BACKGROUND: In light of the significant clinical benefits of antibody-drug conjugates in clinical trials, the human epidermal growth factor receptor 2 (HER2)-low category in breast cancers has gained increasing attention. Therefore, we studied the clinicopathological characteristics of Chinese patients with hormone receptor (HR)-positive/HER2-low early-stage breast cancer and developed a recurrence risk prediction model. METHODS: Female patients with HR-positive/HER2-low early-stage breast cancer treated in 29 hospitals of the Chinese Society of Breast Surgery (CSBrS) from Jan 2015 to Dec 2016 were enrolled. Their clinicopathological data and prognostic information were collected, and machine learning methods were used to analyze the prognostic factors. RESULTS: In total, 25,096 patients were diagnosed with breast cancer in 29 hospitals of CSBrS from Jan 2015 to Dec 2016, and clinicopathological data for 6486 patients with HER2-low early-stage breast cancer were collected. Among them, 5629 patients (86.79%) were HR-positive. The median follow-up time was 57 months (4, 76 months); the 5-year disease-free survival (DFS) rate was 92.7%, and the 5-year overall survival (OS) rate was 97.7%. In total, 412 cases (7.31%) of metastasis were observed, and 124 (2.20%) patients died. Multivariate Cox regression analysis revealed that T stage, N stage, lymphovascular thrombosis, Ki-67 index, and prognostic stage were associated with recurrence and metastasis ( P <0.05). A recurrence risk prediction model was established using the random forest method and exhibited a sensitivity of 81.1%, specificity of 71.7%, positive predictive value of 74.1%, and negative predictive value of 79.2%. CONCLUSION: Most of patients with HER2-low early-stage breast cancer were HR-positive, and patients had favorable outcome; tumor N stage, lymphovascular thrombosis, Ki-67 index, and tumor prognostic stage were prognostic factors. The HR-positive/HER2-low early-stage breast cancer recurrence prediction model established based on the random forest method has a good reference value for predicting 5-year recurrence events. REGISTRITATION ChiCTR.org.cn, ChiCTR2100046766.
Humans ; Female ; Breast Neoplasms/diagnosis* ; Ki-67 Antigen ; Receptor, ErbB-2 ; Prognosis ; Thrombosis ; Receptors, Progesterone

BACKGROUND: : 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.
Breast Neoplasms/metabolism* ; Female ; Humans ; Ki-67 Antigen ; Mastectomy ; Receptor, ErbB-2/metabolism*

Objective:To synthesize a 68Ga-labeled oxalyldiaminopropionic acid (ODAP)-urea based prostate specific membrane antigen (PSMA) targeting probe, and evaluate its properties in vitro and in vivo. Methods:Ligand P151 was synthesized by solid-phase synthesis and its Ki value was determined. The ligand P151 was added into the mixture of 68GaCl 3 and NaOAc solution and was reacted at 95 ℃ for 10 min. The labeling yield and in vitro stability of 68Ga-P151 were determined by high performance liquid chromatography (HPLC). The lipid-water partition coefficient (log P) and cell binding ability were determined. The biodistribution of 68Ga-P151 in normal KM mice was determined. MicroPET imaging of 68Ga-P151 was carried out in prostate cancer 22Rv1 tumor-bearing mice and compared with 68Ga-PSMA 617. Independent sample t test was used to analyze the data. Results:P151 was successfully synthesized with the Ki of 0.58 nmol/L, the labeling yield more than 95% and the radiochemical purity more than 95%. After placement in saline or human serum albumin (HSA) solution at 37 ℃ for 2 h, the radiochemical purity of 68Ga-P151 was still more than 95%, indicating a good stability in vitro. The lipid-water partition coefficient (log P) of 68Ga-P151 was -2.65±0.17, indicating a good hydrophilicity. 68Ga-P151 specifically bound to PSMA in prostate cancer LNCaP cells with the uptake value of (0.83±0.04) percentage injection activity (%IA)/10 5 cells. Biodistribution of normal mice showed that 68Ga-P151 was mainly excreted through kidneys and other organs showed low uptake. MicroPET imaging of tumor-bearing mice showed the maximum standardized uptake value (SUV max: 0.79±0.23 vs 0.54±0.05; t=2.12), tumor/kidney ratio (2.04±0.65 vs 1.88±0.33; t=0.44) and tumor/muscle ratio (12.83±5.18 vs 6.95±1.63; t=2.17) between 68Ga-P151 and 68Ga-PSMA 617 were not significantly different (all P>0.05). Conclusions:68Ga-P151 can be prepared simply and labeled in high yield and show improved pharmacokinetic properties in vivo. The imaging of 68Ga-P151 on PSMA positive tumor is comparable to that of 68Ga-PSMA 617, making it a potential radiopharmaceutical for the diagnosis of prostate cancer.

Objective:To examine the efficacy of docetaxel, carboplatin plus trastuzumab regimen (TCH) as neoadjuvant setting in early-stage human epidermal growth factor receptor 2 (HER2) positive breast cancer.Methods:Totally 522 patients diagnosed with early-stage HER2 positive breast cancer at Breast Disease Center, Peking University First Hospital between January 2013 to December 2018 were enrolled, which constituted 21.8% (522/2 394) of early-stage invasive breast cancer. Clinical pathological factors were retrospectively analyzed. There were 113 female patients underwent TCH neoadjuvant chemotherapy, aging 52(13) years (range: 23 to 69 years). Pathologic complete pathological response(pCR) was defined as ypT0N0M0, and the rate of pCR was calculated. Kaplan-Meier method and Log-rank test were used for survival comparison.Results:Patients who received trastuzumab-based therapy( n=294) had higher disease-free survival (DFS) compared with those who omitted trastuzumab( n=177) (84.4% vs. 72.4%, χ2=4.095, P=0.046). Eighteen of 113 patients (15.9%) experienced grade 3 to 4 chemotherapy-realted toxicity. Grade 3 to 4 neutropenia occurred in 12 patients, while grade 3 to 4 diarrhea occurred in 6 patients. Thirty-one of 113 (27.4%) patients achieved pCR. DFS and overall survival (OS) were similar between patients who achieved pCR and non-pCR (DFS: 91.8% vs. 85.0%, OS: 92.5% vs. 90.5%, all P>0.05). According to Miller-Payne system, patients who achieved G4 to G5 had improved DFS compared with G1 to G3 (89.6% vs. 81.5%, χ2=5.340, P=0.021), but they had similar OS (91.4% vs. 89.1%, χ2=1.008, P=0.315). Conclusions:TCH is an effective regimen in neoadjuvant setting for patients with HER2 positive breast cancer. Patients who achieved G4 to G5 had improved DFS.

Objective:To examine the efficacy of docetaxel, carboplatin plus trastuzumab regimen (TCH) as neoadjuvant setting in early-stage human epidermal growth factor receptor 2 (HER2) positive breast cancer.Methods:Totally 522 patients diagnosed with early-stage HER2 positive breast cancer at Breast Disease Center, Peking University First Hospital between January 2013 to December 2018 were enrolled, which constituted 21.8% (522/2 394) of early-stage invasive breast cancer. Clinical pathological factors were retrospectively analyzed. There were 113 female patients underwent TCH neoadjuvant chemotherapy, aging 52(13) years (range: 23 to 69 years). Pathologic complete pathological response(pCR) was defined as ypT0N0M0, and the rate of pCR was calculated. Kaplan-Meier method and Log-rank test were used for survival comparison.Results:Patients who received trastuzumab-based therapy( n=294) had higher disease-free survival (DFS) compared with those who omitted trastuzumab( n=177) (84.4% vs. 72.4%, χ2=4.095, P=0.046). Eighteen of 113 patients (15.9%) experienced grade 3 to 4 chemotherapy-realted toxicity. Grade 3 to 4 neutropenia occurred in 12 patients, while grade 3 to 4 diarrhea occurred in 6 patients. Thirty-one of 113 (27.4%) patients achieved pCR. DFS and overall survival (OS) were similar between patients who achieved pCR and non-pCR (DFS: 91.8% vs. 85.0%, OS: 92.5% vs. 90.5%, all P>0.05). According to Miller-Payne system, patients who achieved G4 to G5 had improved DFS compared with G1 to G3 (89.6% vs. 81.5%, χ2=5.340, P=0.021), but they had similar OS (91.4% vs. 89.1%, χ2=1.008, P=0.315). Conclusions:TCH is an effective regimen in neoadjuvant setting for patients with HER2 positive breast cancer. Patients who achieved G4 to G5 had improved DFS.

