Top

Published in:

01-02-2011 | Epidemiology

Body weight and risk of breast cancer in BRCA1/2 mutation carriers

Authors: Peggy Manders, Anouk Pijpe, Maartje J. Hooning, Irma Kluijt, Hans F. A. Vasen, Nicoline Hoogerbrugge, Christi J. van Asperen, Hanne Meijers-Heijboer, Margreet G. E. M. Ausems, Theo A. van Os, Encarna B. Gomez-Garcia, Richard M. Brohet, Flora E. van Leeuwen, Matti A. Rookus, HEBON

Published in: Breast Cancer Research and Treatment | Issue 1/2011

Abstract

Obesity is an established risk factor for postmenopausal breast cancer in the general population. However, it is still unclear whether this association also exists in BRCA1/2 mutation carriers. We investigated the association between self-reported anthropometric measures and breast cancer risk in a nationwide retrospective cohort study, including 719 BRCA1/2 carriers, of whom 218 had been diagnosed with breast cancer within 10 years prior to questionnaire completion. All time-varying Cox proportional hazards analyses were stratified by menopausal status. For premenopausal breast cancer, no statistically significant associations were observed for any of the anthropometric measures. The association between body mass index (BMI) at age 18 and premenopausal breast cancer risk suggested a trend of decreasing risk with increasing BMI (HR_{22.50–24.99 vs. 18.50–22.49} = 0.83, 95% CI = 0.47–1.44 and HR_{≥25.00 vs. 18.50–22.49} = 0.41, 95% CI = 0.13–1.27). For postmenopausal breast cancer, being 1.67 m and taller increased the risk 1.7-fold (HR = 1.67, 95% CI = 1.01–2.74) when compared to a height <1.67 m. Compared with a current body weight <72 kg, a current body weight of ≥72 kg increased the risk of postmenopausal breast cancer 2.1-fold (95% CI = 1.23–3.59). A current BMI of ≥25.0 kg/m², an adult weight gain of 5 kg or more, and a relative adult weight gain of 20% or more were all non-significantly associated with a 50–60% increased risk of postmenopausal breast cancer [HR = 1.46 (0.86–2.51), HR = 1.56 (95% CI = 0.85–2.87), and HR = 1.60 (95% CI = 0.97–2.63), respectively], when compared with having a healthy or stable weight. No associations for body weight or BMI at age 18 were observed. In conclusion, menopausal status seemed to modify the association between body weight and breast cancer risk among BRCA1/2 carriers. We observed no clear association between body weight and premenopausal breast cancer, while overweight and weight gain increased postmenopausal breast cancer risk. Carriers may reduce their risk of postmenopausal breast cancer by maintaining a healthy body weight throughout life.

Available only for authorised users

Antoniou AC, Gayther SA, Stratton JF, Ponder BA, Easton DF (2000) Risk models for familial ovarian and breast cancer. Genet Epidemiol 18(2):173–190CrossRefPubMed

Brose MS, Rebbeck TR, Calzone KA, Stopfer JE, Nathanson KL, Weber BL (2002) Cancer risk estimates for BRCA1 mutation carriers identified in a risk evaluation program. J Natl Cancer Inst 94(18):1365–1372CrossRefPubMed

Fodor FH, Weston A, Bleiweiss IJ et al (1998) Frequency and carrier risk associated with common BRCA1 and BRCA2 mutations in Ashkenazi Jewish breast cancer patients. Am J Hum Genet 63(1):45–51CrossRefPubMedPubMedCentral

Risch HA, McLaughlin JR, Cole DE et al (2001) Prevalence and penetrance of germline BRCA1 and BRCA2 mutations in a population series of 649 women with ovarian cancer. Am J Hum Genet 68(3):700–710CrossRefPubMedPubMedCentral

Thompson D, Easton D (2001) Variation in cancer risks, by mutation position, in BRCA2 mutation carriers. Am J Hum Genet 68(2):410–419CrossRefPubMedPubMedCentral

