EPIC Working Groups - Cancer Working Groups

The Breast Cancer Working Group

Breast cancer is the most common cancer in women worldwide. The EPIC Breast Cancer Working Group investigates diet and lifestyle, hormonal, metabolic and genetic factors in relation to breast cancer development and mortality.

Breast cancer is now known to be a heterogeneous disease, with different phenotypes that are likely to have different risk factors. Therefore, the major focus of the Working Group over the past years has been the collection, centralization, and harmonization of receptor status data of tumours, allowing the study of breast cancer risk factors by subtypes.

The main results on breast cancer in EPIC are summarized below.

  • Diet

Results from EPIC found a statistically significant increase in risk of breast cancer in relation to consumption of alcohol,1 for all subtypes of breast cancer. EPIC results also indicate that women with high consumption of alcohol and low consumption of fibre had the highest risk of breast cancer.2 Subsequent analyses suggested that a hormonal signature, reflecting lower levels of sex hormone binding globulin and higher levels of sex steroids may mediated a substantial proportion of the association between alcohol and postmenopausal breast cancer.3

In EPIC, a statistically significant increased risk of breast cancer was also observed with consumption of saturated fat.4 The association with saturated fat intake was more evident in postmenopausal women who never used hormone therapy. In addition, elevated plasma levels of trans-fatty acids, measured in EPIC samples, were associated with an increased risk of estrogen receptor (ER) negative tumours, while an increased synthesis of palmitoleic acid, a marker of de novo lipogenesis, was associated with an increase in overall breast cancer risk.5

A high vegetable intake was associated with lower (mainly hormone receptor-negative) breast cancer risk6 and higher concentrations of plasma ß-carotene and α-carotene were associated with lower breast cancer risk of ER-negative tumours.7

  • Overweight, obesity, and physical activity

In postmenopausal women, overweight (expressed as body mass index [BMI]) was a significant predictor of breast cancer risk8 and high weight gain in middle adulthood increased the risk of breast cancer.9 Moderate and high levels of physical activity, combining recreational and household activities, were associated with a reduced risk, independently of the level of overweight.10

More globally, a healthy lifestyle characterized by a healthy diet, moderate and vigorous-intensity physical activity, avoidance of smoking and alcohol consumption and low BMI was associated with a decreased risk of postmenopausal breast cancer.11

  • Active and passive smoking

Data from EPIC, together with results from other recent cohort studies, suggest that smoking is associated with increased breast cancer risk. Our results provide an important replication, that smoking (passively or actively) increases breast cancer risk and that smoking between menarche and first full-term pregnancy is particularly deleterious.12

  • Endogenous hormones

Data derived from EPIC have also shown that endogenous sex steroid hormones are associated with risk of hormone receptor-positive breast cancer in postmenopausal women.13 Furthermore, in premenopausal women, elevated levels of androgens were associated with an increased risk of breast cancer. Integrating hormone measurements in clinical risk prediction models slightly improved breast cancer risk stratification.14

  • -Omics

EPIC contributed data to the NCI Breast and Prostate Cancer Cohort Consortium (BPC3) where genome-wide association studies were performed and novel loci associated with ER-negative breast cancer identified.15

Epigenetics data have also been acquired on about 500 case-control pairs from EPIC and showed that epigenetic age acceleration and CpG island methylation have a weak, but statistically significant, association with breast cancer risk.16

Targeted metabolomics applied on EPIC samples allowed the identification of novel metabolic pathways potentially involved in breast cancer development, with some metabolites showing positive associations with breast cancer(acylcarnitine C2) while others were inversely associated with risk (several phosphatidylcholines and amino acids).17

The working group is currently working on combining all -omics data generated on EPIC samples, together with lifestyle and dietary data. This will allow comprehensive analyses that could lead to the identification of novel biological pathways pointing either to new risk factors or providing further insight on known relationships between lifestyle and breast cancer.

Selected publications:

  1. Romieu I, Scoccianti C, Chajes V, de Batlle J, Biessy C, Dossus L, Baglietto L, Clavel-Chapelon F, Overvad K, Olsen A, et al: Alcohol intake and breast cancer in the European prospective investigation into cancer and nutrition. Int J Cancer 2015, 137:1921-1930. PMID: 25677034

  2. Romieu I, Ferrari P, Chajes V, de Batlle J, Biessy C, Scoccianti C, Dossus L, Christine Boutron M, Bastide N, Overvad K, et al: Fiber intake modulates the association of alcohol intake with breast cancer. Int J Cancer 2017, 140:316-321. PMID: 27599758

  3. Assi N, Rinaldi S, Viallon V, Dashti SG, Dossus L, Fournier A, Cervenka I, Kvaskoff M, Turzanski-Fortner R, Bergmann M, et al: Mediation analysis of the alcohol-postmenopausal breast cancer relationship by sex hormones in the EPIC cohort. Int J Cancer 2020, 146:759-768. PMID: 30968961

  4. Sieri S, Krogh V, Ferrari P, Berrino F, Pala V, Thiébaut AC, Tjønneland A, Olsen A, Overvad K, Jakobsen MU, et al: Dietary fat and breast cancer risk in the European Prospective Investigation into Cancer and Nutrition. Am J Clin Nutr 2008, 88:1304-1312. PMID: 18996867

