Skip to main content

Advertisement

SpringerLink
Log in

Risk factors for contralateral breast cancer in postmenopausal breast cancer survivors in the NIH-AARP Diet and Health Study

  • Original Paper
  • Published:
Cancer Causes & Control Aims and scope Submit manuscript

Abstract

Purpose

The role of established breast cancer risk factors and clinical characteristics of the first breast cancer in the development of contralateral breast cancer (CBC) among postmenopausal women is unclear.

Methods

We identified 10,934 postmenopausal women diagnosed with a first primary breast cancer between 1995 and 2011 in the NIH-AARP Diet and Health Study. CBC was defined as a second primary breast cancer diagnosed in the contralateral breast ≥ 3 months after the first breast cancer. Exposures included pre-diagnosis risk factors (lifestyle, reproductive, family history) and clinical characteristics of the first breast cancer. We used multivariable Cox proportional hazards regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs).

Results

Over a median follow-up of 6.8 years, 436 women developed CBC. We observed an increasing trend in CBC risk by age (p-trend = 0.002) and decreasing trend by year of diagnosis (p-trend = 0.001) of the first breast cancer. Additional risk factor associations were most pronounced for endocrine therapy (HR 0.68, 95% CI 0.53–0.87) and family history of breast cancer (HR 1.38, 95% CI 1.06–1.80, restricted to invasive first breast cancer). No associations were found for lifestyle (body mass index, physical activity, smoking, alcohol) or reproductive factors (age at menarche, parity, age at first birth, age at menopause).

Conclusions

This study suggests that clinical characteristics of the first breast cancer and family history of breast cancer, but not pre-diagnosis lifestyle and reproductive factors, are strongly associated with CBC risk among postmenopausal women. Future studies are needed to understand how these factors contribute to CBC etiology and to identify further opportunities for prevention.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Data availability

The datasets analyzed during the current study were obtained from the NIH-AARP Diet and Health Study at the National Cancer Institute. The data used in this study are available with the submission of a proposal and approval from the NIH-AARP Steering Committee (https://dietandhealth.cancer.gov/).

Code availability

Code is available upon request.

References

  1. American Cancer Society (2019) Cancer treatment & survivorship facts & figures 2019–2021. American Cancer Society, Atlanta

    Google Scholar 

  2. Chen Y, Thompson W, Semenciw R et al (1999) Epidemiology of contralateral breast cancer. Cancer Epidemiol Biomark Prev 8(10):855–861

    CAS  Google Scholar 

  3. Ramin C, Withrow DR, Davis Lynn BC et al (2021) Risk of contralateral breast cancer according to first breast cancer characteristics among women in the USA, 1992–2016. Breast Cancer Res 23:24

    Article  PubMed  PubMed Central  Google Scholar 

  4. Curtis RE, Freeman DM, Ron E et al (Eds) (2006) New malignancies among cancer survivors: SEER Cancer Registries, 1973–2000. Volume Publication Number 05–5302 National Cancer Institute, NIH, Bethesda, MD

  5. Reiner AS, Sisti J, John EM et al (2018) Breast cancer family history and contralateral breast cancer risk in young women: an update from the Women’s Environmental Cancer and Radiation Epidemiology study. J Clin Oncol 36(15):1513–1520

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Knight JA, Fan J, Malone KE et al (2017) Alcohol consumption and cigarette smoking in combination: a predictor of contralateral breast cancer risk in the WECARE study. Int J Cancer 141(5):916–924

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Brooks JD, John EM, Mellemkjær L et al (2016) Body mass index, weight change, and risk of second primary breast cancer in the WECARE study: influence of estrogen receptor status of the first breast cancer. Cancer Med 5(11):3282–3291

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Sisti JS, Bernstein JL, Lynch CF et al (2015) Reproductive factors, tumor estrogen receptor status and contralateral breast cancer risk: results from the WECARE study. Springerplus 4(1):825

    Article  PubMed  PubMed Central  Google Scholar 

  9. Brooks JD, Boice JD, Stovall M et al (2012) Reproductive status at first diagnosis influences risk of radiation-induced second primary contralateral breast cancer in the WECARE study. Int J Radiat Oncol Biol Phys 84(4):917–924

    Article  PubMed  PubMed Central  Google Scholar 

  10. Brooks JD, John EM, Mellemkjær L et al (2012) Body mass index and risk of second primary breast cancer: the WECARE Study. Breast Cancer Res Treat 131:571–580

