Chinese Breast Cancer Patients Research Articles

Abstract PO3-11-09: Cross-cultural adaptation and psychometric validation of lymphedema patient-reported outcome measurements in Chinese breast cancer patients

Abstract Background: Lymphedema is one of the most common complains reported by breast cancer survivors, which negatively affects the quality of life (QoL). Various internationally recognized patient-reported outcome measurements (PROMs), such as the Upper Limb Lymphedema 27 (ULL-27), Lymphoedema Functioning, Disability and Health questionnaire (Lymph-ICF), Lymphedema Quality of Life Questionnaire for upper limbs (LYMQOL-ARM), and Lymphedema Life Impact Scale Version 2 (LLIS), have been translated into different languages and widely used to assess QoL in patients with breast cancer-related lymphedema (BCRL). However, limited evidence has proved the efficiency of these tools in Chinese patients. In this study, we performed cross-cultural adaptation and psychometric validation of these four PROMs within the Chinese context. Additionally, we also compared the accuracy in detecting BCRL for early diagnosis. Methods: A process of forward–backward translation and cultural adaptation was conducted based on international standards. Content validity was assessed through patient interviews. Internal consistency was evaluated by Cronbach’s alpha coefficient. The correlation analysis of the MOS item short from health survey (SF-36) and each BCRL QoL questionnaires was utilized to indicate the convergent and divergent validity. Clinical validity was assessed by comparing scores among patients with different BCRL stages. Furthermore, questionnaires scores and the known group of lymphedema or not were compared to generate receiver operator characteristic (ROC) curves of these instruments. Results: A total of 204 female breast cancer patients were recruited in this study. Among them, 104 patients (61 with lymphedema and 43 without lymphedema) finished LYMQOL-ARM and ULL-27 questionnaire, while 100 patients (59 with lymphedema and 41 without lymphedema) were assessed by Lymph-ICF and LLIS. The internal consistency was high, with Cronbach's alpha coefficients above 0.9 for all subscales and global scales. The content validity was generally good, except for a few issues reported by the patients. Convergent and divergent validity confirmed the hypotheses of correlation between the tested questionnaire and SF-36 to varying degrees: 100% for ULL-27, 80% for Lymph-ICF, nearly 70% for LLIS, and only 50% for LYMQOL-ARM. LLIS and Lymph-ICF demonstrated strong clinical validity, with significant differences found in total and subscale scores among participants in different BCRL stages (P< 0.05). There were no significant differences between stages for the mood dimension (P=0.132) of LYMQOL-ARM, psychological dimension (P=0.506), social dimension (P=0.083), and total score (P=0.057) of ULL-27. Only the physical concerns and global scale of LLIS and the symptom subscale of Lymph-ICF exhibited acceptable AUC values near 0.7 (AUC 0.725, 95% CI 0.625-0.825, p< 0.029; AUC 0.680, 95% CI 0.573-0.787, p< 0.002; AUC 0.734, 95% CI 0.633-0.834, p< 0.001, respectively). In contrast, other subscales and questionnaires displayed lower AUC values. Conclusion: Lymphedema is a chronic disease that has a relatively low mortality risk but significantly affects the quality of life. Therefore, it is crucial to prioritize patient-reported outcomes in the assessment of lymphedema. Among the four PROMs, LLIS not only showed high internal consistency and content validity more suitable for Chinese patients, but also exhibited better performance in reflecting the presence and severity of lymphedema patients. Consequently, the validated and reliable Chinese version of LLIS is recommended for clinical and scientific practices in the assessment of BCRL, which will help to provide better interventions with a patient-centered focus. Citation Format: Yue Zhou, Bingqiu Xiu, Qi Zhang, Jiong Wu. Cross-cultural adaptation and psychometric validation of lymphedema patient-reported outcome measurements in Chinese breast cancer patients [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-11-09.

Abstract PO4-26-08: Prevalence of HER2-low and IHC >0 to < 1+ in breast cancer and its concordance between historical and rescored results: a multi-center, retrospective study in China

