Journal of Cancer Survivorship

, Volume 8, Issue 3, pp 384–393 | Cite as

Determinants of newly diagnosed comorbidities among breast cancer survivors

  • Nadia Obi
  • Daniela Gornyk
  • Judith Heinz
  • Alina Vrieling
  • Petra Seibold
  • Jenny Chang-Claude
  • Dieter Flesch-Janys



Comorbid conditions have become increasingly relevant for breast cancer care given the large numbers of long-term survivors. Our aim was to identify potential determinants associated with the development of comorbidities after breast cancer.


Self-reported comorbidities and lifestyle were assessed at recruitment and after a median follow up of 69.4 months from diagnosis in a population-based cohort of breast cancer cases aged 50 to 74 years at diagnosis (MARIEplus study). Tumor and therapy data were extracted from medical records. Determinants potentially associated with incident diagnoses of hypertension, cardiovascular diseases (CVD), and osteoporosis were assessed using multivariable Cox proportional hazard regression models.


Follow-up interview was completed by 2,542 women (76.4 % of eligible patients). A diagnosis of hypertension was significantly associated with age, higher education (hazard ratio (HR) 0.54, CI 0.37–0.79), baseline body mass index (BMI; ≥30 kg/m2; HR, 1.90; CI, 1.24–2.90), and trastuzumab medication (HR, 2.16; CI, 1.09–4.33). An increased risk for CVD was associated with age, BMI, and intake of aromatase inhibitors (AI; HR, 1.42; CI, 1.09–1.84). Risk of osteoporosis was also positively associated with AI treatment (HR, 2.15; CI, 1.64–2.82) but inversely associated with a higher BMI (≥30 kg/m2; HR, 0.50; CI, 0.31–0.79).


In breast cancer survivors, treatment with AI constituted a risk factor for incident CVD and osteoporosis. Besides known risk factors, patients who were treated with trastuzumab may have an increased risk for hypertension.

Implications for cancer survivors

Reducing overweight and regular sport/cycling activities may help to prevent CVD after breast cancer. Patients should be monitored for risk factors and advised on possible cardiac side effects of AI and trastuzumab.


Breast cancer survivors Comorbidity Hypertension Osteoporosis Aromatase inhibitor Trastuzumab 



