title: Adjuvant radiotherapy for primary breast cancer in BRCA1 and BRCA2 mutation carriers and risk of contralateral breast cancer with special attention to patients irradiated at younger age.
abstract: The purpose of this study was to estimate the influence of adjuvant radiotherapy for primary breast cancer (BC) on the risk of contralateral BC (CBC) in BRCA1 or BRCA2 (BRCA1/2) mutation carriers, with special attention to patients irradiated at age younger than 40 years. Additionally, tendencies in locoregional treatments and rates of contralateral risk-reducing mastectomy over time were explored. In this retrospective cohort study, 691 BRCA1/2-associated BC patients treated between 1980 and 2013 were followed from diagnosis until CBC or censoring event including ipsilateral BC recurrence, distant metastasis, contralateral risk-reducing mastectomy, other invasive cancer diagnosis, death, or loss to follow up. Hazard ratios (HR) for CBC associated with radiotherapy were estimated using Cox regression. Median follow-up time was 8.6 years [range 0.3–34.3 years]. No association between radiotherapy for primary BC and risk of CBC was found, neither in the total population (HR 0.82, 95 % CI 0.45–1.49) nor in the subgroup of patients younger than 40 years at primary diagnosis (HR 1.36, 95 % CI 0.60–3.09). During follow-up, the number of patients at risk decreased substantially since a large proportion of patients were censored after contralateral risk-reducing mastectomy or BC recurrence. Over the years, increasing preference for mastectomy without radiotherapy compared to breast-conserving surgery with radiotherapy was found ranging from less than 30 % in 1995 to almost 50 % after 2010. The rate of contralateral risk-reducing mastectomy increased over the years from less than 40 % in 1995 to more than 60 % after 2010. In this cohort of BRCA1/2-associated BC patients, no association between radiotherapy for primary BC and risk of CBC was observed in the total group, nor in the patients irradiated before the age of 40 years. The number of patients at risk after 10 and 15 years of follow-up, however, was too small to definitively exclude harmful effects of adjuvant radiotherapy.
authors.forename: Jan
authors.initials: J
authors.lastname: Drooger
authors.forename: Delal
authors.initials: D
authors.lastname: Akdeniz
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Pignol
authors.forename: Linetta B
authors.initials: LB
authors.lastname: Koppert
authors.forename: Danielle
authors.initials: D
authors.lastname: McCool
authors.forename: Caroline M
authors.initials: CM
authors.lastname: Seynaeve
authors.forename: Maartje J
authors.initials: MJ
authors.lastname: Hooning
authors.forename: Agnes
authors.initials: A
authors.lastname: Jager
mesh_terms: D000328:Adult; D000368:Aged; D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; D005260:Female; D006801:Humans; D008408:Mastectomy; D008875:Middle Aged; D009154:Mutation; D016609:Neoplasms, Second Primary / Q000235:genetics / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; D016016:Proportional Hazards Models; D018714:Radiotherapy, Adjuvant / Q000009:adverse effects*; D012307:Risk Factors
chemical_list: D019313:BRCA1 Protein; D024682:BRCA2 Protein