Dr. Claman 1996 Study May Be A Repeat For Oldtimers

Date: Thu, 2 Sep 1999 08:19:45 -0700

Antinuclear Antibodies In Apparently Healthy Women

With Breast Implants

Immunology of Silicones, Vol 210, pp 265-268 (Jan 1996)

HN Claman, MD, AD Robertson, PhD

University of Colorado Health Sciences Center

Denver, CO USA

There has been much controversy about whether women with breast implants are at increased risk for autoimmune disease, particularly scleroderma. Associations between breast implants and autoimmunity have been asserted [8-10] and denied [11-14]. We performed a cross sectional analysis of two cohorts of women with breast implants who considered themselves healthy together with suitable controls. A serum test for antinuclear antibodies (ANA) was the laboratory marker studied.

Patients and Methods

Women with breast implants were recruited to a special Breast Implant Evaluation Clinic primarily through word of mouth and through the news media. Each woman filled out a detailed questionnaire concerning their implant history and a history of possible illnesses, signs, symptoms and concurrent medications. Each woman had a physical examination by a physician. This report only concerns women with implants who considered themselves healthy; they came to the clinic requesting information about implants. This group is called group 1/0 (meaning the presence of implants= 1 and no symptoms = 0).

Control women were recruited by notices placed in the University Hospital. We requested women without implants who considered themselves healthy. This group is called group 0/0 (meaning no implants = 0 and no symptoms = T). These women also filled out a questionnaire and had a brief physical examination by a physician.

Two sequential studies were performed and there was no overlap in patients. The results in patients in Study A (the first study) have been published previously [15]. Because the results in these women were unexpected, we decided to repeat the study with new groups of implanted and control women. This is Study B. The full results of Study B are incorporated into a separate paper which is being prepared for publication. Study A and Study B each include additional symptomatic patients, but the purpose here is only to compare the ANA prevalence in two sequential cohorts of apparently healthy women with implants and controls.

Study A had 19 healthy volunteers (=group 0/0) and 38 women with breast implants who felt well (=group 1/0). ANA tests were done at a University based laboratory. Tests were performed at dilutions of 1:16, 1:64, 1:256, 1:512, etc. A test must have shown staining 1+ at 1:256 to be considered positive in this laboratory. "Trace" readings were ignored.

Study B had 18 healthy volunteers (=group 0/0) and 37 women with breast implants who felt well (=group 1/0). ANA tests were done at a University affiliated laboratory separate from the laboratory used in Study A. Tests were performed at dilutions of 1:40, 1:80, 1:160, etc. In this laboratory, a test must have shown staining 1+ at a dilution of 1:80 to be considered positive. "Trace" readings were ignored.

In each laboratory, the ANA test was done by indirect immunofluorescence using Hep-2 cells as substrate. In all cases, the laboratory technicians were unaware of the patient's status.

Results (Table 1-omitted)

In each study, approximately three quarters of the women were implanted for cosmetic reasons and the rest had reconstruction. About 90% of the implants were silicone gel or double lumen.

In Study A, women with implants who felt well had an 18% prevalence of a positive ANA test compared to 0% in controls (p<0.05). Study B, with different women and a different ANA laboratory, showed that women with implants who felt well had a 35% prevalence of a positive ANA test compared to 6% in controls (p=0.02).

As the methods used in the two studies appeared comparable, we combined the results, showing that 27% of 75 apparently healthy women with implants had a positive ANA test compared with 3% in controls (p=0.002).

In each study there was no correlation between ANA positivity and patient age, type of implant (saline or silicone gel), or indication for implantation (i.e. cosmesis vs reconstruction).

TABULAR DATA OMITTED

Discussion

Biologic effects of silicone products were discussed at length at the March, 1995, symposium at the National Institutes of Health, and many of these papers are included in this volume. Silicone is doubtless less inert than was believed in the past. How relevant the bioactivity of silicone may be to the question of autoimmune disease is not answered at the moment.

The experimental observations that silicone gel can act as an immunologic adjuvant for antibody production in rats [16] indicates that silicone can stimulate the immune system. In a special strain of mice, silicone gel can induce plasmacytomas [17]. It is not yet clear that these observations are relevant to women with implants of various kinds, although all breast implants have silicone in the capsule if not in the lumen.

Our cross-sectional studies of the prevalence of antinuclear antibodies in women with implants who feel well is one of the very few studies which are not retrospective and which appear to be free of ascertainment bias, as none of the women (controls or implanted subjects) had had a previous ANA and none considered themselves to be ill. Furthermore, the two studies were independent as each concerned different groups of women and the ANA tests were done in different laboratories. Therefore the fact that the findings were similar, namely that implanted women had a significantly higher prevalence of positive ANA tests, lends credence to the concept that this is a meaningful and not a chance result.

The ANA titers were in what might be considered to be moderate or low range for the laboratories concerned; and the ANA patterns were, in general, speckled and not strongly suggestive of any particular autoimmune syndrome.

Lastly, one is faced with the question "What is the biologic significance of a positive ANA test in an apparently healthy women?" This question is not easy to answer, as ANA tests are not usually run on healthy women. One follow-up study of asymptomatic women with positive ANA tests indicated that in five years following the discovery of antinuclear antibodies, 12% developed signs or symptoms suggestive of autoimmunity [18]. Other data from years ago found that there was a considerable risk of developing SLE or "questionable connective tissue disease" in women (but not men) found to have a chronic biologic false positive (BFP) test for syphilis [19]. As many consider that a BFP test is a serological indication of autoimmunity (but not necessarily of autoimmune disease), a positive ANA in implanted women may possibly be a harbinger of disease itself in the future. In any case, only careful follow-up studies will answer the question, and it is an important question. One hopes that the current climate of medicolegal activity will calm down so that such studies can be done.

Acknowledgments

We wish to thank Drs. Lawrence Ketch, and Richard Hamman, Ms. Susie Stutsman and the staffs of the Adult CRC and UCHSC Breast Center for their assistance, and Ms. Kathryn Utschinski for preparing the manuscript. Supported in part by NIH AI-34592, NIH RR-00051, and by Dow Corning, Inc.

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