Diagnosis Of Metastatic Breast Cancer Research Articles

Identification of a profile of serum tumor markers for the diagnosis of metastatic breast cancer

Identification of a profile of serum tumor markers for the diagnosis of metastatic breast cancer

Incidence, risk factors and survival of patients with brain metastases at initial metastatic breast cancer diagnosis in China

PurposeTo characterize the incidence, risk factors and survival of patients with brain metastases at initial diagnosis of metastatic breast cancer (MBC) in China. MethodsThe China National Cancer Center database was used to identify 2087 MBC patients diagnosed between 2003 and 2015. Clinicopathological features, treatment and survival information were extracted. Multivariable logistic and Cox regression were performed to determine factors predictive of brain metastases at MBC diagnosis and survival, respectively. ResultsBrain metastases occurred in ninety patients (4.3%) at MBC diagnosis, and in 27 patients (2.5%), 42 patients (7.2%) and 21 patients (5.2%) with hormone receptor positive, human epidermal growth factor receptor 2 negative (HR + HER2-), HER2-positive and triple negative breast cancer (TNBC), respectively. HER2-positive subtype (OR = 2.38; 95% CI 1.40–4.04; p < 0.0001), TNBC subtype (OR = 1.89; 95% CI 1.02–3.51; p = 0.005), and metastases to all three sites of bone, liver and lungs (OR = 3.23; 95% CI 1.52–6.87; p = 0.002) were shown to increase the risk of BM at MBC diagnosis. Median survival after BM was 23.7 months. First-line tyrosine kinase inhibitors (TKI) improved survival compared to trastuzumab-based regimen (44.9 vs 35.4 months, p = 0.09). Factors that independently decreased BM death risk were ECOG<2, brain metastases only and multidisciplinary treatment. ConclusionHER2-positive and TNBC subtypes have a higher incidence of BM at initial MBC diagnosis. Brain screening might be considered in patients with HER2-positive disease at MBC diagnosis, and further prospective randomized study is warranted.

Trends and patterns in the use of opioids among metastatic breast cancer patients

Opioid use among metastatic breast cancer (MBC) patients has not been well-studied. This study examined the trends and patterns of opioid use among working-age, privately insured patients diagnosed with MBC. Using MarketScan data, we identified female patients diagnosed with MBC in 2006–2015. We determined the proportion of patients who filled a prescription for an opioid and calculated days’ supply and daily morphine milligram equivalents (MMEs) from 1 year prior to diagnosis till 1 year after. We assessed the trend in opioid use over the 10-year study period and examined opioid usage patterns after the diagnosis of MBC. Among 24,752 patients included, 11,579 (46.8%) had an opioid prescription within 1 year before diagnosis of MBC, and 20,416 (81.4%) had an opioid prescription within 1 year after diagnosis. The proportion of patients with opioid prescriptions after diagnosis was relatively stable from 2006 to 2015. However, both the median daily MME and median days’ supply decreased over time with most of the decline from the subgroup of patients with prior prescription opioid use. Most patients received an opioid prescription in the first month after diagnosis (57.3%), dropping to approximately 20% from 3 to 12 months after diagnosis. Also, the median days’ supply increased substantially during the year after diagnosis for patients who received opioids (from 7 to 19). Most women with MBC require opioid analgesia within the first month after diagnosis. Judicious, long-term management of pain after diagnosis of MBC will continue to be necessary for many patients.

Impact of body mass index on overall survival in patients with metastatic breast cancer

BackgroundHigh Body mass index (BMI) is a risk factor for breast cancer among postmenopausal women and an adverse prognostic factor in early-stage. Little is known about its impact on clinical outcomes in patients with metastatic breast cancer (MBC). MethodsThe National ESME-MBC observational cohort includes all consecutive patients newly diagnosed with MBC between Jan 2008 and Dec 2016 in the 18 French comprehensive cancer centers. ResultsOf 22 463 patients in ESME-MBC, 12 999 women had BMI data available at MBC diagnosis. Median BMI was 24.9 kg/m2 (range 12.1–66.5); 20% of women were obese and 5% underweight. Obesity was associated with more de novo MBC, while underweight patients had more aggressive cancer features. Median overall survival (OS) of the BMI cohort was 47.4 months (95% CI [46.2–48.5]) (median follow-up: 48.6 months). Underweight was independently associated with a worse OS (median OS 33 months; HR 1.14, 95%CI, 1.02–1.27) and first line progression-free survival (HR, 1.11; 95%CI, 1.01; 1.22), while overweight or obesity had no effect. ConclusionOverweight and obesity are not associated with poorer outcomes in women with metastatic disease, while underweight appears as an independent adverse prognostic factor.

Utilizing Data Visualization to Identify Survival and Treatment Differences Between Women With De Novo and Recurrent Metastatic Breast Cancer

IntroductionDe novo stage IV metastatic breast cancer (MBC) and recurrent MBC are considered the same when determining guideline-based care, but differences in treatment patterns exist. Data visualization can be used to understand these differences and optimize treatment delivery. Patients and MethodsThis retrospective study evaluated treatment patterns for de novo and recurrent MBC using the American Society of Clinical Oncology’s CancerLinQ Discovery database. Spatiotemporal graphics depicting treatment data were generated for MBC subtype and stratified by de novo and recurrent MBC. Descriptive statistics for categorical and continuous variables were calculated. ResultsWe identified 1668 patients diagnosed and treated for MBC: 391 patients with HER2+ MBC, 767 patients with HR+/HER2− MBC, and 510 patients with triple-negative MBC. Median survival from MBC diagnosis for patients with de novo MBC and recurrent MBC was 1.4 years (interquartile range, 0.6-3.0) and 1.8 years (interquartile range, 0.7-4.5), respectively. Both patients with de novo and recurrent HER2+ MBC were often treated with continuous HER2-targeted therapy. Patients with de novo HR+/HER2− MBC often received chemotherapy followed by hormone therapy. This contrasted with treatment trends observed among patients with recurrent HR+/HER2− MBC who, after receiving chemotherapy, seldom went on to receive hormone therapy. Patients diagnosed with triple-negative MBC displayed less heterogeneous treatment trends. ConclusionThere are observable differences in survival and practice patterns between de novo and recurrent MBC. Visualization techniques are effective in assessing large databases and could give researchers and clinicians a clearer understanding of how survival differs by disease subtype, diagnosis status, and practice patterns.

Impact of Primary Subtype on Pattern of Metastases and Survival in Young Women with Metastatic Breast Cancer

Metastatic breast cancer is a heterogeneous disease that varies in biology and organ involvement, and can have a more aggressive course in young patients. This study aimed to describe the pattern of distant metastases of young women with stage 4, or metastatic, breast cancer (MBC). A retrospective study was performed examining women diagnosed with MBC at age 50 years or younger and managed at our institution between 2001 and 2018. Data including primary breast cancer receptor status (ER, PR, and HER2) and distant metastases at MBC diagnosis were recorded. Patients were classified into groups based on receptor status. Metastatic pattern of various MBC groups was assessed using Chi-Square test. Kaplan-Meier method was used to analyze overall survival. 485 patients were eligible for this study. Median age at MBC diagnosis was 42 years (range 25 to 50). Median follow-up time for all patients was 7.1 years. Median survival for all patients is shown in table 1. Primary breast cancer in 230 patients (47%) was ER+ &/or PR+ & HER2- (HR+HER2-), in 78 patients (16%) was ER- & PR- & HER2- (triple-negative), in 59 patients (12%) was ER+ & /or PR+ & HER2+ (HR+HER2+), in 51 patients (11%) was HER2+ & ER- & PR- (HER2+HR-), and in 67 patients (14%) was unclassified. Almost all unclassified patients had unknown HER2 status (65 patients) and received their breast cancer diagnosis prior to 2001 when HER2 testing was not universal, but the majority (45 patients) were known to be hormone receptor positive. 102 patients (21%) had MBC at first diagnosis of breast cancer. The incidence of bone metastasis, brain metastasis, and single metastasis are shown in the table 1. HR+HER2-, HR+HER2+, and unclassified patients had a significantly higher incidence of bone metastasis at MBC diagnosis compared with triple negative and HER2+HR- patients (p<0.05). Conversely, triple negative and HER2+HR- patients had a significantly higher incidence of brain metastasis at MBC diagnosis compared with HR+HER2-, HR+HER2+, and unclassified patients (p<0.05). Incidence of single metastasis at MBC diagnosis was similar across all groups (p = 0.861). Of the 75 patients with single metastasis, 50 had a bone metastasis, 9 had a brain metastasis, and 16 had a metastasis to another site. At MBC diagnosis in young women, the incidence of bone and brain metastasis in HR+HER2+ patients may be closer to that of HR+HER2- patients rather than HER2+HR- patients. In our cohort, the incidence of single metastasis did not appear to vary across primary subtypes.Abstract 2095; TableAll Patients (n = 485)HR+HER2- (n = 230)Triple-negative (n = 78)HR+HER2+ (n = 59)HER2+HR- (n = 51)Unclassified (n = 67)P-valueBone metastasis at MBC diagnosis322 (66%)175 (76%)37 (47%)44 (75%)19 (37%)47 (70%)p<0.05Brain metastasis at MBC diagnosis53 (11%)15 (7%)16 (21%)7 (12%)10 (20%)5 (7%)p<0.05Single metastasis at MBC diagnosis75 (15%)35 (15%)15 (19%)9 (15%)6 (12%)10 (15%)P = 0.861Median Survival (years)3.43.51.45.33.93.1p<0.05 Open table in a new tab

S2706 Metastatic Breast Cancer Presenting as Acute Liver Failure

INTRODUCTION: Up to 20% of acute liver failure (ALF) cases have no known etiology. Of the many causes, initial presentation of metastatic carcinoma is rare, with malignant infiltration of the liver usually diagnosed postmortem. We present a case of fulminant liver failure caused by a new diagnosis of metastatic breast cancer. CASE DESCRIPTION/METHODS: A 55 year old African American female with no significant medical history presented with fatigue and jaundice for one month and one week of pruritus and lower extremity edema. On presentation, she had a MELD-Na of 38 with mild confusion, therefore prompting a rapid inpatient liver transplant evaluation for ALF. Physical exam revealed an obese female in no distress, a distended but soft abdomen with hepatomegaly, scleral icterus, and pitting edema. Further history regarding medications and family history was unrevealing other than having immigrated from Liberia in 2000, a history of a positive PPD with negative chest x-ray follow up, and not up to date on cancer screening. An abdominal ultrasound revealed cirrhotic morphology of the liver, ascites, and marked hepatic echogenicity. Paracentesis fluid was negative for SBP with a SAAG of 2.5 and fluid protein <1.0. An abdominal MRI needed for listing revealed an enlarged liver that was replaced by innumerable ring-enhancing lesions concerning for metastasis (Image 1). A non-targeted liver biopsy revealed metastatic carcinoma consistent with breast primary with no underlying cirrhosis (Images 2 and 3). Transplant workup was terminated and the patient was referred to Oncology and Palliative Care for further management. DISCUSSION: Diffuse metastatic breast cancer causing ALF is rare. Like most patients with ALF, our patient had a rapid decline with symptoms specific to hepatic failure only. Confirming prior liver disease is of paramount importance prior to listing which is why a non-targeted biopsy was obtained in our patient prior to receiving the MRI results. This diagnosis of breast cancer presenting as ALF was surprising given the acuity, lack of prior history or symptoms, and signs of cirrhosis. Rare presentations such as this argue towards liver biopsy prior to listing fulminant liver failure patients of unknown etiology, which is currently not required.Figure 1.: MRI.Figure 2.: H&E: liver with metastatic tumor cells.Figure 3.: GATA-3 immunohistochemical stain (IHC): nuclear positivity of tumor cells (specific to breast primary).

Patients included at CAPO/IPOS World Congress of Psycho-Oncology 2019. Reflections from the invited advocates

Patients included at CAPO/IPOS World Congress of Psycho-Oncology 2019. Reflections from the invited advocates

Prognostic Value and Influence of Receptor Conversion on Treatment Regimen in Metastatic Breast Cancer at the First Time of Recurrence

Purpose: At the first time of metastatic breast cancer recurrence, conversion of the receptors status may occur between primary lesions and metastatic lesions, including the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). Whether the decision of the treatment regimen is based on the primary receptor status or that of metastatic lesions is still unclear. Methods: This study enrolled 411 female patients with a diagnosis of metastatic breast cancer at the first time of recurrence to explore the influence of receptor conversion on prognosis prediction and treatment regimen of patients with metastatic breast cancer. Results: ER and PR changes from negative to positive are both prognostic factors for patients with breast cancer. Patients receiving endocrine therapy showed a better survival after recurrence than those using chemotherapy alone in the ER or PR Prim– Met+ subgroup. Patients in the HER2 Prim– Met+ subgroup using HER2-targeted therapy in multilines showed a post-recurrence survival advantage. In the bone re-biopsy subgroup, the PR change from positive to negative appeared to be more frequent than at other re-biopsy sites. Conclusions: Patients with metastatic breast cancer should perform re-biopsy to clarify the receptor status of the first metastatic lesions, which may provide clinicians valuable evidence to conduct treatments with higher precision.

