Genetic Analysis of Oligo-Metastatic Breast Cancer: Correlation with Clinicopathological Features

2021 ◽  
Author(s):  
Kuikui Jiang ◽  
Danyang Zhou ◽  
Fei Xu ◽  
Wen Xia ◽  
Qiufan Zheng ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Genetic Analysis ◽  
Cancer Patients ◽  
Metastatic Disease ◽  
Metastatic Breast ◽  
Good Prognosis ◽  
Clinicopathological Features ◽  
Breast Cancer Patients ◽  
Significant Difference

Abstract Purpose: We aimed to identify the relationship between the genomic characteristics and clinicopathological features of oligo-metastatic breast cancer.Methods: Oligo-metastatic breast cancer diagnosed by pathology from January 2001 and August 2019 were identified and we matched the poly-metastatic patients based on the clinicopathological features of the oligo-metastatic patients included. The database of all genomic alterations was shown according to the FoundationOne CDx reports. Clinicopathological characteristics were collected and the results of next-generation sequencing were analyzed.Results: A total of 26 breast cancer patients were enrolled in our study, including 14 patients with oligo-metastatic disease and 12 patients with poly-metastatic disease. There was no significant difference in number of gene alteration, tumor mutational burden, variants of unknown significance (VUS), and actional mutation in oligo- and poly-metastasis. PIK3CA, TP53 and ERBB2 were the most common shared alterations identified in patients included. Based on the median time of oligo-progression disease (oligo-PD), we divided the patients with oligo-metastasis into longer oligo-PD group (oligo-PD > 31.04 months) and shorter oligo-PD group (oligo-PD ≤ 31.04 months). The analysis of PIK3CA mutation sites showed that H1047R was associated with a good prognosis in patients with metastatic breast cancer. HER2 positive patients with oligo-metastasis was more likely to have a good prognosis. In addition, VUS might also be a potential prognostic biomarker in metastatic breast cancer. Conclusion: Through the genetic analysis of oligo-metastasis, we found PIK3CA H1047R, HER2 and VUS might predict the different clinical outcomes of breast cancer patients with oligo-metastasis for the individualized treatment.

Efficacy and Safety of Capecitabine Alone or in Combination in Advanced Metastatic Breast Cancer Patients Previously Treated with Anthracycline and Taxane: A Systematic Review and Meta-Analysis

2020 ◽  
Vol 43 (12) ◽  
pp. 694-702
Author(s):  
Louai Alsaloumi ◽  
Shaima Shawagfeh ◽  
Abdikarim Abdi ◽  
Bilgen Basgut
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Adverse Events ◽  
Cancer Patients ◽  
Meta Analysis ◽  
Metastatic Breast ◽  
Efficacy And Safety ◽  
Breast Cancer Patients ◽  
Significant Difference ◽  
Hand Foot Syndrome

<b><i>Background:</i></b> Capecitabine is frequently used alone or combined with other chemotherapy agents for the treatment of metastatic breast cancer in relapsed patients. <b><i>Objective:</i></b> The objective of this meta-analysis is to evaluate the effectiveness and safety of capecitabine monotherapy versus combination in the treatment of metastatic breast cancer patients pretreated with anthracycline and taxane. <b><i>Methods:</i></b> Eligible randomized controlled trials examining the efficacy and safety of capecitabine alone compared to capecitabine combination were systematically searched. Progression-free survival (PFS), overall survival (OS), overall response rate (ORR), and grades 3–4 drug-related adverse events were the outcomes assessed. <b><i>Results:</i></b> A total of 6,714 patients of 9 trials were involved in the pooled analysis. Our findings demonstrated that capecitabine combination is significantly superior to capecitabine monotherapy in improving PFS (hazard ratio [HR] 1.32, 95% CI 1.13–1.54, <i>p</i> &#x3c; 0.0001) and ORR (risk ratio [RR] 0.67, 95% CI 0.54–0.83, <i>p</i> &#x3c; 0.001), but it was insignificant in OS (HR 1.09, 95% CI 0.98–1.22, <i>p</i> = 0.12). On the other hand, the incidence of non-hematological adverse events such as hand-foot syndrome and diarrhea was lower in capecitabine combination compared to capecitabine monotherapy. <b><i>Conclusion:</i></b> Capecitabine-based combination chemotherapy showed superiority over capecitabine monotherapy in terms of PFS and ORR, with no significant difference in OS. Non-hematological adverse effects such as hand-foot syndrome were fewer with a combination regimen. However, hematological adverse events were fewer with capecitabine monotherapy regimen.

scholarly journals TFF1andTFF3mRNAs Are Higher in Blood from Breast Cancer Patients with Metastatic Disease than Those without

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Marwa H. Elnagdy ◽  
Omar Farouk ◽  
Amal K. Seleem ◽  
Hoda A. Nada
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Cancer Patients ◽  
Tumor Cells ◽  
Cancer Metastasis ◽  
Lung Metastases ◽  
Metastatic Breast ◽  
Breast Cancer Patients ◽  
Significant Difference ◽  
High Level

Introduction. Breast cancer metastasis occurs when tumor cells dissociate from the primary tumor and migrate to distant organs through the peripheral bloodstream or lymphatic drainage. Circulating tumor cells (CTCs) originate from primary sites or metastases and circulate in the patients’ bloodstream. Molecular assays for the detection and molecular characterization of CTCs can serve as a liquid biopsy and can represent an alternative to invasive biopsies as a source of tumor tissue in the metastatic patients.Patients and Methods. We analyzed the presence of CTCs in the peripheral blood of 50 breast cancer patients by quantitative real-time reverse transcriptase polymerase chain reaction (RT-qPCR) to detecttrefoil factor family(TFF)1and3genes.Results. We found significant difference in the level of bothTFF1andTFF3mRNA in the blood of nonmetastatic versus metastatic breast cancer patients (p=0.001 and p= 0.038, respectively).TFF1mRNA was detected at higher levels in 34.6% of metastatic breast cancer patients as compared to 0% of nonmetastatic (p= 0.002). As regardsTFF3mRNA, it was detected at higher levels in 46.2% of metastatic breast cancer patients as compared to 4% of nonmetastatic (p= 0.026). Moreover, we found that the high level of bothTFF1andTFF3mRNA was related to estrogen status of the patients. The detection of high level ofTFF1mRNA in CTCs was associated with bone metastases (77.8%), while that ofTFF3was related to lymph node involvement (75%) and lung metastases (68.8%).Conclusion. The combined measurement of bothTFF1andTFF3mRNA level for differentiation of metastatic from nonmetastatic breast cancer gave 57.69% sensitivity and 83.3% specificity.

scholarly journals Effect of CMF-chemotherapy on blood coagulation in patients with breast cancer

2002 ◽  
Vol 10 (2) ◽  
pp. 61-66
Author(s):  
Dragana Petrovic
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Cancer Patients ◽  
Protein C ◽  
Antithrombin Iii ◽  
Metastatic Breast ◽  
Breast Cancer Patients ◽  
Significant Difference ◽  
At Iii ◽  
D Dimer

BACKGROUND: Influences of CMF (cyclophosphamide, methotrexate,5-fluorouracil) chemotherapy on blood coagulation were investigated in 30 patients receiving adjuvant chemotherapy and in 30 patients receiving chemotherapy for metastatic breast cancer. METHODS: In plasma samples of 60 patients (median age 49.5), we evaluated the following parameters 1)Markers of in vivo clotting activation thrombin-antithrombin complex (ELISA) and D-dimer (ELISA), 2) Natural anticoagulants (protein C [PC] and antithrombin III [AT III] by chromogenic methods). The coagulation studies were performed at the beginning and at the end of the first cycle of CMF protocol. RESULTS: Before CMF therapy, significant difference was observed between patients with early stage and patients with metastatic breast cancer in the PC (p<0.01), AT III (p<0.01) and TAT (p<0.01) levels. After CMF therapy, patients with stage II (adjuvant) disease manifested a significant decrease in the level of PC and AT III activity (p<0.01) and an increase in TAT level (p<0.01). In patients with disseminated breast cancer CMF therapy provoked an increased level of TAT and D-dimer with a decreased activity of protein C and antithrombin III. There was significant difference in value of TAT, D- dimer, protein C and antithrombin III between the patients with adjuvant and metastatic breast cancer patients after CMF chemotherapy CONCLUSION: Our results suggest that the application of cytotoxic therapy provokes hypercoagulable condition in breast cancer patients. This effect should be considered when chemotherapy is employed in advanced cancer patients at high risk for thrombosis, or in patients with other risk factors.

