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Old 02-29-2012, 07:14 PM   #44
Mandamoo
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Join Date: Jul 2011
Location: Melbourne, Australia
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Re: any tumor tests to predict which chemos work better?

Ok - I have more information on the type of testing that has been done on my tissue for your information. It is not chemosensitivity testing as far as I understand it.

I don't understand what this means so I will type directly from the report:
Ion Toerren AmpliSeq Analysis of DNA on Formalin Fixed Paraffin Embedded Tissue.
Methodology:
Ion Torrent AmpliSeq (then there a whole lot of other jargin) and Ion Torren TargetSeq (more stuff I don't understand :-) )

The results were:
Somatic Mutations detected:
Gene - TP53
Accession Number X16416
Cosmic ID 10662[1]
cds Mutation Syntax c.743G>A
aa Mutation Syntax p.R248Q
Hg19 Coordinates 17:7577538-7577538
Effect Missense, non-functional
Therapeutics - this mutation confers resistance to doxorubicin and taxanes, in vitro testing shows sensitivity to PRIM-1 but there is no in vivo sensitivity and no induced reactivation with PRIMA-1. pCR was not demonstrated with neoadjucant anthracycline + cyclophosphamide followed by taxane in IDE.

Comments:
a TP53 somatic mutation was identified by both methodologies with a frequency of approximately 28% in the primary tumour and 54% in the lumpy node metastasis. This mutation introduced both contact and structural changes in the L2 and L3 loop and enhances in vitro invasiveness of human lung cancer cells. This mutation has been reported in 874 tumours and 19 families with LiFraumeni syndrome. TP53 mutations have been reported in 23% of breast cancers with this mutation reported 0.69%. An extensive literature search shows low level evidence for resistance to antrhracycline/cyclophospahmide and paclitaxel with increased activity of multiple drug resistance gene product, P=glycoprotein. Preclinical evidence shows the R248Q mutation is not responsive to an experimental drug PRIMA-1 in vivo. Preclinical evidence indicates the possibility of cyclotherapy, combining p53 activators and mitotic inhibitor but these are not available for patient treatment.

The lower limit of detection is estimated to be -5% and this is dependent on the proportion of tumour present in the sample.

Exome sequencing is being performed and additional report will be issued.
This testing methodology is for research use only and is not NATA accredited.

My take on this - correct me please is that this is not chemosensitivity testing but DNA analysis which has determined that the cancer in me has a particular genetic mutation which has previously been shown to be resistant to anthracylcines and taxanes and that currently there are no other suggested effective alternatives (though there are many other cytotoxics to try that are not mentioned).
We hope to redo the lung biopsy and get live tissue for further testing of the metastasis.
Interested in your comments on this type of testing.
Amanda
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Amanda xx
40 year old Mum to three gorgeous kids - son 5 and daughters 8 and 11
Wife to my wonderfully supportive husband of 17 years!
22 February 2011 - Diagnosed Early Breast Cancer IDBC Stage2b (ER/PR -ve, Her2+ve +++) - 38 years old
(L) skin sparing mastectomy with tissue expander, axilla clearance (2/14 affected) clear margins.
Fec*3, Taxotere and herceptin*2 - stopped due to secondary diagnosis

June 24 2011 Stage IV - Skin met, axilla node, multiple lung lesions

Bolero3 trial - Navelbine, Hereptin weekly, daily Everolimus/Placebo
February 2012 - July 2012 Tykerb and Xeloda - skin mets resolved, Lungs initially dramatically reduced but growing again
August 2012 (turn 40!) tykerb and herceptin (denied compassionate use of TDM1) while holidaying in Italy!
September 2012 - January 2013 TDM1 as part of the Th3resa trial - lymph nodes resolved, lungs slowly progressing.
January 2013 - herceptin, carboplatin and Perjeta (compassionate access)
April 2013 - Some progression in lungs and lymph nodes - Abraxane, Herceptin and Perjeta
July 2013 - mixed response - dramatic reduction of most lung disease, progression of smaller lung nodules and cervical and hilar nodes - ? Add avastin.
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