BACKGROUND: Breast cancer patients may experience disease relapse even 10-20 years after primary diagnosis. Recurrence is caused by dormant disseminated tumor cells (DTCs) in the bone marrow (BM). Whereas chemotherapy is unable to eradicate these non-proliferating cells, bisphosponates are currently being discussed as eliminating DTCs. The purpose of our study was to: i) analyze the presence of DTCs in the BM of breast cancer patients 2-10 years after first diagnosis of cancer, and ii) to study the effect of ibandronate on DTCs in those patients with DTC persistence. PATIENTS AND METHODS: Bilateral BM aspirates of 54 individuals diagnosed 2-10 years ago with breast cancer, but currently disease free, were analyzed for DTCs by immunocytochemistry using pan-cytokeratin antibody A45-B/B3. Patients with DTC persistence received oral ibandronate treatment (50 mg per day) for six months and bilateral BM aspirates were analyzed for DTCs again after therapy. RESULTS: DTCs were found in 18/54 (33%) of the patients, with a median number of 3 disseminated tumor cells (range 1-6 cells). These 18 patients received ibandronate orally for 6 months and 17/18 patients were analyzed for DTCs again after therapy. Only 3/17 (18%) patients remained DTC-positive, with the detection of 1 (n=2 patients) and 3 DTCs, respectively. These three DTC-positive patients continued their ibandronate intake for a further six months and re-examination of the BM resulted in no detection of DTCs in any of the three patients. CONCLUSION: Our pilot study indicates the potential effect of ibandronate on DTCs and further studies are needed to demonstrate these findings in a larger patient cohort.
BACKGROUND:Breast cancerpatients may experience disease relapse even 10-20 years after primary diagnosis. Recurrence is caused by dormant disseminated tumor cells (DTCs) in the bone marrow (BM). Whereas chemotherapy is unable to eradicate these non-proliferating cells, bisphosponates are currently being discussed as eliminating DTCs. The purpose of our study was to: i) analyze the presence of DTCs in the BM of breast cancerpatients 2-10 years after first diagnosis of cancer, and ii) to study the effect of ibandronate on DTCs in those patients with DTC persistence. PATIENTS AND METHODS: Bilateral BM aspirates of 54 individuals diagnosed 2-10 years ago with breast cancer, but currently disease free, were analyzed for DTCs by immunocytochemistry using pan-cytokeratin antibody A45-B/B3. Patients with DTC persistence received oral ibandronate treatment (50 mg per day) for six months and bilateral BM aspirates were analyzed for DTCs again after therapy. RESULTS:DTCs were found in 18/54 (33%) of the patients, with a median number of 3 disseminated tumor cells (range 1-6 cells). These 18 patients received ibandronate orally for 6 months and 17/18 patients were analyzed for DTCs again after therapy. Only 3/17 (18%) patients remained DTC-positive, with the detection of 1 (n=2 patients) and 3 DTCs, respectively. These three DTC-positive patients continued their ibandronate intake for a further six months and re-examination of the BM resulted in no detection of DTCs in any of the three patients. CONCLUSION: Our pilot study indicates the potential effect of ibandronate on DTCs and further studies are needed to demonstrate these findings in a larger patient cohort.
Authors: Sabine Kasimir-Bauer; Ann-Kathrin Bittner; Lisa König; Katharina Reiter; Thomas Keller; Rainer Kimmig; Oliver Hoffmann Journal: Breast Cancer Res Date: 2016-02-12 Impact factor: 6.466
Authors: Gaurav Pahouja; Robert Wesolowski; Raquel Reinbolt; Gary Tozbikian; Michael Berger; Neha Mangini; Maryam B Lustberg Journal: Cancer Treat Commun Date: 2015
Authors: Daniele Santini; Luciano Stumbo; Chiara Spoto; Loretta D'Onofrio; Francesco Pantano; Michele Iuliani; Marco Fioramonti; Alice Zoccoli; Giulia Ribelli; Vladimir Virzì; Bruno Vincenzi; Giuseppe Tonini Journal: Breast Cancer Res Date: 2015-09-02 Impact factor: 6.466