Relationship of Ki-67 proliferative index and metastatic tumor of breast cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e22190-e22190
Author(s):  
Kokoro Kobayashi ◽  
Yoshinori Ito ◽  
Akiko Ogiya ◽  
Naoya Gomi ◽  
Rie Horii ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Primary Tumor ◽  
Metastatic Tumor ◽  
Labeling Index ◽  
Proliferation Index ◽  
Luminal Breast Cancer ◽  
Line Treatment ◽  
Metastatic Tumors ◽  
Ki 67 ◽  
Primary Tumors

e22190 Background: The metastatic breast tumor tends to be more aggressive with high proliferation, but this has not been proven in clinical sampling of metastatic tumors. Methods: Forty-eight patients who had histological specimens of both primary and metastatic sites of luminal breast cancer (ER and/or PgR positive and HER2 negative) were examined. We classified them as luminal A (LA) with Ki-67 labeling index of less than 14% and as luminal B (LB) with Ki-67 labeling index of more than 14%. We analyzed their overall survival (OS) and progression free survival (PFS) of 1st line treatment of each subtype of primary and metastatic tumors. Results: Subtypes of primary tumors and metastatic tumors were as follows; the primary tumor: LA; 34 patients (70.8%), LB; 14 (29.2%), metastatic tumors: LA; 21 (43.8%), LB; 27 (56.2%). Patients with LA of the primary tumor demonstrated statistically longer OS (LA; 72.5 months, LB 39.6 months, p=0.009). OS depended on the subtype of the primary tumor. In contrast, patients with LB of a metastatic tumor showed a statistically worse PFS (LA; 20.5 months, LB; 11.5 months, p=0.040). PFS of the 1st line treatment for MBC depended on the subtype of the metastatic tumor. Conclusions: The frequency of LB was increased on metastatic tumors and tended to acquire a higher proliferation index. This suggests that characterization of metastatic tumors could be better as an indicator of subsequent treatment for MBC. [Table: see text]

Neuroendocrine differentiation in metastatic breast cancer following CDK 4/6 inhibitors.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e13029-e13029
Author(s):  
Sakina Sekkate ◽  
Laure Ladrat ◽  
Christelle Pouliquen ◽  
Celine Callens ◽  
Jean Francois Geay ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Aromatase Inhibitor ◽  
Neuroendocrine Differentiation ◽  
Metastatic Breast ◽  
Standard Of Care ◽  
Proliferation Index ◽  
Castration Resistant Prostate Cancer ◽  
Metastatic Tumors ◽  
Ki 67

e13029 Background: First-line treatment with a CDK4/6 inhibitor in combination with an aromatase inhibitor for HR+/HER2- postmenopausal metastatic breast cancer (mBC) is considered as a standard of care based on the compelling data across all landmark trials. Methods: We report our experience about two cases with metastatic breast cancer treated by CDK4/6 inhibitor in combination with an aromatase inhibitor, which develop neuroendocrine differentiation. After observing an unusual massive progression, a biopsy of the metastasis was performed in both patients. Both histological analysis confirmed a lobular breast cancer with small cell neuroendocrine features and a high proliferation index (KI 67 90%). An NGS (Next generation sequencing) profile was realized on primary and metastatic tumors to detect new acquired genomic alterations. Results: The comparative analysis of the NGS results of primary and metastatic tumors revealed the occurrence of several events in both patients under treatment. For one patient, we identified new mutations in the genes CDH1, FANCG, PIK3CA, PTEN and TP53, which did not exist initially. For the second patient, we found an amplification of the segment containing FGFR1, CCND1, FGF4, FGF3, FADD genes and the deletion of the segment containing RB1 andTP53 genes. Such events were not observed on the primary tumor. Conclusions: Prostate adenocarcinoma may develop neuroendocrine features in later stages of castration-resistant prostate cancer but neuroendocrine differentiation is atypical in breast carcinoma. In case of unusual rapidly progressive disease after CDK4/6 inhibitor, biopsy of new metastases should be recommanded to search neuroendocrine differentiation, or druggable mutations to guide the treatment.

