scholarly journals IN6 ADVANCES IN CYTOTOXIC AND OTHER TARGETED THERAPY OUT OF HER2, ER AND TRIPLE NEGATIVE METASTATIC BREAST CANCERS

The Breast ◽  
2013 ◽  
Vol 22 ◽  
pp. S20
Author(s):  
Joseph Gligorov
Keyword(s):  
Targeted Therapy ◽  
Triple Negative ◽  
Metastatic Breast ◽  
Breast Cancers

scholarly journals PIK3CA mutations in Peruvian patients with HER2-amplified and triple negative non-metastatic breast cancers

2014 ◽  
Vol 7 (4) ◽  
pp. 142-148 ◽  
Author(s):  
Carlos A. Castaneda ◽  
Marco Lopez-Ilasaca ◽  
Joseph A. Pinto ◽  
Michelle Chirinos-Arias ◽  
Franco Doimi ◽  
...  
Keyword(s):  
Triple Negative ◽  
Metastatic Breast ◽  
Breast Cancers ◽  
Pik3ca Mutations

Triple Negative Breast Cancer Pathologic Diagnosis and Current Chemotherapy Treatment Options

2014 ◽  
Vol 10 (01) ◽  
pp. 35 ◽  
Author(s):  
Bernardo L Rapoport ◽  
Simon Nayler ◽  
Georgia S Demetriou ◽  
Shun D Moodley ◽  
Carol A Benn ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Hormone Receptors ◽  
Triple Negative ◽  
Treatment Options ◽  
Single Agent ◽  
Metastatic Breast ◽  
Complete Response ◽  
Breast Cancers ◽  
Metastatic Setting

Triple negative breast cancer (TNBC) comprises 12–20 % of all breast cancers and are a heterogeneous group of tumours, both clinically and pathologically. These cancers are characterised by the lack of expression of the hormone receptors oestrogen receptor (OR) and progesterone receptor (PR), combined with the lack of either overexpression or amplification of the human epidermal growth factor receptor-2 (HER2) gene. Conventional cytotoxic chemotherapy and DNA damaging agents continue to be the mainstay of treatment of this disease in the neoadjuvant, adjuvant and metastatic setting. The lack of predictive markers in identifying potential targets for the treatment of TNBC has left a gap in directed therapy in these patients. Platinum agents have seen renewed interest in TNBC based on an increasing body of preclinical and clinical data suggesting encouraging activity. However, comparisons between chemotherapy regimens are mostly retrospective in nature and the best agents or drug combinations for TNBC have not been established in prospective randomised trials. Numerous studies have now shown that TNBC has significantly higher pathological complete response (pCR) rates compared with hormone receptor positive breast cancer when treated with neoadjuvant chemotherapy, and pCR correlates well with better outcomes for these patients. Patients with TNBC account for a larger number of deaths in the setting of metastatic breast cancer. There is no preferred treatment for the first-line metastatic setting. Although individual agents are recommended, given the often aggressive nature of TNBC and the presence of extensive visceral disease, the use of a combination of drugs, rather than a single agent, is often advocated. This review article will outline the pathological diagnosis of TNBC and the treatment options available to these patients in the neoadjuvant, adjuvant and metastatic setting, including an assessment of future directions of treatment.

Effect of mTOR inhibition on sensitivity of triple-negative breast cancer cells to epidermal growth factor inhibition

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 1055-1055 ◽  
Author(s):  
T. Liu ◽  
R. Yacoub ◽  
T. Graham ◽  
L. Yang ◽  
M. Tighiouart ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Triple Negative ◽  
Metastatic Breast ◽  
Mtor Inhibitors ◽  
Egfr Inhibitors ◽  
Breast Cancers ◽  
Mtor Inhibition

