Prospective evaluation of body size and breast cancer risk among BRCA1 and BRCA2 mutation carriers

Shana J Kim; Tomasz Huzarski; Jacek Gronwald; Christian F Singer; Pål Møller; Henry T Lynch; Susan Armel; Beth Y Karlan; William D Foulkes; Susan L Neuhausen; Leigha Senter; Andrea Eisen; Charis Eng; Seema Panchal; Tuya Pal; Olufunmilayo Olopade; Dana Zakalik; Jan Lubinski; Steven A Narod; Joanne Kotsopoulos; Hereditary Breast Cancer Clinical Study Group

doi:10.1093/ije/dyy039

Prospective evaluation of body size and breast cancer risk among BRCA1 and BRCA2 mutation carriers

Int J Epidemiol. 2018 Jun 1;47(3):987-997. doi: 10.1093/ije/dyy039.

Authors

Shana J Kim¹, Tomasz Huzarski², Jacek Gronwald², Christian F Singer³, Pål Møller^{4

5

6}, Henry T Lynch⁷, Susan Armel⁸, Beth Y Karlan⁹, William D Foulkes¹⁰, Susan L Neuhausen¹¹, Leigha Senter¹², Andrea Eisen¹³, Charis Eng¹⁴, Seema Panchal¹⁵, Tuya Pal¹⁶, Olufunmilayo Olopade¹⁷, Dana Zakalik¹⁸, Jan Lubinski², Steven A Narod^{1

19}, Joanne Kotsopoulos^{1

19}; Hereditary Breast Cancer Clinical Study Group

Collaborators

Affiliations

¹ Women's College Research Institute, Women's College Hospital, Toronto, Ontario, Canada.
² Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University, Szczecin, Poland.
³ Department of Obstetrics and Gynecology and Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
⁴ Inherited Cancer Research Group, Department for Medical Genetics, Oslo University Hospital, Oslo, Norway.
⁵ Department of Tumor Biology, Institute of Cancer Research, Oslo University Hospital, Oslo, Norway.
⁶ Surgical Center for Hereditary Tumors, HELIOS University Clinic Wuppertal, University Witten-Herdecke, Wuppertal, Germany.
⁷ Hereditary Cancer Center, Creighton University School of Medicine, Omaha, NE, USA.
⁸ Department of Gynecologic Oncology, Princess Margaret Cancer Center, University Health Network, Toronto, Ontario, Canada.
⁹ Women's Cancer Program, Division of Gynecologic Oncology, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
¹⁰ Program in Cancer Genetics, Department of Oncology and Human Genetics, McGill University, Montréal, Quebec, Canada.
¹¹ Department of Population Sciences, Beckman Research Institute of City of Hope, Duarte, CA, USA.
¹² Division of Human Genetics, Ohio State University Medical Center, Comprehensive Cancer Center, Columbus, OH, USA.
¹³ Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada.
¹⁴ Genomic Medicine Institute, Center for Personalized Genetic Healthcare, Cleveland Clinic, Cleveland, OH, USA.
¹⁵ Mount Sinai Hospital, Toronto, Ontario, Canada.
¹⁶ Vanderbilt-Ingram Cancer Center/Vanderbilt University Medical Center, Nashville, TN, USA.
¹⁷ Department of Medicine, University of Chicago, Chicago, IL, USA.
¹⁸ Cancer Genetics Program, Beaumont Hospital, Royal Oak, MI, USA.
¹⁹ Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada.

Abstract

Background: Although evidence suggests that larger body size in early life confers lifelong protection from developing breast cancer, few studies have investigated the relationship between body size and breast cancer risk among BRCA mutation carriers. Therefore, we conducted a prospective evaluation of body size and the risk of breast cancer among BRCA mutation carriers.

Methods: Current height and body mass index (BMI) at age 18 were determined from baseline questionnaires. Current BMI and weight change since age 18 were calculated from updated biennial follow-up questionnaires. Cox proportional hazards models were used to estimate the hazard ratio (HR) and 95% confidence interval (CI).

Results: Among 3734 BRCA mutation carriers, there were 338 incident breast cancers over a mean follow-up of 5.5 years. There was no association between height, current BMI or weight change and breast cancer risk. Women with BMI at age 18 ≥22.1 kg/m2 had a decreased risk of developing post-menopausal breast cancer compared with women with a BMI at age 18 between 18.8 and 20.3 kg/m2 (HR 0.49; 95% CI 0.30-0.82; P = 0.006). BMI at age 18 was not associated with risk of pre-menopausal breast cancer.

Conclusions: There was no observed association between height, current BMI and weight change and risk of breast cancer. The inverse relationship between greater BMI at age 18 and post-menopausal breast cancer further supports a role of early rather than current or adulthood exposures for BRCA-associated breast cancer development. Future studies with longer follow-up and additional measures of adiposity are necessary to confirm these findings.

Keywords: BMI; BRCA; body size; breast cancer; hereditary cancer.