Objective:The incidence of breast cancer in Chinese women continues to rise. The large breast cancer cohort studies in China are relatively scarce. There are many bottlenecks in the construction of large clinical cohort for breast cancer diagnosis, treatment, and prognoses, such as inconsistent standards, high rates of lost follow-up, repeated construction, and inability to share. To better solving the difficulties and problems faced by large-scale clinical cohort research in China, this project will cooperate with several tertiary A hospitals to establish a breast cancer cohort in Chinese women. It also provides a data platform and technical support for breast cancer multi-center clinical cohort research.Methods:Based on the evidence-based medicine and expert opinion and consensus, we established a breast cancer cohort standardized indicator set-recording baseline information, diagnosis and treatment-related information of the enrolled patients, and collecting biological specimens. According to the technical specification of long-term follow-up for the endpoint, data management, and data security and in the large population-based cohort study, a standardized follow-up system for the diagnosis, treatment, and prognosis of breast cancer prospective cohorts is formed.Results:Based on standardized data sets and the computer discipline’s advantage from the University of Science and Technology Beijing, we integrate the new information technology methods, including dynamic information collection terminals and social networks. Thus, the quality of control programs on compliance and intelligence data was improved, and a Chinese women breast cancer cohort database was developed. By February 2020, 12 147 patients were included in the clinical cohort database. Biological specimens’resources in cohort construction were collected and cooperated with Shandong University to research the multi-center quality control system and shared evaluation system of biobanks. Building an open and shared biobank network and forming a full chain of breast cancer research platform.Conclusion:With the implementation of the "13 th Five-Year Plan" precision medicine research, this study provides a research foundation for precision diagnosis and treatment of breast cancer and provides data support for the country to formulate relevant medical policies.

Objective: To investigate the clinical relevance of prognostic staging according to the AJCC Breast Cancer Staging System, Eighth Edition for evaluation of the prognosis of triple-negative breast cancer. Methods: The clinical data of 293 patients with triple-negative breast cancer who were treated at the Breast Disease Center, Peking University First Hospital, between January 2008 and December 2014, were retrospectively analyzed. All patients were female, with age of 53(16) years (M(Q_R)). The patients were staged according to the AJCC Breast Cancer Staging System, Eighth Edition. Survival analysis was performed by Kaplan-Meier method and Log-rank test. The role of clinical staging and prognostic staging in prognostic evaluation was investigated. Results: In all, 293 patients with triple-negative invasive breast cancer with complete clinical data and follow-up data were treated over a 7-year period. The follow-up time was 64.5(32.8) months, the 5-year overall survival (OS) rate was 83.9%, and the 5-year disease-free survival (DFS) rate was 84.1%. The results showed that clinical staging and prognostic staging were correlated with the DFS rate and OS rate of patients with triple-negative breast cancer (χ² were 15.395 to 50.084,P=0.00). However, these two staging systems yielded different results. The prognostic stage of 91.8%(269/293) patients was higher than that of the original anatomical stage. There were significant differences in disease-free survival rate (χ²=22.357,P=0.00) and overall survival rate (χ²=50.084, P=0.00) among patients with different clinical stages. There were significant differences in disease-free survival rate (χ²=15.395,P=0.00) and overall survival rate (χ²=29.187,P=0.00)among patients with different prognostic stages. Conclusions The prognostic stage according to the AJCC Breast Cancer Staging System, Eighth Edition complements the clinical stage. It has a good predictive value for the prognosis of triple-negative breast cancer.

