implant controversy continues study

[Guest guest]

SILICONE IMPLANT CONTROVERSY CONTINUES

and colleagues' study in the New England Journal of Medicine

suggests no association between breast implants and connective

tissue disease,[1] and an accompanying editorial claims that the US

Food and Drug Administration had been paternalistic and

unnecessarily alarmist in banning these implants? The editorial also

criticizes conclusions drawn on courtroom opinion and not on data --

so let us look at the data.

Olmstead County, Minnesota, has a computerized medical record system

providing excellent opportunities for epidemiological study. The

incidence of most connective tissue diseases has already been

calculated for this patient population. These expected rates (from

the Rochester Epidemiologic Project) suggest that the smallest

detectable relative risk for a sample size of 1000 breast implant

patients followed for 10 years would be 12.5 for any connective

tissue disorder. ( " Any connective tissue disorder " would include

well-defined rheumatic diseases such as systemic lupus

erythematosus, scleroderma, rheumatoid arthritis, Sjogren's

syndrome, and thyroiditis.) In other words, there would need to be

13 cases of well-defined connective tissue disease in the breast

implant population for each case in the controls if statistical

significance were to be achieved. If this number were found it would

imply substantial risk. Any value less than this would be non-

significant statistically and taken by some readers to mean no

associations--yet there could still be a substantial risk (12-fold

or less). The Mayo Clinic study,[1] with only 749 patients followed

for an average of 7.8 years, was not powerful enough to detect

increased risk for connective tissue disease. Furthermore, women

with silicone breast implants seem to develop an atypical rheumatic

disorder;[3-7] the study did not look for atypical disease. Record

review was used but the rheumatic disease experience of the

physicians was not given. The follow-up was too short--those women

who have had problems have had the implants for 9 years on average.

[3,5-7] The laboratory data cannot be interpreted because we are not

told how many women had the tests. The Mayo study does not permit

the conclusion that there is no association between connective

tissue diseases and breast implants; it does show that the relative

risk of well-defined connective tissue disease in patients with

silicone implants is not above 15.

What do we know about silicone implants? The rate of breast fibrous

capsule contracture approaches 70% 2-4 years after implantation[6,7]

and the rate of complications (breast pain, contracture, rupture,

infection, implant migration) requiring surgery approaches 50% at 10

years.[7] The Mayo study noted a 30% failure rate at 7.8 years.[1]

Case-series studies suggest an under-representation of rheumatoid

arthritis and an over-representation of scleroderma.[3,8] A large

epidemiological study recorded a decreased risk of rheumatoid

arthritis in women with breast implants.[9] Rheumatologists who are

investigating the clinical problems of women with these implants

have reported a similar constellation of findings in more than 1000

patients.[3,5,7,10,11] The silicone implant associated syndrome

typically includes arthralgia, myalgia, sicca complex, paraesthesia,

balance disturbance, night sweats, rashes, memory difficulty, and

fatigue.[5] An undifferentiated connective tissue disorder comprises

a small but clinically important subgroup.[3,5,7] Other diffuse,

regional, and local musculoskeletal problems have been described.[5]

Autoantibodies to collagen and extracellular matrix proteins and

abnormalities of cell-mediated immunity have been found in women

with silicone implants and not in controls.[12-14] However, there

does not seem to be a serelogical marker (including antinuclear

antibodies) consistently associated with rheumatic disease in

patients. These findings suggest that silicone implants cause immune

dysfunction and rheumatic disease. Many rheumatologists now think

that these patients have one or more of group of rheumatic illnesses

termed " silicone-related disorders " .

The courtroom has been important in bringing out information about

research on silicone (and lack of it). Research which showed

adjuvant activity and other types of immune dysfunction was kept

from the FDA in 1991; manufacturers' memoranda containing

information on silicone toxicity and immune reactions were

labelled " Please discard after reading " . Human studies to determine

safety were proposed but not done. Only through the legal system has

this information been revealed. The manufacturers, despite years of

study, have not provided data to show safety, and the Mayo Clinic

study throws little light on the matter. The FDA's decision to ban

the use of silicone gel implants except in controlled clinical

studies was a reasonable one, in my view. More research into the

silicone-related disorders is required by a prospective controlled

study. Until the handful of rheumatologists and immunologists who

are investigating the clinical and immunological abnormalities in

these women come up with more answers the controversy will continue.

SE, O'Fallon WM, Kurland LT, et al. Risk of connective

tissue diseases and other disorders after breast implantation. N

Engl J Med 1994; 330: 1697-702.

Angell M. Do breast implants cause systemic disease? Science in the

courtroom. N Engl J Med 1994; 330:1748-49.

Bridges AJ, Conley C, Wang G, Bums DE, Vasey FB. A clinical and

immunologic evaluation of women with silicone breast implants and

symptoms of rheumatic disease. Ann Intern Med 1993; 118: 929-36.

Bridges AJ, Lorden T. Sicca syndrome in women with silicone

implants: absence of serum autoantibodies. Arthritis Rheum 1993; 36:

S191 (abstr).

Bridges AJ. Rheumatic disorders in patients with silicone implants:

a review. J Biomat Sci (in press).

Bridges AJ, Vasey F. Silicone breast implants: history, safety and

potential complications. Arch Intern Med 1993; 53:2638-44.

G. A clinical and laboratory profile of symptomatic women

with sillcone breast implants. Sem Arthritis Rheum 1994;24:29-37.

Spiera H, Kerr LD. Scleroderma following silicone implantation: a

cumulative experience of 11 cases. J Rheumatol 1993; 20: 958-61.

Dugowson CE, Daling J, Koepsell TD, Voight L, JL. Silicone

breast implants and risk for rheumatoid arthritis. Arthritis Rheum

1992; 35:S66 (abstr).

Borenstein D. Clinical manifestations of 100 consecutive women with

silicone breast implants. Arthritis Rheum 1993; 36:S117 (abstr).

Cuellar ML, Scopelitis E, Citera G, et al. A prospective clinical

evaluation of 300 women with silicone breast implants. Arthritis

Rheum 1993;36:S219 (abstr).

Teuber SS, Rowley MJ, Yoshida SH, Ansari AA, Gershwin ME. Anti-

collagen autoantibodies are found in women with silicone breast

implants. J Autoimmunity 1993;6:367-77.

Kossovsky N, Zeidler M, Chun G, et al. Surface dependent antigens

identified by high binding avidity of serum antibodies in a

subpopulation of patients with breast prostheses. J Appl Biomat

1993; 4:281-88.

Ojo-Amaize EA, Conte V, Lin HC, et al. Silicone-specific blood

lymphocyte response in women with silicone breast implants. Clin

Diag Lab Immunol (in press).

~~~~~~~~

By Alan J Bridges University of Wisconsin Hospital, Madison, WI, USA

Copyright 1994 by Lancet. Text may not be copied without the express

written permission of Lancet. Bridges, Alan,