Chinese Breast Research Articles

A comparison of Chinese multicenter breast cancer database and SEER database

There are different characteristics of BC in developing countries and developed countries. We intended to study the factors which influence the survival and prognosis of BC between southern China and the United States. (a) To study the two groups BC patients in southern China from 2001 to 2016 and SEER database from 1975 to 2016. (b) To register, collect and analyze the clinicopathological features and treatment information. Our study found that there are significant differences in tumor size, positive lymph node status and KI-67 between southern China and SEER cohort (P < 0.000). The positive lymph node status may be one of the causes of difference of morbidity and mortality of BC patients in China. Furthermore, the differences in treatment methods may also account for the differences between China and seer databases.

The population characteristic analysis in RecurIndex for clinical decision-making on adjuvant therapy for early breast cancer: Results of a real-world study.

e12514 Background: 28-gene signature (RecurIndex) is the first multi-gene panel for recurrence risk prediction after surgery developed from the Asian breast cancer population. In this study, we aimed to report the clinical and genomic characteristics of Chinese early-stage breast cancer patients whose primary lesions have been evaluated by 28-gene signature testing. Methods: In this study, 363 patients were assessed by 28-gene signatures between November 2019 and August 2021. Of these, 330 (90.9%) had stage I-II, hormone receptor-positive, HER2-negative breast cancer, 16 (4.4%) had triple-negative breast cancer (TNBC), and 17 (4.7%) had HER2-enriched breast cancer. The genomic risks of local and distant recurrence were determined by 28-gene signature respectively; the clinical risk was evaluated by the modified Adjuvant! Online. The molecular subtyping of the 28-gene signature was also compared with immunohistochemistry (IHC) status. In the future analysis, we will report the clinical decisions and outcomes of these patients. Results: The 28-gene signature classified 86.8% (n = 315/363) of patients as genomic Low Risk (LR) and 13.2% (n = 48/363) as genomic High Risk (HR) for local recurrence; 83.7% (n = 304/363) and 16.3% (n = 59/363) for distant recurrence. Among clinical HR patient, a total of 72 patients (64.9%) were deemed to be genomic LR of distant recurrence, and a total of 88 patients (79.3%) were deemed to be genomic LR of local recurrence. The concordance of luminal type identified by IHC or 28-gene based molecular subtyping was 99.1% (n = 327/330); TNBC type was 25% (n = 4/16), and HER2 enriched was 70.6% (n = 12/17). Conclusions: This study showed that in clinical HR patients, 64.9% 28-gene LR patients who could waive their adjuvant chemotherapy and 79.3% who could have the adjuvant radiotherapy adjusted. Additionally, the results of IHC and 28-gene signature-based molecular subtyping were highly consistent in luminal type, while the potential value of TNBC and HER2 enriched subtyping identified by the 28-gene signature needs to be further explored in the future.[Table: see text]

A Culturally Sensitive Social Support Intervention for Chinese American Breast Cancer Survivors (Joy Luck Academy): Protocol for a Randomized Controlled Trial.

BackgroundBreast cancer is the most prevalent type of cancer among Asian American women. Chinese American immigrant breast cancer survivors face unique challenges because of cultural and socioecological factors. They report emotional distress and the need for social, emotional, and spiritual support. However, culturally and linguistically appropriate information for managing survivorship health care is often unavailable.ObjectiveTo improve the health outcomes for this underserved and understudied population, we developed, designed, and launched a randomized controlled trial to test the health benefits of a culturally sensitive social support intervention (Joy Luck Academy). In this paper, we describe the research protocol.MethodsThis randomized controlled trial will enroll Chinese-speaking, stage 0 to 3 breast cancer survivors who have completed treatment within the previous 36 months using a community-based participatory research approach. We will randomly assign 168 participants to the intervention or control group. The intervention arm will attend 7 weekly 3.5-hour peer mentor and educational sessions. The control group will receive the educational information. We will assess health outcomes at baseline, immediately after the Joy Luck Academy, and at 1- and 4-month follow-ups. The primary outcome is quality of life, as measured by the Functional Assessment of Cancer Therapy scale. Secondary outcomes include depressive symptoms, positive affect, fatigue, and perceived stress. We will also explore how the intervention influences cortisol levels. To identify how and to whom the program is effective, we will measure social and personal resources and theorized mechanisms and perform qualitative interviews with a subsample of participants to enhance the interpretation of quantitative data.ResultsRecruitment began in February 2015, and data collection was completed in February 2019. We expect to complete data management by August 2021 and publish results in 2022.ConclusionsIf the Joy Luck Academy is demonstrated to be effective, it may be easily disseminated as an intervention for other groups of Asian American immigrant breast cancer survivors. Furthermore, similar programs could be integrated into other diverse communities.Trial RegistrationClinicalTrials.gov NCT02946697; http://clinicaltrials.gov/ct2/show/NCT02946697.International Registered Report Identifier (IRRID)DERR1-10.2196/30950

Germline PALB2 Mutation in High-Risk Chinese Breast and/or Ovarian Cancer Patients.

