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Use of neoadjuvant data to design adjuvant endocrine therapy trials for breast cancer.

ABSTRACT: Mature outcomes from adjuvant endocrine therapy trials in estrogen receptor-positive breast cancer have enabled comparisons with neoadjuvant clinical trials that have parallel randomizations of treatment in terms of the response of disseminated disease versus the local response within the breast. Imprecise end points, such as 'clinical response', have produced inconsistent results regarding the relationship between neoadjuvant and adjuvant endocrine therapy outcomes. However, the proliferation marker Ki-67, measured during neoadjuvant treatment, has predicted accurately and consistently the results of much larger studies in the adjuvant setting. In this Review, we summarize these trials and discuss the implications for the design of future adjuvant endocrine therapy trials. We conclude that there is sufficient evidence supporting the view that the degree of Ki-67 suppression is a reliable short-term surrogate for the adjuvant potential of endocrine drugs, at least in postmenopausal women. We propose that adjuvant endocrine therapy trials should only be conducted once adequately-powered neoadjuvant studies have indicated superior Ki-67 suppression in patients receiving experimental endocrine treatment versus the standard treatment.

SUBMITTER: Goncalves R

PROVIDER: S-EPMC3518447 | biostudies-other | 2012 Feb

REPOSITORIES: biostudies-other

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Use of neoadjuvant data to design adjuvant endocrine therapy trials for breast cancer.

Goncalves Rodrigo R Ma Cynthia C Luo Jingqin J Suman Vera V Ellis Matthew James MJ

Nature reviews. Clinical oncology 20120228 4

Mature outcomes from adjuvant endocrine therapy trials in estrogen receptor-positive breast cancer have enabled comparisons with neoadjuvant clinical trials that have parallel randomizations of treatment in terms of the response of disseminated disease versus the local response within the breast. Imprecise end points, such as 'clinical response', have produced inconsistent results regarding the relationship between neoadjuvant and adjuvant endocrine therapy outcomes. However, the proliferation m ...[more]

PMID: 22371132

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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:BackgroundAdjuvant endocrine therapy (AET) significantly decreases the risk of breast cancer recurrence and mortality. Notwithstanding the demonstrated efficacy of AET, 31-73% of breast cancer survivors do not persist with AET. The purpose of this study was to explore breast cancer survivors' experiences and perspectives of persisting with AET and to identify the psychosocial and healthcare system factors that influence AET persistence.MethodsInformed by interpretive descriptive methodology and relational autonomy theory, individual interviews were conducted with 22 women diagnosed with early-stage breast cancer who had been prescribed AET. These participants also completed a demographic form and a survey that assessed their perceived risk of recurrence. Interviews were analysed using inductive thematic and constant comparative analysis to iteratively compare data and develop conceptualizations of the relationships among data. Descriptive statistics were used to summarize the quantitative data.ResultsThe personal, social, and structural factors found to influence AET persistence included AET side effects, perception of breast cancer recurrence risk, medication and necessity beliefs, social support, the patient-provider relationship, and the continuity and frequency of follow-up care. For most women, over time, the decision-making process around AET persistence became a balancing act between quality of life and quantity of life. The interplay between the personal, social, and structural factors was complex and the weight women placed on some factors over others influenced their AET persistence or non-persistence.ConclusionExpanding our understanding of the factors affecting breast cancer survivors' AET persistence from their perspective is the first step in developing efficacious, patient-centered interventions aimed at improving AET persistence. In order to improve AET persistence, enhanced symptom management is required, as well as the development of supportive care strategies that acknowledge the values and beliefs held by breast cancer survivors while reinforcing the benefits of AET, and addressing women's reasons for non-persistence. Improved continuity of health care and patient-healthcare provider communication across oncology and primary care settings is also required. The development and evaluation of supportive care strategies that address the challenges associated with AET experienced by breast cancer survivors hold the potential to increase both women's quality and quantity of life.

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.

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Use of neoadjuvant data to design adjuvant endocrine therapy trials for breast cancer.

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Use of neoadjuvant data to design adjuvant endocrine therapy trials for breast cancer.

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