  5. Chajes V, Assi N, Biessy C, Ferrari P, Rinaldi S, Slimani N, Lenoir GM, Baglietto L, His M, Boutron-Ruault MC, et al: A prospective evaluation of plasma phospholipid fatty acids and breast cancer risk in the EPIC study. Ann Oncol 2017, 28:2836-2842. PMID: 28950350

  6. Emaus MJ, Peeters PH, Bakker MF, Overvad K, Tjonneland A, Olsen A, Romieu I, Ferrari P, Dossus L, Boutron-Ruault MC, et al: Vegetable and fruit consumption and the risk of hormone receptor-defined breast cancer in the EPIC cohort. Am J Clin Nutr 2016, 103:168-177. PMID: 26607934

  7. Bakker MF, Peeters PH, Klaasen VM, Bueno-de-Mesquita HB, Jansen EH, Ros MM, Travier N, Olsen A, Tjonneland A, Overvad K, et al: Plasma carotenoids, vitamin C, tocopherols, and retinol and the risk of breast cancer in the European Prospective Investigation into Cancer and Nutrition cohort. Am J Clin Nutr 2016, 103:454-464. PMID: 26791185

  8. Ritte R, Lukanova A, Berrino F, Dossus L, Tjonneland A, Olsen A, Overvad TF, Overvad K, Clavel-Chapelon F, Fournier A, et al: Adiposity, hormone replacement therapy use and breast cancer risk by age and hormone receptor status: a large prospective cohort study. Breast Cancer Res 2012, 14:R76. PMID: 22583394

  9. Emaus MJ, van Gils CH, Bakker MF, Bisschop CN, Monninkhof EM, Bueno-de-Mesquita HB, Travier N, Berentzen TL, Overvad K, Tjonneland A, et al: Weight change in middle adulthood and breast cancer risk in the EPIC-PANACEA study. Int J Cancer 2014, 135:2887-2899. PMID: 24771551

  10. Steindorf K, Ritte R, Eomois PP, Lukanova A, Tjonneland A, Johnsen NF, Overvad K, Østergaard JN, Clavel-Chapelon F, Fournier A, et al: Physical activity and risk of breast cancer overall and by hormone receptor status: the European prospective investigation into cancer and nutrition. Int J Cancer 2013, 132:1667-1678. PMID: 22903273

  11. McKenzie F, Ferrari P, Freisling H, Chajes V, Rinaldi S, de Batlle J, Dahm CC, Overvad K, Baglietto L, Dartois L, et al: Healthy lifestyle and risk of breast cancer among postmenopausal women in the European Prospective Investigation into Cancer and Nutrition cohort study. Int J Cancer 2015, 136:2640-2648. PMID: 25379993

  12. Dossus L, Boutron-Ruault MC, Kaaks R, Gram IT, Vilier A, Fervers B, Manjer J, Tjonneland A, Olsen A, Overvad K, et al: Active and passive cigarette smoking and breast cancer risk: results from the EPIC cohort. Int J Cancer 2014, 134:1871-1888. PMID: 24590452

  13. James RE, Lukanova A, Dossus L, Becker S, Rinaldi S, Tjonneland A, Olsen A, Overvad K, Mesrine S, Engel P, et al: Postmenopausal serum sex steroids and risk of hormone receptor-positive and -negative breast cancer: a nested case-control study. Cancer Prev Res (Phila) 2011, 4:1626-1635. PMID: 21813404

  14. Husing A, Fortner RT, Kuhn T, Overvad K, Tjonneland A, Olsen A, Boutron-Ruault MC, Severi G, Fournier A, Boeing H, et al: Added Value of Serum Hormone Measurements in Risk Prediction Models for Breast Cancer for Women Not Using Exogenous Hormones: Results from the EPIC Cohort. Clin Cancer Res 2017, 23:4181-4189. PMID: 28246273

  15. Siddiq A, Couch FJ, Chen GK, Lindström S, Eccles D, Millikan RC, Michailidou K, Stram DO, Beckmann L, Rhie SK, et al: A meta-analysis of genome-wide association studies of breast cancer identifies two novel susceptibility loci at 6q14 and 20q11. Hum Mol Genet 2012, 21:5373-5384. PMID: 22976474

  16. Ambatipudi S, Horvath S, Perrier F, Cuenin C, Hernandez-Vargas H, Le Calvez-Kelm F, Durand G, Byrnes G, Ferrari P, Bouaoun L, et al: DNA methylome analysis identifies accelerated epigenetic ageing associated with postmenopausal breast cancer susceptibility. Eur J Cancer 2017, 75:299-307. PMID: 28259012

  17. His M, Viallon V, Dossus L, Gicquiau A, Achaintre D, Scalbert A, Ferrari P, Romieu I, Onland-Moret NC, Weiderpass E, et al: Prospective analysis of circulating metabolites and breast cancer in EPIC. BMC Med 2019, 17:178. PMID: 31547832

Contact details/Working Group leader

Laure Dossus, PhD
Biomarkers Group (BMA)
International Agency for Research on Cancer (IARC/WHO)
25 avenue Tony Garnier
CS 90627
69366 LYON CEDEX 07