Feasibility of HER2-directed therapy in an unselected clinical cohort of patients with HER2-positive breast cancer

Trastuzumab has improved survival in HER2-positive breast cancer but is associated with left ventricular dysfunction (LVEF). Knowledge is limited regarding how this may restrict use in a clinical setting. This study investigated the feasibility of Trastuzumab treatment and its potential impacts on clinical outcomes.

A single-center, retrospective, hospital chart-based cohort study of HER2-positive breast cancer patients (2007-2021). Outcomes included reasons for treatment interruptions, ≥10% LVEF reduction, all-cause mortality, and breast cancer recurrence.

Patients were stratified based on Trastuzumab feasibility: A) Full treatment according to protocol; B) Full treatment with interruptions; C) Premature discontinuation; D) Non-initiation. Logistic regression identified predictors of treatment interruption or non-initiation. All-cause mortality was analyzed using Kaplan-Meier estimates, and breast cancer recurrence was assessed using cumulative incidence analysis with death as a competing risk.

The analysis included 560 patients. Among patients treated with Trastuzumab, 71 patients (14.8%) interrupted treatment: 19 with temporary pauses and 52 with premature discontinuation.

LVEF reduction was the primary reason for interruptions.

Non-initiation was predicted by increasing age, type of surgery, and absence of radiotherapy (p≤0.015). Pausing treatment was associated with low baseline LVEF and Epirubicin use (p≤0.039). Discontinuation predictors included smoking, hypertension, and low baseline LVEF (p≤0.035). A total of 10.9% of patients treated with Trastuzumab experienced LVEF reductions during treatment. Of these, only 36.5% were assessed by cardiologists, mostly post-discontinuation. For recurrence the cumulative incidence showed that Group B (temporary interruptions) differed significantly from all other groups (p≤0.002). All-cause mortality analysis revealed that Groups A and B showed significantly better survival outcomes than Groups C and D (p≤0.04)

LVEF reduction was the primary cause of Trastuzumab interruptions. Temporary interruptions did not compromise outcomes, showing favorable results despite interruptions. These findings suggest that temporary interruptions in Trastuzumab treatment may not necessarily compromise patient prognosis, underscoring the complexity and need for improved cardiac management to optimize Trastuzumab adherence and patient prognosis.