Assessment of the impact of residual tumors at different sites post-neoadjuvant chemotherapy on prognosis in breast cancer patients and development of a disease-free survival prediction model.

Background: Residual disease after neoadjuvant chemotherapy (NAC) in breast cancer patients predicts worse outcomes than pathological complete response. Differing prognostic impacts based on the anatomical site of residual tumors are not well studied. Objectives: The study aims to assess disease-free survival (DFS) in breast cancer patients with different residual tumor sites following NAC and to develop a nomogram for predicting 1- to 3-year DFS in these patients. Design: A retrospective cohort study. Methods: Retrospective analysis of 953 lymph node-positive breast cancer patients with residual disease post-NAC. Patients were categorized into three groups: residual disease in breast (RDB), residual disease in lymph nodes (RDN), and residual disease in both (RDBN). DFS compared among groups. Patients were divided into a training set and a validation set in a 7:3 ratio. Prognostic factors for DFS were analyzed to develop a nomogram prediction model. Results: RDB patients had superior 3-year DFS of 94.6% versus 85.2% for RDN and 81.8% for RDBN (p < 0.0001). Clinical T stage, N stage, molecular subtype, and postoperative pN stage were independently associated with DFS on both univariate and multivariate analyses. Nomogram integrating clinical tumor-node-metastasis (TNM) stage, molecular subtype, pathological response demonstrated good discrimination (C-index 0.748 training, 0.796 validation cohort), and calibration. Conclusion: The location of residual disease has prognostic implications, with nodal residuals predicting poorer DFS. The validated nomogram enables personalized DFS prediction to guide treatment decisions.

Understanding the impact of residual tumor location on prognosis after breast cancer treatment After receiving neoadjuvant chemotherapy, a treatment to shrink tumors before surgery, some breast cancer patients may still have residual tumor cells. Our study focuses on how the location of these remaining tumors ­ whether in the breast, lymph nodes, or both ­ affects the likelihood of the cancer not returning within the next 1 to 3 years. This likelihood is known as 'disease-free survival' (DFS). We analyzed data from 953 breast cancer patients who underwent neoadjuvant chemotherapy and still had residual tumors. By comparing DFS among patients with tumors remaining in different locations, we discovered that the specific location of the residual tumor significantly impacts the patient's long-term health and recovery. Additionally, we developed a predictive tool called a 'nomogram' to help doctors and patients assess the risk of cancer recurrence in the next 1 to 3 years. This tool considers various factors such as the size and type of the tumor, as well as the location and extent of the residual tumor after chemotherapy. Our research offers new insights into understanding the risk of recurrence after breast cancer treatment. This work not only enhances our comprehension of breast cancer management but also aids in devising more personalized and effective treatment strategies for patients in the future.

NREP, transcriptionally upregulated by HIF-1α, aggravates breast cancer cell growth and metastasis by promoting glycolysis.

Breast cancer (BC) poses a great threat to women's health. Neuronal regeneration related protein (NREP) is a multifunctional protein that is involved in embryonic development, regeneration, and human disease. However, the biological function of NREP in tumors is rarely reported and its role in BC remains unknown. Bioinformatics analysis showed that NREP is highly expressed and closely correlated with poor survival in BC patients. Under hypoxic conditions, NREP was upregulated in BC cells, and this promotion was reversed by hypoxia-inducible factor HIF-1α suppression. Luciferase reporter system and chromatin immunoprecipitation assays confirmed that HIF-1α directly binds to the promoter of NREP to increase the transcriptional activity of NREP. NREP suppression inhibited cell proliferation, arrested the cell cycle at the G1/S phase, and promoted apoptosis and caspase-3 activity in BC cells. Suppression of NREP decreased the tube formation ability of HUVECs. In addition, NREP downregulation showed an inhibition effect on cell migration, invasion, and EMT of BC cells. In NREP overexpressed cells, all these changes were reversed. In vivo, animal experiments also confirmed that NREP promotes BC tumor growth and metastasis. In addition, NREP promoted cellular glycolysis and enhanced the levels of glucose consumption, ATP, lactate production, and glucose transporters expression in NREP-overexpressed BC cells. In summary, our results demonstrated that NREP could be transcriptional activated by HIF-1α, which may aggravate BC tumor growth and metastasis by promoting cellular glycolysis. This result suggested that NREP may play an essential part in BC progression.