Simple SummaryBreast cancer is the most commonly diagnosed cancer in women globally. BRCA1 and BRCA2 mutations are most prevalent in hereditary breast cancer and are associated with increased risk of breast and ovarian cancer. The PALB2 (partner and localizer of BRCA2) mutation was found to be associated with an increased risk of breast cancer and one of the most common mutations, after BRCA1 and BRCA2, in non-BRCA1/2 breast cancer patients. The prevalence of the PALB2 mutation in breast cancer varies across different ethnic groups; hence, it is of intense interest to evaluate the cancer risk and clinical association of PALB2 mutation in Chinese breast and/or ovarian cancer patients. The prevalence of the PALB2 mutation in breast cancer varies across different ethnic groups; hence, it is of intense interest to evaluate the cancer risk and clinical association of the PALB2 mutation in Chinese breast and/or ovarian cancer patients. We performed sequencing with a 6-gene test panel (BRCA1, BRCA2, TP53, PTEN, PALB2, and CDH1) to identify the prevalence of the PALB2 germline mutation among 2631 patients with breast and/or ovarian cancer. In this cohort, 39 mutations were identified with 24 types of mutation variants, where the majority of the mutations were frame-shift mutations and resulted in early termination. We also identified seven novel PALB2 mutations. Most of the PALB2 mutation carriers had breast cancer (36, 92.3%) and were more likely to have family history of breast cancer (19, 48.7%). The majority of the breast tumors were invasive ductal carcinoma (NOS type) (34, 81.0%) and hormonal positive (ER: 32, 84.2%; PR: 23, 60.5%). Pathogenic mutations of PALB2 were found in 39 probands with a mutation frequency of 1.6% and 1% in breast cancer and ovarian cancer patients, respectively. PALB2 mutation carriers were more likely have hormonal positive tumors and were likely to have familial aggregation of breast cancer.

Efficacy and safety analysis of Chinese patients in monarchE: Abemaciclib combined with adjuvant endocrine therapy for high risk HR+, HER2- early breast cancer.

522 Background: In monarchE, abemaciclib (oral CDK4&amp;6 inhibitor) plus endocrine therapy (ET) as adjuvant treatment for HR+, HER2- high risk early breast cancer (EBC), demonstrated a statistically significant improvement in invasive disease-free survival (IDFS) compared to ET alone. Here we present the efficacy and safety analysis of Chinese patients from monarchE. Methods: The overall study design was reported previously. Eligible patients were randomized to receive abemaciclib (150 mg BID for 2 years) combined with standard adjuvant ET or ET alone. The primary endpoint was IDFS per STEEP criteria. Secondary endpoints included distant relapse-free survival (DRFS), overall survival, and safety. Exploratory subgroup analyses were conducted among Chinese patients enrolled from Mainland China, Hong Kong, and Taiwan in the intent-to-treat (ITT) population. Results: A total of 501 Chinese patients were randomized to receive abemaciclib plus ET (259 patients) or ET alone (242 patients). At the time of data cutoff (July 8, 2020), 356 (71.1%) patients were still in the 2-year treatment period. A total of 26 IDFS events were observed (11 and 15 events in abemaciclib plus ET and ET arm, respectively). Comparing to ET alone, abemaciclib combined with ET reduced the risk of developing invasive disease or death by 34.3% (HR: 0.657, 95% CI: 0.301, 1.435) for Chinese patients, together with a clinically meaningful improvement in the 2-year IDFS rate (95.6% vs 92.1%). The addition of abemaciclib to ET also resulted in an improvement in DRFS (HR: 0.601, 95% CI: 0.245, 1.477) for Chinese patients, with the 2-year DRFS rate at 96.7% (ET alone: 93.4%). In the abemaciclib arm, the most frequent treatment-emergent adverse events (TEAEs) and grade ≥3 TEAEs: diarrhea (90.3% and 5.0%), leukopenia (76.8% and 21.2%), and neutropenia (76.4% and 23.9%), respectively. Conclusions: Abemaciclib combined with adjuvant ET demonstrated clinically meaningful IDFS and DRFS benefits among Chinese patients with HR+, HER2-, high risk EBC, which was consistent with the ITT population as reported previously. The safety profile of abemaciclib in Chinese EBC patients was consistent with global population and also with that observed in Chinese metastatic breast cancer patients. Clinical trial information: NCT03155997.

