breast implants and lymphoma; medical devices

The FDA just issued an alert on breast implant-associated anaplastic large cell lymphoma (BIA-ALCL):

   --see https://www.fda.gov/MedicalDevices/Safety/LetterstoHealthCareProviders/ucm630863.htm for the letter to providers

   --see https://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/ImplantsandProsthetics/BreastImplants/ucm481899.htm for the medical device report

Details:

--660 cases of BIA-ALCL have been reported (note: this is undoubtedly an underestimate, since many were probably not reported as noted in the advisory)

--BIA-ALCL is a lymphoma that arises in the fibrous scar (the "capsule") that develops around the implant. it is not a "breast cancer"

--median age 53, 8.5 years from last implant to diagnosis (this timing is from the last one; several patients have had multiple implant replacements, mostly for capsular contracture), 425 textured implants/39 smooth (196 not specified), 399 filled with silicone/260 saline, 119 implanted for reconstruction/125 for augmentation (416 not specified)

--presentation of BIA-ALCL: 

    --seroma 350; breast swelling or pain 188; capsular contracture 75; peri-implant mass 85; other 226

    --markers: anaplastic lymphoma kinase (ALK) positive in 0/negative in 239/not specified in 421; CD30 status positive in 239/negative in 0/not specified in 421

--incidence: estimated to range from 1 in 3,817 patients with implants, to 1 in 30,000

--treatment: mostly removal of implant and capsule. sometimes chemotherapy and radiation (there is an ongoing registry to evaluate treatments more scientfically, but at this point it seems that chemo and radiation are used if there is tumor outside the surgical margins)

Commentary:

--these BIA-ALCLs seem to develop independent of the type of implant (smooth vs textured), filling (silicone vs saline), indication (prior cancer vs cosmetic), though the majority seem to be in textured implants (though many reports do not include implant type)

    --textured implants are used with the idea that there might be less capsular formation and contracture. though the individual studies have not been conclusive, a recent meta-analysis did find some decrease in capsular contracture with textured implants (moderate quality evidence), with 124/1000 from smooth implants vs 59/1000 textured, though there is evidence of more BIA-ALCL with the textured ones (129 cases vs 11 with smooth implants),  low quality evidence. see https://www.medwave.cl/link.cgi/English/Updates/Epistemonikos/7021

--some of these 660 FDA reported cases were identified as duplicates, leading to 457 unique cases of BIA-ALCL attributable to implants, including 9 deaths. these 457 have basically the same age/etc characteristics as the 660 reported above

--as a perspective, the numbers of identified cases of BIA-ALCL are small compared to the 1.5 mllion patients getting implants worldwide every year

--unclear what the mechanism is for BIA-ALCL: ?methods used to create the textured surface  ?biofilms involved

--this really brings up issues of regulation and monitoring of medical devices:
    --  https://blogs.bmj.com/bmjebmspotlight/2015/08/31/primary-care-corner-with-geoffrey-modest-md-regulation-of-medical-devices/ ,  discusses the really really lax oversight of medical devices by the FDA, as well as the device maker malfeasance in not complying with required post-marketing reviews (on the order of 11.5% being done for what were considered by the FDA as high-risk therapeutic medical devices)

    -- as a related issue, the NY Times had a recent editorial (2/9/19) on the remarkably poor oversight of chemicals in cosmetics (see https://www.nytimes.com/2019/02/09/opinion/cosmetics-safety-makeup.html ). A very similar argument applies to the thousands of new chemicals introduced by industry overall every year, the vast majority without any significant toxicology screening prior to subsequently being introduced into our environment, food chain, etc.  Main points of the editiorial:

        --in 1988, there were Congressional hearings about lots of health and safety issues with cosmetics, the government noting that "nearly 1,000 toxic chemicals were lurking in countless personal care products" and that the FDA was underpowered to adequately police them. and nothing has changed since those hearings 30 years ago

        --there have been several cases in the past about asbestos in baby powder, hair care products that burn the scalp, chemicals in nail polish leading to serious health problems in nail technicians, etc

        --the American cosmetic industry is a $70-billion/year giant; the FDA office dealing with cosmetics has an annual budget of $8 million and 27 staff members. this FDA office's authority is summarized in 2 pages and has not changed since 1938. and the FDA cannot require companies to submit safety data before a product is released on the market, to adhere to standard manufacturing practices, or just to register with the FDA. Companies don't even have to report problems that consumers complain about; even if the FDA does hear of a problem, they cannot demand to inspect the company's records.

            --the FDA is even less able to ensure the safety of imported cosmetics (doubled in last decade), inspecting <1% of the 3 million yearly shipments

        --the cosmetic industry established an overview committee (the Cosmetic Ingredient Review), which has huge conflicts of interest, some of their conclusions run counter to the impartial National Toxicology Program, very few chemicals are considered by them as unsafe (only 11 of more than 5000 evaluated since 1976, their evaluations are based on often minimal available data since they do no direct testing, and these numbers are pretty dramatically different from the 1,000 toxic chemicals cited in the 1988 Congressional hearings), and even if they do recommend some industrial changes, their member companies don't even have to say if they will follow them.

        --and, not so surprisingly, the cosmetic industry has effectively counteracted efforts for more regulation or, for example, adding warning labels to talc-based products, and refer to concerned people as "chemical terrorists", while treating lawmakers to expensive vacations

    --and, many of our long-term food additives, well-integrated into food processing, may have very negative health effects: for example, emulsifiers (used extensively to homogenize foods by stabilizing water/lipid separation to "improve" texture and extend shelf-life, also break down the mucous/surfactant barrier, affect the microbiome ecosystem and may be related to intestinal inflammation/microbiome changes.  ?associated with inflammatory bowel disease ??cancer (eg, see https://www.nhs.uk/news/cancer/common-food-additives-linked-to-bowel-cancer/ )

so, this breast implant issue of increased anaplastic large cell lymphoma really brings up 2 issues:

--people getting implants should be forewarned of the small but real possibility of increased risk of this malignancy; and we clinicians should have heightened concern about any changes in the breast tissue around those with implants (most frequent being seromas); and (though untested) patients should be encouraged to do regular breast self-exams

--and, we really really do need to evaluate/regulate/monitor medical devices as well as industrial chemicals used, whether for cosmetic or other industrial production. this is a huge international public health issue. i should note here that this is not a new Trump thing (though regulation is systematically being decimated now), but has never really been adequately addressed in the past....

geoff

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