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Letrozole plus GnRH analogue as preoperative and adjuvant therapy in premenopausal women with ER positive locally advanced breast cancer

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Abstract

Patients with large ER positive tumors candidate to preoperative chemotherapy may also benefit from a concurrent endocrine intervention, but this issue has been scarcely investigated due to concerns arising from unfavorable results emerged from an adjuvant trial of concurrent tamoxifen and chemotherapy. We retrospectively investigated the activity of letrozole plus GnRH analogue (GnRH-a) administered concurrently with preoperative chemotherapy and as adjuvant treatment in premenopausal women with locally advanced ER positive breast cancer consecutively admitted at the European Institute of Oncology. Results were compared with those of a non-randomized unmatched control group of premenopausal women with locally advanced ER positive breast cancer receiving preoperative chemotherapy, followed by tamoxifen and GnRH-a after surgery. Primary endpoints were pathological complete response (pCR) rate, decrease of Ki67 and disease free survival (DFS). One-hundred and nineteen women constituted the study group, while 95 patients served as controls. The pCR rate was 5.0 vs 1.1% in the study and control group, respectively. A statistically significant greater suppression of Ki67 was observed in patients receiving chemoendocrine therapy as compared with controls (P = 0.003). At a median follow up of 59 months, 26 events occurred in the chemoendocrine group and 48 in the control group. Five-year DFS was 78 vs 41% in the study and in the control group, respectively [adjusted HR 0.46, 95% CI 0.27–0.79, P = 0.0047]. The concurrent administration of letrozole and GnRH-a with preoperative chemotherapy was highly effective in premenopausal women with large ER positive breast cancer in terms of decreased proliferation and of improved DFS. Randomized studies are warranted to establish the role of the addition of endocrine therapy to chemotherapy as standard preoperative approach for ER positive locally advanced breast cancer as well as of letrozole in combination with GnRH-a for the treatment of premenopauasal women with early breast cancer.

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Acknowledgment

The authors are indebted to Novartis FARMA S.p.A. for the help in the revision of English format.

Conflict Of Interest

The authors declare they have no conflict of interest.

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Authors and Affiliations

  1. Research Unit of Medical Senology at the Department of Medicine, European Institute of Oncology, Milano, Italy

    Rosalba Torrisi, Eloise Scarano, Monica Iorfida & Marco Colleoni

  2. Department of Oncology and Hematology, Humanitas Cancer Center, Rozzano, Milano, Italy

    Rosalba Torrisi & Armando Santoro

  3. Division of Epidemiology and Biostastistics, European Institute of Oncology, Milano, Italy

    Vincenzo Bagnardi & Nicole Rotmensz

  4. Department of Statistics University of Milano Bicocca, Milano, Italy

    Vincenzo Bagnardi

  5. Frontier Science and Technology Research Foundation Southern Europe, Milano, Italy

    Vincenzo Bagnardi

  6. Division of Senology, European Institute of Oncology, Milano, Italy

    Paolo Veronesi & Alberto Luini

  7. Medical School, University of Milano, Milano, Italy

    Paolo Veronesi & Giuseppe Viale

  8. Division of Pathology, European Institute of Oncology, Milano, Italy

    Giuseppe Viale

  9. Department of Medicine, European Institute of Oncology, Milano, Italy

    Aron Goldhirsch

Authors
  1. Rosalba Torrisi
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  2. Vincenzo Bagnardi
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  4. Eloise Scarano
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Correspondence to Rosalba Torrisi.

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Torrisi, R., Bagnardi, V., Rotmensz, N. et al. Letrozole plus GnRH analogue as preoperative and adjuvant therapy in premenopausal women with ER positive locally advanced breast cancer. Breast Cancer Res Treat 126, 431–441 (2011). https://doi.org/10.1007/s10549-010-1340-y

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  • DOI: https://doi.org/10.1007/s10549-010-1340-y

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