1. PRECAMA multi-centre study: Molecular Subtypes of Premenopausal Breast Cancer in Latin American Women
Rinaldi S.1, Carayol M.1, Biessy C.1, Olivier M.1, Villar S.1, Porter P.2, Garmendia M.-L.3, Rodríguez A.-C.4, Porras C.5, Sánchez G.6, Torres G.7, Romieu I.1,7, on behalf of the PRECAMA team.
1 IARC, Lyon, France; 2 Fred Hutchinson Cancer Research Center, Seattle, USA; 3 Instituto de Nutrición y Tecnología de los Alimentos, Universidad de Chile, Chile; 4 National Cancer Institute Consultant, USA; 5 Fundación INCIENSA-Proyecto Epidemiológico Guanacaste, San Jose, Costa Rica; 6 Facultad de Medicina, Universidad de Antioquia, Colombia; 7 National Institute of Public Health, Mexico.
Table 1: Tumour characteristics
Table 2: Selected characteristics of the study population description, and association with breast cancer risk
Background
Breast cancer (BC) is the most common cancer among Latin American women with a high proportion of cancer occurring among premenopausal women. Little is known about risk factors, especially for aggressive phenotypes. We are conducting a multicenter, population-based, case-control study to evaluate risk factors of molecular subtypes of premenopausal BC in Latin America.
Methods
Cases and controls (aged 45 years or less) are recruited in Chile, Colombia, Costa Rica and Mexico (and soon from Brazil), and are matched by age and centre.
Standardized protocols are used to collect clinical and exposure data, biological specimens and tumour samples.
Molecular subtypes are defined by immunohistochemistry analysed at a central laboratory (Fred Hutchinson Cancer Research Center, USA) and further stratified by somatic mutation analyses using deep sequencing.
Preliminary statistical analyses were conducted using logistic regression models adjusting for potential confounding factors.
Fig. 1: Targeted sequencing of the tumours
Table 3: Description of selected reproductive variables by receptor status
Results
To date, the study includes 387 cases and 311 controls. The cases had fewer full-term pregnancies, higher ages at first and last pregnancy and shorter duration of breast-feeding compared with the controls.
Tumour characteristics of the cases are shown in Table 1, and results from targeted sequencing of the tumours are shown in Fig. 1.
Selected characteristics of the study population, and their associations with BC risk are shown in Tables 2 and 3, and Fig. 2. Later age at menarche was inversely related to the risk of ER- BC while no association was observed for ER+ BC. Higher age at first pregnancy and last pregnancy were associated with an increased risk of ER+ BC but not with ER- BC. Longer duration of breastfeeding was inversely associated with both ER+ and ER- BC. High intake of milk products, fruits, cereals and low intake of vegetables were associated with increased BC risk.
Somatic mutation screening in a sub-sample of the cases (n=41). A panel of 8 genes frequently mutated in BC was resequenced in DNA from tumour tissue. Overall, 63.4% (26/41) of samples had at least one somatic mutation with an allele frequency >= 5%. Mutation frequencies were similar to those reported in COSMIC (Catalogue of Somatic mutations in Cancer) database (left panel). The distribution of TP53 mutation showed a higher content of G>T mutations than observed in other series (right panel).
Fig. 2: Associations with dietary intakes
Conclusions
These preliminary results suggest that lifestyle factors are involved in the incidence of premenopausal breast cancer in Latin American women. Further analyses of a larger number of cases and controls in the near future will allow the risk factors for specific molecular subtypes to be determined. This will enhance target prevention, treatment and control of the disease.
Precama.iarc.fr
*p < 0.005