Her2/neu-positive disease does not increase risk of locoregional recurrence for patients treated with neoadjuvant doxorubicin-based chemotherapy, mastectomy, and radiotherapy

Int J Radiat Oncol Biol Phys. 2004 Aug 1;59(5):1337-42. doi: 10.1016/j.ijrobp.2004.02.018.

Abstract

Purpose: Preclinical data suggest that overexpression of Her2/neu confers cellular radioresistance. We retrospectively studied whether Her2/neu-positive disease was associated with locoregional recurrence (LRR) after postmastectomy radiotherapy (RT) for breast cancer.

Methods and materials: Data from 337 patients treated in four institutional prospective clinical trials neoadjuvant doxorubicin-based chemotherapy, mastectomy, and RT were reviewed. The trials were conducted between 1989 and 2000. Of the 337 patients, 108 (32%) had tumors that were tested for Her2/neu, with positivity defined by 3+ immunohistochemistry staining or gene amplification detected by fluorescence in situ hybridization. RT was delivered to the chest wall and draining lymphatics (median dose, 50 Gy) followed by a chest wall boost (median dose, 10 Gy).

Results: Thirty-two patients had Her2/neu-positive disease and 76 patients had Her2/neu-negative disease. The Her2/neu-positive tumors were associated with a greater rate of estrogen receptor-negative disease (p = 0.03), the presence of supraclavicular disease at diagnosis (p = 0.027), and a greater number of positive lymph nodes after chemotherapy (p = 0.026). Despite these adverse features, the actuarial overall LRR rate was roughly equivalent for the patients with Her2/neu-positive tumors vs. those with Her2/neu-negative tumors (5-year rate 17.5% vs. 13.9%, respectively; 10-year rate 17.5% vs. 18.9%, respectively; p = 0.757). On Cox regression analysis of LRR adjusted for N stage and estrogen receptor status, the hazard ratio for Her2/neu positivity was 0.89 (95% confidence interval, 0.31-2.59; p = 0.83).

Conclusion: Her2/neu overexpression does not appear to predispose to LRR after neoadjuvant doxorubicin-based chemotherapy, mastectomy, and RT.

MeSH terms

  • Adult
  • Antibiotics, Antineoplastic / therapeutic use
  • Breast Neoplasms / chemistry
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / therapy
  • Chemotherapy, Adjuvant
  • Clinical Trials as Topic
  • Confidence Intervals
  • Doxorubicin / therapeutic use
  • Drug Resistance, Neoplasm
  • Female
  • Humans
  • Lymphatic Metastasis
  • Mastectomy, Radical
  • Neoadjuvant Therapy
  • Neoplasm Proteins / metabolism*
  • Neoplasm Recurrence, Local / metabolism*
  • Radiation Tolerance
  • Receptor, ErbB-2 / metabolism*
  • Receptors, Estrogen / metabolism
  • Regression Analysis
  • Retrospective Studies

Substances

  • Antibiotics, Antineoplastic
  • Neoplasm Proteins
  • Receptors, Estrogen
  • Doxorubicin
  • Receptor, ErbB-2