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简介：AbstractBreast cancer (BC) is the most prevalent malignancy worldwide, and a continued upward trend has been predicted in the coming decades. Screening in selected targeted populations, which is effective in reducing cancer-related mortality, has been widely implemented in many countries. This review summarizes the advances in BC screening techniques, organized or opportunistic BC screening programs across different countries, and screening modalities recommended by different academic authorities. Mammography is the most widely used and effective technique for BC screening. Other complementary techniques include ultrasound, clinical breast examination, and magnetic resonance imaging. Novel screening tests, including digital breast tomosynthesis and liquid biopsies, are still under development. Globally, the implementation status of BC screening programs is uneven, which is reflected by differences in screening modes, techniques, and population coverage. The recommended optimal screening strategies varied according to the authoritative guidelines. The effectiveness of current screening programs is influenced by several factors, including low detection rate, high false-positive rate, and unsatisfactory coverage and uptake rates. Exploration of accurate BC risk prediction models and the development of risk-stratified screening strategies are highly warranted in future research.

简介：AbstractAntibody-drug conjugates (ADCs) combine the high specificity of monoclonal antibodies with the high anti-tumor activity of small molecular cytotoxic payloads. The anti-tumor activity of ADCs is mainly achieved by the direct blocking of the receptor by monoclonal antibodies, direct action and bystander effect of cytotoxic drugs, and antibody-dependent cell-mediated cytotoxicity and complement-dependent cytotoxicity. ADCs have been used in adjuvant therapy and rescue treatment of human epidermal receptor 2 (HER2)-positive breast cancer, greatly improving the prognosis of breast cancer patients. Several ongoing clinical trials of ADC for breast cancer and other solid tumors proved the potential of ADCs will provide more promising treatment options for patients with malignant tumors. This review introduces the mechanism and latest clinical progress of ADC drugs approved for HER2-positive breast cancer to guide clinical practice and conduct research.

简介：AbstractBackground:Breast cancer with low-positive human epidermal growth factor receptor 2 (HER2) expression has triggered further refinement of evaluation criteria for HER2 expression. We studied the clinicopathological features of early-stage breast cancer with low-positive HER2 expression in China and analyzed prognostic factors.Methods:Clinical and pathological data and prognostic information of patients with early-stage breast cancer with low-positive HER2 expression treated by the member units of the Chinese Society of Breast Surgery and Chinese Society of Surgery of Chinese Medical Association, from January 2015 to December 2016 were collected. The prognostic factors of these patients were analyzed.Results:Twenty-nine hospitals provided valid cases. From 2015 to 2016, a total of 25,096 cases of early-stage breast cancer were treated, 7642 (30.5%) of which had low-positive HER2 expression and were included in the study. After ineligible cases were excluded, 6486 patients were included in the study. The median follow-up time was 57 months (4-76 months). The disease-free survival rate was 92.1% at 5 years, and the overall survival rate was 97.4% at 5 years. At the follow-up, 506 (7.8%) cases of metastasis and 167 (2.6%) deaths were noted. Multivariate Cox regression analysis showed that tumor stage, lymphvascular invasion, and the Ki67 index were related to recurrence and metastasis (P < 0.05). The recurrence risk prediction model was established using a machine learning model and showed that the area under the receiving operator characteristic curve was 0.815 (95% confidence interval: 0.750-0.880).Conclusions:Early-stage breast cancer patients with low-positive HER2 expression account for 30.5% of all patients. Tumor stage, lymphvascular invasion, and the Ki67 index are factors affecting prognosis. The recurrence prediction model for breast cancer with low-positive HER2 expression based on a machine learning model had a good clinical reference value for predicting the recurrence risk at 5 years.Trial registration:ChiCTR.org.cn, ChiCTR2100046766.

