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Important TNBC study-King Lab

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Carol3 View Drop Down
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Post Options Post Options   Thanks (0) Thanks(0)   Quote Carol3 Quote  Post ReplyReply Direct Link To This Post Posted: May 30 2013 at 12:24pm
Just wanted to let folks know that I applied back in Oct 2012 and sent in blood work that same month. I just got a letter this week with results.
 
The test performed was the BROCA DNA sequencing. BROCA identifies all classes of DNA mutations including single base pair changes, small insertions/deletions and large gene rearrangements.
 
BROCA includes the following genes: BRCA1, BRCA2, BRIP1, BARD1, CHEK2, MRE11A, NBN, RAD50, RAD51C, RAD51D, XRCC2, PALB2, PTEN, ABRAXAS, STK11, CDH1, TP53, ATM, MLH1, MSH2, MSH6, PMS2, MUTYH, APC, BAP1, BMPR1A, PRSS1, RET, SMAD4, VHL, ATR, CDK4, CDKN2A, RAD51, RAD51B, XRCC3, CHEK1, TP53BP1, BRCC36, UIMC1, BABAM1 AND RBBP8.
 
The letter did not give more detail on what all the genes were related to but did tell if you had mutations clearly damaging to gene function. Variants were categorized as damaging if they clearly damage the gene's protien product.
 
FYI - Carol
DX 3/25/11 TNBC Stage IIa, grade 3, Tumor 2.3, chemo started 4/22/11. 12 Taxol/4 Charboplatin – 4 AC. iSpy2 Trial. Parp Inhibitor ABT-888. BRCA1/2 neg. 20 Rads. 0/2 nodes. Finished 11/23/2011
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Post Options Post Options   Thanks (0) Thanks(0)   Quote 123Donna Quote  Post ReplyReply Direct Link To This Post Posted: May 30 2013 at 12:49pm
Carol,

Thank you for sharing the details about the King study and all the genes they are investigating.  It looks like they are covering a multitude of genes, which is very good for our community.

Donna
DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15

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Post Options Post Options   Thanks (0) Thanks(0)   Quote 123Donna Quote  Post ReplyReply Direct Link To This Post Posted: Jun 12 2013 at 2:51pm
Steve,

I want to once again thank you for letting our community know about this important study.  It's through this type of research that they'll be able to unravel the mystery of Triple Negative Breast Cancer. 

Donna
DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15

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Post Options Post Options   Thanks (0) Thanks(0)   Quote marial Quote  Post ReplyReply Direct Link To This Post Posted: Jul 02 2013 at 12:13am
I received my results over the phone with Jessia but still have not received anything in the mail..and my parents are waiting for their results ..I haven't heard from Jessica in 3 months..and have been emailing monthly
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Post Options Post Options   Thanks (0) Thanks(0)   Quote SagePatientAdvocates Quote  Post ReplyReply Direct Link To This Post Posted: Jul 02 2013 at 12:44am
Dear Marial,

I have just sent an email to Dr. Bernier and her colleagues at the King lab. 

I doubt if I will hear back but I am hoping you will.

At times, I know it seems like a laborious process but as Donna mentioned I believe some important information has come from this trial and I commend the King lab. 

Marial, I hope you and your parents will gain some clarity as soon as possible. I believe the lab is making a conscientious effort to do a careful, accurate job. Thank you for writing and also thank you for your patience.

warmly,

Steve
I am a BRCA1+ grandson, son and father of women affected by breast/oc-my daughter inherited mutation from me, and at 36, was dx 2004 TNBC I am a volunteer patient advocate with SAGE Patient Advocates
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Post Options Post Options   Thanks (0) Thanks(0)   Quote 123Donna Quote  Post ReplyReply Direct Link To This Post Posted: Jul 02 2013 at 8:58am
Marial,

After I talked to Jessica she told me it may be a little while before I get the official written report.  I asked and she sent me the results we discussed in an email.  You may want to call her and ask her to send you the test results in an email.  I found Jessica to be very helpful and responsive when we talked.