Objective To investigate the difference of the expression of estrogen receptor,progesterone receptor,human epidermal growth factor receptor 2 and Ki-67 protein between primary lesions of breast cancer and its synchronous ipsilateral lymph node metastasis,as well as its clinical implications.Methods Retrospectively analyze invasive breast cancer patients treated in Peking University First Hospital from January 2012 to May 2016.The IHC expressions of estrogen receptor,progesterone receptor,human epidermal growth factor receptor 2 and Ki-67 protein in both the primary and lymph node metastatic lesions are compared and analyzed statistically.The count data were represented as n(％),and comparsion between groups were evaluated using the McNemar test.Results One hundred and fifty-six patients were included,of which on 2 cases (1.3％),estrogen receptor status of primary lesions is different from that of lymph node metastases(P =0.500);on 10 cases (6.4％),progesterone receptor status of primary lesions is different from that of lymph node metastases (P =0.344);on 28 cases (18.0％),Ki-67 protein status of primary lesions is different from that of lymph node metastases (P =0.000 18);on 3 cases (1.9％),human epidermal growth factor receptor 2 status of primary lesions is different from that of lymph node metastases (P =1.000).Conclusion There may be difference between primary lesions and lymph node metastases in the expression of estrogen receptor,progesterone receptor,human epidermal growth factor receptor 2 and Ki-67 protein,which can provide a reference for individualized treatment of breast cancer patients.

Objective: To study the clinicopathological characteristics and the prognostic determinants of the invasive lobular carcinoma breast cancer. Methods: This was a retrospective single-center study of invasive lobular breast cancer cases diagnosed from January 2008 to December 2014 at Peking University First Hospital Breast Disease Center. The study enrolled 68 invasive lobular breast cancer patients, which represented 3.64% (68/1 870) of total invasive breast cancer. The median age of all selected patients was 46 years ranging from 36 to 83 years. All patients were restaged based on the 8^th edition of AJCC cancer staging system and follow-up data including disease-free survival (DFS) and overall survival (OS) were analyzed to explore the prognostic determinants. The 5-year OS and DFS were calculated using Kaplan-Meier method; the significance of correlations between clinicopathological features and prognostic factors was estimated using log-rank test. Results: There were significant differences in OS between patients with different anatomic stage, prognostic stage, lymph node metastasis, progesterone receptor (PR) expression, lymphvascular invasion and perineural invasion (χ^2: 4.318 to 32.394, all P<0.05); significant differences in DFS were also observed between patients with different anatomic stage, prognostic stage, lymph node metastasis, PR expression, human epidermal growth factor receptor-2 expression, Ki-67 level, histological grade and lymphvascular invasion (χ^2: 4.347 to 27.369, all P<0.05). Prognostic stages of 52.9% patients changed compared with anatomic stage, among which Luminal subtype mainly downstaged (22/30), however, triple negative subtype mainly upstaged (6/6). Conclusions Anatomic stage, prognostic stage, lymph node metastasis, PR expression, lymphvascular invasion are the prognostic factors of invasive lobular breast cancer. Regard to invasive lobular breast cancer patients, clinicians should pay close attention to the differences between prognostic stage and anatomic stage.

OBJECTIVESTo explore the clinical and pathological characteristics of stage IV breast cancer and to analyze their relationship with the morbidity and prognosis.

METHODSThe records of 66 patients presenting from January 2008 to December 2014 with stage IV breast cancer were reviewed. All of the patients were women and the median age was 57.5 (31 to 80) years, accounted for 3.01% (66/2 189) among the breast cancer patients treated in the same period. Statistical methods were used to analyze the correlation between clinical and pathological characteristics such as T-stage, N-stage, immuno-histo-chemistry and the morbidity and prognosis of stage IV breast cancer. The influence of patients characteristics to metastasis were compared by χ(2) test. Kaplan-Meier curves were reported for overall survival (OS), and the Log-rank test was used to compare the difference in groups. Cox proportional models were fitted for multivariate analysis.

RESULTSThe median survival time of stage IV breast cancer was 56.0 months and the 5-year survival rate was 40%. To metastasis, the effects of age, subtypes, histological grade, hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2)had no significant statistics differences. It was concluded that the expression of HER2 (P=0.003) and HR (P=0.001) as well as single metastasis (P=0.029) were the influencing factors of the survival by multivariate Cox regression analysis. Primary tumor R0 surgery group and no surgery group had no significant statistics differences of overall survival and the 5-year survival rate (P=0.102).

CONCLUSIONSClinical and pathological characteristics have no effect on metastasis. The expression of HER2 and HR as well as single metastasis play important roles in survival.

Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms ; Female ; Humans ; Middle Aged ; Multivariate Analysis ; Neoplasm Staging ; Prognosis ; Proportional Hazards Models ; Receptor, ErbB-2 ; Survival Rate