BACKGROUND:Negative emotions are common in women with benign breast disease (BBD) and may influence breast cancer risk, but the relationship between these emotions, cancer development, and mitigating factors remains unclear. This study aimed to assess the impact of negative emotions on breast cancer risk and identify associated contributing factors. METHODS:This prospective cohort enrolled 3,535 women with BBD from 12 Chinese hospitals. Negative emotions were assessed using the irritability, depression, and anxiety (IDA) scale, and breast pain was evaluated with the breast pain score scale. Associations between negative emotions and breast cancer risk were analyzed using Cox regression models. Factors associated with negative emotions were identified with logistic regression, and mediation analysis was used to explore the roles of life satisfaction, sleep duration, and physical exercise. RESULTS:Nearly half (47%) of participants had high negative emotions (IDA ≥19). During follow-up, 2% developed breast cancer. High negative emotion was associated with a 2.78-fold increased cancer risk (HR = 2.78; 95% confidence interval, 1.34-5.76; P = 0.006), driven by depression and introverted irritability. Negative emotions correlated with physical inactivity, short sleep, life dissatisfaction, and severe breast pain. Life satisfaction (45%), sleep (7%) and exercise (19%) partially mediated the breast pain-negative emotion relationship. CONCLUSIONS:Negative emotions significantly increase breast cancer risk in women with BBD. Addressing modifiable factors like exercise, sleep, and life satisfaction may reduce emotional distress and potentially lower cancer risk. IMPACT:Integrating psychologic assessment and lifestyle interventions into BBD management could improve emotional well-being and mitigate cancer risk.

BACKGROUND:Optimal uptake rates of mammography or ultrasound are essential for breast cancer screening. This study aimed to identify the individual and structural factors affecting breast cancer screening in China, with quantitative adjustment of structural factors to increase individual uptake rates. METHODS:A multicenter prospective cohort study was conducted in 19 provinces across China, recruiting women aged 40-74 years. Logistic regression models identified individual factors affecting screening uptake, whereas linear regression models explored structural factors across 332 randomly selected communities. Adjusted structural approaches were used to improve individual uptake rates. RESULTS:During 2013-2018, uptake rates among 343,244 high-risk women were 40.9% for ultrasound, 36.8% for mammography, and 34.9% for combined screening. Eleven individual-level factors affected ultrasound uptake, with ten for mammography and nine for combined screening. Taking mammography as an example, higher education level (OR [95% CI]: high vs. low: 1.25 [1.21, 1.28]), smoking (OR [95% CI]: yes vs. no: 1.07 [1.05, 1.1]), passive smoking (OR [95% CI]: ≥40 years vs. 0 years: 1.39 [1.35, 1.44]), occupational exposure to hazardous substances (OR [95% CI]: yes vs. no: 1.19 [1.17, 1.22]), metabolic syndrome components (OR [95% CI]: 3 vs. 0: 1.08 [1.05, 1.12]), benign breast disease (OR [95% CI]: yes vs. no: 1.71 [1.66, 1.75]), delivery history (OR [95% CI]: yes vs. no: 1.60 [1.55, 1.66]), and family breast cancer history (OR [95% CI]: yes vs. no: 1.31 [1.29, 1.33]) might increase the likelihood of screening. Two structural-level factors consistently impacted all three screening modalities. Taking mammography as an example, shorter risk assessment-to-screening intervals (β [95% CI]: ≥60 days vs. <7 days: -24.37 [-33.48, -15.25]) and 30- to 60-day reminders for nonattenders (β [95% CI]: 30-60 days vs. 0-14 days: 8.71 [3.18, 14.24]) increased community mammography uptake. Individual-level uptake rates were 1.95 times higher with <7-day vs. ≥60-day assessment-screening intervals, peaking at 50.14% with 30- to 60-day reminder intervals for nonattenders. CONCLUSIONS:This study identified factors associated with breast cancer screening uptake and proposed quantitative adjustments to structural approaches to maximize uptake rates with minimal resources.

Clonal hematopoiesis of indeterminate potential (CHIP) is associated with systemic inflammation and solid tumor progression, but its impact on breast cancer therapy remains unclear. This study investigated whether CHIP influences neoadjuvant chemotherapy (NAC) response and shapes the tumor microenvironment (TME) in breast cancer. We analyzed tumor sequencing data from The Cancer Genome Atlas (TCGA), focusing on mutations in CHIP-driver genes within a variant allele frequency range of 2–33.3

Background: Neoadjuvant immunochemotherapy is a promising approach for triple-negative breast cancer (TNBC), yet the optimal chemotherapy backbone—specifically the incremental benefit of platinum and the necessity of anthracyclines—remains unresolved. We systematically compared the efficacy and safety of diverse neoadjuvant immunotherapy-chemotherapy regimens in TNBC. Methods: Adhering to PRISMA 2020 guidelines, we searched PubMed, Embase, Cochrane Library, and Web of Science for interventional studies published through Dec 15, 2025. Eligible studies reported both pathological complete response (pCR) and safety. We used trial-level random-effects models to estimate pooled relative risks (RRs) and pCR rates with 95% confidence interval (CI) (PROSPERO: CRD420251120106). Findings: Sixteen studies involving 3434 participants were included. Based on six RCTs (N=2469), immunochemotherapy significantly improved pCR over chemotherapy alone (RR, 1·20; 95% CI, 1·10–1·32). The overall pooled pCR rate for immunochemotherapy was 57·9% (95% CI, 54·6%–61·2 %). Overall, pCR rates were similar for platinum-containing (CbP-AC and CbP) vs non-platinum (P-AC) regimens (58.2% [95% CI, 54·0%–62·3%] vs 57·2% [95% CI, 51·4%–62·7%]; P = 0·77) and for adding platinum to anthracyclines (57·3% [95% CI, 51·6%–63·0%] vs 62·2% [95% CI, 58·3%–66·1%]; P = 0·15). Anthracycline-containing regimens (CbP-AC and P-AC) yielded higher pCR than non-anthracycline regimens (CbP) (59·7% [95% CI, 55·8%–63·5%] vs 53·5% [95% CI, 48·9%–58·0%]; P = 0·04). Removing anthracyclines from platinum-based regimens (CbP-AC) significantly reduced pCR (53·5% [95% CI, 49·0%–58·0%] vs 62·2% [95% CI, 58·3%–66·1%]; P = 0·004). Outcomes were comparable for short-course (≤ 6 cycles) vs long-course (> 6 cycles) therapy and for PD-1 vs PD-L1 inhibitors, although short-course therapy reduced serious hematologic toxicities. Interpretation: Neoadjuvant immunochemotherapy improves pCR in TNBC. Anthracyclines remain the backbone, whereas adding platinum provides limited benefit. PD-1 and PD-L1 inhibitors show comparable efficacy, and shorter regimens maintain pCR rates. These findings inform optimization of neoadjuvant strategies.

To develop a predictive model based on the perioperative plasma concentration of amino-terminal pro-brain natriuretic peptide (NT-pro BNP) in elderly patients to assess the risk of severe postoperative complications. Elderly patients (age ≥ 65 years) enrolled in this prospective observational study underwent general surgery. Plasma NT-Pro BNP concentration was measured before surgery and 2 h after surgery. Univariate and multivariate logistic regression analyses were used to identify the significant predictors. To evaluate the model performance, we applied the receiver operating characteristic (ROC) curve, Hosmer-Lemeshow test, and decision curve analysis (DCA) to evaluate the net clinical benefit. Prediction model was visualised by drawing nomogram and establishing web calculator. A total of 174 elderly patients were enrolled; 15 patients (8.6%) developed severe complications. The area under the ROC curve, sensitivity, and specificity of the two prediction models were 0.899 (95% CI 0.845-0.940), 86.67%, 91.82%, 0.956 (95% CI 0.902-0.985), 100%, and 81.42%, respectively. The net benefit of the post-model was higher than pre-model. We established two postoperative severe complication assessment models based on perioperative NT-Pro BNP levels for elderly patients with reliable accuracy. The nomogram and web calculator will be easy to use by clinicians and other researchers.Clinical significance: The biomarker, NT-pro BNP seem to correlate with some postoperative complications, however no studies have evaluated its relationship with severe postoperative complications in elderly patients. In this study, we evaluated the relationship between NT-pro BNP and severe postoperative complications in elderly patients, and established a prediction model and a web calculator based on the prediction model. Clinicians can easily use this prediction model to identify high-risk patients at an early stage.

The potential benefits of pyrotinib for patients with trastuzumab-insensitive, HER2-positive early-stage breast cancer remain unclear. This prospective, multicentre, response-adapted study evaluated the efficacy and safety of adding pyrotinib to the neoadjuvant treatment of HER2-positive breast cancer patients with a poor response to initial docetaxel plus carboplatin and trastuzumab (TCbH). Early response was assessed using magnetic resonance imaging (MRI) after two cycles of treatment. Patients showing poor response, as defined by RECIST 1.1, could opt to receive additional pyrotinib or continue standard therapy. The primary endpoint was the total pathological complete response (tpCR; ypT0/isN0) rate. Of the 129 patients enroled, 62 (48.1%) were identified as MRI-responders (cohort A), 26 non-responders continued with four more cycles of TCbH (cohort B), and 41 non-responders received additional pyrotinib (cohort C). The tpCR rate was 30.6% (95% CI: 20.6-43.0%) in cohort A, 15.4% (95% CI: 6.2-33.5%) in cohort B, and 29.3% (95% CI: 17.6-44.5%) in cohort C. Multivariable logistic regression analyses demonstrated comparable odds of achieving tpCR between cohorts A and C (odds ratio = 1.04, 95% CI: 0.40-2.70). No new adverse events were observed with the addition of pyrotinib. Patients with co-mutations of TP53 and PIK3CA exhibited lower rates of early partial response compared to those without or with a single gene mutation (36.0% vs. 60.0%, P = 0.08). These findings suggest that adding pyrotinib may benefit patients who do not respond to neoadjuvant trastuzumab plus chemotherapy. Further investigation is warranted to identify biomarkers predicting patients' benefit from the addition of pyrotinib.

Background: While disparities in breast cancer prevalence between urban and rural areas have been widely studied in China, economically underdeveloped regions such as Inner Mongolia remain under-researched. As an autonomous region with significant economic challenges, including industrial reliance and environmental health risks, Inner Mongolia exemplifies the intersection of socioeconomic disadvantage and health inequalities. This study aims to explore breast cancer prevalence and screening uptake in Inner Mongolia, focusing on the disparities in early detection services among different socioeconomic groups. Methods: Data from the China Psychological and Behavioral Impact Survey (PBICR) and its breast cancer screening subset were analyzed, covering 1,459,868 women across 12 cities in Inner Mongolia from 2022 to 2024. Variables included demographics, behavioral factors, and family cancer history. Chi-square tests were used to examine differences in screening methods and prevalence across regions. Binary and ordinal logistic regression models identified factors influencing screening comprehensiveness, with a focus on the barriers faced by economically disadvantaged women. Findings: Among the women surveyed, 786 cases of breast cancer were reported, yielding a prevalence rate of 0.05%, consistent with the national average. The highest incidence was observed among women aged 40-50 years. Significant disparities in screening participation and methods were found (e.g., physical exams [χ2 = 1087.8, P < 0.001], ultrasounds [χ2 = 97.276, P < 0.001], X-ray exams [χ2 = 12643, P < 0.001], and pathological exams [χ2 = 219.81, P < 0.001]). Women from poverty-stricken households were less likely to receive comprehensive screening (β = -0.03, 95% CI: [-0.0377, -0.0193], P < 0.001), while younger women (β = -0.06, 95% CI: [-0.0679, -0.0493], P < 0.001) and those with higher education levels (primary school or below: β = -0.75, 95% CI: [-0.7678, -0.7337], university or above: β = 0.323, 95% CI: [0.3163, 0.3300], P < 0.001) were more likely to opt for multiple screening methods. Geographical disparities were also evident, with rural areas exhibiting lower participation rates and more limited access to advanced screening technologies. Interpretation: This study highlights significant health inequalities in breast cancer screening in Inner Mongolia, where economic hardship and geographical isolation disproportionately hinder access to early detection services. The findings suggest that policy interventions should prioritize economically underdeveloped regions to reduce health disparities and promote equitable healthcare access. Theoretically, this study underscores the importance of considering regional economic disparities in health inequality research, extending the current literature’s focus beyond urban-rural divides to encompass broader socioeconomic dimensions.

Cancer caregivers often face substantial psychosocial burdens, which can lead to significant anxiety and depression. This network meta-analysis aimed to evaluate the relative efficacy of various psychosocial interventions in alleviating these symptoms. Following PRISMA guidelines, we conducted a systematic literature search for randomized controlled trials (RCTs) that evaluated psychosocial interventions for cancer caregivers. Data were synthesized using a network meta-analysis to compare the effects of different interventions on anxiety and depression. A total of 35 trials involving 7 types of psychosocial interventions were included. Three interventions—meaning-centered psychotherapy (anxiety: MD = − 5.48, 95

INTRODUCTION:Accurate breast cancer risk prediction is essential for early detection and personalized prevention strategies. While traditional models, such as Gail and Tyrer-Cuzick, are widely utilized, machine learning-based approaches may offer enhanced predictive performance. This systematic review and meta-analysis compare the accuracy of traditional statistical models and machine learning models in breast cancer risk prediction. METHODS:A total of 144 studies from 27 countries were systematically reviewed, incorporating genetic, clinical, and imaging data. Pooled C-statistics were calculated to assess model discrimination, while observed-to-expected (O/E) ratios were used to evaluate calibration. Subgroup and sensitivity analyses were conducted to examine heterogeneity and assess the influence of study bias across various populations. RESULTS:Machine learning-based models demonstrated superior performance, with a pooled C-statistic of 0.74, compared to 0.67 for traditional models. Models that integrated genetic and imaging data showed the highest levels of accuracy, although performance varied by population. Sensitivity analyses excluding high-bias studies showed improved discrimination in models incorporating genetic factors, with the pooled C-statistic increasing to 0.72. Traditional models, such as Gail, exhibited notably poor predictive accuracy in non-Western populations, as evidenced by a C-statistic of 0.543 in Chinese cohorts. CONCLUSION:Machine learning models provide significantly greater predictive accuracy for breast cancer risk, particularly when incorporating multidimensional data. However, issues related to model generalizability and interpretability remain, particularly in diverse populations. Future research should focus on developing more interpretable models and expanding global validation efforts to improve model applicability across different demographic groups.

IntroductionThe impact of distinct primary colorectal cancer (CRC) sites on lung injury and complications remains largely unexplored, despite the palpable differences in surgical positions, procedures, and the resulting mechanically induced respiratory pressures at each site.Materials and methodsThis study employed a forwards-looking approach utilising the propensity score matching (PSM) method; 300 patients with pathological CRC after laparoscopic surgery from April 2019 to May 2023 were enrolled. Two categories were bifurcated based on their surgical locations: the rectosigmoid colon (RSC) group and the descending/ascending colon (DAC) group, with a 2:1 ratio. The occurrence of postoperative pulmonary complications (PPCs) within a 30-day postoperative period was meticulously evaluated. Additionally, assessments have been performed for plasma biomarkers of immune response dynamics and lung injury (plasma soluble advanced glycation end-product receptor [sRAGE], angiopoietin-2 [ANG-2], interleukin-1β/6 [IL-1β/IL-6]) and other parameters.ResultsAlthough the increase in postoperative lung epithelial damage, as indicated by the plasma sRAGE levels, was significant in the RSC group (DAC vs. RSC; 1029.6 [576.8–1365.2] vs. 1271.6 [896.3–1587.6]; odds ratio=0.999; 95% CI: 0.998 to 1.000; P=0.007), a significantly increased percentage of PPCs was observed in the DAC group (DAC vs. RSC; hazard ratio=1.669; 95% CI, 1.141 to 2.439; P=0.008). A univariate Cox proportional hazards model revealed that sRAGE, ANG-2, IL-1β, and IL-6 levels were not correlated with the incidence of time-to-PPCs across the two cohorts (P>0.05). Propensity score-weighted Cox regression and causal mediation analysis further demonstrated that the DAC site directly affected the incidence of PPCs, regardless of the other baseline confounders and clinical covariates related to the tumour site and PPCs.ConclusionThe primary site of CRC is an independent predictor of the development of PPCs. Despite the steep Trendelenburg position of the RSC group inciting more pulmonary stress, inflammation and lung epithelial injury, as indicated by higher sRAGE, it demonstrated a lower PPCs occurrence relative to its DAC counterpart, with a slightly inclined or reversed Trendelenburg position. None of the plasma biomarkers of inflammation or lung injury indicated sufficient prognostic value for PPCs.

Background:To investigate the efficacy and safety of adding tislelizumab to neoadjuvant chemotherapy with nab-paclitaxel and carboplatin (TP) followed by adjuvant tislelizumab for early TNBC to explore the optimal neoadjuvant chemotherapy backbone and courses. Methods:The cTRIO study (ChiCTR2100041675) is a multicenter, prospective, open-label phase II trial across 8 sites in China, evaluating the efficacy and safety of neoadjuvant tislelizumab plus TP followed by adjuvant tislelizumab in patients with early triple-negative breast cancer (TNBC). We included women aged ≥18 years with histologically confirmed early TNBC defined by estrogen receptor immunohistochemistry (IHC) with T1 N1-3 or T2-4 N0-3 stage. Participants received six cycles of neoadjuvant tislelizumab (200 mg on day 1) plus nab-paclitaxel and carboplatin (TP; 125 mg/m2 on days 1 and 8), definitive surgery 3-6 weeks after completion of neoadjuvant therapy, followed by adjuvant tislelizumab every 3 weeks for 1 year. The primary endpoint was pathologic complete response (pCR). Findings:Sixty-two patients were enrolled from March 2021 to October 2022, including 44 cases with programmed cell death ligand 1 (PD-L1) positive and 9 cases at N3. At final analysis, 35/62 patients had achieved pathologic complete response (pCR, 56%; 95% confidence interval [CI], 43%-69%), with 33% (3/9) of N3 cases achieving pCR. The 3-year EFS and OS rates were 82.2% (95% CI, 70.2%-89.7%) and 87.7% (95% CI, 75.6%-94.0%), respectively. The incidence rates of grade ≥3 treatment-related adverse events (TRAEs) and grade ≥3 immune-related adverse events (irAEs) were 53% (33/62) and 5% (3/62), respectively. Patients with a higher PD-L1 combined positive score were less likely to experience relapse (P = 0.0090). Interpretation:Despite being a de-escalating and anthracycline-free neoadjuvant treatment approach, the triplet combination therapy showed promising efficacy and safety, signifying a crucial step toward the optimization of chemoimmunotherapy for early TNBC. Funding:This study was supported by BeOne Medicines, Ltd.

Early prediction of the neoadjuvant therapy efficacy for HER2-positive breast cancer is crucial for personalizing treatment and enhancing patient outcomes. Exosomes, which play a role in tumor development and treatment response, are emerging as potential biomarkers for cancer diagnosis and efficacy prediction. Despite their promise, current exosome detection and isolation methods are cumbersome and time-consuming and often yield limited purity and quantity. In this study, we employed Raman spectroscopy to analyze the molecular changes in exosomes from the sera of HER2-positive breast cancer patients before and after two cycles of neoadjuvant therapy. Utilizing machine learning techniques (PCA, LDA, and SVM), we developed a predictive model with an AUC value exceeding 0.89. Additionally, we introduced an innovative HER2-positive exosome capture and detection system, termed Magnetic beads@HER2-Exos@HER2-SERS detection nanoprobes (HER2-MEDN). This system enabled us to efficiently extract and analyze HER2-positive exosomes, refining our predictive model to achieve an accuracy greater than 0.94. Our study has demonstrated the potential of the HER2-MEDN system in accurately predicting early treatment response, offering novel insights and methodologies for assessing the efficacy of neoadjuvant therapy in HER2-positive breast cancer.

BACKGROUND:Mental health disorders impose a substantial social and economic burden. We conducted a comprehensive assessment of global mental health resource allocation and the associated burdens of mental health disorders, examining the relationship between these two factors. METHODS:We utilized data from the WHO Global Health Observatory and GBD 2021 to encompass 146 countries. We employed spatial autocorrelation analysis and Lorenz curves to characterize the spatial distribution. Additionally, we examined the association between mental health resources and the burdens of mental disorders using a generalized linear regression model (GLM). RESULTS:Countries and territories with higher income levels were more likely to have greater mental health resources (p < 0.05). Globally, the average mental health resource allocation index (IMRA) was 18.14, and Moran's I was 0.509 (p < 0.001). The Lorenz curve of mental health resources lay below the equality line, suggesting that these resources were more concentrated in countries and territories with higher HDI values. Between 2011 and 2021, the age-standardized incidence rate of all mental health disorders increased significantly (EAPC: 1.41 %, 95 % CI: 0.40 % to 2.53 %, p = 0.011). In multivariable GLM, a negative association was observed between the Index of IMRA and total mental health incidence. CONCLUSION:Inequalities in mental health resources persist, and the burdens of mental disorders are increasing globally. Our findings underscore the critical need to reduce the overall burden of mental health disorders through enhanced allocation of prevention-oriented resources. Countries at different levels of human development face distinct challenges and priorities in mental health resource allocation.

Background Neoadjuvant chemotherapy (NAC) has become a standard treatment strategy for breast cancer (BC). However, owing to the high heterogeneity of these tumors, it is unclear which patient population most likely benefit from NAC. Multi-omics offer an improved approach to uncovering genomic and transcriptomic changes before and after NAC in BC and to identifying molecular features associated with NAC sensitivity. Methods We performed whole-exome and RNA sequencing on 233 samples (including matched pre- and post-treatment tumors) from 50 BC patients with rigorously defined responses to NAC and analyzed changes in the multi-omics landscape. Molecular features associated with NAC response were identified and validated in a larger internal, and two external validation cohorts, as well as in vitro experiments. Results The most frequently altered genes were TP53 , TTN , and MUC16 in both pre- and post-treatment tumors. In comparison with pre-treatment tumors, there was a significant decrease in C > A transversion mutations in post-treatment tumors ( P = 0.020). NAC significantly decreased the mutation rate ( P = 0.006) of the DNA repair pathway and gene expression levels (FDR = 0.007) in this pathway. NAC also significantly changed the expression level of immune checkpoint genes and the abundance of tumor-infiltrating immune and stroma cells, including B cells, activated dendritic cells, γδT cells, M2 macrophages and endothelial cells. Furthermore, there was a higher rate of C > T substitutions in NAC nonresponsive tumors than responsive ones, especially when the substitution site was flanked by C and G. Importantly, there was a unique amplified region at 8p11.23 (containing ADGRA2 and ADRB3 ) and a deleted region at 3p13 (harboring FOXP1 ) in NAC nonresponsive and responsive tumors, respectively. Particularly, the CDKAL1 missense variant P409L (p.Pro409Leu, c.1226C > T) decreased BC cell sensitivity to docetaxel, and ADGRA2 or ADRB3 gene amplifications were associated with worse NAC response and poor prognosis in BC patients. Conclusions Our study has revealed genomic and transcriptomic landscape changes following NAC in BC, and identified novel biomarkers ( CDKAL1 P409L , ADGRA2 and ADRB3 ) underlying chemotherapy resistance and poor prognosis, which could guide the development of personalized treatments for BC.

603 Background: The contribution of biological characteristics and treatment patterns to the survival difference between male and female breast cancer patients is understudied, which is controversial but fundamental in determining strategies for cancer treatment and survivorship care. To evaluate the efficacy and safety of additional pyrotinib in patients with HER2-positive breast cancer who had no early response to neoadjuvant trastuzumab in combination with chemotherapy. Methods: A prospective, multicenter, response-adapted study including patients diagnosed with HER2-positive breast cancer from 2020 to 2022 were conducted. A total of 129 female patients from 5 hospitals participated in this neoadjuvant setting study. The primary endpoint was pathological complete response ( pCR), defined as the absence of invasive cancer in both the breast and axilla as determined by a local pathologist after surgery (ypT0ypN0). Results: Among 129 enrolled participants, 62 (48.1%) were identified as MRI-responders (Cohort A), 26 non-responders received 4 more cycles of TCbH (Cohort B), while 41 received additional pyrotinib (Cohort C). The pCR rates were 30.6% (95%CI: 20.6%-43.0%) in Cohort A, 15.4% (95%CI: 6.2%-33.5%) in Cohort B and 29.3% (95%CI: 17.6%-44.5%) in Cohort C. Similar difference patterns of breast pCR rates across 3 cohorts were observed. Multivariable logistic regression analyses showed that, in comparison to those in Cohort A, patients in Cohort C had comparable probability of pCR (OR=1.03, 95%CI: 0.40 to 2.67). The most common adverse events among patients who received pyrotinib were diarrhoea, anaemia, and erythropenia, and no cardiovascular event was observed. Participants with low TMB and no RTK-RAS mutation had a quite low pCR rate of 4%. Conclusions: The addition of pyrotinib to trastuzumab increases the pCR rates among patients who had no early response to neoadjuvant trastuzumab. Further studies are warranted to identify biomarkers predicting those who may benefit from pyrotinib in addition to trastuzumab. Clinical trial information: NCT03847818 .

Objective:Primary resistance to trastuzumab frequently occurs in human epidermal growth factor receptor 2 (HER2)-positive (+) breast cancer patients and remains a clinical challenge. Pyrotinib is a novel tyrosine kinase inhibitor that has shown efficacy in the treatment of HER2+ breast cancer. However, the efficacy of pyrotinib in HER2+ breast cancer with primary trastuzumab resistance is unknown.Methods:HER2+ breast cancer cells sensitive or primarily resistant to trastuzumab were treated with trastuzumab, pyrotinib, or the combination. Cell proliferation, migration, invasion, and HER2 downstream signal pathways were analyzed. The effects of pyrotinib plus trastuzumab and pertuzumab plus trastuzumab were compared in breast cancer cells in vitro and a xenograft mouse model with primary resistance to trastuzumab.Results:Pyrotinib had a therapeutic effect on trastuzumab-sensitive HER2+ breast cancer cells by inhibiting phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) and rat sarcoma virus (RAS)/rapidly accelerated fibrosarcoma (RAF)/mitogen-activated protein kinase (MAPK)/extracellular-signal regulated kinase (ERK) pathways. In primary trastuzumab-resistant cells, pyrotinib inhibited cell growth, migration, invasion, and HER2 downstream pathways, whereas trastuzumab had no effects. The combination with trastuzumab did not show increased effects compared with pyrotinib alone. Compared with pertuzumab plus trastuzumab, pyrotinib plus trastuzumab was more effective in inhibiting cell proliferation and HER2 downstream pathways in breast cancer cells and tumor growth in a trastuzumab-resistant HER2+ breast cancer xenograft model.Conclusions:Pyrotinib-containing treatments exhibited anti-cancer effects in HER2+ breast cancer cells sensitive and with primary resistance to trastuzumab. Notably, pyrotinib plus trastuzumab was more effective than trastuzumab plus pertuzumab in inhibiting tumor growth and HER2 downstream pathways in HER2+ breast cancer with primary resistance to trastuzumab. These findings support clinical testing of the therapeutic efficacy of dual anti-HER2 treatment combining an intracellular small molecule with an extracellular antibody.

Purpose:Periductal mastitis (PDM) is a chronic inflammatory lesion of the breast with an unknown etiology, and it is difficult for clinicians to differentiate it from granulomatous lobular mastitis (GLM), although they have different treatment strategies and prognosis. This study aimed to investigate the differences in their clinicopathologic features to inform treatment strategies.Patients and Methods:Between 2011 and 2020, 121 patients diagnosed with PDM and 57 patients with GLM were retrospective analysis. Patient data were extracted on demographics, clinical presentation, pathologic characteristics, treatments and clinical response. Histopathological evaluations were performed on core needle biopsy specimens. Immunohistochemical stains using antibodies against CD3, CD4, CD8, CD20, and CD138 was performed to define immune cell infiltration.Results:PDM patients had a higher median age compared to GLM patients (38 vs 32, p<0.001). PDM was primarily located in the areolar area, while GLM predominantly affected the peripheral quadrant of the breast (56.20% vs 75.44%, p<0.001). Histopathologically, more ductal dilatation (90.08% vs 3.51%, p<0.001), ductal wall thickening (47.93% vs 1.75%, p<0.001), and ductal rupture (44.63% vs 5.26%, p<0.001) were observed in PDM. GLM presented with significantly more granuloma (94.74% vs 10.74%, p<0.001), microabscess (68.42% vs 28.93%, p<0.001), and lipid vacuole (40.35% vs 8.26%, p<0.001) formation than PDM. Immunohistochemical analysis revealed a significant presence of CD20+ B lymphocytes in PDM and a higher prevalence of CD8+ T lymphocytes in GLM, indicating differing immune responses. Treatment outcomes varied, with PDM patients responding well to surgery and anti-mycobacterial therapy, while GLM patients showed favorable responses to steroid therapy.Conclusion:PDM is a specific entity with a similar clinical presentation but distinct histopathological features and immune profiles to GLM. Further research is needed to elucidate the pathogenesis and optimize therapeutic approaches for these breast inflammatory conditions.

