- Email: [email protected]
Correlation of circulating tumour cells with PET-CT in metastatic breast cancer
abstracts
42P
Genome wide copy number analysis of circulating tumour cells in breast cancer liver metastasis
S. Imani1, Z. Linglin1, M. Maghsoudloo2, Q. Wen1 Oncology Department, Afflicted Hospital of Southwest Medical University, Southwest Medical University, Luzhou, China, 2Department of Bioinformatics, Kish International Campus, University of Tehran, Kish, Iran
1
Background: Circulating tumor cells (CTCs) enter peripheral blood from primary breast cancer tumors and seed liver metastasis (BCLM). The genome-wide sequencing of CTCs offers noninvasive diagnostic factor for survival in BCLM patients, which but has been impeded by low single-cell genome coverage of scarce CTCs. Methods: We conducted a prospective clinical investigation to confirm the diagnostic value of genome-wide sequencing in BCLM. We have developed the genome-wide pattern differences in copy number variations (CNVs) and to improve a CNV signature as an adjunct test for the routine histopathologic classification of BCLM. We compared the consistency and efficiency of genome-wide sequencing of CTCs with other comment detection methods. Furthermore, functional prediction of candidate gene biomarkers was confirmed in BCLM patients. Results: CTCs were isolated from 26 patients with BCLM, 12 of which were successfully profiled for high CTCs (> 15), including matched archival primary tumor from 17 patients. Our results characteristic cancer-metastatic variations and insertions/deletions in exomes of CTCs. Comparison with primary breast tumors in metastatic niches cell revealed similar frequencies of BCLM genomic copy number aberrations. Higher CTCs frequencies (> 35) are correlated with disease severity and metastatic progress, which suggesting effective value of CTCs for variety of staging of BCLM. The CNV pattern of CTC is similar to that of hepatic metastasis, but the mutation pattern of CTC is different from that of primary lesion. Twenty- five genes were identified as a CNV signature of BCLM. Functional pathways analysis shows all these genes might play similar and critical roles in migration and progression of BCLM that could be independent risk factors for BCLM (p < 0.05). Conclusions: Our approach utilized to explore reproducibility of cancer-specific CNVs involved in progression of metastatic breast cancer. Our study contributed a new potential non-invasive biomarker for CTC-based cancer diagnostics of BCLM to monitor therapeutic efficacy of targeted therapies. Editorial acknowledgement: The authorswould like to express their appreciation to appreciate Southwest Medical Universityfor its financial support. We also wish to thank the oncology and pathology technicians of The Affiliated Hospital of Southwest Medical University for their assistance in the work reported here. We also thank the anonymous referee for his/her very helpful comments, which remarkably improved the quality of this research. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
ix16 | Breast cancer, metastatic
43P
A hotspot variants p.H1047R and p.H1047L in p110a/DNp63a complex affects structure, function and contributes to susceptibility metastatic breast cancer
Z. Linglin1, S. Imani1, M. Dehghan Shasaltaneh2, Q. Wen1 Oncology Department, Afflicted Hospital of Southwest Medical University, Southwest Medical University, Luzhou, China, 2Department of Biology, Faculty of Science, University of Zanjan, Zanjan, Iran
1
Background: Hotspot constitutive activating of phosphatidylinositol 3 kinase (PI3K) signaling plays a critical role in metastatic breast cancer (MBC). Our previous studies found that oncogenic hotspot mutations of subunit alpha of PI3K (PIK3CA) within the p110a kinase domain (H1047R and H1047L) leads to cell motility and promotes tumor metastasis in invasive ductal breast carcinomas of Chinese women. This study is aimed to elucidate the mutagenetic, homology modelling and function of hotspot variants p.H1047R and p.H1047L in p110a/DNp63a complex. Methods: Here, an established protocol by integrated molecular dynamics, proteinprotein docking with combination principal component analysis assay were employed to examine the onco-activation inhibitory function of p110a/DNp63a complex between wild and both p110aH1047Rand p110aH1047Lmutation’s conformational diversity. Then, we were confirmed the possible disruption and inhibitory effect of the p110a/DNp63a complex at in vitromodel of MBC. Results: Partial disruption of interaction between the DNA binding domain of DNp63a and kinase domain of p110a were destabilized the conformation of activation loop of p110a/DNp63a complex in three helix regions, including H1 (resid 234-236), H2 (resid 245-249) and H3 (resid 348-355). The molecular dynamics finding clearly confirmed that ABD (resid 16-105) and C2 domain (resid 330-487) in p.H1047R mutant and RBD (resid 187-289) and kinase domain (resid 797-1068) in p.H1047L mutant are maxima difference of residue level displacements and fluctuations of p110a/DNp63a complex. Notably, oncogenic p.H1047L variant is more treatable and distributed structure more than p.H1047R. In vitro result show that abrogation of oncogenic hotspot mutations p.H1047R and p.H1047L in p110a/DNp63a complex significantly induces scattered cell growth, cell migration and invasion in MBC cell lines. Conclusions: Oncogenic hotspot mutant forms, p110aH1047R and p110aH1047L, by reducing the inhibitory effect of the DNp63aon the kinase domain of p110a, contributes to the progressive causatives of MBC, as well as defines a novel symbiotic strategy for understanding complex protein systems in MBC. Legal entity responsible for the study: The authors. Funding: Southwest Medical University. Disclosure: All authors have declared no conflicts of interest.
