Concurrent or sequential letrozole with adjuvant breast radiotherapy: Final results of the CO-HO-RT phase II randomized trial

C. Bourgier, S. Kerns, S. Gourgou, C. Lemanski, M. Gutowski, P. Fenoglietto, G. Romieu, N. Crompton, J. Lacombe, A. Pèlegrin, M. Ozsahin, B. Rosenstein, David Azria

Research output: Contribution to journalArticlepeer-review

32 Scopus citations


Background: We present here final clinical results of the COHORT trial and both translational sub-studies aiming at identifying patients at risk of radiation-induced subcutaneous fibrosis (RISF): (I) radiation-induced lymphocyte apoptosis (RILA) and (ii) candidates of certain single-nucleotide polymorphisms (SNPs). Patients and methods: Post-menopausal patients with stage I-II breast cancer (n = 150) were enrolled and assigned to either concurrent (arm A) or sequential radiotherapy (RT)-letrozole (arm B). Among them, 121 were eligible for RILA and SNP assays. Grade ≥ 2 RISF were the primary end point. Secondary end points were lung and heart events and carcinologic outcome. RILA was performed to predict differences in RISF between individuals. A genome-wide association study was performed to identify SNPs associated with RILA and RISF. Analyses were done by intention to treat. Results: After a median follow-up of 74 months, 5 patients developed a grade ≥2 RISF. No significant difference was observed between arms A and B. Neither grade ≥ 2 lung nor symptomatic cardiac toxicity was observed. Median RILA value of the five patients who had grade ≥ 2 RISF was significantly lower compared with those who developed grade ≤ 1 RISF (6.9% versus 13%, P = 0.02). Two SNPs were identified as being significantly associated with RILA: rs1182531 (P = 4.2 × 10-9) and rs1182532 (P = 3.6 × 10-8); both located within the PHACTR3 gene on chromosome 20q13.33. Conclusions: With long-term follow-up, letrozole can safely be delivered concomitantly with adjuvant breast RT. Translational sub-studies showed that high RILA values were correlated with patients who did not develop RISF. Registered clinical trial: NCT00208273.

Original languageEnglish (US)
Pages (from-to)474-480
Number of pages7
JournalAnnals of Oncology
Issue number3
StatePublished - Mar 1 2016
Externally publishedYes


  • BReast cancer
  • Radiation-induced late effects
  • Radio-hormonotherapy

ASJC Scopus subject areas

  • Hematology
  • Oncology


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