    Article  PubMed  Google Scholar 

  11. Poynter JN, Langholz B, Largent J et al (2010) Reproductive factors and risk of contralateral breast cancer by BRCA1 and BRCA2 mutation status: results from the WECARE study. Cancer Causes Control 21(6):839–846

    Article  PubMed  PubMed Central  Google Scholar 

  12. Knight JA, Bernstein L, Largent J et al (2009) Alcohol intake and cigarette smoking and risk of a contralateral breast cancer: the Women’s Environmental Cancer and Radiation Epidemiology Study. Am J Epidemiol 169(8):962–968

    Article  PubMed  PubMed Central  Google Scholar 

  13. Largent JA, Capanu M, Bernstein L et al (2007) Reproductive history and risk of second primary breast cancer: the WECARE Study. Cancer Epidemiol Biomark Prev 16(5):906–911

    Article  Google Scholar 

  14. Li CI, Malone KE, Porter PL et al (2003) Epidemiologic and molecular risk factors for contralateral breast cancer among young women. Br J Cancer 89(3):513–518

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Bernstein JL, Thompson WD, Risch N et al (1992) Risk factors predicting the incidence of second primary breast cancer among women diagnosed with a first primary breast cancer. Am J Epidemiol 136(8):925–936

    Article  CAS  PubMed  Google Scholar 

  16. Majed B, Dozol A, Ribassin-Majed L et al (2011) Increased risk of contralateral breast cancers among overweight and obese women: a time-dependent association. Breast Cancer Res Treat 126(3):729–738

    Article  PubMed  Google Scholar 

  17. Li CI, Daling JR, Porter PL et al (2009) Relationship between potentially modifiable lifestyle factors and risk of second primary contralateral breast cancer among women diagnosed with estrogen receptor–positive invasive breast cancer. J Clin Oncol 27(32):5312–5318

    Article  PubMed  PubMed Central  Google Scholar 

  18. Vaittinen P, Hemminki K (2000) Risk factors and age-incidence relationships for contralateral breast cancer. Int J Cancer 88(6):998–1002

    Article  CAS  PubMed  Google Scholar 

  19. Cook LS, White E, Schwartz SM et al (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

    Article  CAS  PubMed  Google Scholar 

  20. Horn PL, Thompson WD (1988) Risk of contralateral breast cancer: associations with factors related to initial breast cancer. Am J Epidemiol 128(2):309–323

    Article  CAS  PubMed  Google Scholar 

  21. Bertelsen L, Bernstein L, Olsen JH et al (2008) Effect of systemic adjuvant treatment on risk for contralateral breast cancer in the Women’s Environment, Cancer and Radiation Epidemiology study. J Natl Cancer Inst 100(1):32–40

    Article  CAS  PubMed  Google Scholar 

  22. Boice JD, Harvey EB, Blettner M et al (1992) Cancer in the contralateral breast after radiotherapy for breast cancer. N Engl J Med 326(12):781–785

    Article  PubMed  Google Scholar 

  23. Bouchardy C, Benhamou S, Fioretta G et al (2011) Risk of second breast cancer according to estrogen receptor status and family history. Breast Cancer Res Treat 127(1):233–241

    Article  CAS  PubMed  Google Scholar 

  24. Kurian AW, McClure LA, John EM et al (2009) Second primary breast cancer occurrence according to hormone receptor status. J Natl Cancer Inst 101(15):1058–1065

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Langballe R, Mellemkjær L, Malone KE et al (2016) Systemic therapy for breast cancer and risk of subsequent contralateral breast cancer in the WECARE Study. Breast Cancer Res 18(1):65

    Article  PubMed  PubMed Central  Google Scholar 

  26. Reiner AS, Lynch CF, Sisti JS et al (2017) Hormone receptor status of a first primary breast cancer predicts contralateral breast cancer risk in the WECARE study population. Breast Cancer Res 19(1):83

    Article  PubMed  PubMed Central  Google Scholar 

  27. Saltzman BS, Malone KE, McDougall JA et al (2012) Estrogen receptor, progesterone receptor, and HER2-neu expression in first primary breast cancers and risk of second primary contralateral breast cancer. Breast Cancer Res Treat 135(3):849–855

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Sandberg MEC, Hall P, Hartman M et al (2012) Estrogen receptor status in relation to risk of contralateral breast cancer–a population-based cohort study. PLoS ONE 7(10):e46535

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Schatzkin A, Subar AF, Thompson FE et al (2001) Design and serendipity in establishing a large cohort with wide dietary intake distributions: the National Institutes of Health-American Association of Retired Persons Diet and Health Study. Am J Epidemiol 154(12):1119–1125

    Article  CAS  PubMed  Google Scholar 

  30. Michaud D, Midthune D, Hermansen S et al (2005) Comparison of cancer registry case ascertainment with SEER estimates and self-reporting in a subset of the NIH-AARP Diet and Health Study. J Registry Manage 32:70–75

    Google Scholar 

  31. Wong SM, Freedman RA, Sagara Y et al (2017) Growing use of contralateral prophylactic mastectomy despite no improvement in long-term survival for invasive breast cancer. Ann Surg 265:581–589

    Article  PubMed  Google Scholar 

  32. Fine JP, Gray RJ (1999) A proportional hazards model for the subdistribution of a competing risk. J Am Stat Assoc 94:496–509

    Article  Google Scholar 

  33. Akdeniz DKM, Smith CZA, Koppert LB et al (2020) The impact of lifestyle and reproductive factors on the risk of a second new primary cancer in the contralateral breast: a systematic review and meta-analysis. Cancer Causes Control 31(5):403–416

    Article  PubMed  Google Scholar 

  34. Early Breast Cancer Trialists’ Collaborative Group (2011) Relevance of breast cancer hormone receptors and other factors to the efficacy of adjuvant tamoxifen: patient-level meta-analysis of randomised trials. Lancet 378(9793):771–784

    Article  Google Scholar 

  35. Early Breast Cancer Trialists’ Collaborative Group (2015) Aromatase inhibitors versus tamoxifen in early breast cancer: patient-level meta-analysis of the randomised trials. Lancet 386(10001):1341–1352

    Article  Google Scholar 

  36. Gierach GL, Curtis RE, Pfeiffer RM et al (2017) Association of adjuvant tamoxifen and aromatase inhibitor therapy with contralateral breast cancer risk among US women with breast cancer in a general community setting. JAMA Oncol 3(2):186–193

    Article  PubMed  Google Scholar 

  37. Kramer I, Schaapveld M, Oldenburg HSA et al (2019) The influence of adjuvant systemic regimens on contralateral breast cancer risk and receptor subtype. J Natl Cancer Inst 111(7):709–718

    Article  PubMed  Google Scholar 

  38. Bernstein JL, Thompson WD, Risch N et al (1992) The genetic epidemiology of second primary breast cancer. Am J Epidemiol 136(8):937–948

    Article  CAS  PubMed  Google Scholar 

  39. Reiner AS, John EM, Brooks JD et al (2013) Risk of asynchronous contralateral breast cancer in noncarriers of BRCA1 and BRCA2 mutations with a family history of breast cancer: A report from the Women’s Environmental Cancer and Radiation Epidemiology study. J Clin Oncol 31(4):433–439

    Article  PubMed  Google Scholar 

Download references

Funding

This study was funded by the Intramural Research Program of the National Cancer Institute at the National Institutes of Health. MM is funded by the Health Research Board in Ireland.

Author information

Authors and Affiliations

  1. Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA

    Cody Ramin, Sara J. Schonfeld, Pragati G. Advani & Amy Berrington de González

  2. Division of Population Health Sciences, Royal College of Surgeons in Ireland, Dublin, Ireland

    Maeve Mullooly

  3. Integrative Tumor Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA

    Clara Bodelon & Gretchen L. Gierach

Authors
  1. Cody Ramin
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Maeve Mullooly
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sara J. Schonfeld
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Pragati G. Advani
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Clara Bodelon
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Gretchen L. Gierach
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Amy Berrington de González
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

CR, ABdG conceived and designed the study and conducted and reviewed statistical analysis. All authors substantially contributed to the preparation and critical review of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Cody Ramin.

Ethics declarations

Conflict of interest

All authors declare that they have no conflicts of interest.

Ethical approval

The NIH-AARP Diet and Health Study (Protocol Number: OH95CN025) was approved by the Special Studies Institutional Review Board (SSIRB) of the US National Cancer Institute. This study was conducted in accordance with the ethical standards of the institutional review board and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Consent for publication

All participants provided informed consent by completing and returning the self-administered baseline questionnaire.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 68 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ramin, C., Mullooly, M., Schonfeld, S.J. et al. Risk factors for contralateral breast cancer in postmenopausal breast cancer survivors in the NIH-AARP Diet and Health Study. Cancer Causes Control 32, 803–813 (2021). https://doi.org/10.1007/s10552-021-01432-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10552-021-01432-2

Keywords

Search

Navigation