title: Prognostic significance of oncogenic markers in ductal carcinoma in situ of the breast: a clinicopathologic study.
abstract: Ductal carcinoma in situ (DCIS) is a heterogeneous malignant condition of the breast with an excellent prognosis. Until recently mastectomy was the standard treatment. As the results of the National Surgical Adjuvant Breast and Bowel Project-17 trial and the introduction of the Van Nuys Prognostic Index (VNPI) less radical therapies are used. Objectives are to identify clinicopathologic and biologic factors that may predict outcome. Cases of DCIS diagnosed in two Belgian University Centers were included. Paraffin-embedded material and Hematoxylin and Eosin stained slides of DCIS cases were reviewed and tumor size, margin width, nuclear grade, and comedo necrosis were assessed. Molecular markers (estrogen receptor, progesterone receptor, HER1-4, Ki67, and c-myc) were assayed immunohistochemically. Applied treatment strategies were correlated with the prospective use of the VNPI score. Kaplan-Meier survival plots were generated with log-rank significance and multiple regression analysis was carried out using Cox proportional hazards regression analysis; 159 patients were included with a median age of 54 years (range 29-78); 141 had DCIS and 18 DCIS with microinvasion. The median time of follow-up was 54 months (range 5-253). Twenty-three patients developed a recurrence (14.5%). The median time to recurrence was 46 months (range 5-253). Before the introduction of the VNPI, 37.5% of the DCIS patients showed a recurrence while thereafter 6.7% recurred (p < 0.005). Two recurrences occurred in the VNPI group I (7.1%); seven in the VNPI group II (8.5%) (median time to recurrence 66.3 months) and 14 in the VNPI group III (28.5%) (median time to recurrence 40.2 months) (disease-free survival [DFS]: p < 0.05). A Cox proportional hazards regression analysis indicated that tumor size, margin width, pathologic class, and age were independent predictors of recurrence, but none of the studied molecular markers showed this. Overexpression of HER4 in the presence of HER3 was found to be associated with a better DFS (p < 0.05). This study confirms the value of the VNPI score and questions the benefit of an aggressive approach in the low-risk DCIS lesions. Independent predictors for recurrence included size, margin width, pathologic class, and age, but none of the molecular markers were part of it. Overexpression of HER4 in the presence of HER3 was associated with a better DFS.
authors.affiliation: Department of Medical Oncology, Antwerp University Hospital, Edegem, Belgium. sevilay.altintas@uza.be
authors.forename: Sevilay
authors.initials: S
authors.lastname: Altintas
authors.forename: Kathleen
authors.initials: K
authors.lastname: Lambein
authors.forename: Manon T
authors.initials: MT
authors.lastname: Huizing
authors.forename: Geert
authors.initials: G
authors.lastname: Braems
authors.forename: Fernando Tjin
authors.initials: FT
authors.lastname: Asjoe
authors.forename: Hilde
authors.initials: H
authors.lastname: Hellemans
authors.forename: Eric
authors.initials: E
authors.lastname: Van Marck
authors.forename: Joost
authors.initials: J
authors.lastname: Weyler
authors.forename: Marleen
authors.initials: M
authors.lastname: Praet
authors.forename: Rudy
authors.initials: R
authors.lastname: Van den Broecke
authors.forename: Jan B
authors.initials: JB
authors.lastname: Vermorken
authors.forename: Wiebren A
authors.initials: WA
authors.lastname: Tjalma
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000473:pathology* / Q000601:surgery; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000473:pathology* / Q000601:surgery; D002455:Cell Division; D005260:Female; D016259:Genes, myc; D006133:Growth Substances / Q000032:analysis; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000032:analysis; D008408:Mastectomy; D008875:Middle Aged; D009336:Necrosis; D009361:Neoplasm Invasiveness; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis
chemical_list: D014408:Biomarkers, Tumor; D006133:Growth Substances; D019394:Ki-67 Antigen; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone