Abstract
Breast cancer (BC) survivors are at increased risk of second cancers. Obesity is commonly recognized as a risk factor of BC in postmenopausal period and a prognosis factor in BC regardless of menopausal status. Our aim was to study whether overweight BC survivors were at increased risk of contralateral BC (CBC). Our population was a large cohort of women followed since a first BC without distant spread and/or synchronous CBC. Body mass index (BMI) was assessed at diagnosis time. Binary codings of BMI were used to oppose overweight and obese patients to the others. Survival analyses were used including Cox models. Assumed hypothesis of proportional hazards was explored using graphical methods, Schoenfeld residuals and time-dependant covariates. In case of non-proportional hazards, survival models were computed over time periods. Over 15,000 patients were included in our study. Incidence of CBC was 8.8 (8.3–9.3)/1000 person-years and increased during follow-up. A significant time-dependent association between overweight and CBC was observed. After 10 years of follow-up, we found a significant increased hazard of CBC among patients with a BMI above 25 kg/m2: the adjusted hazard ratio was 1.50(1.21–1.86), P = 0.001. After 10 years of follow-up, our study found a poorer prognosis among overweight BC survivors regarding CBC events. While benefits from diet habits and weight control may be expected during the long-term follow-up, they have yet to be established using randomized clinical trials.
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Abbreviations
- BC:
-
Breast cancer
- BMI:
-
Body mass index
- CBC:
-
Contralateral breast cancer
- HR:
-
Hazard ratio
References
Carmichael AR (2006) Obesity as a risk factor for development and poor prognosis of breast cancer. BJOG 113(10):1160–1166
Rock CL, Demark-Wahnefried W (2002) Nutrition and survival after the diagnosis of breast cancer: a review of the evidence. J Clin Oncol 20(15):3302–3316
Chlebowski RT (2003) The American Cancer Society guide for nutrition and physical activity for cancer survivors: a call to action for clinical investigators. CA Cancer J Clin 53(5):266–267
Pierce JP, Stefanick ML, Flatt SW, Natarajan L, Sternfeld B, Madlensky L, Al-Delaimy WK, Thomson CA, Kealey S, Hajek R et al (2007) Greater survival after breast cancer in physically active women with high vegetable-fruit intake regardless of obesity. J Clin Oncol 25(17):2345–2351
Pierce JP (2009) Diet and breast cancer prognosis: making sense of the Women’s Healthy Eating and Living and Women’s Intervention Nutrition Study trials. Curr Opin Obstet Gynecol 21(1):86–91
Chen Y, Thompson W, Semenciw R, Mao Y (1999) Epidemiology of contralateral breast cancer. Cancer Epidemiol Biomarkers Prev 8(10):855–861
Fowble B, Hanlon A, Freedman G, Nicolaou N, Anderson P (2001) Second cancers after conservative surgery and radiation for stages I–II breast cancer: identifying a subset of women at increased risk. Int J Radiat Oncol Biol Phys 51(3):679–690
Broet P, de la Rochefordiere A, Scholl SM, Fourquet A, Mosseri V, Durand JC, Pouillart P, Asselain B (1995) Contralateral breast cancer: annual incidence and risk parameters. J Clin Oncol 13(7):1578–1583
Gao X, Fisher SG, Emami B (2003) Risk of second primary cancer in the contralateral breast in women treated for early-stage breast cancer: a population-based study. Int J Radiat Oncol Biol Phys 56(4):1038–1045
Shahedi K, Emanuelsson M, Wiklund F, Gronberg H (2006) High risk of contralateral breast carcinoma in women with hereditary/familial non-BRCA1/BRCA2 breast carcinoma. Cancer 106(6):1237–1242
Dignam JJ, Wieand K, Johnson KA, Fisher B, Xu L, Mamounas EP (2003) Obesity, tamoxifen use, and outcomes in women with estrogen receptor-positive early-stage breast cancer. J Natl Cancer Inst 95(19):1467–1476
Majed B, Moreau T, Senouci K, Salmon RJ, Fourquet A, Asselain B (2008) Is obesity an independent prognosis factor in woman breast cancer? Breast Cancer Res Treat 111(2):329–342
Bianchini F, Kaaks R, Vainio H (2002) Overweight, obesity, and cancer risk. Lancet Oncol 3(9):565–574