Metastatic Breast Cancer Presenting as Acute Liver Failure

Acute liver failure (ALF) is a rare clinical syndrome, with up to 20% of cases having no known etiology. Of the many causes, initial presentation of metastatic carcinoma is rare, with malignant infiltration of the liver usually diagnosed postmortem. We present a case of fulminant liver failure caused by a new diagnosis of metastatic breast cancer. A 55-year-old female with no significant medical history presented with fatigue and jaundice for one month and one week of pruritus and lower extremity edema. On presentation, she had a MELD-Na of 38 with confusion, therefore prompting rapid liver transplant evaluation. An abdominal ultrasound revealed cirrhotic morphology of the liver, ascites, and marked hepatic echogenicity. An abdominal MRI needed for listing revealed an enlarged liver that was replaced by innumerable ringenhancing lesions concerning for metastasis. A liver biopsy was performed and revealed metastatic carcinoma consistent with breast primary with no underlying cirrhosis. Transplant workup was terminated, and the patient was referred to Oncology and Palliative Care for further management. We report a clinical lesson regarding the importance of confirming prior liver disease prior to transplant listing. Rare presentations such as this argue towards liver biopsy prior to listing ALF patients of unknown etiology.

1877P Fatigue changes according to systemic therapy type in patients with advanced solid cancer

Systemic inflammation and disease progression are proposed causes of cancer-related fatigue. We aimed to investigate longitudinal changes in fatigue burden according to disease progression, systemic inflammation and therapy type. We prospectively collected validated questionnaires on fatigue (EORTC QLQ-C30, QLQ-FA12) and parameters of systemic inflammation (CRP, interleukin 6, procalcitonin) in patients with solid tumors undergoing palliative systemic cancer therapy. Baseline measurements were performed at start of a new therapy and follow-up measurements at the subsequent re-staging. The median follow-up time was 2 months (range 1-4 months). 79 patients (39/79 (49.4%) females; 40/79 (50.6%) males) with diagnosis of metastatic lung cancer (15/79; 19%), colorectal cancer (15/79; 19%), pancreatic cancer (11/79; 13.9%), sarcoma (11/79; 13.9%), breast cancer (7/79; 8.9%) or other cancers (20/79; 25.3%) were included. 35/79 (44.3%) of patients were treated with chemotherapy (CHT), 17/79 (21.5%) with immune checkpoint inhibitors (ICIs), 8/79 (10.1%) with combinational CHT-ICI, 6/79 (7.6%) with targeted therapies and 13/79 (16.5%) with combinational CHT-targeted therapy. Patients receiving ICI showed a significant reduction in the QLQ-FA12 Interference with daily life symptom scale (p=0.031) while a rising QLQ-FA12 Physical fatigue symptom scale was evident in patients receiving CHT (p=0.046). Levels of procalcitonin rised significantly in patients receiving CHT (p=0.04) while decreased in patients receiving targeted therapy (p=0.026). Patients with a progressive disease showed a significant increase in the QLQ-C30-FA symptom scale (p= 0.013), QLQ-FA12 Physical fatigue symptom scale (p=0.005) and QLQ-FA12 Interference with daily life symptom scale (p=0.022). No association between disease control and type of applied therapy or fatigue level and systemic inflammation was observed. A significant change of fatigue scales and procalcitonin level according to treatment type and disease control could be shown in our prospective patient cohort. Further longitudinal investigation is warranted to investigate the association of systemic inflammation and fatigue burden in different treatment types.

