Biomarker Changes During Neoadjuvant Anastrozole, Tamoxifen, or the Combination: Influence of Hormonal Status and HER-2 in Breast Cancer—A Study from the IMPACT Trialists

2005 ◽  
Vol 23 (11) ◽  
pp. 2477-2492 ◽  
Author(s):  
Mitch Dowsett ◽  
Steve R. Ebbs ◽  
J. Michael Dixon ◽  
Anthony Skene ◽  
Clive Griffith ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Progesterone Receptor ◽  
Treated Group ◽  
Growth Factor Signaling ◽  
Tumor Biopsy ◽  
Tamoxifen Group ◽  
Her 2 ◽  
The Difference ◽  
Induced Changes ◽  
The Impact

Purpose To investigate the relationships between biomarker changes in breast cancer during neoadjuvant (preoperative) endocrine therapy. Patients and Methods The IMPACT trial compared the preoperative use of tamoxifen with anastrozole alone or in combination in postmenopausal women (n = 330) with primary breast cancer. Biomarkers were measured in tumor biopsy specimens taken at baseline, and after 2 and 12 weeks of treatment. Results A decrease in the proliferation marker Ki67 occurred in the majority of patients: 52 (93%) of 56, 46 (85%) of 54, and 37 (84%) of 44 patients in the anastrozole, tamoxifen, and combination groups, respectively. There was a significantly greater suppression of Ki67 in the anastrozole-treated group than in the tamoxifen- or combination-treated groups, which is parallel to the greater efficacy seen for anastrozole over these two treatments in the Arimidex, Tamoxifen, Alone or in Combination adjuvant trial. A positive relationship was noted between estrogen-receptor level and Ki67 suppression in all patients. Ki67 was reduced to a greater extent in progesterone receptor-positive tumors compared with progesterone receptor-negative tumors. HER-2-negative tumors tended to show a greater reduction in Ki67 compared with HER-2-positive tumors, but the difference was only significant in the tamoxifen group after 2 weeks, and in the anastrozole group after 12 weeks. Conclusion These results confirm the value of Ki67 as a molecular marker, and provide information regarding the relationships between treatment-induced changes in Ki67 and other important biomarkers. Studies such as this should help integrate agents targeted at growth factor signaling with endocrine agents in breast cancer.

scholarly journals Study on Estrogen Receptor, Progesterone Receptor and HER-2/ neu Expression Pattern by Immunohistochemistry in 87 cases of Invasive Breast Cancer

KYAMC Journal ◽  
2017 ◽  
Vol 5 (1) ◽  
pp. 436-443
Author(s):  
Md Shahadat Hossain ◽  
Ferdousy Begum ◽  
Ashim Ranjan Barua
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Progesterone Receptor ◽  
Expression Pattern ◽  
Invasive Breast Cancer ◽  
Standard Procedure ◽  
Low Grade ◽  
Positive Reactivity ◽  
Her 2 ◽  
Grade Tumour

Background: Now a day's determination of estrogen receptor (ER), progesterone receptor (PR) and HER-2/neu expression pattern by immunohistochemistry in invasive breast cancer have become the standard procedure for breast cancer management.Objective: To see the expression pattern of estrogen receptor, progesterone receptor and HER-2/neu in Bangladeshi women with invasive breast carcinoma.Method: This cross sectional study was performed in 87 cases of invasive breast cancer. Estrogen receptor (ER), Progesterone receptor (PR) and HER-2/neu expression pattern were assessed by immunohistochemistry using monoclonal antibodies for detecting estrogen and progesterone receptors, and polyclonal antibody for detecting HER-2/neu.Results: All the cases were graded according to Bloom-Richardson grading system. Of those, Grade I tumour was 18 (20.69%), Grade II tumour was 58 (66.67%) and Grade III tumour was 11(12.64%). Both ER and PR positive reactivity were same and it was found 65 (74.71%) and HER-2/neu reactivity pattern were found negative in 59 (67.82%) cases and positive in 28 (32.18%) cases. A statistically significant correlation was found between the expression of ER and low grade tumour (p=0.011) and combined estrogen and progesterone receptor positive reactivity with low grade tumour (p=0.002).Conclusion: ER, PR and HER-2/neu expression do not correlated with each other, so it is recommended that each test should be independently determined by immunohistochemistry in all cases of invasive breast cancer. All equivocal cases of HER-2/neu (score 2+) should be analyzed by FISH technique to find out the percentage of real score.KYAMC Journal Vol. 5, No.-1, Jul 2014, Page 436-443

scholarly journals Antiangiogenic therapy for breast cancer with triple negative phenotype

