[Lani]

Dr. Rachel Schiff of Baylor has worked with Dr. C. Kent Osborne and Graciela Arpino and their team have published much of the original work on AIs working better than tamoxifen for those who are ER+ but PR-, as well as work on the second, faster acting estrogen receptor which sits on the cytoplasmic membrane rather than inside the nucleus and crosstalks with her2 as well as the wonderful study on CURING her2 breast cancer in mice using the triple cocktail of pertuzumab, herceptin and IRESSA (an oral tyrosine kinase inhibitor against EGFR aka her1). Dr. Osborne presented a very elegant talk on how the her family (1,2,3 and 4) and their ligands(the compounds which attach to the receptors and activate them) and ER and IGFR and others crosstalk and how tamoxifen, estrogen depletion (AIs) and others combine with her family inhibitors and how attacking 3 to 4 pathways simultaneously appears to exhaust the cancer's means of escape (I liken cancer to a puppy that wants to go outside and play.. you can shut the front door, but it will find the back door, the door to the garage, and perhaps the playroom door to escape out of if you don't close them all...hopefully the puppy tuckers out and gives up after checking out 3 or 4!) Also at her institution, Baylor, is Jenny Chang whose paper was the last given yesterday. Max Wicha, stem cell theory of breast cancer advocate par excellence, discussed how ER was not on the stem cell but rather on the progenitor cell (can explain this later in more detail--remind me!) and how the role of her2 was to turn a switch which caused there to be a higher percentage of stem cells within the tumor. This was born out by Dr. Chang's neoadjuvant study in which she gave patients lapatinib only after an initial biopsy that showed her2+ breast cancer. After the lapatinib she took a second biopsy and after that, gave chemo and herceptin and a third biopsy.

The second biopsy showed a decreased percentage of cancer stem cells than the first (wish she had done another study with herceptin only first, and then lapatinib with chemo and another with just herceptin then lapatinib, lapatinib and then herceptin and a third with both together...oh well!)

These cancer stem cells are felt to be the only ones within the tumor capable of making cancer recur and to hide out like mildew in your shower after you use bleach containing cleaner...because they are dormant and hide in the form of their protective spore, in the case of mildew, or in their
hidden niche in bone marrow, brain, etc and multiply only rarely, like life in the desert which blooms only after the very rare rains...they are not killed by treatments which rely on the cell dividing to kill them (virtually all chemos). Dr. Wicha has formed a company with Dr. Clarke, the discoverer of the breast cancer stem cell and within the last 10 days it got an enormous infusion of funding from GlaxoSmithKlein according to the Wall Street Journal.

So whether or not you personally believe in the stem cell theory of breast cancer, this institution (Baylor) has researchers at the very pinnacle of her2+ breast cancer research--there are already drugs in development which target stem cell markers and these triple cocktails seem according to most of the leading cancer researchers to be the best hope of taming the beast(please forgive me for comparing it to a puppy, I don't want to insult puppies, just to show that it is very determined and used to getting its own way!) Some drugs which are already FDA approved may turn out to work.

If you can access the Wall Street Journal there is a great article about patients trying to "mix their own cocktails" to cure their/or their children's cancers(not something that I am advocating).

Dr. Schiff did not want to commit herself to do anything but check into what institutional paperwork and protocols might apply until I could assure her that we truly had dedicated patients who intended to fulfil their promise to
provide their specimens( usually $70 to provide much more than they need, so hopefully less and perhaps we can get a grant) and histories (usually just takes a faxed copy of your signature to the department of medical records allowing them to obtain your mammos/xrays/mris and or their reports, lab tests, operative reports, clinic notes, etc.)

I will see if a pre-med I know would like to take this up...would look great on a resume and will check with my local breast cancer advocate organisation to see if they have any volunteers. But there is no point in going further if the samples and medical records releases are not going to materialize.

Perhaps Alaska Angel or Rhonda could start a thread asking who would give a small piece of their surgical specimens, any additional blood requested (if we can get the costs deferred and get it drawn locally), any additional swabbing of the mouth (who knows, they might ask for it) for genetic
material for testing, and who would be willing to give them access (privacy maintained) to your medical records. Something with a colorful graph for yes, no vs maybe might do the trick!

I think it would be a great memorial to those we have lost, an affirmation of hope for those still alive and an effort to prevent our daughters from having this burden hanging over them as well. I personally believe we are much closer to curing her2+ breast cancer than many other cancers which afflict so many. Our understanding of it is growing by leaps and bounds but it can be turbo-accelerated by providing the researchers with enough samples with matching histories to maximize their ability to sift through the various
directions the research is going and point it full-steam ahead in the right direction to benefit all as quickly as possible. A side effect may be to find cures for other cancers with similar behaviors (eg some esophageal cancers express her2).

Am still searching for the card of my second candidate, someone looking into the immunological aspect of her2+ breast cancer, but in the meantime I will provide you with the names of the London researcher and a researcher
in Alabama, who works with some present and past Stanford researchers.

The former is Aleksandra Filipovic, Imperial College London, UK. I will be calling and emailing her to get her to describe her research to you. The latter is Robert Seitz of Applied Genomics of Huntsville, Alabama and I will
have him provide a description of his research and how he would utilize the specimens and medical histories. I would prefer to provide our samples to
nonprofit entities such as universities (he works with university researchers), but as I recall his firm might be able to provide many here with information on their specific tumors, whether immunohistochemical or by gene expression profiling. This might help in the short term those deciding whether their tumor is more likely to respond to one targetted therapy or another. Again, I only had short conversations with the two above (vs Dr. Schiff with whom I have spoken, emailed previously) so I would like for them to further "sell themselves" to those who might wish to donate their specimens.

If you search the abstracts at SABCS you should be able to find that with Robert Seitz's name on it...

Got to get going...more later!