Abstract Background: With Trastuzumab deruxtecan (T-DXd) changing the anti-HER2 treatment paradigm, HER2-low (defined as IHC2+/ISH- and IHC1+) breast cancer patients have emerged as a new targetable population. The lower threshold for HER2 expression that can benefit from HER2-directed antibody-drug conjugates (ADCs) is still being investigated, such as HER2 immunohistochemistry (IHC) >0 to < 1+ (defined as IHC 0 with incomplete and faint staining in ≤10% of tumor cells) in the DESTINY-Breast06 trial. Accurate determination of HER2 scores has become a critical topic in clinical discussions, given its clinical relevance to HER2-directed treatment strategies. Hence, we conduct this study (HER2-PATH, NCT05203458) to evaluate the distribution of HER2 status including HER2 IHC >0 to < 1+ in Chinese patients with breast cancer. Concordance between rescored and historical results was also analyzed. Methods: A retrospective study was conducted in breast cancer patients who underwent surgery at 10 sites in China between July 2021 and July 2022. Archived HER2 IHC slides from these patients were subjected to rescoring by a review committee comprising two readers and one adjudicator. The two readers independently evaluated each slide blinded to the historical scores. If their results matched, the recorded outcome was considered final. In cases of disagreement, the adjudicator made the final judgment. All slides were stained using Ventana 4B5 and scored following the ASCO/CAP 2018 guidelines, including the addition of the IHC >0< 1+ as defined in the DESTINY-Breast06 trial. The prevalence of the rescored HER2 status was calculated, and the concordance between the historical and rescored HER2 status was assessed using the Cohen's Kappa coefficient. Results: A total of 2868 patients were included in the analysis. The rescored results categorized 682 (23.8%) patients as HER2 IHC 0, 871 (30.4%) patients as IHC 1+, 800 (27.9%) patients as IHC 2+, and 515 (18.0%) patients as IHC 3+. The rates of HER2-positive, HER2-low, and HER2 IHC 0 (including HER2 null and HER2 IHC >0 to < 1+) were 21.8%, 54.3% and 23.9%, respectively. Notably, the prevalence of HER2-low was numerically higher in the HR-positive subgroup compared to the HR-negative subgroup (60.2% vs 30.6%). Furthermore, the prevalence of HER2 IHC >0 to < 1+ and HER2 null was 10.6% and 13.2% among all patients, respectively. Among the HR-positive subgroup, the prevalence of HER2 IHC >0 to < 1+ was 10.9%, while the rate was 9.1% among the HR-negative subgroup. Overall, there was an 83.1% concordance between the historical and rescored results for HER2 IHC scores. The concordance rate for IHC 1+ was numerically lower (74.5%) compared to IHC 0 (85.2%), IHC 2+ (81.4%), and IHC 3+ (98.6%). However, considering that 12.0% of IHC 1+ patients turned into IHC 2+ with limited impact on HER2-low diagnosis, the concordance rate for HER2-low remained as 91.6%. Conclusion: HER2-low prevalence in Chinese breast cancer patients was found to be consistent with global data, while additional 10.6% of patients were identified as HER2 IHC >0 to < 1+, which is currently being investigated in a randomized controlled trial comparing T-DXd with SoC. To our knowledge, this is the first study to report the prevalence of HER2-low, including HER2 IHC >0 to < 1+, in the Chinese breast cancer population based on rescored results. The concordance of HER2-low between the historical and rescored results was 91.6%, indicating that most cases could be reproducibly classified. Table: Rescored HER2 Expression Level Citation Format: Hong Lv, Junqiu Yue, Qingfu Zhang, Fangping Xu, Jianming Li, Lingfei Kong, Peng Gao, Guanjun Zhang, Haifeng Yang, Xiu Nie, Wen-Tao Yang. Prevalence of HER2-low and IHC >0 to < 1+ in breast cancer and its concordance between historical and rescored results: a multi-center, retrospective study in China [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-26-08.

Abstract PO3-02-08: Risk factors and a new predictive nomogram for predicting the Non-sentinel Lymph Node Metastasis in 708 early-stage Breast Cancer Patients with Positive Sentinel Nodes in China

Abstract Objective: The management of positive sentinel lymph node biopsies (SLNB) in patients with early-stage breast cancer remains a matter of controversy. Some studies have shown that not all breast cancer patients with positive sentinel lymph nodes (SLNs) benefit from further axillary lymph node dissection (ALND). Our study aims to analyse the risk factors and construct a new nomogram to predict non-sentinel lymph node (NSLN) metastasis in Chinese early-stage breast cancer patients with positive sentinel lymph nodes. Methods: The clinical data of 708 patients with early-stage breast cancer who attended The Fourth Hospital of Hebei Medical University for surgical treatment from January 2016 to December 2021 was retrospectively analyzed. All of them were female breast cancer patients with positive sentinel lymph nodes and underwent ALND. The patients were divided into modeling group and validation group according to the time of treatment. The patients in the modeling group were divided into a positive NSLN group and a negative NSLN group. The characteristics: age, maximum tumor diameter, the number of positive SLNs, proportion of positive SLNs, vessel carcinoma embolus, nerve invasion, status of ER, PR, HER-2 and Ki-67 were included in the analysis. And the independent risk factors of NSLN metastasis were screened by univariate (chi-square test) and multivariate (logistic regression) analysis. A nomogram model was established according to the screened independent risk factors, and the model was externally validated by the validation group. The ROC curve was plotted to calculate the area under the curve (AUC) and evaluate the predictive power of the nomogram model. A calibration curve and decision curve analysis (DCA) were used to evaluate the performance of the model. Results: Among the 708 patients, (modeling group n=410, validation group n=298), the average age, average number of positive SLNs, and NSLN positive rate were 50.9±11.1, 1.55±0.87 and 25.71%. The univariate analysis revealed statistically significant differences in the number of positive SLNs (P< 0.001), the proportion of positive SLNs (P < 0.001), vessel carcinoma embolus (P=0.001), nerve invasion (P=0.012), and ER status (P=0.029) in the NSLN-positive group compared with the negative group. The multifactorial logistic regression analysis revealed that the number of positive SLN (P=0.002; OR: 1.700; 95% CI: 1.219-2.370), the proportion of positive SLN (P=0.048; OR: 3.214; 95% CI: 1.001-10.490), vessel carcinoma embolus (P=0.010; OR: 2.076; 95% CI: 1.194-3.612), nerve invasion (P=0.024; OR: 2.119; 95% CI: 1.221-3.678), and ER status (P=0.045; OR: 2.978; 95% CI: 1.022-8.675) were independent risk factors for NSLN positivity. Furthermore, the nomogram was built using these 5 factors and validated on 298 patients in the validation group. The AUC was 0.728 (P< 0.001; 95%CI: 0.673-0.784) in the modeling group and 0.810 (P<0.001; 95%CI: 0.735-0.886) in the validation group. The calibration curves of the modeling and validation groups were close to the ideal curve, and DCA also showed that the model could be applied in clinical practice. Conclusion: For early-stage breast cancer with positive SLNs, these factors as the positive number of SLNs > 2, the ratio of positive SLNs > 50%, vessel carcinoma embolus, nerve invasion and ER-positive could predict NSLN metastasis well. The proposed nomogram appears to accurately estimate the likelihood of positive NSLNs and may greatly help the surgeon to decide intraoperatively whether to perform further ALND and avoid non-essential ALND as well as postoperative complications. Citation Format: Zhenchuan Song, Xueyi Zhao, Liu Yang. Risk factors and a new predictive nomogram for predicting the Non-sentinel Lymph Node Metastasis in 708 early-stage Breast Cancer Patients with Positive Sentinel Nodes in China [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-02-08.

