Dataset Information

Extended adjuvant aromatase inhibition after sequential endocrine therapy in postmenopausal women with breast cancer: follow-up analysis of the randomised phase 3 DATA trial.

ABSTRACT:

Background

The 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.

Methods

The 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.

Findings

Between 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).

Interpretation

Extended 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.

Funding

AstraZeneca.

SUBMITTER: Tjan-Heijnen VCG

PROVIDER: S-EPMC10041456 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature

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Publications

Extended adjuvant aromatase inhibition after sequential endocrine therapy in postmenopausal women with breast cancer: follow-up analysis of the randomised phase 3 DATA trial.

Tjan-Heijnen Vivianne C G VCG Lammers Senna W M SWM Geurts Sandra M E SME Vriens Ingeborg J H IJH Swinkels Astrid C P ACP Smorenburg Carolien H CH van der Sangen Maurice J C MJC Kroep Judith R JR de Graaf Hiltje H Honkoop Aafke H AH Erdkamp Frans L G FLG de Roos Wilfred K WK Linn Sabine C SC Imholz Alexander L T ALT

EClinicalMedicine 20230320

<h4>Background</h4>The 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.<h4>Methods</h4>The open-label, randomised, phase 3 DATA study was performed in 79 hospitals in the Netherlands (ClinicalTrials.gov, number NCT00301 ...[more]

PMID: 36992863

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Project description:BackgroundBy contrast with many observational studies, women in the Women's Health Initiative (WHI) trial who were randomly allocated to receive oestrogen alone had a lower incidence of invasive breast cancer than did those who received placebo. We aimed to assess the influence of oestrogen use on longer term breast cancer incidence and mortality in extended follow-up of this cohort.MethodsBetween 1993 and 1998, the WHI enrolled 10,739 postmenopausal women from 40 US clinical centres into a randomised, double-masked, placebo-controlled trial. Women aged 50-79 years who had undergone hysterectomy and had expected 3-year survival and mammography clearance were randomly allocated by a computerised, permuted block algorithm, stratified by age group and centre, to receive oral conjugated equine oestrogen (0·625 mg per day; n=5310) or matched placebo (n=5429). The trial intervention was terminated early on Feb 29, 2004, because of an adverse effect on stroke. Follow-up continued until planned termination (March 31, 2005). Consent was sought for extended surveillance from the 9786 living participants in active follow-up, of whom 7645 agreed. Using data from this extended follow-up (to Aug 14, 2009), we assessed long-term effects of oestrogen use on invasive breast cancer incidence, tumour characteristics, and mortality. We used Cox regression models to estimate hazard ratios (HRs) in the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT00000611.FindingsAfter a median follow-up of 11·8 years (IQR 9·1-12·9), the use of oestrogen for a median of 5·9 years (2·5-7·3) was associated with lower incidence of invasive breast cancer (151 cases, 0·27% per year) compared with placebo (199 cases, 0·35% per year; HR 0·77, 95% CI 0·62-0·95; p=0·02) with no difference (p=0·76) between intervention phase (0·79, 0·61-1·02) and post-intervention phase effects (0·75, 0·51-1·09). In subgroup analyses, we noted breast cancer risk reduction with oestrogen use was concentrated in women without benign breast disease (p=0·01) or a family history of breast cancer (p=0·02). In the oestrogen group, fewer women died from breast cancer (six deaths, 0·009% per year) compared with controls (16 deaths, 0·024% per year; HR 0·37, 95% CI 0·13-0·91; p=0·03). Fewer women in the oestrogen group died from any cause after a breast cancer diagnosis (30 deaths, 0·046% per year) than did controls (50 deaths, 0·076%; HR 0·62, 95% CI 0·39-0·97; p=0·04).InterpretationOur findings provide reassurance for women with hysterectomy seeking relief of climacteric symptoms in terms of the effects of oestrogen use for about 5 years on breast cancer incidence and mortality. However, our data do not support use of oestrogen for breast cancer risk reduction because any noted benefit probably does not apply to populations at increased risk of such cancer.FundingUS National Heart, Lung, and Blood Institute; Wyeth.

Project description:ImportanceAromatase inhibitors induce a profound depletion in serum estrogen levels. Postmenopausal obese women receiving aromatase inhibitor therapy may be at increased risk of bone fractures owing to the detrimental association of adiposity with bone quality and the loss of the protective effect of estrogens on bone mineral density.ObjectiveTo determine whether fat body mass (FBM), as measured by dual-energy x-ray absorptiometry, is associated with vertebral fracture prevalence in postmenopausal women undergoing adjuvant aromatase inhibitor therapy for breast cancer.Design, setting, and participantsIn this single-center, cross-sectional study, 556 postmenopausal women with early-stage breast cancer were consecutively enrolled from October 15, 2013, to June 30, 2018, and stratified according to whether they were aromatase inhibitor-naive or aromatase inhibitor-treated for at least 2 years. The database was locked on December 31, 2018, and data analysis was completed on February 28, 2019. Eligible patients in both groups had normal renal function, no metabolic diseases, and no previous or current treatment with antiosteoporotic drugs or glucocorticoids. Previous chemotherapy, but not tamoxifen, was permitted. Data were gathered once, at baseline.Main outcomes and measuresVertebral fracture prevalence associated with FBM in aromatase inhibitor-naive and aromatase inhibitor-treated patients.ResultsOf the 556 women enrolled, the mean age was 63.0 years (95% CI, 62.2-63.8 years). The 195 aromatase inhibitor-treated patients were older than the 361 aromatase inhibitor-naive patients (mean age, 66.1 vs 61.3 years; P < .001), had a higher body mass index (mean, 26.4 vs 25.3; P = .009), were less likely to engage in physical activity (65.3% vs 73.7%; P = .03), and were less likely to consume alcoholic beverages (68.4% vs 80.9%; P = .001). Among the aromatase inhibitor-naive patients, the vertebral fracture prevalence was higher in the subgroup with FBM below the median value than in those with high FBM, but the difference was not statistically significant (19.2% vs 13.3%; P = .13). Conversely, the proportion of vertebral fractures in the aromatase inhibitor-treated group was 20.0% in patients with low FBM vs 33.3% in patients with high FBM (P = .04). An opposite trend in the association of FBM with vertebral fracture prevalence according to aromatase inhibitor group was shown by multivariable analysis in the propensity score-matched sample: odds ratio, 0.38 (95% CI, 0.12-1.19) and 1.94 (95% CI, 0.67-5.64) in the aromatase inhibitor-naive and aromatase inhibitor-treated groups, respectively (odds ratio for the interaction, 5.77 [95% CI, 1.08-30.81]; P for interaction term = .03).Conclusions and relevanceFat body mass may be associated with fragility-related fractures in patients with breast cancer who undergo aromatase inhibitor therapy. If these data are confirmed, obesity could be included in the algorithm for assessing fracture risk and selecting patients to receive bone resorption inhibitors.

Dataset Information

Extended adjuvant aromatase inhibition after sequential endocrine therapy in postmenopausal women with breast cancer: follow-up analysis of the randomised phase 3 DATA trial.

Background

Methods

Findings

Interpretation

Funding

Publications

Extended adjuvant aromatase inhibition after sequential endocrine therapy in postmenopausal women with breast cancer: follow-up analysis of the randomised phase 3 DATA trial.

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