95 % CI


  1. 1.
    American Cancer Society. Cancer facts & figures 2012. Atlanta: American Cancer Society 2012.Google Scholar
  2. 2.
    Cancer survival in England: Patients diagnosed 2005–2009 and followed up to 2010. Office for National Statistics (ONS). London, 2011. Accessed 9 Mar 2013.
  3. 3.
    Hewitt M, Rowland JH, Yancik R. Cancer survivors in the United States: age, health, and disability. J Gerontol A Biol Sci Med Sci. 2003;58(1):82–91.CrossRefPubMedGoogle Scholar
  4. 4.
    Girones R, Torregrosa D, Díaz-Beveridge R. Comorbidity, disability and geriatric syndromes in elderly breast cancer survivors. Results of a single-center experience. Crit Rev Oncol Hematol. 2010;73(3):236–45.CrossRefPubMedGoogle Scholar
  5. 5.
    Rao AV, Demark-Wahnefried W. The older cancer survivor. Crit Rev Oncol Hematol. 2006;60(2):131–43.CrossRefPubMedGoogle Scholar
  6. 6.
    Land LH, Dalton SO, Jorgensen TL, Ewertz M. Comorbidity and survival after early breast cancer. A review. Crit Rev Oncol/Hematol. 2012;81(2):196–205.CrossRefGoogle Scholar
  7. 7.
    Patnaik JL, Byers T, Diguiseppi C, Denberg TD, Dabelea D. The influence of comorbidities on overall survival among older women diagnosed with breast cancer. J Natl Cancer Inst. 2011;103(14):1101–11.PubMedCentralCrossRefPubMedGoogle Scholar
  8. 8.
    Newschaffer CJ, Bush TL, Penberthy LT. Comorbidity measurement in elderly female breast cancer patients with administrative and medical records data. J Clin Epidemiol. 1997;50(6):725–33.CrossRefPubMedGoogle Scholar
  9. 9.
    Baum M, Buzdar A, Cuzick J, et al. Anastrozole alone or in combination with tamoxifen versus tamoxifen alone for adjuvant treatment of postmenopausal women with early-stage breast cancer: results of the ATAC (Arimidex, Tamoxifen Alone or in Combination) trial efficacy and safety update analyses. Cancer. 2003;98(9):1802–10.CrossRefPubMedGoogle Scholar
  10. 10.
    Amir E, Seruga B, Niraula S, Carlsson L, Ocana A. Toxicity of adjuvant endocrine therapy in postmenopausal breast cancer patients: a systematic review and meta-analysis. J Natl Cancer Inst. 2011;103(17):1299–309.CrossRefPubMedGoogle Scholar
  11. 11.
    Chen J, Long JB, Hurria A, Owusu C, Steingart RM, Gross CP. Incidence of heart failure or cardiomyopathy after adjuvant trastuzumab therapy for breast cancer. J Am Coll Cardiol. 2012;60(24):2504–12.CrossRefPubMedGoogle Scholar
  12. 12.
    Harlan LC, Klabunde CN, Ambs AH, et al. Comorbidities, therapy, and newly diagnosed conditions for women with early stage breast cancer. J Cancer Surviv. 2009;3(2):89–98.PubMedCentralCrossRefPubMedGoogle Scholar
  13. 13.
    Khan NF, Mant D, Carpenter L, Forman D, Rose PW. Long-term health outcomes in a British cohort of breast, colorectal and prostate cancer survivors: a database study. Br J Cancer. 2011;105 Suppl 1:S29–37.PubMedCentralCrossRefPubMedGoogle Scholar
  14. 14.
    Flesch-Janys D, Slanger T, Mutschelknauss E, et al. Risk of different histological types of postmenopausal breast cancer by type and regimen of menopausal hormone therapy. Int J Cancer. 2008;123(4):933–41.CrossRefPubMedGoogle Scholar
  15. 15.
    Schmidt ME, Chang-Claude J, Vrieling A, et al. Association of pre-diagnosis physical activity with recurrence and mortality among women with breast cancer. Int J Cancer. 2013;133(6):1431–40.CrossRefPubMedGoogle Scholar
  16. 16.
    De Laet C, Kanis JA, Oden A, et al. Body mass index as a predictor of fracture risk: a meta-analysis. Osteoporos Int. 2005;16(11):1330–8.CrossRefPubMedGoogle Scholar
  17. 17.
    Isidoro B, Lope V, Pedraz-Pingarron C, et al. Validation of obesity based on self-reported data in Spanish women participants in breast cancer screening programmes. BMC Public Health. 2011;11:960.PubMedCentralCrossRefPubMedGoogle Scholar