Carcinomatosis peritoneal secundaria a cáncer de mama ductal infiltrante sincrónico a adenocarcinoma de sigma. Revisión bibliográfica a propósito de un caso tratado en nuestro hospital

AimWe provide a literature review of the diagnosis, treatment and survival of metastatic breast cancer with peritoneal carcinomatosis. Patients and methodsWe present a case treated in our institution and discuss relevant clinical, diagnostic, and therapeutic features. ConclusionExtra-hepatic gastrointestinal metastasis from breast cancer is infrequent (8%-10%). The incidence of peritoneal carcinomatosis is low, with few cases reported in the literature, mostly from invasive lobular carcinoma. Our case of invasive ductal carcinoma is even less frequent.

Serum Carboxypeptidase N1 Serves as a Potential Biomarker Complementing CA15-3 for Breast Cancer.

The incidence and mortality of breast cancer are increasing annually. Breast cancer seriously threatens women's health and quality of life. We aimed to measure the clinical value of CPN1, a new serum marker of breast cancer and to evaluate the efficacy of CPN1 in combination with CA15-3. Seventy samples of breast cancer with lymph node metastasis, seventy-three samples of nonmetastatic breast cancer and twenty-five samples of healthy human serum were collected. Serum CA15-3 concentration was determined by Roche Elecsys, and serum CPN1 concentration was determined by ELISA. In breast cancer patients, serum CPN1 concentration was positively correlated with tumour size, clinical stage and CA15-3 concentration (r = 0.376, P<0.0001). ROC curve analysis showed that the optimal critical concentration of CPN1 for breast cancer diagnosis was 32.8pg/ml. The optimal critical concentration of CPN1 in the diagnosis of metastatic breast cancer was 66.121pg/ml. CPN1 has a greater diagnostic ability for breast cancer (AUCCA15-3=0.702 vs. AUCCPN1=0.886, P<0.0001) and metastatic breast cancer (AUCCA15-3=0.629 vs. AUCCPN1=0.887, P<0.0001) than CA15-3, and the combined detection of CA15-3 and CPN1 can improve the diagnostic efficiency for breast cancer (AUCCA15-3+CPN1=0.916) and for distinguishing between metastatic and non-metastatic breast cancer (AUCCA15-3+CPN1=0.895). CPN1 can be used as a new tumour marker to diagnose and evaluate the invasion and metastasis of breast cancer. The combined detection of CPN1 and CA15-3 is more accurate and has a certain value in clinical application.

Deep learning approaches for bone and bone lesion segmentation on 18FDG PET/CT imaging in the context of metastatic breast cancer.

18FDG PET/CT imaging is commonly used in diagnosis and follow-up of metastatic breast cancer, but its quantitative analysis is complicated by the number and location heterogeneity of metastatic lesions. Considering that bones are the most common location among metastatic sites, this work aims to compare different approaches to segment the bones and bone metastatic lesions in breast cancer.Two deep learning methods based on U-Net were developed and trained to segment either both bones and bone lesions or bone lesions alone on PET/CT images. These methods were cross-validated on 24 patients from the prospective EPICUREseinmeta metastatic breast cancer study and were evaluated using recall and precision to measure lesion detection, as well as the Dice score to assess bones and bone lesions segmentation accuracy.Results show that taking into account bone information in the training process allows to improve the precision of the lesions detection as well as the Dice score of the segmented lesions. Moreover, using the obtained bone and bone lesion masks, we were able to compute a PET bone index (PBI) inspired by the recognized Bone Scan Index (BSI). This automatically computed PBI globally agrees with the one calculated from ground truth delineations.Clinical relevance- We propose a completely automatic deep learning based method to detect and segment bones and bone lesions on 18FDG PET/CT in the context of metastatic breast cancer. We also introduce an automatic PET bone index which could be incorporated in the monitoring and decision process.

Efficacy and toxicity of everolimus plus exemestane in third and later lines treatment of hormone receptor-positive, HER2-negative metastatic breast cancer

