A major real-world study links GLP-1 receptor agonists to improved survival and lower recurrence risk in women with breast cancer, but researchers say clinical trials are needed before these drugs can be considered part of cancer care.
Study: Survival and Recurrence With GLP-1 Receptor Agonists in Breast Cancer. Image Credit: zimmytws / Shutterstock
In a recent study published in JAMA Network Open, researchers investigated the associations between glucagon-like peptide 1 receptor agonists (GLP-1RAs) and all-cause mortality and recurrence-free survival (RFS) among adult female breast cancer (BC) patients.
GLP-1RA Breast Cancer Survival Background
BC is the most common cancer among females in the United States (US), and pre-existing conditions like type 2 diabetes (T2D) and obesity elevate the risk of reduced survival, disease progression, and recurrence. Weight-loss interventions to address obesity among BC patients may augment outcomes.
GLP-1RAs are established treatments for weight loss and T2D. However, the potential protective effects of these agents on recurrence and survival in BC patients are unclear.
Breast Cancer EHR Cohort Study Design
In the present study, researchers investigated the associations between GLP-1RA use and all-cause mortality and RFS in patients with BC. The team obtained data from electronic health records of adult female BC patients from a health research network.
Individuals diagnosed with BC from April 1, 2006, to April 1, 2023, were included. Patients with stage I, II, or III BC were included, while those with stage IV BC, prior malignant neoplasms, or metastatic disease were excluded.
GLP-1RA usage was defined as having at least two prescriptions in the six months prior to or any time after BC diagnosis. The study sample was stratified into T2D and obesity cohorts. GLP-1 use was compared to insulin/metformin or sodium-glucose cotransporter 2 (SGLT2) inhibitors in BC patients with T2D or glycated hemoglobin (HbA1c) ≥ 6.5% (T2D cohort), and to non-use in BC patients with obesity (obesity cohort).
The study’s outcomes included all-cause mortality and RFS (i.e., time from BC diagnosis to first metastatic recurrence). Cohorts were balanced on covariates, including demographics, medications, diagnoses, and procedures, using propensity score matching (PSM).
Cox proportional hazards regression was used to estimate hazard ratios. Survival probabilities of all-cause mortality and RFS at five and 10 years were calculated.
GLP-1RA Mortality and Recurrence Findings
The study included 841,831 BC patients, predominantly White (72%), with a mean age of 69 years. Of these, 652,001 patients with T2D and 573,443 with obesity were included in PSM. In the comparison of GLP-1 use vs non-use, 1,610 BC patients with obesity were included.
For all-cause mortality and RFS in patients with obesity, the 5-year survival probability was 97.4% and 96% with GLP-1 RA use, and 93.2% and 91.3% with non-use, respectively.
The corresponding 10-year estimates were 96% and 87.7% for GLP-1RA use and 88.6% and 90.6% for non-use, respectively. GLP-1RA use was significantly associated with a lower risk of all-cause mortality and metastatic recurrence compared to non-use in BC patients with obesity. However, the authors noted that few patients remained at risk after five years, limiting the precision of later 10-year RFS estimates.
Further, 2,323 BC patients with T2D were included in the comparison of GLP-1RAs to insulin/metformin.
For all-cause mortality, the five-year survival probability was 96.9% with GLP-1RAs and 82.3% with insulin/metformin. At 10 years, the survival probability was 96.9% for GLP-1RA use and 76.4% for insulin/metformin use. GLP-1RA use was significantly associated with a lower risk of all-cause mortality in this cohort compared to insulin/metformin use.
For RFS, the survival probability was 93.4% with insulin/metformin and 97.4% with GLP-1RAs at both five and 10 years. Consistently, GLP-1RA use was associated with a lower recurrence risk than insulin/metformin use. Finally, 4,052 BC patients with T2D were included to compare GLP-1RAs to SGLT2 inhibitors.
For all-cause mortality, the survival probabilities were 86.3% with GLP-1RA use and 88.9% with SGLT2 inhibitors at five years. The corresponding 10-year estimates were 75.5% and 73.4%, respectively.
For RFS, the survival probabilities at five and 10 years were 95% and 90.9% with GLP-1RAs and 93.8% and 89.9% with SGLT2 inhibitors, respectively. In unadjusted analyses, the risk of all-cause mortality and recurrence did not differ significantly between GLP-1RA and SGLT2 inhibitor use, although adjusted models suggested lower hazards with GLP-1RA use.
Breast Cancer Outcomes and Study Limits
In sum, GLP-1RAs were associated with improved all-cause mortality and RFS among adult female BC patients with obesity compared with non-use, and among those with T2D compared with insulin/metformin, while comparisons with SGLT2 inhibitors were less consistent.
The study’s limitations include its reliance on a US sample and a retrospective design, which may introduce bias and limit generalizability.
Other limitations included potential residual confounding, reliance on electronic health record diagnostic codes, lack of medication adherence and patient-level weight-change data, grouping of different GLP-1RAs, and limited precision in later estimates because many patients were censored around 5 years.
Further research is required to determine the optimal timing, tailoring, and potential risks of GLP-1RA treatment in BC patients.
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