Neoadjuvant chemotherapy (NACT) is an important aspect of the management of locally advanced breast cancer, but chemoresistance can limit efficacy. The ability to predict response would allow patient-specific tailoring of treatment regimens and possibly allow the avoidance of toxicity associated with ineffective chemotherapy.
The expression of p-glycoprotein, a 170 kDa membrane glycoprotein encoded by the multidrug resistance 1 (MDR1) gene, has been associated with the development of resistance to chemotherapy. Chintamani and colleagues evaluated the expression of p-glycoprotein in 50 patients with advanced breast cancer to determine whether pretreatment expression could be used to reliably predict response to NACT (3 cycles of cyclophosphamide 600 mg/m2, adriamycin 50 mg/m2 and 5-fluorouracil 600 mg/m2 every 3 weeks). Twenty-six patients (52%) were p-glycoprotein positive. A statistically significant negative correlation was found between clinical response and p-glycoprotein expression (P = 0.05). Thirty patients (60%) showed a clinical response to NACT, and of these, 21 (70%) were p-glycoprotein negative. Seven of nine p-glycoprotein-positive patients who responded to NACT showed only very low levels of expression. Post-NACT increases in p-glycoprotein levels increased the number of p-glycoprotein-positive patients to 72.5%, and the authors suggest that this might reflect development of acquired chemoresistance.
Overall, pre-NACT p-glycoprotein expression is associated with poor response to NACT. In addition, chemotherapy-induced increases in p-glycoprotein levels might be an indication of the development of chemoresistance and could serve as an intermediate endpoint in assessing drug response.
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Lovegrove, C. P-glycoprotein expression predicts response to NACT in breast cancer. Nat Rev Clin Oncol 2, 604 (2005). https://doi.org/10.1038/ncponc0339
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DOI: https://doi.org/10.1038/ncponc0339