Breast Cancer Patients In China Research Articles

Status and clinical response of fertility preservation in young patients with breast cancer

Cancer treatments may improve the long-term survival rate of young patients with breast cancer, but also lead to a decrease in fertility. With the younger incidence of breast cancer in China, the fertility needs of this group have received more attention, and fertility preservation technology suitable for cancer patients is developing continuously. However, there are still many problems in the implementation of fertility preservation for young breast cancer patients in China. Patients and breast surgeons have insufficient understanding and conservative attitudes towards fertility preservation technology. And there is a lack of reproductive experts in the treatment process. What's more, the long-term follow-up and information management of patients undergoing fertility preservation are defective. In response to the above, this paper discusses how to deal with patients with potential reproductive needs in clinical practice from the perspective of breast surgeons. The first is to improve their own understanding of fertility preservation, such as the progress of relevant technologies and applicable population, when to intervene, when and how to get pregnant after cancer treatment. Secondly, education for patients must be strengthened, which should include not only fertility preservation, but also scientific contraceptive methods during cancer treatment and treatment measures for unexpected pregnancy. Finally, hospitals and relevant units should standardize the multidisciplinary team of breast cancer, and strengthen the comprehensive management of young breast cancer patients, thus to provide young breast cancer patients with more scientific cancer treatment programs and more reproductive opportunities.

Medical professionals' knowledge of the use of external breast prostheses among breast cancer patients in China-a cross-sectional study.

Breast loss has a negative effect on women physically, psychologically and socially. External breast prostheses can improve patients' figure physically, increase their self-confidence, and thus improve quality of life. Little is known about the knowledge of medical professionals on the use of external breast prostheses in mainland China. This study sought to examine medical professionals' knowledge of the use of external breast prostheses among breast cancer patients in China. Self-designed questionnaires were administered to 635 medical professionals specializing in breast cancer in China to examine their knowledge. Medical professionals who were older in age, those who had higher levels of education and those who had senior professional titles had a broader professional knowledge of external breast prostheses. Medical professionals who were younger in age and those who had junior professional titles thought that the patients were willing to choose direct-adhesive breast prostheses. Medical professionals who were older in age, those who had higher levels of education, those who had senior professional titles and those who had been working for many (but less than 30) years were more likely to think that patients could wear external breast prostheses shortly after surgery, and at all times except when sleeping. More highly educated doctors, head nurses and medical staffs from the East were more likely to think that patients would accept the use of high-priced external breast prostheses. Medical professionals' knowledge about the wearing of external breast prostheses is lacking. A number of factors, including age, education level, professional title, number of years working years and geographical region have different effects on medical professionals' knowledge. Medical professionals with a good knowledge of external breast prostheses, especially specialist breast nurses, can provide patients with comprehensive information about breast prostheses, assist patients in selecting the appropriate prostheses, understand patients' wearing experiences, and help to reduce patients' physical and mental distress.

Association between 15 known or potential breast cancer susceptibility genes and breast cancer risks in Chinese women.

Objective:There are many hereditary breast cancer patients in China, and multigene panel testing has been a new paradigm of genetic testing for these patients and their relatives. However, the magnitude of breast cancer risks related to multiple breast cancer susceptibility genes are largely unknown in Chinese women.Methods:We screened pathogenic variants in 15 established or potential breast cancer susceptibility genes from 8,067 consecutive Chinese female breast cancer patients and 13,129 Chinese cancer-free female controls. These breast cancer patients were unselected for age at diagnosis or family history.Results:We found that pathogenic variants in TP53 [odds ratio (OR): 16.9, 95% confidence interval (CI): 5.2–55.2]; BRCA2 (OR: 10.4, 95% CI: 7.6–14.2); BRCA1 (OR: 9.7, 95% CI: 6.3–14.8); and PALB2 (OR: 5.2, 95% CI: 3.0–8.8) were associated with a high risk of breast cancer. ATM, BARD1, CHEK2, and RAD51D were associated with a moderate risk of breast cancer with ORs ranging from 2-fold to 4-fold. In contrast, pathogenic variants of NBN, RAD50, BRIP1, and RAD51C were not associated with increased risk of breast cancer in Chinese women. The pathogenic variants of PTEN, CDH1, and STK11 were very rare, so they had a limited contribution to Chinese breast cancer. Patients with pathogenic variants of TP53, BRCA1, BRCA2, and PALB2 more often had early-onset breast cancer, bilateral breast cancer, and a family history of breast cancer and/or any cancer.Conclusions:This study provided breast cancer risk assessment data for multiple genes in Chinese women, which is useful for genetic testing and clinical management of Chinese hereditary breast cancer.

Treating breast cancer patients in China

Treating breast cancer patients in China

A Chinese version of the chemotherapy-induced alopecia distress scale based on reliability and validity assessment in breast cancer patients.

