title: Is administration of trastuzumab an independent risk factor for developing osteonecrosis of the jaw among metastatic breast cancer patients under zoledronic acid treatment?
abstract: One of the most important adverse effects of zoledronic acid (ZA) is osteonecrosis of the jaw (ONJ). In previous literature, several risk factors have been identified in the development of ONJ. In this study, we aimed to determine the role of trastuzumab, an antiangiogenic agent, as an independent risk factor for the development of this serious side effect.Our study included 97 patients (mean age: 54 ± 10 years) with breast cancer, recorded in the archives of the Istanbul Florence Nightingale Breast Study Group, who received ZA therapy due to bone metastases between March 2006 and December 2013. We recorded the patients' ages, weights, duration of treatment with ZA, number of ZA infusions, dental procedures, anticancer treatments (chemotherapy, aromatase inhibitor, trastuzumab), the presence of diabetes mellitus or renal dysfunction, and smoking habits.Thirteen patients (13.40%) had developed ONJ. Among the patients with ONJ, the mean time of exposure to ZA was 41 months (range: 13-82) and the mean number of ZA infusions was 38 (range: 15-56). The duration of treatment with ZA and the use of trastuzumab were observed to be 2 factors that influenced the development of ONJ (P = 0.049 and P = 0.028, respectively).The development of ONJ under ZA treatment may be associated solely with the duration of ZA treatment and the concurrent administration of trastuzumab. These findings show that patients who are administered trastuzumab for metastatic breast cancer while undergoing ZA treatment are prone to developing ONJ. Therefore, we recommend intense clinical observation to avoid this particular condition in patients receiving ZA and trastuzumab.
authors.affiliation: From the Department of Oncology (KNP, CO, CT), Bilim University, Avrupa Florence Nightingale Hospital, Sishane, Istanbul; Department of Radiation Oncology (GA), Gayrettepe Florence Nightingale Hospital, Besiktas; Department of Surgery (DS, SI, VO), Istanbul Florence Nightingale Hospital, Sisli, Istanbul; Department of Radiology (FC), Gayrettepe Florence Nightingale Hospital, Besiktas; Department of Physical Therapy and Rehabilitation (ZE), Bilim University, Florence Nightingale Hospital; Department of Radiology (FA), Istanbul Florence Nightingale Hospital, Sisli; Department of Oncology (GD), Acıbadem Hospital, Maslak Sarıyer; and Department of Oncology (YE), Istanbul Medical Faculty, Capa, Fatih, Istanbul, Turkey.
authors.forename: Kezban Nur
authors.initials: KN
authors.lastname: Pilanci
authors.forename: Gul
authors.initials: G
authors.lastname: Alco
authors.forename: Cetin
authors.initials: C
authors.lastname: Ordu
authors.forename: Dauren
authors.initials: D
authors.lastname: Sarsenov
authors.forename: Filiz
authors.initials: F
authors.lastname: Celebi
authors.forename: Zeynep
authors.initials: Z
authors.lastname: Erdogan
authors.forename: Filiz
authors.initials: F
authors.lastname: Agacayak
authors.forename: Serkan
authors.initials: S
authors.lastname: Ilgun
authors.forename: Coskun
authors.initials: C
authors.lastname: Tecimer
authors.forename: Gokhan
authors.initials: G
authors.lastname: Demir
authors.forename: Yesim
authors.initials: Y
authors.lastname: Eralp
authors.forename: Sait
authors.initials: S
authors.lastname: Okkan
authors.forename: Vahit
authors.initials: V
authors.lastname: Ozmen
mesh_terms: D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects* / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D059266:Bisphosphonate-Associated Osteonecrosis of the Jaw / Q000209:etiology*; D050071:Bone Density Conservation Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001859:Bone Neoplasms / Q000188:drug therapy / Q000556:secondary*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology*; D004164:Diphosphonates / Q000009:adverse effects* / Q000627:therapeutic use; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007093:Imidazoles / Q000009:adverse effects* / Q000627:therapeutic use; D007262:Infusions, Intravenous; D016015:Logistic Models; D008875:Middle Aged; D012189:Retrospective Studies; D012307:Risk Factors; D000068878:Trastuzumab; D016896:Treatment Outcome; D000077211:Zoledronic Acid
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D000077211:Zoledronic Acid; D000068878:Trastuzumab