Congressional Record, Volume 151 Issue 39 (Thursday, April 7, 2005)

[Congressional Record Volume 151, Number 39 (Thursday, April 7, 2005)]
[Extensions of Remarks]
[Pages E590-E594]
From the Congressional Record Online through the Government Publishing Office [www.gpo.gov]

THE SAFETY OF SILICONE BREAST IMPLANTS

______

HON. CHARLIE NORWOOD

of georgia

in the house of representatives

Wednesday, April 6, 2005

Mr. NORWOOD. Mr. Speaker, in addition to my remarks today, I am also
submitting a letter written by Dr. Scott Spear to the Senate Health
Education Labor and Pensions Committee and the House Energy and
Commerce Committee. In it, Dr. Spear, who is the President of the
American Society of Plastic Surgeons, brings to light an important
health issue that the Food and Drug Administration (FDA) is currently
debating: the safety of silicone gel-filled breast implants. The FDA's
General and Plastic Surgery Devices Panel has scheduled an upcoming
hearing that will focus primarily on the safety of these products for
the American consumer. The information that Dr. Spear shares in his
letter is important for us to take note of as this panel continues its
work to make an informed, science-based decision on the safety of these
implants. In addition, I am submitting for the Record a pamphlet
entitled Safety of Silicone Breast Implants that reviews the long term
studies that have been performed on silicone gel-filled breast
implants. Taken along with Dr. Spear's letter, this brochure makes a
compelling argument that in determining the very real and
unquestionably important issue of determining the safety of these
implants, we must set preconceived notions aside, and ensure that
science dictates our actions. I urge my colleagues to review these two
documents and I encourage you to join me in supporting the unbiased and
open-minded work of the FDA panel as it determines the safety of
silicone gel-filled breast implants for American consumers.
March 4, 2005.
U.S. Senate Health, Education, Labor, and Pensions Committee,
U.S. House Energy and Commerce Committee, (Members and
Health Legislative Assistants).
Dear Senators: The Food and Drug Administration (FDA) is
conducting an ongoing regulatory process regarding breast
implants, which the American Society of Plastic Surgeons
(ASPS) fully supports. As physicians and patient advocates,
we support sound science and have confidence that the FDA
will review valid scientific data and make its decisions
based on the best interests of patients. Moreover, we believe
a strong post-market surveillance process will serve the best
interests of our patients.
As part of this process, the FDA's General and Plastic
Surgery Devices Panel will be conducting hearings on April
11-13 regarding the pre-market approval (PMA) applications of
two manufacturers' silicone gel-filled breast implants. The
FDA appointed panel represents areas of expertise and
judgment relevant to the product under review including
academicians in specific fields, such as from radiology,
oncology, biostatistics, ethics, plastic surgery, general
surgery and other disciplines. Each panelist is vigorously
screened and cleared by the FDA in advance of their
participation. Historically, panelists have been permitted to
engage in educational activities promoting patient care.
These activities have not been deemed conflicts of interest.
Anti-breast implant advocates continue to raise this issue to
discredit qualified and reputable clinicians.
As a matter of background, the FDA's General and Plastic
Surgery Devices Panel conducted a similar hearing in October
2003. The

[[Page E591]]

hearings were conducted in a highly open and transparent
process, with more than 20 hours of public testimony and
signification deliberation. Ultimately, the 2003 Advisory
Panel recommended approval of the device with a number of
conditions. The conditions outlined by the panel include
development of a model informed consent form, patient
education, surgeon education, patient follow-up and exams,
annual reports to FDA, implant retrieval testing, a breast
implant registry, and recommendation for removal of ruptured
implants. In January 2004, the FDA decided to postpone action
pending submission of additional manufacturer data outlined
in a revised draft guidance to be addressed at this
subsequent panel hearing.
Given the level of interest in the FDA's review of silicone
breast implants, it is important that Members of Congress are
provided accurate and science-based information concerning
these medical devices.

PATIENT SAFETY

The ASPS believes that the FDA's scrutiny of this product
is appropriate to ensure patient safety. We are not
interested in supporting any device that is not proven safe.
In 2000, the Institute of Medicine (IOM) issued an exhaustive
report that reviewed and analyzed the scientific literature
on silicone breast implants. The IOM concluded that there is
no link between silicone breast implants and systemic
disease. The primary safety issues for women who choose
breast implants are local in nature and include the following
complications: (1) Capsular contracture or tightening of
natural scar tissue around the implant (contracture is
unpredictable and, when severe, may require corrective
surgery); (2) Implant rupture, which carries risk of
additional surgery for replacement; and (3) Infections
associated with breast implants, which are generally not
common. The IOM report noted that while breast implants have
improved over time, patient safety issues associated with
local complications require additional research. The ASPS has
supported and is supporting continued research in these and
other areas.
Our clinical experience over 35 years with breast
augmentation surgery shows an excellent track record and the
demand for breast augmentation surgery has grown steadily
with nearly 250,000 procedures performed in 2003. The ASPS
believes that an important component of patient safety and
satisfaction with breast augmentation depends on patients
being fully informed about both the benefits and risks of the
surgical procedure. Consequently, ASPS has developed a
comprehensive document that covers all of the risks and
potential complications in breast implant surgery for plastic
surgeons to use when discussing the procedure with their
patients.

