title: Clinical response to primary letrozole therapy in elderly patients with early breast cancer: possible role for p53 as a biomarker.
abstract: Primary tamoxifen therapy has been widely used to treat elderly women with ER-positive breast cancer in the past. Aromatase inhibitors may be more beneficial than tamoxifen when used as primary endocrine therapy in elderly patients. We aimed to retrospectively evaluate a series of elderly women with ER-positive breast cancer treated with primary letrozole therapy as sole therapy with a minimum of 5 years follow up. To identify possible predictive biomarkers a pilot immunohistochemical analysis was performed to assess the expression of PR, HER2, EGFR, BCL2 and p53. A total of 45 women, aged more than 70 years with a diagnosis of ER-positive breast cancer that was treated with primary letrozole therapy were identified. A case note review was undertaken to obtain clinical information. Formalin fixed paraffin embedded tumour tissue from diagnostic core biopsies was available for all patients. Immunohistochemical analysis was performed to establish the protein expression status of p53, PR, HER2, EGFR and BCL2. The mean age of the 45 patients was 87 years (range 70-101). Clinical benefit was seen in 60% of the patients. Median progression free survival was 53 months (95% CI - 34-72) and the median time to progression was 43 months (95% CI - 22-64). BCL2 was expressed in 45/45 (100%); PR in 38/45 (84%); EGFR in 13/45 (28%); HER2 in 9/45 (20%) and p53 in 5/45 (11%) of tissue samples. Positive expression of p53 was associated with poor progression free survival (p = 0.03) in this pilot study. This study demonstrates that letrozole as sole treatment appears to be a suitable treatment option for elderly patients with ER-positive breast cancer who are not fit for, or decline, surgery. The analysis of p53 in a larger study is warranted in order to assess its role as a biomarker in this patient group.
authors.affiliation: Postgraduate Medical Institute of the University of Hull, Hull, UK; Breast Care Unit, Hull and East Yorkshire NHS Trust, Hull, UK.
authors.forename: Veerabhadram
authors.initials: V
authors.lastname: Garimella
authors.affiliation: Postgraduate Medical Institute of the University of Hull, Hull, UK; Breast Care Unit, Hull and East Yorkshire NHS Trust, Hull, UK; Hull York Medical School, Hull, UK.
authors.forename: Tasadooq
authors.initials: T
authors.lastname: Hussain
authors.affiliation: Postgraduate Medical Institute of the University of Hull, Hull, UK; Queens Centre for Oncology and Haematology, Hull and East Yorkshire NHS Trust, Hull, UK; Hull York Medical School, Hull, UK.
authors.forename: Vijay
authors.initials: V
authors.lastname: Agarwal
authors.affiliation: Postgraduate Medical Institute of the University of Hull, Hull, UK; Breast Care Unit, Hull and East Yorkshire NHS Trust, Hull, UK.
authors.forename: Selvi
authors.initials: S
authors.lastname: Radhakrishna
authors.affiliation: Breast Care Unit, Hull and East Yorkshire NHS Trust, Hull, UK.
authors.forename: John N
authors.initials: JN
authors.lastname: Fox
authors.affiliation: Breast Care Unit, Hull and East Yorkshire NHS Trust, Hull, UK.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Kneeshaw
authors.affiliation: Histopathology Department, Hull and East Yorkshire NHS Trust, Hull, UK.
authors.forename: Ervine D
authors.initials: ED
authors.lastname: Long
authors.affiliation: Breast Care Unit, Hull and East Yorkshire NHS Trust, Hull, UK.
authors.forename: Tapan K
authors.initials: TK
authors.lastname: Mahapatra
authors.affiliation: Breast Care Unit, Hull and East Yorkshire NHS Trust, Hull, UK.
authors.forename: Penelope L
authors.initials: PL
authors.lastname: McManus
authors.affiliation: Postgraduate Medical Institute of the University of Hull, Hull, UK; Queens Centre for Oncology and Haematology, Hull and East Yorkshire NHS Trust, Hull, UK; Hull York Medical School, Hull, UK.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Lind
authors.affiliation: Postgraduate Medical Institute of the University of Hull, Hull, UK; Breast Care Unit, Hull and East Yorkshire NHS Trust, Hull, UK; Hull York Medical School, Hull, UK.
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Drew
authors.affiliation: Postgraduate Medical Institute of the University of Hull, Hull, UK; Hull York Medical School, Hull, UK. Electronic address: L.Cawkwell@hull.ac.uk.
authors.forename: Lynn
authors.initials: L
authors.lastname: Cawkwell
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D047072:Aromatase Inhibitors / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000737:chemistry* / Q000188:drug therapy* / Q000473:pathology; D018572:Disease-Free Survival; D066246:ErbB Receptors; D005260:Female; D006801:Humans; D000077289:Letrozole; D009570:Nitriles / Q000627:therapeutic use*; D010865:Pilot Projects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis; D012189:Retrospective Studies; D013629:Tamoxifen / Q000008:administration & dosage; D014230:Triazoles / Q000627:therapeutic use*; D016159:Tumor Suppressor Protein p53 / Q000032:analysis*
chemical_list: D000970:Antineoplastic Agents; D047072:Aromatase Inhibitors; D014408:Biomarkers, Tumor; D066246:ErbB Receptors; D000077289:Letrozole; D009570:Nitriles; D019253:Proto-Oncogene Proteins c-bcl-2; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D013629:Tamoxifen; D014230:Triazoles; D016159:Tumor Suppressor Protein p53; C000595707:BCL2 protein, human; C508053:ERBB2 protein, human
keywords: Aromatase inhibitor; Breast cancer; ER; Elderly; Letrozole; p53