44P
Correlation of circulating tumour cells with PET-CT in metastatic breast cancer
V.P.B. Koyyala1, S.D. Saini1, D.C. Doval1, A. Mehta1, M. Suryavanshi1, P. Goyal1, U.D. Maheshwari1, A. Jajodia2, M. Sharma1, S. Goyal1 1 Medical Oncology Department, Rajiv Gandhi Cancer Institute and Research Centre, New Delhi, India, 2Radiodiagnosis, Rajiv Gandhi Cancer Institute and Research Centre, New Delhi, India Background: Circulating tumor cells (CTC) detection has proven to be an important parameter for predicting progression-free and overall survival. CTCs provide a socalled real-time liquid biopsy which gives better opportunities for selection of treatment. Methods: A prospective observational study conducted the Rajiv Gandhi Cancer Institute & Research Centre, New Delhi. 36 treatment naı¨ve patients of metastatic breast cancer were enrolled from April 2016 and May 2018. CTCs were detected using Cellsearch system. Correlation of CTCs with patient’s outcome after chemotherapy in terms of progression-free survival (PFS) and overall survival (OS) were calculated at one year. The level of CTCs in peripheral blood was measured at baseline before chemotherapy and then at 1 month and 6 months of treatment. All patients underwent PETCT scan at 3 months and 6 months of treatment. Results: 36 patients were included in this study. The mean CTCs at baseline was 13.8 (0-48), with 75% of patients having CTC 5. A positive correlation with the number of sites of metastasis with the number of CTCs was noted (p < 0.001 and R ¼ 0.886). Around 11% of the patients had a complete response (CR) after 3 months of therapy as determined by imaging with a mean number of CTCs 21 (median 17) before starting the treatment and 4.25 (median 4.5) at 1 month (P ¼ 0.14). Similarly, partial response at 3 months, the mean CTCs significantly decreased to 6.3 from 12.9 (p ¼ 0.001). Patients with baseline CTCs<5 had a mean PFS of 9.8 months (95% CI of 7.2 to 12.3) and patients with baseline CTCs 5 had a mean PFS of 8.6 months (95% CI of 7.1 to 10.1) (p ¼ 0.37). Patients with CTCs < 5 after one month of treatment had a mean OS of 11.6 months (95% CI of 10.8 to 12.4) and patients with CTCs5 after one of treatment had a mean overall survival of 9.6 months (95% CI of 8.0 to 11.2) (p ¼ 0.08). Conclusions: Our results have implications for both standard care and clinical research in developing countries. More accurate determination of treatment effectiveness early in the course of therapy might spare patient therapy-related toxicity from futile therapy, patient families from financial toxicity and allow treatment to be changed to a more effective regimen.
Volume 30 | Supplement 9 | November 2019
Downloaded from https://academic.oup.com/annonc/article-abstract/30/Supplement_9/mdz418.007/5638716 by University of Connecticut user on 24 November 2019
the correlation between improvement of lipid metabolism and antitumor immune response and cancer prognosis in vivo. Methods: Except for patients with ductal carcinoma in situ, 938 breast cancer patients treated with curative surgery were examined. The correlation between serum levels of total-cholesterol and triglyceride, and clinicopathological features, including pre- and postoperative neutrophil-to-lymphocyte ratio (NLR) and tumor-infiltrating lymphocytes (TILs), and prognosis was evaluated retrospectively. Results: 194 patients were receiving treatment for hyperlipidemia. Recurrence-free survival (RFS) and overall survival (OS) did not differ significantly between users of the drug for hyperlipidemia or non-users (p ¼ 0.782, log-rank) (p ¼ 0.304, log-rank). Among postmenopausal patients with hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative breast cancer, who were treated for hyperlipidemia, the group with good serum lipid control had significantly better RFS (p ¼ 0.014, log-rank). Good serum lipid control was also significantly correlated with low postoperative NLR (p ¼ 0.024). In addition, high-TILs in resected tissues was significantly associated with preoperative serum lipid levels (p ¼ 0.039). In the drug type, lipophilic statin users had lower recurrence rate than hydrophilic statin users (8.2 % vs 16.0 %). Conclusions: Good control of serum lipid metabolism may have a relationship with improvement of tumor immune microenvironment and favorable outcome in postmenopausal HR-positive/HER2-negative breast cancer patients. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
Annals of Oncology
abstracts
Annals of Oncology Legal entity responsible for the study: Rajiv Gandhi Cancer Institute and Research Centre, New Delhi. Funding: Rajiv Gandhi Cancer Institute and Research Centre, New Delhi. Disclosure: All authors have declared no conflicts of interest.