CHOICE

Currently saline-filled breast implants, approved by the
FDA in 2000, are the only implants available for general use
in breast augmentation. Silicone gel-filled implants may only
be used in clinical trials for reconstructive breast surgery
and limited clinical trials for breast augmentation. The
FDA's device approval process will determine whether
requirements for safety and efficacy have been met and
whether women should have additional choices regarding the
type of implants they may select for breast surgery. The
implant type that provides the best aesthetic outcome depends
on a variety of individual patient factors. In all cases,
patient safety and informed decision making should be primary
considerations in selecting a particular type of implant.
Like other implantable medical devices, breast implants may
not last a lifetime. Hundreds of thousands of women
understand this fact and still choose to undergo breast
implant surgery. Current research shows that an overwhelming
majority are happy with their decision.

hiSTORY/SCIENCE

It is important to distinguish between anecdotal and
scientific evidence with regard to breast implants. Anecdotal
evidence and junk science do not provide valid contributions
to the review and analysis of this device. Plastic surgeons
actively support valid scientific research on the safety and
efficacy of breast implants, as well as the psychological
impact of breast augmentation. The following are select areas
of scientific research that Congress should be aware of in
relation to breast implants.
The National Academy of Sciences' Institute of Medicine
report, issued in 2000, found no scientific evidence of an
association between silicone breast implants and disease; the
report represents a comprehensive and unbiased review of
breast implant safety by top experts in a variety of medical
fields. Safety of Silicone Breast Implants, Institute of
Medicine, National Academy Press, 2000.
Recent studies about suicide among Scandinavian women who
have breast implants warrant further investigation. Suicide
is a very complicated problem with many contributing factors;
biological, genetic, social and cultural. It is important to
note that the recent studies do not show a ``cause and
effect'' relationship between breast implants and suicide.
Plastic surgeons and the medical community in the U.S. have
studied breast implants, breast augmentation patients, and
breast reconstruction patients for more than 30 years with no
indication of a relationship between breast implant surgery
and suicide. Further investigation of this issue is
appropriate. Mortality among augmentation mammoplasty
patients. Epidemiology. 2001; 12:321-326. Total and cause
specific mortality among Swedish women with cosmetic breast
implants: prospective study. Brit Med j. 326:527-528, 2003.
The National Institutes of Health (NIH) issued a report to
Congress in May of 2003 on the status of its research on the
long-term health effects of breast implants. The report
stated that there was not sufficient evidence to support any
relationship between breast implants and connective tissue
disorders. The NIH report also cited a recent National Cancer
Institute (NCI) finding that women with breast implants
showed a slight decrease in the risk for breast cancer.
National Institutes of Health. Breast implants: status of
research at the National Institutes of Health, May 2003.
Since the Institute of Medicine report in 2000, numerous
studies have been conducted which investigate the purported
connection of breast implants to cancer. However, researchers
have consistently found no persuasive evidence of causal
association between breast implants and any type of cancer.
Breast Implants and Cancer: Causation, Delayed Detection and
Survival, May, 2001 Plastic and Reconstructive Surgery.
In 2000, the Plastic Surgery Educational Foundation
established the National Breast Implant Registry (NaBIR). It
was founded to collect and analyze data regarding breast
implant surgery to further understand the risks and benefits
of this procedure. To date more than 21,000 women have
registered with NaBIR and there are 316 surgical facilities
entering data. We believe that NaBIR is quickly becoming a
world standard for an electronic breast implant registry, as
it is being considered in a number of European and Latin
American countries. In December of 2002, the European Union
mandated that participating countries implement breast
implant registries by 2004; Denmark, England, Finland, and
Germany have already implemented programs. Australia and
Brazil have also implemented registries.
The ASPS and its members support sound science and have
been leaders in the research on the safety and efficacy of
breast implant surgery. Our primary concern is the safety of
our patients and we are strongly interested in the collection
of accurate and reliable data pertaining to breast implants.
We recently launched the medically-grounded online resource
for women and other concerned parties,
www.reastimplantsafety.org. We encourage you to visit the
site for the latest information on breast implants and
patient safety. We believe that the upcoming hearing of the
FDA General and Plastic Survery Devices panel will again be
rigorous and the panel deliberations will be largely based on
the findings of science, rather than emotion and anecdote.
The ASPS has offered to work with the FDA, public, and
manufacturer in order to address many of the conditions
attached to the panel's affirmative recommendation.
Specifically, the panel recommended that the manufacturer
work with professional organizations to create patient and
surgeon education materials, a model informed consent form,
and establish a breast implant registry and we are responding
to that call. We hear stories every day of women whose lives
have been dramatically improved with the use of this device.
We are hopeful that the FDA's regulatory review process can
continue moving toward a conclusion based on science.
Sincerely,
Scott L. Spear, MD,
ASPS President.
____

Safety of Silicone Breast Implants

BACKGROUND

In October, 2003, the General and Plastic Surgery Devices
Panel convened by the Food and Drug Administration (FDA)
concluded that there was a dearth of long-term safety data
related to silicone breast implants. Contrary to this
contention, there are in fact almost 100 published papers in
the peer-reviewed biomedical literature assessing long-term
effects of cosmetic breast implants, virtually all of which
are reassuring in their lack of evidence for adverse effects.
Concerns about a link between silicone breast implants and
varlious adverse health outcomes were initially raised in the
1980's and early 1990's by anecdotal case reports. However,
as unanimously concluded by several independent expert review
committees by the late 1990's,^1-5 these alleged
health risks have not been supported by the numerous analytic
epidemiologic studies of cosmetic breast implant recipients.
Since publication of these independent reviews from various
countries, including the United States, a large number of
long-term cohort studies of connective tissue diseases,
undefined connective tissue disease, cancer, neurologic
disorders, mother-offspring effects and mortality have been
published.^6-38

CONNECTIVE TISSUE DISEASE

More than 20 case-control and cohort investigations have
been conducted in in North America and Europe to evaluate the
potential association between cosmetic silicone breast
implants and the occurrence of CTDs. Initially, the primary
concern was the occurrence of systemic sclerosis, although
these epidemiologic studies have examined the occurrence of
numerous other CTDs. The published case-control
studies,^39-49 and cohort
studies,^{6,18,35,37,50-59} many of which have been
large, long-term follow-up studies, have been remarkably
consistent in finding no evidence

[[Page E592]]

of an association between silicone breast implants and any
individual CTD or all established CTDs combined. Moreover,
meta-analyses, weight-of-the-evidence, and critical reviews
have unanimously concluded that there is no evidence of an
association between breast implants and any of the CTDs
evaluated individually or combined.^2-5,60-66

``ATYPICAL:'' CONNECTIVE TISSUE DISEASE

An association has also been hypothesized between silicone
breast implants and some new ``atypical'' disease, which does
not fulfill established diagnostic criteria for any known CTD
and may bear some resemblance to fibromyalgia.⁶⁷
Those studies which did include undefined CTD as an outcome,
many of which have been large, long-term follow-up studies,
have been strikingly consistent in finding no convincing
evidence of an association between silicone breast implants
and atypical connective tissue or rheumatic
disease.^{2,5,6,8,14,18.24,46,68}

FIBROMYALGIA

In 2001, Brown et al.\35\ reported an excess of self-
reported fibromyalgia among women who had ruptured implants
with extracapsular silicone migration (extracapsular rupture)
diagnosed by magnetic resonance imaging (MRI). However, this
elevated risk ratio cannot be meaningfully interpreted, due
to the inappropriate use of a combined group of women with
intracapsular rupture and women with intact implants as the
comparison group.^68-70 It is also noteworthy that
the rates of fibromyalgia reported among women with intact
implants or intracapsular ruptures in the study by Brown et
al.\36\ are remarkably high compared with the estimated
prevalence rate of 3.4% for U.S. women\71\ and with similar
or lower prevalence rates reported in many other
countries,^6,55,72-76 indicating a biased selection
of women in that study.
Most recently, Holmich et al.\18\ explicitly tested the
hypothesis of an increased risk of fibromyalgia by rupture
status among 238 unselected women with cosmetic silicone
breast implants. There was no excess of undefined CTD or
other chronic inflammatory condition, including fibromyalgia.
None of the women with extracapsular rupture reported
fibromyalgia. Thus, the finding by Brown et al.\35\ of a
greater than two-fold excess of self-reported fibromyalgia
among women with extracapsular rupture was not confirmed in
the study by Holmich et al.,\18\ who concluded that implant
rupture is not associated with fibromyalgia or other
rheumatic conditions.

BREAST AND OTHER CANCERS

More than 10 epidemiologic studies, many of which have been
large and able to assess long-term risks, have been conducted
in Europe and North America to evaluate the potential
association between cosmetic breast implants and the
incidence of breast or other cancers, notably lung cancer,
cancers of the cervix and vulva, leukemia, and multiple
myeloma.^{17,23,24,32-34,77-83} Although the primary
concern has been breast cancer risk, epidemiologic studies
have been remarkably consistent in finding no evidence of
increased risk for breast or other cancers among women with
breast implants; in fact; in most studies the risk of breast
cancer was below expectation.^1,2,84,85 The rare
reported excesses of lung and cervical cancer are likely due
to confounding by lifestyle factors and/or reproductive
characteristics. In fact only the cohort study by Brinton et
al.,\34\ which reported a significant excess of deaths from
brain cancer, has reported an association with a cancer that
is not a likely result of lifestyle factors such as smoking
or other activities that are unrelated to implants. The
extreme risk estimate for brain cancer reported in this
study, which suffers from several methodological
shortcomings, is inconsistent with the overwhelming weight of
the epidemiologic evidence and is biologically
implausible.\86\