Concordance of Genomic Variants in Matched Primary Breast Cancer, Metastatic Tumor, and Circulating Tumor DNA: The MIRROR Study

2019 ◽  
pp. 1-16 ◽  
Author(s):  
Fernando Moreno ◽  
Javier Gayarre ◽  
Sara López-Tarruella ◽  
María del Monte-Millán ◽  
Antonio C. Picornell ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Primary Tumor ◽  
Metastatic Breast ◽  
Metastatic Tumor ◽  
Circulating Tumor Dna ◽  
Primary Tumors ◽  
Genomic Variants ◽  
Ctdna Analysis ◽  
Tumor Dna

PURPOSE Genetic heterogeneity between primary tumors and their metastatic lesions has been documented in several breast cancer studies. However, the selection of therapy for patients with metastatic breast cancer and the search for biomarkers for targeted therapy are often based on findings from the primary tumor, mainly because of the difficulty of distant metastasis core biopsies. New methods for monitoring genomic changes in metastatic breast cancer are needed (ie, circulating tumor DNA [ctDNA] genomic analysis). The objectives of this study were to assess the concordance of genomic variants between primary and metastatic tumor tissues and the sensitivity of plasma ctDNA analysis to identify variants detected in tumor biopsies. PATIENTS AND METHODS Next-generation sequencing technology was used to assess the genomic mutation profile of a panel of 54 cancer genes in matched samples of primary tumor, metastatic tumor, and plasma from 40 patients with metastatic breast cancer. RESULTS Using Ion Torrent technology (ThermoFisher Scientific, Waltham, MA), we identified 110 variants that were common to the primary and metastatic tumors. ctDNA analysis had a sensitivity of 0.972 in detecting variants present in both primary and metastatic tissues. In addition, we identified 13 variants in metastatic tissue and ctDNA not present in primary tumor. CONCLUSION We identified genomic variants present in metastatic biopsies and plasma ctDNA that were not present in the primary tumor. Deep sequencing of plasma ctDNA detected most DNA variants previously identified in matched primary and metastatic tissues. ctDNA might aid in therapy selection and in the search for biomarkers for drug development in metastatic breast cancer.

scholarly journals Surgery to Oligometastatic Breast Cancer after Excellent Response to Palbociclib and Letrozole Therapy: Pitfall of Ultrasound Therapeutic Evaluation

2021 ◽  
pp. 1601-1607
Author(s):  
Suzuka Fujii ◽  
Shoji Oura ◽  
Shinichiro Makimoto
Keyword(s):  
Breast Cancer ◽  
Cancer Cell ◽  
Growth Factor Receptor ◽  
Metastatic Breast ◽  
Labeling Index ◽  
Pathological Examination ◽  
Luminal Breast Cancer ◽  
Ki 67 ◽  
Positron Emission ◽  
Therapeutic Evaluation

A 48-year-old woman with regional recurrences of breast cancer in the axillar and supraclavicular regions was referred to our hospital. Under the diagnosis of recurrent luminal breast cancer with a high Ki-67 labeling index of >30% and a disease-free interval of 13 years, the patient began to receive palbociclib, letrozole, and luteinizing hormone-releasing hormone agonist, resulting in marked response of the supraclavicular lesion and stable disease of the axillar lesion on ultrasound (US) evaluation. Positron emission tomography (PET)/computed tomography of the axillar and supraclavicular foci showed high and no avidities before and after treatment, respectively. The unmovable neck lesion became movable with the treatment. The patient, therefore, underwent surgical resection of the 2 metastatic foci to examine the discordant therapeutic efficacy against the 2 metastatic foci on 2 image modalities, that is, US and PET, and to possibly get a cure of the breast cancer oligometastasis. Pathological examination showed marked fibrosis and scant cancer cell residuals with microcalcifications in the neck tumor and massive sarcoid-like reaction with scant cancer cell residuals in the axillary nodes. The residual cancer cells showed estrogen and progesterone receptor positivities, human epidermal growth factor receptor type 2 negativity, and an extremely low Ki-67 labeling index of 2.5%. The patient recovered uneventfully and has continued palbociclib-containing endocrine therapy for 1 year without any recurrences. Breast oncologists should well understand the basic principles of internal echo formation on US and take the presence of sarcoid-like reaction in the cancer cell clusters into consideration on the therapeutic evaluation of metastatic breast cancer.

FGFR3 protein expression and gene mutation in primary and metastatic urothelial carcinoma (UC) tumors.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 4577-4577
Author(s):  
Jonathan E. Rosenberg ◽  
Lillian Werner ◽  
Aristotelis Bamias ◽  
Toni K. Choueiri ◽  
Fabio A. B. Schutz ◽  
...  
Keyword(s):  
Protein Expression ◽  
Therapeutic Target ◽  
Primary Tumor ◽  
Scoring Systems ◽  
Metastatic Tumor ◽  
Copy Number Gain ◽  
Tissue Microarrays ◽  
Metastatic Tumors ◽  
Primary Tumors ◽  
Fgfr3 Mutation

4577 Background: FGFR3 protein expression may represent a valid therapeutic target in metastatic UC. The prevalence of both mutation and overexpression is unknown in metastatic UC. Methods: Tissue microarrays of formalin fixed paraffin-embedded urothelial carcinomas (UC) were stained for FGFR3 by immunohistochemistry (IHC) [primary (n=250); metastatic (n=31); of which (n=14) were paired]. FGFR3 immunostaining was scored as negative or positive based on previously reported scoring systems. FGFR3 mutation in primary tumors was assessed by iPlex and confirmed by hME sequencing (n=141) or Affymetrix OncoScan FFPE Express 2.0 (primary: n=17; metastases n=31). Results: FGFR3 IHC positivity was present in 48% of metastases (95% CI=32-65%) and 26% of primary tumors, (95%=CI 21-32%), though strong staining was rare (<1%). Paired primary and metastatic tumors were both negative in 50% of cases, with 14% positive only in the metastasis, 14% positive only in the primary tumor, and 21% positive in both. If the primary tumor showed staining, 71% of the metastases showed staining. FGFR3 IHC staining did not impact overall survival (p=0.8). FGFR3 mutations were observed in 9.6% of metastatic tumors (95% CI=3.3-25%), compared to 3.5% of primary tumors (95% CI=1.5%-8%). Co-occurrence of mutation and FGFR3 DNA copy number gain was observed in one specimen. Conclusions: FGFR3 IHC staining is present 26 % of primary tumors of patients who go on to develop metastatic disease, and nearly half of metastatic tumor sites. FGFR3 mutation frequency in primary and metastatic tumor specimens is low. Further investigation of the frequency of FGFR3 protein expression in metastases is needed. The presence of FGFR3 protein by IHC staining in primary and metastatic specimens suggests that FGFR3 may represent a therapeutic target even in the absence of mutation. Further functional studies are needed.

scholarly journals Discordance in ER, PR, HER2, and Ki-67 Expression Between Primary and Recurrent/Metastatic Lesions in Patients with Primary Early Stage Breast Cancer and the Clinical Significance: Retrospective Analysis of 75 Cases

2021 ◽  
Vol 27 ◽  
Author(s):  
Li Peng ◽  
Zhen Zhang ◽  
Dachun Zhao ◽  
Jialin Zhao ◽  
Feng Mao ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Early Stage ◽  
Receptor Expression ◽  
Early Stage Breast Cancer ◽  
Prognostic Impact ◽  
Metastatic Tumors ◽  
Ki 67 ◽  
Primary Tumors ◽  
Metastatic Lesions

Background: The objective was to explore the discordance in the expression of the estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and Ki-67 between primary and recurrent/metastatic lesions in patients with early stage breast cancer as well as the prognostic impact.Method: Patients with early-stage primary breast cancer and confirmed recurrence/metastasis at Peking Union Medical College Hospital between January 2005 and August 2018 were screened. The details of discordance in each parameter between primary and recurrent/metastatic lesions and progression were recorded. Regression and survival analysis were applied to determine the association and clinical impact of the discordance.Results: We evaluated 75 patients. The discordance rate of ER, PR, HER2, and Ki-67 expression was 9.3, 14.7, 14.7, and 21.5%, respectively. Additionally, 66.7, 11.8, 14.3, and 0% of patients with Luminal A, Luminal B, HER2, and triple-negative primary tumors presented with a different subtype for the recurrent/metastatic tumors, respectively. No statistical difference in progression-free survival was observed according to the subtype of the recurrent or metastatic breast cancer (p &gt; 0.05). Among 69 patients for whom treatment was adjusted after recurrence or metastasis, 66 patients remained recurrence-free during the follow-up period.Conclusion: For patients with early-stage breast cancer, the ER, PR, HER2, and Ki-67 expression profile for recurrent/metastatic tumors does not always match that of the primary tumor. After adjusting treatment according to the receptor expression in recurrent/metastatic lesions, most patients remained progression-free during the follow-up period.

