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if BRCA negative, but family history....

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    Posted: Feb 09 2011 at 8:35am
Dear TNBC Foundation,

I was doing some research this morning on another topic and I came across this study (please see below) and wanted to pass it along..I sense that many here who have TNBC but who have tested BRCA negative and therefore seem to feel that their families are not at increased risk because the woman with TNBC has tested BRCA negative. That may not be the case with families who have a family history of breast cancer as defined below-

The lines that bounced off the page to me were-

"Women with a significant family history of breast cancer (ie, two or more breast cancers under the age of 50 years, or three or more breast cancers at any age), but who test negative for BRCA mutations have approximately a four-fold risk of breast cancer (my italics). Women in these families may be candidates for tamoxifen chemoprevention and/or intensified breast screening with an MRI.”

If the women in the family have all had TNBC I am not sure tamoxifen chemo-prevention makes sense but increase surveillance via MRI certainly seems to be something to talk to your physician about..

all the best,

Steve




Br J Cancer. 2009 January 27; 100(2): 421–425.
Published online 2008 December 16. doi: 10.1038/sj.bjc.6604830.
PMCID: PMC2634722
Copyright 2009, Cancer Research UK
Breast cancer risks in women with a family history of breast or ovarian cancer who have tested negative for a BRCA1 or BRCA2 mutation
K A Metcalfe,1,2* A Finch,2 A Poll,2 D Horsman,3 C Kim-Sing,3 J Scott,3 R Royer,2 P Sun,2 and S A Narod2
1Lawrence S. Bloomberg Faculty of Nursing, University of Toronto, Toronto, ON, Canada
2Women's College Research Institute, Toronto, ON, Canada
3BC Cancer Agency, Vancouver, BC, Canada
*Author for correspondence: Email: Kelly.metcalfe@utoronto.ca
Received September 17, 2008; Revised November 12, 2008; Accepted November 18, 2008.
Small right arrow pointing to: This article has been cited by other articles in PMC.
ABSTRACT
Genetic testing for mutations in BRCA1 and BRCA2 is available in Canada for women with a significant family history of breast cancer. For the majority of tested women, a BRCA1 or BRCA2 mutation is not found, and counselling regarding breast cancer risk is based on the review of the pedigree. In this prospective study, we estimate breast cancer risks in women with a family history of breast cancer and for whom the proband tested negative for a mutation in BRCA1 or BRCA2. Families with two or more breast cancers under the age of 50 years, or with three cases of breast cancer at any age, and who tested negative for a BRCA1 or BRCA2 mutation were identified. Follow-up information on cancer status was collected on all first-degree relatives of breast cancer cases. The standardised incidence ratios (SIRs) for breast cancer were calculated by dividing the observed numbers of breast cancer by the expected numbers of breast cancers, based on the rates in the provincial cancer registries. A total of 1492 women from 365 families were included in the analyses. The 1492 first-degree relatives of breast cancer cases contributed 9109 person-years of follow-up. Sixty-five women developed breast cancer, compared to 15.2 expected number (SIR=4.3). The SIR was highest for women under the age of 40 (SIR=14.9) years and decreased with increasing age. However, the absolute risk was higher for women between the age of 50 and 70 (1% per year) years than for women between 30 and 50 (0.4% per year) years of age. There was no elevated risk for ovarian, colon or any other form of cancer. Women with a significant family history of breast cancer (ie, two or more breast cancers under the age of 50 years, or three or more breast cancers at any age), but who test negative for BRCA mutations have approximately a four-fold risk of breast cancer. Women in these families may be candidates for tamoxifen chemoprevention and/or intensified breast screening with an MRI.


Edited by steve - Feb 09 2011 at 9:20am
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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TracyAMac View Drop Down
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Post Options Post Options   Thanks (0) Thanks(0)   Quote TracyAMac Quote  Post ReplyReply Direct Link To This Post Posted: Feb 09 2011 at 9:54am
Thanks Steve - this is an excellent find! I am glad to see something out there on a potential strategy for BRCA-ve women.

