The role ofTP53pathogenic variants in early-onset HER2-positive breast cancer

• Type: Article in International Scientific Journal
• Date: 2021

Authors

Escudeiro, C (Author) Other; Pinto, C (Author) Other; Vieira, J (Author) Other; Peixoto, A (Author) Other; Pinto, P (Author) Other; Pinheiro, M (Author) Other; Santos, C (Author) Other; Guerra, J (Author) Other; Lisboa, S (Author) Other; Santos, R (Author) Other; Silva, J (Author) Other; Leal, C (Author) Other; Coimbra, N (Author) Other; Lopes, P (Author) Other; Ferreira, M (Author) Other; Sousa, AB (Author) Other; Manuel R Teixeira (Author) ICBAS

Journal

Title: Familial Cancer

Vol. 20

Pages: 173-180

ISSN: 1389-9600

Publisher: Springer Nature

Indexing

ISI Web of Knowledge - 1 Citation

Scopus - 1 Citation

Other information

Authenticus ID: P-00S-VS0

DOI: 10.1007/s10689-020-00212-2

Abstract (EN): Breast cancer is the most frequent event in Li-Fraumeni syndrome associated with germlineTP53variants. Some studies have shown that breast cancers in women with Li-Fraumeni syndrome are commonly HER2-positive, suggesting thatHER2amplification or over-expression in a young woman may be a useful criterion to test for germline variants in theTP53gene. We assessed the prevalence of germlineTP53variants by Sanger sequencing or next-generation sequencing in 149 women with HER2-positive breast cancer diagnosed until age 40. The pattern ofHER2amplification was evaluated with dual-probe FISH in a subset of breast carcinomas from patients with germlineTP53variants as compared with those of noncarriers. Among 149 women tested, three presented a deleteriousTP53germline variant (2%), with one patient diagnosed at age 31 and the other two with bilateral breast cancer at ages 29/33 and 28/32, respectively. Three of the 36 patients (8.3%) with the first breast cancer diagnosed at age 31 or younger presented a pathogenicTP53variant. Additionally, allTP53deleterious variant carriers had a first degree relative diagnosed with different early-onset cancers (frequently not belonging to the Li-Fraumeni syndrome tumor spectrum) diagnosed at age 45 or younger. Higher levels ofHER2amplification were found in breast carcinomas ofTP53pathogenic variant carriers than in those of noncarriers. Deleterious germlineTP53variants account for a small proportion of early-onset HER2-positive breast cancers, but these seem to have higherHER2amplification ratios. AllTP53pathogenic variant carriers found in this study had the first breast carcinoma diagnosed at age 31 or younger and a first-degree relative with early-onset cancer. Further studies are needed to clarify if HER2 status in early-onset breast cancer patients, in combination with other personal and/or familial cancer history, is useful to update theTP53testing criteria.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 8