scholarly journals Biglycan (BGN) is differentially expressed in metastatic breast cancer, both in metastases to the brain and to the lymph nodes.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Primary Tumor ◽  
Metastatic Breast ◽  
Metastatic Tumor ◽  
Clinical Problem ◽  
Differentially Expressed ◽  
Down Regulation ◽  
Primary Tumors ◽  
The Brain

Metastasis to the brain is a clinical problem in patients with breast cancer (1-3). We mined published microarray data (4, 5) to compare primary and metastatic tumor transcriptomes to discover genes associated with brain metastasis in patients with metastatic breast cancer. We found that biglycan, encoded by BGN, was among the genes whose expression was most different in the brain metastases of with patients with metastatic breast cancer as compared to primary tumors of the breast. Interestingly, biglycan was also among the genes most differentially expressed transcriptome-wide when comparing primary tumors of the breast to normal breast tissue. We observed significant down-regulation of biglycan in metastasis to the brain. Molecular functions and down-regulation of BGN may be important for metastasis of primary tumor-derived cancer cells the brain in humans with metastatic breast cancer, and suggests a role for changes in biglycan expression during a spectrum of transformation from benign tissue of the breast, primary tumor and finally to metastasis of the brain.

Effects of melatonin and doxorubicin on primary tumor and metastasis in breast cancer model

2021 ◽  
Vol 21 ◽  
Author(s):  
Gamze Tanriover ◽  
Sayra Dilmac ◽  
Gunes Aytac ◽  
Ammad Ahmad Farooqi ◽  
Muzaffer Sindel
Keyword(s):  
Breast Cancer ◽  
Tumor Growth ◽  
Cancer Patients ◽  
Primary Tumor ◽  
Metastatic Breast ◽  
Suppressor Cells ◽  
Metastatic Tumor ◽  
Breast Cancer Patients ◽  
Primary Tumors ◽  
Ample Evidence

Background: Melatonin exerts oncostatic effects on breast cancer via immunomodulation and anti-oxidation. Doxorubicin is an effective chemotherapeutic agent, but parallel studies also provide ample evidence of an off-target effect of Doxorubicin in breast cancer patients. Objective: Combinatorial use of doxorubicin and melatonin has not been comprehensively analyzed in breast cancer models. We hypothesized that the anti-oxidative, anti-proliferative and anti-inflammatory effects of melatonin could ameliorate the off-target effects of doxorubicin in breast cancer patients and enhance the anti-tumoral effects of doxorubicin. The goal of the study is to test this hypothesis in cancer cell lines and xenografted mice. Methods: The effects of Melatonin and doxorubicin on the cell viability were evaluated in 4T1-Brain Metastatic Tumor (4TBM). Furthermore, the effects of melatonin and doxorubicin on the primary tumors and systemic metastasis were evaluated in the xenografted mice. Lung and liver tissues were removed and metastasis analyses were performed. The levels of p65, phospho-STAT3, CD11b+, GR1+, Ki67, and cleaved caspase-3 proteins were determined with immunohistochemistry and western blot analysis. We examined the effects of melatonin and Melatonin+Doxorubicin combination therapy on 4TBM cells. Results: Our results showed that doxorubicin inhibited the proliferation of metastatic breast cancer cells while melatonin did not affect cells. Tumor growth and metastasis were markedly suppressed in melatonin alone and combination with doxorubicin. The expression of CD11b+ and GR1+ proteins which are indicators of myeloid-derived suppressor cells (MDSCs) were noted to be reduced in both primary tumor and metastatic tissues in melatonin and doxorubicin groups. Conclusion: The combination of melatonin with doxorubicin reduced primary tumor growth and distant metastasis. Based on these results, melatonin is a promising candidate for combinatory use with conventional chemotherapeutics for breast cancer treatment.

scholarly journals Brain metastasis PD-L1 and CD8 expression is dependent on primary tumor type and its PD-L1 and CD8 status