Donna
DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15

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Post Options Post Options   Thanks (0) Thanks(0)   Quote Katdoll Quote  Post ReplyReply Direct Link To This Post Posted: Jul 02 2013 at 3:59pm
It got a letter yesterday with my results a couple days ago, and it included Dr. King's autograph.  Kinda cool.  Her research in all likelihood saved my life, so she is a hero for me.
Tested positive for BRCA1 mutation (187delAG) in 4/09 @ age 44; BSO 9/09; diagnosed w/TNBC in 10/09; 1 cm Stage 1 TNBC IDC, grade 3 + 1.5 cm DCIS; BMX 11/09, nodes clear; chemo (AC/T).
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Post Options Post Options   Thanks (0) Thanks(0)   Quote SagePatientAdvocates Quote  Post ReplyReply Direct Link To This Post Posted: Jul 02 2013 at 6:15pm
Dear Katdoll,

I believe Dr. King's seminal work identifying the BRCA1 mutation has saved tens of thousands of lives. 

I find myself thinking at times what my grandmother's life would have been like if she had been able to watch me grow up instead of passing when I was 2. And I think of my Mother and how she adored children. I was an only child and she never saw her six grandchildren even though I was 24 when I became a father of boy and girl twins. My first little girl was named Sari after my Mother and my daughter Sari was diagnosed with TNBC at age 36, which was 5 years earlier than my Mother's diagnosis.

If only my grandmother and my Mother had the knowledge my daughter had. If..if...if...

Yes the price my daughter paid with the surgeries was traumatic and the scars deep but she is here..9 years later (in August) she is here and we are trying to make plans to take a trip somewhere, in a few months, just the two of us. 

To be honest, my friendship with Dr. King, and my deep admiration of her, is very much based not only on the work she has done but on the graciousness, gentleness and careful explanation she gave me about the BRCA1 mutation before my daughter had her risk-reducing surgeries. I was depressed and petrified, both, at the same time. She imparted her vast knowledge in a logical and caring way that helped me through those awful days. She helped me crawl out of an abyss that was filled with thoughts of losing my daughter after losing my mom. 

Thank you M-C for gracing my life with your presence. And thank you for continuing to work tirelessly to continue to unravel the mysteries. And thank you for your marvelous lab, Jessica and Greta as well.

warmly,

Steve

I am a BRCA1+ grandson, son and father of women affected by breast/oc-my daughter inherited mutation from me, and at 36, was dx 2004 TNBC I am a volunteer patient advocate with SAGE Patient Advocates
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Post Options Post Options   Thanks (0) Thanks(0)   Quote 123Donna Quote  Post ReplyReply Direct Link To This Post Posted: Jul 02 2013 at 6:30pm
Steve,

I find Mary-Claire and the King Lab's research to be a wonderful gift to our community.  While I was impatient to get my results fromr this study, I appreciate the fact that I was able to participate in the study at no cost to me.  This type of genetic testing would be very expensive and not available to many of us.  For some of us the findings could be life saving.

On a sadder note, did you hear or read that the actor, Pierce Brosnan's daughter died of ovarian cancer at the age of 41.  Her mother and grandmother also died from the disease.  I can't help but think that genetic testing could save countless lives, especially in families with similar cancers.

http://www.people.com/people/article/0,,20713827,00.html 
DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15

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Post Options Post Options   Thanks (0) Thanks(0)   Quote SagePatientAdvocates Quote  Post ReplyReply Direct Link To This Post Posted: Jul 02 2013 at 6:40pm
Dear Donna,

my wife called my attention to the Brosnan family tragedy.

What is extremely important and a hallmark of the King Lab studies is that each patient is informed individually as to her results. I am in several studies and neither of them informs me personally. As an example I am in a study regarding prostate cancer and I know they have found several genes that seem to be causative. My dad and his brother both has prostate cancer. Might be informative for my three sons to know if I carry a suspicious mutation other than my BRCA but I will never know...at least not from the study I joined. 

warmly,

Steve
I am a BRCA1+ grandson, son and father of women affected by breast/oc-my daughter inherited mutation from me, and at 36, was dx 2004 TNBC I am a volunteer patient advocate with SAGE Patient Advocates
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Post Options Post Options   Thanks (0) Thanks(0)   Quote marial Quote  Post ReplyReply Direct Link To This Post Posted: Jul 08 2013 at 10:09am
Thank you Steve
 
I understand that things take time and there are delays, I just wish I would receive some correspondence with some  credible information on a timeline.  When my parents submitted it back in January, they were told it should be quick since they are only testing them for the one mutation I had and that it was a fairly simple procedure, etc.  My testing was done and I was just trying to get a written copy of the genes tested and the results.
 