Clinical significance of brain metastases occurrence in HER2 overexpressing metastatic breast cancer patients treated with trastuzumab

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 10593-10593
Author(s):  
V. Mari ◽  
E. Chamorey ◽  
A. Italiano ◽  
F. Van Den Bos ◽  
R. Ferri-Dessens ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Metastatic Breast Cancer ◽  
Cancer Patients ◽  
Metastatic Breast ◽  
Study Cohort ◽  
Breast Cancer Patients ◽  
Specific Patient ◽  
Study Results ◽  
Significant Difference

10593 Background: Recent data report that HER2 overexpressing metastatic breast cancer patients (HER+ MBC pts) treated with trastuzumab (T) have a high rate of Brain metastasis (BM). This study aimed to evaluate the prognostic significance of BM occurrence and the related clinical outcome in a specific patient population. Methods: All the HER+MBC patients treated with trastuzumab (with or without chemotherapy) between 09/1999 and 12/2004 were included in this study. Results: A total of forty three patients were enrolled into the study cohort. The median follow-up was 48 months (range, 11–166). Fifteen patients (35%) developped BM. The median interval from the the first MBC event to BM was 18 months (range, 1–65). In multivariate analysis; younger age was the only factor associated with BM occurrence (46 versus 57 years; p = 0.01). Patients with BM tend to have a longer median duration of response to T than patients without BM (16 months versus 13 months; p = 0.1). At the time of BM appearance, 6 of the 15 patients (40%) were still responding or had achieved extracranial stable disease while receiving trastuzumab. Twelve out of 15 (80%) pts received a whole-brain radiation therapy, and 8 pts continued to receive trastuzumab until extracranial disease progression. The median overall survival for patients diagnosed with BM was 10 months (range, 2–42). At three-year, there was no significant difference in overall survival rates between the two groups. The 3-YS was 63.5% and 66.7% for pts with or without BM, respectively; (p = 0.7). Conclusions: The BM occurrence in HER2+ MBC pts treated with Trastuzumab is not linked to tumour resistance, but likely related to the T inability to cross the blood-brain barrier. There is no impaired survival for these pts treated with effective and appropriate therapy. [Table: see text]

scholarly journals Investigation of the change in the biological structure of the tumor in metastatic breast cancer

2021 ◽  
Vol 8 (3) ◽  
pp. 171-174
Author(s):  
Veysel Haksoyler ◽  
Tolga Koseci ◽  
Timucin Cil ◽  
Berna Bozkurt Duman ◽  
Polat Olgun ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Cancer Patients ◽  
Hormone Receptors ◽  
Tumor Biology ◽  
Metastatic Breast ◽  
Breast Cancer Patients ◽  
Metastatic Site ◽  
Significant Difference ◽  
Her 2

Objective: When metastasis develops in some breast cancer patients, hormone receptors (HR) and Human Epidermal Growth Factor-2 (Her-2) status can change and the tumor alters its character. We tried to determine the rate of these changes in tumor biology in 110 patients that we followed in our clinic and performed the change of the biopsy from the metastatic site (re-bx). We aimed to determine the biological changes of tumors and, contribute to the literature by examining the relationship of these changes with the adjuvant endocrine treatments (ET) or chemotherapy type (CT). Material and Methods: We included 110 metastatic breast cancer patients in our study. These patients had previously completed their local treatments followed by CT, and those with positive HR completed ET. After the first metastasis developed in the patients, we performed metastasectomy or biopsy from the metastatic site. Results: The median ki-67 value was 25% at the time of primary diagnosis and 30% in re-bx. 20.9% of patients estrogen receptor (ER), 31.8%  of patients progesterone receptor (PR) and 26.3% of patients Her-2 changed when metastasis developed. Conclusions: We found that the metastatic tumor has more aggressive properties than the primary tumor. Adjuvant chemotherapy and endocrine treatments or the location of metastasis did not make a significant difference in tumor biology.

scholarly journals MATRIKs METALOPROTEINASE-2 DI METASTASIS KARSINOMA PAYUDARA (Matrix Metalloproteinase-2 In Breast Cancer Metastastis)

2018 ◽  
Vol 21 (1) ◽  
pp. 11
Author(s):  
Besse Rosmiati ◽  
Uleng Bahrun ◽  
Ruland DN Pakasi
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Matrix Metalloproteinase ◽  
Cancer Patients ◽  
Metastatic Breast ◽  
Matrix Metalloproteinase 2 ◽  
Breast Cancer Patients ◽  
Significant Difference ◽  
The Matrix ◽  
The Mean

