P-glycoprotein expression as a predictor of response to neoadjuvant chemotherapy in breast cancer.
BACKGROUND
Chemoresistance is an important factor determining the response of tumor to neoadjuvant chemotherapy (NACT). P-glycoprotein (P-gp) expression-mediated drug efflux is one of the mechanisms responsible for multi-drug resistance. Our study was aimed to determine the role of P-gp expression as a predictor of response to NACT in locally advanced breast cancer (LABC) patients.


METHODS
P-gp expression was performed by real-time quantitative polymerase chain reaction [qRT-PCR] in 76 patients with LABC. Response to adriamycin-based regimen was assessed both clinically and with contrast enhanced computed tomography (CECT) scan before and after NACT. The significance of correlation between tumor and P-gp levels was determined with Chi-square test.


RESULTS
Twenty-one had high and 55 had low P-gp expression. On analyzing P-gp expression with response by World Health Organization (WHO) criteria, statistical significance was obtained (P = 0.038). Similarly, assessment of P-gp expression with response by Response Evaluation in Solid Tumors (RECIST) criteria in 48 patients showed statistical significance (P = 0.0005).


CONCLUSIONS
This study proves that P-gp expression is a determinant factor in predicting response to NACT. Finally, detection of P-gp expression status before initiation of chemotherapy can be used as a predictive marker for NACT response and will also aid in avoiding the toxic side effects of NACT in non-responders.
Department of Surgery, Jawaharlal Institute of Postgraduate Medical Education & Research, Pondicherry, India.
S
S
Vishnukumar
G
G
Umamaheswaran
D
D
Anichavezhi
S
S
Indumathy
C
C
Adithan
K
K
Srinivasan
D
D
Kadambari
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis*; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000032:analysis; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D017024:Chemotherapy, Adjuvant; D019008:Drug Resistance, Neoplasm / Q000502:physiology*; D005260:Female; D006801:Humans; D008875:Middle Aged; D020360:Neoadjuvant Therapy / Q000379:methods*; D060888:Real-Time Polymerase Chain Reaction
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D014408:Biomarkers, Tumor