I so appreciate being able to be part of this study and I do hope they have gained valuable information that may save lives and that will help my sister and daughter in the future.  I just wish they would bring in some research students to help with the dissemination of information to the participants. 
 
I have already done al the surgical options to help lower my recurrence risk..but am anxious to see what the larger outcome of this study might find and what true signifigance my mutation may have.
 
Thanks again all!
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Post Options Post Options   Thanks (0) Thanks(0)   Quote Genie Quote  Post ReplyReply Direct Link To This Post Posted: Sep 27 2013 at 11:40am
After becoming impatient to find out my results in the King Lab study, I emailed Jessica on Monday to see if they had even tested my samples. She replied back right away and set up a phone appointment for this morning. I just got off the phone with her. My results came back positive for the BARD1. She was very informative and friendly. I'm so thankful that I was able to participate in this study for free. She told me that any of my family members could be tested for free if they will contact her. What a great opportunity to see if other family members share this mutation.

I would suggest that any that have not received their results, contact Jessica.

Best wishes to all for a great weekend,
Genie
DX 3/10/08 at age 67, IDC. Stage 1, Grade 3, 1.5 cm.
KI-67 99% at MX . Bilateral mastectomy 4/1/08 Node-, BRCA 1/2-,BARD1+, TX:Cytoxan/Taxotere x4,3 in family with TNBC
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Post Options Post Options   Thanks (0) Thanks(0)   Quote SagePatientAdvocates Quote  Post ReplyReply Direct Link To This Post Posted: Sep 27 2013 at 12:12pm
Dear Genie,

I know it has been a long journey to get your results but I am glad you finally have them and that it may be informative to your family as well.

This study was especially wonderful, from my perspective, because the participants were individually informed and also had a Certified Genetic Counselor to explain results, if needed, plus it was free.

Another great job by Dr. Mary-Claire King and her wonderful colleagues at the King Lab.

By the way Helen Hunt will be playing Dr. King in a new movie called Decoding Annie Parker. 

Friends of mine saw it at a sneak preview the other night and enjoyed it. Dr. King is a true Renaissance woman.

hope to see you in San Antonio, again this year.

warmly,

Steve
I am a BRCA1+ grandson, son and father of women affected by breast/oc-my daughter inherited mutation from me, and at 36, was dx 2004 TNBC I am a volunteer patient advocate with SAGE Patient Advocates
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Post Options Post Options   Thanks (0) Thanks(0)   Quote 123Donna Quote  Post ReplyReply Direct Link To This Post Posted: Sep 27 2013 at 12:20pm
Genie - so glad you got your results and can share this with other family members.  Knowledge is power!  We can't change our heredity, but knowledge about it can help us be vigilant.

Steve - I agree, this study was truly amazing and free!  Thank you so much for sharing.  While I was shocked to get my results showing a mutation, but not finding it related to breast cancer, I have been able to get additional testing and risk reducing surgery.  I did't have a family history of cancer, but then again my family tree is small.  So the study results ended up being a silver lining to me.  My family members will also have the opportunity to be tested at no cost to them.  When I saw my gyn/onc and mentioned Dr. King, he went on and on about her.  You could tell he held her in the highest esteem possible by any colleague.  

I'm looking forward to seeing the movie, Decoding Annie Parker when it comes out in my area.

Thanks for all you do for us.

Donna


DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15

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Post Options Post Options   Thanks (0) Thanks(0)   Quote Genie Quote  Post ReplyReply Direct Link To This Post Posted: Sep 27 2013 at 2:26pm
Thanks for your responses, Steve & Donna! And yes, Steve, I will be volunteering again this year at the Breast Cancer Symposium in December. Don't know yet what days I will be volunteering but would love to see you while you are here in San Antonio.

