Background: Palbociclib combined with endocrine therapy has been approved as a front-line treatment for hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2−) advanced breast cancer (ABC). A key challenge remains to uncover biomarkers to identify those patients who may benefit from palbociclib treatment.Methods: We retrospectively analyzed the values of Ki67 and progesterone receptor (PR) as detected by immunohistochemistry in 81 ABC patients with palbociclib and hormone therapy treatment, and evaluated the impact on progression-free survival (PFS).Results: In the total population, women with Ki67 ≥14% had marginally significantly shorter PFS than those with Ki67 <14% (P=0.062). Patients with Ki67 ≥30% had significantly shorter PFS than those with Ki67 <30% (P=0.048). Meanwhile, PR ≥20% was associated with longer PFS. Moreover, the change of Ki67 or PR from primary tissue to metastatic lesions was related to PFS. As for the hormone therapy subgroup, there were significant associations between Ki67 and PR levels and PFS in the aromatase inhibitors (AIs) subgroup. Patients with Ki67 ≥14% or Ki67 ≥30% had shorter PFS than those with Ki67 <14% or Ki67 <30%, respectively (P=0.024, P<0.001). Additionally, the change of Ki67 or PR from primary tissue to metastatic lesions was related to PFS. When both Ki67 and PR were considered, there were significant differences between the different cohorts. Compared with patients with Ki67 ≥14% and PR <20%, those with Ki67 <14% and PR ≥20% had significantly longer PFS. In addition, patients with Ki67 <30% and PR ≥20% had significantly longer PFS than those with Ki67 ≥30% and PR <20%. Furthermore, in the AI cohort, patients with Ki67 <14% and PR ≥20% had significantly longer PFS than those with Ki67 ≥14% and PR <20%. Women with Ki67 <30% and PR ≥20% had significantly longer PFS than those with Ki67 ≥30% and PR <20%. Conclusions:The present study indicates that both Ki67 and PR have great impacts on palbociclib and hormone therapy and may contribute to selecting more effective partners for palbociclib.

Triple negative breast cancer (TNBC) accounts for approximately 15–20% of all breast cancer cases and is usually more aggressive with a poorer clinical outcome compared with other breast cancer subtypes. Evidence of the involvement of microRNAs (miRNAs) in cancer has provided an opportunity for the development of novel effective therapeutic targets in TNBC. In the present study, the miRNA expression profiles of the human breast cancer cell line, MDA-MB-231, and MCF-7 cells, was evaluated by using miRNA microarray analysis. A total of 107 differentially expressed miRNAs (57 upregulated and 50 downregulated) were identified in MDA-MB-231 cells compared with MCF-7 cells. Five prominently dysregulated miRNAs (miR-200c-3p, miR-221-3p, miR-222-3p, miR-192-5p and miR-146a) were further confirmed by reverse transcription-quantitative polymerase chain reaction. In addition, gene ontology analysis and pathway enrichment analysis revealed that the dysregulated miRNAs and predicted targets were found to be involved in the mitogen-activated protein kinase, Wnt, and transforming growth factor-β signaling pathways, which were known to contribute to TNBC progression and metastasis. Finally, miRNA gene network analyses suggested that miR-200c may serve as a crucial miRNA in breast cancer. Taken together, these findings may provide a comprehensive view of the function of aberrant miRNAs involved in TNBC, and dysregulated miRNAs hold promise as potential biomarkers and therapeutic targets for patients with TNBC.

Endocrine treatment plus CDK4/6 inhibitors have become standard of care for estrogen receptor positive (ER+) breast cancer. Although immune checkpoint inhibitors (ICIs) have shown promising antitumor activity in a variety of cancer types, only limited success has been achieved for metastatic breast cancer (mBC) patients, especially the ER+ subtype, which usually exhibit lower tumor mutation burden (TMB) compared with other subtypes and therefore perceived as immunologically quiescent. Here we present a case of an ER+/HER2- but TMB-high mBC patient who had significant response to combination therapy with anti-PD-1 antibody camrelizumab and vinorelbine and obtained partial response (PR) with a progression-free survival (PFS) of 5 months after failure of multiple lines of therapy. Our case indicates that TMB may serve as a potential biomarker in immunotherapy selection for normally immunologically “cold” tumors such as ER+ mBC, also molecular monitoring during the whole treatment course plays an important role in patient management.

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Background Though BRCA1 mutation is the most susceptible factor of breast cancer, its prognostic value is disputable. Here in this study, we use a novel method which based on whole-genome analysis to evaluate the chromosome instability (CIN) value and identified the potential relationship between CIN and prognosis of breast cancer patients with germline-BRCA1 mutation. Materials and methods Sanger sequencing or a 98-gene panel sequencing assay was used to screen for BRCA1 germline small mutations in 1151 breast cancer patients with high-risk factors. MLPA assay was employed to screen BRCA1 large genomic rearrangements in familial breast cancer patients with BRCA1 negative for small mutations. Thirty-two samples with unique BRCA1 germline mutation patterns were further subjected to CIN evaluation by LPWGS (low-pass whole-genome sequencing) technology. Results Firstly, 113 patients with germline BRCA1 mutations were screened from the cohort. Further CIN analysis by the LPWGS assay indicated that CIN was independent from the mutation location or type of BRCA1. Patients with high CIN status had shorter disease-free survival rates (DFS) (HR = 6.54, 95% CI 1.30–32.98, P = 0.034). The TP53 copy loss was also characterized by LPWGS assay. The rates of TP53 copy loss in CIN high and CIN low groups were 85.71% (12/14) and 16.67% (3/18), respectively. Conclusion CIN-high is a prognostic factor correlated with shorter DFS and was independent with the germline BRCA1 mutation pattern. Higher CIN values were significantly correlated with TP53 copy loss in breast cancer patients with germline BRCA1 mutation. Our results revealed a reliable molecular parameter for distinguishing patients with poor prognosis from the BRCA1-mutated breast cancer patients.