scholarly journals Biomarker and multigene assay testing in ER positive, HER-2 negative breast carcinomas: An international guidelines-based approach

2021 ◽  
Vol 26 ◽  
pp. 300574
Author(s):  
Bradley M. Turner ◽  
Hani Katerji ◽  
Huina Zhang ◽  
David G. Hicks
Keyword(s):  
Breast Carcinomas ◽  
International Guidelines ◽  
Er Positive ◽  
Multigene Assay ◽  
Her 2

scholarly journals Induction of Apoptosis in MDA-MB-231 Cells Treated with the Methanol Extract of Lichen Physconia hokkaidensis

2021 ◽  
Vol 7 (3) ◽  
pp. 188
Author(s):  
Ji-In Noh ◽  
Seul-Ki Mun ◽  
Eui Hyeon Lim ◽  
Hangun Kim ◽  
Dong-Jo Chang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Prolonged Exposure ◽  
Methanol Extract ◽  
Growth Factor Receptor ◽  
Annexin V ◽  
Er Positive ◽  
Her 2 ◽  
Induction Of Apoptosis ◽  
Mcf 7

Physconia hokkaidensis methanol extract (PHE) was studied to identify anticancer effects and reveal its mechanism of action by an analysis of cytotoxicity, cell cycles, and apoptosis biomarkers. PHE showed strong cytotoxicity in various cancer cells, including HL-60, HeLa, A549, Hep G2, AGS, MDA-MB-231, and MCF-7. Of these cell lines, the growth of MDA-MB-231 was concentration-dependently suppressed by PHE, but MCF-7 was not affected. MDA-MB-231 cells, triple-negative breast cancer (TNBC) cells, do not express estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER-2), whereas MCF-7 cells are ER-positive, PR-positive, and HER-2-negative breast cancer cells. The number of cells in sub-G1 phase was increased after 24 h of treatment, and annexin V/PI staining showed that the population size of apoptotic cells was increased by prolonged exposure to PHE. Moreover, PHE treatment downregulated the transcriptional levels of Bcl-2, AMPK, and p-Akt, whereas it significantly upregulated the levels of cleaved caspase-3, cleaved caspase-9, and cleaved-PARP. In conclusion, it was confirmed that the PHE exhibited selective cytotoxicity toward MDA-MB-231, not toward MCF-7, and its cytotoxic activity is based on induction of apoptosis.

Short Preoperative Treatment With Erlotinib Inhibits Tumor Cell Proliferation in Hormone Receptor–Positive Breast Cancers

2008 ◽  
Vol 26 (6) ◽  
pp. 897-906 ◽  
Author(s):  
Marta Guix ◽  
Nara de Matos Granja ◽  
Ingrid Meszoely ◽  
Theresa B. Adkins ◽  
Bobbye M. Wieman ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Tumor Cell ◽  
Growth Factor Receptor ◽  
Preoperative Treatment ◽  
Breast Cancers ◽  
Tumor Cell Proliferation ◽  
Hormone Receptor Positive ◽  
Er Positive ◽  
Her 2

Purpose To administer the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor erlotinib to patients with operable untreated breast cancer during the immediate preoperative period and to measure an antiproliferative and/or a proapoptotic effect in the post-therapy specimen and determine a biomarker profile associated with evidence of erlotinib-mediated cellular activity. Patients and Methods Newly diagnosed patients with stages I to IIIA invasive breast cancer were treated with erlotinib 150 mg/d orally for 6 to 14 days until the day before surgery. Erlotinib plasma levels were measured by tandem mass spectrometry the day of surgery. Drug-induced changes in tumor cell proliferation and apoptosis were assessed by Ki67 immunohistochemistry and terminal deoxynucleotidyl transferase–mediated deoxyuridine triphosphate-biotin nick-end labeling analysis, respectively, in biopsies from the pretherapy and surgical specimens. Biopsies were also evaluated for P-EGFR, P-HER-2, P-MAPK, P-Akt, P-S6, and S118 P-ERα. Results In drug-sensitive PC9 xenografts, 5 days of treatment with erlotinib were enough to induce a maximal inhibition of cell proliferation and induction of apoptosis. Forty-one patients completed preoperative treatment with erlotinib. Grade ≤ 2 rash and diarrhea were the main toxicities. Erlotinib inhibited tumor cell proliferation (Ki67), P-EGFR, and P-HER-2. The inhibition of proliferation occurred in estrogen receptor (ER) –positive but not in human epidermal growth factor receptor 2 (HER-2) –positive or triple-negative cancers. Treatment was associated with a significant reduction of P-MAPK, P-Akt, P-S6, and S118 P-ERα in hormone receptor–positive cancers. Conclusion A presurgical approach to evaluate cellular responses to new drugs is feasible in breast cancer. EGFR inhibitors are worthy of testing against ER-positive breast cancers but are unlikely to have clinical activity against HER-2–positive or triple-negative breast cancers.

scholarly journals The Evaluation of HER-2 Status with Immunohistochemical and Molecular Analyses In Breast Carcinomas

