Skip to main content
Erschienen in: Breast Cancer Research and Treatment 1/2020

03.04.2020 | Epidemiology

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

verfasst von: Anh N. Le, Joanna Harton, Heena Desai, Jacquelyn Powers, Kristin Zelley, Angela R. Bradbury, Katherine L. Nathanson, Payal D. Shah, Abigail Doucette, Gary M. Freedman, Peter Gabriel, Susan M. Domchek, Suzanne P. MacFarland, Kara N. Maxwell

Erschienen in: Breast Cancer Research and Treatment | Ausgabe 1/2020

Einloggen, um Zugang zu erhalten

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.
Anhänge
Nur mit Berechtigung zugänglich
Literatur
1.
Zurück zum Zitat Mai PL, Best AF, Peters JA, DeCastro RM, Khincha PP, Loud JT, Bremer RC, Rosenberg PS, Savage SA (2016) Risks of first and subsequent cancers among TP53 mutation carriers in the National Cancer Institute Li-Fraumeni syndrome cohort. Cancer 122(23):3673–3681CrossRef Mai PL, Best AF, Peters JA, DeCastro RM, Khincha PP, Loud JT, Bremer RC, Rosenberg PS, Savage SA (2016) Risks of first and subsequent cancers among TP53 mutation carriers in the National Cancer Institute Li-Fraumeni syndrome cohort. Cancer 122(23):3673–3681CrossRef
3.
Zurück zum Zitat Bougeard G, Renaux-Petel M, Flaman J-M, Charbonnier C, Fermey P, Belotti M, Gauthier-Villars M, Stoppa-Lyonnet D, Consolino E, Brugieres L, Caron O, Benusiglio PR, Bressac-de Paillerets B, Bonadona V, Bonaiti-Pellie C, Tinat J, Baert-Desurmont S, Frebourg T (2015) Revisiting Li-Fraumeni syndrome from TP53 mutation carriers. J Clin Oncol 33(21):2345–2352CrossRef Bougeard G, Renaux-Petel M, Flaman J-M, Charbonnier C, Fermey P, Belotti M, Gauthier-Villars M, Stoppa-Lyonnet D, Consolino E, Brugieres L, Caron O, Benusiglio PR, Bressac-de Paillerets B, Bonadona V, Bonaiti-Pellie C, Tinat J, Baert-Desurmont S, Frebourg T (2015) Revisiting Li-Fraumeni syndrome from TP53 mutation carriers. J Clin Oncol 33(21):2345–2352CrossRef
4.
Zurück zum Zitat Kratz CP, Achatz MI, Brugieres L, Frebourg T, Garber JE, Greer MC, Hansford JR, Janeway KA, Kohlmann WK, McGee R, Mullighan CG, Onel K, Pajtler KW, Pfister SM, Savage SA, Schiffman JD, Schneider KA, Strong LC, Evans DGR, Wasserman JD, Villani A, Malkin D (2017) Cancer screening recommendations for individuals with Li-Fraumeni syndrome. Clin Cancer Res 23(11):e38–e45. https://doi.org/10.1158/1078-0432.CCR-17-0408 CrossRefPubMed Kratz CP, Achatz MI, Brugieres L, Frebourg T, Garber JE, Greer MC, Hansford JR, Janeway KA, Kohlmann WK, McGee R, Mullighan CG, Onel K, Pajtler KW, Pfister SM, Savage SA, Schiffman JD, Schneider KA, Strong LC, Evans DGR, Wasserman JD, Villani A, Malkin D (2017) Cancer screening recommendations for individuals with Li-Fraumeni syndrome. Clin Cancer Res 23(11):e38–e45. https://​doi.​org/​10.​1158/​1078-0432.​CCR-17-0408 CrossRefPubMed
5.
Zurück zum Zitat Abdel Razek AAK, Gaballa G, Denewer A, Tawakol I (2010) Diffusion weighted MR imaging of the breast. Acad Radiol 17(3):382–386CrossRef Abdel Razek AAK, Gaballa G, Denewer A, Tawakol I (2010) Diffusion weighted MR imaging of the breast. Acad Radiol 17(3):382–386CrossRef