Abstract PO1-13-01: Safety profiles of Chinese breast cancer patients who received abemaciclib in MONARCH plus and monarchE study

Abstract Aim: Abemaciclib demonstrated efficacy with tolerable safety profile in Chinese patients (CN pts) with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer (ABC) and high-risk early breast cancer (EBC). The overall safety profile of abemaciclib in Chinese ABC and EBC pts was consistent with overall population in the MONARCH plus and monarchE studies. To better understand the safety of abemaciclib in CN pts, beyond the previously reported most frequent adverse events (AEs), we report a comprehensive summary of other selected AEs in CN pts in the two trials. Methods: Study designs of MONARCH plus (NCT02763566) and monarchE (NCT03155997) studies were reported previously. To report detailed characteristics of a selected AE profile, including alanine aminotransferase increased, aspartate aminotransferase increased, blood creatinine increased, fatigue, nausea, and vomiting, data were pooled across all CN pts from these two phase 3 studies. The safety population was defined as all randomized patients receiving at least 1 dose of Abemaciclib or endocrine therapy. Data cutoff time is May 18, 2020 and July 1, 2022, respectively. Results: Among 6052 participants in the overall safety population, 875 CN pts (14.5%) were included (512/3100 abemaciclib, 363/2952 placebo). CN pts treated with abemaciclib indicated consistent AE profiles in combination with different endocrine therapies (aromatase inhibitors or Fulvestrant). Detailed characteristics of selected AEs are summarized in table. No deaths due to the selected AEs were reported in CN pts. Conclusion: The selected AEs of abemaciclib group were in low severity with limited grade 3-4 events. Those AEs were tolerable and generally manageable in CN pts in the MONARCH plus and monarchE trials. Citation Format: Zhimin Shao, Qingyuan Zhang, Quchang Ouyang, Qiang Liu, Jifeng Feng, Hui-Ping Li, Xiaojia Wang, Ning Liao, Liu Yang, Qinyi Zhu, Chenxi Qian, Zefei Jiang. Safety profiles of Chinese breast cancer patients who received abemaciclib in MONARCH plus and monarchE study [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-13-01.

Abstract PO1-11-12: Factors associated with treatment failure for chemotherapy-induced nausea and vomiting (CINV) among breast cancer patients receiving adjuvant chemotherapy

Abstract Background Cancer patients often consider CINV as one of the most disturbing side effects of cytotoxic chemotherapy. Adriamycin and cyclophosphamide (AC), considered by many to be part of the standard adjuvant regimen for breast cancer patients, is highly emetogenic. Despite adopting optimal antiemetic prophylaxis, the control of CINV remains modest for some patients. Among Chinese breast cancer patients receiving adjuvant AC chemotherapy, the present analysis aims to determine the association of the number of risk factors for CINV with (i) likelihood of antiemetic treatment failure; (ii) time to first vomiting in 1st AC cycle. Methods: We retrieved data from three previously reported prospective antiemetic studies on patients who received AC, in whom different antiemetic regimens were administered. Treatment failure was defined as (i) not achieving CR (CR= no vomiting and no use of rescue medication over 120 hours after start of AC), or (ii) experiencing nausea (nausea VAS >/= 5mm during the 120 hours). Multivariate logistic regression models were applied to identify potential factors associated with the development of CINV. The Cochran–Armitage trend test was utilized to assess possible trends in the relationship between treatment failure and number of identified risk factors. The time-to-treatment failure curves, as classified by the number of identified factors in each subgroup, were evaluated using the Kaplan–Meier method. Results: Based on multivariate analysis of 303 breast cancer patients, not achieving CR was more likely among non-obese patients, not receiving guideline recommended prophylactic antiemetic regimens, history of motion sickness and history of vomiting in pregnancy. Experience of nausea was more likely in non-obese patients, not receiving guideline recommended prophylactic antiemetic regimens, and history of motion sickness. Treatment failure in terms of ‘no CR’ was associated with increased number of risk factors that an individual patient displayed; the figures increased from 18.8% for those with 0 risk factor to 94.1% for those with 4 risk factors (p < 0.0001). Treatment failure in terms of nausea was associated also with increased number of risk factors; the figures increased from 25.9% for those with 0 risk factor to 83.3% for patients with 3 risk factors (p < 0.0001). Time to first vomiting was significantly related to number of identified factors (p < 0.0001). Among patients who had 0, 1, 2 and 3 risk factors, the 24-hour rate of ‘no vomiting’ were 81.3%, 80.3%, 66.7%, 53.7% and 17.7%, respectively; similar trends were observed for analyses on 48-hour and 72-hour rates. Conclusions: The present study confirmed that reported risk factors for CINV in the literature were important in Chinese breast cancer patients receiving AC chemotherapy. Furthermore, patients who had more risk factors had increased likelihood of treatment failure and shorter time to first vomiting. Funding: Madam Diana Hon Fun Kong Donation for Cancer Research Citation Format: Winnie Yeo, Nicole Ngai, Horatio Yeo, Dong Lai, Elizabeth Pang, Carol Kwok, Thomas Lau, Frankie Mo. Factors associated with treatment failure for chemotherapy-induced nausea and vomiting (CINV) among breast cancer patients receiving adjuvant chemotherapy [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-11-12.

Weight management personas of breast cancer patients undergoing chemotherapy in China: a multi-method study

BackgroundMobile health (mHealth) may be an ideal solution for breast cancer (BC) patients in China to access weight management interventions. User retention and engagement are the main challenges faced by mHealth applications. A user persona, which is a user-centered design process, can lead to the development of mHealth that is more acceptable to the needs of target users. This study aimed to investigate the variety of experiences in weight management and the behavioral preferences of BC patients receiving chemotherapy to develop users’ personal information and persona development for the design and implementation of mHealth interventions.MethodsSixteen individual semi-structured in-depth interviews were conducted with BC patients receiving chemotherapy. We employed the thematic analysis method to analyze the interview transcripts in NVivo 11 software. The themes obtained from the analysis were used as the subdomains of personas. A proforma was designed to extract each participant’s experience in each subdomain. Patients who exhibited similar experience in subdomains were grouped into a persona using affinity diagrams. The personas were named according to their prominent features. A questionnaire survey was conducted to validate the personas and to test whether the personas that were generated from the qualitative interview data were applicable to the Chinese population with BC.ResultsFour themes were identified as subdomains of weight management personas: the perception of weight management while undergoing chemotherapy, symptoms and emotional disturbance, changes in diet and exercise, and health literacy and information seeking. Five personas were ultimately obtained: (1) positive weight controllers, (2) patients who were inactive due to fatigue, (3) young patients who avoided communication, (4) overweight patients with treatment priority, and (5) patients who engaged in irregular exercise. Finally, the quantitative study showed that 51.58% of patients chose one of these five personas to represent themselves in weight management. None of the patient reported selecting options that were not explicitly outlined in the questionnaire and provided personalized descriptions of their weight management characteristics.ConclusionsThe selected personas were developed from in-depth interviews on biopsychosocial areas. They highlight different weight management patterns in Chinese BC patients and provide implications for both the design of mHealth systems and traditional interventions.

Risk Factors Associated with Chemotherapy-Induced Nausea and Vomiting Among Women with Breast Cancer Receiving Highly Emetogenic Chemotherapy: Individual Patient-Based Analysis of Three Prospective Antiemetic Trials.

Although risk factors related to chemotherapy-induced nausea and vomiting (CINV) have been identified in previous studies, only a few studies have evaluated the risk factors associated with contemporary antiemetic prophylaxis, including olanzapine/aprepitant- or NEPA-containing regimens. This study aimed to identify the risk factors associated with CINV development in Chinese breast cancer patients receiving doxorubicin and cyclophosphamide chemotherapy. Data from 304 patients enrolled in 3 previously reported prospective antiemetic studies were included. Multivariate logistic regression models were used to predict risk factors associated with CINV occurrence. Additionally, the likelihood of treatment failure in relation to the number of risk factors in individual patients was evaluated. Multivariate analysis of the entire study group revealed that obesity status (defined as body mass index/= 25.0 kg/m2) and the use of olanzapine/aprepitant- or NEPA-containing anti-emetic regimens were associated with a high likelihood, while a history of motion sickness was associated with a lower likelihood, complete response (CR), and "no nausea" in the overall phase. A history of vomiting during pregnancy was also associated with a lower likelihood of an overall CR. Patients with an increasing number of risk factors had a higher likelihood of treatment failure and shorter time to first vomiting. Those who did not achieve CR and "no nausea" in the first cycle were less likely to achieve these parameters in the subsequent cycle of chemotherapy. The present study confirmed previously reported risk factors for CINV in Chinese breast cancer patients receiving doxorubicin and cyclophosphamide. Further optimization of CINV control is required for patients with identifiable risk factors; olanzapine/aprepitant- or NEPA- containing prophylaxis are the preferred contemporary anti-emetics regimens for Chinese breast cancer patients undergoing doxorubicin and cyclophosphamide chemotherapy.

The HLA-I landscape confers prognosis and antitumor immunity in breast cancer.

Breast cancer is a highly heterogeneous disease with varied subtypes, prognoses and therapeutic responsiveness. Human leukocyte antigen class I (HLA-I) shapes the immunity and thereby influences the outcome of breast cancer. However, the implications of HLA-I variations in breast cancer remain poorly understood. In this study, we established a multiomics cohort of 1156 Chinese breast cancer patients for HLA-I investigation. We calculated four important HLA-I indicators in each individual, including HLA-I expression level, somatic HLA-I loss of heterozygosity (LOH), HLA-I evolutionary divergence (HED) and peptide-binding promiscuity (Pr). Then, we evaluated their distribution and prognostic significance in breast cancer subtypes. We found that the four breast cancer subtypes had distinct features of HLA-I indicators. Increased expression of HLA-I and LOH were enriched in triple-negative breast cancer (TNBC), while Pr was relatively higher in hot tumors within TNBCs. In particular, a higher Pr indicated a better prognosis in TNBCs by regulating the infiltration of immune cells and the expression of immune molecules. Using the matched genomic and transcriptomic data, we found that mismatch repair deficiency-related mutational signature and pathways were enriched in low-Pr TNBCs, suggesting that targeting mismatch repair deficiency for synthetic lethality might be promising therapy for these patients. In conclusion, we presented an overview of HLA-I indicators in breast cancer and provided hints for precision treatment for low-Pr TNBCs.