Chemotherapy-induced alopecia is a common and emotionally traumatic side effect on breast cancer patients. In order to make up for the deficiency of measuring tools in China, our study aims at translating the chemotherapy-induced alopecia distress scale (CADS) into Chinese and evaluating the psychometric properties of the Chinese version of CADS (CADS-C) in breast cancer patients. The validity and reliability of CADS-C were measured by a questionnaire survey among 301 breast cancer patients from Chinese mainland. Construct validity was assessed through factor analysis and contrasted group comparisons. The validity of the content was examined by an experts group. The internal consistency and test-retest reliability were evaluated by calculating Cronbach's alpha and the intraclass correlation coefficient. The content validity index was 0.94; a structure with three factors was revealed by exploratory factor analysis which explained 65.40% of the variance and proved by confirmatory factor analysis. The contrasted group comparisons showed significant differences among different degrees of alopecia. The average variance extracted and composite reliability and correlations between CADS and body image, quality of life and self-esteem proved the convergent validity. The Cronbach's alpha and the intraclass correlation coefficient of the total scale were 0.90 and 0.89 respectively, indicating satisfactory internal consistency and time stability. The scale appears to be a reliable and valid tool to measure chemotherapy-induced alopecia distress among breast cancer patients in China.

Clinical Practice Status of Sentinel Lymph Node Biopsy for Early-Stage Breast Cancer Patients in China: A Multicenter Study.

BackgroundSentinel lymph node biopsy (SLNB) was introduced over 30 years ago, but the application of SLNB in China is unclear. This study aimed to explore the real-world implementation of SLNB among early-stage breast cancer patients in China.MethodsA multi-center, retrospective study was conducted among primary breast cancer patients from 37 hospitals in China in 2018. Their clinical data were collected and analyzed, including the implementation status of SLNB in China, subsequent processing of sentinel lymph nodes (SLNs) containing metastases, and the effect of neoadjuvant chemotherapy (NAC) on SLNB.ResultsSLNB surgery was performed on 43.5% of early-stage breast cancer patients in China and 11,942 patients who underwent SLNB were enrolled in this study. The majority of SLNBs were performed using a single mapping agent. A combination of blue dye and radiotracer or fluorescence imaging was used in only 14.9% of patients. The mean (SD) number of resected SLNs was 4.0 (2.1). For the patients with 1 or 2 positive SLNs, 83.0% of them continued to receive axillary lymph node dissection (ALND), while others did not. For the patients with three or more positive SLNs, 97.2% of them continued to receive ALND, among which 82.9% accepted radiotherapy simultaneously. Of the patients who underwent SLN surgery, 5.5% (654/11,942) were receiving NAC. Among them, 51.9% received SLNB before NAC, and the rest received SLNB after NAC. In biopsy-proven positive nodes, 64.7% positive SLNs turned negative after NAC.ConclusionSLNB has been promoted in China, but it is not widely used compared to in developed countries. Furthermore, the usage of the dual tracer technique in SLNB is not high. Chinese breast surgeons are more conservative regarding the omission of ALND in 1 or 2 SLNs-positive patients.

Abstract 2492: Unique genomic and transcriptomic characteristics in young Chinese patients with HR+/HER2- invasive breast cancer

Abstract Hormone receptor positive and human epidermal growth factor receptor 2 negative (HR+/HER2-) is generally associated with a more favorable outcome in breast cancer, where age may play roles in the prognosis of invasive breast cancer. Earlier studies have found that the effect of age on the outcomes varied by tumor subtypes. Younger patients (< 40 years of age) were associated with significant increases in risk of breast cancer death with HR+/HER2- tumors comparing to their older counterpart. Although it has been observed in a clinical setting, the involved signaling pathways and driver genes remain unknown at a genomic level. In this study, in order to seek the relevance of unique genomic features and gene expression signatures in young HR+/HER2- breast cancer patients (<40 years old), we conducted whole genomic sequencing and transcriptomic sequencing of two cohorts of primary HR+/HER2- invasive breast cancer patients in China, relatively young group (age < 40 at diagnosis, ranging 34-39, N=25) and old group (age ≥50 at diagnosis, ranging 53-68, N=26). There was no statistically significant difference in ki67 and TMB between two groups. We then performed comprehensive analysis and comparison of two cohorts on somatic mutation, copy number aberrations, and differential gene expression using Sentieon somatic mutation pipeline, Sequenza and HISAT2-StringTie-Ballgown pipeline. At genomic level, we found that the recurrent somatic alterations in some genes (particularly GATA3, ERBB2, TP53) were higher in young patients than in old patients with HR+/HER2- invasive breast cancer, while PIK3CA mutation associated with improved outcome was lower in young patients. Furthermore, the copy number aberrations localized at some critical regions, such as 14q11.2-13.1, were more frequent in young patients than in older patients. The coding genes in the featured chromosome regions were involved in multiple biological functions, such as cell proliferation and cell motility, and critically associated with prognosis. RNAseq-based differential gene expression analysis further confirmed the difference in the pathway developments between young and old patients. In conclusion, our study revealed specific genomic and transcriptomic characteristics in young breast cancer patients with HR+/HER2- invasive breast cancer compared to their old counterpart. The results indicated that the younger patients who carry these candidate risk genomic and transcriptomic features may lead to poor prognosis outcomes. Citation Format: Hong Hu, Zhenyu Hu, Ke Liu, Jintao Hu, Fengyu Li, Boyang Cao, Kang Shao, Wenzhao Shi, Gang Feng, Wenbin Zhou. Unique genomic and transcriptomic characteristics in young Chinese patients with HR+/HER2- invasive breast cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2492.

Development and validation of a nomogram for predicting survival of advanced breast cancer patients in China

BackgroundThere is a lack of prognostic models predicting the overall survival (OS) of advanced breast cancer (ABC) patients in China. MethodsData from the China National Cancer Center database that recorded 4039 patients diagnosed with breast cancer between 1987 and 2019 were extracted and a total of 2263 ABC participants were enrolled in this study, which were further randomized 3:1 and divided into training (n = 1706) and validation (n = 557) groups. The nomogram was built based on independent predictors identified by univariate and multivariate cox regression analyses. The discriminatory and predictive capacities of the nomogram were assessed by Harrell’s concordance index (C-index) and calibration plots. ResultsUnivariate and multivariate analyses found that age, Eastern Cooperative Oncology Group (ECOG) score, T-stage, N-stage, tumor subtype, the presence of distant lymph node (DLN)/liver/brain metastasis, local therapy, efficacy of first-line therapy and metastatic-free interval (MFI) were significantly related to OS (all P < 0.05). These variables were incorporated into a nomogram to predict the 2-year and 3-year OS of ABC patients. The C-indexes of the nomogram were 0.700 (95% confidence interval [CI]: 0.683–0.717) for the training set and 0.686 (95% CI: 0.652–0.719) for the validation set. The calibration curves revealed satisfactory consistency between actual survival and nomogram prediction in both the internal and external validations. The nomogram was capable of stratifying patients into different risk cohorts. ConclusionsWe constructed and validated a nomogram that might serve as an efficient tool to provide prognostic prediction for ABC patients and guide the physicians to make personalized treatment decisions.

Clinical spectrum and prognostic value of TP53 mutations in circulating tumor DNA from breast cancer patients in China.

Background TP53 mutations are common in breast cancer. There is currently no large‐scale cohort study to investigate the TP53 landscape in breast cancer patients from China. The predictive value of TP53 mutations for the efficacy of human epidermal growth factor receptor 2 (HER2)‐targeted therapy in breast cancer remains controversial. In the present study, we aimed to analyze the clinical spectrum and prognostic value of TP53 mutations in circulating tumor DNA (ctDNA) from breast cancer patients in China.MethodsWe retrospectively analyzed the clinical data and TP53 mutation features in ctDNA samples from 804 patients with metastatic breast cancer. TP53 mutations were detected by target region capture‐based next‐generation sequencing. The relationship between TP53 mutation status and disease‐free survival (DFS) was analyzed in 444 patients with metastatic breast cancer. Moreover, the relationship between TP53 mutation status and progression‐free survival (PFS) was analyzed in 55 HER2‐positive patients treated with first‐line trastuzumab‐based therapy. Kaplan‐Meier analysis was performed to estimate the survival curves of the different subgroups, and the log‐rank test was used to compare the curves. A Cox regression model was used to estimate multivariable‐adjusted hazard ratios and their 95% confidence intervals (CIs) associated with the DFS and PFS.ResultsAmong the 804 investigated patients, 431 (53.6%) patients harbored TP53 mutations. TP53 mutations were differentially distributed among different molecular subtypes of breast cancer (P < 0.05). Patients with TP53 mutations had a shorter DFS than those with wild‐type TP53 (hazard ratio = 1.32, 95% CI = 1.09‐1.61, P = 0.005). TP53 mutations in exons 5‐8 were associated with worse outcome (hazard ratio = 1.50, 95% CI = 1.11‐2.03, P = 0.009). However, TP53 mutation status was not significantly associated with PFS in HER2‐positive patients who received first‐line trastuzumab‐based therapy (P = 0.966). Interestingly, in the taxane combination group, patients with TP53 mutations exhibited longer PFS than those without TP53 mutations (hazard ratio = 0.08, 95% CI = 0.02‐0.30, P < 0.001). However, in the non‐taxane combination group, patients with TP53 mutations displayed shorter PFS than those with wild‐type TP53 (hazard ratio = 4.84, 95% CI = 1.60‐14.66, P = 0.005).Conclusions TP53 mutations in exons 5‐8 may be an independent prognostic marker for short DFS in patients with metastatic breast cancer. TP53 mutations had opposite effects on trastuzumab‐treated patients treated with and without taxanes.

Development and validation of a nomogram for predicting survival of advanced breast cancer patients in China.

e13064 Background: The prognosis of patients with advanced breast cancer (ABC) varied according to different prognostic factors. This study aimed to establish a nomogram to predict the overall survival (OS) of ABC patients in China. Methods: Data from the China National Cancer Center database that recorded 4039 patients diagnosed with breast cancer between 1987 and 2019 were extracted and a total of 2263 ABC patients with complete relevant information were included in this study, which were further randomized 3:1 and divided into training ( n = 1706) and validation ( n = 557) cohorts. The nomogram was built based on independent predictors identified by univariate and multivariate analyses. Harrell′s concordance index (C-index) and calibration plots were used to assessed the discriminatory and predictive capacities of the nomogram. Results: With a median OS of 45.4 months, the 2-year and 3-year OS rates of ABC patients were 75.2% and 60.2%, respectively. Univariate and multivariate analyses found that age, Eastern Cooperative Oncology Group (ECOG) performance status, T-stage, N-stage, tumor subtype, the presence of distant lymph node (DLN)/liver/brain metastasis, local therapy, efficacy of first-line therapy and metastatic-free interval (MFI) were significantly associated with OS (all P &lt; 0.05). These variables were incorporated into a nomogram to predict the 2-year and 3-year OS of ABC patients. The C-indexes of the nomogram were 0.700 (95% confidence interval [CI]: 0.683-0.717) and 0.686 (95% CI: 0.652-0.719) for the training and the validation sets, respectively. The calibration curves revealed satisfactory agreement between actual survival and nomogram prediction in both the internal and external validations. The nomogram was able to stratify patients into different risk groups. Conclusions: We developed and validated a nomogram that might serve as an efficient tool to provide individual prediction for ABC patients and guide the physicians to make personalized treatment decisions for individual ABC patients.

Financial toxicity and its associated patient and cancer factors among women with breast cancer in China.

e19402 Background: The term “Financial toxicity(FT)” is widely used to describe the distress or hardship patients suffering from the financial burden of cancer treatment[1]. Increased evidences have showed that cancer-associated FT is common and has a negative impact on patients’ mental health, quality and length of life[1,2]. The scale of COmprehensive Score for financial Toxicity-Functional Assessment of Chronic Illness Therapy (COST-FACIT) was used to assess the FT of cancer patients, which has been validated and widely used internationally [3] and China [4]. To our knowledge, little is known about the FT of breast cancer patients in China. The aim of this study is to assess the FT and to investigate patients and cancer characteristic that associated with it in patients in central China. Methods: This was a cross-sectional study among 188 patients with stage 0-III women breast cancer admitted in Bethune hospital in Taiyuan, Shanxi province during January - May 2019. FT was self-reported using the COST-FACIT. Patients’ socio-demographic factors, clinical examination, and cancer treatment were collected from questionnaire and hospital record. The financial concern and coping strategy was self-reported. Factors associated with FT was identified using linear regression analysis. Results: One hundred and sixty-six (88.2%) completed the questionnaire. The COST score ranged 0-40 with a mean of 21.2 (median 22.5, standard deviation 8.1). On multivariate linear regression analysis, older age (β coefficient: 0.19, 95% CI: 0.10-0.29, p&lt;0.001), higher household income (β coefficient: 3000-5000 Yuan: 6.48, 95% CI: 2.78-10.17, p =0.001; ≥ 5000 Yuan: 11.17, 95% CI: 7.25-15.09, p&lt;0.001) were positively associated with COST scores. Advanced cancer stage was the strongest predictor of FT among the cancer characteristics (β coefficient: -1.81, 95% CI: -3.17, -0.46, p=0.009). To cope with the FT, 131 (78.8%) patients decreased non-medical expenses, and 56 (33.7%) reduced or quit treatment. Conclusions: FT was significantly associated with patient’s age, income, and cancer stage. Women having financial concerns after diagnosis were more likely to reduce their non-medical expenses and even quit treatments. Clinicians should take into account the FT levels in all patients and work out appropriate treatment strategies for optimal clinical outcome.

Patterns of sexual health in patients with breast cancer in China: a latent class analysis.