  18. 18.
    Spencer EA, Appleby PN, Davey GK, Key TJ. Validity of self-reported height and weight in 4808 EPIC-Oxford participants. Public Health Nutr. 2002;5(4):561–5.CrossRefPubMedGoogle Scholar
  19. 19.
    Li J, Siegrist J. Physical activity and risk of cardiovascular disease—a meta-analysis of prospective cohort studies. Int J Environ Res Public Health. 2012;9(2):391–407.PubMedCentralCrossRefPubMedGoogle Scholar
  20. 20.
    Goldhirsch A, Ingle JN, Gelber RD, et al. Thresholds for therapies: highlights of the St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2009. Ann Oncol. 2009;20(8):1319–29.PubMedCentralCrossRefPubMedGoogle Scholar
  21. 21.
    Ligibel JA, James OA, Fisher M, Daniel GW, Winer EP, Keating NL. Risk of myocardial infarction, stroke, and fracture in a cohort of community-based breast cancer patients. Breast Cancer Res Treat. 2012;131(2):589–97.CrossRefPubMedGoogle Scholar
  22. 22.
    Lonning PE, Geisler J, Krag LE, et al. Effects of exemestane administered for 2 years versus placebo on bone mineral density, bone biomarkers, and plasma lipids in patients with surgically resected early breast cancer. J Clin Oncol. 2005;23(22):5126–37.CrossRefPubMedGoogle Scholar
  23. 23.
    Geisler J, Lonning PE. Impact of aromatase inhibitors on bone health in breast cancer patients. J Steroid Biochem Mol Biol. 2010;118(4–5):294–9.CrossRefPubMedGoogle Scholar
  24. 24.
    Cheung AM, Tile L, Cardew S, et al. Bone density and structure in healthy postmenopausal women treated with exemestane for the primary prevention of breast cancer: a nested substudy of the MAP.3 randomised controlled trial. Lancet Oncol. 2012;13(3):275–84.CrossRefPubMedGoogle Scholar
  25. 25.
    Arimidex, Tamoxifen, Alone or in Combination Trialists' Group, Buzdar A, Howell A, Cuzick J, Wale C, Distler W, et al. Comprehensive side-effect profile of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: long-term safety analysis of the ATAC trial. The Lancet Oncology. 2006;7(8):633–43.CrossRefPubMedGoogle Scholar
  26. 26.
    Mouridsen H, Keshaviah A, Coates AS, et al. Cardiovascular adverse events during adjuvant endocrine therapy for early breast cancer using letrozole or tamoxifen: safety analysis of BIG 1-98 trial. J Clin Oncol. 2007;25(36):5715–22.CrossRefPubMedGoogle Scholar
  27. 27.
    McCaig F, Renshaw L, Williams L, et al. A study of the effects of the aromatase inhibitors anastrozole and letrozole on bone metabolism in postmenopausal women with estrogen receptor-positive breast cancer. Breast Cancer Res Treat. 2010;119(3):643–51.CrossRefPubMedGoogle Scholar
  28. 28.
    Untch M, Jackisch C, Thomssen C, Nitz U, von Minkwitz G, Kaufmann M. Adjuvant treatment with trastuzumab in patients with breast cancer. Dtsch Arztebl. 2006;103(50):3406–10.Google Scholar
  29. 29.
    Gianni L, Dafni U, Gelber RD, et al. Treatment with trastuzumab for 1 year after adjuvant chemotherapy in patients with HER2-positive early breast cancer: a 4-year follow-up of a randomised controlled trial. Lancet Oncol. 2011;12(3):236–44.CrossRefPubMedGoogle Scholar
  30. 30.
    Hysing J, Wist E. Cardiotoxic effects of trastuzumab. Tidsskr Nor Laegeforen. 2011;131(22):2239–41.CrossRefPubMedGoogle Scholar
  31. 31.
    Senkus E, Jassem J. Cardiovascular effects of systemic cancer treatment. Cancer Treat Rev. 2011;37(4):300–11.CrossRefPubMedGoogle Scholar
  32. 32.
    Goldhirsch A, Gelber RD, Piccart-Gebhart MJ, de Azambuja E, Procter M, Suter TM et al. 2 years versus 1 year of adjuvant trastuzumab for HER2-positive breast cancer (HERA): an open-label, randomised controlled trial. The Lancet, published online 18-7-2013.Google Scholar