in 3000 RPM for 15 minutes. After that, the plasma was analyzed with ELISA technique with reagent (Bioassay Technology Laboratory). Data was analyzed using SPSS for windows version 20. Results:
The challenge of evaluating new targeted therapies: Opportunities in stratifying the therapeutic response per tumour location 1
1
2
1
Characteristic
Median concentration CD36 (ng/mL)
p
BC Healthy
0.21 (-0.05 up to 0.70) 0.57 (0.13 up to 1.05) 0.21 (-0.05 up to 0.70) 0.21 (-0.05 up to 0.70) 0.20 (-0.05 up to 0.70) 0.23 (-0.05 up to 0.70) 0.21 (-0.05 up to 0.67) 0.21 (-0.02 up to 0.70) 0.22 (-0.02 up to 0.36) 0.23 (0.16 up to 0.70) 0.21 (-0.05 up to 0.70) 0,20 (-0,02 up to 0,67) 0.22 (0.10 up to 0.53) 0.21 (-0.05 up to 0.70) 0.26 (0.13 up to 0.70) 0.20 (-0.05 up to 0.70) 0.23 (-0.05 up to 0.70)
0.00
3
H. Beaumont , N. Faye , A. Iannessi , C. Klifa , C-Y. Hsieh Sciences Department, Median Technologies, Valbonne, France, 2Radiology, Centre Anticancer Antoine Lacassagne, Nice, France, 3Medical Oncology, Aslan Pharmaceuticals, Singapore
1
Background: Compared with conventional cancer chemotherapy, tyrosine kinase inhibitors show novel patterns of radiology response, therefore using chemotherapybased response criteria can be suboptimal. Coupling the tumor’s volume as an imaging biomarker with a stratified analysis of the therapeutic response per sites of disease may offer more insightful information in drug efficacy. We propose to compare the therapeutic response between Varlitinib plus Capecitabine (VC) and Lapatinib plus Capecitabine (LC) in analyzing the changes of tumor’s volume per tumor’s locations in patients with HER2-positive metastatic breast cancer after trastuzumab therapy. Methods: We retrospectively analyzed data from the ASLAN001-003 study (NCT02338245). At baseline, 42 patients displayed at least one target lesion, representing a set of 88 target lesions: Lung (31%), Breast (26%), liver (23%), nodes (17%), miscellaneous (3%). Responses were evaluated at week 12 on 35 patients (14 VC; 21 LC). Between two arms, we compared responses using non-parametric tests and compared the proportion of tumor at each location using the Chi-square test. We used the R software for statistics, p < 0.05 was considered a significant difference. Results: The distribution of tumor size at baseline was different at the different tumor locations (p < 0.001). Between the two arms the proportion of tumor at each location were not equivalent with p ¼ 0.126 and 0.06 for breast and lung tumors respectively. The global average change from baseline was VC¼-64.1% and LC¼-26.59% (p ¼ 0.13) The average change of breast tumors was significantly different in the VC (-84.2%) and the LC (-24.9%) (p < 0.001) arm. Between breast and liver tumors, the average response was significantly different (p ¼ 0.007) in the VC arm, while not in the LC arm (p ¼ 0.94). Also, between nodal and liver tumors with p ¼ 0.06 in the VC and p ¼ 0.99 in LC arm. Conclusions: The therapeutic response differed across tumor locations, the differential response was drug-dependent. For a fair comparison, the proportion of tumor at each tumor location must be balanced between arms. The stratification of the therapeutic response can be used for assessing new therapies, helping designing cocktails or refining drug’s indications. Clinical trial identification: ASLAN001-003 - NCT02338245. Legal entity responsible for the study: Median Technologies/Aslan Pharmaceuticals. Funding: Has not received any funding. Disclosure: H. Beaumont: Full / Part-time employment: Median Technologies. N. Faye: Full / Parttime employment: Median Technologies. C. Klifa: Full / Part-time employment: Median Technologies. C-Y. Hsieh: Full / Part-time employment: Aslan Pharmaceuticals. All other authors have declared no conflicts of interest.
