Predict LE with genes that promote inflammation

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kira66715
kira66715 Member Posts: 4,681
edited May 2016 in Lymphedema

This just came out--it shows that those of us who have a robust inflammation response are more likely to get LE--other studies have shown that those of us who share some genes with primary LE are far more likely to get LE--the Finegold work out of Pittsburgh. 

There is a wonderful blog on breast cancer (IMO), called Nancy's point,http://nancyspoint.com/ where she writes "Share, don't compare"--the genetics of LE is a large part of why some women can get away with out getting it, no matter what they do, and others of us got it with minimal insult.

http://www.ncbi.nlm.nih.gov/pubmed/24502445

Lymphat Res Biol. 2014 Feb 6. [Epub ahead of print]

Cytokine Candidate Genes Predict the Development of Secondary Lymphedema Following Breast Cancer Surgery.

Leung G1, Baggott C, West C, Elboim C, Paul SM, Cooper BA, Abrams G, Dhruva A, Schmidt BL, Kober K, Merriman JD, Leutwyler H, Neuhaus J, Langford D, Smoot BJ, Aouizerat BE, Miaskowski C.

Author information

Abstract

Abstract Background: Lymphedema (LE) is a frequent complication following breast cancer
treatment. While progress is being made in the identification of
phenotypic risk factors for the development of LE, little information is
available on the molecular characterization of LE. The purpose of this
study was to determine if variations in pro- and anti-inflammatory
cytokine genes were associated with LE following breast cancer treatment. Methods and Results: Breast cancer
patients completed a number of self-report questionnaires. LE was
evaluated using bioimpedance spectroscopy. Genotyping was done using a
custom genotyping array. No differences were found between patients with
(n=155) and without LE (n=387) for the majority of the demographic and
clinical characteristics. Patients with LE had a significantly higher
body mass index, more advanced disease, and a higher number of lymph
nodes removed. Genetic associations were identified for three genes
(i.e., interleukin (IL4) 4 (rs2227284), IL 10 (rs1518111), and nuclear
kappa factor beta 2 (NFKB2 (rs1056890)) associated with inflammatory
responses. Conclusions: These genetic associations suggest a role for a
number of pro- and anti-inflammatory genes in the development of LE
following breast cancer treatment.

http://www.ncbi.nlm.nih.gov/pubmed/22351697

Clin Cancer Res. 2012 Apr 15;18(8):2382-90. doi: 10.1158/1078-0432.CCR-11-2303. Epub 2012 Feb 20.

Connexin 47 mutations increase risk for secondary lymphedema following breast cancer treatment.

Finegold DN1, Baty CJ, Knickelbein KZ, Perschke S, Noon SE, Campbell D, Karlsson JM, Huang D, Kimak MA, Lawrence EC, Feingold E, Meriney SD, Brufsky AM, Ferrell RE.

Author information

Abstract

PURPOSE:

Secondary lymphedema
is a frequent complication of breast cancer associated with surgery,
chemotherapy, or radiation following breast cancer treatment. The
potential contribution of genetic susceptibility to risk of developing
secondary lymphedema following surgical trauma, radiation, and other tissue insults has not been studied.

EXPERIMENTAL DESIGN:

To determine whether women with breast cancer and secondary lymphedema had mutations in candidate lymphedema
genes, we undertook a case-control study of 188 women diagnosed with
breast cancer recruited from the University of Pittsburgh Breast Cancer
Program (http://www.upmccancercenter.com/breast/index.cfm) between 2000
and 2010. Candidate lymphedema
genes, GJC2 (encoding connexin 47 [Cx47]), FOXC2, HGF, MET, and FLT4
(encoding VEGFR3), were sequenced for mutation. Bioinformatics analysis
and in vitro functional assays were used to confirm significance of
novel mutations.

RESULTS:

Cx47 mutations were identified in individuals having secondary lymphedema
following breast cancer treatment but not in breast cancer controls or
normal women without breast cancer. These novel mutations are
dysfunctional as assessed through in vitro assays and bioinformatics
analysis and provide evidence that altered gap junction function leads
to lymphedema.

