Breast Cancer The PRECAMA Study Dr. Isabelle Romieu Head, Section of Nutrition and Metabolism
Estimated incidence of breast cancer (2008) Age- standardised rates per 100,000 GLOBOCAN 2008 (globocan.iarc.fr)
Estimated age-standardised incidence and mortality rates in Moroccan Women
Nutrition- Energy Balance, and Breast Cancer Factors that modify the risk of BC in premenopausal women: Decrease Increase Ø Convincing: Breastfeeding Alcohol Ø Probable: Adiposity Height Greater Birth weight Ø Limited (sug): Physical Activity Ø Limited (incon): Foods and nutrients Factors that modify the risk of BC in post-menopausal women Decrease Increase Ø Convincing: Breastfeeding Alcohol Body fatness Height Ø Probable: Physical Activity Abdominal fatness, weight gain Ø Limited (sug): Total fat Ø Limited (incon): Foods and nutrients WCRF/AICR, 2007
Prevalence of BMI >30 population over 15 years by gender Women Men WHO
Obesity in women Morocco Obesity among women increased from 6.4% to 16% between 1984/1985 to1998/1999 in women. The prevalence of obesity was 20.9 % in women and 6.0 % in men (P < 0.0001) The prevalence of overweight was 32.9 % in women v. 26.8 % in men (P < 0.0001). In women, the risk of obesity and overweight increased with age, with the highest risk being in individuals aged 45-54 years (OR = 3.02, 95 % CI 2.06, 4.44) compared to individuals <35 years old. Married women were more prone to obesity and overweight (OR = 2.42, 95 % CI 1.50, 3.91) than single women. Rguibi M. 2005;El Rhazi K 2011
Sedentary Behavior. Less than 30 minutes of moderate physical activity (equivalent to brisk walking) on fewer than 5 days/week, or less than 20 minutes of vigorous physical activity (equivalent to running) on fewer than 3 days/ week.
Correlates of physical activity in Morocco. Population based survey with IPAQ Mean age was 41.4 years (26.2-56.6). Of the 2613 subjects, 48.1% were women and 58% lived in urban areas. The prevalence of the lowest physically active category was 16.5% overall, 24% in women and 9% in men (p < 0.001). Unemployed (18.6%) and retired individuals (17.9%), housewives (28.2%) and married persons (19.7%) reported lower levels of physical activity. In women, the main determinants of low PA levels were living in an urban area and being a housewife. Najdi A et al Prev Med 2011
Carbohydrate, GI/GL and Breast Cancer Insulin may affect breast cancer risk by direct mitogenic effects or by increased levels of IGF-1 Null results for overall association in most prospective studies Dietary carbohydrates may increase breast cancer primarily in individuals with underlying insulin resistance Carbohydrate intake may increase ER - breast cancer risk Cho et al., Cancer Epidemiol Biomark Prev 2003; Nielsen et al., J Nutr 2005
Glycemic load, Carbohydrate intake and Breast Cancer (ER - ) in Postmenopausal women- EPIC Romieu I et al in press AJCN
Fiber Intake and Breast Cancer- EPIC Cases/PY HR 95%CI Total dietary fiber < 17.6 (17.6-20.2] (20.2-22.8] (22.8-26.3] > 26.3 Fiber from vegetables < 2.5 (2.5-3.7] (3.7-5.0] (5.0-6.9] > 6.9 Fiber from fruits < 2.2 (2.2-3.5] (3.5-4.9] (4.9-6.9] > 6.9 2364/742695 2369/725641 2236/727601 2291/732849 2316/741653 2297/747592 2376/734830 2351/736099 2340/730114 2212/721805 2199/726980 2306/728655 2246/731516 2388/738673 2437/744616 1.00 1.01 0.93 0.93 0.95 1.00 1.00 0.96 0.94 0.90 1.00 1.01 0.96 0.96 0.97 0.96-1.07 0.88-0.99 0.87-0.99 0.89-1.01 0.94-1.06 0.90-1.02 0.88-1.00 0.84-0.96 0.95-1.07 0.90-1.02 0.90-1.02 0.91-1.04 P-trend p = 0.03 p = <0.001 p = 0.24 Fiber from cereals < 4.7 (4.7-6.4] (6.4-8.3] (8.3-10.9] > 10.9 2321/738095 2345/737905 2344/738138 2235/732043 2331/724258 1.00 1.01 1.02 1.00 1.01 0.95-1.07 0.96-1.09 0.94-1.06 0.95-1.08 p = 0.84 0.85 0.95 1.05 HR Models were stratified by study center and age, adjusted by menopausal status, weight, height, smoking status, level of schooling, physical activity, age at menarche, age at first full-term birth, ever use of contraceptive pill, ever use of hormones, energy intake, alcohol; Ferrari et al., submitted
Daily energy and macronutrient intakes among Moroccan women by BMI class Mokhtar N et al 2001
Vitamin D and Breast Cancer Khan QJ et al, 2010
Vitamin D and Breast Cancer CAMA study- Mexico Vit D tertiles Cases/Controls OR 95%CI P-trend ng/ml ALL 20 313/232 1.00 21-25 156/208 0.69 0.48-0.97 > 25 104/199 0.53 0.36-0.78 P = 0.001 PRE 20 98/89 1.00 21-25 58/82 0.75 0.41-1.40 > 25 38/87 0.40 0.20-0.81 P = 0.01 POST 20 213/137 1.00 21-25 98/124 0.63 0.40-0.99 > 25 65/105 0.55 0.33-0.90 P = 0.01 0.25 0.5 1 Odds ratios were adjusted for BMI, height, FHBC, age at first full term pregnancy, number of full term pregnancies, social economic status, use of exogeneous hormones, physical activity, breast feeding, alcohol consumption, energy intake and season of blood collection. Fedirko V et al, CCC
