Breast Cancer Cells are in Biopsy Channel in Postoperative Material from Mastectomies Preformed 3 days after Core Needle Biopsy (CNB) but They Do Not Persist at Biopsy Channel Apart from the Tumor after 10 Days from the CNB Procedure-a Study of seven Case

2015 ◽  
Vol 21 (5) ◽  
pp. 558-561
Author(s):  
Piotr Lewitowicz ◽  
Andrzej Wincewicz ◽  
Agata Horecka-Lewitowicz ◽  
Jaroslaw Matykiewicz ◽  
Dorota Koziel ◽  
...  
Author(s):  
Jun Hua ◽  
Zhe Zhang ◽  
Lili Zhang ◽  
Yan Sun ◽  
Yuan Yuan

Abstract Purpose This study aimed to investigate the possibility of UCP-2 inhibitor in reducing acquired resistance of trastuzumab to improve the outcome of patients receiving trastuzumab therapy by exploring the relationship between UCP-2 expression and HER2 signaling pathway and examining whether UCP-2 expression was modulated by trastuzumab treatment. Methods 32 women diagnosed with primary HER2-positive breast cancer were recruited in this study. Needle biopsy was obtained from patients before they received at least four cycles neoadjuvant therapy containing trastuzumab in combination with chemotherapy. Surgical tumor biopsy was obtained during surgical procedure after the neoadjuvant therapy. Levels of HER2 phosphorylation and UCP-2 expression were detected by immunohistochemistry (IHC) and compared between tumor needle biopsy tissue and surgical tumor samples of these patients, as well as in BT474 breast cancer cells before and after trastuzumab treatment. HER2-selective phosphorylation/kinase activity inhibitor ONT-380 was used to identify the correlation between HER2 phosphorylation level and UCP-2 expression. UCP-2 inhibitor Genipin was then used to evaluate the apoptosis index in BT474 cells treated with trastuzumab. Results UCP-2 expression was significantly elevated in surgical tumor samples from breast cancer patients receiving trastuzumab in a neoadjuvant setting. We further confirmed our findings in HER2-positive BT474 cell line and found that trastuzumab treatment induced phosphorylation of HER2 and the overexpression of UCP-2, and the latter can be reversed by HER2 selective kinase inhibitor ONT-380. Moreover, UCP-2 inhibitor Genipin significantly enhanced the proliferation suppression effects of trastuzumab and markedly promoted apoptosis. Conclusion Taken together, our study identified UCP-2 as a novel therapeutic target for HER2 positive breast cancer and UCP-2 inhibitor may have great potential to enhance the response rate and efficacy of trastuzumab therapy.


2021 ◽  
pp. 1-6
Author(s):  
Emma C. Dunne ◽  
Edel M. Quinn ◽  
Maurice Stokes ◽  
John M. Barry ◽  
Malcolm Kell ◽  
...  

INTRODUCTION: Atypical intraductal epithelial proliferation (AIDEP) is a breast lesion categorised as “indeterminate” if identified on core needle biopsy (CNB). The rate at which these lesions are upgraded following diagnostic excision varies in the literature. Women diagnosed with AIDEP are thought to be at increased risk of breast cancer. Our aim was to identify the rate of upgrade to invasive or in situ carcinoma in a group of patients diagnosed with AIDEP on screening mammography and to quantify their risk of subsequent breast cancer. METHODS: We conducted a retrospective review of a prospectively maintained database containing all patients diagnosed with AIDEP on CNB between 2005 and 2012 in an Irish breast screening centre. Basic demographic data was collected along with details of the original CNB result, rate of upgrade to carcinoma and details of any subsequent cancer diagnoses. RESULTS: In total 113 patients were diagnosed with AIDEP on CNB during the study period. The upgrade rate on diagnostic excision was 28.3% (n = 32). 6.2% (n = 7) were upgraded to invasive cancer and 22.1% (n = 25) to DCIS. 81 patients were not upgraded on diagnostic excision and were offered 5 years of annual mammographic surveillance. 9.88% (8/81) of these patients went on to receive a subsequent diagnosis of malignancy. The mean time to diagnosis of these subsequent cancers was 65.41 months (range 20.18–145.21). CONCLUSION: Our data showing an upgrade rate of 28% to carcinoma reflects recently published data and we believe it supports the continued practice of excising AIDEP to exclude co-existing carcinoma.


2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Seongyeong Kim ◽  
Dongjin Shin ◽  
Ahrum Min ◽  
Minjung Kim ◽  
Deukchae Na ◽  
...  

