Effect of trastuzumab on the reduction of hormone receptor expression by neoaduvant chemotherapy in HER2-positive breast cancer

Abstract

11114 Background: Neoadjuvant chemotherapy (NAC) in primary breast cancer is actively used around the world. Lower ER expression is related to an increased sensitivity of NAC and ER/PgR expression decreases after NAC. Estrogen Receptor (ER) function is coordinated by crosstalk with growth factor signaling, especially that of HER2. Moreover, trastuzumab (T) has an established role in the management of HER-2 positive breast cancer in conjunction with chemotherapy. We examined the effectiveness of NAC and changes in the biological markers, particularly the ER/PgR status after NAC with or without T. Methods: Since April 2002, 143 patients with tumors ≥3 cm in diameter or lymph node metastases have received NAC and surgery. The treatment regimen were as follows; ET in 60 cases, FEC-DOC in 68 cases, and T with anthracycline and taxane in 15 cases. The items investigated were ER/PgR, Ki-67, HER2 and p53. The correlation between the changes in these factors after NAC and the treatment regimen was investigated. Results: The clinical response rate (CR+PR) was 84% in all patients. The pathological CR (pCR) rate was 7.7% in the ET, 20.9% in the FEC-DOC and 33.3% in the T regimen. The Ki67 values and ER/PgR status significantly correlated with pCR. Regarding the changes in biological markers, Ki67 values significantly decreased after NAC in all regimens. In the hormone receptor (HR) positive cases, ER and PgR positive cell rates significantly decreased (ER: 79.8% to 58.3% and PgR: 58.3% to 34.0%). However, in the arm with T, there were no significant changes in ER and PgR positive cell rates (ER: 72.7% to 69.2% and PgR: 50.3% to 38.1%). Conclusions: Lower ER/PgR expression and higher Ki-67 significantly correlated with pCR. Moreover, ER/PgR positive cell rates and Ki67 values significantly decreased after using chemotherapy. However, it appears that the T regimen may restore ER/PgR expression. Thus, ER and HER-2 expression may modify tumor biology via cross-talk even in NAC cases. No significant financial relationships to disclose.