The beneficial role of Asian-based RecurIndex test in the prognostic prediction in Chinese male breast cancer patients

RecurIndex, a multigene profiling assay, can predict the risk of local recurrence and distant metastasis in female breast cancer (FBC), but its role in male breast cancer (MBC) remains unclear. In this study, the clinicopathological data of 43 consecutive MBC patients undergoing surgeries between 2009 and 2018 were retrospectively analysed. Their paraffin-embedded tissue sections were examined by RecurIndex test which comprised 2 models: recurrence index for local recurrence (RI-LR) and recurrence index for distant recurrence (RI-DR). Of 43 patients, there were 26 low-risk and 17 high-risk patients assessed by RI-LR, while 17 low-risk and 26 high-risk patients by RI-DR. For RI-LR, tumor N stage showed statistically significant (P < 0.001) between low- and high-risk patients; for RI-DR, differences were pronounced in tumor grade (P = 0.033), T stage (P = 0.043) and N stage (P = 0.003). In terms of clinical outcomes, the overall survival (OS) of low- and high-risk patients stratified by RI-LR showed no statistically significant differences (P = 0.460), while high-risk patients identified by RI-DR had a significantly worse distant recurrence-free survival (DRFS) (P = 0.035), progression-free survival (PFS) (P = 0.019) and OS (P = 0.044) than low-risk patients. Overall, RI-DR can effectively predict the DRFS, PFS and OS of MBC patients and identify those at low risk of recurrence, which may serve as a potential prognostic tool for MBC.

Characteristics of BRCA1/2 pathogenic germline mutations in chinese NSCLC patients and a comparison with HBOC

Background and purposesThe pathogenic BRCA1/2 germline mutations contributed to Hereditary Breast and Ovarian Cancer (HBOC) susceptibility. The features of BRCA1/2 germline mutations in non-small cell lung cancer (NSCLC) have not been systematically studied. Here we performed the first study investigating the characteristics of pathogenic BRCA1/2 germline mutations in Chinese NSCLC patients and compared them with those from Chinese HBOC.MethodsInformation on BRCA1/2 germline mutations from 9010 Chinese NSCLC patients were collected from available studies and analyzed, and compared with the BRCA1/2 germline mutations from Chinese HBOC BRCA1/2 database (LOVD database, 20,523 patients).Results19 (20 carriers, 0.22 %) pathogenic BRCA1 and 60 (66 carriers, 0.73 %) pathogenic BRCA2 germline mutations from NSCLC were identified. The carrier frequency of BRCA1/2 in Chinese NSCLC patients (86/9010 = 0.95 %) was significantly lower than that in Chinese breast and ovary cancer patients (1481/20,523 = 7.2 %) (P < 0.001). We found that frameshift and nonsense mutations were the predominant types of BRCA1/2 mutation in NSCLC, with no obvious hot spot mutations. No significant difference in the ratio of frameshift and nonsense mutations was found between BRCA1 and BRCA2 in NSCLC. 5 out of 19 mutations in BRCA1 and 23 out of 60 mutations in BRCA2 were novel mutations found in NSCLC that have never been reported in Chinese HBOC. A trend of higher percentage of BRCA1 nonsense mutations in the carriers was revealed in NSCLC compared with HBOC, while no such difference was found in BRCA2 in all types of mutations.ConclusionsBRCA1/2 germline mutations from NSCLC exhibited distinct characteristics compared with those from HBOC in Chinese population, including lower carrier frequency than HBOC, higher ratio of nonsense mutations and carriers than HBOC, and novel BRCA1/2 germline mutations never found in HBOC.

Characteristics and subtypes of depressive symptoms in Chinese female breast cancer patients of different ages: a cross-sectional study

PurposeTo identify the characteristics and subtypes of depressive symptoms and explore the relationship between depressive subtypes and age among Chinese female breast cancer patients.MethodIn this cross-sectional study, 566 breast cancer patients were recruited from three tertiary comprehensive hospital in Shandong Province, China through convenient sampling from April 2013 to June 2019. Depressive symptoms were measured using the Patient Health Questionnaire-9 (PHQ-9). Data analyses included descriptive analyses, latent class analysis.ResultsThere were significant differences in specific depressive symptoms by age group, but no significant difference in total scores on PHQ-9. The depressive subtypes were severe (Class 4), relatively severe (Class 3; with lower psychomotor agitation/retardation and suicidal ideation), moderate (Class 2; with higher psychomotor agitation/retardation and suicidal ideation), and mild depressive symptoms (Class 1). The distribution of depression subtypes is different in various age groups. In the 45–59 age groups, severe symptoms subtype showed the highest ratios (i.e. 50.3%).ConclusionThis is the first study that analyses depressive symptom characteristics and identifies depressive subtypes in Chinese women with breast cancer across ages to explore symptom heterogeneity. Our findings can contribute to identifying the mechanisms behind these relationships and developing targeted interventions for patients with specific depressive subtypes.

1206P Computing HRD score by a capture-based NGS panel reveal its prevalence in Chinese breast, ovarian, prostate and pancreatic cancer patients

Previous studies have shown the treatment indication for poly(ADP-ribose) polymerase inhibitors could expand to patients with instable genome, characterized by homologous recombination deficiency (HRD) status beyond those with BRCA mutations (NOVA trials, ARIEL2/3 trials and QUADRA trials). Recent studies showed that pancreatic and prostate cancer patients with BRCA mutations could also benefit from PARPi treatment. Therefore, evaluating HRD status in Breast, Ovarian, Prostate and Pancreatic cancers could reveal additional cases who may potentially benefit from this novel target therapy. We developed an HRD score algorithm, termed as 3DMedHRD, to characterize genomic instability of tumors using over 10000 SNPs. It combines three classical factors, including loss of heterozygosity score (LOH), telomeric allelic imbalance score (TAI), large-scale state transition score (LST), along with an optimized tumor ploidy and purity prediction algorithm. The method was trained using 45 BRCA-deficient and 25 BRCA-intact tumor samples. HRD score cutoff was determined to achieve 95% sensitivity. BRCA-deficiency was defined to possess deleterious germline or somatic mutation in BRCA1 or BRCA2, with loss of second allele by LOH in the affected gene. The cutoff was subsequently evaluated by an independent cohort to demonstrate similar performance. We then applied the model to characterize the population frequency of HRD positivity across tumor types using samples collected in a local LDT lab in Shanghai. The observed frequency of patients with deleterious BRCA 1/2 mutation are 10.4%, 21.6%, 5.1% and 4.1% for Breast (n = 106), Ovarian (n = 134), Prostate (n = 59), Pancreatic cancers (n = 270) respectively. The corresponding percentage of HRD positive cases in BRCA wildtype patients are 38.7%, 35.1%, 10.2% , 5.6%. When considering patients with either BRCA1/2 mutations or positive HRD status, the population frequencies are 49.1%, 56.7%, 15.3%, 9.6%. We here report the development of the 3DMedHRD score as a biomarker to quantify the “genomic scar” of tumor tissues. A retrospective analysis of over 500 cases first time revealed HRD population frequencies in a Chinese cohort.

Genetic mutation profile of Chinese HER2-positive breast cancers and genetic predictors of responses to Neoadjuvant anti-HER2 therapy

PurposeDespite the therapeutic success of existing HER2-targeted therapies, tumors respond quite differently to them. This study aimed at figuring out genetic mutation profile of Chinese HER2-positive patients and investigating predictive factors of neoadjuvant anti-HER2 responses.MethodsWe employed two cohorts. The first cohort was comprised of 181 HER2-positive patients treated at Guangdong Provincial People’s Hospital from 2012 to 2018. The second cohort included 40 patients from the first cohort who underwent HER2-targeted neoadjuvant chemotherapy. Genetic mutations were characterized using next-generation sequencing. We employed the most commonly used definition of pathological complete response (pCR)-eradication of tumor from both breast and lymph nodes (ypT0/is ypN0).ResultsIn Chinese HER2-positive breast cancer patients, TP53 (74.6%), CDK12 (64.6%) and PIK3CA (46.4%) have the highest mutation frequencies. In cohort 2, significant differences were found between pCR and non-pCR groups in terms of the initial Ki67 status, TP53 missense mutations, TP53 LOF mutations, PIK3CA mutations and ROS1 mutations (p = 0.028, 0.019, 0.005, 0.013, 0.049, respectively). Furthermore, TP53 LOF mutations and initial Ki67 status (OR 7.086, 95% CI 1.366–36.749, p = 0.020 and OR 6.007, 95% CI 1.120–32.210, p = 0.036, respectively) were found to be predictive of pCR status.ConclusionTP53 LOF mutations and initial Ki67 status in HER2-positive breast cancer are predictive of pCR status after HER2-targeted NACT.

Abstract IA22: Understanding the unique experience among Chinese immigrant breast cancer survivors

Abstract Purpose: Little is known about the psychosocial barriers among immigrant Chinese American breast cancer survivors. The aim of the present study was to explore the psychosocial needs and challenges of Chinese American immigrant breast cancer survivors, and to develop and test culturally sensitive interventions to overcome these challenges. Methods: Study one used the expressive writing approach to explore the experiences among Chinese immigrant breast cancer survivors. The participants were recruited through community-based organizations in Southern California, most of whom were diagnosed at Stages I and II (33% and 48%, respectively). Participants, on average, had been living in the USA for 19 years. Participants were asked to write three 20-minute essays related to their experience with breast cancer (in 3 weeks). Participants' writings were coded with line-by-line analysis, and categories and themes were generated. Study two used the expressive writing approach as an intervention among this population. Results: Study one found that emotion suppression, perceived stigma about being a breast cancer survivor, and concerns about fulfilling multiple roles were reflected in the writings. Participants indicated their reluctance to disclose cancer diagnosis to family and friends and mentioned barriers of communicating with their husbands. Participants felt unfamiliar with the health care system and encountered language barriers. On the other hand, post-traumatic growth was also reflected in the writings. Study two found that expressive writing intervention facilitated post-traumatic growth and increased quality of life among this population. Conclusions: Counseling services addressing concerns about stigma and communication among family members may benefit patients' adjustments. Tailor-made information in Chinese about diagnosis and treatment for breast cancer and health insurance in the USA as well as interventions to facilitate finding benefits and to reduce stress and stigma may also help patients go through the course of recovery. Citation Format: Qian Lu, Qiao Chu, Krystal Warmoth, Nelson Young, Lucy Young, Alice Loh, Carol Wang. Understanding the unique experience among Chinese immigrant breast cancer survivors [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr IA22.

Abstract A060: Socioeconomic status and quality of life among Chinese American breast cancer survivors: The role of post-traumatic growth

Abstract Purpose: Socioeconomic disparities in psychosocial adjustment to breast cancer has garnered little attention. Those who are medically underserved with little to no access to quality health care are more likely to be diagnosed with late-stage cancer, have more complications, and face psychosocial and cultural factors that impact their quality of life. Socioeconomic status (SES) is a multidimensional construct that is typically comprised of income, education, and occupation. Recent research suggests that these indicators impact cancer health in independent manners. Moreover, increasing evidence supports the health protective features of having meaning in life. A recurrent theme is resilience – the ability to regain or maintain well-being in the face of adversity. The perceived benefits one reports (e.g. better relationship quality, greater sense of self-efficacy, etc.) after experiencing a stressful life event is known as post-traumatic growth (PTG). This study examines the relationships between SES indicators (e.g. education, household income), quality of life (QOL), and the role of PTG as an underlying mechanism in the impact of SES in psychosocial adjustment to breast cancer among Chinese American breast cancer survivors (CABCS). Methods: 136 CABCS completed a baseline questionnaire from a larger, intervention study. Results: Education and household income were all positively related to overall quality of life. Education was positively related to functional QOL and additional breast cancer concerns. Annual household income was positively related to all QOL domains. Regression analyses revealed an association between household income with PTG and PTG with overall QOL. Bootstrapping analyses supported a full mediation as the indirect effect of household income on overall QOL through PTG was statistically significant. Further examining QOL subscales, PTG was associated with better social QOL and household income showed a significant indirect effect on social QOL through PTG suggesting PTG fully mediates the effect of household income on social QOL. PTG was associated with better emotional QOL and less breast cancer concerns. However, the total effect of household income on emotional QOL was non-significant. The total effect of PTG on breast cancer was marginally significant (p = .06). Analyses for education failed to reveal any significant direct or indirect effect on overall QOL and its subscales through PTG. Conclusion: These findings suggest that SES indicators such as household income and educational attainment are differentially related to QOL domains among CABCS. Household income is linked to better social and emotional QOL through reported PTG suggesting that findings benefits within adversity including reported meaning may enhance well-being. This underscores the differential role of socioeconomic indicators when assessing health outcomes and the importance of implementing psychosocial interventions that facilitate PTG in improving QOL among immigrant cancer survivors. Citation Format: Carol Wang, Qian Lu. Socioeconomic status and quality of life among Chinese American breast cancer survivors: The role of post-traumatic growth [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr A060.

Abstract A099: Benefit finding and depressive symptoms: The role of socioeconomic status and positive affect among immigrant cancer survivors

Abstract Purpose: Benefit finding, or finding benefits within adversity, has been shown to be linked to better psychological well-being among those who have undergone trauma such as cancer patients and survivors of natural disasters. According to the National Cancer Institute, up to 25% of cancer survivors experience symptoms of depression. Positive emotions have been shown to promote positive meaning and buffer against depressive symptoms among individuals whom have undergone through challenging life circumstances (Tugade &amp; Frederickson, 2004; Frederickson et al., 2003) and resilient individuals report using greater positive emotions following a challenging task which predicted faster cardiovascular recovery (Tugade &amp; Frederickson, 2004). Furthermore, literature has documented ethnic and racial disparities in cancer survival and care. However, socioeconomic disparities in psychosocial adjustment to breast cancer have garnered little attention. This study addresses this gap by examining the association between benefit finding and depressive symptoms, state positive affect as an underlying mechanism, and the potential moderating role of socioeconomic indicators (i.e., personal income, household income, and education) among Chinese American breast cancer survivors (CABCS). Methods: Ninety-six CABCS completed a questionnaire packet assessing these variables. Results: Benefit finding was positively associated with positive affect and negatively associated with depressive symptoms. Educational attainment but neither personal nor household income was negatively associated with depressive symptoms. Positive affect explained the relationship between benefit finding and depressive symptoms. Only educational attainment moderated the relation between benefit finding and depressive symptoms such that benefit finding was most beneficial for those with high educational attainment. Conclusion: This study suggests that benefit finding is linked to lower depressive symptoms among CABCS through the mechanism of positive emotions. That is, positive emotions may broaden an individual's personal resources (e.g., social and psychological) that enhance health and well-being and help regulate negative emotions, thereby promoting resiliency. Furthermore, socioeconomic indicators such as education and income may be differentially related to depressive symptoms among CABCS. These findings underscore the importance of implementing psychosocial interventions targeted at increasing benefit finding and positive affectivity to address socioeconomic disparities among immigrant cancer survivors. Citation Format: Carol Wang, Qian Lu. Benefit finding and depressive symptoms: The role of socioeconomic status and positive affect among immigrant cancer survivors [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr A099.

A nomogram based on genetic and clinicopathologic features to predict the nonsentinel lymph node metastases in Chinese women breast cancer patients.

e12577 Background: Sentinel lymph node biopsy (SLNB) is the standard treatment for breast cancer patients with clinically negative axilla. However, axillary lymph node dissection (ALND) is still the standard care for sentinel lymph node (SLN) positive patients. Clinical data reveals 20–60 % of patients without non-sentinel lymph node metastasis (NSLNM) after ALND. Unnecessary ALND increases the risk of lymphedema and detracts from quality of life. In this study, we expect to develop a nomogram based on genetic and clinicopathologic features to predict the risk of NSLN metastasis in SLN-positive Chinese women breast cancer patients. Methods: This retrospective study collected data from 310 women breast cancer patients who underwent SLNB followed by ALND and without any neo-adjuvant therapy in Chinese PLA General Hospital, China, between 2016 and 2017. Genetic features contain 96 single nucleotide polymorphisms (SNPs) associated with breast cancer susceptibility and prognosis based on the GWAS studies and clinical information. SNP genotyping was identified by the quantitative PCR detection platform. The genetic features were divided into two clusters by the gene functions and signaling pathways. The polygenic risk score (PRS) was used to evaluate the combined effect of each SNP cluster. Least absolute shrinkage and selection operator (LASSO) regression model was adopted for feature selection and nomogram construction. Internal validation was performed and the area under ROC curve (AUC) was assessed. Results: 81 patients of 310 patients (26%) had a positive axillary NSLNM. The LASSO regression analysis identified the clinicopathologic characteristics including molecular subtype, cN-stage, number of positive SLNs and number of negative SLNs as significant predictors of NSLNM. Furthermore, two SNP clusters were also showed statistically significant in the prediction of NSLNM. In internal validation, the average AUC of the nomogram was 0.795 and the model was well calibrated. Conclusions: We present a new nomogram by combining genetic and clinicopathologic factors to achieve higher sensitivity and specificity comparing with traditional clinicopathologic factors to predict NSLNM in Chinese women breast cancer. It is recommended that more validations are required in prospective studies among different patient populations.

Distinct genomic profiles of 589 Chinese early-stage breast cancer.

