title: Tissue inhibitor of metalloproteinase-4 is elevated in early-stage breast cancers with accelerated progression and poor clinical course.
abstract: An increasing number of breast cancer patients are diagnosed with small, localized, early-stage tumors. These patients are typically thought to have a good prognosis for long-term disease-free survival, but epidemiological studies indicate that up to 30% may have a recurrence within 3 to 5 years of diagnosis. Identifying patients with a high risk of recurrence and/or progression is important because they could be more aggressively treated at diagnosis to improve their chances for disease-free survival. Recent evidence suggests that elevated levels of the matrix metalloproteinase inhibitor, tissue inhibitor of metalloproteinase (TIMP)-4, are associated with malignant progression of ductal carcinoma in situ, a precancerous lesion. To examine the association of TIMP-4 with survival outcomes, we conducted a retrospective immunohistochemical analysis of 314 cases from patients with early-stage disease, defined as tumors smaller than 2 cm and no spread to lymph nodes (tumor-node-metastasis staging: T1N0MX). We found that tumors with elevated levels of TIMP-4 were correlated with a reduced probability of long-term disease-free survival, especially in patients with estrogen receptor-negative tumors. Our findings prompt further evaluation of TIMP-4 as a simple prognostic marker that may help identify patients with early-stage breast cancer who could benefit from more aggressive treatment at diagnosis.
authors.affiliation: Department of Hematology/Oncology, Lankenau Hospital, 100 Lancaster Ave., Wynnewood, PA 19096, USA.
authors.forename: Michaelann
authors.initials: M
authors.lastname: Liss
authors.forename: Nandhini
authors.initials: N
authors.lastname: Sreedhar
authors.forename: Albert
authors.initials: A
authors.lastname: Keshgegian
authors.forename: Guido
authors.initials: G
authors.lastname: Sauter
authors.forename: Michael R
authors.initials: MR
authors.lastname: Chernick
authors.forename: George C
authors.initials: GC
authors.lastname: Prendergast
authors.forename: U Margaretha
authors.initials: UM
authors.lastname: Wallon
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor; D001943:Breast Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000378:metabolism / Q000473:pathology; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D011960:Receptors, Estrogen / Q000378:metabolism; D012189:Retrospective Studies; D019714:Tissue Inhibitor of Metalloproteinases / Q000096:biosynthesis*; D000097792:Tissue Inhibitor of Metalloproteinase-4
chemical_list: D014408:Biomarkers, Tumor; D011960:Receptors, Estrogen; D019714:Tissue Inhibitor of Metalloproteinases; D000097792:Tissue Inhibitor of Metalloproteinase-4
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