Breast cancer is a prevalent malignant tumor in females, and 5%-10% cases are related to hereditary susceptibility. At present, domestic genetic counseling for breast cancer still has shortcomings in standardized procedures, genetic testing, multidisciplinary collaboration and individualized intervention. Based on updated global and domestic evidences and Chinese population epidemiological features, this consensus, formulated by the Committee for Integrative Prevention and Screening of Breast Cancer, China Anti-Cancer Association, adopts the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system for evidence grading. Centered on full-cycle management of hereditary breast cancer, it specifies standardized workflow of genetic counseling from the perspectives of risk assessment, genetic testing, precise treatment, preventive intervention, long-term follow-up, fertility guidance, and ethical norms and constructs a closed-loop management system of “testing-interpretation-intervention-follow up”, in order to guide clinical practice for medical staff, patients, high-risk relatives and public health administrators.
Hormone receptor-positive and HER-2-negative (HR+/HER-2-) breast cancer is the most common molecular subtype of breast cancer. The cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) combined with endocrine therapy regimen has developed as a standard first-line treatment option for patients with HR+/HER-2- advanced breast cancer. In the post-CDK4/6i era, histone acetyltransferases inhibitor (HATi) serves as a new and effective epigenetic therapy. Among them, inhibitors targeting KAT6A inhibits the estrogen signal transduction of HR+/HER-2- breast cancer by regulating the acetylation of tumor cells and its downstream pathway, thereby reversing endocrine resistance. In this article, we summarize the research progress of molecular mechanisms of histone acetyltransferase and HATi in the treatment of HR+/HER-2- breast cancer, and explore its therapeutic prospect in breast cancer treatment.
To analyze the efficacy of eribulin alone or combination therapy in different molecular subtypes of advanced breast cancer based on multicenter data.
Methods
This retrospective study collected clinical data of 184 patients with advanced breast cancer who received eribulin treatment between January 2021 and December 2024 at the Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (n=121), Beijing Chaoyang District Sanhuan Cancer Hospital (n=40), and Shenzhen Hospital of Cancer Hospital, Chinese Academy of Medical Sciences (n=23). According to molecular subtypes of breast cancer, it was classified into 4 groups: hormone receptor-positive (HR+) /HER-2- (n=88), HR+/HER-2+ (n=9), HR-/HER-2+ (n=11), and triple negative breast cancer (TNBC) (n=76). Based on treatments, patients were categorized into 3 groups: eribulin alone, combination with antiangiogenic agents, or combination with other chemotherapeutic agents. The primary endpoint was progression-free survival (PFS); secondary endpoint included objective response rate (ORR) and clinical benefit rate (CBR). The survival curve was plotted using the Kaplan-Meier method, and Log-rank method was used for survival analysis.
Results
The median PFS of all 184 patients was 4.6 months (95%CI: 3.9–5.3), the ORR was 33.1% (61/184), and CBR was 82.6% (152/184). The median PFS of HR+/HER-2-, HR+/HER-2+, HR-/HER-2+, and TNBC were 5.0 (95%CI: 4.1-5.9), 4.1 (95%CI: 2.7-5.5), 3.5 (95%CI: 2.2-4.8), and 4.4 (95%CI: 3.6-5.3) months, respectively, with no statistically significant difference between the 4 groups (χ2=2.654, P>0.05); The ORRs were 39.8% (35/88), 22.2% (2/9), 36.4% (4/11), and 26.3% (20/76), respectively; The CBRs were 83.0% (73/88), 77.8% (7/9), 72.7% (8/11), and 84.2% (64/76), respectively. In the HR+/HER-2- group, the median PFS of 71 patients who had previously received cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) treatment was 5.3 months (95% CI: 4.4-6.3), with an ORR of 39.4% (28/71). The median PFS of patients receiving combination therapy with elibulin (n=121) and without antivascular therapy (n=63) were 4.5 months (95%CI: 3.8–5.2) and 4.9 months (95%CI: 3.4–6.5) respectively, with no statistically significant difference (χ2=1.693, P>0.05) . Among combination treatments, the median PFS of eribulin combined with bevacizumab, anlotinib, and apatinib were 4.4 (95%CI: 3.4–5.4) , 4.5 (95%CI: 3.6-5.4) , and 2.9 months, respectively, with no statistically significant difference (χ2=0.855, P>0.05) .
