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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

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Abstract

Background

Estrogen receptor (ER) and/or progesterone receptor expression occurs in ∼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.

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Authors and Affiliations

  1. Siteman Comprehensive Cancer Center, Washington University School of Medicine, 660 South Euclid Ave, Campus Box 8056, St Louis, MO, USA

    Aruna Kommarreddy, Yu Tao & Matthew J. Ellis

  2. Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, USA

    Claudine Isaacs & Nellie Novielli

  3. Dana Farber Cancer Institute, Harvard University, Boston, MA, USA

    Lyndsay Harris

  4. Singapore National Cancer Institute, Singapore, Singapore

    Zee Wang Wong

  5. Duke Comprehensive Cancer Center, Duke University, Durham, NC, USA

    P. Kelly Marcom & Gretchen Mann

Authors
  1. P. Kelly Marcom
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  2. Claudine Isaacs
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  3. Lyndsay Harris
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  4. Zee Wang Wong
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  5. Aruna Kommarreddy
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  6. Nellie Novielli
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  7. Gretchen Mann
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  8. Yu Tao
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  9. Matthew J. Ellis
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Corresponding author

Correspondence to Matthew J. Ellis.

Additional information

Note: Aspects of this work were presented at the ASCO Annual Meeting 2005.

Disclosure: Washington University conflicts of interest committee requires the following disclosures. Novartis Pharma and Genentech provided financial support for this clinical trial. Dr␣M.J. Ellis is a paid consultant for Novartis and Genentech and has also received speaking honoraria.

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Marcom, P.K., Isaacs, C., Harris, L. 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 102, 43–49 (2007). https://doi.org/10.1007/s10549-006-9307-8

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  • DOI: https://doi.org/10.1007/s10549-006-9307-8

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