Warner E, Foulkes W, Goodwin P et al (1999) Prevalence and penetrance of BRCA1 and BRCA2 gene mutations in unselected Ashkenazi Jewish women with breast cancer. J Natl Cancer Inst 91(14):1241–1247CrossRefPubMed

Couch FJ, Weber BL (1996) Mutations and polymorphisms in the familial early-onset breast cancer (BRCA1) gene. Breast Cancer Information Core. Hum Mutat 8(1):8–18CrossRefPubMed

Shattuck-Eidens D, Oliphant A, McClure M et al (1997) BRCA1 sequence analysis in women at high risk for susceptibility mutations. Risk factor analysis and implications for genetic testing. JAMA 278(15):1242–1250CrossRefPubMed

Breast Cancer Information Core (BIC) http://research.nhgri.nih.gov/bic/. Accessed 8 Feb 2010

10.

Antoniou AC, Spurdle AB, Sinilnikova OM et al (2008) Common breast cancer-predisposition alleles are associated with breast cancer risk in BRCA1 and BRCA2 mutation carriers. Am J Hum Genet 82(4):937–948CrossRefPubMedPubMedCentral

11.

Meijers-Heijboer H, van den Ouweland A, Klijn J et al (2002) Low-penetrance susceptibility to breast cancer due to CHEK2(*)1100delC in noncarriers of BRCA1 or BRCA2 mutations. Nat Genet 31(1):55–59CrossRefPubMed

12.

Rebbeck TR, Kantoff PW, Krithivas K et al (1999) Modification of BRCA1-associated breast cancer risk by the polymorphic androgen-receptor CAG repeat. Am J Hum Genet 64(5):1371–1377CrossRefPubMedPubMedCentral

13.

Narod SA (2006) Modifiers of risk of hereditary breast cancer. Oncogene 25(43):5832–5836CrossRefPubMed

14.

Antoniou A, Pharoah PD, Narod S et al (2003) Average risks of breast and ovarian cancer associated with BRCA1 or BRCA2 mutations detected in case Series unselected for family history: a combined analysis of 22 studies. Am J Hum Genet 72(5):1117–1130CrossRefPubMedPubMedCentral

15.

King MC, Marks JH, Mandell JB (2003) Breast and ovarian cancer risks due to inherited mutations in BRCA1 and BRCA2. Science 302(5645):643–646CrossRefPubMed

16.

Narod S, Lynch H, Conway T, Watson P, Feunteun J, Lenoir G (1993) Increasing incidence of breast cancer in family with BRCA1 mutation. Lancet 341(8852):1101–1102CrossRefPubMed

17.

Calle EE, Kaaks R (2004) Overweight, obesity and cancer: epidemiological evidence and proposed mechanisms. Nat Rev Cancer 4(8):579–591CrossRefPubMed

18.

Renehan AG, Tyson M, Egger M, Heller RF, Zwahlen M (2008) Body-mass index and incidence of cancer: a systematic review and meta-analysis of prospective observational studies. Lancet 371(9612):569–578CrossRefPubMed

19.

World Cancer Research Fund/American Institute for Cancer Research (2007) Food, nutrition, physical activity, and the prevention of cancer: a global perspective. IARC, Washington DC

20.

Chang-Claude J, Becher H, Eby N, Bastert G, Wahrendorf J, Hamann U (1997) Modifying effect of reproductive risk factors on the age at onset of breast cancer for German BRCA1 mutation carriers. J Cancer Res Clin Oncol 123(5):272–279PubMed

21.

Nkondjock A, Robidoux A, Paredes Y, Narod SA, Ghadirian P (2006) Diet, lifestyle and BRCA-related breast cancer risk among French-Canadians. Breast Cancer Res Treat 98(3):285–294CrossRefPubMed

22.

