title: The clinical value of HER-2 overexpression and PIK3CA mutations in the older breast cancer population: a FOCUS study analysis.
abstract: Studies to confirm the effect of acknowledged prognostic markers in older breast cancer patients are scarce. The aim of this study was to evaluate the prognostic value of HER-2 overexpression and PIK3CA mutations in older breast cancer patients. Female breast cancer patients aged 65 years or older, diagnosed between 1997 and 2004 in a geographical region in The Netherlands, with an invasive, non-metastatic tumour and tumour material available, were included in the study. The primary endpoint was relapse-free period and secondary endpoint was relative survival. Determinants were immunochemical HER-2 scores (0/1+, 2+ or 3+) and PIK3CA as a binary measure. Overall, 1698 patients were included, and 103 had a HER-2 score of 3+. HER-2 overexpression was associated with a higher recurrence risk (5 years recurrence risk 34 % vs. 12 %, adjusted p = 0.005), and a worse relative survival (10 years relative survival 48 % vs. 84 % for HER-2 negative; p = 0.004). PIK3CA mutations had no significant prognostic effect. We showed, in older breast cancer patients, that HER-2 overexpression was significantly associated with a worse outcome, but PIK3CA mutations had no prognostic effect. These results imply that older patients with HER-2 overexpressing breast cancer might benefit from additional targeted anti-HER-2 therapy.
authors.affiliation: Department of Surgery, Leiden University Medical Center, Albinusdreef 2, 2300 RC, Leiden, The Netherlands.
authors.forename: Charla C
authors.initials: CC
authors.lastname: Engels
authors.affiliation: Department of Surgery, Leiden University Medical Center, Albinusdreef 2, 2300 RC, Leiden, The Netherlands. m.kiderlen@lumc.nl.|Department of Geriatrics and Gerontology, Leiden University Medical Center, Leiden, The Netherlands. m.kiderlen@lumc.nl.
authors.forename: Mandy
authors.initials: M
authors.lastname: Kiderlen
authors.affiliation: Department of Surgery, Leiden University Medical Center, Albinusdreef 2, 2300 RC, Leiden, The Netherlands.|Department of Geriatrics and Gerontology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Esther
authors.initials: E
authors.lastname: Bastiaannet
authors.affiliation: Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Ronald
authors.initials: R
authors.lastname: van Eijk
authors.affiliation: Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Antien
authors.initials: A
authors.lastname: Mooyaart
authors.affiliation: Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Vincent T H B M
authors.initials: VT
authors.lastname: Smit
authors.affiliation: Department of Geriatrics and Gerontology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Anton J M
authors.initials: AJ
authors.lastname: de Craen
authors.affiliation: Department of Surgery, Leiden University Medical Center, Albinusdreef 2, 2300 RC, Leiden, The Netherlands.
authors.forename: Peter J K
authors.initials: PJ
authors.lastname: Kuppen
authors.affiliation: Department of Clinical Oncology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Judith R
authors.initials: JR
authors.lastname: Kroep
authors.affiliation: Department of Surgery, Leiden University Medical Center, Albinusdreef 2, 2300 RC, Leiden, The Netherlands.
authors.forename: Cornelis J H
authors.initials: CJ
authors.lastname: van de Velde
authors.affiliation: Department of Surgery, Leiden University Medical Center, Albinusdreef 2, 2300 RC, Leiden, The Netherlands.
authors.forename: Gerrit Jan
authors.initials: GJ
authors.lastname: Liefers
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D058534:Class I Phosphatidylinositol 3-Kinases; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009154:Mutation; D009426:Netherlands; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics* / Q000378:metabolism; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D016019:Survival Analysis; D015854:Up-Regulation
chemical_list: D058534:Class I Phosphatidylinositol 3-Kinases; D019869:Phosphatidylinositol 3-Kinases; D018719:Erb-b2 Receptor Tyrosine Kinases; C484760:PIK3CA protein, human; C508053:ERBB2 protein, human
keywords: Anti-HER2 therapy; Breast cancer; Competing risk; Epidemiology; Geriatric oncology; HER-2; PIK3CA; Prognostic markers