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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.

Publication ,  Journal Article
Marcom, PK; Isaacs, C; Harris, L; Wong, ZW; Kommarreddy, A; Novielli, N; Mann, G; Tao, Y; Ellis, MJ
Published in: Breast Cancer Res Treat
March 2007

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.

Duke Scholars

Published In

Breast Cancer Res Treat

DOI

ISSN

0167-6806

Publication Date

March 2007

Volume

102

Issue

1

Start / End Page

43 / 49

Location

Netherlands

Related Subject Headings

  • Triazoles
  • Trastuzumab
  • Receptors, Estrogen
  • Receptor, erbB-2
  • Receptor, ErbB-2
  • Oncology & Carcinogenesis
  • Nitriles
  • Middle Aged
  • Letrozole
  • In Situ Hybridization, Fluorescence
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Marcom, P. K., Isaacs, C., Harris, L., Wong, Z. W., Kommarreddy, A., Novielli, N., … Ellis, M. J. (2007). 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, 102(1), 43–49. https://doi.org/10.1007/s10549-006-9307-8
Marcom, P Kelly, Claudine Isaacs, Lyndsay Harris, Zee Wang Wong, Aruna Kommarreddy, Nellie Novielli, Gretchen Mann, Yu Tao, and Matthew J. Ellis. “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 102, no. 1 (March 2007): 43–49. https://doi.org/10.1007/s10549-006-9307-8.
Marcom PK, Isaacs C, Harris L, Wong ZW, Kommarreddy A, Novielli N, et al. 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.
Marcom, P. Kelly, et al. “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, vol. 102, no. 1, Mar. 2007, pp. 43–49. Pubmed, doi:10.1007/s10549-006-9307-8.
Marcom PK, Isaacs C, Harris L, Wong ZW, Kommarreddy A, Novielli N, Mann G, Tao Y, Ellis MJ. 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):43–49.
Journal cover image

Published In

Breast Cancer Res Treat

DOI

ISSN

0167-6806

Publication Date

March 2007

Volume

102

Issue

1

Start / End Page

43 / 49

Location

Netherlands

Related Subject Headings

  • Triazoles
  • Trastuzumab
  • Receptors, Estrogen
  • Receptor, erbB-2
  • Receptor, ErbB-2
  • Oncology & Carcinogenesis
  • Nitriles
  • Middle Aged
  • Letrozole
  • In Situ Hybridization, Fluorescence