46P
Plasma soluble CD36 of breast cancer based on pathological and clinical characteristics
A.R. Romadhoni1, A. Rachman2, C. Irawan2, S. Koesnoe2 Internal Medicine, RSUPN (Rumah Sakit Cipto Mangunkusumo), Jakarta, Indonesia, 2 Internal Medicine, Cipto Mangunkusumo General Hospital (RSCM) University of Indonesia, Jakarta, Indonesia
1
Background: Breast cancer is one of the malignant diseases with the highest prevalence around the world, including Indonesia. Data from Global Cancer Statistics 2018 (GLOBOCAN) predicted that up to 2.1 billion women were diagnosed with breast cancer; therefore, it became one of the top four cancerous diseases in women. Several studies have revealed the role of CD36 molecule in breast cancer and there are several gaps in CD36 expression knowledge. In tumor adhesion, CD36 is involved in cellular interaction with collagen in the extracellular matrix. Some measurement methods of CD36 expression molecules include gene expression measurement through micro-assay, total RNA analysis, and plasma examination through ELISA techniques already done in subjects with non alcoholic fatty liver disease, diabetes mellitus, insulin resistance, coronary arterial disease, carotid atherosclerosis, chronic kidney disease, and ischaemic stroke. However, concentration measurement of CD36 plasma molecule in breast cancer using ELISA technique has not yet been done in previous studies. Methods: This is a cross-sectional study, was held during June 2018 up to February 2019. Sampling methods were taken consecutively in 118 subjects, consisted of 76 BC subjects, 42 normal subjects. Inclusion criteria included women aged 18 to 70 years old, having pathological invasive breast cancers, and subjects were willing to sign the informed consent sheets. Exclusion criteria included subjects with disease progressivity during therapy, diabetes mellitus, stroke, liver, coronary arterial disease, chronic kidney disease. Subjects were then drawn 2 cc of the peripheral blood,and then was centrifuged
Volume 30 | Supplement 9 | November 2019
Metastatic BC Non metastatic BC BC with LN metastatic BC without LN metastatic Luminal tumor HER2 tumor Triple negative tumor G1 G2 G3 Unknown grade
Tumor size > 2 cm Tumor size 2 cm BC with BMI 23 BC with BMI < 23
> 0.05 > 0.05 > 0.05
> 0.05
> 0.05 > 0.05
Conclusions: Plasma CD36 concentration of breast cancer is lower than the healthy. There are insignificant differences of plasma CD36 concentration profile breast cancer patients based on metastatic status, lymph node metastatic, molecular subtype, invasive cancer histologic grade, and body mass index. Legal entity responsible for the study: The Ethics Committee of The Faculty of Medicine, University of Indonesia. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
47P
Investigation of the use of a novel S-1 administration method for treating metastatic and recurrent breast cancer
M. Miki1, S. Takao2, M. Konishi3, Y. Shigeoka4, M. Miyashita5, H. Suwa6, M. Imamura7, T. Okuno8, K. Hirokaga2, Y. Miyoshi7, K. Murase7, A. Yanai7, K. Yamagami9, K. Akazawa10 1 Breast Surgical Oncology, Kobe University Hospital, Kobe, Japan, 2Breast Surgical Oncology, Hyogo Cancer Center, Akashi, Japan, 3Breast Surgical Oncology, Hyogo Prefectural Nishinomiya Hospital, Nishinomiya, Japan, 4Oncology, Yodogawa Christian Hospital, Osaka, Japan, 5Breast Surgical Oncology, Konan Hospital, Kobe, Japan, 6 Breast Surgical Oncology, Hyogo Prefectural Amagasaki General Medical Center, Amagasaki, Japan, 7Breast Surgical Oncology, Hyogo Colledge of Medicine, Nishinomiya, Japan, 8Breast Surgical Oncology, Nishikobe Medical Center, Kobe, Japan, 9 Breast Surgical Oncology, Shinko Hospital, Kobe, Japan, 10Medical Infomatics, Niigata University, Niigata, Japan Background: When considering treatment for metastatic and recurrent breast cancer, it is necessary to select drugs with emphasis on side effects and QOL. In Japan, oral 5FU drugs have often been used for initial treatment. In the conventional schedule of S-1 for 4-week administration period followed by 2-week rest, the inferiority of S-1 to T has already been proved. In this study, we examined the efficacy and safety of the schedule of S-1 for 2-week administration period followed by 1-week rest, which is considered to have less side effects and better compliance. Methods: We enrolled individuals with HER2-negative breast cancer who had not received chemotherapy after diagnosis of metastatic breast cancer. S-1 (40-60 mg, twice daily) was administered consecutively for 14 days followed by 7 days of rest (1 course). The primary endpoint was progression-free survival (PFS); the secondary endpoints were overall survival (OS), time to treatment failure (TTF), response rate (RR), disease control rate (DCR), and adverse events. Results: Between September 1, 2013 and August 31, 2016, 32 patients were enrolled. Median PFS was 7.8 months (1.4-35.4 months), and median OS was 25.2 months (4.847.8 months). TTF was 9.1 months. RR was 31.3%, and the DCR was 78%. The cumulative rates of the relative total administration dose of S-1 was 95.6%. Incidence of grade 3 side effects were neutropenia (9.4%), leukopenia (3.1%), anorexia (3.1%), ocular symptoms (3.1%), and an increase in total bilirubin levels (3.1%).
