Abstract P1-14-06: Significance of examining biomarkers of residual tumors after neoadjuvant chemotherapy using trastuzumab in combination with anthracycline and taxane in patients with primary HER2-positive breast cancer
Authors: Kurozumi S , Takei H , Inoue K , Matsumoto H , Hayashi Y , Ninomiya J , Kubo K , Tsuboi M , Nagai S , Ookubo F , Oba H , Kurosumi M , Horiguchi J , Takeyoshi I 
Published: August 2014

Abstract
Background: Neoadjuvant chemotherapy (NAC) with taxane and FEC concurrently with trastuzumab is a potent regimen in women with HER2-positive breast cancer (BC), and several studies revealed high pCR rates in BC patients treated with this regimen. In the present study, we compared the status of biomarkers before and after NAC, and evaluated rates and patterns of discordant biomarker expression. We also evaluated differences of prognosis between patients with discordant biomarker expression and those with concordant expression.
Patients and Methods: We investigated 118 Japanese women with invasive HER2 positive BC. Patients received 12 cycles of paclitaxel or 4 cycles of docetaxel followed by 4 cycles of FEC-75 with concomitant trastuzumab for 24 weeks and were followed for ≥1 year after surgery. Of these, 27 patients with residual tumors 5 mm or larger were analyzed. HER2, ER, PgR, and Ki67 were examined in primary and residual tumors. Furthermore, recurrence-free survival (RFS) and overall survival (OS) were analyzed between patients classified based on these biomarkers.
Results: Patients with pCR after NAC (75/118; 63.5%) had significantly better RFS than non-pCR patients (median follow-up: 41 months). Residual tumors were obtained from 27 of 43 non-pCR patients and examined for immunohistochemical biomarker expression. In 14/27 non-pCR patients (51.9%), residual tumors were HER2 negative, despite being HER2 positive before NAC: HER2 score changed from 3+ to 0 or 1+ in 8/18 patients (44.4%) and from 2+ to 0 or 1+ in 6/9 (66.7%). ER expression changed in 2 patients (1 positive to negative and 1 negative to positive). Patterns of biomarker expression in residual tumors were HER2 (+)/ER (–), 6 patients (22.2%); HER2 (+)/ER (+), 7 (25.9%); HER2 (–)/ER (+), 11 (40.7%); and triple negative (TN), 3 (11.1%). Recurrence was observed in 8/27 (29.6%) non-pCR patients, and patterns of biomarker expression in residual tumors were HER2 (+)/ER (–), 3 patients; HER2 (+)/ER (+), 2; and HER2 (–)/ER (+), 3. In addition, 1 patient with a HER2 (+)/ER (+) tumor and 1 patient with a HER2 (−)/ER (+) tumor died. RFS and OS were not statistically different between patients classified based on ER and Ki67 expressions. However, in the 18 non-pCR patients with primary tumor HER2 score of 3+ (overexpression of HER2 protein), the 10 with HER2-positive residual tumors showed significantly lower RFS than the 8 with HER2-negative (p &lt; 0.04).
Conclusions: Although this regimen achieved a high pCR rate in HER2-positive BC patients, about 40% still had residual tumors. In the present study, we found that positive HER2 expression seen in pre-NAC tumors became negative in 52% of residual tumors after NAC. Theses HER2-negative residual tumors might not respond well to trastuzumab therapy, and residual tumors remaining HER2 positive might show low or no response to trastuzumab therapy. Moreover, the prognosis seems worse for non-pCR patients with HER2-positive residual tumors. However, Ki67 was not a significant prognostic factor. Examining biomarker expression of residual tumors after NAC seems very important for deciding further adjuvant therapy.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-14-06.