Amaç: Siklin bağımlı kinaz 4-6 inhibitörü ve fulvestrant gibi tedavilerin tek başına ya da kombinasyon halinde kullanılmasının hormone reseptör (HR)-pozitif metastatik meme kanseri (MMK) tedavisinde daha etkin olduğunun gösterilmesiyle günlük pratikte everolimus/eksemestan tedavisi daha ileriki basamaklarda kullanılmaya başlamıştır. Bu çalışmanın amacı HR-pozitif HER2-negatif MMK tedavisinde üçüncü ve sonraki basamaklarda everolimus/eksemestan kombinasyon tedavisinin etkinliğini ve toksisitelerini gerçek yaşam verileri ile değerlendirmektir.Yöntemler: Bu çalışma retrospektif kohort çalışmasıdır. Kasım 2013 - Mart 2020 tarihleri arasında merkezimizde HR-pozitif HER2-negatif MMK tanısıyla everolimus/eksemestan kombinasyon tedavisi alanlar çalışmaya dahil edilmiştir. Hastaların klinikopatolojik özellikleri ve tedavi ilişkili toksisiteler retrospektif olarak incelenmiştir.Bulgular: Çalışmaya dahil edilen 33 hastanın ortanca yaşı 59’du (30-77). Hastaların 23’ünün (%69,7) visseral metastazı varken 10 (%30,3) hastanın yalnızca kemik metastazı vardı. Everolimus/eksemestan tedavisi 22 (%66,6) hastaya üçüncü basamakta, 11 (%33,3) hastaya ise sonraki basamaklarda verilmişti. Ortanca takip süresi 15.5 (0,3-35,5) aydı. Ortanca progresyonsuz sağkalım (PS) 7,0 (5,1-9,0, 95% CI) ay; ortanca genel sağkalım ise 21,3 (13,4-29,2, 95% CI) aydı. Yalnızca kemik metastazı olan hastalarla visseral metastazı olan hastalar arasında ortanca PS açısından fark yoktu (7,2–6,4 ay; P=0,96).Sonuç: Everolimus/eksemestan kombinasyonu HR-pozitif HER2-negatif MMK tedavisinde ileriki basamaklarda da etkin ve tolere edilebilir bir tedavi seçeneğidir.

Comparison of the cell-free DNA genomics in patients with metastatic breast cancer (MBC) who develop brain metastases versus those without brain metastases.

1094 Background: The genomics of patients with metastatic breast cancer (MBC) who develop brain metastases (BM) is not well understood given the difficulty in obtaining brain tumor for genotyping. We compared tumor genotyping results via cell-free DNA (cfDNA) collected at MBC diagnosis in patients who developed BM after MBC diagnosis with those who did not develop BM (non-BM). Methods: Patients at an academic institution who had cfDNA testing (Guardant 360/Next generation sequencing, 73 gene assay) at MBC diagnosis between 1/2016-12/2017, with ≥ 6 months of follow-up post testing, were identified. A chart review was done to identify tumor subtype, demographics, cfDNA results, and development of BM at or after MBC diagnosis. Pearson’s chi-squared and Wilcoxon rank sum tests were used to determine differences in clinical and cfDNA characteristics in BM vs. non-BM (p&lt;0.05 for statistical significance). Results: CfDNA results were available for 49 patients, of whom 13 (27%) developed BM (4 with BM at MBC diagnosis). The median time to BM development was 11 months. While patients with BM were younger at MBC diagnosis than non-BM (median age BM 53 vs. non-BM 61, p=0.05), they had similar subtype (BM vs. non-BM: HR+/HER2- 62% vs. 69%, HER2+ 8% vs. 14%, TNBC 23% vs. 17%, unknown 8% vs. 0%, p=0.3), de-novo vs. recurrent disease (BM vs. non-BM: de-novo 8% vs. 14%, recurrent 92% vs. 86%, p=0.6), and visceral disease (BM vs. non-BM: 77% vs. 56%, p=0.2) distributions. All patients with BM had ≥1 detectable cfDNA mutation vs. 88% of non-BM. While the median mutant allele frequency of the most common mutation was similar in BM vs. non-BM (2.4% vs. 3.7%, p=0.5), the mutation pattern varied. Patients with BM more often had mutations in BRCA1 (15% vs. 3%, p=0.1), APC (15% vs. 0%, p=0.02), and CDKN2A (15% vs. 0%, p=0.02), compared to non-BM. In 4 patients with BM at MBC diagnosis, mutations in APC (50%), CDKN2A (50%), and BRCA 1/2 (25%) were noted; 1 had coexisting APC and BRCA1/2 mutations and another had coexisting APC and CDKN2A mutations. Conclusions: Patients with MBC who develop BM may have different cfDNA genomics, particularly BRCA1, APC, and CDKN2A mutations. Further research is needed to determine the predictive value of cfDNA at MBC diagnosis in the identification of patients at higher risk of developing BM. [Table: see text]

Cell-free DNA comparative analysis of hormone receptor-positive, first-line metastatic breast cancer genomic landscape in the United States and China.