This study aimed to identify unobserved distinct latent classes/subgroups of breast cancer (BC) patients in China with respect to various sexual health measures and examine the association of the latent membership with individual characteristics. In a cross-sectional study, 123 BC patients were analyzed. Their sexual health was measured using the Female Sexual Functioning Index (FSFI). Latent class analysis (LCA) was used to examine the patterns of sexual health in patients. Associations of the latent class membership with individual characteristics were examined using multinomial logistic regression. Three a priori unknown distinct latent classes of patients were identified with respect to the 19 FSFI sexual health measures: 50 patients (41.6%) were classified in class 1 "No Impairment Group," 49 patients (39.4%) in class 2 "Organic Sexual Dysfunction Group," and 24 patients (19.1%) in class 3 "Poor Sexual Health Group." Income and anxiety were positively, whereas disease duration was negatively associated with the likelihood of being in class 2 than in class 1, patients with recurrence of cancer were likely to be in classes 2 and 3. Patients classified in class 3 were more likely to have better prior body image and have more severe menopausal symptoms, whereas less likely to have better post body image and have better partner relationships. The findings revealed the heterogeneity of sexual health among BC patients in China and may guide to identify the high-risk patients and enable early intervention.

Patterns of posttraumatic stress disorder and posttraumatic growth among breast cancer patients in China: A latent profile analysis.

The aim of this study was to identify the patterns of posttraumatic responses among breast cancer (BC) patients, to explore the variables associated with these patterns, and to compare anxiety and depression on various posttraumatic response patterns. A questionnaire survey was conducted with a sample of 612 BC patients who were currently undergoing treatment. The questionnaire package included Posttraumatic Stress Disorder Symptom Scale (PSS), Posttraumatic Growth Inventory (PTGI), Network of Relationships Inventory, Generalized Anxiety Disorder-7 (GAD-7), and Patient Health Questionnaire-9 (PHQ-9). Modeling was performed using a latent profile analysis (LPA) to explore patterns of posttraumatic responses among BC patients. Based on the fitting indicators of LPA, three-class patterns model of posttraumatic responses was optimal. Resisting group (34.6%): patients reported mild posttraumatic stress symptoms (PTSS) and mild posttraumatic growth (PTG). Growth group (47.4%): patients showed mild PTSS and high PTG. Struggling group (18.0%): patients showed high PTSS and high PTG. BC patients with lower income were more likely to belong to Resisting group and Struggling group. BC patients with high levels of social support were more likely to belong to Growth group. Patients in Struggling group had the highest levels of anxiety and depression. This study showed that there was heterogeneity in posttraumatic response patterns of BC patients. The results provided theoretical base guiding the development of health care schemes and psychological interventions for patients, suggesting the necessity of differentiated health care for BC patients with different posttraumatic response patterns.

Efficacy, late complications, and cosmetic outcomes of targeted intraoperative radiotherapy in breast-conserving surgery for early-stage breast cancer: a single-centre study in China.

The purpose of this study was to evaluate the efficacy, late complications, and cosmetic outcomes of targeted intraoperative radiotherapy for the treatment of Chinese patients with early-stage breast cancer. Between September 2014 and May 2017, breast cancer patients undergoing targeted intraoperative radiotherapy at our facility were retrospectively recruited for this study. Intraoperative radiotherapy was performed with a 50-kV X-ray source in an Intrabeam system (Carl Zeiss Meditec, Oberkochen, Germany). The one-time prescribed irradiation dose to the tumour bed was 20Gy. Recurrence, death, late complications, and cosmetic outcomes were recorded. Late radiotoxicity was assessed based on the grading criteria of the Radiation Therapy Oncology Group. A total of 77 patients who were treated with targeted intraoperative radiotherapy only were recruited. The cohort had a mean age of 58years; patients with T1, N0, and invasive ductal carcinoma accounted for 75.3, 89.6, and 84.4%, respectively; the median follow-up duration was 40months; there were 2 patients of recurrence and 2 patients of death. There were no patients of cardiac toxicity or skin or lung radiotoxicity of grade 2 or above. The main complications were breast oedema (18.2%), seroma (15.6%), chromatosis (9.1%), induration (7.8%), pain (5.2%), skin depression (2.6%), mild dry cough (2.6%), delayed wound healing (1.3%), and wound infection (1.3%). Seventy-three patients participated in the cosmetic outcome evaluation, which yielded an excellent or good rate of 95.9%. Due to its low recurrence rates, lack of high-grade late radiotoxicity, and excellent cosmetic outcomes, targeted intraoperative radiotherapy may be a suitable treatment for select early-stage breast cancer patients in China.