Feasibility of online managing cancer and living meaningfully (CALM) in Chinese patients with metastatic breast cancer: a pilot randomized control trial

Metastatic breast cancer could cause various psychological symptoms. Managing Cancer and Living Meaningfully (CALM) is a brief, manualized psychotherapy that has been validated for advanced cancer patients. We conducted a pilot randomized control trial (RCT) to verify the feasibility and preliminary efficacy of CALM therapy in this population. Patients who met the inclusion criteria were randomly assigned into CALM or Wait-list Control (WLC) groups. Patients in the CALM group received CALM therapy and usual care; patients in WLC group first received usual care and then underwent CALM therapy after completing all assessments. All patients were asked to complete three assessments: T0(baseline), T1(3 months), and T2(6 months). The primary outcomes was death anxiety; other outcomes were depression, distress, suicide ideation, attachment security, spiritual well-being and quality of life at the end of life. Analysis of Covariance (ANCOVA) and t-test were used for statistics analysis. Thirty-six patients were randomly assigned to either of the two groups, with 34 patients completing the three assessments. At six months, we found significant between group differences in suicide ideation, distress, and life completion between the CALM and WLC groups. At T2, patients in CALM group reported lower levels of depression (F = 5.016, p = 0.033, partial η2 = 0.143), distress (F = 7.969, p = 0.010, partial η2 = 0.257), attachment avoidance (F = 4.407, p = 0.044, partial η2 = 0.128), and better sense of life completion (F = 5.493, p = 0.026, partial η2 = 0.155) than patients in the WLC group. Compared with results of the T0 assessments, we found significant differences in socres for depression (T2&T0, t = − 2.689, p = 0.011, Cohen’s d = 0.940) and distress (T2&T0, t = − 2.453, p = 0.022, Cohen’s d = 0.965) between the two groups. CALM therapy was well received by the study population, and CALM therapy can reduce depression, distress, attachment avoidance while improving quality of life in Chinese metastatic breast cancer patients. A Phase III RCT was recommended to verify the impact of CALM therapy on psychological burden and survival in this population.Trial registration: This study is part of the “Preliminary application study for Managing Cancer and Living Meaningfully (CALM) therapy in Chinese advanced cancer patients” clinical trial, with the Trial Registration Number of ChiCTR1900023129 (13/05/2019) in the Chinese Clinical Trial Registry (ChiCTR) website. (https://www.chictr.org.cn/index.html).

Clinical sequencing defines the somatic and germline mutation landscapes of Chinese HER2-Low Breast Cancer

More than half of the breast cancer initially labeled as human epidermal growth factor receptor 2 (HER2)-negative actually exhibited low HER2 levels (IHC 1+ or IHC 2+/FISH-) and were classified as HER2-low breast cancer. Previous research emphasized the significant biological heterogeneity in HER2-low breast cancer, highlighting the importance of accurately characterizing HER2-low tumors to promote the precise management of antibody‒drug conjugates. In this study, we established a large-scale targeted sequencing cohort (N = 1907) representing Chinese HER2-low breast cancer patients with detailed clinical annotation. Our research findings revealed that HER2-low breast cancer demonstrated distinct clinical pathological characteristics and mutation landscapes compared to HER2-zero group. When compared to HER2-zero tumors, HER2-low tumors exhibited a higher proportion of Luminal B subtypes and better disease-free survival. In hormone receptor (HR)-positive breast cancer, HER2-low group showed a higher frequency of GATA3 somatic mutations, BRCA2 germline mutations, and mutations in the DNA damage repair pathway. In contrast, in HR-negative breast cancer, the HER2-low group displayed a higher frequency of PIK3CA mutations and PI3K pathway alterations. These findings offered valuable insights for the precise targeted treatment of HER2-low breast cancer in different HR statuses.

Abstract A040: Cellular ecosystem of breast tumor microenvironment in Chinese breast cancer patients

Abstract Background: Current evidence has demonstrated the important role of tumor microenvironment (TME) in cancer initiation and progression. However, the dynamic interactions among various cells and their communities in TME remain largely unknown. Recently, EcoTyper, was developed to discover different cell states and their ecosystems in silico using bulk gene expression data. The application of this tool in the Pan-Cancer analysis identified distinct cell states and ecotypes (co-association patterns between cell states) that act as strong classifiers for cancer types and subtypes. In this study, we aimed to discover the TME ecosystems in breast tumors from an East Asian population and associate them with well annotated clinical features and breast cancer (BC) risk factors. Methods: We applied the EcoTyper framework to tumor RNA-Seq data from 242 Hong Kong BC patients to identify carcinoma ecotypes (CEs) and associated them with intrinsic subtype (PAM50), driver gene mutations (based on whole genome/exome sequencing analyses), and well-known BC risk factors. Additionally, we used The Cancer Genome Atlas BC (TCGA-BRCA) data, which was part of the initial EcoTyper Pan-Cancer analysis, as a quality control and comparison dataset. The TCGA patients were predominantly of European ancestry and had similar age distribution (median=58 years) compared to HK patients (median=60 years). The distribution of PAM50 subtype was also similar between the two datasets, with HK having a slightly higher proportion of luminal A (38% vs. 33% in TCGA) and a lower proportion of basal (11% vs. 20% in TCGA). Results: Among all ten ecotypes, the frequency of each CE was very similar between HK and TCGA. In both datasets, the prevalence of these CEs varied by tumor subtype. CE1 and CE6 were enriched in luminal A and rare in basal, while CE9 was rarely found in luminal A but showed high prevalence in HER2-enriched and basal subtypes. CE7 was enriched in luminal B (especially in HK, where among tumors with CE7, 82% of them were luminal B), CE10 was enriched in HER2-enriched (especially in HK, where 41% of tumors with CE10 were HER2-enriched), and CE2 was enriched for basal subtype. CE8 was enriched for luminal A in HK and luminal B in TCGA. The presence of CE2, CE9, or CE10 was associated with higher prevalence of TP53 somatic mutations, particularly in HK. Among the BC risk factors examined, we did not find any statistically significant associations with any CEs, probably due to the small sample size. The work of assessing the associations with the abundance of each cell state and CE is currently ongoing. Conclusions: We replicated cellular ecosystems and their associations with tumor subtypes and driver gene mutations in an East Asian population, demonstrating its generalizability and potential utility in refining BC subtypes. Next, we plan to extend the analysis to paired adjacent normal tissue to further assess the role of these ecosystems in shaping TME heterogeneity and tumor evolution. Citation Format: Hela Koka, Xin Li, Difei Wang, Difei Wang, Kristine Jones, Kristine Jones, Aurelie Vogt, Aurelie Vogt, Bin Zhu, Amy Hutchinson, Amy Hutchinson, Belynda Hicks, Belynda Hicks, Priscilla Ming Yi Lee, Lap Ah Tse, Xiaohong R Yang. Cellular ecosystem of breast tumor microenvironment in Chinese breast cancer patients [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Breast Cancer Research; 2023 Oct 19-22; San Diego, California. Philadelphia (PA): AACR; Cancer Res 2024;84(3 Suppl_1):Abstract nr A040.

