Stratification of Prognosis by Biological Features Following Neoadjuvant Chemotherapy in Luminal Breast Cancer

Abstract

Background/Aim: There are few models predicting breast cancer prognosis among patients receiving neoadjuvant chemotherapy (NAC) for estrogen receptor (ER)-positive/ human epidermal growth factor receptor 2 (HER2)-negative (luminal) breast cancer. We examined whether biological features (BFs) of residual tumors are prognostic factors following NAC. Patients and Methods: We enrolled patients with remnant tumors following NAC for luminal breast cancer and evaluated clinical stage, pathological stage, BFs prior to NAC, and BFs following NAC as prognostic factors. BFs were divided into high and low risk using the previously reported YR-IHC4 model calculated according to ER, progesterone receptor (PgR), HER2, and the proliferation marker Ki-67. Results: A total of 57 patients were enrolled in the current study. We observed a statistically significant difference in relapse-free survival (RFS) between the BF risk categories via YR-IHC4 predictions following NAC (p=0.044). The 5-year RFS rates of the BF low-and high-risk groups following NAC were 84.2% and 52.5%, respectively. Conclusion: BFs of residual tumors following NAC may be important prognostic factors in luminal breast cancer.Patients with breast cancer who achieve pathological complete response (pCR) following neoadjuvant chemotherapy (NAC) are reported to have improved event-free survival and overall survival (OS) (1). However, response-guided treatment following NAC has recently been administered to patients without pCR. For example, in patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer who present with residual invasive disease following NAC, prognoses were improved by changing the postoperative treatment to trastuzumab emtansine (from trastuzumab) (2).Estrogen receptor (ER)-positive/HER2-negative (luminal) breast cancer, which accounts for 60-70% of all breast cancers (3, 4), has a low pCR rate (5) and lacks management evidence with respect to non-pCR cases. Thus, there is a need to identify non-pCR luminal breast cancer cases with high risk of recurrence.Biological features (BFs) and conventional anatomical factors are important prognostic factors (6). Oncotype DX recurrence scores (RS) are available as a means of expressing the BFs as predictive factors with respect to chemotherapy and overall prognostic factors (7). There are some reports that RS can be predicted using four immunostaining markers [ER, progesterone receptor (PgR), HER2, and Ki-67] that are measured in daily clinical practice (8,9). We also previously reported a model based on these four factors to predict RS ≥26 (10). The cutoff value of 26 points is a guide in the TAILORx (11) and RxPONDER (12) trials. Ueno et al. (13) reported that, in neoadjuvant endocrine therapy (NET), the combination of pre-and post-treatment RS provides pivotal information for predicting prognosis. However, to our knowledge, no study has examined the prediction of prognosis based only on the BFs of the residual tumors following NAC, in which physiology changes more dramatically tha...