简介：AbstractBackground:Female breast cancer (FBC) has become the most prevalent malignancy worldwide. We aimed to evaluate the global and regional burden in epidemiological trends and factors associated with the incidence and mortality of FBC.Methods:FBC incidence and mortality in 60 selected countries by cancer registry data integrity in 2020 were estimated from the GLOBOCAN database, and their association with the human development index (HDI) was further evaluated. Trends of age-standardized rates of incidence and mortality in 60 countries from 2000 through 2019 were evaluated by joinpoint regression analysis using data of Global Burden of Disease 2019. The association between potential behavioral, metabolic, and socioeconomic risk factor exposure at the nation level retrieved from the World Bank and Global Health Observatory and the incidence and mortality of FBC were evaluated by multivariate linear regression.Results:FBC incidence and mortality varied greatly in the 60 included countries. Higher incidence and mortality rates were typically observed in countries with higher HDIs and vice versa. During 2000 to 2019, significantly increasing trends in incidence and mortality were observed in 26 (average annual percent changes [AAPCs], 0.35-2.96) and nine countries (AAPC, 0.30-1.65), respectively, while significantly decreasing trends in both incidence and mortality were observed in 22 countries, most of which were high-HDI countries. Among the population aged ≥40 years, there were 26 and 11 countries showing significantly increased trends in incidence and mortality, respectively. Ecological analysis showed that countries with higher prevalence rates of high cholesterol and higher health expenditures were more likely to have higher FBC incidence, and countries with higher rates of obesity and poorer universal health coverage were more likely to have higher FBC mortality.Conclusions:Despite decreased or stabilized FBC incidence and mortality rates were observed in some countries with high HDI over the past decades, disease burden became even severer in developing countries, especially for the population aged ≥40 years. Effective targeted preventive programs are strongly encouraged to reduce the FBC disease burden worldwide.

简介：AbstractBackground:Re-biopsy of metastasis in advanced breast cancer (ABC) has become an international convention to assist the diagnosis and evaluation of tumor heterogeneity. This study aimed to detect diagnostic diversity and inconsistencies among estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) expression levels between primary and metastatic lesions.Methods:We conducted a retrospective analysis of 1670 cases of ABC patients who had undergone at least one lesion re-biopsy from January 2010 to December 2018. The pathological diagnosis of biopsies, distribution of biopsy sites, and severe puncture complications at each site were collected. In addition, the inconsistency rates and related factors of ER, PR, and HER2 expression between primary and metastatic lesions were analyzed fully considering patients’ demographic profiles and disease characteristics.Results:In total, 1670 cases of breast cancer (BC) patients diagnosed by pathology underwent one to four biopsies of recurrences or metastases in different sites or at different stages during the rescue treatment, producing 2019 histopathological specimens which were analyzed in the study. Pathological diagnosis showed that eight patients had benign pathological diagnoses, 11 patients had second primary malignant tumors but without recurrences of breast cancer, and 17 patients had pathologically confirmed breast cancer recurrences combined with second primary cancer. In 1173 patients who presented ER, PR, and HER2 expressions in primary and metastatic lesions, the inconsistency rates of ER, PR, and HER2 were 17.5% (205/1173), 31.3% (367/1173), and 13.9% (163/1173), respectively. The multivariate analysis showed that the age at the onset of breast cancer or adjuvant endocrine therapy was an independent factor affecting changes in PR expression level. Except one liver puncture with local hemorrhage and two lung punctures with hemopneumothorax, no other severe puncture complications occurred in 1950 non-surgical rebiopsies.Conclusions:The pathological diagnosis of metastasis re-biopsy of ABC was diverse, and the ER, PR, and HER2 expression levels were inconsistent between primary and metastatic lesions. Therefore, more attention should be paid to perform biopsies of relapsed and metastatic breast cancers routinely in clinical practice.

简介：AbstractBackground:Weight gain during chemotherapy in patients with breast cancer contributes to their poor prognosis. However, a growing number of studies have found that metabolic disorders seem to play a more important role in breast cancer prognosis than weight gain. This study aimed to explore the prognostic effects of body mass index (BMI), weight gain, and metabolic disorders on the overall survival (OS) and prognosis of patients with breast cancer who underwent chemotherapy.Methods:Data from the inpatient medical records of patients with breast cancer who underwent chemotherapy at the Beijing Cancer Hospital Breast Cancer Center from January to December 2010 were retrospectively collected, and the patients were followed up until August 2020.Results:A total of 438 patients with stages I to III breast cancer met the inclusion and exclusion criteria. Forty-nine (11.19%) patients died, while 82 (18.72%) patients had tumor recurrence and metastasis at the last follow-up (August 2020). From the time of diagnosis until after chemotherapy, no significant differences were observed in the body weight (t = 4.694, P < 0.001), BMI categories (χ2 = 19.215, P = 0.001), and incidence of metabolic disorders (χ2 = 24.841, P < 0.001); the BMI categories and weight change had no effect on the OS. Both univariate (χ2 = 6.771, P = 0.009) and multivariate survival analyses (hazard ratio = 2.775, 95% confidence interval [CI]: 1.326-5.807, P = 0.007) showed that low high-density lipoprotein cholesterol (HDL-C) levels at diagnosis had a negative impact on the OS. The multivariate logistic regression analysis showed that the HDL-C level at diagnosis (odds ratio [OR] = 2.200, 95% CI: 0.996-4.859, P = 0.051) and metabolic disorders after chemotherapy (OR= 1.514, 95% CI: 1.047-2.189, P = 0.028) are risk factors for poor prognosis in patients with breast cancer.Conclusions:Chemotherapy led to weight gain and aggravated the metabolic disorders in patients with breast cancer. Low HDL-C levels at diagnosis and metabolic disorders after chemotherapy may have negative effects on the OS and prognosis of patients with breast cancer.

简介：AbstractBackground:Pathological complete response (pCR) of axillary lymph nodes (ALNs) is frequently achieved in patients with clinically node-positive breast cancer after neoadjuvant chemotherapy (NAC), and ALN status is an important prognostic factor for breast cancer patients. This study aims to develop a new predictive clinical model to assess the ALN pCR rate after NAC.Methods:This was a retrospective series of 467 patients who had biopsy-proven positive ALNs at diagnosis and underwent ALN dissection from 2007 to 2014 at the National Cancer Center/Cancer Hospital of the Chinese Academy of Medical Sciences. We analyzed the clinicopathologic features of the patients and developed a nomogram to predict the probability of ALN pCR. A multivariable logistic regression stepwise model was used to construct a nomogram to predict ALN pCR in node-positive patients. The adjusted area under the receiver operating characteristic curve (AUC) was calculated to quantify the ability to rank patients by risk. Internal validation was performed using the 50/50 hold-out validation method. The nomogram was externally validated with prospective cohorts of 167 patients from 2016 to 2018 at the Cancer Hospital of the Chinese Academy of Medical Sciences and 114 patients from 2018 to 2020 at Beijing Tiantan Hospital.Results:In this retrospective study, 115 (24.6%) patients achieved ALN pCR after NAC. Multivariate analysis showed that clinical tumor stage (Odds ratio [OR]: 0.321, 95% confidence interval [CI]: 0.121-0.856; P = 0.023); primary tumor response (OR: 0.189; 95% CI: 0.123-0.292; P < 0.001), and estrogen receptor status (OR: 0.530, 95% CI: 0.304-0.925; P = 0.025) were independent predictors of ALN pCR. The nomogram was constructed based on the result of multivariate analysis. In the internal validation of performance of nomogram, the AUCs for the training and test sets were 0.719 and 0.753, respectively. The nomogram was validated in external cohorts with AUCs of 0.720, which demonstrated good discriminatory power in these data sets.Conclusion:We developed a nomogram to predict the likelihood of axillary pCR in node-positive breast cancer patients after NAC. The predictive model performed well in multicenter prospective external validation. This practical tool could provide information to surgeons regarding whether to perform additional ALN dissection after NAC.Trial registration:ChiCTR.org.cn, ChiCTR1800014968.