BREAST CANCER DETECTION

Concern has been raised that the ability to detect early
breast cancer is limited in women with breast implants. The
hypothesis that breast implants may interfere with physical
breast examination or mammographic visualization of breast
tumors, leading to delays in breast cancer diagnosis and
worse prognosis among women receiving implants, is based on
the findings of a few early clinical studies,^87,88
many of them originating from the same clinic. However, the
interpretation of these clinical case series is hampered by
potential referral or ascertainment bias, small sample size
and absence of a control group. The results of numerous
analytic epidemiologic studies, which used control groups to
provide comparison data, consistently show that women with
breast implants do not in fact present with more advanced
stages of breast cancer or experience shorter survival (the
clinically relevant outcomes), thus indicating no delay in
breast cancer detection following breast
augmentation.^{19,32,71,89-97}
In a recently published large-scale study,⁹⁸
women receiving silicone gel implants for breast
reconstruction after breast cancer had significantly lower
mortality rates than those women who did not receive breast
implants after cancer surgery. Thus, there is no evidence
that silicone gel implants adversely affect survival
following breast cancer.

NEUROLOGIC DISEASE

With respect to other outcomes, during the past six years,
three large, population-based cohort studies have been
conducted to evaluate risk for neurologic disease among women
with cosmetic breast implants,^9,}28,}99 and no
association has been found.

OFFSPRING EFFECTS AND BREASTFEEDING

Similarly, three epidemiologic
investigations,^10,15,100 all population-based
retrospective cohort studies, have examined health outcomes
among children born to mothers with silicone breast implants,
and none has found evidence of adverse health outcomes among
the children. Concerns about possible contamination of breast
milk with silicone compounds and of potential adverse health
effects to infants who are breastfed by mothers with silicone
breast implants are not supported by the scientific
literature. In fact, the American Academy of Pediatrics
¹⁰¹ policy statement on the transfer of drugs and
other chemicals into human milk concluded that ``The
Committee on Drugs does not feel that the evidence currently
justifies classifying silicone implants as a contraindication
to breastfeeding.'' Similarly, the Institute of Medicine of
the National Academy of Sciences ² concluded that
``convincing evidence is available that silicon
concentrations in breast milk are the same in mothers with
and without breast implants, and thus there are no data to
support transmission of silicone to infants in breast milk of
mothers with implants.''

RUPTURE INCIDENCE

There has been only one published study to date that
directly examined the true incidence rate of breast implant
rupture by repeated MRI.\21\ In a follow-up to their rupture
prevalence study,¹² in which 271 women study had a
baseline MRI in 1999, a repeat MRI was performed two years
later and a rupture incidence analysis was performed based on
317 implants (in 186 women). The authors found an overall
rupture incidence rate for definite ruptures of 5.3% per
year. The rupture rate increased significantly with implant
age. For ``third generation'' implants (barrier-coated, low
bleed implants available since 1988), the percentage of
implants that remained intact was estimated as 98% at 5 years
and 83%-85% at 10 years.\21\ Only one prospective study to
date has been conducted to address the possible health
implications of ruptured, in situ silicone breast implants.
In this unique study, Holmich et al,\25\ examined the
possible health implications, including changes over time in
MRI findings, serological markers, or self-reported breast
symptoms, of untreated silicone breast implant ruptures.
Sixty-four women with implant rupture diagnosed by MRI were
followed for two years, and a second MRI was performed. A
control group of women with no evidence of rupture on either
MRI was used for comparison. The majority of women had no
visible MRI changes of their ruptured implants. There was no
increase in autoantibody levels, and no increase in reported
breast hardness. Women did report a significant increase in
non-specific breast changes compared with women in the
control group. The authors concluded that, for most women,
rupture is a harmless condition which does not appear to
progress or to produce significant clinical symptoms.

LONG-TERM FOLLOW-UP

Over the past six years, the majority of the epidemiologic
cohort studies were performed in Scandinavia, where unique
nationwide databases and data-linking possibilities exist.
Table 1 presents the average years of follow-up and the
maximum years of follow-up for these cohort studies, by
country:

TABLE 1
------------------------------------------------------------------------
Ave. yrs. of Max. yrs. of
Country follow-up follow-up
------------------------------------------------------------------------
Denmark......................... 9 23
Breiting et al.\24\............. 19 35
Finland......................... 10 30
Sweden.......................... 11 29
------------------------------------------------------------------------

These studies had, on average, a decade of follow-up and
almost three decades of follow-up for the longest term
implant recipients. In the recent Danish study by Breiting et
al.,\24\ the average years of follow-up was 19, with a
maximum of 35 years. Thus, the large body of nationwide
investigations originating in these populations belies the
assertion that there is a dearth of data on long-term effects
of silicone breast implants.

SUICIDE

Four mortality studies have reported elevated risks of
suicide among women with cosmetic breast implants compared
with the general population.^20,29,30,34Recently,
however, the suicide excess has been shown to be related to
pre-implant psychiatric disorders.³⁰

SUMMARY

In summary, after almost a decade of extensive
epidemiologic research, the weight of the epidemiologic
evidence is overwhelmingly reassuring that there are no long-
term adverse effects associated with silicone breast
implants.

REFERENCES

1. International Agency for Research on Cancer. Surgical
implants and other foreign bodies. IARC Monograph on the
Evaluation of Carcinogenic Risks to Humans, Volume 74. Lyon:
IARC Press, 1999.
2. Bondurant S, Ernster V, Herdman R. Safety of Silicone
Breast Implants, Report of the Committee on the Safety of
Silicone Breast Implants (IOM). Washington, D.C.: National
Academy Press, 1999.
3. Independent Review Group, Rogers J, et al. Silicone gel
breast implants: The report

[[Page E593]]

of the Independent Review Group. Cambridge, England: Crown,
1998.
4. Janowsky EC, Kupper LL, Hulka BS. Meta-analyses of the
relation between silicone breast implants and the risk of
connective tissue diseases. N Engl J Med 2000;342:781-790.
5. Tugwell P, Wells G, Peterson J, et al. Do silicone
breast implants cause rheumatologic disorders? A systematic
review for a court-appointed national science panel.
Arthritis Rheum 2001;44:2477-2484.
6. Kjoller K, Friis S, Mellemkjaer L, et al. Connective
tissue disease and other rheumatic conditions following
cosmetic breast implantation in Denmark. Arch Intern Med
2001;161:973-979.
7. Kjoller K, Holmich LR, Fryzek JP, et al. Self-reported
musculoskeletal symptoms among Danish women with cosmetic
breast implants. Ann Plast Surg 2004;52:1-7.
8. Fryzek JP, Signorello LB, Hakelius L, et al. Self-
reported symptoms among women after cosmetic breast implant
and breast reduction surgery. Plast Reconstr Surg
2001;107:206-213.
9. Winther JF, Friis S, Baach FW, et al. Neurological
disease among women with silicone breast implants in Denmark.
Acta Neural Scand 2001;103:93-96.
10. Signorello LB, Fryzek JP, Blot WJ, et al. Offspring
health risk after cosmetic breast implantation in Sweden. Ann
Plast Surg 2001;46:279-286.
11. Jensen B, Kjoller K, McLaughlin JK, et al. Muscular
rheumatism following breast surgery in Denmark. Clin Exp
Rheum 2001;19:229.
12. Holmich L, Kjoller K, Vejborg I, et al. Prevalence of
silicone breast implant rupture among Danish women. Plast
Reconst Surg 2001;108:848-858.
13. Kjoller K, Holmich LR, Jacobsen PH, et al. Capsular
contracture after cosmetic breast implant surgery in Denmark.
Ann Plast Surg 2001;47:359-366.
14. Jensen B, Bliddal H, Kjoller K, et al. Rheumatic
manifestations in Danish women with silicone breast implants.
Clin Rheumatol 2001;20:345-352.
15. Kjoller K, Friis S, Signorello LB, et al. Health
outcomes in offspring of Danish mothers with cosmetic breast
implants. Ann Plast Surg 2002;48:238-245.
16. Jensen B, Wittrup IH, Friis S, et al. Self-reported
symptoms among Danish women following cosmetic breast implant
surgery. Clin Rheum 2002;21:35-42.
17. Pukkala E, Boice JD Jr, Hovi S-L, et al. Incidence of
breast and other cancers among Finnish women with cosmetic
breast implants, 1970-1999. J Long Term Eff Med Implants
2002;12:271-279.
18. Holmich LR, Kjoller K, Fryzek JP, et al. Self-reported
diseases and symptoms by rupture status among unselected
Danish women with cosmetic silicone breast implants. Plast
Reconstr Surg 2003;111:723-732.
19. Holmich LR, Mellemkjaer L, Gunnarsdottir KA, et al.
Stage of breast cancer at diagnosis among women with cosmetic
