Breast Cancer Symposium 2008

[gpawelski]

Direct anti-tumor and anti-vascular effects were studied of Tykerb, Nexavar and Avastin in fresh biopsy specimens of breast cancer and presented at the American Society of Clinical Oncology Breast Cancer Symposium on September 5, 2008.

While the other clinically-available 'nib' drugs have been shown to have anti-vascular activity, anti-vascular activity of Tykerb has not been previously reported.

Angiogenesis studies are limited by the clinical relevance of laboratory model systems. They don't do "real world" studies under "real world" conditions. Patient outcomes need to be reported in real-time, so patients and cancer physicians can learn immediately if and how patients are benefiting from new drug therapies.

Cell culture detection of microvascular cell death in clinical specimens of human neoplasms and peripheral blood can identify the activity of both single drugs and combinations of drugs at the level of individual patients with individual cancers. It works by measuring drug effects (real-time) upon endothelial cells which make up blood vessels.

Drugs like Avastin had striking anti-microvascular effects but minimal anti-tumor effects. Tarceva and Gleevec had mixed antitumor and anti-microvascular effects. Anti-microvascular effects of Tarceva and Iressa were equal to those of Sutent and Nexavar. Anti-microvascular additivity was observed between Avastin and other drugs on an individual basis.

Conclusions of the study had shown that Tykerb has antivascular activity superior to that of Nexavar. Avastin + Tykerb may be the first clinically-exploitable antivascular drug combination. High dose, intermittent 'bolus' schedules of Tykerb to coincide with Avastin administration may be clinically advantageous, even in HER2-negative tumors.

The system utilized for the study was a functional profiling assay, which may be used to individualize antivascular therapy. It can be adapted for simple, inexpensive and sensitive/specific detection of tissue and circulating microvascular cells in a variety of neoplastic and non-neoplastic conditions, for drug development, and individualized cancer treatment.

It can accurately sort drugs into categories of above average probability of providing clinical benefit on one hand and below average probability of providing clinical benefit on the other hand, based both on tumor response and patient survival.

Source: http://www.weisenthal.org/Weisenthal_ASCO.pdf

[gpawelski]

Microaggregates (microscopic collection of platelets, leukocytes or fibrin particles that occurs in blood) which mimic the native environment of cells contained in biopsied tissue are used to assess and predict the effects of various treatments on the viability of cell types contained in the microaggregate.

There is a need for improved methods to predict the activity of treatments which target the microvasculature of tumors. Avastin is an anti-cancer drug which targets the microvasculature of tumors. The ********* cost of Avastin is more than $40,000 for ten months of treatment for a relatively small percentage of patient that can derive substantial benefit from it.

The most commonly used in vitro methods involve isolating and culturing endothelial cells. Once the cells have been cultured, the effect of drugs are studied using cell death endpoints.

Normally, Avastin is administered to a patient on a trial basis and then early treatment effects are assessed by means of external diagnositc scanning (MRI) and/or post-treatment tumor biopsies, with histopathologic evaluation of treatment effects. This approach has many disadvantages, including expense of treatment, exposure of patient to potential toxicity of ultimately ineffective therapy, and the expense of diagnostic studies (MRI). Such studies also lack the ability to test multiple different treatments simultaneously without risk to the patient as is possible with in vitro methods.

In vitro methods are able to detect and/or quantify viability changes in the microvasculature of microaggregates of cells isolated from biopsied neoplastic tissues in response to treatments. The observed microvascular and other cellular changes serve as tests to predict the in vivo activity of the tested treatments, while able to detect specific effects on endothelial cells, and also permit the observation of effects of the same or concomitantly administered treatment on the surrounding cells (a particular drug may affect both endothelial cells and the surrounding cells).

[gpawelski]

ER and PR tests in breast cancer, which detect only VEGF expression, or even overexpression, are valuable not because they measure expression of estrogen and progesterone but rather because they detect (and supposedly measure) the ER and PR receptors in the nucleus. The presence of positive IHC staining of such receptors in at least 10% of nuclei implies that the tumor is hormonally dependent and that, therefore, depriving the cells of the hormone will kill them or retards their growth.

Unlike a test for the presence of receptors to a specific antigen, which only "implies" dependence upon that antigen, an AngioRx assay is functional in that it actually assesses the direct or indirect effect of the drug upon the cell, whether it is a tumor cell or an endothelial cell. VEGF just happens to be one molecule which has been implicated in the process but there may be more.

If it were the only protein involved, then one would expect that VEGF expression would correlate with Avastin activity 100% of the time but it actually does so only about 20% of the time. The AngioRx assay doesn't just focus on VEGF or any one protein or mechanism. Whether it's VEGF alone (unlikely) or in combination with other proteins and other mechanical factors, the assay works by assessing the net effect of all those factors.

http://weisenthalcancer.com/Professionals%20Pages/AngioRxProfessional.htm

[simmons19]

The 15th UICC Reach to Recovery International Breast Cancer Support Conference - May 13 to 15, 2009 - Brisbane Convention and Exhibition Centre, Brisbane, Australia

Welcome to The 15th UICC Reach to Recovery International Breast Cancer Support Conference - the first ever worldwide forum across Asia-Pacific, Europe, Africa as well as North, Central and South America for breast cancer consumers, support organisations and health professionals to meet and address common goals.

Breast cancer is the most common cancer among women. In 2002 there were more than one million new cases of breast cancer diagnosed globally - this represents 10 per cent of the world's cancer burden and 23 per cent of all female cancers. There are now more than four million women living with breast cancer worldwide. Breast cancer is a local, national and global concern.

The 15th UICC Reach to Recovery International Breast Cancer Support Conference will be convened in Brisbane by the Cancer Council Queensland. We warmly invite you, your fellow consumers, and colleagues to visit our city and join us for this event.