Trastuzumab decreases the incidence of clinical relapses in patients with early breast cancer presenting chemotherapy-resistant CK-19mRNA-positive circulating tumor cells: results of a randomized phase II study

Background: Since the detection of circulating tumor cells (CTCs), which express that human epidermal growth factor receptor 2 (HER2) is an adverse prognostic factor in early breast cancer patients, we investigated the effect of trastuzumab on patients’ clinical outcome. Patients and methods: Seventy-five women with HER2-negative breast cancer and detectable CK19 messenger RNA (mRNA)-positive CTCs before and after adjuvant chemotherapy were randomized to receive either trastuzumab (n = 36) or observation (n = 39). CK19 mRNA-positive CTCs were detected by RT-PCR and double-stained CKpositive/HER2-positive cells by immunofluorescence. The primary end point was the 3-year disease-free survival rate. Results: Fifty-one (89%) of the 57 analyzed patients had HER2-expressing CTCs. After trastuzumab administration, 27 of 36 (75%) women became CK19 mRNA negative compared with 7 of 39 (17.9%) in the observation arm (P = 0.001). After a median follow-up time of 67.2 months, 4 (11%) and 15 (38%) relapses were observed in the trastuzumab and observation arm, respectively (P = 0.008); subgroup analysis indicated that this effect was mainly confined to women with more than three involved axillary lymph nodes (P = 0.004). The median DFS was also significantly higher for the trastuzumab-treated patients (P = 0.008). Conclusion: Administration of trastuzumab can eliminate chemotherapy-resistant CK19 mRNA-positive CTCs, reduce the risk of disease recurrence and prolong the DFS.