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. 2020 May;181(1):181-188.
doi: 10.1007/s10549-020-05612-7. Epub 2020 Apr 3.

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

Anh N Le  1 , Joanna Harton  2 , Heena Desai  1 , Jacquelyn Powers  1 , Kristin Zelley  3 , Angela R Bradbury  1   4 , Katherine L Nathanson  4   5   6 , Payal D Shah  1   4 , Abigail Doucette  7 , Gary M Freedman  4   7 , Peter Gabriel  4   7 , Susan M Domchek  1   4 , Suzanne P MacFarland  3   8 , Kara N Maxwell  9   10   11
Affiliations

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

Anh N Le et al. Breast Cancer Res Treat. 2020 May.

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.

Keywords: Breast cancer; Li-Fraumeni syndrome; Radiation-induced malignancy; Radiotherapy.

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Conflict of interest statement

COMPLIANCE WITH ETHICAL STANDARDS

Disclosure of potential conflicts 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.

Figures

Fig. 1
Fig. 1. Personal cancer trajectory of breast cancer patients with LFS.
Cancer diagnoses are depicted as a function of age for patients with one or more breast cancers only, multiple primary tumors with breast cancer as first diagnosis, and multiple primary tumors with another cancer as first diagnosis. PC-11–1 and PC-21–1 presented with a malignant phyllodes tumor in the breast as their first diagnosis, coded as a soft-tissue sarcoma. PC-27–1 developed a radiation-induced sarcoma 4 years after radiotherapy for breast cancer. PC-67–1 developed thyroid cancer 10 years following radiotherapy for breast cancer
Fig. 2
Fig. 2. Incidence of radiation-induced sarcoma and recurrence by radiation treatment regimen.
Flow sheet depicting the treatment history of 51 patients in the LFS breast cancer cohort. Data shows the number of patients that developed of sarcoma in the radiation field. BC, breast cancer; NOS, not specified otherwise; PMRT, post-mastectomy radiotherapy; XRT, radiotherapy
See this image and copyright information in PMC

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