Recommendations of the Austrian Working Group on Pulmonary Pathology and Oncology for predictive molecular and immunohistochemical testing in non-small cell lung cancer

Summary

The introduction of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) in the therapy of non-small cell lung cancer (NSCLC) with activating mutations of the EGF receptor has opened a new area of lung cancer treatment strategies and led to an enthusiastic search for additional genetic aberrations. Genetic drivers such as EML4-ALK (EML4: echinoderm microtubule-associated protein-like 4; ALK: anaplastic lymphoma kinase) and proto-oncogene tyrosine protein kinase transcribed from the ROS1-gene (ROS1) rearrangements have been detected and specific treatment options have been developed. A new approach to treatment in lung cancer is immunotherapy by antibodies interfering with immune checkpoint controls. Diagnostic and predictive immunohistochemical staining and molecular tests have to follow specific rules, if applied in daily practice. The Austrian Working Group on Pulmonary Pathology and Oncology (AWGPPO) has presented an updated version of the previous recommendations published in 2013. Questions raised during the past 3 years will be addressed: selection of tissue, order of diagnostic immunohistochemical and molecular tests, "reflex" testing, the issue of resistance mechanisms, significance of liquid biopsies, and use and interpretation of antibody reactions for immune checkpoint markers.

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Searching for the Achilles’ heel of cancer

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ASCO 2016: highlights in breast cancer

Summary

At the 2016 ASCO Annual Meeting, several pertinent studies in the field of breast cancer were presented. MA17.R was the first randomized phase III trial to evaluate the prolongation of adjuvant aromatase-inhibitor (AI) therapy from 5 to 10 years; while a significant reduction of disease-free survival events was observed in the extended treatment group, the absolute difference was relatively small and longer endocrine therapy resulted in a higher fracture rate. A combined analysis of three North American trials emphasized the superiority of anthracycline containing adjuvant chemotherapy regimens compared with docetaxel/cyclophosphamide (TC), while the PANTHER trial investigated dose-dense tailored adjuvant treatment. In metastatic breast cancer, the main interest was on cyclin-dependent kinase (CDK) 4/6 inhibitors. In PALOMA-2, the addition of palbociclib to letrozole prolonged progression-free survival (PFS) from 14.5 to 24.8 months resulting in the longest PFS data ever reported in the first-line setting. A subgroup analysis of premenopausal patients accrued to PALOMA-3 indicated that in this patient subset, ovarian function suppression plus fulvestrant and palbociclib yielded results comparable to the postmenopausal population. ESR1 mutations were another focus of interest as these activating mutations in the gene coding for the estrogen receptor alpha apparently evolve under the selection pressure of AI therapy.

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Recommendations of the Austrian Working Group on Pulmonary Pathology and Oncology for predictive molecular and immunohistochemical testing in non-small cell lung cancer

Summary

The introduction of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) in the therapy of non-small cell lung cancer (NSCLC) with activating mutations of the EGF receptor has opened a new area of lung cancer treatment strategies and led to an enthusiastic search for additional genetic aberrations. Genetic drivers such as EML4-ALK (EML4: echinoderm microtubule-associated protein-like 4; ALK: anaplastic lymphoma kinase) and proto-oncogene tyrosine protein kinase transcribed from the ROS1-gene (ROS1) rearrangements have been detected and specific treatment options have been developed. A new approach to treatment in lung cancer is immunotherapy by antibodies interfering with immune checkpoint controls. Diagnostic and predictive immunohistochemical staining and molecular tests have to follow specific rules, if applied in daily practice. The Austrian Working Group on Pulmonary Pathology and Oncology (AWGPPO) has presented an updated version of the previous recommendations published in 2013. Questions raised during the past 3 years will be addressed: selection of tissue, order of diagnostic immunohistochemical and molecular tests, "reflex" testing, the issue of resistance mechanisms, significance of liquid biopsies, and use and interpretation of antibody reactions for immune checkpoint markers.

from Cancer via ola Kala on Inoreader http://ift.tt/2gkYd8m
via IFTTT

Searching for the Achilles’ heel of cancer

from Cancer via ola Kala on Inoreader http://ift.tt/2g77zSw
via IFTTT

ASCO 2016: highlights in breast cancer

Summary

At the 2016 ASCO Annual Meeting, several pertinent studies in the field of breast cancer were presented. MA17.R was the first randomized phase III trial to evaluate the prolongation of adjuvant aromatase-inhibitor (AI) therapy from 5 to 10 years; while a significant reduction of disease-free survival events was observed in the extended treatment group, the absolute difference was relatively small and longer endocrine therapy resulted in a higher fracture rate. A combined analysis of three North American trials emphasized the superiority of anthracycline containing adjuvant chemotherapy regimens compared with docetaxel/cyclophosphamide (TC), while the PANTHER trial investigated dose-dense tailored adjuvant treatment. In metastatic breast cancer, the main interest was on cyclin-dependent kinase (CDK) 4/6 inhibitors. In PALOMA-2, the addition of palbociclib to letrozole prolonged progression-free survival (PFS) from 14.5 to 24.8 months resulting in the longest PFS data ever reported in the first-line setting. A subgroup analysis of premenopausal patients accrued to PALOMA-3 indicated that in this patient subset, ovarian function suppression plus fulvestrant and palbociclib yielded results comparable to the postmenopausal population. ESR1 mutations were another focus of interest as these activating mutations in the gene coding for the estrogen receptor alpha apparently evolve under the selection pressure of AI therapy.

from Cancer via ola Kala on Inoreader http://ift.tt/2gkQozy
via IFTTT

Aryl hydrocarbon receptor induced intratumoral aromatase in breast cancer

Abstract

Purpose

Aryl hydrocarbon receptor (AhR) inhibits estrogen receptor (ER) pathway, which may suppress estrogen-dependent cell proliferation. However, the correlation between AhR stimulation and intratumoral estrogen synthesis, especially through aromatase, has not been reported to date. In the present study, we examined this correlation in breast cancer cells.

Methods

We examined AhR and aromatase immunoreactivity in 29 patients with invasive ductal carcinoma. We performed in vitro studies using three breast carcinoma cell lines, MCF-7, T47D, and MDA-MB-231.

Results

AhR stimulation induced the mRNA expression of the aromatase gene in vitro in three breast carcinoma cell lines, and increased estrogen synthesis in MCF-7 cell line. Results of microarray analysis showed that AhR-induced aromatase expression was associated with BRCA1 induction. Analysis of patients with breast cancer showed a significant positive correlation between intratumoral AhR and aromatase status. We also compared the effects of AhR stimulation on the induction of intratumoral estrogen synthesis and inhibition of the ER signaling pathway, because AhR exerts contradictory effects on estrogen action in breast carcinoma cells. AhR-induced aromatase expression persisted for a significantly longer duration than AhR-induced ER pathway inhibition. Moreover, breast carcinoma cells treated with an AhR agonist tended to show earlier cell proliferation after removing the agonist than cells not treated with the AhR agonist.

Conclusion

The results of the present study suggest that AhR stimulates estrogen-dependent progression of breast carcinoma by inducing aromatase expression under some conditions. These results provide new insights on the possible roles of environmental toxins in breast cancer development.

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