Rock CL, Flatt SW, Newman V, Caan BJ, Haan MN, Stefanick ML, Faerber S, Pierce JP (1999) Factors associated with weight gain in women after diagnosis of breast cancer Women’s Healthy Eating and Living Study Group. J Am Diet Assoc 99(10):1212–1221
Stoll BA (1999) Perimenopausal weight gain and progression of breast cancer precursors. Cancer Detect Prev 23(1):31–36
Rothman KJ (2008) BMI-related errors in the measurement of obesity. Int J Obes (Lond) 32(Suppl 3):S56–S59
Berrino F, De Angelis R, Sant M, Rosso S, Bielska-Lasota M, Coebergh JW, Santaquilani M (2007) Survival for eight major cancers and all cancers combined for European adults diagnosed in 1995–99: results of the EUROCARE-4 study. Lancet Oncol 8(9):773–783
Dawson LA, Chow E, Goss PE (1998) Evolving perspectives in contralateral breast cancer. Eur J Cancer 34(13):2000–2009
Prentice AM (2006) The emerging epidemic of obesity in developing countries. Int J Epidemiol 35(1):93–99
WHO (2000) Obesity: preventing and managing the global epidemic. Report of a WHO consultation. World Health Organ Tech Rep Ser 894(i–xii):1–253
Gross AJ, Clark V (1975) Survival distributions: reliability applications in the biomedical sciences. Wiley, New York
Therneau TM, Grambsch PM (2000) Modeling survival data: extending the Cox model, 1st edn. Springer-Verlag, New York
Guthrie JR, Dennerstein L, Dudley EC (1999) Weight gain and the menopause: a 5-year prospective study. Climacteric 2(3):205–211
Hilsenbeck SG, Ravdin PM, de Moor CA, Chamness GC, Osborne CK, Clark GM (1998) Time-dependence of hazard ratios for prognostic factors in primary breast cancer. Breast Cancer Res Treat 52(1–3):227–237
Pichon MF, Broet P, Magdelenat H, Delarue JC, Spyratos F, Basuyau JP, Saez S, Rallet A, Courriere P, Millon R et al (1996) Prognostic value of steroid receptors after long-term follow-up of 2257 operable breast cancers. Br J Cancer 73(12):1545–1551
Warwick J, Tabar L, Vitak B, Duffy SW (2004) Time-dependent effects on survival in breast carcinoma: results of 20 years of follow-up from the Swedish Two-County Study. Cancer 100(7):1331–1336
Claus EB, Stowe M, Carter D, Holford T (2003) The risk of a contralateral breast cancer among women diagnosed with ductal and lobular breast carcinoma in situ: data from the Connecticut Tumor Registry. Breast 12(6):451–456
Cook LS, White E, Schwartz SM, McKnight B, Daling JR, Weiss NS (1996) A population-based study of contralateral breast cancer following a first primary breast cancer (Washington, United States). Cancer Causes Control 7(3):382–390
Ji J, Hemminki K (2007) Risk for contralateral breast cancers in a population covered by mammography: effects of family history, age at diagnosis and histology. Breast Cancer Res Treat 105(2):229–236
Kurian AW, McClure LA, John EM, Horn-Ross PL, Ford JM, Clarke CA (2009) Second primary breast cancer occurrence according to hormone receptor status. J Natl Cancer Inst 101(15):1058–1065
Kollias J, Ellis IO, Elston CW, Blamey RW (1999) Clinical and histological predictors of contralateral breast cancer. Eur J Surg Oncol 25(6):584–589
Majed B, Moreau T, Asselain B (2009) Overweight, obesity and breast cancer prognosis: optimal body size indicator cut-points. Breast Cancer Res Treat 115(1):193–203
Verkooijen HM, Bouchardy C, Vinh-Hung V, Rapiti E, Hartman M (2009) The incidence of breast cancer and changes in the use of hormone replacement therapy: a review of the evidence. Maturitas 64(2):80–85
de la Rochefordiere A, Mouret-Fourme E, Asselain B, Scholl SM, Campana F, Broet P, Fourquet A (1996) Metachronous contralateral breast cancer as first event of relapse. Int J Radiat Oncol Biol Phys 36(3):615–621
McTiernan A, Irwin M, Vongruenigen V (2010) Weight, physical activity, diet, and prognosis in breast and gynecologic cancers. J Clin Oncol 28(26):4074–4080
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The authors would like to thank Roland Sage for his invaluable help.
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Majed, B., Dozol, A., Ribassin-Majed, L. et al. Increased risk of contralateral breast cancers among overweight and obese women: a time-dependent association. Breast Cancer Res Treat 126, 729–738 (2011). https://doi.org/10.1007/s10549-010-1153-z
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DOI: https://doi.org/10.1007/s10549-010-1153-z