doi:10.1093/annonc/mdz418 | ix17
Downloaded from https://academic.oup.com/annonc/article-abstract/30/Supplement_9/mdz418.007/5638716 by University of Connecticut user on 24 November 2019
Table: 46P Profile of plasma CD36 concentration 45P
42P
Genome wide copy number analysis of circulating tumour cells in breast cancer liver metastasis
S. Imani1, Z. Linglin1, M. Maghsoudloo2, Q. Wen1 Oncology Department, Afflicted Hospital of Southwest Medical University, Southwest Medical University, Luzhou, China, 2Department of Bioinformatics, Kish International Campus, University of Tehran, Kish, Iran
1
Background: Circulating tumor cells (CTCs) enter peripheral blood from primary breast cancer tumors and seed liver metastasis (BCLM). The genome-wide sequencing of CTCs offers noninvasive diagnostic factor for survival in BCLM patients, which but has been impeded by low single-cell genome coverage of scarce CTCs. Methods: We conducted a prospective clinical investigation to confirm the diagnostic value of genome-wide sequencing in BCLM. We have developed the genome-wide pattern differences in copy number variations (CNVs) and to improve a CNV signature as an adjunct test for the routine histopathologic classification of BCLM. We compared the consistency and efficiency of genome-wide sequencing of CTCs with other comment detection methods. Furthermore, functional prediction of candidate gene biomarkers was confirmed in BCLM patients. Results: CTCs were isolated from 26 patients with BCLM, 12 of which were successfully profiled for high CTCs (> 15), including matched archival primary tumor from 17 patients. Our results characteristic cancer-metastatic variations and insertions/deletions in exomes of CTCs. Comparison with primary breast tumors in metastatic niches cell revealed similar frequencies of BCLM genomic copy number aberrations. Higher CTCs frequencies (> 35) are correlated with disease severity and metastatic progress, which suggesting effective value of CTCs for variety of staging of BCLM. The CNV pattern of CTC is similar to that of hepatic metastasis, but the mutation pattern of CTC is different from that of primary lesion. Twenty- five genes were identified as a CNV signature of BCLM. Functional pathways analysis shows all these genes might play similar and critical roles in migration and progression of BCLM that could be independent risk factors for BCLM (p < 0.05). Conclusions: Our approach utilized to explore reproducibility of cancer-specific CNVs involved in progression of metastatic breast cancer. Our study contributed a new potential non-invasive biomarker for CTC-based cancer diagnostics of BCLM to monitor therapeutic efficacy of targeted therapies. Editorial acknowledgement: The authorswould like to express their appreciation to appreciate Southwest Medical Universityfor its financial support. We also wish to thank the oncology and pathology technicians of The Affiliated Hospital of Southwest Medical University for their assistance in the work reported here. We also thank the anonymous referee for his/her very helpful comments, which remarkably improved the quality of this research. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
ix16 | Breast cancer, metastatic
43P
A hotspot variants p.H1047R and p.H1047L in p110a/DNp63a complex affects structure, function and contributes to susceptibility metastatic breast cancer
Z. Linglin1, S. Imani1, M. Dehghan Shasaltaneh2, Q. Wen1 Oncology Department, Afflicted Hospital of Southwest Medical University, Southwest Medical University, Luzhou, China, 2Department of Biology, Faculty of Science, University of Zanjan, Zanjan, Iran
1
Background: Hotspot constitutive activating of phosphatidylinositol 3 kinase (PI3K) signaling plays a critical role in metastatic breast cancer (MBC). Our previous studies found that oncogenic hotspot mutations of subunit alpha of PI3K (PIK3CA) within the p110a kinase domain (H1047R and H1047L) leads to cell motility and promotes tumor metastasis in invasive ductal breast carcinomas of Chinese women. This study is aimed to elucidate the mutagenetic, homology modelling and function of hotspot variants p.H1047R and p.H1047L in p110a/DNp63a complex. Methods: Here, an established protocol by integrated molecular dynamics, proteinprotein docking with combination principal component analysis assay were employed to examine the onco-activation inhibitory function of p110a/DNp63a complex between wild and both p110aH1047Rand p110aH1047Lmutation’s conformational diversity. Then, we were confirmed the possible disruption and inhibitory effect of the p110a/DNp63a complex at in vitromodel of MBC. Results: Partial disruption of interaction between the DNA binding domain of DNp63a and kinase domain of p110a were destabilized the conformation of activation loop of p110a/DNp63a complex in three helix regions, including H1 (resid 234-236), H2 (resid 245-249) and H3 (resid 348-355). The molecular dynamics finding clearly confirmed that ABD (resid 16-105) and C2 domain (resid 330-487) in p.H1047R mutant and RBD (resid 187-289) and kinase domain (resid 797-1068) in p.H1047L mutant are maxima difference of residue level displacements and fluctuations of p110a/DNp63a complex. Notably, oncogenic p.H1047L variant is more treatable and distributed structure more than p.H1047R. In vitro result show that abrogation of oncogenic hotspot mutations p.H1047R and p.H1047L in p110a/DNp63a complex significantly induces scattered cell growth, cell migration and invasion in MBC cell lines. Conclusions: Oncogenic hotspot mutant forms, p110aH1047R and p110aH1047L, by reducing the inhibitory effect of the DNp63aon the kinase domain of p110a, contributes to the progressive causatives of MBC, as well as defines a novel symbiotic strategy for understanding complex protein systems in MBC. Legal entity responsible for the study: The authors. Funding: Southwest Medical University. Disclosure: All authors have declared no conflicts of interest.