Mapping function from FACT-B to EQ-5D-5\u2009L using multiple modelling approaches: data from breast cancer patients in China

BackgroundThe Functional Assessment of Cancer Therapy-Breast (FACT-B) is the most commonly used scale for assessing quality of life in patients with breast cancer. The lack of preference-based measures limits the cost-utility of breast cancer in China. The goal of this study was to explore whether a mapping function can be established from the FACT-B to the EQ-5D-5 L when the EQ-5D health-utility index is not available.MethodsA cross-sectional survey of adults with breast cancer was conducted in China. All patients included in the study completed the EQ-5D-5 L and the disease-specific FACT-B questionnaire, and demographic and clinical data were also collected. The Chinese tariff value was used to calculate the EQ-5D-5 L utility scores. Five models were evaluated using three different modelling approaches: the ordinary least squares (OLS) model, the Tobit model and the two-part model (TPM). Total scores, domain scores, squared terms and interaction terms were introduced into models. The goodness of fit, signs of the estimated coefficients, and normality of prediction errors of the model were also assessed. The normality of the prediction error is determined by calculating the root mean squared error (RMSE), the mean absolute deviation (MAD), and the mean absolute error (MAE). Akaike information criteria (AIC) and Bayes information criteria (BIC) were also used to assess models and predictive performances. The OLS model was followed by simple linear equating to avoid regression to the mean.ResultsThe performance of the models was improved after the introduction of the squared terms and the interaction terms. The OLS model, including the squared terms and the interaction terms, performed best for mapping the EQ-5D-5 L. The explanatory power of the OLS model was 70.0%. The AIC and BIC of this model were the smallest (AIC = -705.106, BIC = -643.601). The RMSE, MAD and MAE of the OLS model, Tobit model and TPM were similar. The MAE values of the 5-fold cross-validation of the multiple models in this study were 0.07155~0.08509; meanwhile, the MAE of the TPM was the smallest, followed by that of the OLS model. The OLS regression proved to be the most accurate for the mean, and linearly equated scores were much closer to observed scores.ConclusionsThis study establishes a mapping algorithm based on the Chinese population to estimate the EQ-5D-5 L index of the FACT-B and confirms that OLS models have higher explanatory power and that TPMs have lower prediction error. Given the accuracy of the mean prediction and the simplicity of the model, we recommend using the OLS model. The algorithm can be used to calculate EQ-5D scores when EQ-5D data are not directly collected in a study.

Reliability and validity of the Chinese version of the Sickness Experience Questionnaire in breast cancer patients

Objective To evaluate the reliability and validity of the Chinese version of the Sickness Experience Questionnaire (CESQ) in breast cancer patients, and to provide a scientific basis for caring for female breast cancer patients and reducing the level of stigma. Methods The English version of CESQ was translated and culturally adjusted. 200 questionnaires were sent out to breast cancer patients in our hospital from May 2017 to August 2018 by convenient sampling method. 190 questionnaires were effectively recovered. Sixty patients were randomly selected and retested after 2 weeks. Reliability and validity was examined by SPSS21.0 and AMOS21.0. Results The Chinese version of CESQ scale Cronbach α coefficient was 0.819, Guttman′s split-half reliability coefficient was 0.844, the correlation coefficient between each item score was 0.405-0.809, and the correlation coefficient between each item score and CESQ total score was 0.499-0.812 (P <0.05). The test-retest reliability coefficient was 0.898. Four experts rated the Chinese version of CESQ with a content validity index of 0.801 to 1.000, an overall consistency content validity index CVI of 0.804, and an average content validity index of 0.830. Principal component analysis was used to conduct exploratory factor analysis. After the orthogonal rotation of the variance, one common factor was obtained, and the cumulative variance contribution rate was 55.65%. Using AMOS 17.0, the data was subjected to confirmatory factor analysis with a chi-square/degree-of-freedom ratio of 1.20 and a goodness-of-fit index of 0.909. The approximate error root mean square was 0.069, the gauge fit index was 0.957, the relative fit index was 0.944, and the value-added fit index was 0.904. Non-standard fit The index was 0.907, the comparative fit index was 0.911, and the normalized regression coefficient was 0.435-0.668. Conclusions The Chinese version of CESQ has a good reliability and validity in evaluating the stigma of breast cancer patients. It has application value in evaluating the stigma of breast cancer patients in China. Key words: Breast neoplasms; Stigma; Reliability; Validity

Abstract CT053: BAT8001, a potent anti-HER2 antibody drug conjugate with a novel uncleavable linker to reduce toxicity for patients with HER2-positive tumor

