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Frequency of radiation-induced malignancies post-adjuvant radiotherapy for breast cancer in patients with Li-Fraumeni syndrome

  • Epidemiology
  • Published:
Breast Cancer Research and Treatment Aims and scope Submit manuscript

Abstract

Purpose

Women with Li-Fraumeni syndrome (LFS), a cancer predisposition syndrome caused by germline mutations in TP53, have an over 50% risk of developing breast cancer by age 70. Patients with LFS are at risk for radiation-induced malignancies; however, only small case series have prior investigated radiation risks in the treatment of breast cancer. We therefore aimed to investigate the risk of malignancy in breast cancer patients with LFS following adjuvant radiotherapy.

Methods

A single-institution retrospective chart review was conducted for female breast cancer patients with confirmed germline TP53 mutation. The frequency of radiation-induced malignancies in LFS patients was compared to non-LFS breast cancer cases reported in the Penn Medicine Cancer Registry via statistical analyses.

Results

We identified 51 female LFS breast cancer patients with 74 primary diagnoses. Fifty-seven% had a history of breast cancer only, and 25% had breast cancer as their presenting diagnosis of LFS. LFS-associated breast cancers were predominantly invasive ductal carcinoma (48%) and HER2+ (58%). Twenty patients underwent adjuvant radiotherapy with a median follow-up of 12.5 (2–20) years. Of 18 patients who received radiation in a curative setting, one (6%) patient developed thyroid cancer, and one (6%) patient developed sarcoma in the radiation field. This risk for radiation-induced malignancy associated with LFS was higher for both sarcoma and thyroid cancer in comparison with the control cohort.

Conclusions

We found a lower risk of radiation-induced secondary malignancies in LFS breast cancer patients than previously reported in the literature (33% risk of radiation-induced sarcoma). These findings suggest that LFS may not be an absolute contraindication for radiotherapy in breast cancer. The potential risk for locoregional recurrence without radiotherapy must be weighed against the long-term risk for radiation-induced malignancies in consideration of adjuvant radiotherapy for LFS breast cancer patients.

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Data availability

The datasets during and/or analyzed during the current study are available from the corresponding author on reasonable request.

Abbreviations

LFS:

Li-Fraumeni syndrome

LFL:

Li-Fraumeni-like

BC:

Breast cancer

LRR:

Locoregional recurrence

IDC:

Invasive ductal carcinoma

DCIS:

Ductal carcinoma in situ

MDLC:

Mixed ductal and lobular carcinoma

NOS:

Not otherwise specified

HR:

Hormone receptor

ER:

Estrogen receptor

XRT:

Radiotherapy

N/A:

Not applicable

i/d:

Insufficient data

BLM:

Bilateral mastectomy

ULM:

Unilateral mastectomy

PM:

Partial mastectomy

CW:

Chest wall

NED:

No evidence of disease

Decd.:

Deceased

Met.:

Metastatic

OC:

Other cause

sp:

Splicing

trunc:

Truncating

DBD:

DNA binding domain

TD:

Tetramerization domain

LGR:

Large genomic rearrangement

PMRT:

Post-mastectomy radiotherapy

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Funding

This work is supported by the Institute for Translational Medicine and Therapeutics at the University of Pennsylvania (ITMAT MHB, ANL, SPM, KNM), the National Cancer Institute (K08CA21531, KNM), and the Burroughs Wellcome Foundation (1017184, KNM).

Author information

Authors and Affiliations

  1. Division of Hematology/Oncology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA

    Anh N. Le, Heena Desai, Jacquelyn Powers, Angela R. Bradbury, Payal D. Shah, Susan M. Domchek & Kara N. Maxwell

  2. Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA

    Joanna Harton

  3. Division of Oncology, Department of Pediatrics, Children’s Hospital of Philadelphia, Philadelphia, PA, 19104, USA

    Kristin Zelley & Suzanne P. MacFarland

  4. Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, 19104, USA

    Angela R. Bradbury, Katherine L. Nathanson, Payal D. Shah, Gary M. Freedman, Peter Gabriel, Susan M. Domchek & Kara N. Maxwell

  5. Division of Translational Medicine and Human Genetics, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA

    Katherine L. Nathanson

  6. Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA

    Katherine L. Nathanson & Kara N. Maxwell

  7. Department of Radiation Oncology, University of Pennsylvania, Philadelphia, PA, 19104, USA

    Abigail Doucette, Gary M. Freedman & Peter Gabriel

  8. Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA

    Suzanne P. MacFarland

Authors
  1. Anh N. Le
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  2. Joanna Harton
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  14. Kara N. Maxwell
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Contributions

Study concept and design were performed by ANL and KNM. Data acquisition was performed by ANL, AD, and PG. Data analysis and interpretation were performed by ANL, JH, and KNM. Figure generation was by ANL, HD, and KNM. Writing was performed by ANL, AB, AD, HD, JH, GF, PG, JP, SMD, SPM, KN, PDS, KNM, and KZ.

Corresponding author

Correspondence to Kara N. Maxwell.

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Conflict of interest

Author SMD has received honoraria from Clovis, Bristol-Myers Squibb, and AstraZeneca. Author AB has an advisory role at AstraZeneca and Merck and has received research fund not related to this manuscript from AstraZeneca and Merck. All other authors declare that they have no potential conflict of interest.

Ethical approval

All studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

This single-institution human subjects' retrospective chart review is qualified for exempt status and does not require informed consent or waiver of consent.

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Le, A.N., Harton, J., Desai, H. et al. Frequency of radiation-induced malignancies post-adjuvant radiotherapy for breast cancer in patients with Li-Fraumeni syndrome. Breast Cancer Res Treat 181, 181–188 (2020). https://doi.org/10.1007/s10549-020-05612-7

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  • DOI: https://doi.org/10.1007/s10549-020-05612-7

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