BACKGROUND:Breast cancer (BC) risk-stratification tools for Asian women that are highly accurate and can provide improved interpretation ability are lacking. We aimed to develop risk-stratification models to predict long- and short-term BC risk among Chinese women and to simultaneously rank potential non-experimental risk factors. METHODS:The Breast Cancer Cohort Study in Chinese Women, a large ongoing prospective dynamic cohort study, includes 122,058 women aged 25-70 years old from the eastern part of China. We developed multiple machine-learning risk prediction models using parametric models (penalized logistic regression, bootstrap, and ensemble learning), which were the short-term ensemble penalized logistic regression (EPLR) risk prediction model and the ensemble penalized long-term (EPLT) risk prediction model to estimate BC risk. The models were assessed based on calibration and discrimination, and following this assessment, they were externally validated in new study participants from 2017 to 2020. RESULTS:The AUC values of the short-term EPLR risk prediction model were 0.800 for the internal validation and 0.751 for the external validation set. For the long-term EPLT risk prediction model, the area under the receiver operating characteristic curve was 0.692 and 0.760 in internal and external validations, respectively. The net reclassification improvement index of the EPLT relative to the Gail and the Han Chinese Breast Cancer Prediction Model (HCBCP) models for external validation was 0.193 and 0.233, respectively, indicating that the EPLT model has higher classification accuracy. CONCLUSIONS:We developed the EPLR and EPLT models to screen populations with a high risk of developing BC. These can serve as useful tools to aid in risk-stratified screening and BC prevention.

e12628 Background: Neoadjuvant therapy (NAT) has now been widely used for patients with operable breast cancer (BC) to test drug sensitivity. Studies have indicated that early assessment of clinical response to NAT can help identify patients who are resistant to initial regimens, providing an additional opportunity to change treatment plan. However, there is a lack of evidence regarding the optimal timing for conducting early evaluations of clinical response. This prospective study was conducted to evaluate the association between early evaluation of clinical response at different timing (post 2 cycles versus post 4 cycles) and pCR post NAT, in order to determine the most appropriate timing for NAT response evaluation. Clinical evaluations using ultrasound and MRI (magnetic resonance imaging) were also compared. Methods: A prospective cohort study including BC patients who received NAT was conducted between January 2018 and December 2023. Multivariable logistic regression analysis was used to estimate the Odds Ratios (OR) and 95% confidence intervals (CI) for the clinical response evaluated at different timings in association with pCR. The heterogeneity of the associations for the post-cycle 2 and post-cycle 4 assessments was assessed. Linear regression analyses were used to assess the associations between extent of tumor reduction post 2 cycles and that post 4 cycles of NAT. Agreement of tumor measurements using ultrasound and MRI was also assessed. Results: A total of 186 BC patients were consecutively enrolled and included in this analysis. 55 (29.6%) of them achieved pCR. Partial response (PR) post 2 cycles and 4 cycles of NAT were both significantly associated with pCR post NAT, though the point estimate of association for PR post 2 cycles of NAT (OR=5.06, 95%CI:2.29-12.09) was more evident than that post 4 cycles (OR=2.79, 95%CI:1.20-7.21). Extent of tumor reduction post two cycles of NAT was highly correlated with that post four cycles (r=0.89, 95%CI=0.79-0.98, P< 0.01). Poor concordance was observed between ultrasound and MRI measurements of tumor size, whether at initial diagnosis (r=0.66, adjusted r2=0.43) or after two cycles of NAT (r=0.59, adjusted r2=0.35). Among those patients who had PR post 2 cycles of NAT, tumor reduction by greater than 50% was not associated with higher probability of reaching pCR in comparison to those lower than 50% (OR=1.86, 95%CI=0.82-4.37, P=0.143). Conclusions: Tumor response assessed using MRI after two cycles of NAT was highly correlated with pCR, and may be adopted as an optimal strategy for early evaluation of the efficacy of NAT regimen. Further studies are warranted to evaluate changes in treatment plan at early phase of NAT for those resistant to initial regimens.