8.
Zurück zum Zitat De Moura J, Kavalec FL, Doghman M, Rosati R, Custodio G, Lalli E, Cavallari GMD, Santa Maria J, Figueiredo BC (2010) Heterozygous TP53stop146/R72P fibroblasts from a Li-Fraumeni syndrome patient with impaired response to DNA damage. Int J Oncol 36(4):983–990PubMed De Moura J, Kavalec FL, Doghman M, Rosati R, Custodio G, Lalli E, Cavallari GMD, Santa Maria J, Figueiredo BC (2010) Heterozygous TP53stop146/R72P fibroblasts from a Li-Fraumeni syndrome patient with impaired response to DNA damage. Int J Oncol 36(4):983–990PubMed
9.
Zurück zum Zitat Kasper E, Angot E, Colasse E, Nicol L, Sabourin J-C, Adriouch S, Lacoume Y, Charbonnier C, Raad S, Frebourg T, Flaman J-M, Bougeard G (2018) Contribution of genotoxic anticancer treatments to the development of multiple primary tumours in the context of germline TP53 mutations. Eur J Cancer 101:254–262CrossRef Kasper E, Angot E, Colasse E, Nicol L, Sabourin J-C, Adriouch S, Lacoume Y, Charbonnier C, Raad S, Frebourg T, Flaman J-M, Bougeard G (2018) Contribution of genotoxic anticancer treatments to the development of multiple primary tumours in the context of germline TP53 mutations. Eur J Cancer 101:254–262CrossRef
11.
Zurück zum Zitat Surveillance, Epidemiology, and End Results (SEER) Program released April 2019, based on the November 2018 submissions Surveillance, Epidemiology, and End Results (SEER) Program released April 2019, based on the November 2018 submissions
12.
Zurück zum Zitat Melhem-Bertrandt A, Bojadzieva J, Ready KJ, Obeid E, Liu DD, Gutierrez-Barrera AM, Litton JK, Olopade OI, Hortobagyi GN, Strong LC, Arun BK (2012) Early onset HER2-positive breast cancer is associated with germline TP53 mutations. Cancer 118(4):908–913CrossRef Melhem-Bertrandt A, Bojadzieva J, Ready KJ, Obeid E, Liu DD, Gutierrez-Barrera AM, Litton JK, Olopade OI, Hortobagyi GN, Strong LC, Arun BK (2012) Early onset HER2-positive breast cancer is associated with germline TP53 mutations. Cancer 118(4):908–913CrossRef
13.
Zurück zum Zitat Limacher JM, Frebourg T, Natarajan-Ame S, Bergerat JP (2001) Two metachronous tumors in the radiotherapy fields of a patient with Li-Fraumeni syndrome. Int J Cancer 96(4):238–242CrossRef Limacher JM, Frebourg T, Natarajan-Ame S, Bergerat JP (2001) Two metachronous tumors in the radiotherapy fields of a patient with Li-Fraumeni syndrome. Int J Cancer 96(4):238–242CrossRef
14.
Zurück zum Zitat Salmon A, Amikam D, Sodha N, Davidson S, Basel-Vanagaite L, Eeles RA, Abeliovich D, Peretz T (2007) Rapid development of post-radiotherapy sarcoma and breast cancer in a patient with a novel germline 'de-novo' TP53 mutation. Clin Oncol (R Coll Radiol) 19(7):490–493CrossRef Salmon A, Amikam D, Sodha N, Davidson S, Basel-Vanagaite L, Eeles RA, Abeliovich D, Peretz T (2007) Rapid development of post-radiotherapy sarcoma and breast cancer in a patient with a novel germline 'de-novo' TP53 mutation. Clin Oncol (R Coll Radiol) 19(7):490–493CrossRef
15.
