Pharmacoproteomic analysis of prechemotherapy and postchemotherapy plasma samples from patients receiving neoadjuvant or adjuvant chemotherapy for breast carcinoma.
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.
Pusztai
Lajos
L
Department of Breast Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030-4009, USA. lpusztai@mdanderson.org
Gregory
Betsy W
BW
Baggerly
Keith A
KA
Peng
Bo
B
Koomen
John
J
Kuerer
Henry M
HM
Esteva
Francisco J
FJ
Symmans
W Fraser
WF
Wagner
Peter
P
Hortobagyi
Gabriel N
GN
Laronga
Christine
C
Semmes
O John
OJ
Wright
George L
GL
Drake
Richard R
RR
Vlahou
Antonia
A
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols; D014408:Biomarkers, Tumor / Q000097:blood; D001707:Biopsy, Needle; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D016022:Case-Control Studies; D017024:Chemotherapy, Adjuvant; D003520:Cyclophosphamide; D004317:Doxorubicin / Q000008:administration & dosage; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D008408:Mastectomy / Q000379:methods; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D017239:Paclitaxel / Q000008:administration & dosage; D011182:Postoperative Care; D011300:Preoperative Care; D040901:Proteomics; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D016019:Survival Analysis; D016896:Treatment Outcome
D014408:Biomarkers, Tumor; D004317:Doxorubicin; D003520:Cyclophosphamide; D017239:Paclitaxel; D005472:Fluorouracil