Dataset Information

Impact of premenopausal status at breast cancer diagnosis in women entered on the placebo-controlled NCIC CTG MA17 trial of extended adjuvant letrozole.

ABSTRACT:

Background

MA17 showed improved outcomes in postmenopausal women given extended letrozole (LET) after completing 5 years of adjuvant tamoxifen.

Patients and methods

Exploratory subgroup analyses of disease-free survival (DFS), distant DFS (DDFS), overall survival (OS), toxic effects and quality of life (QOL) in MA17 were performed based on menopausal status at breast cancer diagnosis.

Results

At diagnosis, 877 women were premenopausal and 4289 were postmenopausal. Extended LET was significantly better than placebo (PLAC) in DFS for premenopausal [hazard ratio (HR) = 0.26, 95% confidence interval (CI) 0.13-0.55; P = 0.0003] and postmenopausal women (HR = 0.67; 95% CI 0.51-0.89; P = 0.006), with greater DFS benefit in those premenopausal (interaction P = 0.03). In adjusted post-unblinding analysis, those who switched from PLAC to LET improved DDFS in premenopausal (HR = 0.15; 95% CI 0.03-0.79; P = 0.02) and postmenopausal women (HR = 0.45; 95% CI 0.22-0.94; P = 0.03).

Conclusions

Extended LET after 5 years of tamoxifen was effective in pre- and postmenopausal women at diagnosis, and significantly better in those premenopausal. Women premenopausal at diagnosis should be considered for extended adjuvant therapy with LET if menopausal after completing tamoxifen.

SUBMITTER: Goss PE

PROVIDER: S-EPMC3551482 | biostudies-literature | 2013 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Impact of premenopausal status at breast cancer diagnosis in women entered on the placebo-controlled NCIC CTG MA17 trial of extended adjuvant letrozole.

Goss P E PE Ingle J N JN Martino S S Robert N J NJ Muss H B HB Livingston R B RB Davidson N E NE Perez E A EA Chavarri-Guerra Y Y Cameron D A DA Pritchard K I KI Whelan T T Shepherd L E LE Tu D D

Annals of oncology : official journal of the European Society for Medical Oncology 20121001 2

<h4>Background</h4>MA17 showed improved outcomes in postmenopausal women given extended letrozole (LET) after completing 5 years of adjuvant tamoxifen.<h4>Patients and methods</h4>Exploratory subgroup analyses of disease-free survival (DFS), distant DFS (DDFS), overall survival (OS), toxic effects and quality of life (QOL) in MA17 were performed based on menopausal status at breast cancer diagnosis.<h4>Results</h4>At diagnosis, 877 women were premenopausal and 4289 were postmenopausal. Extended ...[more]

PMID: 23028039

Similar Datasets

Project description:BackgroundEarly endometrial cancer with low-risk pathological features can be successfully treated by surgery alone. External beam radiotherapy added to surgery has been investigated in several small trials, which have mainly included women at intermediate risk of recurrence. In these trials, postoperative radiotherapy has been shown to reduce the risk of isolated local recurrence but there is no evidence that it improves recurrence-free or overall survival. We report the findings from the ASTEC and EN.5 trials, which investigated adjuvant external beam radiotherapy in women with early-stage disease and pathological features suggestive of intermediate or high risk of recurrence and death from endometrial cancer.MethodsBetween July, 1996, and March, 2005, 905 (789 ASTEC, 116 EN.5) women with intermediate-risk or high-risk early-stage disease from 112 centres in seven countries (UK, Canada, Poland, Norway, New Zealand, Australia, USA) were randomly assigned after surgery to observation (453) or to external beam radiotherapy (452). A target dose of 40-46 Gy in 20-25 daily fractions to the pelvis, treating five times a week, was specified. Primary outcome measure was overall survival, and all analyses were by intention to treat. These trials were registered ISRCTN 16571884 (ASTEC) and NCT 00002807 (EN.5).FindingsAfter a median follow-up of 58 months, 135 women (68 observation, 67 external beam radiotherapy) had died. There was no evidence that overall survival with external beam radiotherapy was better than observation, hazard ratio 1.05 (95% CI 0.75-1.48; p=0.77). 5-year overall survival was 84% in both groups. Combining data from ASTEC and EN.5 in a meta-analysis of trials confirmed that there was no benefit in terms of overall survival (hazard ratio 1.04; 95% CI 0.84-1.29) and can reliably exclude an absolute benefit of external beam radiotherapy at 5 years of more than 3%. With brachytherapy used in 53% of women in ASTEC/EN.5, the local recurrence rate in the observation group at 5 years was 6.1%.InterpretationAdjuvant external beam radiotherapy cannot be recommended as part of routine treatment for women with intermediate-risk or high-risk early-stage endometrial cancer with the aim of improving survival. The absolute benefit of external beam radiotherapy in preventing isolated local recurrence is small and is not without toxicity.

Project description:BackgroundSuppression of ovarian estrogen production reduces the recurrence of hormone-receptor-positive early breast cancer in premenopausal women, but its value when added to tamoxifen is uncertain.MethodsWe randomly assigned 3066 premenopausal women, stratified according to prior receipt or nonreceipt of chemotherapy, to receive 5 years of tamoxifen, tamoxifen plus ovarian suppression, or exemestane plus ovarian suppression. The primary analysis tested the hypothesis that tamoxifen plus ovarian suppression would improve disease-free survival, as compared with tamoxifen alone. In the primary analysis, 46.7% of the patients had not received chemotherapy previously, and 53.3% had received chemotherapy and remained premenopausal.ResultsAfter a median follow-up of 67 months, the estimated disease-free survival rate at 5 years was 86.6% in the tamoxifen-ovarian suppression group and 84.7% in the tamoxifen group (hazard ratio for disease recurrence, second invasive cancer, or death, 0.83; 95% confidence interval [CI], 0.66 to 1.04; P=0.10). Multivariable allowance for prognostic factors suggested a greater treatment effect with tamoxifen plus ovarian suppression than with tamoxifen alone (hazard ratio, 0.78; 95% CI, 0.62 to 0.98). Most recurrences occurred in patients who had received prior chemotherapy, among whom the rate of freedom from breast cancer at 5 years was 82.5% in the tamoxifen-ovarian suppression group and 78.0% in the tamoxifen group (hazard ratio for recurrence, 0.78; 95% CI, 0.60 to 1.02). At 5 years, the rate of freedom from breast cancer was 85.7% in the exemestane-ovarian suppression group (hazard ratio for recurrence vs. tamoxifen, 0.65; 95% CI, 0.49 to 0.87).ConclusionsAdding ovarian suppression to tamoxifen did not provide a significant benefit in the overall study population. However, for women who were at sufficient risk for recurrence to warrant adjuvant chemotherapy and who remained premenopausal, the addition of ovarian suppression improved disease outcomes. Further improvement was seen with the use of exemestane plus ovarian suppression. (Funded by Pfizer and others; SOFT ClinicalTrials.gov number, NCT00066690.).

Dataset Information

Impact of premenopausal status at breast cancer diagnosis in women entered on the placebo-controlled NCIC CTG MA17 trial of extended adjuvant letrozole.

Background

Patients and methods

Results

Conclusions

Publications

Impact of premenopausal status at breast cancer diagnosis in women entered on the placebo-controlled NCIC CTG MA17 trial of extended adjuvant letrozole.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets