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Subtype-specific risk factors for postmenopausal breast cancer: findings from the PLCO trial

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Abstract

Objective

The aim of this analysis is to evaluate the relative weight of different epidemiological risk factors on the development of different breast cancer subtypes (i.e. luminal, Her2+ overexpressed or triple negative).

Methods

De-identified datasets of female participants recruited within the Prostate, Lung, Colorectal, and Ovarian (PLCO) trial were accessed. Multivariate Cox regression analysis was utilized to assess factors affecting the development of breast cancer (regardless of subtype). Additional multivariate analyses were conducted to assess factors affecting the development of the three principal subtypes of breast cancer (ER+/Her2− breast cancer; Her2 overexpressed breast cancer and ER−/Her2− breast cancer).

Results

A total of 73,570 eligible participants were evaluated in the current analysis of which 2370 participants subsequently developed breast cancer. The following factors were associated with a higher risk of ER+/Her2− breast cancer: white race (P < 0.001), nulliparity (P < 0.001), higher body mass index (P = 0.003), prior exposure to hormone treatment (P = 0.004) and breast cancer in first-degree female relatives (P < 0.001). The following factors were associated with a higher risk of Her2 overexpressed breast cancer: prior exposure to hormone treatment (P = 0.002) and breast cancer in first-degree female relatives (P = 0.001). The following factors were associated with a higher risk of ER−/Her2− breast cancer: black race (P = 0.013), younger age (P = 0.017) and breast cancer in first-degree female relatives (P 0.023).

Conclusions

There is considerable heterogeneity in risk factors among patients with different subtypes of breast cancer. In particular, factors associated with high estrogen levels seem to be associated with luminal breast cancer rather than other breast cancer subtypes.

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Data availability

De-identified PLCO trial datasets are available from the NCI platform: https://biometry.nci.nih.gov/cdas/plco/.

Abbreviations

PLCO:

Prostate, lung, colorectal and ovary

SEER:

Surveillance, epidemiology and end results

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Acknowledgements

This work is based on the PLCO trial datasets which were accessed after approval from the NCI. Neither the NCI nor the investigators of the primary PLCO trial are responsible for the results of this analysis

Funding

None.

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Authors and Affiliations

  1. Clinical Oncology Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt

    O. Abdel-Rahman

  2. Department of Oncology, Cross Cancer Institute, University of Alberta, Edmonton, AB, Canada

    O. Abdel-Rahman

  3. Department of Oncology, Tom Baker Cancer Centre, University of Calgary, Calgary, AB, T2N4N1, Canada

    P. A. Tang & W. Y. Cheung

Authors
  1. O. Abdel-Rahman
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  2. P. A. Tang
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  3. W. Y. Cheung
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Contributions

OA: conducted the analyses and wrote the manuscript. PT and WC: revised the manuscript. All authors have read and approved the manuscript. All authors have approved the final version of the manuscript.

Corresponding author

Correspondence to O. Abdel-Rahman.

Ethics declarations

Conflict of interest

All authors declare that they have no competing interest.

Ethical approval

This study is a secondary analysis based on publicly available de-identified datasets of the PLCO trial. Primary PLCO trial was approved by the IRBs of all included centers. Details of IRB approval for each center were provided in the original publications of the PLCO trial (Ref [6]) as well as in the clinicaltrials.gov records of the PLCO trial (NCT00002540).

Informed consent

All participants provided written informed consent prior to inclusion into the PLCO trial.

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Abdel-Rahman, O., Tang, P.A. & Cheung, W.Y. Subtype-specific risk factors for postmenopausal breast cancer: findings from the PLCO trial. Clin Transl Oncol 22, 1885–1891 (2020). https://doi.org/10.1007/s12094-020-02329-3

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  • DOI: https://doi.org/10.1007/s12094-020-02329-3

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