breast implants. Br J Cancer 2003;88:832-838.
20. Pukkala E, Kulmala I, Hove S-L, et al. Causes of death
among Finnish women with cosmetic breast implants, 1971-2001.
Ann Plast Surg 2003;51:339-342.
21. Holmich LR, Friis S, Fryzek JP, et al. Incidence of
silicon breast implant rupture. Arch Surg 2003;138:801-806.
22. Jensen B, Wiik A, Wittrup IH, et al. Silicate
antibodies in Danish women with silicone breast implants.
Rheumatology (Oxford) 2003;42:1032-1035.
23. Mellemkjaer L, Kjoller K, Friis S, et al. Cancer
occurrence after cosmetic breast implantation in Denmark. Int
J Cancer 2000;88:301-306.
24. Brelting VB, Holmich LR, Brandt B, et al. Long-term
health status of Danish women with silicone breast implants.
Plast Reconstr Surg 2004;114:271-276.
25. Holmich LR, Vejborn IM, Conrad C, et al. Untreated
silicone breast implant rupture. Plast Reconstr Surg
2004;114:204-214.
26. Jensen B, Wittrup IH, Wiik A, et al. Antipolymer
antibodies in Danish women with silicone breast implants. J
Long Term Eff Med Implants 2004;14:73-80.
27. Jensen B, Wittrup IH, Wiik A., et al. Antipolymer
antibodies in Danish women with fibromyalgla. Clin Exp
Rheumatol 2004;22:227-229.
28. Nyren O, McLaughlin JK, Yin L, et al. Breast Implants
and risk of neurologic disease: a population-based cohort
study in Sweden. Neurol 1998;50:956-961.
29. Koot VCM, Peeters PHM, Granath F, et al. Total and
cause specific mortality among Swedish women with cosmetic
breast implants: prospective study Br Med J 2003;326: 527-
528.
30. Jacobsen PH, Holmich LR, McLaughlin JK, et al.
Mortality and suicide among Danish women with cosmetic breast
implants. Arch Intern Med 2004;164:2450-2455.
31. Mellemkjaer L, Kjoller K, Friis S, et al. Cancer
occurrence after cosmetic breast implantation in Denmark. Int
J Cancer 2000;88:301-306.
32. Brinton LA, Lubin JH, Burich MC, et al. Breast cancer
following augmentation mammoplasty. Cancer Causes Control
2000;11; 819-827.
33. Brinton LA, Lubin JH, Burich MC, et al. Cancer risk at
sites other than the breast following augmentation
mammoplasty. Ann Epidemiol 2001;11:248-256.
34. Brinton LA, Lubin JH, Burich MC, et al. Mortality among
augmentation mammoplasty patients. Epidemiol 2001;12:321-326.
35. Brown SL, Pennello G, Berg WA, et al. Silicone gel
breast implant rupture, extracapsular silicone, and health
status in a population of women. J Rheumatol 2001;28:996-
1003.
36. Englert H, Joyner E, McGill N, et al. Women's health
after plastic surgery. Int Med J 2001;31:77-89.
37. Brinton LA, Buckley LM, Dvorkina O, et al. Risk of
connective tissue disorders among breast implant recipients.
Am J Epidemliol 2004;160:619-627.
38. Kulmala I, McLaughlin JK, Pakkanen M, et al. Local
complications after cosmetic breast implant surgery in
Finland. Ann Plast Surg 2004;53:413-419.
39. Burns CJ, Laing TJ, Gillespie BW, et al. The
epidemiology of scleroderma among women: Assessment of risk
from exposure to silicone and silica. J Rheumatol
1996;23:1904-1911.
40. Dugowson CE, Daling J, Koepsell TD, et al. Silicone
breast implants and risk for rheumatoid arthritis. 56th
Annual Meeting. American College Rheumatology. Arthr Rheum
1992;35:Suppl: S66.
41. Englert H, Morris D, March L. Scleroderma and silicone
gel breast prostheses--the Sydney study revisited. Aust. N.
Z. J. Med. 1996;26:349-355.
42. Goldman JA, Greenblatt J, Joines R, et al. Breast
implants, rheumatoid arthritis, and connective tissue
diseases in clinical practice. J. Clin. Epidemiol.
1995;48:571-582.
43. Hochberg MC, Perlmutter DL; Medsger TA, et al. Lack of
an association between augmentation mammoplasty and systemic
sclerosis (scleroderma). Arthr. Rheum. 1996;7:1125-1131.
