Faculty Collaboration Database

Concurrent or sequential letrozole with adjuvant breast radiotherapy: final results of the CO-HO-RT phase II randomized trial. Ann Oncol 2016 Mar;27(3):474-80

Date

12/19/2015

Pubmed ID

26681684

Pubmed Central ID

PMC4907345

DOI

10.1093/annonc/mdv602

Scopus ID

2-s2.0-84959905660 (requires institutional sign-in at Scopus site)   28 Citations

Abstract

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.

Author List

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

Author

Sarah L. Kerns PhD Associate Professor in the Radiation Oncology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Aged
Aged, 80 and over
Antineoplastic Agents
Apoptosis
Breast Neoplasms
Combined Modality Therapy
Female
Fibrosis
Genome-Wide Association Study
Humans
Middle Aged
Nitriles
Nuclear Proteins
Polymorphism, Single Nucleotide
Radiotherapy, Adjuvant
Triazoles