2015 ◽  
Vol 25 (1) ◽  
Author(s):  
Nuket Eliyatkin ◽  
Hakan Ozgur ◽  
Pinar Ercetin ◽  
Safiye Aktas ◽  
Ali Kupelioglu
Keyword(s):  
Breast Carcinomas ◽  
Molecular Analyses ◽  
Her 2

Analysis of Low Estrogen Receptor (ER+) Breast Carcinomas in a Large Community Breast Cancer Center in Northern California

2021 ◽  
Vol 156 (Supplement_1) ◽  
pp. S26-S27
Author(s):  
G Bulusu ◽  
K Duncan ◽  
A Wheeler
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Histological Grade ◽  
Statistical Significance ◽  
Cancer Center ◽  
Pathology Report ◽  
Breast Cancers ◽  
Breast Carcinomas ◽  
Ki 67 ◽  
Er Positive

Abstract Introduction/Objective Estrogen Receptor (ER) expression in breast cancers is a crucial factor for endocrine therapy in patients with tumors expressing ER in ≥1% of tumor cells. The 2019 guidelines published by ASCO/CAP states that breast cancers that have a 1% to 10% of cells staining Estrogen Receptor (ER) positive should be reported as ER Low Positive cases. This study aims to address this subset of low-positive ER tumors and compare the clinical features to other known breast cancer subtypes. Methods/Case Report We conducted a retrospective review of a prospectively maintained breast cancer registry from 2013 to 2021 at Mills-Peninsula Medical Center, a Sutter Health Affiliate. The study reviewed patient charts with respect to the pathology report, operative report, chemotherapy regimen, and clinical outcomes. Statistical analyses were conducted using R Project for Statistical Coding, with The Student’s T-test used to compare continuous variables. Two-sided P values less than 0.05 indicate statistical significance. Results (if a Case Study enter NA) Our study identified 1316 cases of invasive breast carcinomas, of which 29 (2.16%) demonstrated ER Low-Positive expression. We aimed to evaluate the clinical and pathological features, such as histological grade, ER, PR, HER-2, Ki-67%, and patient age for these tumors. We found that ER Low-Positive tumors demonstrated higher mean histological grade morphology (2.5 out of 3, p<0.001) that was similar to that of Triple Negative Breast Cancers (TNBC) (3 of 3, p<0.001) than to High ER-Positive (1.6 of 3, p<0.001) cancers. Further observations, through examining proliferation rates by utilizing the Ki-67 index, indicate comparative trends between the ER Low-Positive cohort and the TNBC cohort. Conclusion The results suggest that the ER Low-Positive carcinomas, despite reported as ER-positive cases, present with similar clinicopathological features to those of ER-negative tumors. Through this study and future research, we would like to emphasize a stricter set of guidelines that can be adopted to reduce variability for reporting biomarkers. This standardization will allow oncologists to provide more appropriate treatment options and improve the quality of patient care.

Immunohistochemical COX-2 overexpression correlates with HER-2/neu overexpression in invasive breast carcinomas: A pilot study

2011 ◽  
Vol 207 (3) ◽  
pp. 182-187 ◽  
Author(s):  
İbrahim Metin Çiriş ◽  
Kemal Kürşat Bozkurt ◽  
Şirin Başpinar ◽  
Fatma Nilgün Kapucuoğlu
Keyword(s):  
Pilot Study ◽  
Breast Carcinomas ◽  
Her 2 ◽  
Cox 2 ◽  
Invasive Breast Carcinomas

Abstract P5-21-22: Palbociclib in highly pretreated metastatic ER-positive HER-2 negative breast cancer

2018 ◽  
Author(s):  
G Hoste ◽  
K Punie ◽  
H Wildiers ◽  
P Neven ◽  
P Berteloot ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Er Positive ◽  
Her 2

HER-2/neu expression in ovarian clear cell carcinomas

2003 ◽  
Vol 13 (1) ◽  
pp. 28-31 ◽  
Author(s):  
H. Iwamoto ◽  
H. Fukasawa ◽  
T. Honda ◽  
S. Hirata ◽  
K. Hoshi
Keyword(s):  
Breast Carcinoma ◽  
Cell Carcinoma ◽  
San Francisco ◽  
Clear Cell ◽  
Clear Cell Carcinoma ◽  
Metastatic Breast ◽  
Breast Carcinomas ◽  
Ovarian Clear Cell Carcinoma ◽  
Clinical Prognosis ◽  
Her 2

