Agustí Barnadas1, Luis Manso2, Concepción de la Piedra3, Cristina Meseguer4, Carmen Crespo5, Patricia Gómez6, Lourdes Calvo7, Purificación Martinez8, Manuel Ruiz-Borrego9, Antonia Perelló10, Antonio Antón11, Manuel Codes12, Mireia Margelí13, Adolfo Murias14, Javier Salvador15, Miguel Ángel Seguí16, Ana de Juan17, Joaquín Gavilá18, María Luque19, Diego Pérez20, Pilar Zamora21, Alberto Arizcuma22, José Ignacio Chacón23, Lucía Heras24, Marta Martin-Fernández25, Ignacio Mahillo-Fernández26, Ignacio Tusquets27. 1. Medical Oncology Department, Hospital de la Santa Creu i Sant Pau, Sant Antoni Maria Claret, 167, 08025 Barcelona, Spain; Medicine Department, Universitat Autònoma de Barcelona, Barcelona, Spain. Electronic address: ABarnadasM@santpau.cat. 2. Medical Oncology Department, Hospital Universitario 12 de Octubre, Avda. de Córdoba, s/n, 28041 Madrid, Spain. Electronic address: luis_manso@hotmail.com. 3. Bioquímica Investigación, Instituto de Investigación Sanitaria Fundación Jiménez Díaz, Avda. Reyes Católicos, 2, 28040 Madrid, Spain. Electronic address: CPiedra@fjd.es. 4. Medical Department, Novartis Farmacéutica S.A., Gran Via de les Corts Catalanes, 764, 08013 Barcelona, Spain. Electronic address: cristina.meseguer@novartis.com. 5. Medical Oncology Department, Hospital Ramón y Cajal, Ctra. de Colmenar Viejo, Km. 9100, 28034 Madrid, Spain. Electronic address: ccrespo.hurc@salud.madrid.org. 6. Oncology Department, Hospital Vall d'Hebrón, Passeig de la Vall d'Hebron, 119-129, 08035 Barcelona, Spain. Electronic address: pagomez@vhebron.net. 7. Oncology Department, Complejo Hospitalario Universitario de A Coruña, As Xubias, 84, 15006 A Coruña, Spain. Electronic address: Lourdes.Calvo.Martinez@sergas.es. 8. Oncology Department, Hospital Universitario Basurto, Avda. de Montevideo, 18, 48013 Bilbao, Spain. Electronic address: purificacion.martinezdelprado@osakidetza.net. 9. Oncology Department, Hospital Universitario Virgen del Rocío, Avda. Manuel Siurot, 0, 41013 Sevilla, Spain. Electronic address: manuel.ruiz.borrego.sspa@juntadeandalucia.es. 10. Medical Oncology Service, Hospital Universitari Son Dureta, Andrea Doria, 55, 07014 Palma de Mallorca, Spain. Electronic address: antonia.perellom@ssib.es. 11. Medical Oncology Department, Hospital Universitario Miguel Servet, Paseo Isabel la Católica, 1-3, 50009 Zaragoza, Spain. Electronic address: aantont@gmail.com. 12. Medical Oncology Department, Hospital Virgen Macarena, Avda. Dr. Fedriani, 3, 41007 Sevilla, Spain. Electronic address: manuelcodesvillena@gmail.com. 13. Medical Oncology Department, Institut Català d'Oncologia, Hospital Universitari Germans Trias i Pujol, Crta. Canyet, 08916 Badalona, Spain. Electronic address: mmargeli@iconcologia.net. 14. Oncology Department, Hospital Insular de Gran Canaria, Plaza Doctor Pasteur, s/n, 35016 Las Palmas de Gran Canaria, Spain. Electronic address: amuriasrosales@gmail.com. 15. Medical Oncology Department, Hospital Universitario Nuestra Señora de Valme, Avda. de Bellavista, s/n, 41014 Sevilla, Spain. Electronic address: jsalvad2002@yahoo.es. 16. Medical Oncology Department, Corporació Sanitària Parc Taulí, Parc Taulí, 1, 08208 Sabadell, Spain. Electronic address: msegui@tauli.cat. 17. Oncology Department, Hospital Universitario Marqués de Valdecilla, Avda. Valdecilla, s/n, 39008 Santander, Spain. Electronic address: ajuan@humv.es. 18. Medical Oncology Department, Fundación Instituto Valenciano de Oncología, Profesor Beltrán Bàguena, 8, 46009 Valencia, Spain. Electronic address: jogagre@hotmail.com. 19. Medical Oncology Department, Hospital Universitario Central de Asturias, Celestino Villamil, s/n, 33006 Oviedo, Spain. Electronic address: malucab@hotmail.com. 20. Oncology Department, Hospital Costa del Sol, Autovía A-7, Km. 187, 29603 Marbella, Málaga, Spain. Electronic address: dipema2026@gmail.com. 21. Medical Oncology Service, Hospital Universitario La Paz, Paseo de la Castellana, 261, 28046 Madrid, Spain. Electronic address: zamorapilar@gmail.com. 22. Oncology Department, Hospital General Río Carrión, Avda. Donantes de Sangre, s/n, 34005 Palencia, Spain. Electronic address: aarizcun@gmail.com. 23. Medical Oncology Department, Hospital Virgen de la Salud, Avda. de Barber, 30, 45071 Toledo, Spain. Electronic address: jignaciochacon@gmail.com. 24. Oncology Service, Hospital de la Creu Roja, Avinguda Josep Molins, 29-41, 08906 L'Hospitalet de Llobregat, Spain. Electronic address: lucia.heras@sanitatintegral.org. 25. Bioquímica Investigación, Instituto de Investigación Sanitaria Fundación Jiménez Díaz, Avda. Reyes Católicos, 2, 28040 Madrid, Spain. Electronic address: mmartinf@fjd.es. 26. Epidemiology Department, Instituto de Investigación Sanitaria Fundación Jiménez Díaz, Avda. Reyes Católicos, 2, 28040 Madrid, Spain. Electronic address: IMahillo@fjd.es. 27. Medicine Department, Universitat Autònoma de Barcelona, Barcelona, Spain; Medical Oncology Department, Hospital del Mar, Passeig Marítim de la Barceloneta, 25-29, 08003 Barcelona, Spain. Electronic address: ITusquets@parcdesalutmar.cat.
