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Trastuzumab clears HER2/neu-positive isolated tumor cells from bone marrow in primary breast cancer patients.
Rack, Brigitte; Jückstock, Julia; Günthner-Biller, Maria; Andergassen, Ulrich; Neugebauer, Julia; Hepp, Philip; Schoberth, Alexandra; Mayr, Doris; Zwingers, Thomas; Schindlbeck, Christian; Friese, Klaus; Janni, Wolfgang.
Affiliation
  • Rack B; Department of Gynecology and Obstetrics, Klinikum Innenstadt, Ludwig-Maximilians-Universitaet Muenchen, Maistr. 11, 80337 Munich, Germany. brigitte.rack@med.uni-muenchen.de
Arch Gynecol Obstet ; 285(2): 485-92, 2012 Feb.
Article in En | MEDLINE | ID: mdl-21717141
ABSTRACT

PURPOSE:

Isolated tumor cells (ITC) in the bone marrow of breast cancer patients increase the risk of recurrence and decrease survival, both at primary diagnosis and during follow-up. We tested the efficacy of trastuzumab in clearing HER2/neu-positive ITC from the marrow of patients completing primary treatment.

METHODS:

Ten recurrence-free patients with persistent HER2/neu-positive ITC after routine adjuvant treatment received trastuzumab 6 mg/kg q3w for 12 months in a non-randomized pilot phase II interventional study. Bone marrow ITC HER2/neu status was evaluated at baseline, after treatment for 3, 6 and 12 months, and yearly thereafter, in combination with clinical follow-up. Median follow-up was 23 (15-64) months after baseline bone marrow aspiration.

RESULTS:

Trastuzumab for 12 months eradicated HER2/neu-positive ITC from bone marrow in all patients (P = 0.002) and significantly reduced the number of ITC-positive patients (P = 0.031). However, HER2/neu-negative ITC persisted in three patients immediately after treatment and were detected at yearly bone marrow aspiration in five patients. Two patients with ITC counts ≥5 at yearly follow-up developed metastases and one died.

CONCLUSION:

This is the first evidence that trastuzumab is effective in clearing HER2/neu-positive cells from bone marrow during recurrence-free follow-up in breast cancer patients. It also suggests, thanks to the antigen shift phenomenon, an important prognostic role for HER2/neu expression on marrow ITC as a real-time biopsy. However, treatment was mainly effective in patients with HER2/neu-positive ITC. Given the heterogeneity of minimal residual disease, these patients might benefit from a combination of targeted treatment approaches.
Subject(s)

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Bone Marrow / Breast Neoplasms / Receptor, ErbB-2 / Antibodies, Monoclonal, Humanized / Neoplastic Cells, Circulating / Antineoplastic Agents Type of study: Clinical_trials / Observational_studies / Prognostic_studies / Risk_factors_studies Limits: Adult / Aged / Female / Humans / Middle aged Language: En Journal: Arch Gynecol Obstet Journal subject: GINECOLOGIA / OBSTETRICIA Year: 2012 Type: Article Affiliation country: Germany

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Bone Marrow / Breast Neoplasms / Receptor, ErbB-2 / Antibodies, Monoclonal, Humanized / Neoplastic Cells, Circulating / Antineoplastic Agents Type of study: Clinical_trials / Observational_studies / Prognostic_studies / Risk_factors_studies Limits: Adult / Aged / Female / Humans / Middle aged Language: En Journal: Arch Gynecol Obstet Journal subject: GINECOLOGIA / OBSTETRICIA Year: 2012 Type: Article Affiliation country: Germany