Abstract T-DM1, an antibody drug conjugate (ADC), has been approved by FDA for patients with HER2-positive, metastatic breast cancer who previously received trastuzumab and a taxane. DM1 is released because it is connected to the linker of T-DM1 by a thio-ether bond, which can be broken via retro-Michael addition. To improve the antibody-drug stability, we created an anti-HER2 ADC (BAT8001) which used a novel uncleavable linker to connect trastuzumab and a payload of maytansine derivative. BAT8001 exhibits similar level of potency against proliferation of HER2-overexpressed cells as T-DM1 and demonstrates strong inhibition activity on tumor growth in both cell-line and patient-derived xenograft models. Pharmacokinetics (PK) study in monkey reveals BAT8001 has similar level of exposure, half-life, and Cmax as T-DM1. BAT8001 Ph1 clinical trial in patients with HER2+ late-stage breast cancer recently was completed. The clinical study used standard “3+3” multiple-dose escalation method, evaluated BAT8001 safety, PK and explored the efficacy. Twenty-nine subjects were randomized and 27 subjects received the treatment with escalated dose 1.2mg/kg, 2.4mg/kg,3.6mg/kg, 4.8mg/kg and 6.0mg/kg. Two subjects died during the screening time without treatment due to disease progression. Nineteen (79.2%) subjects completed at least 4-cycle treatment. The PK parameter (Cmax and AUC(0-t)) values demonstrated dose-dependent linear relationship. In the safety evaluation, the incidences of AE and AE with CTCAE &amp;gt;=3 increased when dose escalated. The platelet count decrease and AST elevation were found to be the most common and severe AEs. Three subjects had serious adverse events (SAE) of bone destruction which were considered to be not investigated-drug related by the PI. Among those 3 subjects, 2 subjects withdrew from the study due to the SAE and 1 subject continued the treatment. The preliminary efficacy assessment after 10 months treatment found that 1 (3.7%) patient exhibited the complete response (CR), 5 (18.5%) patients exhibited the partial responses (PR), and 5(18.5%) patients exhibited the stable diseases. Based on the information above, the dose of 3.6mg/kg achieved target drug exposure and was found to be the effective and well-tolerated, which was selected to be the dose in the confirmatory clinical trial. Currently, a Phase 3, multicenter, randomized, open-label, controlled trial evaluating the efficacy and safety of BAT8001 has been initiated in patients with HER2+ metastatic breast cancer who previously received trastuzumab separately or in combination with taxanes. The trial is designed to compare BAT8001 versus lapatinib combined with capecitabine which is 2nd-line standard of care for metastatic breast cancer patients in China. This Phase 3 trial plans to recruit approximately 410 patients and by Jan 2019 more than 130 patients have received the treatment of BAT8001. The BAT8001 benefit-risk profile continues to support further development and the clinical results will be revealed by early 2020. Citation Format: Shusen Wang, Fei Xu, Ruoxi Hong, Wen Xia, Jin-Chen Yu, Weijia Tang, Jin Wei, ShuQiang Song, Zhaohe Wang, Li Zhang, Shengfeng Li. BAT8001, a potent anti-HER2 antibody drug conjugate with a novel uncleavable linker to reduce toxicity for patients with HER2-positive tumor [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr CT053.

Deleterious Mutations in DNA Repair Gene FANCC Exist in BRCA1/2-Negative Chinese Familial Breast and/or Ovarian Cancer Patients.

Introduction: FANCC is reported as a novel susceptibility gene for breast cancer, however, its mutation remains unclear in Chinese population. We aimed to identify the germline mutations of FANCC in high-risk breast cancer patients in China.Methods: 255 BRCA1/2-negative Chinese familial breast and/or ovarian cancer (FBOC) patients were recruited for FANCC germline mutations screen. For whom 90 patients were detected by PCR-sequencing assay, and another 165 patients were detected by a 98-gene panel sequencing assay. The 98-gene panel sequencing assay was also used to screen other possible gene mutations for the patients with FANCC mutations detected by PCR-sequencing assay. Two hundred and fifty sporadic breast cancer (SBC) patients and 248 female non-cancer controls (FNCCs) were recruited for the genotyping analysis. Immunohistochemistry (IHC) analysis was used to evaluate the FANCC expression in patients with FANCC mutation.Results: We found one rare FANCC deleterious mutation (c.339G>A, p.W113X, 0.4%) and two novel non-synonymous variants (c.51G>C, p.Q17H, 0.4% and c.758C>A, p.A253E, 0.4%) in FBOC patients, whereas none of above mutations was identified in SBC patients or FNCCs. We also found that one novel synonymous variant (c.903A>G, p.A301A) existed in one FBOC patient. Additionally, two non-synonymous SNPs rs201407189 (c.973G>A, p.A325T) and rs1800367 (c.1345G>A, p.V449M), and two synonymous SNPs rs55719336 (c.816C>T, p.I272I) and rs79722116 (c.1407G>A, p.T469T) were identified in FBOC patients.Conclusion: FANCC deleterious mutations exist in Chinese FBOC patients and investigations on the penetrance and spectrum of FANCC mutations need to be further conducted.

Prevalence and clinical outcomes of germline mutations in BRCA1/2 and PALB2 genes in 2769 unselected breast cancer patients in China.

