The combination of letrozole and trastuzumab as first or second-line biological therapy produces durable responses in a subset of HER2 positive and ER positive advanced breast cancers

Breast Cancer Res Treat. 2007 Mar;102(1):43-9. doi: 10.1007/s10549-006-9307-8. Epub 2006 Aug 8.


Background: Estrogen receptor (ER) and/or progesterone receptor expression occurs in approximately 50% HER2 positive (HER2+) breast cancers and cross-talk between the estrogen and HER2 pathways promotes endocrine therapy resistance. The efficacy of the aromatase inhibitor letrozole in combination with trastuzumab was therefore tested in a Phase 2 study.

Methods: Patients with ER+ and/or PgR+ and HER2+ (IHC 2+ or 3+ or FISH+) advanced breast cancer were treated with trastuzumab plus letrozole until disease progression or unacceptable toxicity.

Results: Thirty-three patients were enrolled, of which thirty one were considered evaluable. The majority of patients (82%) had received tamoxifen and 82% had HER2 FISH+ and/or IHC 3+ tumors. Eight patients responded (1 CR and 7 PR) for an overall response rate (ORR) of 26% and a clinical benefit rate (CBR) of 52%. The median time to progression (TTP) was 5.8 months and the median duration of response (DOR) was 20.6+ months. Excluding IHC 2+, FISH- tumors, the OR was 24%, CBR 44%, TTP 5.5 months and DOR 17+ months. The combination was well tolerated with only two toxicity events requiring termination of study medication.

Conclusions: Combined trastuzumab and letrozole treatment for patients with HER2+ and ER+ advanced breast cancer produced durable responses consistently lasting at least 1 year in one quarter of the patients. While these data are promising for a subgroup, for half the patients, trastuzumab plus letrozole was inactive. This finding demonstrates ER+ HER2+ advanced disease is heterogeneous and additional agents will be required for optimal management based on targeted therapeutics alone.

Publication types

  • Clinical Trial, Phase II

MeSH terms

  • Adult
  • Aged
  • Antibodies, Monoclonal / administration & dosage*
  • Antibodies, Monoclonal / adverse effects
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Breast Neoplasms / chemistry
  • Breast Neoplasms / drug therapy*
  • Female
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization, Fluorescence
  • Letrozole
  • Middle Aged
  • Nitriles / administration & dosage*
  • Nitriles / adverse effects
  • Receptor, ErbB-2 / analysis*
  • Receptors, Estrogen / analysis*
  • Trastuzumab
  • Triazoles / administration & dosage*
  • Triazoles / adverse effects


  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Nitriles
  • Receptors, Estrogen
  • Triazoles
  • Letrozole
  • Receptor, ErbB-2
  • Trastuzumab