Ruijie Niu

Background: The benefit of adjuvant chemotherapy in invasive lobular carcinoma (ILC) is still unclear. The objective of the current study was to elucidate the effectiveness of adjuvant chemotherapy in hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, pT1b-c/N0–1/M0 ILC. Methods: Based on Surveillance, Epidemiology, and End-Results (SEER) database, we identified original 12,334 HR-positive, HER2-negative, pT1b-c/N0–1/M0 ILC patients, who were then divided into adjuvant chemotherapy group and control group. End-points were overall survival (OS) and breast cancer-specific mortality (BCSM). Aiming to minimize the selection bias of baseline characteristics, Propensity Score Matching (PSM) method was used. Results: In a total of 12,334 patients with HR-positive, HER2-negative, pT1b-c/N0–1/M0 ILC, 1785 patients (14.5%) were allocated into adjuvant chemotherapy group and 10,549 (85.5%) into control group. Used PSM, the 1785 patients in adjuvant chemotherapy group matched to the 1785 patients in control group. By Kaplan-Meier survival analyses, we observed no beneficial effect of adjuvant chemotherapy on OS in both original samples (P = 0.639) and matched samples (P = 0.962), however, ineffective or even contrary results of adjuvant chemotherapy on BCSM both in original samples (P = 0.001) and in matched samples (P = 0.002). In both original and matched multivariate Cox models, we observed ineffectiveness of adjuvant chemotherapy on OS (hazard ratio (HR) for overall survival = 0.82, 95% confidence interval (CI) [0.62–1.09]; P = 0.172 and HR = 0.90, 95%CI [0.65–1.26]; P = 0.553, respectively), unexpectedly promoting effect of adjuvant chemotherapy on BCSM (HR = 2.33, 95%CI [1.47–3.67]; P = 0.001 and HR = 2.41, 95%CI [1.32–4.39]; P = 0.004, respectively). Standard surgery was beneficial to the survival of patients. Lymph node metastasis was detrimental to survival and radiotherapy brought survival benefit in original samples, but two issues had unobvious effect in matched samples. Conclusion: In this study, adjuvant chemotherapy did not improve survival for patients with HR-positive, HER2-negative pT1b-c/N0–1/M0 ILC.

Triple-negative breast cancer (TNBC) is a type of breast cancer with a high degree of malignancy. Because of the remarkable biological characteristics of high invasion, metastasis and recurrence, TNBC is often accompanied by a poor prognosis. As a molecular characteristic of TNBC, high expression of CD147 has been confirmed by a large number of studies. However, the mechanism of CD147 expression regulation in TNBC remains elusive. In this study, we investigated the roles of miR-890 in inhibiting CD147. Quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR) was used to detect CD147 mRNA and miR-890 level, and western blotting was used to detect CD147 protein. Bioinformatics screening and 3′-Untranslated Region (3′-UTR) luciferase assays were used to analyze the microRNAs (miRNA) binding site. Cell proliferation, apoptosis and invasion were assessed by using CCK-8, flow cytometry and transwell assays. The upregulation of miR-890 inhibited cell proliferation and invasion, induced apoptosis in MDA-MB-231 and HCC-70 TNBC cells by negatively regulating its target gene, CD147, and the upregulation of CD147 rescued the inhibitory effects of miR-890. miR-890 targeted CD147 by binding to its 3′-UTR. Further results showed that the upregulation of miR-890 also inhibited the expression of MMPs, the downstream genes of CD147, and promoted the cleavage of Caspase-3. The CD147 recovery experiment was further confirmed by the activity changes in the downstream MMPs of CD147. In addition, it was confirmed that the effect of CD147 in promoting TNBC cell proliferation and invasion, inhibiting apoptosis was related to the change in caspase-3 activity. The downregulation of miR-890 is the potential cause of high CD147 expression in TNBC, which can promote the malignant transformation of TNBC.

Breast cancer is the most frequent malignancy in women and drug resistance is the major obstacle for its successful chemotherapy. In the present study, we analyzed the involvement of an oncofetal gene, sal-like 4 (SALL4), in the tumor proliferation and drug resistance of human breast cancer. Our study showed that SALL4 was up-regulated in the drug resistant breast cancer cell line, MCF-7/ADR, compared to the other five cell lines. We established the lentiviral system expressing short hairpin RNA to knockdown SALL4 in MCF-7/ADR cells. Down-regulation of SALL4 inhibited the proliferation of MCF-7/ADR cells and induced the G1 phase arrest in cell cycle, accompanied by an obvious reduction of the expression of cyclinD1 and CDK4. Besides, down-regulating SALL4 can re-sensitize MCF-7/ADR to doxorubicin hydrochloride (ADMh) and had potent synergy with ADMh in MCF-7/ADR cells. Depletion of SALL4 led to a decrease in IC50 for ADMh and an inhibitory effect on the ability to form colonies in MCF-7/ADR cells. With SALL4 knockdown, ADMh accumulation rate of MCF-7/ADR cells was increased, while the expression of BCRP and c-myc was significantly decreased. Furthermore, silencing SALL4 also suppressed the growth of the xenograft tumors and reversed their resistance to ADMh in vivo. SALL4 knockdown inhibits the growth of the drug resistant breast cancer due to cell cycle arrest and reverses tumor chemo-resistance through down-regulating the membrane transporter, BCPR. Thus, SALL4 has potential as a novel target for the treatment of breast cancer.