Jessica did tell me that the BARD1 mutation carries a risk for breast and ovarian cancer so I am hoping and praying that my family members are open to being tested for that gene.

I too am looking forward to the movie, Decoding Annie Parker.

Thank you Steve & Donna! You have both helped those of us on the forum in more ways than you will ever know.

Love & hugs,
Genie
DX 3/10/08 at age 67, IDC. Stage 1, Grade 3, 1.5 cm.
KI-67 99% at MX . Bilateral mastectomy 4/1/08 Node-, BRCA 1/2-,BARD1+, TX:Cytoxan/Taxotere x4,3 in family with TNBC
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Post Options Post Options   Thanks (0) Thanks(0)   Quote Loveforlife Quote  Post ReplyReply Direct Link To This Post Posted: Sep 27 2013 at 4:39pm
I can't tell from the thread if this study is closed to new participants at this time. Anyone know the answer?
Dx 1/2011 2b, Gr 3, TNBC, AC/T chemo, L lumpectomy/re-excision/lymph node diss/rads. DX DCIS R Breast 4/2012 - Lumpectomy/Rads.
DX Lung Spine mets 5/2013 Carbo/Gemzar 10/2013 Xeloda 1/2014 Ixempra
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Post Options Post Options   Thanks (0) Thanks(0)   Quote 123Donna Quote  Post ReplyReply Direct Link To This Post Posted: Sep 27 2013 at 11:24pm


Originally posted by steve steve wrote:


<span ="Apple-style-span" style="font-family: arial; font-size: small; line-height: normal; "><blockquote ="cite">
Dear TNBC Family,

I just heard back from Dr. Mary-Claire King and she reports that "enrollment in the study is closed." Also, she informed me that in the next few months all DNA from every participant will be sequenced, the results evaluated and the results provided to participants. However, there is no precise schedule to all of this so that there is "no one size fits all" date that can be given.

She explained that- 

"Research and clinical testing occur in different time frames. Because we are searching for new mutations in new genes, and therefore a great deal more follow up is required, the time frame is inevitably longer than for a more limited test."

Dr. Bernier is a breast surgeon and will be returning to her practice after her fellowship in the King Lab working on this important project. I wanted to take this opportunity to thank her for her work on the study and I wish her much success in her career as a breast surgeon. On a personal level I am a bit sad that enrollment is closed but I believe much good came from the study. I don't have any specifics but I am certain that some women are now better informed than they were, previously. One of the marvelous things about all of Dr. King's studies, to date, is that the participant is informed of the results.

Thanks to all at the King Lab for this study and to all, please be patient..

warmly,

Steve
</span>


Based on Steve's post I believe the study is now closed. It was a great opportunity for our TNBC family and hopefully other opportunities will be available in the future.
DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15

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Thanks for the answer that the study is closed. 
Dx 1/2011 2b, Gr 3, TNBC, AC/T chemo, L lumpectomy/re-excision/lymph node diss/rads. DX DCIS R Breast 4/2012 - Lumpectomy/Rads.
DX Lung Spine mets 5/2013 Carbo/Gemzar 10/2013 Xeloda 1/2014 Ixempra
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Post Options Post Options   Thanks (0) Thanks(0)   Quote 123Donna Quote  Post ReplyReply Direct Link To This Post Posted: Oct 30 2013 at 7:17am
Evaluation of all 24 genes implicated in breast cancer explains occurrence when women have normal BRCA genes

Since 1994, many thousands of women with breast cancerfrom families severely affected with the disease have been tested for inherited mutations in BRCA1 and BRCA2. The vast majority of those patients were told that their gene sequences were normal.

With the development of modern genomics sequencing tools, the discovery of additional genes implicated in breast cancer and the change in the legal status of genetic testing for BRCA1 and BRCA2, it is now possible to determine how often families in these circumstances actually do carry cancer-predisposing mutations in BRCA1, BRCA2, or another gene implicated in breast cancer, despite the results of their previous genetic tests.