44P
Correlation of circulating tumour cells with PET-CT in metastatic breast cancer
V.P.B. Koyyala1, S.D. Saini1, D.C. Doval1, A. Mehta1, M. Suryavanshi1, P. Goyal1, U.D. Maheshwari1, A. Jajodia2, M. Sharma1, S. Goyal1 1 Medical Oncology Department, Rajiv Gandhi Cancer Institute and Research Centre, New Delhi, India, 2Radiodiagnosis, Rajiv Gandhi Cancer Institute and Research Centre, New Delhi, India Background: Circulating tumor cells (CTC) detection has proven to be an important parameter for predicting progression-free and overall survival. CTCs provide a socalled real-time liquid biopsy which gives better opportunities for selection of treatment. Methods: A prospective observational study conducted the Rajiv Gandhi Cancer Institute & Research Centre, New Delhi. 36 treatment naı¨ve patients of metastatic breast cancer were enrolled from April 2016 and May 2018. CTCs were detected using Cellsearch system. Correlation of CTCs with patient’s outcome after chemotherapy in terms of progression-free survival (PFS) and overall survival (OS) were calculated at one year. The level of CTCs in peripheral blood was measured at baseline before chemotherapy and then at 1 month and 6 months of treatment. All patients underwent PETCT scan at 3 months and 6 months of treatment. Results: 36 patients were included in this study. The mean CTCs at baseline was 13.8 (0-48), with 75% of patients having CTC 5. A positive correlation with the number of sites of metastasis with the number of CTCs was noted (p < 0.001 and R ¼ 0.886). Around 11% of the patients had a complete response (CR) after 3 months of therapy as determined by imaging with a mean number of CTCs 21 (median 17) before starting the treatment and 4.25 (median 4.5) at 1 month (P ¼ 0.14). Similarly, partial response at 3 months, the mean CTCs significantly decreased to 6.3 from 12.9 (p ¼ 0.001). Patients with baseline CTCs<5 had a mean PFS of 9.8 months (95% CI of 7.2 to 12.3) and patients with baseline CTCs 5 had a mean PFS of 8.6 months (95% CI of 7.1 to 10.1) (p ¼ 0.37). Patients with CTCs < 5 after one month of treatment had a mean OS of 11.6 months (95% CI of 10.8 to 12.4) and patients with CTCs5 after one of treatment had a mean overall survival of 9.6 months (95% CI of 8.0 to 11.2) (p ¼ 0.08). Conclusions: Our results have implications for both standard care and clinical research in developing countries. More accurate determination of treatment effectiveness early in the course of therapy might spare patient therapy-related toxicity from futile therapy, patient families from financial toxicity and allow treatment to be changed to a more effective regimen.
Volume 30 | Supplement 9 | November 2019
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the correlation between improvement of lipid metabolism and antitumor immune response and cancer prognosis in vivo. Methods: Except for patients with ductal carcinoma in situ, 938 breast cancer patients treated with curative surgery were examined. The correlation between serum levels of total-cholesterol and triglyceride, and clinicopathological features, including pre- and postoperative neutrophil-to-lymphocyte ratio (NLR) and tumor-infiltrating lymphocytes (TILs), and prognosis was evaluated retrospectively. Results: 194 patients were receiving treatment for hyperlipidemia. Recurrence-free survival (RFS) and overall survival (OS) did not differ significantly between users of the drug for hyperlipidemia or non-users (p ¼ 0.782, log-rank) (p ¼ 0.304, log-rank). Among postmenopausal patients with hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative breast cancer, who were treated for hyperlipidemia, the group with good serum lipid control had significantly better RFS (p ¼ 0.014, log-rank). Good serum lipid control was also significantly correlated with low postoperative NLR (p ¼ 0.024). In addition, high-TILs in resected tissues was significantly associated with preoperative serum lipid levels (p ¼ 0.039). In the drug type, lipophilic statin users had lower recurrence rate than hydrophilic statin users (8.2 % vs 16.0 %). Conclusions: Good control of serum lipid metabolism may have a relationship with improvement of tumor immune microenvironment and favorable outcome in postmenopausal HR-positive/HER2-negative breast cancer patients. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
Annals of Oncology
abstracts
Annals of Oncology Legal entity responsible for the study: Rajiv Gandhi Cancer Institute and Research Centre, New Delhi. Funding: Rajiv Gandhi Cancer Institute and Research Centre, New Delhi. Disclosure: All authors have declared no conflicts of interest.
