title: Impact of triple negative phenotype on breast cancer prognosis.
abstract: Triple negative (TN) [estrogen receptor (ER), progesterone receptor (PgR)] (ER-/PgR-/Her2/neu-) breast cancer (BC) is an aggressive disease without tumor-specific treatment options. Our objective is to evaluate the relative contribution of combined Her2/neu (Her2) and hormone receptor (HR) status to BC progression. A prospective primary BC cohort of 1550 patients at our institution, stage I-IV, from 1998 to 2003 were categorized by HR and Her2 status into ER+/PgR+/Her2- (HR+/Her2-) (n = 1134), ER+/PgR+/Her2+ [triple positive (TP)] (n = 138), ER-/PgR-/Her2- (TN) (n = 183), and ER-/PgR-/Her2+ (HR-/Her2+) (n = 95). Clinical variables were chart abstracted and vital and disease status updated annually. Log-rank tests and Cox regression analyses were used to assess associations with survival. Patient age ranged from 21 to 88 years and average length of follow-up was 4.24 years. Overall survival at 5 years was 94% (HR+/Her2-), 91% (TP), and 81% (TN and HR-/Her2+) (log rank test = 22.22, p < 0.001). Disease-specific survival at 5 years was 98% (HR+/Her2-), 93% (TP), 88% (TN), and 86% (HR-/Her2+) (log rank test = 25.85, p < 0.001) and 5-year relapse-free survival was 95% (HR+/Her2-), 89% (TP), 84% (TN), and 76% (HR-/Her2+) (log rank test = 20.29, p < 0.001). In a model adjusted for age, race, TNM stage, and treatment using HR+/Her2- patients as the reference group, recurrence risk was 1.98 for TP (95% CI = 1.02 to 3.84), 2.32 for TN (95% CI = 1.32 to 4.08), and 4.25 for HR-/Her2+ patients (95% CI = 2.33, 7.75). A hierarchy of BC phenotypes defined by HR and Her2 status exists with progressively worse disease outcomes by category.
authors.affiliation: Swedish Cancer Institute at Swedish Medical Center, Swedish Cancer Institute, Seattle, WA, USA. hank.kaplan@swedish.org
authors.forename: Henry G
authors.initials: HG
authors.lastname: Kaplan
authors.forename: Judith A
authors.initials: JA
authors.lastname: Malmgren
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D001707:Biopsy, Needle; D001943:Breast Neoplasms / Q000235:genetics / Q000401:mortality* / Q000628:therapy*; D015331:Cohort Studies; D003131:Combined Modality Therapy; D016001:Confidence Intervals; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D009367:Neoplasm Staging; D016017:Odds Ratio; D010641:Phenotype; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism*; D011980:Receptors, Progesterone / Q000235:genetics / Q000378:metabolism*; D012189:Retrospective Studies; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone