title: High levels at baseline of serum pyridinoline crosslinked carboxyterminal telopeptide of type I collagen are associated with worse prognosis for breast cancer patients.
abstract: It is speculated that adjuvant use of bisphosphonate reduces recurrence in breast cancer patients through suppression of bone resorption. To determine the prognostic impact of bone resorption markers, we investigated serum levels of the pyridinoline crosslinked carboxyterminal telopeptide of type I collagen (1CTP) and N-terminal crosslinking telopeptides of type I collagen (NTX). 1CTP and NTX were measured at baseline (before operation or neoadjuvant therapies) and afterward in 469 patients operated on breast cancer. The optimal cutoff value of 1CTP for relapse-free survival (RFS) was set at 3.6 ng/ml with an area under the receiver operating characteristics curve of 0.641 [95% confidence interval (CI) = 0.560-0.721; p = 0.0011]. However, we were unable to determine a significant cutoff value for NTX. RFS was significantly worse for 1CTP-high patients with than for those with low levels of 1CTP (p = 0.0002). Multivariate analysis with tumor size, lymph node metastasis, and nuclear grade showed that 1CTP was a significant independent prognostic factor (hazard ratio = 2.04, 95% CI = 1.13-3.68; p = 0.018). Worse prognosis for the subset with high 1CTP levels applied only to postmenopausal patients (p = 0.0002). RFS of 130 patients whose 1CTP changed from low at baseline to high at 6 months postoperatively showed RFS almost as poor as that for patients with high 1CTP throughout. These findings suggest that 1CTP may be useful not only for identifying patients with unfavorable prognosis, but also for selecting patients who may benefit from administration of bone-modifying agents in an adjuvant setting.
authors.affiliation: Division of Breast and Endocrine Surgery, Department of Surgery, Hyogo College of Medicine, Mukogawa-cho 1-1, Nishinomiya, Hyogo, 663-8501, Japan.
authors.forename: Michiko
authors.initials: M
authors.lastname: Imamura
authors.affiliation: Division of Breast and Endocrine Surgery, Department of Surgery, Hyogo College of Medicine, Mukogawa-cho 1-1, Nishinomiya, Hyogo, 663-8501, Japan.
authors.forename: Arisa
authors.initials: A
authors.lastname: Nishimukai
authors.affiliation: Division of Breast and Endocrine Surgery, Department of Surgery, Hyogo College of Medicine, Mukogawa-cho 1-1, Nishinomiya, Hyogo, 663-8501, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Higuchi
authors.affiliation: Division of Breast and Endocrine Surgery, Department of Surgery, Hyogo College of Medicine, Mukogawa-cho 1-1, Nishinomiya, Hyogo, 663-8501, Japan.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Ozawa
authors.affiliation: Division of Breast and Endocrine Surgery, Department of Surgery, Hyogo College of Medicine, Mukogawa-cho 1-1, Nishinomiya, Hyogo, 663-8501, Japan.
authors.forename: Ayako
authors.initials: A
authors.lastname: Yanai
authors.affiliation: Division of Breast and Endocrine Surgery, Department of Surgery, Hyogo College of Medicine, Mukogawa-cho 1-1, Nishinomiya, Hyogo, 663-8501, Japan.
authors.forename: Yoshimasa
authors.initials: Y
authors.lastname: Miyagawa
authors.affiliation: Division of Breast and Endocrine Surgery, Department of Surgery, Hyogo College of Medicine, Mukogawa-cho 1-1, Nishinomiya, Hyogo, 663-8501, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Murase
authors.affiliation: Sakita Clinic, Nishinomiya, Hyogo, Japan.
authors.forename: Isao
authors.initials: I
authors.lastname: Sakita
authors.affiliation: Uminosato Clinic, Minamiawaji, Hyogo, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Hatada
authors.affiliation: Division of Breast and Endocrine Surgery, Department of Surgery, Hyogo College of Medicine, Mukogawa-cho 1-1, Nishinomiya, Hyogo, 663-8501, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Takatsuka
authors.affiliation: Division of Genome Medicine, Institute for Genome Research, University of Tokushima, Tokushima, Tokushima, Japan.
authors.forename: Toyomasa
authors.initials: T
authors.lastname: Katagiri
authors.affiliation: Division of Breast and Endocrine Surgery, Department of Surgery, Hyogo College of Medicine, Mukogawa-cho 1-1, Nishinomiya, Hyogo, 663-8501, Japan. ymiyoshi@hyo-med.ac.jp.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Miyoshi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D047072:Aromatase Inhibitors / Q000627:therapeutic use; D050071:Bone Density Conservation Agents / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000097:blood* / Q000401:mortality* / Q000473:pathology / Q000628:therapy; D024042:Collagen Type I / Q000097:blood*; D000069448:Denosumab / Q000627:therapeutic use; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis / Q000473:pathology; D008875:Middle Aged; D015999:Multivariate Analysis; D010455:Peptides / Q000097:blood*; D010748:Phosphopeptides / Q000097:blood*; D017698:Postmenopause; D011347:Procollagen / Q000097:blood*; D011379:Prognosis
chemical_list: D047072:Aromatase Inhibitors; D050071:Bone Density Conservation Agents; D024042:Collagen Type I; C062121:N-propeptide type I collagen; D010455:Peptides; D010748:Phosphopeptides; D011347:Procollagen; C052929:collagen type I trimeric cross-linked peptide; D000069448:Denosumab
keywords: 1CTP; Bisphosphonate; Bone turnover marker; Breast cancer; Metastasis