Conclusion
Eribulin alone or in combination therapy all have a certain anti-tumor activity in patients with advanced breast cancer of different molecular types (including CDK4/6i drug resistant HR+/HER-2- subtype) .
To evaluate the efficacy and safety of three cyclin-dependent kinase 4/6 (CDK4/6) inhibitors (abemaciclib, dalpiciclib, and ribociclib) currently available in China for patients with hormone receptor (HR)-positive/HER-2-negative (HR+/HER-2-) breast cancer.
Methods
Clinical data of 337 HR+/HER-2- breast cancer patients who received CDK4/6 inhibitor therapy at four hospitals in Jilin Province (the First, Second, and Third Bethune Hospitals of Jilin University, and Jilin Provincial Cancer Hospital) from March 2021 to December 2025 were retrospectively collected. Patients were stratified by clinical stage into the early-stage cohort (stage Ⅱ–Ⅲ, n=160) and the advanced-stage cohort (stage Ⅳ, n=177), and by different CDK4/6 inhibitors received, into the abemaciclib group (n=82), dalpiciclib group (n=119), and ribociclib group (n=136). Survival curves were plotted using the Kaplan-Meier method and intergroup comparisons were performed using the log-rank test. Analyze the occurrence of adverse events (AE) in each group of patients, and the factors influencing AE were analyzed using multivariate logistic regression.
Results
All patients were followed up until January 1, 2026. In the early-stage cohort, the 3-year invasive disease-free survival rates for the abemaciclib, dalpiciclib, and ribociclib groups were 83.2%, 87.4%, and 100%, respectively,indicating a significant difference across the three groups (χ2=7. 338,P=0. 025). In the advanced-stage cohort, the median progression-free survival in the three groups was 32.0 months (95%CI: 25.3–NA), 36.7 months (95%CI: 30.4–NA), and 24.2 months (95%CI: 22.2–NA), respectively, with no statistically significant difference (χ2=3. 292,P=0. 193). The overall incidences of AE in the early-stage cohort were 97.2% (35/36), 96.8% (30/31), and 97.8% (91/93) for the abemaciclib, dalpiciclib, and ribociclib groups, respectively; in the advanced-stage cohort, the corresponding incidences were 95.7% (44/46), 97.7% (86/88), and 97.7%(42/43), respectively, with no statistically significant difference in both cohorts (χ2=0.125, 0.525; P=0.939, 0.769). The AE profiles differed substantially among the three CDK4/6 inhibitors. The abemaciclib group showed the highest incidences of anemia [early-stage cohort: 55.6% (20/36); advanced-stage cohort: 69.6% (32/46)], diarrhea [early-stage cohort: 88.9% (32/36); advanced-stage cohort: 89.1% (41/46)], interstitial lung disease (ILD) [early-stage cohort: 5.6% (2/36); advanced-stage cohort: 8.7% (4/46)], and venous thromboembolism (VTE) [early-stage cohort: 2.8% (1/36); advanced-stage cohort: 6.5% (3/46)]. The dalpiciclib group had the highest incidences of neutropenia [early-stage cohort: 93.5% (29/31); advanced-stage cohort: 94.3% (83/88)] and leukopenia [early-stage cohort: 93.5% (29/31); advanced-stage cohort: 95.4% (84/88)]. The ribociclib group showed the highest incidences of elevated alanine aminotransferase (ALT) /aspartate aminotransferase (AST) [early-stage cohort: 34.4% (32/93)/36.6% (34/93); advanced-stage cohort: 39.5% (17/43) for both] and QTc interval prolongation [early-stage cohort: 1.1% (1/93); advanced-stage cohort: 2.3% (1/43)]. Multivariate logistic regression analysis revealed that drug type was an independent risk factor for grade ≥3 AEs. In the early-stage cohort, both abemaciclib (OR=2.847, 95%CI: 1.270–6.384, P=0.011) and dalpiciclib group (OR=7.047, 95%CI: 2.776–17.889, P<0.001) had a higher risk of grade ≥3 AEs compared with ribociclib group. In the advanced-stage cohort, dalpiciclib group (OR=4.670, 95%CI: 2.054–10.618, P<0.001) had a significantly higher risk of grade ≥3 AEs than abemaciclib group, while the risk in ribociclib group was not significantly different from that in the abemaciclib group (OR=2.365, 95%CI: 0.948–5.900, P=0.065).