Targeted axillary dissection after neoadjuvant chemotherapy for highly selective patients with initial cN1 breast cancer: A single-center prospective trial.

BACKGROUND: Sentinel lymph node (SLN) biopsy is gradually accepted as the standard of care in breast cancer patients with down-staged axillary disease after neoadjuvant chemotherapy (NAC). However, it is still difficult to precisely define pre-NAC clinical node-positive (cN1) and post-NAC clinical node-negative (ycN0). This prospective single-center trial was designed to evaluate the feasibility and accuracy of standard targeted axillary dissection (TAD) after NAC in highly selective pre-NAC cN1 patients (not considering ultrasound-based axillary ycN staging). METHODS: This prospective trial included patients with initial pre-NAC cT1-3N1M0 invasive breast cancer but with a rigorous definition of cN1 from the Affiliated Cancer Hospital of Zhengzhou University. When NAC was effective (including complete and partial responses) and preoperative axillary palpation was negative, preoperative ultrasound-based axillary staging was not considered, and all patients underwent TAD followed by axillary lymph node (LN) dissection. The detection rate (DR) and false-negative rate (FNR) of TAD were calculated. RESULTS: A total of 82 patients were included, and 77 of them were eligible for data analysis. The DR for TAD was 94.8% (73/77). There were 26 patients with one abnormal LN at the time of diagnosis based on ultrasound, 45 patients with two, and 2 patients with three. One patient had one TAD LN, four patients had two TAD LNs, and 68 patients had three or more TAD LNs. Preoperative axillary palpation yielded negative results for all 73 patients who successfully underwent TAD. Preoperative ultrasound-based ycN0 and ycN+ conditions were detected for 52 and 21 cases, respectively. The FNR was 7.4% (2/27) for standard TAD (≥3 SLNs), which was lower than that of all successful TAD (≥1 SLN; 10.0%, 3/30). CONCLUSIONS: In rigorously defined pre-NAC cN1 breast cancer patients, standard TAD is feasible for those with negative axillary palpation after NAC, and FNR is also less than 10%. REGISTRATION: chictr.org.cn , ChiCTR2100049093.

The Impact of Sentinel Lymph Node Biopsy on Female Patients With T3-4c Breast Cancer and 1-2 Positive Lymph Nodes: A Population-Based Cohort Study.

PURPOSE: This study aimed to evaluate the efficacy of sentinel lymph node biopsy (SLNB) in patients diagnosed with cT3-4c breast cancer with no more than 2 positive sentinel lymph nodes. METHODS: Using data from the Surveillance, Epidemiology, and End Results (SEER) database, this retrospective study identified patients diagnosed with T3-4c breast cancer between 2010 and 2015. These patients were then categorized into 2 groups: the SLNB group, which underwent examination of 1-5 regional lymph nodes and the axillary lymph node dissection (ALND) group, which underwent examination of ≥10 regional lymph nodes. Propensity score matching analysis was used to assess the efficacy of SLNB in cT3-4c patients. RESULTS: A total of 1139 patients were included in the analysis, with 423 and 716 patients in the SLNB and ALND groups, respectively. The 10-year overall survival (OS) and breast cancer-specific survival (BCSS) rates in the SLNB group were 66.1% and 76.3%, respectively, compared with 66.0% and 73.8%, respectively. Statistical analysis revealed no significant differences between the 2 groups in terms of OS (HR = 1.00, 95% CI = 0.80-1.25, P = .997) and BCSS (HR = 1.08, 95% CI = 0.83-1.41, P = .551). Even after 1:1 propensity score matching, there were no significant differences in OS (HR = 0.87, 95% CI = 0.65-1.16, P = .341) and BCSS (HR = 0.82, 95% CI = 0.59-1.16, P = .266) between the 2 groups. CONCLUSION: This study demonstrates that SLNB does not adversely affect the survival of cT3-4c breast cancer patients with 1-2 sentinel lymph node metastases.