44. Lai S, Goldman JA. Child AH, et al. Fibromyalgia,
hypermobility, and breast implants. J. Rheumatol.
2000;27:2237-2241.
45. Laing TJ, Gillepsie BW, Lacey JV, et al. The
association between silicone exposure and undifferentiated
connective tissue disease among women in Michigan and Ohio.
Arthr. Rheum. 1996;39:S150.
46. Laing TJ, Schottenfeld D, Lacey JV Jr., et al.
Potential risk factors for undifferentiated connective tissue
disease among women: implanted medical devices. Am. J.
Epidemiol. 2001;154:610-617.
47. Strom BL, Reidenberg MM, Freundlich B, et al. Breast
silicone implants and risk of systemic lupus erythematosus.
J. Clin. Epidemiol. 1994;47:1211-1214.
48. Williams HJ, Weismann MH, Berry CC. Breast implants in
patients with differentiated and undifferentiated connective
tissue disease. Arthr. Rheum. 1997;40:437-440.
49. Wolfe F, Anderson J. Silicone filled breast implants
and the risk of fibromyalgia and rheumatoid arthritis. J.
Rheumatol. 1999;26:2025-2028.
50. Edworthy SM, Martin L, Barr SG, et al. A clinical study
of the relationship between silicone breast implants and
connective tissue disease. J. Rheumatol. 1998;25:254-260.
51. Friis S, Mellemkjaer L, McLaughlin JK, et al.
Connective tissue disease and other rheumatic conditions
following breast implants in Denmark. Ann. Plast. Surg.
1997;39:1-8.
52. Gabriel SE, O'Fallon WM, Kurland LT. et al. Risk of
connective-tissue diseases and other disorders after breast
implantation. N. Engl. J. Med. 1994,330:1697-1702.
53. Giltay EJ, Bernelot Moens HJ, Riley AH, et al. Silicone
breast prostheses and rheumatic symptoms: A retrospective
follow up study. Ann. Rheum. Dis. 1994;53:194-196.
54. Hennekens CH, Lee I, Cook NR, et al. Self-reported
breast implants and connective tissue diseases in female
health professionals. A retrospective cohort study. JAMA
1996;275:616-621.
55. Nyren 0, Josefsson S, McLaughlin JK, et al. Risk of
connective tissue disease and related disorders among women
with breast implants: A nation-wide retrospective cohort
study in Sweden. Br. Med. J. 1998;316:417-422.
56. Park AJ, Black RJ, Sarhadi NS, et al. Silicone gel-
filled breast implants and connective tissue diseases. Plast.
Reconstr. Surg. 1998;101:261-268.
57. Sanchez-Guerrero J, Colditz GA, Karlson EW, et al.
Silicone breast implants and the risk of connective-tissue
diseases and symptoms. N. Engl. J. Med. 1995;332:1666-1670.
58. Schusterman MA, Kroll SS, Reece GP, et al. Incidence of
autoimmune disease in patients after breast reconstruction
with silicone gel implants versus autogenous tissue: A
preliminary report. Ann. Plast. Surg. 1993;31:1-6.
59. Wells KE, Cruse CW, Baker JL Jr, et al. The health
status of women following cosmetic surgery. Plast. Reconstr
Surg. 1994;93:907-912.
60. Blackburn WD, Everson MP. Silicone-associated rheumatic
disease: An unsupported myth. Plast. Reconstr. Surg.
1997;99:1362-1367.
61. Hochberg MC, Perlmutter DL. The association of
augmentation mammoplasty with connective tissue disease,
including systemic sclerosis (scleroderma): A meta-analysis.
Curr. Top. Microbiol. Immunol. 1996;210:411-417.
62. Lamm SH. Silicone breast implants, breast cancer and
specific connective tissue diseases: A systematic review of
the data in the epidemiological literature. Int. J. Toxicol.
1998;17:497-527.
63. Lewin SL, Miller TA. A review of epidemiologic studies
analyzing the relationship between breast implants and
connective tissue diseases. Plast. Reconstr. Surg.
1997;100:1309-1313.
64. Silverman BG, Brown SL, Bright RA, et al. Reported
complications of silicone gel breast implants: An
epidemiologic review. Ann. Intern. Med. 1996;124:744-756.