Abstract B016: Recapitulation of gene expression-based immune subtypes of breast cancer using immunohistochemical staining

Abstract Using gene expression profiling data, we previously identified three immune subtypes (low-TIL, high-TIL, high-ISG) of breast cancer (BC) among Chinese BC patients in Hong Kong (HK) (Zhu et al., Breast Cancer Res, 2017). To investigate if standard in situ immunohistochemical (IHC) staining could capture the BC immune landscape, we analyzed archival tissue sections from 148 HKBC patients who were previously characterized based on gene expression. Dual IHC staining for 8 immune markers (CD3, CD8, CD20, FOXP3, CD68, CD163, PDL1, and IDO1) and PanCK was performed. Digitized whole slide images for each marker were analyzed using high-accuracy machine learning algorithms trained to quantify the percentage of positively stained regions. Strong correlations were found between IHC immune markers and gene expression-based immune and intrinsic subtypes. Compared to patients with lower level of tumor-infiltrating lymphocytes (low-TIL) classified based on gene expression data, those in the high-TIL subtype (characterized by high T cell and immune checkpoint gene expression) showed higher proportions of CD3, CD8, CD20, FOXP3, CD68, and PDL1 IHC positively stained cells. Similarly, the high-ISG subtype (with increased interferon-stimulated gene expression and TP53 somatic mutations) had higher proportions of CD3, CD8, CD20, FOXP3, and CD68 stained cells than the low-TIL subtype and in particular exhibited high CD163 staining, indicative of a proinflammatory tumor microenvironment. CD8, CD20, CD163, PDL1, and IDO1 expression varied significantly by PAM50 subtypes, with luminal (A and B) subtypes showing lower staining than non-luminal (HER2 and Basal) subtypes. A distinctive feature, however, of luminal B tumors was the higher infiltration by CD163-expressing cells when compared with the luminal A subtype. Except for FOXP3, all examined IHC markers showed significantly higher expression in patients with somatic TP53 mutations (CD3: P= 0.003, CD8: P= 0.005, CD20: P= 0.003, CD68: P= 0.002, CD163: P= 0.002, PDL1: P= 0.003, and IDO1: P= 0.013). On the other hand, expression of these markers did not significantly vary by PIK3CA mutation or germline APOBEC3A/B deletion polymorphism, which is more prevalent among East Asians than other populations and was previously linked to BC risk and immune environment. Of the BC risk factors assessed, only body mass index (BMI) demonstrated associations with immune cell densities, with higher BMI associated with lower expression of CD3, CD8, and CD20. This study sheds further light on the in situ immune landscape of gene expression-based BC subtypes, suggesting that standard IHC assessment of immune markers could refine BC subtype classification for clinical and epidemiological use. Citation Format: Mustapha Abubakar, Hela Koka, Priscilla Lee, Scott Lawrence, Karun Mutreja, Difei Wang, Bin Zhu, Shelly Tse, Xiaohong R Yang. Recapitulation of gene expression-based immune subtypes of breast cancer using immunohistochemical staining [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Breast Cancer Research; 2023 Oct 19-22; San Diego, California. Philadelphia (PA): AACR; Cancer Res 2024;84(3 Suppl_1):Abstract nr B016.

The Influence of Pharmaceutical Care in Patients with Breast Cancer Receiving Adjuvant Endocrine Therapy

Objectives: Our objective was to explore the effect of a pharmaceutical care program on adherence to adjuvant endocrine therapy (AET) in breast cancer patients. Methods: Female breast cancer patients taking AET (N=429) were enrolled in the study; the pharmaceutical care program was implemented and the effect of this intervention was evaluated. The primary outcomes were scores on an 8-item medication adherence scale Chinese version (MMAS), beliefs about medicines questionnaire specific (BMQ), 5-level EuroQol 5 dimensions questionnaire (EQ-5D-5L) and a patient satisfaction questionnaire (PSQ-18). Results: We found statistically significant difference in scores on MMAS and BMQ-concern (p < .05) before and after intervention. The MMAS score was 6.12 (±1.21), 7.15 (±0.92) and 7.18 (±0.96) at baseline, 6 months and 12 months, respectively. The BMQ-concern score was 15.64 (±2.14), 12.26 (±2.85), 11.56 (±2.27) at baseline, 6 months and 12 months separately. Conclusion: The pharmaceutical care program significantly improved medication adherence and reduced patients' medication concerns to adjuvant endocrine therapy in Chinese breast cancer patients.