Zurück zum Zitat Heymann S, Delaloge S, Rahal A, Caron O, Frebourg T, Barreau L, Pachet C, Mathieu M-C, Marsiglia H, Bourgier C (2010) Radio-induced malignancies after breast cancer postoperative radiotherapy in patients with Li-Fraumeni syndrome. Radiat Oncol 5:104CrossRef Heymann S, Delaloge S, Rahal A, Caron O, Frebourg T, Barreau L, Pachet C, Mathieu M-C, Marsiglia H, Bourgier C (2010) Radio-induced malignancies after breast cancer postoperative radiotherapy in patients with Li-Fraumeni syndrome. Radiat Oncol 5:104CrossRef
16.
Zurück zum Zitat Evans DGR, Birch JM, Ramsden RT, Sharif S, Baser ME (2006) Malignant transformation and new primary tumours after therapeutic radiation for benign disease: substantial risks in certain tumour prone syndromes. J Med Genet 43(4):289–294CrossRef Evans DGR, Birch JM, Ramsden RT, Sharif S, Baser ME (2006) Malignant transformation and new primary tumours after therapeutic radiation for benign disease: substantial risks in certain tumour prone syndromes. J Med Genet 43(4):289–294CrossRef
17.
Zurück zum Zitat Birch JM, Alston RD, McNally RJ, Evans DG, Kelsey AM, Harris M, Eden OB, Varley JM (2001) Relative frequency and morphology of cancers in carriers of germline TP53 mutations. Oncogene 20(34):4621–4628CrossRef Birch JM, Alston RD, McNally RJ, Evans DG, Kelsey AM, Harris M, Eden OB, Varley JM (2001) Relative frequency and morphology of cancers in carriers of germline TP53 mutations. Oncogene 20(34):4621–4628CrossRef
18.
Zurück zum Zitat Recht A, Comen EA, Fine RE, Fleming GF, Hardenbergh PH, Ho AY, Hudis CA, Hwang ES, Kirshner JJ, Morrow M, Salerno KE, SledgeSolin GWLJ, Spears PA, Whelan TJ, Somerfield MR, Edge SB (2017) Postmastectomy radiotherapy: an American Society of Clinical Oncology, American Society for Radiation Oncology, and Society of Surgical Oncology focused guideline update. Ann Surg Oncol 24(1):38–51CrossRef Recht A, Comen EA, Fine RE, Fleming GF, Hardenbergh PH, Ho AY, Hudis CA, Hwang ES, Kirshner JJ, Morrow M, Salerno KE, SledgeSolin GWLJ, Spears PA, Whelan TJ, Somerfield MR, Edge SB (2017) Postmastectomy radiotherapy: an American Society of Clinical Oncology, American Society for Radiation Oncology, and Society of Surgical Oncology focused guideline update. Ann Surg Oncol 24(1):38–51CrossRef
Metadaten
Titel
Frequency of radiation-induced malignancies post-adjuvant radiotherapy for breast cancer in patients with Li-Fraumeni syndrome
verfasst von
Anh N. Le
Joanna Harton
Heena Desai
Jacquelyn Powers
Kristin Zelley
Angela R. Bradbury
Katherine L. Nathanson
Payal D. Shah
Abigail Doucette
Gary M. Freedman
Peter Gabriel
Susan M. Domchek
Suzanne P. MacFarland
Kara N. Maxwell
Publikationsdatum
03.04.2020
Verlag
Springer US
Erschienen in
Breast Cancer Research and Treatment / Ausgabe 1/2020
Print ISSN: 0167-6806
Elektronische ISSN: 1573-7217
DOI
https://doi.org/10.1007/s10549-020-05612-7

Weitere Artikel der Ausgabe 1/2020

Breast Cancer Research and Treatment 1/2020 Zur Ausgabe

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.