Kotsopoulos J, Olopado OI, Ghadirian P et al (2005) Changes in body weight and the risk of breast cancer in BRCA1 and BRCA2 mutation carriers. Breast Cancer Res 7(5):R833–R843CrossRefPubMedPubMedCentral

23.

Pijpe A, Manders P, Brohet RM et al (2010) Physical activity and the risk of breast cancer in BRCA1/2 mutation carriers. Breast Cancer Res Treat 120(1):235–244CrossRefPubMed

24.

Abrahamson PE, Gammon MD, Lund MJ et al (2006) General and abdominal obesity and survival among young women with breast cancer. Cancer Epidemiol Biomarkers Prev 15(10):1871–1877CrossRefPubMed

25.

Calle EE, Rodriguez C, Walker-Thurmond K, Thun MJ (2003) Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. adults. N Engl J Med 348(17):1625–1638CrossRefPubMed

26.

Koster A, Harris TB, Moore SC et al (2009) Joint associations of adiposity and physical activity with mortality: the National Institutes of Health-AARP Diet and Health Study. Am J Epidemiol 169(11):1344–1351CrossRefPubMedPubMedCentral

27.

Carmichael AR (2006) Obesity and prognosis of breast cancer. Obes Rev 7(4):333–340CrossRefPubMed

28.

Cleveland RJ, Eng SM, Abrahamson PE et al (2007) Weight gain prior to diagnosis and survival from breast cancer. Cancer Epidemiol Biomarkers Prev 16(9):1803–1811CrossRefPubMed

29.

Kellen E, Vansant G, Christiaens MR, Neven P, Van LE (2009) Lifestyle changes and breast cancer prognosis: a review. Breast Cancer Res Treat 114(1):13–22CrossRefPubMed

30.

Andrieu N, Goldgar DE, Easton DF et al (2006) Pregnancies, breast-feeding, and breast cancer risk in the International BRCA1/2 Carrier Cohort Study (IBCCS). J Natl Cancer Inst 98(8):535–544CrossRefPubMedPubMedCentral

31.

Andrieu N, Easton DF, Chang-Claude J et al (2006) Effect of chest X-rays on the risk of breast cancer among BRCA1/2 mutation carriers in the international BRCA1/2 carrier cohort study: a report from the EMBRACE, GENEPSO, GEO-HEBON, and IBCCS Collaborators’ Group. J Clin Oncol 24(21):3361–3366CrossRefPubMed

32.

Brohet RM, Goldgar DE, Easton DF et al (2007) Oral contraceptives and breast cancer risk in the international BRCA1/2 carrier cohort study: a report from EMBRACE, GENEPSO, GEO-HEBON, and the IBCCS Collaborating Group. J Clin Oncol 25(25):3831–3836CrossRefPubMed

33.

Antoniou AC, Goldgar DE, Andrieu N et al (2005) A weighted cohort approach for analysing factors modifying disease risks in carriers of high-risk susceptibility genes. Genet Epidemiol 29(1):1–11CrossRefPubMed

34.

WHO Expert Committee (1995) Physical status: the use and interpretation of anthropomerty. WHO technical report series 854

35.

Heideman WH, Russell NS, Gundy C, Rookus MA, Voskuil DW (2009) The frequency, magnitude and timing of post-diagnosis body weight gain in Dutch breast cancer survivors. Eur J Cancer 45(1):119–126CrossRefPubMed

36.

Gorber SC, Tremblay M, Moher D, Gorber B (2007) A comparison of direct vs. self-report measures for assessing height, weight and body mass index: a systematic review. Obes Rev 8(4):307–326CrossRefPubMed

37.

Rebbeck TR, Kauff ND, Domchek SM (2009) Meta-analysis of risk reduction estimates associated with risk-reducing salpingo-oophorectomy in BRCA1 or BRCA2 mutation carriers. J Natl Cancer Inst 101(2):80–87CrossRefPubMedPubMedCentral

38.

