Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2012 Feb 15;118(4):908-13.
doi: 10.1002/cncr.26377. Epub 2011 Jul 14.

Early onset HER2-positive breast cancer is associated with germline TP53 mutations

Amal Melhem-Bertrandt  1 , Jasmina Bojadzieva, Kaylene J Ready, Elias Obeid, Diane D Liu, Angelica M Gutierrez-Barrera, Jennifer K Litton, Olufunmilayo I Olopade, Gabriel N Hortobagyi, Louise C Strong, Banu K Arun
Affiliations

Early onset HER2-positive breast cancer is associated with germline TP53 mutations

Amal Melhem-Bertrandt et al. Cancer. .

Erratum in

  • Cancer. 2012 May 1;118(9):2561

Abstract

Background: Germline TP53 mutations predispose to early onset breast cancer in women and are associated with Li-Fraumeni syndrome. Published data on the pathological characteristics of breast cancer among women with TP53 mutations is limited.

Methods: We retrospectively reviewed the clinical records of women who underwent genetic testing for suspected germline TP53 mutations and who were diagnosed with breast cancer between 2000 and 2011. The pathological characteristics of the breast tumors from patients testing positive for a mutation (cases) were compared with those testing negative (controls).

Results: Patients who tested positive for germlineTP53 mutations (n = 30) were compared with controls (n = 79). Human epidermal growth factor receptor 2 (HER2) amplification and/or overexpression was found in 67% of the tumors from the cases, compared with 25% for the controls (P = .0001). Among patients with a mutation, 70% had estrogen receptor- and/or progesterone receptor-positive tumors, compared with 68% in the control group (P = .87). After adjusting for age at breast cancer diagnosis, having a HER2-positive tumor increased the odds of testing positive for a germline TP53 mutation (odds ratio, 6.9; 95% confidence interval, 2.6-18.2). For each yearly increment in age at breast cancer diagnosis, there was decreased likelihood of having a TP53 mutation of 5% (odds ratio, 0.95; 95% confidence interval0.91-0.99).

Conclusions: This study suggests an association between germline TP53 mutations and early onset HER2-positive breast cancer. If confirmed in a larger cohort, these results could guide genetic testing strategies, lead to chemoprevention trials incorporating HER2-targeted therapies, and elucidate some of the molecular pathways involved in breast cancer.

PubMed Disclaimer

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Li FP, Fraumeni JF., Jr Rhabdomyosarcoma in children: epidemiologic study and identification of a familial cancer syndrome. J Natl Cancer Inst. 1969 Dec;43(6):1365–1373. - PubMed
    1. Birch JM, Blair V, Kelsey AM, et al. Cancer phenotype correlates with constitutional TP53 genotype in families with the Li-Fraumeni syndrome. Oncogene. 1998 Sep 3;17(9):1061–1068. - PubMed
    1. Petitjean A, Achatz MI, Borresen-Dale AL, Hainaut P, Olivier M. TP53 mutations in human cancers: functional selection and impact on cancer prognosis and outcomes. Oncogene. 2007 Apr 2;26(15):2157–2165. - PubMed
    1. Hisada M, Garber JE, Fung CY, Fraumeni JF, Jr, Li FP. Multiple primary cancers in families with Li-Fraumeni syndrome. J Natl Cancer Inst. 1998 Apr 15;90(8):606–611. - PubMed
    1. Olivier M, Goldgar DE, Sodha N, et al. Li-Fraumeni and related syndromes: correlation between tumor type, family structure, and TP53 genotype. Cancer Res. 2003 Oct 15;63(20):6643–6650. - PubMed

Publication types

MeSH terms