HER-2 /neu is a 185-kDa glycoprotein and a transmembrane receptor with tyrosine kinase activity. Its overexpression is observed in 25–30% of primary breast carcinomas and is associated with a poor clinical prognosis. Recently, the U.S. Food and Drug Administration and the Japanese Ministry of Health, Welfare, and Labor approved the use of trastuzumab (Herceptin, Genentech, South San Francisco, CA) for the treatment of patients with metastatic breast carcinomas overexpressing HER-2 /neu. Results of clinical trials with Herceptin suggest that it may prolong the survival of patients with advanced metastatic breast carcinoma. Relatively little is known concerning the relationship between HER-2 /neu status and ovarian clear cell carcinoma. If HER-2 /neu overexpression status were demonstrable in ovarian clear cell carcinoma and a clinical correlation between overexpression and prognosis could be established, a rationale for clinical use of Herceptin for this tumor could be established. Our aim was to evaluate HER-2 /neu status in ovarian clear cell carcinomas. Fifteen ovarian clear cell carcinoma cases were immunostained for HER-2 /neu using HercepTest (DAKO, Glostrup, Denmark). Overexpression of HER-2 /neu was detected in only one case. Unlike in breast carcinoma, HER-2 /neu overexpression appeared to be uncommon in ovarian clear cell carcinomas. Herceptin may thus target only a small proportion of ovarian clear cell carcinomas and be of limited clinical value for treatment of this carcinoma.

Relation between cathepsin D expression and other prognostic factors in breast carcinomas

1995 ◽  
Vol 41 (11) ◽  
pp. 1585-1591 ◽  
Author(s):  
R M Shaheen ◽  
S Miseljic ◽  
R D Wiehle ◽  
J L Wittliff
Keyword(s):  
Standardized Testing ◽  
Cathepsin D ◽  
Epidermal Growth Factor Receptors ◽  
Reference Laboratory ◽  
Breast Carcinomas ◽  
Human Breast ◽  
Progestin Receptor ◽  
Her 2 ◽  
Epidermal Growth ◽  
Reference Specimens

Abstract We evaluated cathepsin D concentrations in 318 breast carcinoma specimens with a standardized IRMA and established distribution values of 5.9-217.8 nmol/g (median 51.8). Concentrations of cathepsin D did not correlate with age or with concentrations of HER-2/neu oncoprotein, estrogen receptor, or epidermal growth factor receptors. A significant correlation was observed between cathepsin D and progestin receptor (P = 0.009), but only in postmenopausal patients. In our role as a National Reference Laboratory for conducting interlaboratory comparisons of tumor markers, we evaluated cathepsin D assay proficiency by using control samples with intra- and interassay CVs of 2-8% and 10-13%, respectively. Human reference specimens containing known quantities of cathepsin D were developed to facilitate standardized testing. The IRMA procedure and the use of quality-assurance samples permits evaluation of the clinical significance of cathepsin D in human breast cancer trials.

Predictors of response to primary systemic therapy (PST) with docetaxel and trastuzumab in HER2-positive breast cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 11100-11100
Author(s):  
M. Rao ◽  
J. J. Griggs ◽  
L. M. Schiffhauer ◽  
P. Messina ◽  
P. Bourne ◽  
...  
Keyword(s):  
Survival Data ◽  
Disease Free Survival ◽  
Left Ventricular ◽  
Response To Therapy ◽  
Left Ventricular Ejection ◽  
Ventricular Ejection Fraction ◽  
Er Positive ◽  
Her 2 ◽  
Disease Free

11100 Background: The purpose of this study was to assess the relationship between estrogen receptor (ER) status, amplification of HER-2, and tumor response to PST with docetaxel and trastuzumab in breast cancers positive for HER-2 by immunohistochemistry (IHC). Long-term disease-free survival data are also reported. Methods: Eligible patients were those with T2 or T3 tumors and overexpression of HER-2 via IHC. Docetaxel 100 mg/sq m q. 3 weeks × 4 with growth factor support and weekly trastuzumab × 12 were given before surgery. The Miller-Payne system was used to define pathologic responses (PR) in the excision specimen (0, 1, 2 - no/minimal response; 3 - 4 partial response, pPR; 5 - complete response, pCR). Adjuvant therapy was given at the discretion of the treating oncologist. Results: Of 22 enrolled patients, 19 were assessable. 17 of the 19 subjects had subsequent FISH confirmation of HER-2 status. Six subjects (31%) had a pCR. Of these, 5 had strong amplification of HER-2 and 5 had tumors that were ER-negative. A pPR occurred in an additional 2 subjects (10%). Of the 11 subjects who had no or minimal PR (Miller-Payne 0 - 2), 8 were found to have no amplification for HER-2 and 9 had tumors that were ER-positive. Postoperative (adjuvant) chemotherapy was given to 17 patients. All 12 patients with ER-positive tumors received adjuvant hormonal therapy. Three patients had an asymptomatic decline in left ventricular ejection fraction (LVEF) of 10 - 15% after anthracycline containing chemotherapy, and one had symptomatic non-ischemic cardiomyopathy of unclear etiology 4 years after completion of study therapy and an anthracycline. With a median follow up of 56 months, all 19 participants are alive and disease-free. Conclusion: PST with a 12-week course of trastuzumab and docetaxel is safe and effective, produces a substantial pCR rate, and may result in excellent long-term recurrence-free and overall survival. The subset of patients with tumors that were IHC-positive, but FISH-negative for HER-2, and ER-positive had minimal or no response to therapy, highlighting the importance of identifying patients most likely to respond to trastuzumab-based regimens. [Table: see text]

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