552 Background: Extensive efforts by The Cancer Genome Atlas (TCGA) Network had provided much of our current understanding of the molecular profile of various solid tumors including breast tumors; however, Asian patients were underrepresented in this cohort. In this study, we aimed to elucidate the comprehensive genetic alteration profile of early-stage breast tumors among Chinese patients. Methods: Surgical tissue samples from 589 Chinese women with stage I-III breast cancer with various histology and molecular subtype consecutively diagnosed at Guangdong Provincial People’s Hospital were sequenced using a panel targeting 520 cancer-related genes spanning 1.64Mb of the human genome. Clinical and genomic data from our cohort was compared with publicly-available data from 1,046 stage I-III breast cancer patients from the TCGA dataset. Results: Based on the analysis of the genetic alteration profile from our cohort, at least one genetic alteration was observed from 98% of the tumor samples, with TP53 (47%), PIK3CA (45%), ERBB2 (30%), and CDK12 (18%) as the most commonly altered genes. The most common genetic alteration types were copy number amplification (43.6%) and missense mutations (36.8%). As compared with the TCGA dataset, our cohort is mostly composed of women 50 years and younger (59.1% vs. 30.4%, P&lt; 0.001), with significantly fewer patients with lobular carcinoma histology (2.4% vs. 19.0%, P&lt; 0.001), and significantly more patients with pathologic stage I tumors (23.3% vs. 17.3%, P= 0.012). Consistently, genetic alterations detected from our cohort affected genes involved in PI3K (63% vs. 56%, P= 0.009) and cell cycle (23% vs. 35%, P&lt; 0.001) pathways, with statistically different genetic alteration rates as compared with the TCGA dataset. Comparison of genetic alteration profile between the two cohorts revealed that our cohort had more frequent genetic alterations in genes including PIK3CA ( P&lt; 0.001), TP53, particularly in hotspot mutations Q192* ( P&lt; 0.001) and A307V/del ( P= 0.02), and ERBB2 amplification ( P&lt; 0.001). Conclusions: Our study contributes to the understanding of the key pathways and specific genetic alterations harbored by Chinese patients with early-stage breast cancer that could potentially be developed as markers of treatment response to targeted therapeutics.

The role of acculturation in the relationship between self-stigma and psychological distress among Chinese American breast cancer survivors

ABSTRACT Attitudes about breast cancer have improved in the USA, yet stigma is still present in some ethnic and immigrant populations and affecting survivors’ experiences. Chinese American breast cancer survivors report negative beliefs and stigma to be a major stressor; this could result in mental health consequences. We hypothesized that greater self-stigma will be related to greater psychological distress (namely, depressive symptoms, and perceived stress). Furthermore, we expected that the association between self-stigma and psychological distress will be stronger among Chinese American breast cancer survivors who are less acculturated to the USA than those who are highly acculturated. One hundred and thirty-six Chinese American breast cancer survivors completed questionnaires that measured self-stigma, acculturation, depressive symptoms, perceived stress, and demographic information. Hierarchical linear regressions were conducted to examine the main effect of stigma on depressive symptoms and perceived stress, and the moderating effect of acculturation. As predicted, self-stigma was associated with greater depressive symptoms and perceived stress among Chinese American breast cancer survivors, especially those who are less acculturated. Self-stigma may play a part in psychological adjustment among Chinese American breast cancer survivors. Interventions that incorporate techniques to reduce self-stigma could be beneficial for Chinese American breast cancer survivors, especially for those who are less acculturated to American society.

Abstract P5-03-10: The spectrum of BRCA1 and BRCA2 mutations and clinicopathologic characteristics of young-onset breast cancer in BRCA-carriers and non-carriers

Abstract Background: For now, Seldom studies have reported that relationship between BRCA1/2 mutation and their clinical characteristics in young-onset breast cancers. This study is the first article which characterizes the risk factor profiles in Chinese patients selected by the age of onset (&amp;lt;40 years old).Patient and method:A total of 1371 consecutive unselected Chinese young-onset breast cancer patients were collected form Fujian Union hospital, China, screened for germline BRCA1/2 mutation. The full-exome sequencing in the next generation sequencing technology was performed in all patients to examine the BRCA1/2 mutation.Result: In our study, 25 (1.8%) and 61 (4.4%) patients were identified with BRCA1 and BRCA2 mutation among the unselected early-onset breast cancer patients, respectively. BRCA1 mutations were associated with pregnancies (p=0.026), BRCA1-carriers had a higher likelihood of HR positive(p&amp;lt;0.001), or HER-2 negative(p&amp;lt;0.001), or high grade(p=0.002) than non-carriers. Among BRCA2 mutations, the age of onset was younger than non-carriers(P=0.017), BRCA2-carriers were more likely to have lymph node metastasis(P=0.004). with HR positive or HER-2 negative were likely to detected positive for BRCA2(p&amp;lt;0.001). Citation Format: Lili Chen, Fangmeng Fu, Jinxing Lv, Chuan Wang. The spectrum of BRCA1 and BRCA2 mutations and clinicopathologic characteristics of young-onset breast cancer in BRCA-carriers and non-carriers [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-03-10.

Comprehensive profiling of BRCA1 and BRCA2 variants in breast and ovarian cancer in Chinese patients.