Matrix Metalloproteinase-2 is a family of extra cellular matrix degrading proteinases. Study results on the role of MMP-2 in breastcancer progression and metastasis are still controversial. The aim of this study was to know the MMP-2 level by analyzing in metastaticand non metastatic breast cancer patients by using a cross sectional design, it was carried out in the Wahidin Sudirohusodo, Ibnu Sina,Labuang Baji Hospitals and at the Research Unit of UNHAS Makassar from April 2012 until June 2012. The 56 breast cancer patientswere divided into two groups: metastatic and non metastatic based on their thorax photo, ultrasonography and/or bone scan results. Theywere also divided into early and advanced stage, based on their TNM staging. The matrix metalloproteinase-2 level was determined byELISA method. The result of this study showed that the mean levels of MMP-2 in metastatic and non metastatic breast cancer were 20.18ng/mL and 17.14 ng/mL, respectively. The independent sample T test showed there was a significant difference (p=0.018) in MMP-2levels between metastatic and non metastatic breast cancer. The mean level of MMP-2 in early and advanced stages was 17.10 ng/mLand 18.31 ng/mL, respectively, the independent sample T test showed no significant difference of MMP-2 level between both stages. Oneway ANOVA test showed no significant difference of MMP-2 level based on tumour size and regional lymph node infiltration. The MMP-2contributed to the metastasis in breast cancer patients. The matrix metalloproteinase-2 level in metastatic was higher than in the nonmetastatic breast cancer, so this condition could be used as a biomarker to predict the metastasis of breast cancer.

HER2 amplification and overexpression between primary and liver metastatic breast cancer: Significance and implication.

2014 ◽  
Vol 32 (26_suppl) ◽  
pp. 150-150
Author(s):  
Casey B. Williams ◽  
Pradip De ◽  
Jessica Klein ◽  
Kirstin Anne Williams ◽  
Brigitte Cyr ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Cancer Patients ◽  
Metastatic Disease ◽  
Primary Tumor ◽  
Metastatic Breast ◽  
Her2 Status ◽  
Her2 Expression ◽  
Breast Cancer Patients ◽  
Long Term Treatment

150 Background: The systemic management of metastatic breast cancer (MBC) is mostly based on the ER or HER2 status of the primary tumor. However, the hormonal status or the amplificaction/overexpression HER2 may change in every metastatic site because of the effects of the long-term treatment of metastatic cancer with endocrine therapy, chemotherapy, or targeted agents. The purpose of this study was to investigate the frequency of change in HER2 expression in primary and distant metastatic tumors (especially in liver) in HER2+ breast cancer patients. Methods: We retrospectively analyzed the results of 31 consecutive metastatic breast cancer patients that were seen in our center over 4 months from February 2014 through May 2014. All patients were rebiopsied after consultation and samples were sent for standard immunohistochemistry (IHC) for ER, PR, and HER2 and formalin-fixed, paraffin-embedded (FFPE) samples were sent for genomic (Foundation Medicine) and proteomic analysis (Theranostics). All results from the metastatic samples were compared to the baseline IHC and/or FISH results for HER2. Results: A change in HER2 status was observed in 26% of the cases. 16% of cases underwent a negative to positive conversion in HER2 status while 10% of cases underwent a positive to negative conversion. It is notable that all 5 patients that underwent a negative to positive conversion in HER2 status had biopsies taken from metastatic disease in the liver. Overall, 45% of patients with metastatic disease in the liver had a negative to positive conversion in HER2 status. Conclusions: The results of this study emphasize the significance of confirming HER2 expression in a recurrence lesion. This discordance may be due to the increasing level of genetic instability occurring throughout disease progression that can significantly influence the alterations of the HER2 gene. If feasible, HER2 reassessment in metastatic lesions should be carefully taken into account, especially for metastases coming from non-HER2 amplified breast cancer. Although HER2 status is usually appraised in primary tumor, knowledge of the HER2 status in metastases may be of potential value for therapeutic decision making.