in 3000 RPM for 15 minutes. After that, the plasma was analyzed with ELISA technique with reagent (Bioassay Technology Laboratory). Data was analyzed using SPSS for windows version 20. Results:
The challenge of evaluating new targeted therapies: Opportunities in stratifying the therapeutic response per tumour location 1
1
2
1
Characteristic
Median concentration CD36 (ng/mL)
p
BC Healthy
0.21 (-0.05 up to 0.70) 0.57 (0.13 up to 1.05) 0.21 (-0.05 up to 0.70) 0.21 (-0.05 up to 0.70) 0.20 (-0.05 up to 0.70) 0.23 (-0.05 up to 0.70) 0.21 (-0.05 up to 0.67) 0.21 (-0.02 up to 0.70) 0.22 (-0.02 up to 0.36) 0.23 (0.16 up to 0.70) 0.21 (-0.05 up to 0.70) 0,20 (-0,02 up to 0,67) 0.22 (0.10 up to 0.53) 0.21 (-0.05 up to 0.70) 0.26 (0.13 up to 0.70) 0.20 (-0.05 up to 0.70) 0.23 (-0.05 up to 0.70)
0.00
3
H. Beaumont , N. Faye , A. Iannessi , C. Klifa , C-Y. Hsieh Sciences Department, Median Technologies, Valbonne, France, 2Radiology, Centre Anticancer Antoine Lacassagne, Nice, France, 3Medical Oncology, Aslan Pharmaceuticals, Singapore
1
Background: Compared with conventional cancer chemotherapy, tyrosine kinase inhibitors show novel patterns of radiology response, therefore using chemotherapybased response criteria can be suboptimal. Coupling the tumor’s volume as an imaging biomarker with a stratified analysis of the therapeutic response per sites of disease may offer more insightful information in drug efficacy. We propose to compare the therapeutic response between Varlitinib plus Capecitabine (VC) and Lapatinib plus Capecitabine (LC) in analyzing the changes of tumor’s volume per tumor’s locations in patients with HER2-positive metastatic breast cancer after trastuzumab therapy. Methods: We retrospectively analyzed data from the ASLAN001-003 study (NCT02338245). At baseline, 42 patients displayed at least one target lesion, representing a set of 88 target lesions: Lung (31%), Breast (26%), liver (23%), nodes (17%), miscellaneous (3%). Responses were evaluated at week 12 on 35 patients (14 VC; 21 LC). Between two arms, we compared responses using non-parametric tests and compared the proportion of tumor at each location using the Chi-square test. We used the R software for statistics, p < 0.05 was considered a significant difference. Results: The distribution of tumor size at baseline was different at the different tumor locations (p < 0.001). Between the two arms the proportion of tumor at each location were not equivalent with p ¼ 0.126 and 0.06 for breast and lung tumors respectively. The global average change from baseline was VC¼-64.1% and LC¼-26.59% (p ¼ 0.13) The average change of breast tumors was significantly different in the VC (-84.2%) and the LC (-24.9%) (p < 0.001) arm. Between breast and liver tumors, the average response was significantly different (p ¼ 0.007) in the VC arm, while not in the LC arm (p ¼ 0.94). Also, between nodal and liver tumors with p ¼ 0.06 in the VC and p ¼ 0.99 in LC arm. Conclusions: The therapeutic response differed across tumor locations, the differential response was drug-dependent. For a fair comparison, the proportion of tumor at each tumor location must be balanced between arms. The stratification of the therapeutic response can be used for assessing new therapies, helping designing cocktails or refining drug’s indications. Clinical trial identification: ASLAN001-003 - NCT02338245. Legal entity responsible for the study: Median Technologies/Aslan Pharmaceuticals. Funding: Has not received any funding. Disclosure: H. Beaumont: Full / Part-time employment: Median Technologies. N. Faye: Full / Parttime employment: Median Technologies. C. Klifa: Full / Part-time employment: Median Technologies. C-Y. Hsieh: Full / Part-time employment: Aslan Pharmaceuticals. All other authors have declared no conflicts of interest.