简介：AbstractBackground:Despite improvements in disease diagnosis, treatment, and prognosis, breast cancer is still a leading cause of cancer death for women. Compelling evidence suggests that targeting cancer stem cells (CSCs) have a crucial impact on overcoming the current shortcomings of chemotherapy and radiotherapy. In the present study, we aimed to study the effects of T cells and a critical anti-tumor cytokine, interferon-gamma (IFN-γ), on breast cancer stem cells.Methods:BALB/c mice and BALB/c nude mice were subcutaneously injected with 4T1 tumor cells. Tumor growth and pulmonary metastasis were assessed. ALDEFLOURTM assays were performed to identify aldehyde dehydrogenasebright (ALDHbr) tumor cells. ALDHbr cells as well as T cells from tumor-bearing BALB/c mice were analyzed using flow cytometry. The effects of CD8+ T cells on ALDHbr tumor cells were assessed in vitro and in vivo. The expression profiles of ALDHbr and ALDHdim 4T1 tumor cells were determined. The levels of plasma IFN-γ were measured by enzyme-linked immunosorbent assay, and their associations with the percentages of ALDHbr tumor cells were evaluated. The effects of IFN-γ on ALDH expression and the malignancy of 4T1 tumor cells were analyzed in vitro.Results:There were fewer metastatic nodules in tumor-bearing BALB/c mice than those in tumor-bearing BALB/c nude mice (25.40 vs. 54.67, P < 0.050). CD8+ T cells decreased the percentages of ALDHbr 4T1 tumor cells in vitro (control vs. effector to target ratio of 1:1, 10.15% vs. 5.76%, P < 0.050) and in vivo (control vs. CD8+ T cell depletion, 10.15% vs. 21.75%, P < 0.001). The functions of upregulated genes in ALDHbr 4T1 tumor cells were enriched in the pathway of response to IFN-γ. The levels of plasma IFN-γ decreased gradually in tumor-bearing BALB/c mice, while the percentages of ALDHbr tumor cells in primary tumors increased. IFN-γ at a concentration of 26.68 ng/mL decreased the percentages of ALDHbr 4T1 tumor cells (22.88% vs. 9.88%, P < 0.050) and the protein levels of aldehyde dehydrogenase 1 family member A1 in 4T1 tumor cells (0.86 vs. 0.49, P < 0.050) and inhibited the abilities of sphere formation (sphere diameter <200 μm, 159.50 vs. 72.0; ≥200 μm, 127.0 vs. 59.0; both P < 0.050) and invasion (89.67 vs. 67.67, P < 0.001) of 4T1 tumor cells.Conclusion:CD8+ T cells and IFN-γ decreased CSC numbers in a 4T1 mouse model of breast cancer. The application of IFN-γ may be a potential strategy for reducing CSCs in breast cancer.

简介：AbstractBackground:This study aimed to reveal the treatment patterns and clinical outcomes of diverse palbociclib-based regimens in Han patients with estrogen receptor-positive (ER+) metastatic breast cancer in routine clinical practice.Methods:The clinical data of patients with ER+ metastatic breast cancer treated with palbociclib were collected from the National Cancer Center database. The efficacy profile of palbociclib in this Han population was evaluated, especially for various combination regimens. The efficacy of palbociclib-based therapy in patients with prior everolimus treatment was also assessed.Results:A total of 186 patients from 89 cities in 18 provinces in China were enrolled. The median progression-free survival (PFS) was similar among different palbociclib-combined groups (P = 0.566): 10.0 months (95% confidence interval [CI] 3.8–16.1) in the +exemestane group, 9.7 months (95% CI 6.3–13.1) in the +letrozole group, 7.8 months (95% CI 5.5–10.2) in the +fulvestrant group, 7.2 months (95% CI 3.2–11.3) in the +toremifene group, and 6.1 months (95% CI 1.2–11.0) in the +anastrozole group. Thirty-four patients (18.3%) had received everolimus for their metastatic disease before the prescription of palbociclib. The disease control rate was significantly lower in patients who had received previous everolimus than in the everolimus-naïve group (50.0% vs. 82.2%, P < 0.001). Patients pre-treated with everolimus had significantly worse PFS than those in the everolimus-naïve group (3.4 months vs. 8.8 months, P = 0.001). After propensity score matching, patients pre-treated with everolimus had similar PFS (4.4 months, 95% CI 0.5–8.2) compared with everolimus-naïve patients (6.1 months, 95% CI 4.7–7.5, P = 0.439).Conclusions:Various palbociclib-based regimens have promising efficacy in ER+ metastatic breast cancer in real-world settings, even in patients who had been pre-treated with everolimus.

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