Assessment of the prognostic role of a 94-single nucleotide polymorphisms risk score in early breast cancer in the SIGNAL/PHARE prospective cohort: no correlation with clinico-pathological characteristics and outcomes.

BACKGROUND: Genome-wide association studies (GWAS) have to date identified 94 genetic variants (single nucleotide polymorphisms (SNPs)) associated with risk of developing breast cancer. A score based on the combined effect of the 94 risk alleles can be calculated to measure the global risk of breast cancer. We aimed to test the hypothesis that the 94-SNP-based risk score is associated with clinico-pathological characteristics, breast cancer subtypes and outcomes in early breast cancer. METHODS: A 94-SNP risk score was calculated in 8703 patients in the PHARE and SIGNAL prospective case cohorts. This score is the total number of inherited risk alleles based on 94 selected SNPs. Clinical data and outcomes were prospectively registered. Genotyping was obtained from a GWAS. RESULTS: The median 94-SNP risk score in 8703 patients with early breast cancer was 77.5 (range: 58.1-97.6). The risk score was not associated with usual prognostic and predictive factors (age; tumor, node, metastasis (TNM) status; Scarff-Bloom-Richardson grade; inflammatory features; estrogen receptor status; progesterone receptor status; human epidermal growth factor receptor 2 (HER2) status) and did not correlate with breast cancer subtypes. The 94-SNP risk score did not predict outcomes represented by overall survival or disease-free survival. CONCLUSIONS: In a prospective case cohort of 8703 patients, a risk score based on 94 SNPs was not associated with breast cancer characteristics, cancer subtypes, or patients' outcomes. If we hypothesize that prognosis and subtypes of breast cancer are determined by constitutional genetic factors, our results suggest that a score based on breast cancer risk-associated SNPs is not associated with prognosis. TRIAL REGISTRATION: PHARE cohort: NCT00381901 , Sept. 26, 2006 - SIGNAL cohort: INCa RECF1098, Jan. 28, 2009.

Stage-related changes in functional capacity in Hodgkin's disease: assessment by cardiopulmonary exercise testing before initiation of treatment.

Our aim was to examine indices of cardiorespiratory capacity at rest and during exercise before initiation of therapy for Hodgkin's disease. We prospectively studied 24 patients divided into two groups according to the disease stage. Group 1 included eight patients in stage IA and four in stage IIA; group 2 included four patients in stage IIB, six in stage III, and two in stage IV. All patients underwent detailed cardiopulmonary evaluations at rest using electrocardiogram, echocardiogram, spirometry, and measurement of pulmonary diffusing capacity (DLCO), and during exercise using a cardiopulmonary exercise test. Groups 1 and 2 were similar with respect to sex distribution (eight women and four men in each), mean age (35+/-36 vs37+/-4.6 years), body mass index, and hemoglobin concentration (12.7+/-0.2 vs 12.1+/-0.3 g l-1). All patients had a normal cardiovascular status. All patients in group 1 had normal cardiorespiratory measurements at rest and during exercise. Forced vital capacity was significantly lower in group 2 (84.8+/-2.7% predicted) than in group 1 (105+/-3%, P<0.0001), without abnormalities in DLCO or in resting and exercise oxygen diffusion. Likewise, percentage predicted VO2max (65+/-4 vs 97+/-6, P<0.0002), oxygen pulse at peak exercise (0.12+/-0.01 vs 0.17+/-0.01, P<0.001), and DeltaVO2/DeltaW slope (8.4+/-0.3 vs 10.2+/-0.4, P<0.003) were significantly lower in group 2 than in group 1. Functional capacity during exercise was markedly reduced in patients suffering from Hodgkin's disease in advanced stages. This loss of exercise capacity appeared mainly related to a peripheral disorder.