Abstract P3-01-15: Circulating tumor cell subset analysis to assess lifestyle interventions for breast cancer patients after neoadjuvant chemotherapy
Authors: Gao H , Cohen EN , Yang P , Austin TA , Haddad R , Wu Q , Basen-Engquist KM , Ochoa JM , Arun BK , Perkins GH , Tin S , Vallone VS , Mallaiah SG , West CB , Thompson AS , Chaoul A , Cohen L , Reuben JM 
Published: May 2019

Background:Circulating tumor cells (CTCs) are an independent predictor of survival in patients with breast cancer. In addition, mesenchymal (EMT-CTC) and stem-like (Stem-CTC) CTCs contribute to disease progression. The objective of the overall study is to determine whether a comprehensive lifestyle intervention program started prior to radiotherapy can modulate changes in CTC subsets that are correlated with disease recurrence and progression. For these analyses we examined the association between medical and treatment-related factors and CTCs.

Patients and Methods: Seventy-eight patients with stage II/III breast cancer were recruited and randomized to either the intervention group or a standard care group. The intervention group (n=42) had in-person lifestyle counseling across the 4-6 weeks of radiotherapy (XRT) followed by video counseling for the subsequent 12 months. The standard care group (n=36) was provided patient-education materials for cancer prevention including information on diet, exercise, and stress management, without counseling. Blood samples were collected prior to initiation of XRT, end of XRT, and at 3-month intervals thereafter for up to 5 years. CTC subsets were detected by AdnaTest EMT2 kit (Qiagen, Venlo, Netherlands). Samples were considered positive for CTCs if any one of breast (EPCAM, MUC1, and HER2), EMT (TWIST1), or stem cell-related (ALDH1, AKT2, and PI3Kalpha) genes were detected by PCR above the manufacturer's suggested threshold.

Results: The median age of patients was 49 years (range 26-82 years). Thirty-four patients were overweight (BMI 24.4-30) and 44 patients were obese (BMI &gt;30). Forty-five patients were HR+Her2-, 12 patients were HR+Her2+, 5 patients were HR-Her2+, and 16 patients were TNBC. Sixteen patients were stage IIA or IIB, 34 patients were stage IIIA or IIIB, 27 patients were stage IIIC, and 1 was stage IV. Sixty-seven of 78 patients received neoadjuvant chemotherapy (NACT); 13 patients achieved a complete pathological response (pCR). The median follow-up was 21.6 months. CTC data of both intervention and standard groups were similar at baseline. Presence of CTCs at baseline or follow-up time points was not correlated to HR/Her2 status, stage, obesity, or pCR, but was significantly correlated with receiving NACT. Patients without NACT had significantly higher CTCs than patients who underwent NACT (Fisher Exact Test p=0.010). Furthermore, CTCs by the detection of any gene 3 months after completing XRT was associated with shorter PFS (log-rank p=0.016) and OS (p=0.03).

Conclusions:This is an interim analysis of the prognostic potential of CTCs detected by AdnaTest EMT2 kit in non-metastatic breast cancer. We observed a lower proportion of patients with CTCs following neoadjuvant chemotherapy. However, the relative small sample size and short follow-up time preclude drawing conclusions to the efficacy of using CTCs as surrogate measures for lifestyle interventions, although the presence of CTCs in peripheral blood of patients 3 months after radiation therapy can be a promising indicator of disease relapse and overall survival.

Citation Format: Gao H, Cohen EN, Yang P, Austin TA, Haddad R, Wu Q, Basen-Engquist KM, Ochoa JM, Arun BK, Perkins GH, Tin S, Vallone VS, Mallaiah SG, West CB, Thompson AS, Chaoul A, Cohen L, Reuben JM. Circulating tumor cell subset analysis to assess lifestyle interventions for breast cancer patients after neoadjuvant chemotherapy [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-01-15.