrinsically resistant to endocrine agents, as well as the finding that inhibiting cyclin-dependent kinases 4 and 6 and mammalian target of rapamycin appears to potentially reverse this resistance in patients with metastatic disease, evaluation of these agents in the early-stage setting is ongoing.
| S-EPMC6469352 | 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:The third-generation aromatase inhibitors (AIS) are largely replacing tamoxifen in the adjuvant treatment of early-stage breast cancer in postmenopausal women with hormone receptor-positive tumours. To date, multiple trials have been conducted comparing tamoxifen treatment with an AI, and all have demonstrated improved disease-free survival with AI treatment. Trials have included direct 5-year comparisons between tamoxifen and an AI, switching to an AI within 5 years after initial tamoxifen treatment, or extending treatment with an AI after 5 years of completed tamoxifen treatment. Some of these trials have been completed; others are ongoing; and head-to-head trial comparisons of individual AIS are also in progress. The present article summarizes the data obtained from various clinical trials of hormonal therapy for early breast cancer. It also reviews recent data so as to shed light on the current status of these therapies. The focus is on the efficacy of treatment with an AI. Toxicity is discussed in the second article in this supplement.
| S-EPMC2722048 | biostudies-literature
Project description:BackgroundMost premenopausal patients with early breast cancer (eBC) are diagnosed with hormone receptor-positive disease and therefore candidate for adjuvant endocrine therapy (ET).Patients and methodsThe Gruppo Italiano Mammella (GIM) 23-POSTER (GIM23) is a multicenter, prospective, observational study conducted in 26 Italian institutions, aiming to evaluate ET choices for premenopausal patients affected by hormone receptor-positive eBC in a real-world setting. Here we report also the results in terms of type of ET prescribed according to the definition of high-risk patients by monarchE and NATALEE trials.ResultsBetween October 2019 and June 2022, 600 premenopausal patients were included, with a median age of 46 years. Almost half (271, 45.2 %) of the patients had stage I disease, while 254 (42.3 %) and 60 (10.0 %) patients had stage II and III, respectively. Overall, 149 (25.1 %) patients received tamoxifen alone, 83 (14.0 %) tamoxifen with ovarian function suppression (OFS), while 361 (60.9 %) received aromatase inhibitor (AI) with OFS. Patients treated with AI and OFS had higher number of metastatic axillary nodes, higher grade and more often received chemotherapy (all p < 0.001). According to the inclusion criteria of the monarchE and NATALEE trials, 81 patients (15.6 %) were considered high-risk for the monarchE and received AI with OFS in 88.9 % of the cases, while 231 patients (44.4 %) were considered high-risk for the NATALEE trial and received AI with OFS in 74.5 % of cases.ConclusionsAI with OFS is the most prescribed adjuvant ET among premenopausal patients, especially in the presence of high-risk features.
| S-EPMC11325348 | biostudies-literature
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.
| S-EPMC8841328 | biostudies-literature
Project description:IntroductionAnti-estrogen therapy has been shown to reduce mammographic breast density (MD). We hypothesized that a short-term change in breast density may be a surrogate biomarker predicting response to adjuvant endocrine therapy (ET) in breast cancer.MethodsWe analyzed data for 1,065 estrogen receptor (ER)-positive breast cancer patients who underwent surgery between 2003 and 2006 and received at least 2 years of ET, including tamoxifen and aromatase inhibitors. MD was measured using Cumulus software 4.0 and expressed as a percentage. MD reduction (MDR) was defined as the absolute difference in MD of mammograms taken preoperatively and 8-20 months after the start of ET.ResultsAt a median follow-up of 68.8 months, the overall breast cancer recurrence rate was 7.5% (80/1065). Mean MDR was 5.9% (range, -17.2% to 36.9%). Logistic regression analysis showed that age < 50 years, high preoperative MD, and long interval between start of ET to follow-up mammogram were significantly associated with larger MDR (p < 0.05). In a survival analysis, tumor size, lymph node positivity, high Ki-67 (≥ 10%), and low MDR were independent factors significantly associated with recurrence-free survival (p < 0.05). Compared with the group showing the greatest MDR (≥ 10%), the hazard ratios for MDRs of 5-10%, 0-5%, and < 0% were 1.33, 1.92, and 2.26, respectively.ConclusionsMD change during short-term use of adjuvant ET was a significant predictor of long-term recurrence in women with ER-positive breast cancer. Effective treatment strategies are urgently needed in patients with low MDR despite about 1 year of ET.
