Ruixian Chen

Heat shock protein 90 (HSP90), a highly conserved member of the heat shock protein family, regulates various proteins and signaling pathways involved in cancer, making it a promising target for cancer therapy. Traditional HSP90 inhibitors have demonstrated significant antitumor potential in preclinical trials, with over 20 compounds advancing to clinical trials and showing promising results. However, the limited clinical efficacy and shared toxicity of these inhibitors restrict their further clinical use. Encouragingly, developing novel inhibitors using conventional medicinal chemistry approaches─such as selective inhibitors, dual inhibitors, protein-protein interaction inhibitors, and proteolysis-targeting chimeras─is expected to address these challenges. Notably, the selective inhibitor TAS-116 has already been successfully marketed. In this Perspective, we summarize the structure, biological functions, and roles of HSP90 in cancer, analyze the clinical status of HSP90 inhibitors, and highlight the latest advancements in novel strategies, offering insights into their future development.

PURPOSE: The status of human epidermal growth factor receptor 2 (HER2) is important for treatment decision-making of breast cancer and was commonly determined by core needle biopsy (CNB). The concordance of CNB with surgical excision biopsy (SEB) has been verified, but remain unclear according to the newly developed classification of HER2 status. Our study aimed to re-evaluate the diagnostic value of CNB for determining HER2 status in breast cancer, especially in the HER2-low population. METHODS: Eligible breast cancer patients in West China Hospital between January 1, 2007 and December 31, 2021 were enrolled consecutively and data were extracted from the Hospital Information System. The agreement of HER2 status between CNB and SEB was calculated by concordance rate and κ statistics, as well as the sensitivity, specificity, positive, and negative predictive values (PPV & NPV). Logistic models were used to explore potential factors associated with the discordance between both tests. RESULTS: Of 1829 eligible patients, 1097 (60.0%) and 1358 (74.2%) were consistent between CNB and SEB by pathological and clinical classifications, respectively, with κ value being 0.46 (0.43-0.49) and 0.57 (0.53-0.60). The sensitivity (50.9%-52.7%) and PPV (50.5%-55.2%) of CNB were especially low among IHC 1+ and 2+/ISH - subgroups by pathological classifications; however, it showed the highest sensitivity (77.5%) and the lowest specificity (73.9%) in HER2-low population by clinical classifications. Advanced N stages might be a stable indicator for the discordance between both tests. CONCLUSION: The diagnostic value of CNB was limited for determining HER2 status in breast cancer, especially in HER2-low population.

BACKGROUND: The number of elderly patients diagnosed with breast cancer is increasing worldwide. However, treatment decisions for these patients are highly variable. Although researchers have identified the effects of surgery, radiotherapy, endocrine therapy, and chemotherapy in elderly patients with breast cancer, clinicians still struggle to make appropriate decisions for these patients. METHODS: We identified 75,525 female breast cancer patients aged ≥ 70 years in the Surveillance, Epidemiology, and End Results (SEER) database treated between January 1, 2010, and December 31, 2016. The patients were further divided into training and testing cohorts. The cumulative occurrence of breast cancer-specific deaths (BCSDs) and other cause-specific deaths (OCSD) was calculated using the cumulative incidence function. In the univariate analysis, risk factors were screened using the Fine-Gray model. In the multivariate analysis for competing risks, the sub-distribution hazard ratio with a 95% confidence interval for each independent predictor associated with BCSD was calculated for the construction of nomograms. Based on the above analyses, a competing risk nomogram was constructed to predict the probability of BCSD in the 1st, 3rd, and 5th years after treatment. During validation, the concordance index (C-index) was selected to quantify the predictive ability of the competing risk model. RESULTS: A total of 33,118 patients were included in this study, with 24,838 in the training group and 8,280 in the testing group. Age, race, marital status, cancer grade, tumor stage, node stage, estrogen receptor status, progesterone receptor status, human epidermal growth factor receptor--2 status, and treatment including surgery, radiation, and chemotherapy were used to establish a nomogram. The C-index of 0.852 (0.842-0.862) in the training cohort and 0.876 (0.868-0.892) in the testing cohort indicated satisfactory discriminative ability of the nomogram. Calibration plots showed favorable consistency between the nomogram predictions and actual observations in both the training and validation cohorts. CONCLUSIONS: Our study identified independent predictors of BCSD in elderly patients with breast cancer. A prognostic nomogram was developed and validated to aid clinical decision-making.

Background: Patients with cancer show greater susceptibility and vulnerability to severe acute respiratory syndrome coronavirus 2 infection. However, data on the vaccination status among patients with breast cancer and any structured analysis of the factors influencing patients’ decisions regarding vaccines are lacking. Methods: This cross-sectional study on patients with breast cancer in China was conducted from 1 June 2022, to 17 June 2022. Every participant completed an online questionnaire about their vaccination status and any adverse reactions, and a scale based on the Health Belief Model (HBM) to assess the vaccination status of respondents and their willingness to receive following doses or boosters. Results: Among the 1132 participants, 55.2% had received a COVID-19 vaccine. The incidence of adverse events per dose was around 40%. Vaccine hesitancy of 61.9% was observed among patients who had not fully received three doses of vaccine or boosters. The only variable found to be associated with vaccine hesitancy was time since diagnosis (p < 0.05). In the HBM scale, vaccine hesitancy was closely related to a low level of perceived susceptibility, a low level of perceived benefit, a high level of perceived barriers and a low level of agreement with doctors’ advice. Conclusions: For patients with breast cancer, perceived susceptibility, benefits and barriers should be prioritized, and the advice from authoritative doctors is a vital cue to action.

BACKGROUND: Currently, the proportion of standard chemotherapy for elderly patients is much lower than that for young patients, with little evidence from clinical trials supporting the use of chemotherapy for elderly patients. The effectiveness of chemotherapy for the elderly suffering from breast cancer remains to be further verified. METHODS: A total of 75,525 female breast cancer patients aged 70 years or older were hereby identified, all from the Surveillance, Epidemiology, and End Results (SEER) database from January 1, 2010 to December 31, 2016. Kaplan-Meier analysis and multivariable Cox proportional model were performed to evaluate the effectiveness of chemotherapy on overall survival (OS) and breast cancer-specific survival (BCSS). Propensity score matching (PSM) (PSM ratio: 1:1, caliper: 0.2 standard deviation of propensity score) was applied to construct balanced cohorts with or without chemotherapy based on demographic and pathophysiological characteristics. RESULTS: A total of 33,177 eligible patients were included, with 5273 (15.89%) receiving chemotherapy. Through PSM, 8360 patients were successfully matched, and balances between groups were almost reached. In the matched data set, multivariable Cox analysis reveals that chemotherapy was associated with a 36% and 21% risk reduction on OS (HR = 0.64, 95% CI 0.58 to 0.71) and BCSS (HR = 0.79, 95% CI 0.69 to 0.91), respectively. Furthermore, subgroups with more adjacent lymph nodes involved by tumor, or nonluminal A, were inclined to benefit more from chemotherapy. Moreover, chemotherapy did not increase the chances of dying from heart disease. CONCLUSIONS: The present study provided evidence that chemotherapy may improve the prognosis of elderly breast cancer, especially for those subpopulations that benefit more from chemotherapy treatment.