Two major studies: Switching to a new regimen may improve outcomes in some patients The more important of the two oral presentations of the GeparTrio trial was the results of the GeparTrio trial, a clinical study of neoadjuvant chemotherapy, presented by von Minckwitz. In patients receiving 2 cycles of neoadjuvant chemotherapy with the TAC regimen, different strategies were adopted depending on the efficacy of the TAC regimen. If patients achieved CR/PR (those who were effective), randomized groups were treated with 4 or 6 more cycles of the TAC regimen. If the efficacy was SD (nullifiers) after 2 cycles of TAC regimen, the randomized group was given 4 cycles of TAC regimen or 4 cycles of NX (vincristine + capecitabine). The primary aim of the study was to compare the remission rates of those who were effective versus those who were not, and the secondary aim was to compare the DFS and OS of conventional neoadjuvant chemotherapy strategy (conventional arm) versus efficacy-guided therapy (response-guided arm). 1390 patients with effective TAC were randomized to TAC x 4 cycles or TAC x 6 cycles; 622 HER2-positive patients were not treated with trastuzumab. The results showed that the pCR was significantly higher for those who were effective than for those who were ineffective, but for those who were effective, there was no difference in pCR for either the TAC regimen for 6 or 8 cycles, and patients on the TAC×8 regimen had a significantly longer DFS (HR=0.79, P=0.026) and a trend toward a benefit in OS (HR=0.76, P=0.061); similarly, for patients who were ineffective, there was no difference in pCR for either continuing TX or switching to NX, there was no difference in pCR, but patients also had significantly longer DFS with TAC×2-NX×4 compared with TAC×6 (HR=0.6, P=0.001), and the difference in OS was not significant. Patients with an efficacy-guided treatment strategy (TAC×8 or TAC×2-NX×4) had a longer DFS (HR=0.71, P<0.001) and OS (HR=0.79, P=0.048) compared to patients receiving conventional TAC×6 cycles. Further analysis of the efficacy according to the phenotype of breast cancer showed that the benefit of DFS was concentrated in the Luminal A (P=0.003), Luminal B (HER2 negative, P=0.006; HER2-positive, P=0.04) subtypes. In contrast, for patients with both HER2-positive (P=1.0) and triple-negative (P=0.5) subtypes, no additional benefit in DFS was seen by adjusting the regimen according to efficacy. For both subtypes, as well as the Luminal B (HER2-negative) type, DFS was prolonged in patients who achieved pCR. In terms of study design, there are some issues with GeparTrio's trial, such as the choice of regimen and number of cycles, and the setting of study endpoints, but the results of the study are still very interesting to consider. First, for neoadjuvant chemotherapy, most scholars believe that if it is not effective for one chemotherapy regimen, it is likely to be ineffective for other treatment regimens as well, but the GeparTrio trial showed that although the efficiency did not increase after switching to a new regimen, it resulted in a benefit in DFS and even OS. Secondly, the efficacy of neoadjuvant chemotherapy for different breast cancer subtypes has been judged by pCR, with Luminal B, HER2-positive, and triple-negative (or basal-like) subtypes having a higher chance of achieving pCR, while Luminal A subtypes, with a low chance of achieving pCR, have difficulty benefiting from neoadjuvant chemotherapy. The GeparTrio trial, however, suggests that patients with Luminal A, when regimens are adjusted according to efficacy, can lead to a prolongation of DFS. The achievement of pCR with chemotherapy had no impact on survival in Luminal A patients. pCR is not a good predictor of benefit from neoadjuvant chemotherapy in Luminal A patients. This is probably the most important insight from the GeparTrio study. pCR is not a "one size fits all" indicator for neoadjuvant chemotherapy and should not be the only criterion for prognosis. Of course, this result can only suggest that in Luminal A patients, it is better to adjust the regimen according to the efficacy than not to adjust it, but it does not yet indicate that in Luminal A patients, if the neoadjuvant chemotherapy regimen is adjusted according to the efficacy, it is the best treatment choice for these patients, which is better than neoadjuvant endocrine therapy or postoperative adjuvant chemotherapy. And it is not known whether the choice of a 2-cycle TAC regimen followed by randomization rather than a 4-cycle TAC regimen followed by randomization had an impact on the outcome of the final trial. Another interim result of the GAIN study is the results of the first interim efficacy analysis of the GAIN study reported by Mobus, Germany. This multicenter phase III randomized controlled clinical study (3023 patients) compared the efficacy of a postoperative regimen of intensive ETC given for 3 cycles (group A1) with a 4 cycle EC regimen sequenced with 4 cycles of TX regimen (group A2) in patients with lymph node positive breast cancer. Patients were given prophylactic erythropoietin and long-acting G-CSF during intensive chemotherapy. patients were then further randomized on a 2:1 basis to receive ibandronate: 50 mg/d (group B1) or observation alone (group B2). Although this was a study on postoperative adjuvant chemotherapy, only the results of ibandronate were reported at this congress because the chemotherapy component did not meet the definition of ineffective in the interim analysis. However, the investigators mentioned that the regimen was revised after enrolling 1500 patients, prophylactic ciprofloxacin was given, and the dose of CTX was adjusted downward to 2000 mg/m2. suggesting greater chemotherapy toxicity with the intensive ETC regimen. Three focuses: exploration of different regimens, drug efficacy and efficacy prediction The remaining chemotherapy part of the research progress revolves around three parts: (1) For the exploration of postoperative adjuvant chemotherapy regimens, such as the WSG Plan B study, the PACS08 study of the addition of Ixabepilone to adjuvant therapy. Among them, the ADEBAR phase III clinical study from Germany compared the efficacy of FE120C (epirubicin + cyclophosphamide + 5-FU) and E90C-D regimens (epirubicin + cyclophosphamide + docetaxel) in patients with greater than three axillary lymph nodes, and the preliminary results showed a significant increase in hematologic toxicity in the FE120C regimen. While the Japanese NSAS-BC02 study reported the final analysis results comparing the AC-P regimen, AC-D regimen, 8 cycles of DTX (docetaxel), and 8 cycles of PTX (paclitaxel) in patients treated with postoperative adjuvant chemotherapy, the results showed that 8 cycles of PTX alone had the worst DFS among the four groups, while no statistical difference was seen in the remaining three regimens, suggesting that 8 cycles of docetaxel docetaxel could be one of the treatment options. (2) To explore the efficacy and toxicity of different chemotherapeutic agents (e.g. albumin paclitaxel, TS-1, Eribulin, oral docetaxel, etc.) in different conditions of advanced breast cancer. The ML25241 study led by Professor Xu Binghe from Cancer Hospital of Chinese Academy of Medical Sciences reported the results of the first interim analysis comparing TX (capecitabine + docetaxel) and NX (capecitabine + vincristine) regimens followed by single agent capecitabine maintenance in patients receiving advanced first-line chemotherapy, and the preliminary results showed that the two regimens were close in efficacy and different in toxicity. (3) The predictive role of various biological indicators or assays, such as HER2, TOP2A, TIMP-1, PAM50 proliferation index, and circulating tumor cells (CTCs) on chemotherapeutic efficacy, were also reported in several studies. Conclusion Throughout the conference, no surprising advances were brought in chemotherapy and numerous controversies of neoadjuvant/adjuvant chemotherapy still exist. The direction of future development remains the impact of different types, biological features and manifestations, and different stages of disease on the choice of chemotherapy regimens, and the selection of appropriate patients to receive chemotherapy, whether in neoadjuvant, adjuvant or advanced patients, is the focus of future research.