Approach to linking breast cancer phenotypes to genetic variations

Hi,

A - As Gerard Perret said, it depends on the subtype, but only four subtypes have strong link to clinic and/or genomic values (Basal-like, HER2, Luminal A, Luminal B).

B - By using genome-wide technique, you will have to compute a big amount of data, but your study will not be supervised as if you choose target specific polymorphisms. That is a nice way to discover new pathway.
@Winton Gibbons: a result found in a genome-wide study should (must) be verified by external validation, to avoid internal bias. Then you can choose cross-platform validation to strengthen your result.
Most of reviewers will ask you that before being published. On GEO website (http://www.ncbi.nlm.nih.gov/geo/) you can find a lot of data shared.

C - For genomic study: the best sample is snap frozen biopsy or tumor resection (if you could have this) stored in liquid nitrogen, then paraffin-embedded sample may be a good alternative. Affymetrix will release a FFPE array soon with a very high resolution.
For a quick diagnostic: blood may be simple to use and to collect, then use a protein dosage on oestrogen receptor, uPA and PAI-1.

dear friend,
If you present an outlined and prepared scenario for peer-reviewing, I might suggest you to read recent works on PUBMED.

Thank you Zuheir and Ellen...looking into your suggestions as well!

a.My suggestion that it would be able to run BRCA1, 2 as well as thymidine kinase 1 comfortably (Nisman B, Allweis T, Kaduri L, Maly B, Gronowitz S, Hamburger T, Peretz T. Cancer Biomark. Serum thymidine kinase 1 activity in breast cancer. Cancer . Biomark. 2010 ;7(2):65-72).

c.Paraffin sections of cancer tisssue by immunohistochemistry is the way to go (Michiko S., et al., ONCOLOGY REPORTS 23: 1345-1350, 2010). The blood markers also are useful, such as CA-15-3 and thymidine kinase 1 (Q. He, et. al, Anticancer Research, 26:4753-4759, 2006 ; Nisman B, et al., Urology. 2010 76(2):513.1-6).

1.germline mutations in BRCA1 or BRCA2 lead to a very high probability of developing breast and/or ovarian cancer.
2.Breast screening programmes for women at increased risk do not increase anxiety in women who do not require further investigation, but women who are referred for further investigations are evidently more anxious.
3.blood test CA-15-3 and CEA

Thank you all, I have got quite some insight from the above replies.
a. Our laboratory would be able to run BRCA1,2 analysis as well as p53 comfortably.

b. @Winton Gibbons: I have not come across the biological plausibility. It is definitely an approach I will read up on and see how it fits into our scheme of things

c. In our registry we already have a tissue repository and it seems that this will be the best way to go. We were keen to avoid taking too many samples from the patients as well.

I agree with you Dr. Windon. I think androgen receptors and EGFR should be added to the list. In addition, BRCA1 and 2 mutations may have some value. Urine seems to have little value in diagnostic workup, but CA 15-3 in blood arouses optimism. Of course paraffin sections, and cancer tisssue is of great utility for conducting marker studies by immunohistochemistry, microarrays and q PCR.

a. ER, PR, HER2, Ki-67 and p53 (also see, "Rouzier R, Perou CM, Symmans WF et al. Breast Cancer molecular subtypes respond differently to preoperative chemotherapy." Clinical Cancer Research 2005; 11:5678-5685
b. with all due respect, genome-wide studies most often do not validate (a degree of freedom problem statistically, even with even reasonably large samples - there have been all these bootstrapping approaches, hold-out sampling methods with voting, etc. - they most often don't validate). much is being discussed these days about this. biological plausibility, even with a large set of genes, seems to yield better results.
c. while there are historically, somewhat useful blood markers, such as CA-15-3 and CEA, most of the markers are too in low abundance in blood (or may not even be present). immuno-histochemistry using tissue is the way to go

The answer to question A. In my opinion Cytotoxic T lymphocyte antigen-4 (CTLA-4) have been shown to have the greatest potential for clinical application in sporadic breast cancer?

The answer to question C. It all depend on the parameter you are looking for like for example if you want to no the extend of kidney damage and wants to measure Beta-2 microblobulin than Urine is the best. For different biochemical parameters Blood. Prognostic marker in breast cancer with the follow-up than paraffin blocks.

A-its depend on the subtype ( at least five )
B-genome-wide
C-blood for the isolation of circulating tumor cells