title: Optimum duration of neoadjuvant letrozole to permit breast conserving surgery.
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.
authors.affiliation: Breast Unit, University College London Hospitals NHS Trust, 250 Euston Road, London, NW1 2PQ, UK, robert.carpenter@uclh.nhs.uk.
authors.forename: Robert
authors.initials: R
authors.lastname: Carpenter
authors.forename: Julie C
authors.initials: JC
authors.lastname: Doughty
authors.forename: Carolyn
authors.initials: C
authors.lastname: Cordiner
authors.forename: Nuala
authors.initials: N
authors.lastname: Moss
authors.forename: Ashu
authors.initials: A
authors.lastname: Gandhi
authors.forename: Chris
authors.initials: C
authors.lastname: Wilson
authors.forename: Chris
authors.initials: C
authors.lastname: Andrews
authors.forename: Gillian
authors.initials: G
authors.lastname: Ellis
authors.forename: Gerald
authors.initials: G
authors.lastname: Gui
authors.forename: Anthony I
authors.initials: AI
authors.lastname: Skene
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D047072:Aromatase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality / Q000601:surgery*; D005260:Female; D006801:Humans; D000077289:Letrozole; D015412:Mastectomy, Segmental; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D060787:Neoplasm Grading; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D009570:Nitriles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome; D014230:Triazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D047072:Aromatase Inhibitors; D009570:Nitriles; D014230:Triazoles; D000077289:Letrozole