TY - JOUR
T1 - Contralateral breast cancer risk in patients with breast cancer and a germline-BRCA1/2 pathogenic variant undergoing radiation
AU - van Barele, Mark
AU - Akdeniz, Delal
AU - Heemskerk-Gerritsen, Bernadette A M
AU - Genepso
AU - Andrieu, Nadine
AU - Noguès, Catherine
AU - van Asperen, Christi J
AU - Wevers, Marijke
AU - Ausems, Margreet G E M
AU - de Bock, Geertruida H
AU - Dommering, Charlotte J
AU - Gómez-García, Encarnacion B
AU - van Leeuwen, Flora E
AU - Mooij, Thea M
AU - Easton, Douglas F
AU - Antoniou, Antonis C
AU - Evans, D Gareth
AU - Izatt, Louise
AU - Tischkowitz, Marc
AU - Frost, Debra
AU - Brewer, Carole
AU - Olah, Edit
AU - Simard, Jacques
AU - Singer, Christian F
AU - Thomassen, Mads
AU - Kast, Karin
AU - Rhiem, Kerstin
AU - Engel, Christoph
AU - de la Hoya, Miguel
AU - Foretová, Lenka
AU - Jakubowska, Anna
AU - Jager, Agnes
AU - Sattler, Margriet G A
AU - Schmidt, Marjanka K
AU - Hooning, Maartje J
PY - 2023/11/8
Y1 - 2023/11/8
N2 - BACKGROUND: Radiation-induced secondary breast cancer (BC) may be a concern after radiation therapy (RT) for primary breast cancer (PBC), especially in young patients with germline (g)BRCA-associated BC who already have high contralateral BC (CBC) risk and potentially increased genetic susceptibility to radiation. We sought to investigate whether adjuvant RT for PBC increases the risk of CBC in patients with gBRCA1/2-associated BC.METHODS: The gBRCA1/2 pathogenic variant carriers diagnosed with PBC were selected from the prospective International BRCA1/2 Carrier Cohort Study. We used multivariable Cox proportional hazards models to investigate the association between RT (yes vs no) and CBC risk. We further stratified for BRCA status and age at PBC diagnosis (<40 and >40 years). Statistical significance tests were 2-sided.RESULTS: Of 3602 eligible patients, 2297 (64%) received adjuvant RT. Median follow-up was 9.6 years. The RT group had more patients with stage III PBC than the non-RT group (15% vs 3%, P < .001), received chemotherapy more often (81% vs 70%, P < .001), and received endocrine therapy more often (50% vs 35%, P < .001). The RT group had an increased CBC risk compared with the non-RT group (adjusted hazard ratio [HR] = 1.44; 95% confidence interval [CI] = 1.12 to 1.86). Statistical significance was observed in gBRCA2 (HR = 1.77; 95% CI = 1.13 to 2.77) but not in gBRCA1 pathogenic variant carriers (HR = 1.29; 95% CI = 0.93 to 1.77; P = .39 for interaction). In the combined gBRCA1/2 group, patients irradiated when they were younger than or older than 40 years of age at PBC diagnosis showed similar risks (HR = 1.38; 95% CI = 0.93 to 2.04 and HR = 1.56; 95% CI = 1.11 to 2.19, respectively).CONCLUSIONS: RT regimens minimizing contralateral breast dose should be considered in gBRCA1/2 pathogenic variant carriers.
AB - BACKGROUND: Radiation-induced secondary breast cancer (BC) may be a concern after radiation therapy (RT) for primary breast cancer (PBC), especially in young patients with germline (g)BRCA-associated BC who already have high contralateral BC (CBC) risk and potentially increased genetic susceptibility to radiation. We sought to investigate whether adjuvant RT for PBC increases the risk of CBC in patients with gBRCA1/2-associated BC.METHODS: The gBRCA1/2 pathogenic variant carriers diagnosed with PBC were selected from the prospective International BRCA1/2 Carrier Cohort Study. We used multivariable Cox proportional hazards models to investigate the association between RT (yes vs no) and CBC risk. We further stratified for BRCA status and age at PBC diagnosis (<40 and >40 years). Statistical significance tests were 2-sided.RESULTS: Of 3602 eligible patients, 2297 (64%) received adjuvant RT. Median follow-up was 9.6 years. The RT group had more patients with stage III PBC than the non-RT group (15% vs 3%, P < .001), received chemotherapy more often (81% vs 70%, P < .001), and received endocrine therapy more often (50% vs 35%, P < .001). The RT group had an increased CBC risk compared with the non-RT group (adjusted hazard ratio [HR] = 1.44; 95% confidence interval [CI] = 1.12 to 1.86). Statistical significance was observed in gBRCA2 (HR = 1.77; 95% CI = 1.13 to 2.77) but not in gBRCA1 pathogenic variant carriers (HR = 1.29; 95% CI = 0.93 to 1.77; P = .39 for interaction). In the combined gBRCA1/2 group, patients irradiated when they were younger than or older than 40 years of age at PBC diagnosis showed similar risks (HR = 1.38; 95% CI = 0.93 to 2.04 and HR = 1.56; 95% CI = 1.11 to 2.19, respectively).CONCLUSIONS: RT regimens minimizing contralateral breast dose should be considered in gBRCA1/2 pathogenic variant carriers.
KW - BRCA1 Protein/genetics
KW - BRCA2 Protein/genetics
KW - Breast Neoplasms/genetics
KW - Cohort Studies
KW - Female
KW - Humans
KW - Prospective Studies
U2 - 10.1093/jnci/djad116
DO - 10.1093/jnci/djad116
M3 - Journal article
C2 - 37369040
SN - 0027-8874
VL - 115
SP - 1318
EP - 1328
JO - Journal of the National Cancer Institute
JF - Journal of the National Cancer Institute
IS - 11
ER -