Abstract
The aim of this multicenter, prospective, longitudinal phase IV study was to establish the optimal duration of neoadjuvant letrozole that would allow breast conservation surgery (BCS) in patients with early breast cancer who were initially unsuitable. Primary, invasive, estrogen-receptor- and/or progesterone-receptor-positive breast cancer patients, with large tumors (≥T2 i.e., >20 mm) not initially suitable for BCS, received 2.5 mg letrozole p.o. daily. Patients continued treatment until they became eligible for BCS, progressed, failed to meet criteria for BCS and withdrew for scheduled mastectomy, withdrew for other reasons, or completed 12 months of letrozole treatment without a BCS decision being made. A total of 146 patients were enrolled; seven patients who did not have a valid postbaseline tumor assessment were excluded from the final efficacy analysis. At study closure, 69 % of patients (96 of 139) were eligible for BCS. The median time to achieve a tumor response sufficient to allow BCS with neoadjuvant letrozole was 7.5 months (95 % CI 6.3–8.5 months). Letrozole was well tolerated, and most adverse events were mild-to-moderate (grade 1–2). The results from this trial suggest that extended letrozole therapy in the neoadjuvant setting (7.5 months), as opposed to conventional treatment of 4 months, is optimal to achieve maximum reduction in tumor volume sufficient for BCS.
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Acknowledgments
The authors take full responsibility for the content of this publication and confirm that it reflects their viewpoint and medical expertise. They also wish to acknowledge StemScientific, funded by Novartis Pharmaceuticals UK, for providing editorial support. Novartis did not influence the content of the manuscript, nor did the authors receive financial compensation for authoring the manuscript. The authors would also like to acknowledge the following study investigators: Lester Barr, Hugh Bishop, Michael Dixon, Abigail Evans, Clive Griffith, Frances Kenny, Alison Lannigan, Duraisamy Ravichandran, Elizabeth Shah, Michael Shere, Alistair Thompson, Mysore Venkatachala, Constantinos Yiangou, and Charles Zammit.
Conflict of interest
Carolyn Cordiner, Nuala Moss, Ashu Gandhi, Chris Wilson, Gillian Ellis, Gerald Gui, and Anthony I. Skene declare that they have no conflicts of interest. Robert Carpenter has performed a consultant/advisory role for Novartis, and has received funding from Novartis. Julie C. Doughty has received remuneration from Pfizer and Novartis, and has performed a consultant/advisory role for Novartis and Roche. Chris Andrews is an employee and stock owner of Novartis.
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The study was performed in accordance with the International Conference on Harmonization Guidelines for Good Clinical Practice; applicable local regulations were observed along with ethical principles according to the Declaration of Helsinki.
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Carpenter, R., Doughty, J.C., Cordiner, C. et al. Optimum duration of neoadjuvant letrozole to permit breast conserving surgery. Breast Cancer Res Treat 144, 569–576 (2014). https://doi.org/10.1007/s10549-014-2835-8
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DOI: https://doi.org/10.1007/s10549-014-2835-8