94MO - The prognostic and predictive effect of BMI in postmenopausal HR+ breast cancer patients receiving (extended) endocrine therapy - DATA trial analysis

Background

This study determines the prognostic and predictive effect of body mass index (BMI) on the disease-free survival (DFS) of postmenopausal hormone receptor-positive (HR+) breast cancer patients who received (extended) endocrine therapy.

Methods

Patients with a BMI of ≥18.5 kg/m² were identified from the randomised, phase III DATA trial (NCT00301457), which evaluated the use of six versus three years of anastrozole in postmenopausal women with HR+ breast cancer who were disease-free after two to three years of adjuvant tamoxifen. Patients were categorised as normal weight (18.5-24.9 kg/m²), overweight (25-29.9 kg/m²), or obese (≥30 kg/m²). The primary endpoint was DFS. Multivariable Cox regression analyses were performed. The prognostic impact of BMI was evaluated from date of randomisation, whereas the predictive impact of BMI on the efficacy of extended anastrozole was evaluated from three years after randomisation, i.e. treatment divergence (adapted DFS).

Results

Overall, 1,781 patients were included: 678 (38%) normal weight, 712 (40%) overweight, and 391 (22%) obese patients. After a median follow-up of 13.1 years, overweight and obese patients had a worse DFS when compared with normal weight patients (hazard ratio (HR)=1.16; 95% confidence interval (CI) 0.97-1.38, p=0.10; and HR=1.26; 95% CI 1.03-1.54, p=0.03, respectively). In women aged <60 years, overweight was associated with a worse DFS (HR=1.29; 95% CI 1.00-1.67, p=0.05) as was obesity (HR=1.83; 95% CI 1.36-2.46, p<0.001), but this was not observed in women aged ≥60 years (HR=1.04; 95% CI 0.82-1.33, p=0.72; and HR=0.94; 95% CI 0.72-1.23, p=0.63, respectively) (p-interaction = 0.009). The effect of extended anastrozole on adapted DFS did not differ between normal weight (HR=1.00; 95% CI 0.74-1.35, p=1.00), overweight (HR=0.74; 95% CI 0.56-0.98, p=0.04), and obese patients (HR=0.97; 95% CI 0.69-1.36, p=0.85) (p-interaction=0.24).

Conclusions

In HR+ breast cancer patients aged <60 years at randomisation, overweight and obesity were adverse prognostic factors for DFS. In patients aged ≥60 years, this adverse prognostic effect was not observed. The effect of extended anastrozole on adapted DFS did not differ between BMI classes.

Clinical trial identification

NCT00301457.

Legal entity responsible for the study

MUMC+.

Funding

AstraZeneca.

Disclosure

S.W.M. Lammers: Financial Interests, Institutional, Funding: AstraZeneca; Financial Interests, Institutional, Research Grant: Eli Lilly. S.M.E. Geurts: Financial Interests, Institutional, Funding: AstraZeneca; Financial Interests, Institutional, Research Grant: Roche, Pfizer, Novartis, Eli Lilly, Daiichi Sankyo, Gilead; Financial Interests, Personal, Invited Speaker: AstraZeneca. A.C.P. Swinkels: Financial Interests, Institutional, Funding: AstraZeneca. C.H. Smorenburg: Financial Interests, Institutional, Leadership Role: Board of Dutch national breast cancer guidelines. J.R. Kroep: Financial Interests, Institutional, Advisory Board: AstraZeneca, MSD, Eisai, Eli Lilly, GSK; Financial Interests, Institutional, Invited Speaker: MSD; Financial Interests, Institutional, Research Grant: AstraZeneca. A.H. Honkoop: Financial Interests, Institutional, Research Grant: Dutch Breast Cancer Research Group; Financial Interests, Institutional, Advisory Board: Eli Lilly; Financial Interests, Personal, Other, Support to attend the ESMO 2022 congress: Pfizer. S.C. Linn: Financial Interests, Institutional, Research Grant: AstraZeneca, Eurocept Plaza, Roche, Genentech, Gilead Sciences, Tesaro, Novartis, Dutch Cancer Society, ZonMW, A Sister's Hope, [Z]aan de Wandel, Agendia; Financial Interests, Institutional, Other, Consulting fees: AstraZeneca, ERC (EU), NWO (Dutch Research Council); Financial Interests, Institutional, Other, Payment or honoraria: Daiichi Sankyo; Financial Interests, Institutional, Other, Support for attending meetings: ESMO, Daiichi Sankyo, ERC (EU), NWO (Dutch Research Council); Non-Financial Interests, Institutional, Product Samples, Drug: Genentech, Roche, Gilead Sciences, Novartis, AstraZeneca; Non-Financial Interests, Institutional, Product Samples, Gene expression tests: Agendia; Other, Institutional, Ownership Interest: Patent (UN23A01/P-EP) pending on a method for assessing homologous recombination deficiency in ovarian cancer cells; Other, Institutional, Leadership Role, Chair: Trial Steering Committee of the PIONEER trial (Cambridge University); Other, Institutional, Advisory Role, Member: Health Council of the Netherlands - Independent scientific advisory body for government and parliament. A.L.T. Imholz: Financial Interests, Institutional, Funding: AstraZeneca. M.M. Smidt: Financial Interests, Institutional, Research Grant: Dutch Cancer Society, Servier Pharma, Nutricia, Kankeronderzoekfonds Limburg, ZonMw, The Jules Coenegracht Foundation, Academische Alliantie, NWA-ORC, TKI. I.J.H. Vriens: Financial Interests, Institutional, Funding: AstraZeneca; Financial Interests, Institutional, Research Grant: Pfizer, Eli Lilly. V.C.G. Tjan-Heijnen: Financial Interests, Institutional, Funding: AstraZeneca; Financial Interests, Personal and Institutional, Research Grant: Novartis, Eli Lilly, AstraZeneca; Financial Interests, Institutional, Research Grant: Roche, Pfizer, Daiichi Sankyo, Gilead; Financial Interests, Personal, Advisory Role: AstraZeneca, Eli Lilly, Novartis. All other authors have declared no conflicts of interest.