1059 Background: Metastatic breast cancer (MBC) is a heterogeneous disease associated with known somatic mutations of variable biological value in different subtypes. Furthermore, the clinical evolution of the disease demonstrates clonal evolution resulting in disease resistance more accurately detected using blood-based sequencing. Few studies have explored differences in genomic features of tumors across populations. Here, we performed circulating tumor DNA (ctDNA) sequencing to compare the genomic landscape of patients with hormone-receptor positive MBC at time of first recurrence or de-novo metastatic diagnosis in the United States (US) and China. Methods: Twenty-three US patients from Northwestern University and 65 Chinese patients from Peking University had ctDNA sequencing from plasma performed using the harmonized CLIA-certified, 152-gene PredicineCARE assay in laboratories in the US and China, respectively. The data analysis was conducted in China. Institutional Review Boards at each site approved the study. Fisher’s exact test was performed to compare mutational frequencies across populations. Results: Median age of patients at MBC diagnosis was 51 in the US cohort and 55 in the Chinese cohort. 87% of US patients and 82% of Chinese patients had received prior therapy for primary breast cancer, including endocrine therapy. Mutations were detected in 17 of 23 (74%) US patients and 59 of 65 (91%) Chinese patients. CNAs were observed in 57% of US patients and 58% of Chinese patients. The most common mutations detected in US patients were TP53 (26%), PIK3CA (22%), AKT1 (22%), CDH1 (17%), PTEN (13%), and ESR1 (9%) vs. PIK3CA (46%), TP53 (35%), ESR1 (12%), and BRCA2 (11%) in Chinese patients. Frequency of AKT1 and CDH1 mutations were significantly higher in the US population (P &lt; 0.05), while PIK3CA mutations were higher in the Chinese population (P &lt; 0.05). CNA gains in CCND3 and CDK4 were significantly higher in the US cohort, and FGFR1 was significantly more common in the Chinese cohort (all P &lt; 0.05). Conclusions: To our knowledge, this is a first cross-regional comparison study in HR+ MBC patients in the US and China using a harmonized cfDNA NGS platform. At a population level, there were notable differences observed in somatic variants in two cohorts. Future sequencing efforts and clinical trials should include patients of diverse ethnic backgrounds to explore the impact of differences in genomic landscape on probability of benefit from treatments. A larger validation cohort is required to confirm these findings.

Recruitment and retention in a self-directed “walking” intervention: Feasibility study in women with metastatic breast cancer during active treatment.

e13084 Background: Health related quality of life (HRQOL) and physical function are greatly impacted by the diagnosis and treatment of metastatic breast cancer (MBC). This study investigates the ability of women with MBC to engage in moderate walking during active treatment, with exercise monitored through a FitbitTM activity tracker. Methods: This is a single-site feasibility study of a home-based, self-directed physical activity intervention for women with MBC who could have had up to three lines of treatment. Questionnaires were completed at baseline, 12 weeks, and 24 weeks. Results: Sixty patients were consented, with mean age 55 (SD 11.1), 21% non-white, and 56% ECOG = 0. 36% were in their 3rd or 4th line of chemotherapy treatment. 65% had metastases to the bone, 46% to the lung, and 33% to the liver; mean number of metastasis sites was 2 (range 1 to 4). N = 52 completed all baseline measurements; N = 40 remained in the study at 3 months, and N = 29 at 6 months. Of the N = 31 (52%) lost to attrition, N = 6 were due to death, N = 5 due to deterioration, and N = 20 due to patient withdrawal from the study. Mean walking steps per day of at least 4000 was achieved in months 1, 2 and 3 by 41%, 50%, and 41% of participants. In months 4, 5 and 6, these percentages were 45%, 51% and 39%. On a scale from 1 = very confident to 10 = not at all confident about “continuing to walk or be physically active after completing the study”, confidence scores were 2.8 (SD 2.8) at 3 months and 2.9 (2.9) at 6 months. Conclusions: Forty-nine percent of women with MBC who signed up for a home-based walking program during active treatment were able to complete the 24-week intervention, with high proportions of these women walking more than 4000 steps per day. Moderate walking is feasible for women with MBC on active treatment.

