Circulating tumor cells as a prognostic marker for efficacy in the randomized phase III JO21095 trial in Japanese patients with HER2-negative metastatic breast cancer.
Prognostic effects of circulating tumor cells (CTCs) have been reported in metastatic breast cancer (MBC). However, few phase III trials have investigated the potential role of CTCs in treatment selection. We explored potential relationships between CTCs, efficacy, and differential treatment effects.



Patients with HER2-negative MBC were randomized to receive either concurrent capecitabine plus docetaxel (XT) or sequential single-agent docetaxel followed by single-agent capecitabine at progression (T → X). Blood samples were collected at baseline, on day 1 of cycles 2 and 3, and at progression. CTCs were counted using the CellSearch®System. The relationship between baseline CTC count and outcomes was investigated using a pre-defined threshold of 2 CTCs/7.5 mL.



At screening, 44% of the 148 enrolled patients had positive CTC score. In multivariate analyses of pooled treatment arms, positive baseline CTC and triple-negative disease were strongly associated with worse progression-free survival (PFS) and overall survival (OS). Patients with positive CTC score at the baseline had worse OS, irrespective of change in CTC (decreased versus remaining positive) at cycle 2. The prognostic effect of baseline CTC count on OS appeared slightly less pronounced in XT-treated pts. compared with T → X.



A baseline CTC count ≥2 CTCs/7.5 mL was associated with worse prognosis. However, some improvement in PFS and OS was shown with concurrent XT, thus baseline CTC could be a predictive marker. As the current trial was not designed to evaluate a change in chemotherapy according to on-treatment CTC changes, prospective investigation is required.
Department of Breast Oncology, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-ku, Nagoya, 464-8681, Japan. hiwata@aichi-cc.jp.
Hiroji
H
Iwata
Department of Surgery, Breast Oncology, National Hospital Organization Osaka National Hospital, Osaka, Japan.
Norikazu
N
Masuda
Department of Surgery, Kansai Medical University Medical Center, Osaka, Japan.
Daigo
D
Yamamoto
Department of Breast Surgery, Sagara Hospital, Kagoshima, Japan.
Yoshiaki
Y
Sagara
Department of Surgery, Niigata Cancer Center Hospital, Niigata, Japan.
Nobuaki
N
Sato
Department of Breast and Endocrine Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
Yutaka
Y
Yamamoto
Department of Breast Oncology, Juntendo University Hospital, Tokyo, Japan.
Mitsue
M
Saito
Department of Breast Oncology, Jichi Medical University Hospital, Tochigi, Japan.
Takashi
T
Fujita
Department of Thoracic and Cardiovascular Surgery, Wakayama Medical University, Wakayama, Japan.
Shoji
S
Oura
Department of Breast Oncology, Shizuoka Cancer Center, Shizuoka, Japan.
Junichiro
J
Watanabe
Department of Breast Surgery, NTT West Osaka Hospital, Osaka, Japan.
Masami
M
Tsukabe
Department of Surgery, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo, Japan.
Kazumi
K
Horiguchi
Biostatistics Center, Kurume University, Fukuoka, Japan.
Satoshi
S
Hattori
Medical Affairs, Chugai Pharmaceutical CO., LTD., Tokyo, Japan.
Yoshimasa
Y
Matsuura
Department of Surgery, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo, Japan.
Katsumasa
K
Kuroi
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D014408:Biomarkers, Tumor; D001943:Breast Neoplasms / Q000188:drug therapy / Q000401:mortality* / Q000473:pathology*; D002452:Cell Count; D017326:Clinical Trials, Phase III as Topic; D005260:Female; D006801:Humans; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D009362:Neoplasm Metastasis; D009360:Neoplastic Cells, Circulating / Q000473:pathology*; D011379:Prognosis; D016032:Randomized Controlled Trials as Topic; D018719:Erb-b2 Receptor Tyrosine Kinases; D016019:Survival Analysis; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases
Circulating tumor cells; HER2-negative; Metastatic breast cancer; Phase III trial; Prognostic factor