Chemotherapy, Genetic Susceptibility, and Risk of Venous Thromboembolism in Breast Cancer Patients.
OBJECTIVE
Venous thromboembolism (VTE) is highly heritable and a serious complication of cancer and its treatment. We examined the individual and joint effects of chemotherapy and genetic susceptibility on VTE risk in patients with breast cancer.


METHODS
A Swedish population-based study including 4,261 women diagnosed with primary invasive breast cancer between 2001 and 2008 in Stockholm, followed until 2012. Risk stratification by chemotherapy and genetic susceptibility [a polygenic risk score (PRS), including nine established VTE loci] was assessed using Kaplan-Meier and flexible parametric survival analyses, adjusting for patient, tumor, and treatment characteristics.


RESULTS
In total, 276 patients experienced a VTE event during a median follow-up of 7.6 years. Patients receiving chemotherapy [HR (95% CI) = 1.98; 1.40-2.80] and patients in the highest 5% of the PRS [HR (95% CI) = 1.90; 1.24-2.91] were at increased risk of developing VTE. Chemotherapy and PRS acted independently on VTE risk and the 1-year cumulative incidence in patients carrying both risk factors was 9.5% compared with 1.3% in patients not having these risk factors (P < 0.001). Stratified analyses by age showed that the risk-increasing effect of PRS was stronger in older patients (P interaction = 0.04), resulting in an excess risk among genetically susceptible patients receiving chemotherapy aged ≥ 60 years (1-year cumulative incidence = 25.0%).


CONCLUSIONS
Risk stratification by chemotherapy and genetic susceptibility identifies patients with breast cancer at high VTE risk, who could potentially benefit from thromboprophylaxis. Our results further suggest that genetic testing is more informative in older patients with breast cancer. Clin Cancer Res; 22(21); 5249-55. ©2016 AACR.
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. judith.brand@ki.se.
Judith S
JS
Brand
Department of Oncology-Pathology, Radiumhemmet, Karolinska Institutet and Karolinska University Hospital, Cancer Centre Karolinska, Stockholm, Sweden.
Elham
E
Hedayati
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Keith
K
Humphreys
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.|Department of Pediatrics, Örebro University Hospital, Örebro, Sweden.
Jonas F
JF
Ludvigsson
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Anna L V
AL
Johansson
Department of Oncology-Pathology, Radiumhemmet, Karolinska Institutet and Karolinska University Hospital, Cancer Centre Karolinska, Stockholm, Sweden.
Jonas
J
Bergh
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Per
P
Hall
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Kamila
K
Czene
D001943:Breast Neoplasms / Q000150:complications* / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D012307:Risk Factors; D016019:Survival Analysis; D013548:Sweden; D054556:Venous Thromboembolism / Q000209:etiology* / Q000235:genetics*