BC phenotypes Understanding BC etiology? Data support the hypothesis that different patterns of receptor expression correspond to different types of breast tumor. Thus, we suggest that it would be prudent to divide breast cancer cases according to hormone receptor status (ER, PR, HER2 ) and status of the tumor. This categorization may also be useful in understanding differences in breast cancer risk profiles among ethnic groups (e.g. Caucasian versus African American), where the mix of ER/PR types may differ. Colditz G, 2004
PRECAMA Molecular Subtypes of Premenopausal Breast Cancer in La;n American Women: A mul;center popula;on based case- control study
Opportunity For Cancer Research on Cancer Etiology in Latin America Rapid epidemiological transition with increasing trends in cancer and NCDs Rapid nutritional transition Rapid change in life style Variability in food intake Micronutrient deficiencies Different life styles and environmental exposures Different ethnic groups and population admixture
Molecular Subtypes of Premenopausal Breast Cancer in Latin American Women: PRECAMA Multicenter population based case-control study. Breast cancer is a leading cause of death in Latin America Large number of incident cases among premenopausal women Little information on breast cancer phenotypes (i.e. receptors status) and specific risk factor Limited data suggest more aggressive types of tumors BC in Hispanic could comprise distinct subtypes Specific subtypes are likely to have different risk factor profiles Major relevance for treatment and preventive actions Participating countries: Brazil, Chile, Colombia, Costa Rica and Mexico
Objectives and hypothesis Advance the prevention and management of BC in Latin America (LA) through a better understanding of their molecular, pathological and risk factor patterns Develop a multi-centric case-control study on BC in centers across LA with structured collection of individual, clinical, pathological information and biological specimens according to strictly controlled protocols Characterize the subtypes of premenopausal BC on the basis of their molecular and pathological phenotypes Improve the identification of specific endogenous and exogenous factors and disentangle the interplay of these different factors with regard to breast tumor subtypes and other characteristics. Through these activities, provide advanced training, induce a structuring effect on the BC research community in LA and influence the public health agenda regarding the management of BC.
PRECAMA Study Standardized protocol for clinical and exposure data (reproductive history, lifestyle, anthropometry, diet, environment) biological specimens, and tumor sampling and analyses Recruitment of 500 cases/500 controls per centers (expected 2000 cases/ 2000 controls) Molecular subtypes of premenopausal BC (FHCRC and MAC, IARC) Classification into Luminal A, Luminal B, Basal like, HER2+/ERbased on IHC biomarkers (ER,PR, HER2, EGFR,CK5/6, Ki67) Analyses of tumor DNA for TP53 mutations (classification into non mutated (WT) and mutated subtypes) Identification of specific endogenous risk factors for specific subtypes of BC DNA extraction from lymphocytes to assess population admixture (AIMS), mutations in BC susceptibility genes (BRCA1, BRCA2,TP53) and specific SNPs
PRECAMA Study Exogenous risk factors for specific subtypes of BC Socio-demographic factors, ethnicity, reproductive and clinical history, use of hormones and family history of cancer Body silhouette at different ages Anthropometric measurements Life style factors Occupation, environmental risk factors Diet (FFQ) Physical activity Biomarkers (blood) Lipid profile, C-peptide, IGF1, IGFBP3, estrone Nutritional biomarkers such as folate, vitamin D and fatty acids Metabolomic analyses (urine)
Current Status Procols have been finalized Research and ethical committee approval from participating centres Development of website Pilot work is starting mid-april( Chile, Costa Rica, Columbia, Mexico Samples of Tumor slides will be send FHCRC for IHC analyses and simultaneous analyses within research study centers Part of blood and urinary samples will be sent at IARC for biological markers analyses Analysis of tumor mutations will be conducted at IARC Training of Latin American Scientists Plan to include other LA countries Plan to include follow up of cases to assess determinants of survival
IARC Collaborators Amina Amadou Carine Biessy Veronique Chajes Pietro Ferrari Veronika Fedirko Sabina Rinaldi Nadia Slimani romieui@iarc.fr