CONCLUSIONS:

Our findings challenge the view that secondary lymphedema
is solely due to mechanical trauma and support the hypothesis that
genetic susceptibility is an important risk factor for secondary lymphedema.

A priori recognition of genetic risk (i) raises the potential for early
detection and intervention for a high-risk group and (ii) allows the
possibility of altering surgical approach and/or chemo- and radiation
therapy, or direct medical treatment of secondary lymphedema with novel connexin-modifying drugs.

Comments

  • Binney4
    Binney4 Member Posts: 8,609
    edited March 2014

    Kira, thank you for always being on top of the LE news!

    Now, if we could just develop some simple, painless, non-invasive tests to determine before BC treatment exactly who's dealing with these confounded genes, and then counteract the effect to prevent the LE. Aaaaaaaahhh!

    Someday!
    Binney

  • kira66715
    kira66715 Member Posts: 4,681
    edited March 2014

    Binney, Rockson is always testing ketoprofen, but it doesn't seem like a "cure". And as we've discussed, payment in medicine is for procedures--not thinking, so I'm not surprised at the surgeons finding their way into LE.

    As we also discussed, any surgeon can do any surgery, and insurance will start to pay for it, once it's determined not to be experimental. A few years ago, when LVA was still considered experimental, I talked to one of the main surgeons and he said it was not a cure. 

    Funny how that's changed.

    Several years ago, there was a great study where patients were told they were going to get arthroscopic clean out surgery for arthritis, and all were taken to the OR, all were put to sleep and everyone got a scar, but only half got surgery. And there was NO difference. And yet the surgery is still being done, and still paid for.

    And searching pubmed, there's a similar study from last year--in New England Journal

    http://www.ncbi.nlm.nih.gov/pubmed/24369076

    N Engl J Med. 2013 Dec 26;369(26):2515-24. doi: 10.1056/NEJMoa1305189.

    Arthroscopic partial meniscectomy versus sham surgery for a degenerative meniscal tear.

    Sihvonen R1, Paavola M, Malmivaara A, Itälä A, Joukainen A, Nurmi H, Kalske J, Järvinen TL; Finnish Degenerative Meniscal Lesion Study (FIDELITY) Group.

    Collaborators (9)

    Author information

    Abstract

    BACKGROUND:

    Arthroscopic partial meniscectomy is one of the most common orthopedic procedures, yet rigorous evidence of its efficacy is lacking.

    METHODS:

    We conducted a multicenter, randomized, double-blind, sham-controlled trial in 146 patients 35 to 65 years of age who had knee symptoms consistent with a degenerative medial meniscus tear and no knee osteoarthritis. Patients were randomly assigned to arthroscopic partial meniscectomy or sham surgery.
    The primary outcomes were changes in the Lysholm and Western Ontario
    Meniscal Evaluation Tool (WOMET) scores (each ranging from 0 to 100,
    with lower scores indicating more severe symptoms) and in knee pain after exercise (rated on a scale from 0 to 10, with 0 denoting no pain) at 12 months after the procedure.

    RESULTS:

    In
    the intention-to-treat analysis, there were no significant
    between-group differences in the change from baseline to 12 months in
    any primary outcome. The mean changes (improvements) in the primary
    outcome measures were as follows: Lysholm score, 21.7 points in the
    partial-meniscectomy group as compared with 23.3 points in the sham-surgery
    group (between-group difference, -1.6 points; 95% confidence interval
    [CI], -7.2 to 4.0); WOMET score, 24.6 and 27.1 points, respectively
    (between-group difference, -2.5 points; 95% CI, -9.2 to 4.1); and score
    for knee pain
    after exercise, 3.1 and 3.3 points, respectively (between-group
    difference, -0.1; 95% CI, -0.9 to 0.7). There were no significant
    differences between groups in the number of patients who required
    subsequent knee surgery (two in the partial-meniscectomy group and five in the sham-surgery group) or serious adverse events (one and zero, respectively).

