Literature DB >> 25959805

Clinical outcomes in women with breast cancer and a PALB2 mutation: a prospective cohort analysis.

Cezary Cybulski1, Wojciech Kluźniak1, Tomasz Huzarski1, Dominika Wokołorczyk1, Aniruddh Kashyap1, Anna Jakubowska1, Marek Szwiec2, Tomasz Byrski1, Tadeusz Dębniak1, Bohdan Górski1, Victoria Sopik3, Mohammad R Akbari3, Ping Sun3, Jacek Gronwald1, Steven A Narod4, Jan Lubiński1.   

Abstract

BACKGROUND: Mutations in PALB2 predispose to breast cancer, but the effect on prognosis of carrying a PALB2 mutation has not been ascertained. We aimed to estimate the odds ratio for breast cancer in women with an inherited mutation in PALB2 and 10-year survival after breast cancer in patients who carry a PALB2 mutation.
METHODS: Between 1996 and 2012, patients with invasive breast cancer were recruited prospectively from 18 hospitals in Poland and genotyped for two deleterious mutations in PALB2 (509_510delGA and 172_175delTTGT). A control group of 4702 women without cancer was recruited for comparison. The primary endpoint was death from any cause, as determined by medical records from the Polish Ministry of the Interior and Administration. In patients with breast cancer, 10-year survival of carriers of a PALB2 mutation was calculated and compared with that of non-carriers.
FINDINGS: 17 900 women with breast cancer were invited to participate, of whom 12 529 were genotyped successfully. A PALB2 mutation was present in 116 (0·93%, 95% CI 0·76-1·09) of 12 529 patients and in ten (0·21%, 0·08-0·34) of 4702 controls (odds ratio 4·39, 95% CI 2·30-8·37; p<0·0001). 10-year survival for women with breast cancer and a PALB2 mutation was 48·0% (95% CI 36·5-63·2), compared with 74·7% (73·5-75·8) for patients with breast cancer without a mutation (adjusted hazard ratio for death 2·27, 95% CI 1·64-3·15; p<0·0001).
INTERPRETATION: Women with a PALB2 mutation face an increased risk of breast cancer and might be at a higher risk of death from breast cancer compared with non-carriers. Increased surveillance should be offered to unaffected women who carry a PALB2 mutation. FUNDING: Polish National Science Centre.
Copyright © 2015 Elsevier Ltd. All rights reserved.

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Year:  2015        PMID: 25959805     DOI: 10.1016/S1470-2045(15)70142-7

Source DB:  PubMed          Journal:  Lancet Oncol        ISSN: 1470-2045            Impact factor:   41.316


  52 in total

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