Clinicopathologic features of invasive breast cancer (BC) diagnosed in carriers of germline PALB2, CHEK2 and ATM pathogenic variants.

1549 Background: While germline pathogenic variants (PVs) in BRCA1/2 account for a large proportion of hereditary breast cancer (BC), PVs in PALB2, CHEK2 and ATM are increasingly detected. However, the phenotype and clinical features of invasive BC with these PVs have not been fully described. Methods: We identified patients with a PV or likely PV in PALB2, CHEK2 or ATM tested clinically at Stanford between 2014 - 2019 who provided informed consent to be included in a prospective cancer genetics registry. Data on baseline demographics, genetic testing history, and clinicopathologic features of diagnosed BC were collected. For patients with a subsequent diagnosis of metastatic BC, we calculated disease-free interval (DFI). Results: 130 patients met inclusion criteria for analysis: ATM (N=39), CHEK2 (N=58), PALB2 (N=33). Nearly all (98.5%) were women, with 2 male BC in ATM carriers. Non-Hispanic White ethnicity was most common in ATM (64.1%, 95% CI 48.4%-77.3%) and CHEK2 carriers (69.0%, 95% CI 56.1%-79.4%), but comprised only 39.4% (95% CI 24.7%-56.4%) in PALB2 carriers. Asian/Pacific Islander (24.2%, 95% CI 12.6%-41.3%) and Hispanic (30.3%, 95% CI 17.3%-47.5%) ethnicities were enriched among PALB2 mutation carriers. In total, 97.7% learned of their PV status only after a preceding diagnosis of BC and 43.1% were diagnosed with BC at age ≤ 45. Data regarding invasive BC subtypes, incidence of subsequent primary BC, and metastatic recurrence are listed below in the table. Additional data on stage, grade and sites of metastatic spread will be presented. Conclusions: We observed clinically important differences in the spectrum of BC subtypes among carriers of ATM, CHEK2 and PALB2 PVs, in addition to racial/ethnic differences with Asian/Pacific Islander and Hispanic ethnicity enriched among carriers of PALB2 PVs. [Table: see text]

174P Occurrence of brain metastasis and treatment patterns among patients with HER2-positive metastatic breast cancer

The risk of brain metastasis (BM) is high (up to 50%) among patients diagnosed with HER2-positive (HER2+) metastatic breast cancer (MBC) compared with HER2-negative MBC. There are limited real-world data on the timing of BM development and subsequent treatment among such patients. The objective of this observational study was to assess BM occurrence and treatment among women with HER2+ MBC. Women ≥18 years old and diagnosed with HER2+ MBC between 6/1/2012 and 5/31/2018 were included in the study. Data were abstracted from electronic medical records from a network of community oncology practices maintained in the Vector Oncology Data Warehouse and included clinical and demographic characteristics, timing of BM diagnosis and treatment patterns. Of 372 study eligible patients, 165 (44.4%) had a record of BM. The majority of patients with BM were white (n=99; 60.0%) with a median age of 54 (range 29-83) years at MBC diagnosis. There were 82 patients (49.7%) with de novo MBC and 89 (53.9%) had hormone-receptor positive tumours. There were 37 patients (22.4%) with a record of BM at the time of initial MBC diagnosis (baseline), 63 (38.2%) developed BM during the first-line treatment, 23 (13.9%) during the second-line and 42 (25.5%) during the third-line or beyond. The median time to develop BM from initial MBC diagnosis was 12.5, 18.3 and 22.8 months, respectively. Post-BM systemic treatments varied. Among those with baseline BM (n=37), the most common regimens were trastuzumab plus pertuzumab along with taxane (n=13; 35.1%), trastuzumab monotherapy (n=3; 8.1%) and tamoxifen monotherapy (n=3; 8.1%). In patients who developed BM during follow-up (n=128), the most common regimens included pertuzumab plus trastuzumab (n=27; 21.1%), ado-trastuzumab emtansine monotherapy (n=13; 10.2%), and trastuzumab monotherapy (n=11; 8.6%). BM were common among patients with HER2+ MBC, and occurred at various points during the course of treatment. Post-BM systemic therapy varied widely, which may indicate a lack of standard of care for patients with HER2+ MBC after BM diagnosis and an unmet need in this patient population. Further analysis on treatment efficacy is required to understand whether treatment needs are met.