title: Expression of ras p21, p53 and c-erbB-2 in advanced breast cancer and response to first line hormonal therapy.
abstract: Several oncogenes and tumour-suppressor genes have been identified that may have an important role in the development of human breast carcinoma. Furthermore, some of these gene alterations may be linked to the development of invasion and subsequent metastasis. Alterations in the expression of ras p21, p53 and c-erbB-2 have all been linked to tumours with rapid cellular proliferation, but the evidence that they are of prognostic importance in patients with breast cancer is conflicting. This study explores the relationship between expression of these oncoproteins and clinical outcome in 92 patients with either locally advanced or metastatic breast cancer treated with primary endocrine therapy. Specimens of the primary carcinoma were available for analysis of hormone receptor, Ki67 labelling index, epidermal growth factor receptor (EGFR), c-erbB-2, p53 and ras p21. Clinical response was measured according to UICC criteria after 6 months of treatment and all patients were followed for time to progression and overall survival. As shown previously, oestrogen receptor (ER) negativity, high Ki67 labelling index and EGFR overexpression were associated with a shorter time to progression and overall survival. However, no statistically significant relationship existed between expression of ras p21, p53 or c-erbB-2 and response to treatment, time to progression or overall survival. We conclude that staining for these three oncoproteins has no role in therapeutic decision-making in patients with advanced breast cancer. The negative finding implies that while abnormal expression of these genes may have an important role in the development of breast cancer, the variations in growth characteristics of advanced breast cancer may be influenced by other factors.
authors.affiliation: Professional Unit of Surgery, Nottingham City Hospital, UK.
authors.forename: S G
authors.initials: SG
authors.lastname: Archer
authors.forename: A
authors.initials: A
authors.lastname: Eliopoulos
authors.forename: D
authors.initials: D
authors.lastname: Spandidos
authors.forename: D
authors.initials: D
authors.lastname: Barnes
authors.forename: I O
authors.initials: IO
authors.lastname: Ellis
authors.forename: R W
authors.initials: RW
authors.lastname: Blamey
authors.forename: R I
authors.initials: RI
authors.lastname: Nicholson
authors.forename: J F
authors.initials: JF
authors.lastname: Robertson
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D066246:ErbB Receptors / Q000032:analysis; D004965:Estrogen Antagonists / Q000627:therapeutic use*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D017273:Goserelin / Q000627:therapeutic use*; D006801:Humans; D019394:Ki-67 Antigen; D015993:Life Tables; D008535:Megestrol / Q000031:analogs & derivatives* / Q000627:therapeutic use; D019290:Megestrol Acetate; D008593:Menopause; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D009687:Nuclear Proteins / Q000032:analysis; D016016:Proportional Hazards Models; D016283:Proto-Oncogene Proteins p21(ras) / Q000096:biosynthesis* / Q000235:genetics; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis / Q000235:genetics*; D011960:Receptors, Estrogen / Q000032:analysis; D013629:Tamoxifen / Q000627:therapeutic use*; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D018931:Antineoplastic Agents, Hormonal; D066246:ErbB Receptors; D004965:Estrogen Antagonists; D017273:Goserelin; D019394:Ki-67 Antigen; D008535:Megestrol; D019290:Megestrol Acetate; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D016283:Proto-Oncogene Proteins p21(ras); D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D013629:Tamoxifen; D016159:Tumor Suppressor Protein p53; C501009:HRAS protein, human