This was the challenge addressed by Mary-Claire King, Ph.D., American Cancer Society Professor of Medicine and Genome Sciences, and Tomas Walsh, Ph.D., Associate Research Professor of Medical Genetics, both at the University of Washington, Seattle. They conducted complete genomic sequencing of all genes implicated in breast cancer on DNA samples from breast cancer patients who had normal BRCA1 and BRCA2 commercial test results. The commercial testing occurred because the patients had a severe family history of breast cancer, defined as a family with three or more relatives affected by breast or ovarian cancer.

The results were presented by Dr. Walsh at the American Society of Human Genetics 2013 meeting in Boston.

The researchers found that over 25 percent of index patients with normal results from commercial testing of BRCA1 and BRCA2, but with families severely affected by breast cancer, could be resolved by sequencing all genes known to be involved in breast cancer.

Sequencing was carried out using BROCA, an openly available, targeted capture and genomic sequencing approach that was developed and validated by Drs. Walsh and King in 2010. BROCA detects all single base substitutions, insertions and deletions and copy number variants in all 24 genes implicated in breast cancer.

The researchers used BROCA to test 2,285 members of 743 families with at least three relatives with breast or ovarian cancer. Each of those families included at least one woman with breast cancer who had received normal results from complete commercial genetic testing for BRCA1 and BRCA2. The commercial tests were based on both Sanger sequencing and supplementary testing for large genomic rearrangements in both genes.

Of the 743 families, 26% (191) were resolved by BROCA. The 191 resolved families were found to harbor 149 different inherited, damaging mutations in 18 distinct genes.

Of the 191 resolved families, 35% (66) carried inherited, damaging mutations in BRCA1 or BRCA2 that were not detected by commercial sequencing. The scientists explained that the BRCA mutations were not detected by commercial testing for one of two reasons. In some families, the patient who was tested had normal sequences of BRCA1 and BRCA2, but her relatives with breast cancer carried a mutation in one of those genes. In other families, both the patient who was tested and her relatives carried a BRCA1 or BRCA2 mutation of a type not reported by commercial testing.

In the remaining families resolved by BROCA, 65% (125) carried inherited, damaging mutations in genes other than BRCA1 or BRCA2 that also have been associated with breast cancer. The researchers found that 18 different genes harbored cancer-predisposing mutations in those 125 families, but each affected person carried a mutation in only one gene.

Carriers of mutations in some of the genes were at significantly increased risk of ovarian cancer for women and increased risk of breast cancer in men as well as in women.

Comprehensive testing is rapidly becoming more widespread. "It is important to determine more precisely the risks associated with damaging mutations in each of these genes so as to incorporate them most effectively into clinical care," Dr. Walsh said.

These assessments are best undertaken by sharing data across all centers that carry out genetic testing for breast and ovarian cancer risk, said Dr. King.

http://www.medicalnewstoday.com/releases/267950.php

DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15

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Post Options Post Options   Thanks (0) Thanks(0)   Quote SagePatientAdvocates Quote  Post ReplyReply Direct Link To This Post Posted: Oct 30 2013 at 7:56am
Dear Donna,

as always, thank you for this important post. I think the results of the study are extremely important for our community. Testing BRCA1/2- negative may not be the end of the story. I have worked/am working with several families with profound histories of breast/ovarian cancer who have tested BRCA1/2- negative; however, further testing may show other mutations that may be the cause of the cancer in those families. THe knowledge of another gene mutation may be as important to that family as the BRCA mutation and it may be extremely important for loved ones to be tested if the mutation is determined to be in the family.

Here is some info on the BROCA test. Many of you have written, or told me privately, that you are disappointed that the free study offered by the King lab is closed.


I am going to try to get more details on the BROCA test and while the turnaround time is long (84 days) it may be worthwhile for some here to take. As always, please consult your Certified Genetic Counselor, if possible. 

There is an 800 number listed for questions and I will be calling it today with some questions I have about the BROCA test and will revert.

1-800-713-5198

warmly,

Steve


Edited by steve - Oct 30 2013 at 8:14am
I am a BRCA1+ grandson, son and father of women affected by breast/oc-my daughter inherited mutation from me, and at 36, was dx 2004 TNBC I am a volunteer patient advocate with SAGE Patient Advocates
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