Cardiotoxicity manifestations in metastatic breast cancer patients treated with trastuzumab as first line.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e13011-e13011
Author(s):  
Shira Sherman ◽  
Tamar Barkan ◽  
Rinat Yerushalmi
Keyword(s):  
Breast Cancer ◽  
Heart Failure ◽  
Metastatic Breast Cancer ◽  
Cancer Patients ◽  
Metastatic Disease ◽  
Metastatic Breast ◽  
Significant Decline ◽  
Left Ventricular Ejection ◽  
Breast Cancer Patients ◽  
First Line

e13011 Background: Trastuzumab is a monoclonal antibody that targets the human epidermal growth factor receptor-2 (HER2). Its use may result in cardiotoxicity. There are no formal guidelines for left ventricular ejection fraction (LVEF) monitoring in patients with metastatic disease treated with trastuzumab. Our local guideline include an echocardiogram every 3 months for these patients. Methods: We collected data from electronic records and hard copy files of patients treated with Trastuzumab as first line, between the years 2011-2014. Results: One hundred patients met the inclusion criteria. Median treatment duration of all patients was 30 months, with an average of 12 echocardiogram follow-ups per patient. Ninety-nine patients (99%) received additional chemotherapy. Thirty patients (30%) also received Pertuzumab. Ten (10%) of the eligible 100 patients showed significant decline in EF (≥10%) to a final LVEF of < 50%. The median follow-up duration of these patients was 52 months. Median EF at the beginning of treatment was 61.5% in all patients. Cardiotoxicity occurred at an average of 23 months [median 18 months] after beginning of Trastuzumab treatment (range; 3-54 months), with an average EF decline of 14% (range; 10-18%). Three patients (30%) required treatment change due to the decline in EF. Temporary cessation of treatment was necessary in 4 (40%) of the patients for a period of time between 4 weeks to 8 months. The remaining 3 patients (30%), although developing significant decline in EF, did not require treatment cessation or change. None of the 10 patients presented any other clinical sign of cardiotoxicity. In the group with cardiac events, there were no previous reports of congestive heart failure (CHF), ischemic heart failure (IHF), myocardial infraction (MI) or diabetes. Only one patient was a smoker and another received hormone replacement therapy. The average age of this group at the time of diagnosis of metastatic disease was younger (50.6 vs. 55.8, P-value 0.5). Conclusions: Monitoring heart function by trimonthly echocardiogram does not seem to be the optimal monitoring modality in metastatic breast cancer patients who receive a trastuzumab-containing regimen as first line. This study results suggest that less frequent monitoring may be sufficient, thus diminishing patients' inconvenience and allowing better allocation of health care resources.

Serum HER-2/neu and Response to the Aromatase Inhibitor Letrozole Versus Tamoxifen

2003 ◽  
Vol 21 (10) ◽  
pp. 1967-1972 ◽  
Author(s):  
A. Lipton ◽  
S.M. Ali ◽  
K. Leitzel ◽  
L. Demers ◽  
H.A. Harvey ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Cancer Patients ◽  
Elevated Serum ◽  
Metastatic Breast ◽  
Normal Serum ◽  
Breast Cancer Patients ◽  
Strong Trend ◽  
Significant Difference ◽  
Her 2

Purpose: To determine the effect of elevated serum HER-2/neu on the response of metastatic breast cancer patients to an aromatase inhibitor versus an antiestrogen. Patients and Methods: Five hundred sixty-two estrogen receptor–positive metastatic breast cancer patients were randomized to first-line hormone therapy with either letrozole or tamoxifen. An automated enzyme-linked immunosorbent assay was used to detect serum HER-2/neu. Results: For patients with normal serum HER-2/neu (70.5%), objective response rate (ORR; 39% in letrozole-treated patients v 26% in tamoxifen-treated patients; P = .008), clinical benefit (CB; 57% v 45%; P = .016), time to progression (TTP; median, 12.2 v 8.5 months; P = .0019), and time to treatment failure (TTF; median, 11.6 v 6.2 months; P = .0066) were significantly better in patients treated with letrozole. In the elevated HER-2/neu group (29.5%), there was no significant difference in ORR (17% in letrozole-treated patients v 13% in tamoxifen-treated patients; P = .45) or CB (33% v 26%; P = .31), but there was a strong trend in favor of a longer TTP with letrozole (median, 6.1 v 3.3 months; P = .0596) and a significantly longer TTF with letrozole (median, 6.0 v 3.2 months; P = .0418). Multivariate analysis revealed that elevated serum HER-2/neu was a negative predictor for ORR and TTP. Conclusion: Patients with normal serum HER-2/neu receiving letrozole demonstrated a significantly greater ORR and CB and longer TTP and TTF than patients receiving tamoxifen. Although in patients with elevated serum HER-2/neu there was no significant difference between letrozole and tamoxifen in ORR or CB, there was a strong trend favoring longer TTP and significantly longer TTF with letrozole.

Sign in / Sign up

Export Citation Format

Share Document