1055 Background: The outcome for patients with triple negative (TN) cancers is poor at least in part because of a lack of targeted therapies. Although 50% of TN breast cancers over-express EGFR, the use of EGFR inhibitors as single agents in patients with unselected and TN metastatic breast cancers has produced disappointing results. Likewise, mTOR inhibitors have modest activity as single agents in metastatic breast cancer. mTOR inhibitors have been demonstrated to activate the Akt pathway by a possible feedback mechanism, which could potentially sensitize TN breast cancer cells to upstream inhibitors. We have previously demonstrated that EGFR inhibitors in combination with rapamycin (RAPA) decrease cell survival, increase apoptosis, and are synergistic in TN breast cancer cells, compared to any of the agents alone (AACR 2008). We, therefore, evaluated the combination of mTOR and EGFR inhibition in vivo. Methods: Athymic mice were inoculated with TN (MDA-MB-231) breast cancer cells. One week after cell inoculation, mice were treated with vehicle, lapatinib 75mg/kg by mouth daily, RAPA 3mg/kg IP biweekly, or the combination. After 4 weeks of treatment, mice were sacrificed and tumors were assessed for target proteins by Western blotting and immunohistochemistry Results: The combination of RAPA and lapatinib resulted in a significant decrease in TN breast tumor volume (76 mm3), compared to rapamycin alone (133 mm3, p = 0.01), lapatinib alone (183 mm3, p < 0.0001) or control (188 mm3, p = 0.005). Neither lapatinib nor RAPA alone inhibited tumor growth significantly compared to control (p > 0.05). Interestingly, in contrast to our findings in vitro, the increase in pAkt noted in RAPA treated tumors was not decreased by lapatinib, despite the significant decrease in tumor size in tumors treated with the combination. Conclusions: These studies demonstrate that the combination of mTOR inhibition and lapatinib significantly inhibit TN breast cancer growth, compared with either agent alone. Given the lack of targeted therapies in TN breast cancers, these data support the possibility that mTOR inhibition can sensitize TN breast cancers to EGFR inhibitors. A clinical trial evaluating the combination of lapatinib and RAD001 as second-line therapy for TN metastatic breast cancer is planned. [Table: see text]

Treatment pattern by hormone receptors and HER2 status in patients with metastatic breast cancer in the United Kingdom, Germany, France, Spain, and Italy (EU-5): Results from a physician survey.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 570-570 ◽  
Author(s):  
Mitch DeKoven ◽  
Vijayveer Bonthapally ◽  
Won Chan Lee ◽  
Prathamesh Pathak ◽  
Xiaolong Jiao ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Targeted Therapy ◽  
Triple Negative ◽  
Specific Treatment ◽  
Metastatic Breast ◽  
Stage Iv ◽  
Her2 Status ◽  
The Uk ◽  
The Eu

570 Background: The differences in country-specific treatment patterns across Europe for Stage IV metastatic breast cancer (mBC) patients have not been extensively studied. This study compared treatment choices, by biomarker status, between various lines of therapy (LOT) in clinical practice in the EU-5 countries among newly diagnosed stage IV mBC patients. Methods: The IMS LifeLink Oncology Analyzer (OA) database, based upon practicing oncologist surveys, was used to identify mBC patients aged ≥21 and surveyed between July 2008 – June 2010. The database encompasses over 100,000 unique patients per year, treated by nearly 3,000 physicians, including nearly 60,000 patients and 800 physicians in the EU5. Results: A total of 152,311 mBC patients were included in the study. In Italy, 30.8% of HER2+/HR+ patients received chemotherapy following mBC diagnosis, as compared to only 8.6% in France. The majority of these patients in France received chemotherapy plus a HER2 targeted therapy (58.2%) as their first treatment. For HER2+/ HR- patients, chemotherapy plus a HER2 targeted therapy was provided to the majority of the patients in France (70.8%), with the UK providing this regimen to the fewest patients with this biomarker status (44.9%). Monotherapy hormonal regimens were given as a first LOT for HER2-/HR+ patients (UK 64.7%, Spain 52.8%). Triple negative patients received chemotherapy (UK 84.1% as compared to France 57.3%) or chemotherapy plus bevacizumab (France 36.6% as compared to UK 0.9%) as a first treatment. Conclusions: Thisstudy confirmed that chemotherapy combined with HER2-targeted therapy was the most frequent initial treatment option for HER2+ patients, while the vast majority of ER/PR+ patients were initially treated by hormonal therapy, suggesting that a personalized medicine approach has been accepted in the EU-5. However, the use of HER2-targeted therapy and bevacizumab greatly varied; while they were most frequently used in France, they were least frequently opted for in the UK. Also, fewer treatment options existed for triple negative patients and patients with HER2+ disease following trastuzumab treatment.