Abstract
BACKGROUND: We evaluated the evolution and predictive value of bone turnover markers (BTMs) and circulating tumor cells (CTCs) with respect to mortality, disease progression (DP) and skeletal-related events (SREs), in patients with bone metastatic breast cancer (BmBCa). The correlation between BTMs and CTCs was also studied. METHODS: In a 2-year observational, multicenter study, the levels of three BTMs (N- and C-terminal telopeptides of collagen I [NTX and αα-CTX], and bone-specific alkaline phosphatase [BSAP]) and CTCs were analyzed every three months. Patients received zoledronic acid (4mg every 28days) from the baseline visit. RESULTS: 234 patients were analyzed. The levels of the BTMs were increased at baseline and significantly decreased after 3months (P<0.05). In the Cox regression univariate analyses significant hazard ratios (HRs) for death were found for pathological BSAP values at baseline (5.03 [95% CI: 1.214-20.839; P=0.0259]) and at 3months (3.41 [95% CI: 1.367-8.498; P=0.0085]). HRs >2 were found for increased baseline and 3-month levels of NTX and CTC (P<0.05). Only increased baseline BSAP levels were associated with DP (HR=2.25 [95% CI: 1.391-3.626; P=0.0009]). No biomarker was associated with SREs. In the multivariate analysis, pathologic levels at 3months of NTX and BSAP were significantly associated with mortality (HRs=3.59 [95% CI: 1.375-9.382; P=0.0091] and 3.25 [95% CI: 1.293-8.189; P=0.0120], respectively). CTC and BSAP were correlated during all study timepoints (P<0.05). CONCLUSIONS: Baseline levels of NTX, BSAP and CTCs, and changes after treatment initiation with bisphosphonates, may be useful for the prognostic assessment of patients with BmBCa. BSAP showed the strongest prognostic value.
BACKGROUND: We evaluated the evolution and predictive value of bone turnover markers (BTMs) and circulating tumor cells (CTCs) with respect to mortality, disease progression (DP) and skeletal-related events (SREs), in patients with bone metastatic breast cancer (BmBCa). The correlation between BTMs and CTCs was also studied. METHODS: In a 2-year observational, multicenter study, the levels of three BTMs (N- and C-terminal telopeptides of collagen I [NTX and αα-CTX], and bone-specific alkaline phosphatase [BSAP]) and CTCs were analyzed every three months. Patients received zoledronic acid (4mg every 28days) from the baseline visit. RESULTS: 234 patients were analyzed. The levels of the BTMs were increased at baseline and significantly decreased after 3months (P<0.05). In the Cox regression univariate analyses significant hazard ratios (HRs) for death were found for pathological BSAP values at baseline (5.03 [95% CI: 1.214-20.839; P=0.0259]) and at 3months (3.41 [95% CI: 1.367-8.498; P=0.0085]). HRs >2 were found for increased baseline and 3-month levels of NTX and CTC (P<0.05). Only increased baseline BSAP levels were associated with DP (HR=2.25 [95% CI: 1.391-3.626; P=0.0009]). No biomarker was associated with SREs. In the multivariate analysis, pathologic levels at 3months of NTX and BSAP were significantly associated with mortality (HRs=3.59 [95% CI: 1.375-9.382; P=0.0091] and 3.25 [95% CI: 1.293-8.189; P=0.0120], respectively). CTC and BSAP were correlated during all study timepoints (P<0.05). CONCLUSIONS: Baseline levels of NTX, BSAP and CTCs, and changes after treatment initiation with bisphosphonates, may be useful for the prognostic assessment of patients with BmBCa. BSAP showed the strongest prognostic value.