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Aug 8, 2021 04:48PM
Aug 8, 2021 05:13PM
Hey, Jjdrayton, fellow Lynch person here. I have an MSH6 mutation. And a premenopausal breast cancer diagnosis. I believe that eventually the connection will be considered proven.
The main thing I want to say (other than dang!) is that since the data on Lynch and breast cancer so far is "mixed", it is very unlikely a physician will advise you to take any action based on a possible connection of Lynch with breast cancer. So we are on our own.
I asked a doctor who is actively involved in researching Lynch as breast cancer, about extra breast surveillance for family members with the mutation (but no bc diagnosis). The doctor said, "I don' t think there is enough novel and compelling evidence in 2020 to warrant any practice changes. (I believe there is a link, as did Henry Lynch.) There currently are no formal guidelines for MSH6 carriers as evidence for risk association is deemed insufficient." I asked my genetic counselor to run my question by the team at my own institution, and the team said there is "not sufficient evidence to perform enhanced [breast] surveillance for MSH6 carriers."
As you may know, in the United States (and other countries have similar bodies) the National Comprehensive Cancer Network aka NCCN regularly convenes a panel of experts to make evidence-based recommendations for testing, treatment, etc. No physician is going to gainsay current guidelines. Not going to happen. Now, I do believe in the value of evidence-based medicine. But, science moves slowly, and I think sometimes there is preliminary evidence or clues that are good enough to influence an individual person about their own care. Sometimes the stakes are high enough to push the boundaries.
Is that the case with your surgery decision? I don't know, but I think I might ask the genetics counselor, surgeon, and medical oncologist something like this: I understand we do not have enough evidence for a connection of PMS2 and breast cancer. If you knew that a woman with a similar history to mine had a mutation that *was* proven to confer, let's say a 27% risk of breast cancer, how would that affect the treatment plan for her? Is that a big enough figure that you would you advise single or double mastectomy? Or enhanced surveillance with MRI and mammograms alternating every six months? Some mutations such as BRCA carry a risk high enough to recommend mastectomy. What about lower-risk gene mutations? How do we think about those numbers?
Let me tell you, anyone in my family who has the mutation will get enhanced screening, one way or another! It turns out to be a matter of age plus one-side family history that qualified one of them, and both-sides family history that qualified another. The youngest one has not tested yet. They will be offered screening younger than usual based simply on family history, but if they test positive for the mutation I will insist they start even earlier, I don't care how coy the doctors are about their precious data. (And the fourth living person with the mutation had post-menopausal breast cancer.)
I assume you have read this paper and the relevant ones listed in the notes?
In the above study, "The prevalence of breast cancer differed based on mutation type (p=0.0043), as 27% of women with a PMS2 mutation were diagnosed with breast cancer, compared to 3%, 4%, and 9% in MLH1, MSH2, and MSH6 patients. The average age at diagnosis for women with a PMS2 mutation was 46.7 years."
Also see this one which implicates PMS2 and MSH6:
Please keep in touch if you are able. I'm so sorry cancer is interfering with what should be simply a time of joy for you.
2011 Stage I ITCs sn, premenopausal, Oncotype 16. 2014 Stage IV mets breast,liver. TaxolNEAD. Ibrance+letrozole 2yrs. Fas+afinitor nope. XelodaNEAD 2yrs. Eribulin,Doxil nope. SUMMIT FaslodexHerceptinNeratinib for Her2mut NEAD
2011, ILC, 1cm, Stage IA, Grade 1, 0/1 nodes, ER+/PR+, HER2-
2014, ILC, 2cm, Stage IV, metastasized to liver/other, Grade 2, ER+/PR+, HER2-
Tamoxifen pills (Nolvadex, Apo-Tamox, Tamofen, Tamone)