Transforming growth factor-induced gene TGFBI is correlated with the prognosis and immune infiltrations of breast cancer

BackgroundTransforming growth factor β (TGFβ) is a critical regulator of lung metastasis of breast cancer and is correlated with the prognosis of breast cancer. However, not all TGFβ stimulated genes were functional and prognostic in breast cancer lung metastatic progress. In this study, we tried to determine the prognosis of TGFβ stimulated genes in breast cancer.MethodsTGFβ stimulated genes in MDA-MB-231 cells and lung metastasis-associated genes in LM2-4175 cells were identified through gene expression microarray. The prognosis of the induced gene (TGFBI) in breast cancer was determined through bioinformatics analysis and validated using tissue microarray. The immune infiltrations of breast cancer were determined through “ESTIMATE” and “TIMER”.ResultsTGFBI was up-regulated by TGFβ treatment and over-expressed in LM2-4175 cells. Through bioinformatics analysis, we found that higher expression of TGFBI was associated with shorted lung metastasis-free survival, relapse-free survival, disease-free survival, and overall survival of breast cancer. Moreover, the prognosis of TGFBI was validated in 139 Chinese breast cancer patients. Chinese breast cancer patients with higher TGFBI expression had lower overall survival. Correspondingly, breast cancer patients with higher TGFBI methylation had higher overall survival. TGFBI was correlated with the score of the TGFβ signaling pathway and multiple immune-related signaling pathways in breast cancer. The stromal score, immune score, and the infiltrations of immune cells were also correlated with TGFBI expression in breast cancer.ConclusionsTGFβ-induced gene TGFBI was correlated with the prognosis and immune infiltrations of breast cancer.

Efficacy, safety, and predictive model of Palbociclib in the treatment of HR-positive and HER2-negative metastatic breast cancer

PurposeThis research designeded to: 1. Analyze the efficacy and safety of Palbociclib treatment in HR-positive and HER2-negative (HR + /HER2-) metastatic breast cancer(MBC) patients. 2. Establish and validate a nomogram model for predicting the progression-free survival (PFS) rates of 6 months, 12 months, and 18 months in HR + /HER2- MBC patients after receiving Palbociclib plus endocrine therapy (ET).Patients and methods1. This research retrospectively analyzed the efficacy and safety of Palbociclib combined with ET in 214 patients with HR + /HER2- MBC. 2. A nomogram was designed and constructed with the retrospective clinical data of 214 patients with HR + /HER2- MBC who received Palbociclib plus ET at Zhejiang Cancer Hospital in China from August 2018 to August 2022. Among these patients, 161 were randomly assigned to the training cohort, while 53 to the validation cohort. The predictive accuracy of the nomogram was assessed through the analysis the area under the receiver operating characteristic(ROC) curve, calibration curve, and decision curve analysis(DCA).Results1. Median PFS was 7.17 months (95% CI: 7.61—10.05 months), with an objective response rate (ORR) of 2.80% and a disease control rate (DCR) of 34.58%. The most prevalent grade 3–4 adverse event was neutropenia (38.79%). 2. Multiple variable analysis of the training set revealed that age < 60 years old, PR < 20%, Ki-67 ≥ 20%, luminal B molecular subtype, primary resistance to ET, receipt of late-stage chemotherapy, and presence of liver metastasis or ≥ 2 visceral metastases were independent prognostic factors associated with poor PFS (P < 0.05). Then, the predictive model underwent development and validation utilizing the aforementioned parameters. On the one hand, the area under the ROC curve (AUC) values of the training set at 6 months, 12 months, and 18 months were 0.771, 0.783, and 0.790, respectively, indicating a strong predictive ability of the developed model. On the other hand, the AUC of the validation set at 6 months, 12 months, and 18 months were 0.720, 0.766, and 0.754, respectively, suggesting the favorable discriminatory ability of the model. The calibration curves also exhibited a good fit with the ideal curves, and the DCA demonstrated the clinical applicability of the model. The nomogram's different scores could distinguish PFS.ConclusionThis retrospective study demonstrates the efficacy of Palbociclib in Chinese breast cancer patients. Moreover, the clinical parameters showed a significant association with the prognosis of HR + /HER2- MBC, and the prognostic models constructed based on these variables also displayed robust predictive power, which could offer more intuitive and convenient references for clinical doctors to formulate follow-up treatment plans.

BRCA1 and BRCA2 germline mutations in Chinese Hakka breast cancer patients

ObjectiveTo investigate the prevalence of BRCA1/2 gene variants and evaluate the clinical and pathological characteristics associated with these variants in Chinese Hakka breast cancer patients.MethodsA total of 409 breast cancer patients were analyzed based on next-generation sequencing results, with 337 categorized as non-carriers and 72 as carriers of BRCA1/2 variants. Data on the patients’ BRCA1/2 gene mutation status, clinical and pathological characteristics, as well as menstrual and reproductive information, were collected, analyzed, compared, and tabulated. Logistic regression analysis was performed to explore the relationship between clinical characteristics and pathogenic variants.ResultsAmong the patients, 72 were identified as carriers of pathogenic or likely pathogenic variants in BRCA1/2, while 337 had likely benign or benign mutations. The BRCA1 c.2635G > T (p. Glu879*) variant was detected at a high frequency, accounting for 12.5% (4/32) of the BRCA1 mutations, while the c.5164_5165del (p.Ser1722Tyrfs*4) variant was common among the BRCA2 mutations, accounting for 17.5% (7/40). It was observed that a higher proportion of BRCA1 carriers had the triple-negative breast cancer subtype, whereas more BRCA2 carriers exhibited estrogen receptor (ER) + and progesterone receptor (PR) + subtypes. Multivariate logistic regression analysis revealed that a family history of cancer (OR = 2.36, 95% CI = 1.00–5.54), bilateral cancer (OR = 4.78, 95% CI 1.61–14.20), human epidermal growth factor receptor 2 (HER2)- (OR = 8.23, 95% CI 3.25–20.84), and Ki67 ≥ 15% (OR = 3.88, 95% CI 1.41–10.65) were associated with BRCA1/2 mutations, with the age at diagnosis, age at menarche, and premenopausal status serving as covariates.ConclusionsThe most common pathogenic variant of the BRCA1 and BRCA2 in breast cancer patients was c.2635G > T and c.5164_5165del, respectively. Additionally, a family history of cancer, bilateral cancer, HER2-, and Ki67 ≥ 15% were identified as independent predictors of BRCA1/2 pathogenic variants.