| S-EPMC3680951 | biostudies-literature
Project description:ImportanceAdjuvant endocrine therapy (AET) reduces breast cancer recurrence, but symptom burden is a key barrier to adherence. Black women have lower AET adherence and worse health outcomes than White women.ObjectiveTo investigate the association between symptom burden and AET adherence differences by race.Design, setting, and participantsA retrospective cohort study using electronic health records with patient-reported data from a large cancer center in the US. Patients included Black and White women initiating AET therapy for early-stage breast cancer from August 2007 to December 2015 who were followed for 1 year from AET initiation. Sixty symptoms classified into 7 physical and 2 psychological symptom clusters were evaluated. For each cluster, the number of symptoms with moderate severity at baseline, and symptoms with 3-point or greater increases during AET were counted. Adherence was measured as the proportion of days covered by AET during the first-year follow-up. Multivariable regressions for patients' adherence adjusting for race, symptom measures, sociodemographic characteristics, and clinical characteristics were conducted. Kitagawa-Blinder-Oaxaca decomposition was used to quantify racial differences in adherence explained by symptoms and patient characteristics. Analyses were conducted from July 2021 to January 2022.ExposuresPhysical and psychological symptoms at baseline and changes during AET.ResultsAmong 559 patients (168 [30.1%] Black and 391 [69.9%] White; mean [SD] age 65.5 [12.1] years), Black women received diagnoses younger (mean [SD] age at diagnosis, 58.7 [13.7] vs 68.5 [10.0] years old) than White women, with more advanced stages (30 Black participants [17.9%] vs 31 White participants [7.9%] had stage III disease at diagnosis), and lived in areas with fewer adults attaining high school education (mean [SD], 78.8% [7.8%] vs 84.0% [9.3%]). AET adherence in the first year was 78.8% for Black and 82.3% for White women. Black women reported higher severity in most symptom clusters than White women. Neuropsychological, vasomotor, musculoskeletal, cardiorespiratory, distress, and despair symptoms at baseline and increases during the follow-up were associated with 1.2 to 2.6 percentage points decreases in adherence, which corresponds to 4 to 9 missed days receiving AET in the first year. After adjusting for psychological symptoms, being Black was associated with 6.5 percentage points higher adherence than being White.Conclusions and relevanceIn this cohort study, severe symptoms were associated with lower AET adherence. Black women had lower adherence rates that were explained by their higher symptom burden and baseline characteristics. These findings suggest that better symptom management with a focus on psychological symptoms could improve AET adherence and reduce racial disparities in cancer outcomes.
| S-EPMC9366541 | biostudies-literature
Project description:The importance and role of the estrogen receptor (ER) pathway has been well-documented in both breast cancer (BC) development and progression. The treatment of choice in women with metastatic breast cancer (MBC) is classically divided into a variety of endocrine therapies, 3 of the most common being: selective estrogen receptor modulators (SERM), aromatase inhibitors (AI) and selective estrogen receptor down-regulators (SERD). In a proportion of patients, resistance develops to endocrine therapy due to a sophisticated and at times redundant interference, at the molecular level between the ER and growth factor. The progression to endocrine resistance is considered to be a gradual, step-wise process. Several mechanisms have been proposed but thus far none of them can be defined as the complete explanation behind the phenomenon of endocrine resistance. Although multiple cellular, molecular and immune mechanisms have been and are being extensively studied, their individual roles are often poorly understood. In this review, we summarize current progress in our understanding of ER biology and the molecular mechanisms that predispose and determine endocrine resistance in breast cancer patients.
| S-EPMC6543000 | biostudies-literature