Triple-negative breast cancer (TNBC) has become a difficult and blind area in breast cancer management due to the lack of clear drug targets, the poor effect of chemotherapy in some patients, and the ease of recurrence within a short period of time after surgery. In the opinion of Professor Qiang Liu from Sun Yat-sen Memorial Hospital of Sun Yat-sen University, there are two outstanding highlights of research on new TNBC targets in recent years – immunotherapy and targeting Androgen receptor (AR) therapy. The role of AR in breast cancer is gaining attention. In addition, HRD (homologous recombinant DNA repair defect), CD8+/FOXP3+ TILs and the predictive value of the gene tags ROR and RespondR for triple negative breast cancer as well as the exploration of other therapeutic targets also provided a lot of information at the meeting. In the interview, Prof. Qiang Liu focused on the role and value of androgen receptors among them. In addition, Prof. Qiang Liu’s team has a meta-analysis related to estrogen beta receptor expression included in this conference, please also join us to learn more about the study and the story behind the study. The significance of androgen receptor in triple negative breast cancer from the ENZA study There were many talks at ASCO that focused on triple negative breast cancer, and three of them were related to the role of androgen receptor (AR) in triple negative breast cancer, among which the ENZA study is very noteworthy, which is a further deepening of the TBCRC 011 study from 2013. An article published in J Clin Invest in 2011 pointed out that TNBC can be divided into seven subclasses based on the different expression of genes. Among them, the Luminal AR subclass, which does not exhibit the traditional basal-like phenotype of TNBC, expresses the cellular features of the Luminal-type epithelium and is AR-positive. The results of the TBCRC 011 study were published in the journal Clin Cancer Research in 2013. The investigators used bicalutamide to treat AR-positive TNBC patients, although the study had a small number of cases, with only 26 cases entering the effectiveness analysis and 5 patients achieving partial remission, for an efficiency rate of 19%. In the ENZA study presented at this year’s ASCO, investigators used the more potent oral AR antagonist enzalutamide – which was approved by the FDA in 2012 for the treatment of depression-resistant prostate cancer – with significantly better efficacy than bicalutamide, and two pivotal trials showed that enzalutamide compared with bicalutamide prolonged PFS in depression-resistant prostate cancer by 3-4 times. 3 to 4 times longer. 118 intention-to-treat patients were enrolled in the ENZA study, 75% were AR positive (89 patients), and 75 of these patients with post-baseline assessments entered the final study analysis. The results showed a clinical benefit rate (CBR, including complete remission, partial remission and stable disease) of 35% at 16 weeks and 29% at 24 weeks. 2 patients achieved complete remission and 5 patients achieved partial remission. Although this value is not high, patients with effective treatment were maintained effective for a long time. The overall side effects of the drug were minimal, with the most common grade 3 or higher side effect being fatigue, which also occurred in only 5% of cases. In addition, in the ENZA study, the investigators tested and analyzed relevant biomarkers and found an androgen-driven gene tag (PREDICT AR), and patients carrying this tag had a better response to treatment. In patients treated with enzalutamide in first and second line, the PFS of patients positive for this tag was 9.3 months, and its predictive value was better than that of immunohistochemistry for AR. Professor Qiang Liu believes that this is an important experimental result and this study tells us that for AR-positive TNBC, blocking the AR pathway may be an effective and safe option, while AR immunohistochemistry is not necessarily the most appropriate biomarker to distinguish its benefit or not. However, the label needs further independent validation and there is no uniform antibody or assay for AR immunohistochemistry, leading to excessive variation in the proportion of AR-positive patients in triple-negative breast cancer between studies (10%-75%), a problem that needs to be addressed in this area of research. Associated with the fact that ovarian suppression unexpectedly prolonged the survival of TNBC patients in last year’s POEMS study, TNBC may be effective against certain endocrine therapies and deserves further investigation. The significance of estrogen receptor beta in endocrine therapy The abstract by Prof. Qiang Liu’s team included in this year’s ASCO is a meta-analysis analyzing the relationship between high ER-β expression and patient survival prognosis. The estrogen receptor (ER), a frequent clinical test and the main target of endocrine therapy, refers to ER-α. In fact, ER includes two subtypes, ER-α and ER-β, and ER-β can be subdivided into five subtypes, ER-β1 to ER-β5. Although ER-β is also an estrogen receptor, its significance in the development and regression of breast cancer has been unknown. This is the main reason why Professor Qiang Liu conducted the study. This analysis included 15 studies that included 3897 breast cancer patients with ER-β1 and 1505 breast cancer patients with ER-β2 information. Patients with high expression of ER-β1 protein had significantly higher 5-year overall and disease-free survival, while those with high expression of ER-β2 protein also had significantly better 5-year disease-free survival. More importantly, the prognostic guidance of ER-β1 is applicable to ER-α positive or negative patients. In other words, as long as ER-β is highly expressed, the prognosis of patients is better regardless of whether ER-α is positive or not, which means that ER-β itself is a better indicator of breast cancer prognosis. However, whether ER-β is a target for endocrine therapy cannot be conclusively determined because there are no prospective controlled studies. But at least for ER-α-positive patients treated with triamcinolone acetonide and aromatase inhibitors, the higher the ER-β, the better the prognosis of the patients. This is unlike some studies that suggest that ER-β is a “good” molecule and that inhibiting it may have a bad effect – “we have found no evidence of that so far,” said Professor Liu Qiang. “