I would also say to our fellow forum members, if they or other family members have also had other types of BC's and/or other non-breast cancers, especially if diagnosed before age 50, please ensure your onc. and genetic counsellor is aware of this.  There are many other genetic tests that can be looked at even if you are BRCA neg. like myself. e.g. P53 and Chek2 (the latter being a fairly recently developed and expensive test)  Of course finding mutations in some genes does not necessarily alter treatment but may result in increased survellinace

Tracy in Toronto
TN&non-TN tumors April/10 Gr3&2;1 metaplastic
Rmast.1/9 nodes w/isolated t.cells
Taxotere&Cytoxan x6
Bone cancer 1980 age17;surgery&chemo AC+Methotrexate
BRCA-ve
On hormone therapy & Metformin Trial
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Post Options Post Options   Thanks (0) Thanks(0)   Quote snugltz Quote  Post ReplyReply Direct Link To This Post Posted: Feb 09 2011 at 11:26am
Steve
When I talked with you you asked if any family members had cancer.  I said no, except an uncle who lived in sun got skin cancer.  I have since found out that my dad brother died of cancer under 50, and another bro also has it, and three of his sisters have breast cancer, along with some of my cousins, both male and female have cancers of various kinds.  Except for the one brother I believe all were over 50 of my fathers siblings, however the cousins are not all that old.  Since I was 58 at dx, should I now tell my oncologist about this and maybe get tested. Also my daughter in law had breast cancer at 18.  Does this put my granddaughter at a high risk since I also have it?
1 cm, 0/2 neg nodes, lumpectomy 6/16/10, cytoxin/taxotere 4x every three weeks, rad start 11/8 33X
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Post Options Post Options   Thanks (0) Thanks(0)   Quote SagePatientAdvocates Quote  Post ReplyReply Direct Link To This Post Posted: Feb 09 2011 at 12:23pm
Dear snugltz,

I am glad you did further checking....your family sounds like a classic BRCA family unfortunately...I would definitely give this information to your oncologist and the most important person to speak to would be a Certified Genetic Counselor (CGC) and bring a complete “cancer family tree” to the meeting.

Is your dad still alive...that would be the ideal starting place if he is...If he is and tests positive and then you tested negative you would be a “true” negative. If he is negative and you tested positive you would know that you got the mutation from your mother’s side. But, again, all best to be checked out with a CGC. If you need help finding one please send me a PM or please feel free to call me again.

If your DIL had breast cancer at 18 she did not inherit a predisposition to get it from you. But having cancer at that age should certainly, again, warrant a meeting with a CGC. If your DIL were to test positive it might put your granddaughter at risk to have the mutation...If you were test positive then your son should test as well to see if he inherited the mutation from you. 

As you can see, this can get complicated and please see a CGC. They are trained to give you all the possibilities...

It may also be important to let your extended family (cousins etc.) know about the mutation if a family member tests positive. Again a good CGC can craft a letter to be sent out to various relatives alerting them of the danger and suggesting they meet with a CGC. And, unfortunately, some of your relatives may respond with “I don’t want to know” which can be frustrating...but all you can do is give them the info...I would not pressure them to test, even though, in my view they should...I have gone through this in my family and all I can tell you is that it can be a difficult process.

Finally, to perhaps confuse you some more....if there are four people in your family with breast, ovarian cancer and they have all tested negative for the mutation Dr. Mary-Claire King at the University of Washington has a study called “mystery families” and she is trying to see if there are other mutations involved in those families. She is the scientist who first identified and named the BRCA1 mutation. She is a brilliant researcher and a marvelous woman. She helped me greatly when I found out that my daughter and I carried the mutation. Snugltz, of anyone, if your family were to qualify I can put you in touch with Dr. King’s CGC.

all the best,

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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