2021 ◽  
Vol 23 (1) ◽  
pp. 88-92
Author(s):  
Inna P. Ganshina ◽  
Kristina A. Ivanova ◽  
Olga O. Gordeeva ◽  
Aleksandr V. Arkhipov ◽  
Liudmila G. Zhukova
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Malignant Tumors ◽  
Antiangiogenic Therapy ◽  
Treatment Strategies ◽  
Her 2 ◽  
Triple Negative Phenotype ◽  
The Impact ◽  
Negative Phenotype

Triple-negative breast cancer is 1024% of all cases of breast cancer and is characterized by the absence of estrogen, progesterone, and HER-2 receptors in the tumor. The therapy of this illness is a difficult clinical case. In contrast to hormone-positive and HER-2-positive phenotypes, in which we successfully use targeted drugs (antiestrogens and anti-HER-2 drugs), for triple-negative breast cancer we have not had such targets for a long time. Thus, despite the impressive results of immunotherapy of triple-negative breast cancer, there remains a fairly large group of patients with negative PD-L1 status, for whom it is necessary to develop other treatment strategies. One of the approaches in the treatment of malignant tumors includes not the impact on tumor cells, but the process of angiogenesis. Antiangiogenic drugs have positively proven themselves in the treatment of a large number of malignant tumors but are underestimated for breast cancer (including triple-negative phenotype). The use of bevacizumab in combinations with cytostatic drugs in breast cancer therapy (including triple-negative breast cancer) has been studied in a large number of clinical trials but was undeservedly forgotten in some countries due to the revoked FDA registration. This review presents the role of bevacizumab in the treatment of patients with triple-negative breast cancer and suggests the conditions when the administration of this drug is justified and leads to better results.

scholarly journals Molecular Mechanisms of Antitumor Activity of PAMAM Dendrimer Conjugates with Anticancer Drugs and a Monoclonal Antibody

Polymers ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 1422 ◽  
Author(s):  
Marcinkowska ◽  
Stanczyk ◽  
Janaszewska ◽  
Gajek ◽  
Ksiezak ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Monoclonal Antibody ◽  
Antitumor Activity ◽  
Molecular Mechanisms ◽  
Pamam Dendrimer ◽  
Breast Cancer Cell Lines ◽  
Cytotoxic Action ◽  
Her 2 ◽  
The Impact ◽  
Dendrimer Conjugates

Taxanes are considered fundamental drugs in the treatment of breast cancer, but despite the similarities, docetaxel (doc) and paclitaxel (ptx) work differently. For this reason, it is interesting to identify mechanisms of antitumor activity of PAMAM dendrimer conjugates that carry docetaxel or paclitaxel and monoclonal antibody trastuzumab, specifically targeted to cells which overexpressed HER-2. For this purpose, the impact on the level of reactive oxygen species, the mitochondrial membrane potential, cell cycle distribution and the activity of caspases-3/7, -8 and -9 of PAMAM-doc-trastuzumab and PAMAM-ptx-trastuzumab conjugates was determined and compared with free docetaxel and paclitaxel toward HER-2-positive (SKBR-3) and negative (MCF-7) human breast cancer cell lines. Moreover, apoptosis and necrosis were studied using flow cytometry and confocal microscopy, respectively. Our studies show the complexity of the potential mechanism of cytotoxic action of PAMAM-drug-trastuzumab conjugates that should be sought as a resultant of oxidative stress, mitochondrial activation of the caspase cascade and the HER-2 receptor blockade.

scholarly journals A Rare Case of Triple Positive Metachronous Breast Cancer

2019 ◽  
Vol 7 ◽  
pp. 232470961989210
Author(s):  
Hardik S. Chhatrala ◽  
John Khuu ◽  
Lara Zuberi
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Brain Metastasis ◽  
Progesterone Receptor ◽  
Rare Case ◽  
Contralateral Breast Cancer ◽  
Contralateral Breast ◽  
Her 2 ◽  
Metachronous Breast Cancer ◽  
Aggressive Clinical Course

