Prognostic value of lymphopenia in early breast cancer: learnings from the prospective CANTO cohort.

BACKGROUND

Lymphopenia has been associated with poor outcomes in metastatic breast cancer (BC), but its prognostic relevance in early-stage disease remains unclear. This study aimed to evaluate the prognostic value of baseline lymphopenia in patients with non-metastatic BC using data from the prospective French CANTO cohort (NCT01993498).

METHODS

10,854 patients with baseline absolute lymphocyte count (ALC) were analysed. Lymphopenia was defined as ALC < 1.0 × 10⁹ cells/L, measured before any cancer treatment. Relapse-free survival (RFS), overall survival (OS), and treatment-related toxicities were assessed using Kaplan-Meier estimates, piecewise-Cox regression models, and cause-specific hazard analyses considering pre-specified time periods.

RESULTS

Baseline lymphopenia was observed in 342 patients (3.1%). It was associated with ECOG performance status > 0, hypoalbuminemia, and prior neoplasia. Lymphopenia correlated with inferior 5-year RFS (89.1% vs. 92.9%) and OS (92.5% vs. 96.4%). In multivariable analyses, lymphopenia was associated with increased risk of early relapse during the first 24 months (HR = 2.11; 95%CI: 1.28-3.48; p = 0.003), but not beyond, and no independent prognostic impact on OS was observed. No significant differences were found in surgical complications or chemotherapy dose intensity, though granulocyte colony-stimulating factor use was higher among lymphopenic patients.

CONCLUSION

Baseline lymphopenia is uncommon in early BC but may serve as a marker of early relapse risk. Although it does not independently predict long-term survival, its presence could reflect underlying tumour aggressiveness or patient frailty. These findings support further investigation of lymphocyte subpopulations to refine prognostic stratification in early BC.

TRIAL REGISTRATION: Approved by French ethics committee in 2011 (ID-RCB:2011-A01095- 36,11-039 /NCT01993498 [20FEB2012]).