Advances in screening and treatment have reduced mortality from breast cancer. Once the disease progresses to metastasis, survival is limited. We have initiated the SToRM clinical cohort to study the contribution of the patient’s genetic background to clinically relevant phenotypes in metastasis.
1502 women were included in SToRM at metastatic progression from March 2012 to May 2014. A genome wide association study was carried out in 1250 patients, using the Illumina HumanCore Exome chip set. This chip set is composed of over 250,000 variants designed to capture common variation across the genome, as well as over 200,000 variants in coding regions. Patients are followed through contact with their clinical team to capture information regarding their treatment and survival. SToRM is designed to complement the SIGNAL/PHARE cohort of over 10,000 early breast cancer patients.
Delay between primary diagnosis and metastasis (average 58.5 months (±73.5)), and tumor type (luminal like (n = 747), HER2 + (n = 249), triple negative (n = 194), is available for SToRM patients. As of April 2017, 875 deaths are reported. As expected, survival probability is highly correlated with tumor type (p = 2.27x10−38), with triple negative patients showing median survival after metastatic diagnosis of less than 24 months, while median survival for luminal and HER2+ patients is longer than 36 months. Overall, no variants show associations with survival. There are, however, borderline associations between a number of variants and survival among triple negative and HER2+ patients. As of July 2017, median follow-up in SIGNAL is 3.8 years, and 7 years in PHARE, 1497 patients have progressed, and 154 deaths have been reported.
Genetic variants are important factors of risk for developing breast cancer. We have just begun to scratch the surface of the wealth of data that the SIGNAL/PHARE and SToRM clinical cohorts provide with respect to genetics and response to treatment and survival among breast cancer patients. Understanding how genetic variants influence outcomes may lead to better understanding of breast cancer in general. Furthermore, genetic variants associated with response to treatment may be used as stratification variables in future clinical trials.
Clinical trial identification
SToRM: NCT01460186, SIGNAL/PHARE: NCT00381901/RECF1098
Legal entity responsible for the study
SToRM: Centre Léon Bérard, SIGNAL/PHARE: INCa
Foundation Cancer de Sein-Parlons On!, INCa
All authors have declared no conflicts of interest.