Effect of neoadjuvant chemotherapy on bone marrow micrometastases in women with locally advanced breast cance

Abstract

697 Background: Approximately 30% of women newly diagnosed with breast cancer will have tumor cells present in their bone marrow. In this study, we have examined bone marrow for the presence of breast cancer cells in women with locally advanced breast cancer undergoing neoadjuvant chemotherapy. Methods: Women with clinical stage II or III breast cancer were enrolled into a prospective randomized phase II trial. Women underwent bone marrow aspirations prior to and after 4 cycles of chemotherapy with epirubicin and docetaxel. Bone marrow mononucleated cells were isolated by Ficoll gradient, and 2–4x106 cells from each iliac crest were examined for the presence of cytokeratin positive cells after staining with AE1/AE3. Results: 34 patients have been enrolled since March 2003 (planned accrual 120). Bone marrow was analyzed from 29 patients. 58% of women were postmenopausal. The average tumor size was 4.5 cm and all tumors were grade II or III. 62% of tumors were estrogen receptor positive and 24% of tumor overexpressed Her-2. 55% of patients had detectable bone marrow micrometastases at the time of diagnosis. The number of cytokeratin positive cells detected ranged from 1–23. Patients with cytokeratin positive bone marrows tended to have estrogen receptor negative tumors (50% versus 23%) and clinically detectable axillary adenopathy (75% versus 46%). There was no difference in the average tumor size between the two groups. 16 women had bone marrow analysis after chemotherapy. None of the women who had negative bone marrows prior to chemotherapy had positive marrows after chemotherapy (7/7). Of the 9 women with positive bone marrows prior to chemotherapy, 6 had negative marrows after chemotherapy. Conclusions: Over 50% of women presenting with advanced breast cancer have tumor cells detectable in their bone marrow at the time of diagnosis. This subset of women tends to have estrogen receptor negative cancers and clinically positive axilla. Preliminarily, it appears that chemotherapy may result in the clearance of bone marrow micrometastases in a significant portion of women with detectable micrometastases prior to chemotherapy. Our study is ongoing. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis; Pfizer