Pharmacoproteomic analysis of prechemotherapy and postchemotherapy plasma samples from patients receiving neoadjuvant or adjuvant chemotherapy for breast carcinoma

• Published in: Cancer 2004-05, Vol.100 (9), p.1814-1822
• Main Authors: Pusztai, Lajos, Gregory, Betsy W., Baggerly, Keith A., Peng, Bo, Koomen, John, Kuerer, Henry M., Esteva, Francisco J., Symmans, W. Fraser, Wagner, Peter, Hortobagyi, Gabriel N., Laronga, Christine, Semmes, O. John, Wright, George L., Drake, Richard R., Vlahou, Antonia
• Format: Article
• Language: English
• Subjects: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Biological and medical sciences; biomarkers; Biomarkers, Tumor - blood; Biopsy, Needle; Breast Neoplasms - drug therapy; Breast Neoplasms - mortality; Breast Neoplasms - pathology; Breast Neoplasms - surgery; Case-Control Studies; Chemotherapy, Adjuvant; Cyclophosphamide; Doxorubicin - administration & dosage; Drug Administration Schedule; Female; Fluorouracil - administration & dosage; Humans; Mastectomy - methods; Medical sciences; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; paclitaxel; Paclitaxel - administration & dosage; Postoperative Care; Preoperative Care; preoperative chemotherapy; Proteomics; Risk Assessment; SELDI‐MS; Sensitivity and Specificity; Survival Analysis; Treatment Outcome; Tumors
• ISSN: 0008-543X; 1097-0142
• DOI: 10.1002/cncr.20203

BACKGROUND In this study, proteomic changes were examined in response to paclitaxel chemotherapy or 5‐fluorouracil, doxorubicin, and cyclophosphamide (FAC) chemotherapy in plasma from patients with Stage I–III breast carcinoma. The authors also compared the plasma profiles of patients with cancer with the plasma profiles of healthy women to identify breast carcinoma–associated protein markers. METHODS Sixty‐nine patients and 15 healthy volunteers participated in the study. Plasma was sampled on Day 0 before chemotherapy and on Day 3 posttreatment in the 69 patients or 3 days apart in the 15 healthy women. Twenty‐nine patients received preoperative chemotherapy, and 40 received postoperative chemotherapy. Surface‐enhanced laser desorption/ionization mass spectrometry was used to generate protein mass profiles. RESULTS Few changes were observed in plasma during treatment. Only 1 protein peak was identified (mass/charge ratio [m/z], 2790) that was induced by paclitaxel and, to a lesser extent, by FAC chemotherapy. This proteomic response was detectable in 80% of patients who were treated preoperatively but also was present with lesser intensity in approximately 40% of patients treated postoperatively. There was no clear correlation between induction of m/z 2790 during a single course of treatment and final tumor response to preoperative chemotherapy. Five other peaks also were identified that discriminated between plasma from patients with breast carcinoma and plasma from normal women. These same peaks also were detectable in a subset of patients who already had undergone surgery to remove their tumors. CONCLUSIONS A single chemotherapy‐inducible SELDI‐MS peak and five other peaks that distinguished plasma obtained from patients with breast carcinoma from plasma obtained from normal, healthy women were identified. The (as yet unsequenced) proteins represented by these peaks are candidate markers of micrometastatic disease after surgery. Cancer 2004. © 2004 American Cancer Society. Proteomic changes were examined in response to chemotherapy in patients with Stage I–III breast carcinoma, and plasma profiles from patients with breast carcinoma were compared with the profiles from healthy women to identify breast carcinoma‐associated protein markers. Five mass peaks were identified that were absent in healthy women and one unique chemotherapy‐induced peak. These peaks may represent markers that have the potential to detect and monitor micrometastatic disease afte