In the present study, in order to investigate the role of signal transducer and activator of transcription 3 (STAT3) in estrogen receptor (ER)-positive breast cancer prognosis, we evaluated the phosphorylated STAT3 (p-STAT3) status and investigated its effect on the outcome in a pooled analysis and in a large prospective adjuvant trial. By using the TCGA repository, we developed gene signatures that reflected the level of p-STAT3. Using pooled analysis of the expression data from luminal breast cancer patients, we assessed the effects of the p-STAT3 expression signature on prognosis. We further validated the p-STAT3 prognostic effect using immunohistochemistry (IHC) and immunofluorescence staining of p-STAT3 tissue microarrays from a large randomised prospective trial. Our analysis demonstrated that p-STAT3 expression was elevated in luminal A-type breast cancer (Kruskal-Wallis test, P<10e-10) and was significantly associated with a good prognosis (log-rank, P<10e-10). Notably, the p-STAT3 expression signature identified patients with a good prognosis irrespective of the luminal subtype (log-rank: luminal A, P=0.026; luminal B, P=0.006). p-STAT3 staining by IHC in the stroma or tumour was detected in 174 out of 610 ER-positive samples (28.5%) from the BIG 2-98 randomised trial. With a median follow-up of 10.1 years, p-STAT3 was associated with a reduced risk of recurrence in ER-positive/HER2-negative breast cancer (Cox univariate HR, 0.66; 95% CI, 0.44-0.98; P=0.04). On the whole, our data indicate that p-STAT3 is associated with an improved outcome in ER-positive breast cancer.
Acupuncture may help treat specific cancer-related symptoms. Here, we summarize our clinical trials that sought to determine acupuncture's role in managing cancer-related symptoms. Trials have been conducted to determine acupuncture's ability to mitigate cancer-related symptoms including dyspnea, fatigue, xerostomia, lymphedema, hot flashes, postoperative ileus, pain and dysfunction after neck dissection, and postthoracotomy pain. Published studies indicate that acupuncture versus placebo acupuncture failed to reduce cancer-related dyspnea. Both true and sham acupuncture alleviated fatigue slightly, but no significant differences between groups emerged. Compared with sham acupuncture, our research showed that acupuncture significantly improved saliva production in patients with xerostomia and significantly reduced lymphedema patients' arm circumference in a pilot study. However, acupuncture failed to significantly reduce hot flashes and was no more successful than sham acupuncture in reducing postoperative ileus. Significant reductions in pain and dysfunction occurred in cancer patients after neck dissection. In a feasibility study, acupuncture was found to be acceptable to lung cancer patients and did not interfere with standard postoperative care. In summary, acupuncture is a potential candidate for the treatment of some important cancer-related symptoms. Large clinical trials and research to investigate mechanistic pathways are warranted.
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