Abstract Background Metastatic breast cancer (mBC) is a complex and life-threatening disease and although it is difficult to cure, patients can benefit from sequential anticancer treatment, including endocrine therapy, targeted therapy and cytotoxic chemotherapy. The patient-derived xenograft (PDX) model is suggested as a practical tool to predict the clinical outcome of this disease as well as to screen novel drugs. This study aimed to establish PDX models in Korean patients and analyze their genomic profiles and utility for translational research. Methods Percutaneous core needle biopsy or punch biopsy samples were used for xenotransplantation. Whole exome sequencing and transcriptome analysis were performed to assess the genomic and RNA expression profiles, respectively. Copy number variation and mutational burden were analyzed and compared with other metastatic breast cancer genomic results. Mutational signatures were also analyzed. The antitumor effect of an ATR inhibitor was tested in the relevant PDX model. Results Of the 151 cases studied, 40 (26%) PDX models were established. Notably, the take rate of all subtypes, including the hormone receptor-positive (HR +) subtype, exceeded 20%. The PDX model had genomic fidelity and copy number variation that represented the pattern of its donor sample. TP53, PIK3CA, ESR1, and GATA3 mutations were frequently found in our samples, with TP53 being the most frequently mutated, and the somatic mutations in these genes strengthened their frequency in the PDX model. The ESR1 mutation, CCND1 amplification, and the APOBEC signature were significant features in our HR + HER2- PDX model. Fulvestrant in combination with palbociclib showed a partial response to the relevant patient’s tumor harboring the ESR1 mutation, and CCND1 amplification was found in the PDX model. AZD6738, an ATR inhibitor, delayed tumor growth in a relevant PDX model. Conclusions Our PDX model was established using core needle biopsy samples from primary and metastatic tissues. Genomic profiles of the samples reflected their original tissue characteristics and could be used for the interpretation of clinical outcomes.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e12626-e12626
Author(s):  
Klara Geršak ◽  
Barbara Gazic ◽  
Andreja Klevisar Ivancic ◽  
Nina Ruzic Gorenjec ◽  
Cvetka Grasic Kuhar

e12626 Background: Morphological evaluation of tumor lymphocyte infiltration (TIL) in breast cancer (BC) is gaining importance in the clinical setting, as it provides good prognostic information. Most institutions adhere to TIL working group guidelines for evaluating TIL, while having to settle on an acceptable error margin due to its subjective nature, which leads to intra and inter-observer scoring discordance. We aimed to analyze both at our institution, using experienced and inexperienced examiners, with a continuous variable scoring system. Methods: 209 BC core needle biopsy (CNB) samples were stained using hematoxylin-eosin. The percentage of stromal TIL was scored using a numerical variable ranging from 1 to 100. The examination group consisted of two experienced pathologists (pathologist A and B) and one inexperienced examiner - a medical oncology resident with a learning process containing study of the TIL working group analysis criteria and about 100 samples analysed together with an experienced pathologist Pathologist A and the resident analyzed the study samples twice, pathologist B once. Intraclass correlation coefficient (ICC) was used to measure overall intra and inter-observer agreement. Statistical analysis was performed using Google Sheets and Python. Results: 203 CNB samples were analysed (6 were excluded due to inadequate quality or an inconclusive diagnosis). Patients were aged 26 to 79 years (median 49). Sample size ranged from 1 to 16 mm (median 8). The proportion of BC subtypes was: luminal A-like 18%, luminal B-like 39%, HER2+ 10%, luminal B-like HER2+ 12%, TNBC 18%, not defined 2%. The highest proportion of high stromal TIL (≥50%) was seen in HER2+ (30%) and TNBC (22%) subtypes, as observed by pathologist A. We found good intra and inter-observer ICC (Table). Conclusions: Acceptable intra and inter-observer variability was observed in experienced pathologists, suggesting that the proposed methodology could reliably be used in clinical practice, research and trials. Interestingly, variability analysis of scores from a trained non-pathologist has also produced good results. However, it is important to note that inexperienced scoring could be prone to errors, for example counting non-lymphocyte cells as such, not recognizing regions of necrosis or sample damage, or not distinguishing between the tumor and peripheral stroma. Intraclass correlation: two-way random, single score (ICC2); pathologist A and resident (R) first and second analysis (A1, A2, R1, R2); pathologist B analysis (B1). Interpretation of ICC: <0.50 poor; 0.50-0.75 moderate; 0.75-0.90 good (0.75 = minimal acceptable value for a reliable clinical measurement); >0.90 excellent. Clinical trial information: 2018-000547-11. [Table: see text]


Sign in / Sign up

Export Citation Format

Share Document