Real-World Impact of Adjuvant Anti-HER2 Treatment on Characteristics and Outcomes of Women With HER2-Positive Metastatic Breast Cancer in the ESME Program

Oncologist. 2023 Oct 3;28(10):e867-e876. doi: 10.1093/oncolo/oyad137.

Abstract

Background: Although adjuvant cancer treatments increase cure rates, they may induce clonal selection and tumor resistance. Information still lacks as whether (neo)adjuvant anti-HER2 treatments impact the patterns of recurrence and outcomes of HER2-positive (HER2+) metastatic breast cancer (MBC). We aimed to assess this in the large multicenter ESME real-world database.

Patients and methods: We examined the characteristics and outcomes (overall survival (OS) and progression-free survival under first-line treatment (PFS1)) of HER2+ patients with MBC from the French ESME program with recurrent disease, as a function of the previous receipt of adjuvant trastuzumab. Multivariable analyses used Cox models adjusted for baseline demographic, prognostic factors, adjuvant treatment received, and disease-free interval.

Results: Two thousand one hundred and forty-three patients who entered the ESME cohort between 2008 and 2017 had a recurrent HER2+ MBC. Among them, 56% had received (neo)adjuvant trastuzumab and 2.5% another anti-HER2 in this setting. Patients pre-exposed to trastuzumab were younger, had a lower disease-free interval, more HR-negative disease and more metastatic sites. While the crude median OS appeared inferior in patients exposed to adjuvant trastuzumab, as compared to those who did not (37.2 (95%CI 34.4-40.3) versus 53.5 months (95% CI: 47.6-60.1)), this difference disappeared in the multivariable model (HR = 1.05, 95%CI 0.91-1.22). The same figures were observed for PFS1.

Conclusions: Among patients with relapsed HER2+ MBC, the receipt of adjuvant trastuzumab did not independently predict for worse outcomes when adjusted to other prognostic factors.

Keywords: HER2 positive; anti-HER2-targeted agents; breast cancer; de novo metastatic; pertuzumab; trastuzumab.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols
  • Breast Neoplasms* / drug therapy
  • Breast Neoplasms* / pathology
  • Chemotherapy, Adjuvant*
  • Disease-Free Survival
  • Female
  • Humans
  • Progression-Free Survival
  • Receptor, ErbB-2* / genetics
  • Receptor, ErbB-2* / metabolism
  • Trastuzumab* / therapeutic use

Substances

  • Receptor, ErbB-2
  • Trastuzumab