# Clinical Significance of Achieving No Evidence of Disease in HER2-Positive Metastatic Breast Cancer: A Multicenter Study by Turkish Oncology Group (TOG)

## TL;DR

A subset of HER2-positive metastatic breast cancer patients can achieve long-term disease control, with no evidence of disease being linked to better outcomes.

## Contribution

This study identifies radiologic no evidence of disease (NED) as a meaningful clinical outcome in HER2-positive metastatic breast cancer patients.

## Key findings

- Nearly half of long-term responders achieved radiologic NED after trastuzumab-based therapy.
- NED was associated with significantly longer progression-free survival compared to non-NED patients.
- ECOG performance status, HER2 IHC 3+ expression, and high-grade tumors predicted NED attainment.

## Abstract

Although HER2-positive metastatic breast cancer is generally considered incurable, a subset of patients can experience durable disease control with anti-HER2 therapy. In this multicenter retrospective study, we examined the clinical significance of achieving radiologic no evidence of disease (NED) in patients who remained progression-free for at least 36 months after first-line trastuzumab-based treatment. Nearly half of these long-term responders achieved radiologic NED, and this status was associated with longer progression-free survival. Better performance status, HER2 IHC 3+ expression, and high-grade tumors were associated with a greater likelihood of achieving NED. These findings suggest that radiologic NED may be a clinically meaningful response state in selected patients with HER2-positive metastatic breast cancer. However, because this study was retrospective and restricted to long-term responders, the results should be interpreted cautiously and confirmed in prospective studies.

Background: Achieving no evidence of disease (NED) in HER2-positive metastatic breast cancer (MBC) has been proposed as a response-state marker for durable disease control. However, its clinical significance and predictive factors are not yet well established. Methods: In this multicenter retrospective study at 13 oncology centers in Turkey, we analyzed 118 patients with stage IV HER2-positive MBC who received trastuzumab-based first-line therapy and remained progression-free for at least 36 months. Patients were stratified by radiologically defined NED status according to RECIST v1.1. Clinicopathological features were compared between groups, and predictors of NED were identified using logistic regression. Progression-free survival (PFS) was estimated by Kaplan–Meier analysis and assessed with Cox regression. Results: Of the 118 patients, 55 (46.6%) achieved NED. Compared with patients who did not achieve NED, those attaining NED were younger (median 46 vs. 53 years, p = 0.013), had better ECOG performance status (p = 0.005), were more likely to have HER2 IHC 3+ status (p = 0.015), and higher histologic grade tumors (p = 0.013). In multivariable logistic regression, ECOG PS 0 (vs. 1 ; OR = 5.99, p = 0.005), HER2 IHC 3+ (vs. IHC 2+/ISH+; OR = 4.79, p = 0.035), and histologic grade ≤2 (vs. grade 3 ; OR = 0.25, p = 0.011) were independently associated with NED attainment. Patients who achieved NED had experienced significantly longer PFS than those who did not (median 131 months vs. 66 months; p < 0.005). In multivariate Cox regression, NED remained independently associated with prolonged PFS (HR = 0.24, p = 0.003). Metastasis-directed local therapy and treatment regimen (trastuzumab vs. trastuzumab + pertuzumab) were not independently associated with NED attainment or PFS. Conclusions: In this multicenter cohort of pre-selected long-term responders, nearly half of HER2-positive MBC patients achieved radiologic NED. Radiologic NED was independently associated with prolonged PFS within this enriched population. Factors associated with NED attainment included favorable ECOG performance status, HER2 IHC 3+ expression, and high tumor grade; given the wide confidence intervals, these estimates should be interpreted cautiously as exploratory and hypothesis-generating.