Effects of trastuzumab on locoregional recurrence in human epidermal growth factor receptor 2-overexpressing breast cancer patients treated with chemotherapy and radiotherapy

Breast Cancer Res Treat. 2018 Dec;172(3):619-626. doi: 10.1007/s10549-018-4966-9. Epub 2018 Sep 12.

Abstract

Purpose: In the present study, the ability of adjuvant trastuzumab to reduce locoregional recurrence in patients with human epidermal growth factor receptor 2 (HER2)-overexpressing breast cancer receiving adjuvant chemotherapy and radiotherapy (RT) was investigated.

Materials and methods: We retrospectively included 520 patients with HER2-overexpressing breast cancer who received surgery followed by adjuvant RT and cytotoxic chemotherapy from 2003 to 2011. Adjuvant trastuzumab was administered to 286 patients. Propensity score matching was conducted to compare trastuzumab-treated and non-treated cohorts.

Results: Median follow-up duration was 7.1 years (range 1.1-14.1 years). Propensity score matching yielded 171 matched pairs of patients with no significantly different clinical factors. An improved 7-year locoregional control (LRC) rate was observed in the trastuzumab-treated cohort compared with the non-treated cohort (95.6% vs. 89.9%, p = 0.014). Based on multivariate analysis, hormone receptor negativity (hazard ratio [HR] = 5.348, p = 0.007), positive lymph node ratio > 0.25 (HR = 2.549, p = 0.040), and lack of adjuvant trastuzumab (HR = 3.401, p = 0.017) were identified as significant risk factors for poor LRC. Adjuvant trastuzumab significantly reduced the locoregional recurrence rate in patients with one or two risk factors (7-year LRC = 95.0% vs. 84.2%, p = 0.007); however, the benefit of adjuvant trastuzumab was non-significant in patients with no risk factors (7-year LRC = 95.8% vs. 97.9%, p = 0.75).

Conclusions: Adjuvant trastuzumab improved LRC in patients with HER2-overexpressing breast cancer receiving adjuvant RT and cytotoxic chemotherapy, especially in hormone receptor-negative, HER2-enriched subtype, and high positive lymph node ratio breast cancer.

Keywords: Locoregional control; Modern chemotherapy; Radiotherapy; Trastuzumab.

MeSH terms

  • Adult
  • Antineoplastic Agents, Immunological / administration & dosage
  • Antineoplastic Agents, Immunological / adverse effects
  • Antineoplastic Agents, Immunological / therapeutic use*
  • Biomarkers, Tumor
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / mortality
  • Breast Neoplasms / pathology
  • Breast Neoplasms / therapy*
  • Combined Modality Therapy
  • Female
  • Follow-Up Studies
  • Gene Expression*
  • Humans
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Recurrence, Local
  • Neoplasm Staging
  • Propensity Score
  • Receptor, ErbB-2 / genetics*
  • Receptor, ErbB-2 / metabolism
  • Retreatment
  • Retrospective Studies
  • Time-to-Treatment
  • Trastuzumab / administration & dosage
  • Trastuzumab / adverse effects
  • Trastuzumab / therapeutic use*
  • Treatment Failure
  • Treatment Outcome

Substances

  • Antineoplastic Agents, Immunological
  • Biomarkers, Tumor
  • ERBB2 protein, human
  • Receptor, ErbB-2
  • Trastuzumab