Metachronous contralateral breast cancer (MCBC) is defined as contralateral breast cancer (BC) diagnosed more than 1 year after previous BC diagnosis. More BC survivors are at risk of MCBC given improved life expectancy with the availability of advanced cancer care. Estrogen receptor/progesterone receptor negative and HER-2-positive status of first BC are independent risk factors for the development of MCBC. We present a rare case of triple positive (estrogen receptor, progesterone receptor, HER-2 positive) MCBC patient who eventually developed brain metastasis within 15 months despite a near complete pathologic response of primary tumor. This case highlights that even in this era of antiestrogen and anti-HER-2 therapies, triple positive MCBC can have an aggressive clinical course, especially with brain metastasis as the first sign of metastasis.

Azurin, highly potent and selective anticancer agent for breast cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 13106-13106
Author(s):  
T. Yamada ◽  
R. Mehta ◽  
D. Majumdar ◽  
A. M. Chakrabarty ◽  
T. K. Das Gupta
Keyword(s):  
Breast Cancer ◽  
Tumor Growth ◽  
Cancer Cells ◽  
Tumor Volume ◽  
Tumor Regression ◽  
Treated Group ◽  
Redox Protein ◽  
The Mean ◽  
The Difference ◽  
Mcf 7

13106 Background: The use of live or attenuated pathogenic bacteria in the treatment of cancer dates back to the late nineteen hundreds when William B. Coley first reported that inducing Streptococcal infection resulted in tumor regression. However, the hazards of using live bacteria are obvious. Similarly, the results of using attenuated bacteria have been spotty and enthusiasm for it has waxed and waned. Recently, we have shown that redox protein azurin (14 kDa) secreted by an opportunistic pathogen, Pseudomonas aeruginosa, is not only cytotoxic to cancer cells in vitro but also produces tumor regression in athymic mice without producing any toxicity (PNAS, 99, 14098–14103, 2002; Science’s STKE, 158, tw416, 2002). Methods: In this study, we show the effect of 1mg/kg of azurin injected i.p. starting 72 hours after inoculation of 5x107 MCF-7 breast cancer cells in estradiol pretreated nude mice for 28 days (n = 20, control = 10, azurin-treated = 10). Results: Univariate analysis of the data showed the difference in tumor growth rates between control animals and azurin-treated animals was significant. For instance, 22 days after the start of treatment, the mean tumor volume in azurin-treated animals was only 22% of the mean tumor volume in the control mice (i.e., 0.0267 cm3 + 0.124 cm3 respectively, P = 0.0179 Kruskal-Wallis test). At the end of the experiment on the 29th day there was a reduction in the tumor volume by 85% in the treated group. We used a multivariate model, where the tumor growth over time was taken to be exponential with coefficients that were subject specific mixed effect (For control, tumor volumes = exp (−4.23 + 0.06 time) while for the treated group it was tumor volume = exp (−4.23 + 0.03 time)). The difference is statistically significant (P = 0.0456). Taken together, this in vivo data shows azurin exerts an inhibitory effect in the growth and progression of MCF-7 tumor xenotransplants. During the 28 days of treatment, treated animals did not show any sign of toxicity. Conclusions: Bacterial redox protein azurin can be explored as a novel therapeutic agent for treatment of breast cancer. Recently, we have prepared a truncated version of azurin which has 28 amino acids. It appers that this chemically synthesized peptide (2.8 kDa) has similar properties as azurin. No significant financial relationships to disclose.

Prospective monitoring of circulating tumor cells in breast cancer patients treated with primary systemic therapy—A translational project of the German Breast Group study GeparQuattro

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 21085-21085 ◽  
Author(s):  
V. Mueller ◽  
S. Riethdorf ◽  
S. Loibl ◽  
M. Komor ◽  
J. Houber ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Metastatic Breast ◽  
Primary Diagnosis ◽  
Breast Cancer Patients ◽  
Primary Systemic Therapy ◽  
Her 2 ◽  
The Impact

