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

Since the detection of circulating tumor cells (CTCs) which express HER2 is an adverse prognostic factor in early breast cancer patients, we investigated the effect of trastuzumab on patients' clinical outcome. Seventy five women with HER2 (-) breast cancer and detectable CK19 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 CK(+)/HER2(+) cells by immunofluorescence. The primary endpoint was the 3-year disease-free survival rate. 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 to seven of 39 (17.9%) in the observation arm (p = 0.001). After a median follow up time of 67.2 months, four (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 > 3 involved axillary lymph nodes (p = 0.004). The median DFS was also significantly higher for the trastuzumab-treated patients (p = 0.008). Administration of trastuzumab can eliminate chemotherapy-resistant CK19 mRNA-positive CTCs, reduce the risk of disease recurrence and prolong the DFS.