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CommandoBarbie

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Reply with quote  #1 
Hi Edge!  

I realize that this topic may not be one included in your research, and if that's the case please don't spend a lot of time on this.  Just let me know.

I have Rheumatoid Arthritis and Sjogren's Syndrome.  I am borderline for additional autoimmune diseases.  While being treated for triple negative breast cancer in '07, we stopped all of my arthritis drugs (I had just switched from Remicade to Enbrel; I also took methotrexate and an anti inflammatory). Thankfully, during tx,  I was symptom free of RA and all other autoimmune issues).  After tx ended, I went back on Enbrel, methotrexate, and an anti inflammatory with really good results. 

In '11 I developed oroparyngeal cancer. This cancer was not a recurrence, but a new primary. I was in tx from October until January, and again stopped all RA drugs during this time.  My RA had been in remission until recently.  After my second cancer, my Rheumatologist was hesitant to allow me to resume the TNF blockers.  He discussed this with my Onc, and he agrees, no more Enbrel. 

My question for you is are you aware of any breast cancer research that included RA patients?  I'd like to research alternatives to TNF's, but I'm not finding much information.  Is it a correct assumption that while TNF blockers carry an increase of lymphoma and leukemia, does a previous dx increase the risk even more so? Any info would be greatly appreciated.  And again, if its not something you are familiar with, no harm no foul.

Carynn

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edge

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Reply with quote  #2 

Carynn:


I have indeed reviewed this issue  several times.  Here are my thoughts:

 

I would not agree with the conclusions of your rheumatologist and your oncologist: although there have been some inconsistent findings in the arena of TNF  inhibitor therapy and cancer risk, once a critical review and appraisal of the most robust, methodologically strong studies, review and meta-analyses is undertaken, the weight of the data to  date does not support an association between such therapy and elevated cancer risk except on a weaker scale for non-melanoma skin cancer. 

 

Thus although a meta-analysis, commissioned by the European Medicines Agency, of 74 randomized controlled trials involving 15,418 patients treated with TNF-α blockers, could neither “refute nor verify” any link, the safety review conducted by the European League Against Rheumatism (EULAR) Task Force (Nam et al., Ann Rheum Dis, 2010) found no increased malignancy risk compared with conventional DMARDsm and the EULAR Task Force noted that Data from US, Canadian, Swedish, German, Spanish and UK registries and long-term, open-label extension data have shown no overall increased risk of malignancy, and although an increased occurrence of non-melanoma skin cancer, central nervous system tumors and colorectal cancer was suggested in the Swedish cohort, the numbers were small, and in any case not found to be statistically significant.

 

And recent evidence continues to weigh in on the side of no elevated risk: so, Xavier Mariette at INSERM (France) and colleagues (Ann Rheum Dis, 2011) conducted a comprehensive systematic review and meta-analysis and concluded that TNF inhibitor treatments do not increase the risk of malignancy, particularly lymphoma.  In confirmation, Park & Ranganathan at Washington University School of Medicine (Discov Med, 2012) concluded that "It is comforting that the data from these studies do not support an increased risk of cancer, except non-melanoma skin cancer, with the use of TNF-α antagonists in adults with RA". They wisely noted that "based on currently available data, the use of TNF-α inhibitors in adult patients with RA does not increase the risk of malignancies overall". They cautiously note that with respect to the risk of lymphoma, this is further compounded by the fact that rheumatoid arthritis (RA) itself may increase lymphoma risk. Again, there appears to be an increased risk for non-melanoma skin cancer with the use of these agents in adults with RA, so it would be imperative that  they be monitored regularly for pre-malignant and malignant skin lesions.

 

And again, the recent lifetime risk of TNF inhibitors (Kaminska et al., J Dermatolog Treat, 2011) study found that the risks of lymphoma, demyelinating diseases, and tuberculosis with TNF-α inhibitors are lower than risks patients face on a regular basis.

 

More recently still, we have several other cross-confirmative studies: the just completed review from Brigham and Women's Hospital (Solomon, Mercer, Kavanaugh, Arthritis & Rheumatism, 2012) observed a consistent lack of association between TNF inhibitors and cancer across the 11 observational studies / epidemiologic analyses included.

 

As to the issue of TNF inhibitors and cancer risk in patients with prior malignancy, Will Dixon at The University of Manchester and colleagues (Arthritis Care Res, 2010) did what I regard as the most relevant study, since no previous published studies have been able to address the question as to whether anti-TNF therapy influences the rate of malignancy in patients with prior malignancy. They assessed the influence of anti–tumor necrosis factor therapy (TNF inhibitors) on cancer incidence in patients with rheumatoid arthritis with a prior malignancy (including patients with breast cancer), using results from the British Society for Rheumatology Biologics Register (BSRBR).  They showed that in patients with RA and prior malignancy, the rate of incident malignancy is not increased in patients selected to receive anti-TNF therapy after an average of 3 years of follow-up (again, as in many but not all studies, patients with prior melanoma may be at particular risk of incident malignancy). This  finding was further confirmed by Anja Strangfeld and colleagues in Germany (Arthritis Res Ther, 2010) in research on  incident or recurrent malignancies among patients with rheumatoid arthritis exposed to TNF inhibitors, using the  German biologics register RABBIT where  it was found that there were no significant differences in the overall incidence of malignancies in patients exposed or unexposed to anti-TNF treatment were found, nor in the risk of recurrent malignancies (including patients with breast cancer).

 

Therefore at this time, critical appraisal of the most  methodologically robust systematic reviews, meta-analyses, and individual studies, including in populations with prior malignancy does not support excess cancer risk from TNF inhibitors in RA populations (with suitable caution for patients with prior skin malignancies).  



 

Lifestyle interventions of benefit include exercise and physical activity, and a number of studies substantiate the effectiveness of comprehensive occupational therapy (including wrist working splints and finger splints), all designed to assure a high degree of mobility and flexibility.

 

In terms of CAM, both preclinical and  human clinical pilot trials support a  positive role on pain and inflammation from curcumin (at least 1 - 2 grams daily), as well as boswellic acids (dosed as per the Edge-CAM regimen), and recent reviews including the  authoritative Cochrane Review have found evidence of clinically  relevant benefit from (1) omega-3 fatty acids (at doses of 2+ grams of EPA/DHA total content daily), (2) high daily intake of  gamma-linolenic acids/GLA (at least  1 grams daily) in the form of borage oil or blackcurrant oil, and with both omega-3 and GLA improvements increased over time.



Constantine Kaniklidis

Breast Cancer Watch

edge@evidencewatch.com

CommandoBarbie

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Reply with quote  #3 
Edge - thanks so much for your quick response.  I sure like what you had to say there.

I will definitely discuss with the Rhuemy next week.  Thank you again.  I really appreciate your input.

Carynn 

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