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Plasma soluble CD36 of breast cancer based on pathological and clinical characteristics
A.R. Romadhoni1, A. Rachman2, C. Irawan2, S. Koesnoe2 Internal Medicine, RSUPN (Rumah Sakit Cipto Mangunkusumo), Jakarta, Indonesia, 2 Internal Medicine, Cipto Mangunkusumo General Hospital (RSCM) University of Indonesia, Jakarta, Indonesia
1
Background: Breast cancer is one of the malignant diseases with the highest prevalence around the world, including Indonesia. Data from Global Cancer Statistics 2018 (GLOBOCAN) predicted that up to 2.1 billion women were diagnosed with breast cancer; therefore, it became one of the top four cancerous diseases in women. Several studies have revealed the role of CD36 molecule in breast cancer and there are several gaps in CD36 expression knowledge. In tumor adhesion, CD36 is involved in cellular interaction with collagen in the extracellular matrix. Some measurement methods of CD36 expression molecules include gene expression measurement through micro-assay, total RNA analysis, and plasma examination through ELISA techniques already done in subjects with non alcoholic fatty liver disease, diabetes mellitus, insulin resistance, coronary arterial disease, carotid atherosclerosis, chronic kidney disease, and ischaemic stroke. However, concentration measurement of CD36 plasma molecule in breast cancer using ELISA technique has not yet been done in previous studies. Methods: This is a cross-sectional study, was held during June 2018 up to February 2019. Sampling methods were taken consecutively in 118 subjects, consisted of 76 BC subjects, 42 normal subjects. Inclusion criteria included women aged 18 to 70 years old, having pathological invasive breast cancers, and subjects were willing to sign the informed consent sheets. Exclusion criteria included subjects with disease progressivity during therapy, diabetes mellitus, stroke, liver, coronary arterial disease, chronic kidney disease. Subjects were then drawn 2 cc of the peripheral blood,and then was centrifuged
Volume 30 | Supplement 9 | November 2019
Metastatic BC Non metastatic BC BC with LN metastatic BC without LN metastatic Luminal tumor HER2 tumor Triple negative tumor G1 G2 G3 Unknown grade
Tumor size > 2 cm Tumor size 2 cm BC with BMI 23 BC with BMI < 23
> 0.05 > 0.05 > 0.05
> 0.05
> 0.05 > 0.05
Conclusions: Plasma CD36 concentration of breast cancer is lower than the healthy. There are insignificant differences of plasma CD36 concentration profile breast cancer patients based on metastatic status, lymph node metastatic, molecular subtype, invasive cancer histologic grade, and body mass index. Legal entity responsible for the study: The Ethics Committee of The Faculty of Medicine, University of Indonesia. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
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Investigation of the use of a novel S-1 administration method for treating metastatic and recurrent breast cancer
M. Miki1, S. Takao2, M. Konishi3, Y. Shigeoka4, M. Miyashita5, H. Suwa6, M. Imamura7, T. Okuno8, K. Hirokaga2, Y. Miyoshi7, K. Murase7, A. Yanai7, K. Yamagami9, K. Akazawa10 1 Breast Surgical Oncology, Kobe University Hospital, Kobe, Japan, 2Breast Surgical Oncology, Hyogo Cancer Center, Akashi, Japan, 3Breast Surgical Oncology, Hyogo Prefectural Nishinomiya Hospital, Nishinomiya, Japan, 4Oncology, Yodogawa Christian Hospital, Osaka, Japan, 5Breast Surgical Oncology, Konan Hospital, Kobe, Japan, 6 Breast Surgical Oncology, Hyogo Prefectural Amagasaki General Medical Center, Amagasaki, Japan, 7Breast Surgical Oncology, Hyogo Colledge of Medicine, Nishinomiya, Japan, 8Breast Surgical Oncology, Nishikobe Medical Center, Kobe, Japan, 9 Breast Surgical Oncology, Shinko Hospital, Kobe, Japan, 10Medical Infomatics, Niigata University, Niigata, Japan Background: When considering treatment for metastatic and recurrent breast cancer, it is necessary to select drugs with emphasis on side effects and QOL. In Japan, oral 5FU drugs have often been used for initial treatment. In the conventional schedule of S-1 for 4-week administration period followed by 2-week rest, the inferiority of S-1 to T has already been proved. In this study, we examined the efficacy and safety of the schedule of S-1 for 2-week administration period followed by 1-week rest, which is considered to have less side effects and better compliance. Methods: We enrolled individuals with HER2-negative breast cancer who had not received chemotherapy after diagnosis of metastatic breast cancer. S-1 (40-60 mg, twice daily) was administered consecutively for 14 days followed by 7 days of rest (1 course). The primary endpoint was progression-free survival (PFS); the secondary endpoints were overall survival (OS), time to treatment failure (TTF), response rate (RR), disease control rate (DCR), and adverse events. Results: Between September 1, 2013 and August 31, 2016, 32 patients were enrolled. Median PFS was 7.8 months (1.4-35.4 months), and median OS was 25.2 months (4.847.8 months). TTF was 9.1 months. RR was 31.3%, and the DCR was 78%. The cumulative rates of the relative total administration dose of S-1 was 95.6%. Incidence of grade 3 side effects were neutropenia (9.4%), leukopenia (3.1%), anorexia (3.1%), ocular symptoms (3.1%), and an increase in total bilirubin levels (3.1%).
doi:10.1093/annonc/mdz418 | ix17
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Table: 46P Profile of plasma CD36 concentration 45P