APOBEC3B gene expression as a novel predictive factor for pathological complete response to neoadjuvant chemotherapy in breast cancer

// Yoshitaka Fujiki 1 , Yutaka Yamamoto 1 , Aiko Sueta 1 , Mutsuko Yamamoto-Ibusuki 2 , Lisa Goto-Yamaguchi 1 , Mai Tomiguchi 1 , Takashi Takeshita 1 and Hirotaka Iwase 1 1 Department of Breast and Endocrine Surgery, Kumamoto University Graduate School of Medical Sciences, Chuo-Ku, Kumamoto 860-8556, Japan 2 Department of Molecular-Targeting Therapy for Breast Cancer, Kumamoto University Hospital, Chuo-Ku, Kumamoto 860-8556, Japan Correspondence to: Yutaka Yamamoto, email: ys-yama@triton.ocn.ne.jp Keywords: APOBEC3B; breast cancer; neoadjuvant chemotherapy; predictive factor; pathological complete response Received: September 24, 2017      Accepted: May 12, 2018      Published: July 17, 2018 ABSTRACT Background: Apolipoprotein B mRNA editing enzyme catalytic polypeptide-like 3B (APOBEC3B) is a gene editing enzyme with cytidine deaminase activity and high expression of its mRNA in breast tumors have been shown to be associated with progressive cases and poor prognosis. In this study, we aimed to examine the relationship between the expression of APOBEC3B and the effect of neoadjuvant chemotherapy (NAC) using pretreatment biopsy tissue, and examined whether the expression of APOBEC3B influenced chemotherapy efficacy. Methods: We retrospectively selected a total of 274 patients with primary breast cancer who received NAC in more than 4 courses and underwent surgery at our institute. We assessed the expression of APOBEC3B mRNA using pretreatment biopsy specimens of NAC by quantitative real-time PCR (qRT-PCR) and examined the relationship between APOBEC3B mRNA expression and sensitivity to chemotherapy using pathological complete response (pCR) as an indicator. Further, we assessed the prognostic value of APOBEC3B in the patients receiving NAC. Results: APOBEC3B mRNA expression levels were successfully assessed in 173 (63.1%) of the 274 specimens. The total pCR rate was 36.4% (n = 63). An association between APOBEC3B expression levels and pCR was observed (Wilcoxon test, P ≤ 0.0001). The patients were divided into two groups, low (n = 66) and high (n = 107), according to the APOBEC3B expression levels, using the cut-off value calculated by the receiver operating characteristics (ROC) curve for pCR. The rate of pCR was significantly higher among the patients in the high group than among those in the low group (47.7% vs 18.2%, P ≤ 0.0001). High APOBEC3B expression was significantly associated with high nuclear grade (P = 0.0078), high Ki-67 labeling index (P = 0.0087), estrogen receptor (ER) negativity (P ≤ 0.0001) and human epidermal growth factor receptor 2 (HER2) negativity (P = 0.032). Tumor size (P = 0.011), ER (P ≤ 0.0001), HER2 (P = 0.0013) and APOBEC3B expression (P = 0.037) were independent predictive factors for pCR in multivariate analysis. However, there was no association between APOBEC3B expression and prognosis. Conclusions: Our study showed that APOBEC3B mRNA expression correlated with sensitivity to NAC in breast cancer patients. In contrast to previous studies, APOBEC3B mRNA expression was not associated with breast cancer prognosis in patients receiving NAC.