[[Page E594]]

65. Wong O. A critical assessment of the relationship
between silicone breast implants and connective tissue
diseases. Reg Toxicol. Pharmacol. 1996;23:74-85.
66. Lipworth L, Tarone RE, McLaughlin JK. Silicone breast
implants and connective tissue disease: an updated review of
the epidemiologic evidence. Ann. Plast. Surg. 2004;52:598-
601.
67. Wolfe F. ``Silicone related symptoms'' are common in
patients with fibromyalgia: no evidence for a new disease. J.
Rheumatol. 1992;26:1172-1175.
68. Lipworth L, Tarone RE, McLaughlin JK. Breast implants
and fibromyalgia: a review of the epidemiologic evidence.
Ann. Plast. Surg. 2004;54:284-287.
69. Bowlin SJ. Correspondence: silicone gel breast
implants. J Rheumatol 2001;28:2760-2761.
70. Bowlin SJ. Correspondence: silicone gel breast
implants. J Rheumatol 2002;29:2468-2469.
71. Wolfe F, Ross K, Anderson J, et al. The prevalence and
characteristics of fibromyalgia in the general population.
Arth Rheum 1995;38:19-28.
72. Cardiel MH, Rojas-Serrano J. Community based study to
estimate prevalence, burden of illness and help seeking
behavior in rheumatic diseases in Mexico City. A COPCORD
study. Clin Exp Rheumatol. 2002;20:617-624.
73. Lundberg G, Gerdle B. Tender point scores and their
relations to signs of mobility, symptoms, and disability in
female home care personnel and the prevalence of fibromyalgia
syndrome. J Rheumatol. 2002;29:603-613.
74. White KP, Speechley M, Harth M, et al. The London
Fibromyalgia Epidemiology Study: The prevalence of
fibromyalgia syndrome in London, Ontario. J Rheumatol
1999;26:1570-1576.
75. Makela M. Hellovaara M. Prevalence of primary
fibromyalgia in the Finnish population. BMJ 1991;303:216-219.
76. Lawrence RC, Helmick CG, Arnett FC, et al. Estimates of
the prevalence of arthritis and selected musculoskeletal
disorders in the United States. Arthritis Rheum 1998;41:778-
799.
77. Brinton LA, Malone KE, Coates RJ, et al. Breast
enlargement and reduction: results from a breast cancer case-
control study. Plast Reconstr Surg 1996;97:269-275.
78. Bryant H. Brasher P. Breast implants and breast
cancer--reanalysis of a linkage study. N Engl J Med
1995;332:1535-1539.
79. Deapen DM, Bernstein L, Brody GS. Are breast implants
anticarcinogenic? A 14-year follow-up of the Los Angeles
study. Plast Reconstr Surg 1997;99:1346-1353.
80. Kern KA, Flannery JT, Kuehn PG. Carcinogenic potential
of silicone breast implants: a Connecticut statewide study.
Plast Reconstr Surg 1997;100:737-747.
81. Malone KE, Stanford JL, Daling JR, et al. Implants and
breast cancer. Lancet 1992;339:1365.
82. Park AJ, Chetty U, Watson ACH. Silicone breast implants
and breast cancer. Breast 1998;7:22-26.
83. McLaughlin JK, Nyren O, Blot WJ, et al. Cancer risk
among women with cosmetic breast implants: a population-based
cohort study in Sweden. JNCI 1998;90:156-158.
84. European Committee on Quality Assurance and Medical
Devices in Plastic Surgery. Consensus declaration on breast
implants, June 23, 2000. Israel, European Committee on
Quality Assurance (EQUAM). 4th Consensus Declaration.
85. National Institutes of Health. Breast implants: status
of research at the National Institutes of Health. 7/16/2003.
Available online at: http://www4.od.nih.gov/orwh/
implants.pdf. Accessed December 31, 2004.
86. McLaughlin JK, Lipworth L. Brain cancer and cosmetic
breast implants: A review of the epidemiologic evidence. Ann
Plast Surg 2004;52:115-117.
87. Fajardo LL, Harvey JA, McAleese KA, et al. Breast
cancer diagnosis in women with subglandular silicone gel-
filled augmentation implants. Radiology 1995;194:859-862.
88. Silverstein MJ, Handel N, Gamagami P, et al. Breast
cancer diagnosis and prognosis in women following
augmentation with silicone gel-filled prostheses. Eur. J.
Cancer 1992;28:635-640.
89. Hoshaw SJ, Klein PJ, Clark BD, et al. Breast implants
and cancer: causation, delayed detection, and survival. Plast
Reconst Surg 2001;107:1393-1408.
90. Joseph E, Wells KE, Anastasi GW, et al. Survival from
breast carcinoma after augmentation mammoplasty. In:
Proceedings of the 67th Annual Scientific Meeting of the
American Society of Plastic and Reconstructive Surgeons, the
Plastic Surgery Educational Foundation, and the American
Society of Maxillofacial Surgeons, Boston, MA, October 3-7,
1998.
91. Birdsell DC, Jenkins H, Berkel H. Breast cancer
diagnosis and survival in women with and without breast
implants. Plast. Reconstr. Surg. 1993;92:795-800.
92. Cahan AC, Ashikari R, Pressman P, et al. Breast cancer
after breast augmentation with silicone implants. Ann Surg
Oncol 1995;2:121-125.
93. Clark CP, Peters GN, O'Brien KM. Cancer in the
augmented breast. Cancer 1993;72:2170-2174.
94. Deapen D, Hamilton A, Bernstein L, et al. Breast cancer
stage at diagnosis and survival among patients with prior
breast implants. Plast. Reconstr. Surg. 2000;105:535-540.
95. Jakubietz MG, Janis JE, Jakubietz RG, et al. Breast
augmentation: cancer concerns and mammography--a literature
review. Plast Reconstr Surg 2004;113:117e-122e.
96. Miglioretti DL, Rutter CM, Geller BM, et al. Effect of
breast augmentation on the accuracy of mammography and cancer
characteristics. JAMA 2004;291:442-450.
97. Jakub JW, Ebert MD, Cantor A. et al. Breast cancer in
patients with prior augmentation: presentation, stage, and
lymphatic mapping. Plast Reconstr Surg 2004;114:1737-1742.
98. Le GM, O'Malley CD, Glaser SL, et al. Breast implants
following mastectomy in women with early stage breast cancer:
prevalence and impact on survival. Breast Cancer Res
2005;7:R184-R193.
99. Winther JF, Bach FW, Friis S, et al. Neurologic disease
among women with breast implants. Neurol 1998;50:951-955.
100. Kjoller K, McLaughlin J.K, Friis S, et al. Health
outcomes in offspring of mothers with breast implants.
Pediatrics 1998;102:1112-1115.
101. American Academy of Pediatrics. The transfer of drugs
and other chemicals into human milk. Pediatrics 2001;108:776-
789.