    CONCLUSIONS:

    In this trial involving patients without knee
    osteoarthritis but with symptoms of a degenerative medial meniscus
    tear, the outcomes after arthroscopic partial meniscectomy were no
    better than those after a sham surgical procedure.
    (Funded by the Sigrid Juselius Foundation and others; ClinicalTrials.gov number, NCT00549172.).


    Look, we all want a cure for this, and brave people are putting themselves out there as essentially guinea pigs, but a surgical mentality is not to establish long term relationships with patients.

    Hopefully as we understand risks and eliminate unneccesary risks in treatment--like less ALND, more careful radiation planning, awareness of the risks of chemo and LE, careful handling of the tissues in surgery, careful post op instructions and if we can identify high risk people early--we can make the burden of LE far less.

  • carol57
    carol57 Member Posts: 3,567
    edited March 2014

    Kira , I wonder then if those of us taking statins long-term are not supposed to have LE. Isn't the point of that class of drugs to reduce inflammation and the inflammatory response?

  • kira66715
    kira66715 Member Posts: 4,681
    edited March 2014

    Carol, if only it was that simple. When Rockson was still talking to me, he told me that ibuprofen made people swell, but ketoprofen did not. Both are anti-inflammatory agents.

    Statins do seem to have both long term benefits and some harms--raise glucose levels, muscular issues, and ?cognitive issues. 

    And the long awaited newest lipid guidelines came out to huge controversy--the risk calculator seems flawed....

  • KS1
    KS1 Member Posts: 632
    edited March 2014

    For what it is worth, about a year and a half ago, the physiatrist I was seeing for LE put me on high dose corticosteroids for 5 days for a reason unrelated to LE.  I had been struggling with a bad flare for many months and, at the point I was put on steroids, my LE was pretty unstable ... I had to be ultra-careful about everything and could only wear garments for 6 or 8 hours before having to wrap.  Given that many people swell on steroids, I was worried my LE would go wild, but the opposite happened

    Day 3 of steroids, I could see my knuckles and bend my pinky for the first time in 10 months.  The doc was shocked at the improvement and said something like "LE isn't just a plumbing problem ... it's about inflammation."     Since then, my LE has been easier to manage.   Maybe it wasn't the steroids, but the timing sure seemed like it was.  KS1

  • kira66715
    kira66715 Member Posts: 4,681
    edited March 2014

    KS1, that's so interesting that the steroids turned it around. I remember how stubborn it was. It isn't just a plumbing problem.

  • juneping
    juneping Member Posts: 1,594
    edited March 2014

    thanks for posting. i had 35 nodes removed....i am very concern about my poor arm.

  • tessu
    tessu Member Posts: 1,564
    edited November 2015

    kira, you seem to be up to date on cutting edge research. Are there any studies abut whether naprosyn helps LE (like ketoprofen) or worsens it (like ibuprofen)? (I'm not that computer search savvy, haven't found that myself). Thanks

  • paintThesky
    paintThesky Member Posts: 56
    edited November 2015

    I was wondering about the Naproxen as well. Sometimes the ache in my upper arm and breast at days end is bad, and I need something for pain. Ibuprofen tears up my stomach.

  • shaz101
    shaz101 Member Posts: 718
    edited December 2015

    has anyone tried ketoprofen? I'm thinking of asking my doctor to prescribe it for me. I'm so sick of this LE it's getting worse.

  • SusanSnowFlake
    SusanSnowFlake Member Posts: 165
    edited December 2015

    Over my head, does this have something to do with people who have auto-immune conditions such as psoriasis, psoriatic arthritis, MS etc. and a link with LE?

  • Sannoliver1
    Sannoliver1 Member Posts: 25
    edited May 2016

    Bumpes to ask of anyone else has tried ketoprofen with success. I too would like to try. My LE is pretty mild but it's in both arms.

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