A study of the mediating effect of social support on self-disclosure and demoralization in Chinese older adult homebound breast cancer patients.

Demoralization is common in older adult homebound breast cancer patients, seriously affecting their quality of life. This study aimed to investigate the demoralization of older adult homebound breast cancer patients and to analyse the mediating effects of social support between self-disclosure and demoralization. The study enrolled 368 older adult homebound breast cancer patients reviewed in outpatient clinics of three hospitals from January 2022 to August 2023. A questionnaire survey was conducted using the general information questionnaire, the distress disclosure index (DDI), the social support revalued scale (SSRS), and the demoralization scale (DS). Path analysis was conducted to test the hypothesised serial mediation model. The total scores of self-disclosure, social support, and demoralization were 37 (25-42), 34 (19-48.75), and 46.5 (35-68), respectively. The results indicated a positive correlation between self-disclosure and social support (p < 0.01). In contrast, a statistically significant negative correlation was observed between self-disclosure, social support, and various demoralization dimensions (p < 0.01). Social support played a partial mediation effects between self-disclosure and demoralization, indirect effect =0.6362, SE = -0.591, 95% CI (-0.785 ~ -0.415); Self-disclosure direct effect demoralization, direct effect =0.3638, SE = -0.337, 95% CI (-0.525 ~ -0.144); total effect, SE = -0.929, 95% CI (-0.945 ~ -0.904). Social support a partial mediated between self-disclosure and demoralization in Chinese older adult homebound breast cancer patients. Clinical staff should focus on developing a social support system for Chinese older adult homebound breast cancer patients, encouraging patients to reveal their minds, and providing psychological counselling to enhance self-confidence and rebirth from adversity.

The bicarbonate status of the Chinese primary breast cancer patients with different clinicopathology and molecular subtypes

The bicarbonate status of the Chinese primary breast cancer patients with different clinicopathology and molecular subtypes

“All about the value?” Decisional needs of breast reconstruction for breast cancer patients in the Chinese context: A mixed-methods study

ObjectiveTo explore breast cancer (BC) patients' participation in breast reconstruction (BR) decision-making and specific decisional needs, especially the manifestations and causes of decisional conflicts, in China. MethodsA mixed-methods study was conducted using triangulation of data from interviews and a questionnaire survey with health care professionals (HCPs) and BC patients with BR decision-making experience at 5 Beijing centers. The Ottawa Decision Support Framework guided (ODSF) the qualitative and quantitative data analyses. ResultsA total of 82.53% of Chinese BC patients would consider BR. Seven themes captured patients' BR decisional needs per the ODSF: inadequate support/resources (100%, 58.82%) and knowledge (75%, 52.94%) were most frequently cited. Health beliefs (unclear values) reflected Chinese characteristics. Patients had inadequate knowledge (M=19.99/50, SD=8.67) but positive BR attitudes (M=59.48/95, SD=10.45). ConclusionsBR decisions for Chinese BC patients are complex and often accompanied by decisional conflicts. Inadequate knowledge and inadequate support and resources contribute to these conflicts, emphasizing the need for culturally tailored information and support to promote SDM. Practice implicationsHCPs need specialized training in SDM to guide patients in decision-making. It is essential to provide relevant resources and support that are culturally and clinically appropriate for Chinese patients.

Exploring fear of cancer recurrence and related factors among breast cancer patients: A cross-sectional study.

Fear of cancer recurrence (FCR) is a multifaceted concept influenced by individual characteristics, social support, psychological factors. This study aims to identify distinct FCR profiles among breast cancer patients and explore the associated variables with these patterns. A cross-sectional study was conducted from April 2022 to March 2023. A convenience sample of 339 patients completed a questionnaire that assessed general and disease-related data, including the Fear of Progression Questionnaire-Short Form, Social Support Rating Scale, Medical Coping Modes Questionnaire. Statistical analysis involved latent profile analysis (LPA) and multinomial logistic regression. Three latent patterns of FCR were found: the low fear (28.9%), the moderate fear (51.3%), and the high fear (18.0%). The study identified the social support, family monthly income, employment status, utilization of confrontation coping mode and avoidance coping mode, as factors that impacted the FCR. Social support, family monthly income, employment status, and medical coping modes have been found to impact the FCR among newly diagnosed breast cancer patients. Healthcare professionals should focus on addressing FCR at diagnosis and implement effective interventions, such as promoting social support and encouraging adaptive coping, to alleviate this concern. Urgently addressing the FCR in Chinese breast cancer patients is imperative due to its profound influence on their holistic health. Through advanced LPA, we categorized the FCR progression, highlighting risks. These findings have implications for healthcare strategies, offering new insights to manage the FCR and improve patient well-being. Our study adds a fresh perspective to the factors underlying the FCR in breast cancer patients, contributing to the broader comprehension and management of this complex survivorship issue. No patient or public contribution.