Patterns of mutation enrichment in metastatic triple-negative breast cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e12596-e12596
Author(s):  
Cesar H. Saravia ◽  
Claudio J. Flores ◽  
Luis Jesus Schwarz ◽  
Leny Bravo ◽  
Jenny Zavaleta ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Multiple Testing ◽  
Triple Negative ◽  
Metastatic Breast ◽  
Genetic Alterations ◽  
Breast Cancers ◽  
Number Variation ◽  
Cancer Project ◽  
Chisquare Test

e12596 Background: Triple-Negative breast cancer (TNBC) is a group of heterogeneous tumors with aggressive biology. The purpose of this research was to evaluate enrichment patterns of genomic alterations in metastatic TNBC (mTNBC). Methods: We retrieved genomic data (mutations and copy number variation) from 550 primaries TNBC (pTNBC) from the projects METABRIC and TCGA and 58 mTNBC from the projects “Mutational Profile of Metastatic Breast Cancers” and “The metastatic Breast Cancer Project”. Differences in the proportions of mutations between primary vs. metastatic tumors were evaluated by the Chisquare test and the percentage of enrichment in mTNBC was estimated. Pvalues were adjusted for multiple testing with the Benjamini-Hochberg method with and a FDR < 0.05. In addition we conducted an analysis of the hallmarks of cancers enriched in mTNBC. Results: In total, mutations in eight genes were significantly enriched in mTNBC after correcting for multiple testing. These genes included TTN, HMCN1, RELN, PKHD1L1, DMD, FRAS1 and RYR3. In the other hand, only amplification of RPS6KB2 was enriched in mTNBC. Deletions were enriched more frequently in the genes TET1, RHOA, EPHA5, SET, KCNJ5, ABCG4, NKX3-1, SDHB, IGF2, BRCA1, among others. The hallmark of “genetic instability and mutation” was over represented while the hallmark “activating immune destruction” was the least represented between the enriched genetic alterations in mTNBC. Conclusions: Despite the study limitations, we identified that deletions are the aberrations more commonly enriched in mTNBC while some biological processes could be targetable in order to improve the therapeutic opportunities in TNBC.

Characterisation of GATA3 expression in invasive breast cancer: differences in histological subtypes and immunohistochemically defined molecular subtypes

2017 ◽  
Vol 70 (11) ◽  
pp. 926-934 ◽  
Author(s):  
Tang Shaoxian ◽  
Yu Baohua ◽  
Xu Xiaoli ◽  
Cheng Yufan ◽  
Tu Xiaoyu ◽  
...  
Keyword(s):  
Breast Carcinoma ◽  
Triple Negative ◽  
Metastatic Breast ◽  
Her2 Overexpression ◽  
Specific Marker ◽  
Breast Cancers ◽  
Breast Carcinomas ◽  
Histological Subtypes ◽  
Intrinsic Subtypes ◽  
Gata3 Expression

AimsGATA-binding protein 3 (GATA3) is a sensitive and relatively specific marker in breast and urothelial carcinomas. Its diagnostic utility in primary and metastatic breast cancers has been explored and confirmed. However, the relationship between GATA3 expression and different breast carcinoma intrinsic subtypes has not been specifically defined in the literature despite a few reports with a small number of cases. The aim of the current investigation is to clarify GATA3 expression among different histological subtypes and surrogate molecular breast carcinoma subtypes in a large series of cases.MethodsImmunohistochemical staining of GATA3, GCDFP15 and mammaglobin was performed in a cohort of 1637 cases of primary invasive breast carcinoma. The association of GATA3 expression with different histological and surrogate intrinsic subtypes was assessed and compared with the expression of GCDFP15 and mammaglobin.ResultsThe overall positivity of GATA3 across the various immunohistochemistry-based surrogate intrinsic subtypes was 99.51% for luminal A-like, 97.70% for luminal B-like, 68.50% for HER2 overexpression and 20.16% for triple negative breast cancers. GATA3 expression was positively correlated with estrogen receptor (ER)-positive (luminal subtypes) breast carcinomas. For luminal-like and HER2 overexpression subtypes, GATA3 was much more sensitive than GCDFP15 and mammaglobin. For triple negative tumours, GATA3 was less sensitive than GCDFP15.ConclusionsGATA3 exhibits a relatively high sensitivity for breast carcinomas. It is more sensitive than GCDFP15 and mammaglobin in luminal-like and HER2 overexpression subtypes. GATA3 expression is associated with breast carcinomas of luminal subtype and low histological grade.

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