Conclusion
All three CDK4/6 inhibitors demonstrated favorable efficacy and acceptable safety in patients with HR+/HER-2- breast cancer; however, their AE profiles and risk of grade ≥3 AEs differ significantly.
To identify influencing factors for recurrence and metastasis in patients with HER-2 positive breast cancer, and to establish a risk prediction model.
Methods
According to the inclusion and exclusion criteria, a total of 209 HER-2 positive breast cancer patients from four tertiary hospitals in Shandong Province between January 2021 and December 2024 were retrospectively enrolled as the training set, and 121 patients from two tertiary hospitals between January 2024 and May 2025 were included as the external validation set. The clinicopathological data of patients were collected and analyzed. Univariate analysis and LASSO regression were performed to screen for predictive factors, and multivariate logistic regression was adopted to determine the final variables for constructing a nomogram. Receiver operating characteristic (ROC) curve, calibration curve and decision curve analysis (DCA) were used to evaluate the discrimination, calibration and clinical practicability of the model.
Results
Seven predictive variables were finally screened out by multivariate logistic regression, including age, time since diagnosis, tumor size, family history, lymphedema, completion of targeted therapy and completion of chemotherapy. The results showed that time since diagnosis ≥1 year (OR=2.520, 95%CI: 1.017-6.245, P=0.046) and tumor diameter >5 cm (OR=2.998, 95%CI: 1.209-7.431, P=0.018) were risk factors for recurrence and metastasis in patients with HER-2 positive breast cancer; age ≥50 years (OR=0.366, 95%CI: 0.149-0.898, P=0.028) , completion of targeted therapy (OR=0.334, 95%CI: 0.128-0.872, P=0.025) and completion of chemotherapy (OR=0.028, 95%CI: 0.005-0.150, P=0.001) were protective factors. A nomogram was constructed based on the 5 statistically significant variables. In the training set, the area under the ROC curve (AUC) of the model was 0.865 (95%CI: 0.808-0.922) with a specificity of 0.963; the Hosmer-Lemeshow test yielded a good calibration (χ2=4.632, P=0.462). The AUC of the external validation set was 0.817 (95%CI: 0.715-0.919) with a specificity of 0.946 and the results of Hosmer-Lemeshow test showed a good calibration (χ2=6.833, P=0.555). DCA indicated stable and considerable clinical net benefit by applying this model within the risk threshold range of 0.2-0.8.
Conclusion
Patient age, time since diagnosis, tumor size, chemotherapy completion and targeted therapy completion are influencing factors for recurrence and metastasis in patients with HER-2 positive breast cancer. The prediction model established based on the above-mentioned factors can provide references for individualized clinical risk assessment.
To detect the expression levels of serum biomarkers in patients with mass-stage granulomatous lobular mastitis (GLM), breast cancer and breast fibroadenoma based on high-throughput sequencing results, and to explore their diagnostic values.
Methods
A cross-sectional diagnostic trial was conducted. A total of 165 patients (55 cases in each group) with mass-stage GLM, breast cancer and breast fibroadenoma in the First Hospital of Hunan University of Chinese Medicine from December 2021 to October 2022 were enrolled. Surgical pathological diagnosis was used as the gold standard. General data including age, gender, height, weight and body mass index (BMI) were collected; routine blood tests, liver and kidney function tests were performed. RT-PCR was adopted to detect the serum expression levels of miR-451a, miR-5571-3p, CLN6, 11β-hydroxysteroid dehydrogenase type 1 (HSD11B1) and phosphodiesterase type 4 (PDE4). Statistical differences in clinical indicators and the serum levels of the five biomarkers among the three groups were analyzed. The receiver operating characteristic (ROC) curve and area under the curve (AUC), Pearson correlation analysis and sensitivity analysis adjusting for age as a confounding factor were used to evaluate the diagnostic efficacy, correlation and result robustness of the five serum biomarkers.
