P-glycoprotein: the intermediate end point of drug response to induction chemotherapy in locally advanced breast cancer.
Expression and clinical relevance of p-glycoprotein (p-gp) were evaluated in 31 cases of locally advanced breast cancer and 9 cases involving inflammatory breast cancer after induction chemotherapy. The de novo p-gp expression rate was 26% and increased up to 58% (p = 0.03) with the FAC (5-fluorouracil, adriamycin, cyclophosphamide) regimen. Although more clinically complete responders were found in the secondary p-gp negative group (p = 0.02), this difference was not found in pathological tumor response. Moreover, as the grade of the secondary p-gp expression increased, the chemotherapeutic effect decreased, suggesting an inverse relationship between p-gp expression and drug effect (p = 0.04). When we subgrouped the patients into 4 groups using these two parameters, p-gp negative patients presenting with a high drug effect showed a low recurrence rate (p = 0.05) and marginal survival benefits (p = 0.09) as opposed to patients with a low drug effect. But in p-gp positive groups, the recurrence rate was the same between the two groups regardless of the drug effect. Thus, in the p-gp negative patient with a high drug effect, adjuvant chemotherapy with the same regimen as induction chemotherapy may induce more prognostically favorable results. Therefore, clinical application of the secondary p-gp detection can be used as an intermediate endpoint in evaluating drug response for an induction regimen.
Chung
H C
HC
Yonsei Cancer Center, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.
Rha
S Y
SY
Kim
J H
JH
Roh
J K
JK
Min
J S
JS
Lee
K S
KS
Kim
B S
BS
Lee
K B
KB
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis*; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D003520:Cyclophosphamide / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D004317:Doxorubicin; D003520:Cyclophosphamide; D005472:Fluorouracil