To gain more information on the prevalence of germline mutations in BRCA1/2 and PALB2 genes in the Chinese population, and to explore the effects of the mutation status of these genes on clinical outcomes in patients with breast cancer, we performed a screening for BRCA1/2 and PALB2 mutations in a consecutive series of unselected breast cancer patients in the Chinese population. A total of 2,769 cases were enrolled between June 1993 and September 2017. All of the exons and exon-intron boundaries of the BRCA1/2 and PALB2 genes were screened with next-generation sequencing. Of the 2,769 breast cancer patients, BRCA1, BRCA2 and PALB2 mutations accounted for 2.7% (n = 74), 2.7% (n = 76), and 0.9% (n = 24), respectively. The BRCA1 gene had the highest mutation frequency in patients with triple-negative breast cancer (TNBC), which was 9.6% (n = 42), while the BRCA2 gene had the highest mutation frequency in patients with Luminal, which was 3.2% (n = 58). The disease-free survival (DFS) of BRCA1 mutation carriers was significantly lower than that of noncarriers (adjusted HR = 2.20, 95% CI = 1.15-4.18, p = 0.017). The mutation status of the PALB2 gene was significantly associated with the decline in overall survival (OS) (adjusted HR = 8.38, 95% CI = 2.19-32.11, p = 0.002). No significant difference was found between BRCA2 pathogenic mutation carriers and noncarriers. These results demonstrate that BRCA1 mutation status may be associated with a worse disease progression in patients with breast cancer, and women who harbored a PALB2 mutation might be at a higher risk of death due to breast cancer compared to noncarriers.

Abstract P4-14-14: Clinicopathological features and endocrine therapy mode of ER low expression (1%-9%) breast cancer patients in China

Abstract Purpose: Since 2010, ASCO/CAP recommended that ER be considered positive if ≥1% tumor cells with positive nuclear staining by immunohistochemistry (IHC) in breast cancer. ASCO/CAP also recommended considering endocrine therapy (ET) in ER positive patients. However, most breast cancers are either ER negative or ER strongly positive (≥10%), and tumors with low ER (1-9%) expression are rare. Up to now, the effect of ET is controversial for these patients with ER 1-9% and unfortunately, we know little about the clinical information of this subgroup. In this study, we analyzed the clinicopathological characteristics and ET mode of patients with low ER expression. We sought to figure out whether the ASCO/CAP guidelines affect clinical ET decision in China and Which features are important considerations for doctors to choose ET. We also evaluated the efficacy of ET in these patients. Methods: Patients diagnosed stage I-III primary invasive breast cancer with ER low expression (1-9%) between January 2008 and December 2016 were retrospectively identified from six hospitals in China. Result: 457 patients (2.7%) had low expression of ER (1-9%) of 17216 patients. Mean age at diagnosis was 49 years. 288 patients (49.9%)were younger than 50 years old. 254 patients (55.6%) had stage II disease and 37 patients (8.1%) had lymphovascular invasion (LVI). 260 patients (56.9%) were HER2 positive; 408 patients had PR negative or low expression; 327 patients' (71.6%) Ki-67 status were &amp;gt; 20%. 388 patients (85%) received chemotherapy. Of those 388 patients, 90% patients received anthracycline combined with taxol chemotherapy regimens. 170 patients (37.2%)received ET. Before 2010, only 25.7% patients with low ER expression received ET. The proportion of ET increased after the 2010 ASCO/CAP guideline was published. In 2013, 50% patients received ET. The rate of ET was totally different in six hospitals. 55% patients received ET in the hospital with highest rate, while only 4% patients received ET in the hospital with lowest rate. Using the univariate logistic regression analysis of ET, ER expression, PR expression, Ki-67 status and LVI were associated with the rate of ET. But after adjustment for other covariates, only ER level was significantly associated with the rate of ET. Compared to patients with ER&amp;lt;5% tumors, patients with ER≥5% tumors had a significantly higher probability of ET rate (OR, 2.882; 95% CI: 1.928-4.308; P &amp;lt; 0.001). Median follow time was 30 months. The 5-year RFS rate was 85%. Younger age and positive lymph nodes were associated with worse RFS. Survival rate did not differ significantly between patients with or without ET (without ER vs with ET: OR, 0.870; 95% CI: 0.508-1.448; p=0.61). Conclusions: 2010 ACSO/CAP recommendation indeed result in an increase of ET rate for patients with 1%-9% ER positive. But these patients do not appear to benefit from ET. Prospective studies are needed for these patients and we need more accurate way to evaluate ER levels, which associate with endocrine response. Citation Format: Fu P, Wang S, Yao M, Xiang A, Li J, Wang H, Geng C, Jin F, Yin Y, Huang X, Jiang Z. Clinicopathological features and endocrine therapy mode of ER low expression (1%-9%) breast cancer patients in China [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-14-14.