Lakhani SR, Van DV, Jacquemier J et al (2002) The pathology of familial breast cancer: predictive value of immunohistochemical markers estrogen receptor, progesterone receptor, HER-2, and p53 in patients with mutations in BRCA1 and BRCA2. J Clin Oncol 20(9):2310–2318CrossRefPubMed

39.

Hosey AM, Gorski JJ, Murray MM et al (2007) Molecular basis for estrogen receptor alpha deficiency in BRCA1-linked breast cancer. J Natl Cancer Inst 99(22):1683–1694CrossRefPubMed

40.

Gorski JJ, Kennedy RD, Hosey AM, Harkin DP (2009) The complex relationship between BRCA1 and ERalpha in hereditary breast cancer. Clin Cancer Res 15(5):1514–1518CrossRefPubMedPubMedCentral

41.

Lahmann PH, Hoffmann K, Allen N et al (2004) Body size and breast cancer risk: findings from the European Prospective Investigation into Cancer and Nutrition (EPIC). Int J Cancer 111(5):762–771CrossRefPubMed

42.

van den Brandt PA, Spiegelman D, Yaun SS et al (2000) Pooled analysis of prospective cohort studies on height, weight, and breast cancer risk. Am J Epidemiol 152(6):514–527CrossRefPubMed

43.

Hankinson SE, Willett WC, Colditz GA et al (1998) Circulating concentrations of insulin-like growth factor-I and risk of breast cancer. Lancet 351(9113):1393–1396CrossRefPubMed

44.

Stoll BA (1992) Does extra height justify a higher risk of breast cancer? Ann Oncol 3(1):29–30PubMed

45.

Willett W (1990) Nutritional epidemiology. Oxford University Press, New York

46.

Ballard-Barbash R (1994) Anthropometry and breast cancer. Body size—a moving target. Cancer 74(3 Suppl):1090–1100CrossRefPubMed

47.

Trichopoulos D, Lipman RD (1992) Mammary gland mass and breast cancer risk. Epidemiology 3(6):523–526CrossRefPubMed

48.

Morimoto LM, White E, Chen Z et al (2002) Obesity, body size, and risk of postmenopausal breast cancer: the Women’s Health Initiative (United States). Cancer Causes Control 13(8):741–751CrossRefPubMed

49.

Metcalfe KA, Birenbaum-Carmeli D, Lubinski J et al (2008) International variation in rates of uptake of preventive options in BRCA1 and BRCA2 mutation carriers. Int J Cancer 122(9):2017–2022CrossRefPubMedPubMedCentral

Title: Body weight and risk of breast cancer in BRCA1/2 mutation carriers
Authors: Peggy Manders
Anouk Pijpe
Maartje J. Hooning
Irma Kluijt
Hans F. A. Vasen
Nicoline Hoogerbrugge
Christi J. van Asperen
Hanne Meijers-Heijboer
Margreet G. E. M. Ausems
Theo A. van Os
Encarna B. Gomez-Garcia
Richard M. Brohet
Flora E. van Leeuwen
Matti A. Rookus
HEBON
Publication date: 01-02-2011
Publisher: Springer US
Published in: Breast Cancer Research and Treatment / Issue 1/2011
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-010-1120-8

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras

Prof. Fabrice Barlesi

Developed by: Springer Medicine

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 1/2011

CTEN (C-terminal tensin-like), a novel oncogene overexpressed in invasive breast carcinoma of poor prognosis

Erratum to: A pilot study of dose-dense adjuvant paclitaxel without growth factor support for women with early breast carcinoma

Association between polymorphisms of trinucleotide repeat containing 9 gene and breast cancer risk: evidence from 62,005 subjects

The ErbB3 binding protein EBP1 regulates ErbB2 protein levels and tamoxifen sensitivity in breast cancer cells

New conflicting results obtained in the subgroup analysis of RAD51 135G>C polymorphism and breast cancer risk

Germline mutations in PALB2 in African-American breast cancer cases

Keynote webinar | Spotlight on antibody–drug conjugates in cancer