21085 Background: The impact of circulating tumor cells (CTC) in patients with primary breast cancer is still unclear. Primary systemic treatment (PST) allows the assessment of therapeutic efficacy in breast cancer patients without long follow-up periods. Here we present first results on the presence of CTC in peripheral blood of patients enrolled in the “GeparQuattro” study. Methods: This study incorporates three different chemotherapy approaches and additional Trastuzumab (Herceptin®) treatment for patients with HER-2/neu-positive tumors. Recruitment finished in November 2006 and not all patients have completed therapy yet. We used the CellSearch™ system to evaluate CTC before PST from 245 patients and after PST from 67 patients. CTC from 45 samples were also examined for HER-2/neu expression by immunocytochemistry in the CellSearch™ system. Results: Before PST we detected CTC in 54/245 patients (22%). CTC numbers in 7.5 mL blood ranged between 1 and 200 (mean 6.5). In 8 CTC-positive samples (3.3%) = 5 CTC were found. Her-2/neu-positive CTC were observed in 25/45 cases (55.6%). CTC could be detected in 7/67 patients (10.4%) after PST (1 or 2 CTC). Before and after PST blood was analyzed from 43 patients, 27 of them were CTC-negative at both time points. Ten initially CTC-positive cases were CTC-negative after PST whereas 6 cases were detected CTC-positive after PST although no CTC could be found before PST. Conclusions: With the CellSearch™ system CTC can be detected in non-metastatic breast cancer patients at primary diagnosis and also after PST. To our knowledge, this is the largest study evaluating the presence of CTC in this context. With the availability of response information from more patients, it will be possible to examine the correlation between the incidence of CTC and response as well as kinetics of HER-2/neu expression during Trastuzumab treatment. [Table: see text]

Results of ENCORE 301, a randomized, phase II, double-blind, placebo-controlled study of exemestane with or without entinostat in postmenopausal women with locally recurrent or metastatic estrogen receptor-positive (ER+) breast cancer progressing on a nonsteroidal aromatase inhibitor (AI).

2011 ◽  
Vol 29 (27_suppl) ◽  
pp. 268-268 ◽  
Author(s):  
D. A. Yardley ◽  
R. Ismail-Khan ◽  
P. Klein
Keyword(s):  
Breast Cancer ◽  
Postmenopausal Women ◽  
Hormonal Therapy ◽  
Stage Iv ◽  
Phase Iii ◽  
Controlled Study ◽  
Growth Factor Signaling ◽  
Intrinsic Resistance ◽  
Double Blind ◽  
The Impact

268 Background: Hormonal therapy, including AIs, is the mainstay of ER+ breast cancer (BC) treatment; however, both acquired and intrinsic resistance limits its clinical benefit. Entinostat is a novel, oral, class I selective histone deacetylase inhibitor that has been shown to inhibit growth factor signaling pathways that mediate AI resistance. This study was designed to evaluate the impact of the addition of entinostat to exemestane therapy on progression-free survival (PFS). Methods: Postmenopausal women with ER+ advanced BC who had progressed on a non-steroidal AI were randomized to exemestane 25 mg daily + entinostat 5 mg or placebo weekly. Results: A total of 130 women were enrolled (66 exemestane+placebo; 64 exemestane+entinostat). All but 1 patient had Stage IV disease, and 82% had measurable disease. All patients had received prior hormonal therapy (1 prior line 42%; >1 prior line 58%), and 62% had received prior chemotherapy (33% in the advanced BC setting). Analysis of the intent-to-treat population showed that PFS was significantly (defined prospectively as p <0.10) longer with exemestane+entinostat than with exemestane+placebo (4.28 versus 2.27 months, respectively; hazard ratio [HR] = 0.73; p=0.06). Entinostat combined with exemestane was well-tolerated with the most frequent adverse events (AEs) consisting of fatigue, gastrointestinal disturbances, and hematologic abnormalities. AEs with a ≥20% higher incidence with exemestane+entinostat than with exemestane+placebo were fatigue (46% versus 26%, respectively) and uncomplicated neutropenia (25% versus 0%, respectively). The serious AE rate was similar for exemestane+entinostat (13%) and exemestane+placebo (12%). Conclusions: Exemestane+entinostat significantly prolonged the median PFS and reduced the risk of disease progression by 27% versus exemestane+placebo (HR = 0.73). In light of these positive data, a phase III evaluation of this combination is planned.

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