2020 ◽  
Vol 8 (2) ◽  
pp. e000597
Author(s):  
Florian Camy ◽  
Georgia Karpathiou ◽  
Jean Marc Dumollard ◽  
Nicolas Magne ◽  
Jean Luc Perrot ◽  
...  
Keyword(s):  
Primary Tumor ◽  
Metastatic Tumor ◽  
Molecular Data ◽  
Tumor Type ◽  
Metastatic Tumors ◽  
Primary Tumors ◽  
Kaplan Meier ◽  
Product Limit ◽  
Simple Regression Analysis ◽  
Primary Tumor Type

BackgroundBrain metastases (Bmets) are frequent; however, limited data exist on the efficacy of immunotherapy in these lesions. The aims of the study were to analyze the immunohistochemical expressions of programmed death ligand 1 (PD-L1) and CD8 in Bmets and to compare them with their expressions in paired primary tumors, as well as correlate the results with clinicopathological features.MethodsThis is a retrospective study of 233 patients with Bmets and 111 paired primaries. Clinical, histological, and molecular data were recorded and compared with the immunohistochemical results of PD-L1 and CD8 expressions. The statistical analysis included χ2 test, Cramer’s V test, factorial analyses of variance, simple regression analysis, and Kaplan-Meier analysis with log-rank product limit estimation.ResultsPD-L1 expression was found in 23.6% of Bmets and in 29.0% of primary tumors with concordant expression between them in 75.5% of cases. Bmets PD-L1 expression was associated with primary tumor PD-L1 expression and the primary tumor type. Significant CD8 peritumoral expression was found in 68.6% of Bmets and in 87.7% of primary tumors. CD8 expression was concordant between primary and metastatic tumors in 73.3% of cases. Bmets CD8 expression was associated with primary tumor CD8 expression and primary tumor type. PD-L1 expression was associated with CD8 expression in both primary and metastatic tumors. The concordance between primary and metastatic tumor PD-L1 expression was independent of all factors studied. The concordance between primary and metastatic CD8 expressions was marginally associated to the time of Bmets development. No prognostic role for PD-L1 and CD8 expression in Bmets was found.ConclusionPD-L1 and CD8 Bmets expressions are associated with the primary tumor type and its PD-L1 and CD8 expressions. No factor predicts the discordance for PD-L1 expression, while time to Bmets development is associated with CD8 expression discordance.

The functional relationship between in vivo bromodeoxyuridine labeling index and Ki-67 proliferation index in human breast cancer

1998 ◽  
Vol 49 (2) ◽  
pp. 155-164 ◽  
Author(s):  
William H. Goodson ◽  
Dan H. Moore ◽  
Britt-Marie Ljung ◽  
Karen Chew ◽  
Carmina Florendo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Human Breast Cancer ◽  
Functional Relationship ◽  
Labeling Index ◽  
Proliferation Index ◽  
Human Breast ◽  
Ki 67

scholarly journals The Progression Potential of Peritoneal Dissemination Nodules From Gastrointestinal Tumors

2011 ◽  
Vol 96 (4) ◽  
pp. 352-357 ◽  
Author(s):  
Hayato Yamauchi ◽  
Toshinaga Suto ◽  
Wakako Kigure ◽  
Hiroki Morita ◽  
Toshihide Kato ◽  
...  
Keyword(s):  
Primary Tumor ◽  
Therapeutic Strategy ◽  
Peritoneal Dissemination ◽  
Mean Value ◽  
Labeling Index ◽  
Gastrointestinal Cancers ◽  
Ki 67 ◽  
Primary Tumors ◽  
The Mean ◽  
Cancer Dissemination

Abstract It is necessary to examine the characteristics of the dissemination nodules to establish a therapeutic strategy for peritoneal dissemination from digestive malignancy. Ki-67 expression as a proliferation marker in peritoneal dissemination nodules was investigated. The subjects were 15 patients with gastrointestinal cancers who underwent resection of the primary tumor and disseminated nodules. The expression of Ki-67 in both primary tumor and peritoneal dissemination nodule from each patient was evaluated by immunohistochemistry. Ki-67 labeling index in the original tumor was higher than that in the disseminated nodule in 13 of 15 patients (P &lt; 0.0001). The mean value of Ki-67 labeling index was 42.2% in the 15 original tumors and 18.7% in the 15 disseminated nodules. Proliferative activity in the disseminated nodules was lower than that in the primary tumors. Further examination about characteristics of cancer dissemination is needed to treat patients with peritoneal metastasis.

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