The identification and interpretation of germline BRCA1/2 variants become increasingly important in breast and ovarian cancer (OC) treatment. However, there is no comprehensive analysis of the germline BRCA1/2 variants in a Chinese population. Here we performed a systematic review and meta-analysis on such variants from 94 publications. A total of 2,128 BRCA1/2 variant records were extracted, including 601 from BRCA1 and 632 from BRCA2. In addition, 414, 734, 449, and 307 variants were also recorded in the BIC, ClinVar, ENIGMA, and UMD databases, respectively, and 579 variants were newly reported. Subsequent analysis showed that the overall germline BRCA1/2 pathogenic variant frequency was 5.7% and 21.8% in Chinese breast and OC, respectively. Populations with high-risk factors exhibited a higher pathogenic variant percentage. Furthermore, the variant profile in Chinese is distinct from that in other ethnic groups with no distinct founder pathogenic variants. We also tested our in-house American College of Medical Genetics-guided pathogenicity interpretation procedure for Chinese BRCA1/2 variants. Our results achieved a consistency of 91.2-97.6% (5-grade classification) or 98.4-100% (2-grade classification) with public databases. In conclusion, this study represents the first comprehensive meta-analysis of Chinese BRCA1/2 variants and validates our in-house pathogenicity interpretation procedure, thereby providing guidance for further PARP inhibitor development and companion diagnostics in the Chinese population.

Pharmacokinetics of pertuzumab administered concurrently with trastuzumab in Chinese patients with HER2-positive early breast cancer.

In the APHINITY study (NCT01358877, BIG 4-11/BO25126/TOC4939G), pertuzumab added to trastuzumab and chemotherapy significantly improved invasive disease-free survival as adjuvant treatment for patients with HER2-positive early breast cancer. The objective of this analysis was to assess the pharmacokinetics of pertuzumab in combination with trastuzumab in Chinese patients with early breast cancer. Samples for pertuzumab and trastuzumab pharmacokinetic analysis were taken from Chinese patients during cycle 1 of treatment and at steady-state in cycle 10. Noncompartmental analysis was used to estimate minimum and maximum serum concentrations (Cmax and Cmin), area under the concentration-time curve, clearance, and other pharmacokinetic parameters. In 15 patients, mean steady-state Cmax and Cmin pertuzumab serum concentrations (368 ± 177 μg/ml, and 122 ± 47 μg/ml, respectively) were numerically higher than observed previously in a pharmacokinetic analysis of the global population in APHINITY and in patients treated in the metastatic setting. The geometric mean ratio and corresponding 90% confidence interval for trastuzumab Cmax and Cmin in the presence (n = 15) or absence (n = 17) of pertuzumab were 104.6 (91.09-120) and 98.23 (84.58-114), respectively, indicating no apparent impact of pertuzumab on the pharmacokinetics of trastuzumab. Increases in pertuzumab Cmax and Cmin were not associated with an increase in adverse events. The APHINITY Chinese pharmacokinetic substudy analysis supports the dosing regimen for pertuzumab (840 mg loading dose followed by 420 mg maintenance doses every 3 weeks administered by intravenous infusion) in a Chinese HER2-positive early breast cancer patient population.

Cell Counts, rather than Proportion, of CD8/PD-1 Tumor-Infiltrating Lymphocytes in a Tumor Microenvironment Associated with Pathological Characteristics of Chinese Invasive Ductal Breast Cancer.

Objective This study is aimed at investigating the association of exhausted CD8+ tumor-infiltrating lymphocytes with clinic-pathological factors. Methods 133 patients diagnosed with primary invasive ductal breast cancer were recruited into the cross-sectional study consecutively. Immunohistochemistry was used to detect biomarker expression on formalin-fixed and paraffin-embedded sections. Double staining of CD8 and PD-1 was conducted on lymphocytes. Results The proportion of CD8+/PD-1− TILs was 16% among patients with axillary lymph node metastasis, significantly lower than those without metastasis (24%). The expression of CK7, CK20, or Ki-67 was not related with the proportion of phenotypes of CD8/PD-1 TILs. Younger patients had more cell counts of CD8+/PD-1− TILs than elderly patients (18/HPF vs. 9/HPF, p < 0.05). Patients with axillary lymph node metastasis had less CD8+/PD-1− TILs than those without metastasis (11/HPF vs. 27/HPF, p < 0.05). Median counts of CD8+/PD-1− TILs among patients with CK20 and E-Cad expression were 33/HPF and 14/HPF, significantly higher than those among patients with negative CK20 (16/HPF) and E-Cad expression (6/HPF). Ki-67 index had a significant correlation with cell counts of CD8+/PD-1+ TILs and CD8+/PD-1− TILs, and the correlation coefficients were 0.19 and 0.21 (p < 0.05), respectively. Conclusion The proportion of CD8+/PD-1− TILs was related with metastatic status of the axillary lymph node but cell counts of CD8+/PD-1− TILs were related with metastatic status of the axillary lymph node and expression of CK7, CK20, E-Cad, and Ki-67. Absolute cell counts, not proportion of CD8/PD-1 TILs, were more likely to distinguish clinic and pathologic characteristics of breast cancer.