  33. 33.
    Bowles EJA, Wellman R, Feigelson HS, et al. Risk of heart failure in breast cancer patients after anthracycline and trastuzumab treatment: a retrospective cohort study. JNCI. 2012;104(17):1293–305.PubMedCentralCrossRefPubMedGoogle Scholar
  34. 34.
    Romond EH, Jeong JH, Rastogi P, et al. Seven-year follow-up assessment of cardiac function in NSABP B-31, a randomized trial comparing doxorubicin and cyclophosphamide followed by paclitaxel (ACP) with ACP plus trastuzumab as adjuvant therapy for patients with node-positive, human epidermal growth factor receptor 2-positive breast cancer. J Clin Oncol. 2012;30(31):3792–9.PubMedCentralCrossRefPubMedGoogle Scholar
  35. 35.
    Schmitz KH, Prosnitz RG, Schwartz AL, Carver JR. Prospective surveillance and management of cardiac toxicity and health in breast cancer survivors. Cancer. 2012;118(8 Suppl):2270–6.CrossRefPubMedGoogle Scholar
  36. 36.
    Harris EER, Correa C, Hwang WT, et al. Late cardiac mortality and morbidity in early-stage breast cancer patients after breast-conservation treatment. J Clin Oncol. 2006;24(25):4100–6.CrossRefPubMedGoogle Scholar
  37. 37.
    Braithwaite RS, Chlebowski RT, Lau J, George S, Hess R, Col NF. Meta-analysis of vascular and neoplastic events associated with tamoxifen. J Gen Intern Med. 2003;18(11):937–47.PubMedCentralCrossRefPubMedGoogle Scholar
  38. 38.
    Slanger T, Mutschelknauss E, Kropp S, Braendle W, Flesch-Janys D, Chang-Claude J. Test-retest reliability of self-reported reproductive and lifestyle data in the context of a German case-control study on breast cancer and postmenopausal hormone therapy. Ann Epidemiol. 2007;17(12):993–8.CrossRefPubMedGoogle Scholar
  39. 39.
    Silliman RA, Lash TL. Comparison of interview-based and medical-record based indices of comorbidity among breast cancer patients. Med Care. 1999;37(4):339–49.CrossRefPubMedGoogle Scholar
  40. 40.
    Kriegsman DM, Penninx BW, van Eijk JT, Boeke AJ, Deeg DJ. Self-reports and general practitioner information on the presence of chronic diseases in community dwelling elderly. A study on the accuracy of patients’ self-reports and on determinants of inaccuracy. J Clin Epidemiol. 1996;49(12):1407–17.CrossRefPubMedGoogle Scholar
  41. 41.
    Fuchs J, Busch M, Lange C, Scheidt-Nave C. Prevalence and patterns of morbidity among adults in Germany. Results of the German telephone health interview survey German Health Update (GEDA) 2009. Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz. 2012;55(4):576–86.CrossRefPubMedGoogle Scholar
  42. 42.
    Moebus S, Hanisch J, Aidelsburger P, Bramlage P, Wasem J, Jockel KH. Impact of 4 different definitions used for the assessment of the prevalence of the metabolic syndrome in primary healthcare: the German Metabolic and Cardiovascular Risk Project (GEMCAS). Cardiovasc Diabetol. 2007;6(1):22.PubMedCentralCrossRefPubMedGoogle Scholar
  43. 43.
    Garriguet D. Bone health: osteoporosis, calcium and vitamin D. Health Rep. 2011;22(3):7–14.Google Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Nadia Obi
    • 1
    • 4
  • Daniela Gornyk
    • 1
  • Judith Heinz
    • 1
  • Alina Vrieling
    • 2
    • 3
  • Petra Seibold
    • 2
  • Jenny Chang-Claude
    • 2
  • Dieter Flesch-Janys
    • 1
  1. 1.University Cancer Center HamburgUniversity Medical Center Hamburg-EppendorfHamburgGermany
  2. 2.Department of Cancer EpidemiologyGerman Cancer Research Center (DKFZ)HeidelbergGermany
  3. 3.Department for Health EvidenceRadboud University Medical CentreNijmegenThe Netherlands
  4. 4.Clinical Cancer Registry/Cancer Epidemiology, University Cancer Center Hamburg (UCCH)University Medical Center Hamburg-EppendorfHamburgGermany

Personalised recommendations