Purpose Breast cancer is the most common cancer in females and the leading cause of death worldwide. The effects of statins on breast cancer prognosis have long been controversial; thus, it is important to investigate the relationship between statin type, exposure time, and breast cancer prognosis. This study sought to explore the effect of statins, as well as the different effects of statin solubility and variable follow-up times, on breast cancer prognosis.

Human epidermal growth factor receptor 2 (HER2) protein overexpression or gene amplification is an important predictive biomarker for identifying patients with breast cancer, who may benefit from HER2-targeted therapy. However, little is known about the molecular landscape and efficacy of HER2-targeted therapy in patients with HER2-mutated metastatic breast cancer. We analysed the HER2 mutation features of 1184 patients with invasive breast cancer. In addition, a single-arm, prospective, phase-II study (NCT03412383) of pyrotinib was conducted in patient with metastatic HER2 amplification-negative, mutation-positive breast cancer. Peripheral blood was collected from each patient and circulating tumour DNA (ctDNA) sequencing was performed using a 1021 gene panel. HER2 mutations were detected in 8.9% (105/1184) of patients. The HER2 amplification-positive patients had a higher mutation frequency than the HER2 amplification-negative patients (19.5% vs. 4.8%, P < 0.001). A multivariate Cox regression analysis indicated that patients with HER2 mutations had a shorter progression-free survival (PFS) than HER2 wild-type patients (median PFS 4.7 months vs. 11.0 months, hazard ratio 2.65, 95% confidence interval 1.25–5.65, P = 0.011). Ten HER2 amplification-negative, mutation-positive patients who received pyrotinib monotherapy were ultimately included in the efficacy analysis. The median PFS was 4.9 months. The objective response rate (complete response + partial response) was 40.0% and the clinical benefit rate (complete response + partial response + stable disease over 24 weeks) was 60%. In conclusion, a HER2 gene mutation analysis is potentially useful to identify biomarkers of trastuzumab resistance in HER2 amplification-positive patients. Patients with HER2-mutated, non-amplified metastatic breast cancers may benefit from pyrotinib.

e21606 Background:Breast cancer is the most common cancer in females. The effects of statins on breast cancer prognosis have long been controversial, so it is important to investigate the relationship between statin type, exposure time, and breast cancer prognosis. This study sought to explore the effect of statins on breast cancer prognosis. Methods:We searched the MEDLINE, EMBASE, Cochrane Library between October 15, 2016 and January 20, 2017. Searches combined the terms “breast neoplasms[MeSH]”, “statins”, “prognosis” or “survival” or “mortality” with no limit on publication date. Data were analyzed using Stata/SE 11.0. Results: 7 studies finally met the selection criteria and 197,048 included women. Overall statin use was associated with lower cancer-specific mortality and all-cause mortality (HR 0.73, 95% CI 0.59-0.92, P = 0.000 and HR 0.72, 95% CI 0.58-0.89, P = 0.000). Lipophilic statins were associated with decreased breast cancer-specific and all-cause mortality (HR 0.57, 95% CI 0.46-0.70, P = 0.000 and HR 0.57, 95% CI 0.48-0.69, P = 0.000); however, hydrophilic statins were weakly protective against only all-cause mortality (HR 0.79, 95% CI 0.65-0.97, P = 0.132) and not breast cancer-specific mortality (HR 0.94, 95% CI 0.76-1.17, P = 0.174). Of note, more than four years of follow-up did not show a significant correlation between statin use and cancer-specific mortality or all-cause mortality (HR 0.84, 95% CI 0.71-1.00, P = 0.616 and HR 0.95, 95% CI 0.75-1.19, P = 0.181), while groups with less than four years of follow-up still showed the protective effect of statins against cancer-specific mortality and all-cause mortality (HR 0.62, 95% CI 0.44-0.87, P = 0.000 and HR 0.61, 95% CI 0.45-0.80, P = 0.000). Conclusions:Although statins can reduce breast cancer patient mortality, the benefit appears to be constrained by statin type and follow-up time. Lipophilic statins showed a strong protective function in breast cancer patients, while hydrophilic statins only slightly improved all-cause mortality. Finally, the protective effect of statins could only be observed in groups with less than four years of follow-up.

Low-dose metronomic chemotherapy can achieve disease control with reduced toxicity compared to conventional chemotherapy in maximum tolerated dose. Characterizing the gut microbiota of cancer patients under different dosage regimens may describe a new role of gut microbiota associated with drug efficacy. Therefore, we evaluated the composition and the function of gut microbiome associated with metronomic capecitabine compared to conventional dosage. Methods: The fecal samples of HER2-negative metastatic breast cancer patients treated with capecitabine as maintenance chemotherapy were collected and analyzed by 16S ribosome RNA gene sequencing. Results: A total of 15 patients treated with metronomic capecitabine were compared to 16 patients under a conventional dose. The unweighted-unifrac index of the metronomic group was statistically significantly lower than that of the routine group (P = 0.025). Besides that, the Bray-Curtis distance-based redundancy analysis illustrated that the microbial genera between the two groups can be separated partly. Nine Kyoto Encyclopedia of Genes and Genomes (KEGG) modules were enriched in the metronomic group, while no KEGG modules were significantly enriched in the routine group. Moreover, univariate and multivariate analyses suggested that the median progression-free survival (PFS) was significantly shorter in patients with the gut microbial composition of Slackia (9.2 vs. 32.7 months, P = 0.004), while the patients with Blautia obeum had a significantly prolonged PFS than those without (32.7 vs. 12.9 months, P = 0.013). Conclusions: The proof-of-principle study suggested that the gut microbiota of patients receiving metronomic chemotherapy was different in terms of diversity, composition, and function from those under conventional chemotherapy, and the presence of specific bacterial species may act as microbial markers associated with drug resistance monitoring and prognostic evaluation.