Dairy foods, calcium, and risk of breast cancer overall and for subtypes defined by estrogen receptor status: a pooled analysis of 21 cohort studies

You Wu; Ruyi Huang; Molin Wang; Leslie Bernstein; Traci N Bethea; Chu Chen; Yu Chen; A Heather Eliassen; Neal D Freedman; Mia M Gaudet; Gretchen L Gierach; Graham G Giles; Vittorio Krogh; Susanna C Larsson; Linda M Liao; Marjorie L McCullough; Anthony B Miller; Roger L Milne; Kristine R Monroe; Marian L Neuhouser; Julie R Palmer; Anna Prizment; Peggy Reynolds; Kim Robien; Thomas E Rohan; Sven Sandin; Norie Sawada; Sabina Sieri; Rashmi Sinha; Rachael Z Stolzenberg-Solomon; Shoichiro Tsugane; Piet A van den Brandt; Kala Visvanathan; Elisabete Weiderpass; Lynne R Wilkens; Walter C Willett; Alicja Wolk; Anne Zeleniuch-Jacquotte; Regina G Ziegler; Stephanie A Smith-Warner

doi:10.1093/ajcn/nqab097

Dairy foods, calcium, and risk of breast cancer overall and for subtypes defined by estrogen receptor status: a pooled analysis of 21 cohort studies

Am J Clin Nutr. 2021 Aug 2;114(2):450-461. doi: 10.1093/ajcn/nqab097.

Authors

You Wu¹, Ruyi Huang^{2

3

4}, Molin Wang^{5

6

7}, Leslie Bernstein⁸, Traci N Bethea^{9

10}, Chu Chen¹¹, Yu Chen¹², A Heather Eliassen^{5

7}, Neal D Freedman¹³, Mia M Gaudet¹⁴, Gretchen L Gierach¹³, Graham G Giles^{15

16

17}, Vittorio Krogh¹⁸, Susanna C Larsson^{19

20}, Linda M Liao¹³, Marjorie L McCullough^{11

14}, Anthony B Miller²¹, Roger L Milne^{15

16

17}, Kristine R Monroe²², Marian L Neuhouser¹¹, Julie R Palmer^{9

10}, Anna Prizment^{23

24}, Peggy Reynolds²⁵, Kim Robien²⁶, Thomas E Rohan²⁷, Sven Sandin^{28

29

30}, Norie Sawada³¹, Sabina Sieri¹⁸, Rashmi Sinha¹³, Rachael Z Stolzenberg-Solomon¹³, Shoichiro Tsugane³¹, Piet A van den Brandt^{32

33}, Kala Visvanathan³⁴, Elisabete Weiderpass³⁵, Lynne R Wilkens³⁶, Walter C Willett^{1

5

7}, Alicja Wolk^{19

20}, Anne Zeleniuch-Jacquotte¹², Regina G Ziegler¹³, Stephanie A Smith-Warner^{1

5}

Affiliations

¹ Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
² Department of Medical Education, E-DA Hospital and School of Medicine for International Students, School of Medicine, I-SHOU University, Kaohsiung City, Taiwan.
³ Department of Family Medicine, National Taiwan University Hospital, Taipei, Taiwan.
⁴ Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
⁵ Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
⁶ Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
⁷ Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
⁸ Department of Population Sciences, Beckman Research Institute, City of Hope, Duarte, CA, USA.
⁹ Slone Epidemiology Center at Boston University, Boston, MA, USA.
¹⁰ Department of Medicine, Boston University School of Medicine, Boston, MA, USA.
¹¹ Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
¹² Division of Epidemiology, Department of Population Health and Department of Environmental Medicine, New York University School of Medicine, New York, NY, USA.
¹³ Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, MD, USA.
¹⁴ Department of Population Science, American Cancer Society, Atlanta, GA, USA.
¹⁵ Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Victoria, Australia.
¹⁶ Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Victoria, Australia.
¹⁷ Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, Victoria, Australia.
¹⁸ Epidemiology and Prevention Unit Department of Research, IRCCS National Cancer Institute Foundation, Milan, Italy.
¹⁹ Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
²⁰ Unit of Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institute, Stockholm, Sweden.
²¹ Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada.
²² Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
²³ Division of Hematology, Oncology and Transplantation, University of Minnesota Medical School, Minneapolis, MN, USA.
²⁴ Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, MN, USA.
²⁵ Department of Epidemiology and Biostatistics, University of California San Francisco, Berkeley, CA, USA.
²⁶ Department of Exercise and Nutrition Sciences, Milken Institute School of Public Health, George Washington University, WA, USA.
²⁷ Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, USA.
²⁸ Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden.
²⁹ Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
³⁰ Seaver Autism Center for Research and Treatment at Mount Sinai, New York, NY, USA.
³¹ Epidemiology and Prevention Group, Center for Public Health Sciences, National Cancer Center, Tokyo, Japan.
³² Department of Epidemiology, GROW-School for Oncology and Developmental Biology, Maastricht University, Maastricht, The Netherlands.
³³ Department of Epidemiology, Care and Public Health Institute (CAPHRI), Maastricht University, Maastricht, The Netherlands.
³⁴ Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
³⁵ International Agency for Research on Cancer, WHO, Lyon, France.
³⁶ University of Hawaii Cancer Center, Honolulu, HI, USA.

Abstract

Background: Epidemiologic studies examining the relations between dairy product and calcium intakes and breast cancer have been inconclusive, especially for tumor subtypes.

Objective: To evaluate the associations between intakes of specific dairy products and calcium and risk of breast cancer overall and for subtypes defined by estrogen receptor (ER) status.

Method: We pooled the individual-level data of over 1 million women who were followed for a maximum of 8-20 years across studies. Associations were evaluated for dairy product and calcium intakes and risk of incident invasive breast cancer overall (n = 37,861 cases) and by subtypes defined by ER status. Study-specific multivariable hazard ratios (HRs) were estimated and then combined using random-effects models.

Results: Overall, no clear association was observed between the consumption of specific dairy foods, dietary (from foods only) calcium, and total (from foods and supplements) calcium, and risk of overall breast cancer. Although each dairy product showed a null or very weak inverse association with risk of overall breast cancer (P, test for trend >0.05 for all), differences by ER status were suggested for yogurt and cottage/ricotta cheese with associations observed for ER-negative tumors only (pooled HR = 0.90, 95% CI: 0.83, 0.98 comparing ≥60 g/d with <1 g/d of yogurt and 0.85, 95% CI: 0.76, 0.95 comparing ≥25 g/d with <1 g/d of cottage/ricotta cheese). Dietary calcium intake was only weakly associated with breast cancer risk (pooled HR = 0.98, 95% CI: 0.97, 0.99 per 350 mg/d).

Conclusion: Our study shows that adult dairy or calcium consumption is unlikely to associate with a higher risk of breast cancer and that higher yogurt and cottage/ricotta cheese intakes were inversely associated with the risk of ER-negative breast cancer, a less hormonally dependent subtype with poor prognosis. Future studies on fermented dairy products, earlier life exposures, ER-negative breast cancer, and different racial/ethnic populations may further elucidate the relation.

Keywords: breast cancer; calcium; cheese; dairy products; diet; milk; pooled analysis; yogurt.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Breast Neoplasms / prevention & control*
Calcium / administration & dosage*
Cohort Studies
Dairy Products*
Female
Humans
Multivariate Analysis
Receptors, Estrogen / genetics
Receptors, Estrogen / metabolism*
Risk Factors

Substances

Receptors, Estrogen
Calcium

Abstract

Publication types

MeSH terms

Substances

Grants and funding