Results
The BMI in the GLM group, breast cancer group and fibroadenoma group was 23.9±3.6, 22.4±3.9 and 21.3±3.2 respectively, with a statistically significant difference (F=10.136, P<0.001). There were significant differences in white blood cell count (WBC), neutrophil count (N), neutrophil-to-lymphocyte ratio (NLR), C-reactive protein (CRP), platelet count (PLT) and globulin (GLO) among the three groups (H=73.693, 72.788, 33.533, 56.689, 20.531, 35.497, all P<0.001); all above indicators were significantly higher in the GLM group than in the fibroadenoma group and breast cancer group (P<0.05). Comparison of the serum levels of miR-451a, miR-5571-3p, CLN6, HSD11B1, and PDE4 among the three groups revealed significant differences (H=99.760, 80.560, 73.550, 75.966, 74.998, all P<0.001). Compared with the fibroadenoma group, the expression of miR-451a and miR-5571-3p was significantly increased in the GLM group [0.95 (0.58, 1.19) and 7.36 (4.38, 9.50)], but significantly decreased in the breast cancer group [0.08 (0.05, 0.14) and 0.48 (0.22, 0.72)] (P<0.001, P<0.01). The CLN6 expression was significantly elevated in both the GLM and breast cancer groups, indicating a significant difference between two groups [1. 14 (0. 80, 1. 69) and 1.38 (1. 00, 2. 22), P<0.001]. The breast cancer group showed significantly higher levels of HSD11B1 and PDE4 [1.80 (1.17, 2.66) and 1.40 (1.01, 2.40)] than the GLM group [0.93 (0.55, 1.37) and 0.69 (0.47, 1.13)] (P<0.01). For GLM group, miR-451a (AUC=0.96, 95%CI: 0.91–1.00), miR-5571-3p (AUC=0.90, 95%CI: 0.85-0.96), and the combined detection of miR-451a and miR-5571-3p (AUC=1.00, 95%CI: 1.00-1.00) exhibited high diagnostic value. For breast cancer group, the combined detection of miR-451a and miR-5571-3p (AUC=0.98, 95%CI: 0.96-1.00) showed high diagnostic value; miR-451a (AUC=0.85, 95%CI: 0.79-0.92), miR-5571-3p (AUC=0.83, 95%CI: 0.76–0.90), HSD11B1 (AUC=0.84, 95%CI: 0.77-0.91) and PDE4 (AUC=0.83, 95%CI: 0.76-0.90) demonstrated good diagnostic value; CLN6 (AUC=0.75, 95%CI: 0.67-0.83) had moderate diagnostic value. For fibroadenoma group, CLN6 had high diagnostic value (AUC=0.91, 95%CI: 0.86-0.95); HSD11B1 (AUC=0.88, 95%CI: 0.83-0.93) and PDE4 (AUC=0.88, 95%CI: 0.83-0.94) showed good diagnostic value; the combined detection of miR-451a and miR-5571-3p (AUC=0.76, 95%CI: 0.63-0.88) had moderate diagnostic value. Correlation analysis demonstrated that miR-451a was moderately positively correlated with miR-5571-3p (r=0.637, P<0.05), CLN6 with HSD11B1 (r=0.402, P<0.05), and HSD11B1 with PDE4 (r=0.503, P<0.05). Both miR-451a and miR-5571-3p also showed moderate positive correlations with WBC, N, NLR and CRP (r=0.434–0.659, all P<0.05).
Conclusion
miR-451a and miR-5571-3p, especially their combined detection, show high diagnostic value for mass-stage GLM. The combination of miR-451a and miR-5571-3p for breast cancer and CLN6 for breast fibroadenoma show promising potential in diagnostic value, which may provide evidences for differential diagnosis.