Anne Kasper, PhD, Finding My Way, October 14, 2003

My name is Dr. Anne Kasper and I am a partner in Finding My Way, a support service for breast cancer patients in Bethesda, Maryland. I am also the senior editor and author of the book Breast Cancer: Society Shapes an Epidemic.

Breast cancer patients have more choices than ever before. While it’s important to have choices, when a woman is diagnosed with breast cancer, the choices can be difficult to make.

• Three out of four women newly diagnosed with breast cancer can choose to have a lumpectomy with radiation instead of mastectomy.

• If a woman needs or wants a mastectomy, she can choose saline breast implants, silicone gel implants, or autologous tissue transfer procedures.

How important is it that silicone gel breast implants be widely available to cancer patients? Under the current restrictions, the vast majority of women who want silicone gel implants for reconstruction are able to get them.

But, breast cancer patients tend to be cautious. They want to live long lives. However, they also are concerned about cosmesis and how they will look after cancer treatment. Many will choose lumpectomy, which allows them to keep their breasts, preserving their appearance and the sensory feelings of the breasts. Women tell us that they only want silicone gel implants if they can be assured that they are safe. Women are often encouraged to choose implants and a rosy picture is painted about the benefits of implant reconstruction. However, in our practice women are often disappointed to have reconstructed breasts that have none of the sensory, sexual, and maternal capacities of a normal breasts and that often have complications.

Many reconstruction patients who choose silicone gel implants are happy with their implants at first. Unfortunately, many women experience the kinds of complications that Inamed found, such as:

46% will need additional surgery within 2 or 3 years
25% will have their implants removed within 2 or 3 years
6% will have a ruptured implant
6% will have moderate to severe breast pain
6% will suffer from necrosis, a complication in which their skin or breast tissue dies and the wound takes a long time to heal

In the Inamed core study of breast cancer patients, only 6% of the implants broke during the first 2 or 3 years, but over time we know that percentage increases. This is much more serious than when a saline implant breaks. When silicone gel implants break, the silicone can leak into the lungs, lymph nodes, and other organs. To determine the safety of silicone gel implants, Inamed should have studied the health of women whose implants broke — especially since cancer patients have compromised immune systems. Unfortunately, they did not.

Another shortcoming of the Inamed research is that it included only 6 African American breast cancer patients in the core study and only 5 Asian American women. Obviously, this is not appropriate data on which the FDA could make a safety decision for all American women. Both groups have approximately the same rates of cancer as white women, and African American women are especially susceptible to autoimmune disease. These women must be studied to determine if implants are safe for them.

The bottom line, though, is that the complication rates for breast cancer patients are very high in just the first two or three years. What will these women’s lives be like in the next 5 or 10 or even 20 years? Most breast cancer patients are living long lives. Many choose mastectomy as a way to “get it over with” and “put cancer behind them.” With re-operation rates of 46% in the first two or three years, and higher rupture rates in the years to come, many women will not consider implants a satisfactory and safe choice at all.

It is unusual to ask for more than 2 years of safety data for a new product, but silicone gel breast implants are not new. Inamed is asking for approval for an implant that has not changed much if at all in more than a dozen years. If FDA had strictly enforced their restrictions on breast implants, which were established in 1992, we would have 10-year data by now, instead of 2-3 years.

If the FDA approves silicone gel implants based on the data provided, it sends the message that they are not as concerned as women have a right to expect about the health and safety of breast cancer patients, and especially women of color.

If the FDA allows silicone gel implants to remain on the market, but only as part of clinical trials, and this time requires a third party to monitor the studies, then perhaps breast cancer patients will finally get the information they need to make a meaningful choice.

Claudia Miller, MD, University of Texas Health Science Center, April 2005.

My name is Dr. Claudia Miller. I have no financial interests in this hearing, and I’m here at my own expense. I’m a professor at University of Texas Health Science Center in San Antonio. I’m an allergist/immunologist. And my research is focused on people who report chronic disabling symptoms following some environmental exposure, the symptoms you have heard about today.

I have served as a consultant to the Department of Veterans Affairs on Gulf War veterans, the EPA on sick buildings, the National Institute of Dental and Craniofacial Research on temporomandibular joint implants, where, by the way, you see similar kinds of complaints.

What unites ill Gulf War veterans, sick building occupants, and patient with implants who are having problems is the fact that following a well-defined exposure event, a subset, not every one, a subset of them, go on to lose their prior natural tolerance for a wide variety of substances that are structurally unrelated.

Thereafter, common foods, medications, alcoholic beverages, caffeine, chemical inhalants, like diesel exhaust, and fragrances you have heard about today, exposures that never bothered people before suddenly trigger symptoms in them. And these can be disabling.

This two-step disease process — and has come to be known as toxicant-induced loss of tolerance, or TILT. It does not appear to matter whether the exposure that initiated this, which is at the bottom of the right-hand slide, was endogenous or exogenous. The body’s response is remarkably similar.

We have reported on 87 individuals with surgical implants, three-quarters of them with breast implants. Sixty-nine percent reported rupture. Seventy-eight percent had one or more implants removed. Of those who had undergone explanation, less than ten percent reported their health status as greatly improved.

Using a validated questionnaire, we found that the symptom severity scores of implant recipients rivaled those of the environmental exposed groups we were studying. And there were four of those.

Compared to controls, implant recipients reported much more severe adverse responses to everyday chemical exposures as well as having problems with various foods, medications, alcoholic beverages, and caffeine.

Toxicant-induced loss of tolerance is a new paradigm for environmentally induced disease that differs from classical toxicity and allergy.

Affected individuals may be completely unaware of the intolerances resulting from this because of a phenomenon we call masking. If a person is reacting to many different things and having symptoms as a result of those, then the symptoms may overlap in time. And, consequently, they feel sick all of the time, often reporting chronic fatigue or flu-like illness that won’t go away.

Recent Canadian studies show that genetic polymorphisms may determine who is more vulnerable to developing this illness. And in September I will be chairing a meeting on the toxicant-induced loss of tolerance sponsored by two NIH institutes where we’ll be discussing various aspects, clinical models, animal models, and so on, in order to understand this problem better in providing you with a questionnaire that I showed a moment ago to help physicians and researchers better understand this problem.

And I will be happy to provide you with any references. Thank you.

Cynthia Pearson, Executive Director National Women’s Health Network, July 9, 2002

My name is Cynthia Pearson and I am Executive Director of the National Women ‘s Health Network, a nonprofit, nonpartisan organization that has been dedicated to improving women’s health for more than 25 years.

The Network has been examining the safety of breast implants for more than a dozen years, and our primary concern has been the lack of safety information. When we first became involved in this issue, there were no studies of women in the published research literature, and although almost a million women had breast implants, no breast implant had ever been approved by the FDA. Today, there are quite a few published studies of the safety of breast implants, and saline implants made by two manufacturers are approved by the FDA. Nevertheless, the Network remains very concerned because there have been more than 150,000 adverse reaction reports to the FDA for women with breast implants, and there are still no long-term safety studies.

This meeting provides the first opportunity to re-visit the FDA’s approval of saline breast implants since they were approved in 2000. The manufacturers’ studies were strongly criticized by the FDA’s Advisory Committee two years ago because of the poor quality of their research. One might expect that the manufacturers would have been grateful that their implants were approved despite the high complication rates and poor quality of the data, and would have therefore made sure that their 5-year studies were better designed and analyzed. Instead, the new studies have many of the same flaws as the previous studies, and the response rate is even worse than it was at the PMA meeting in 2000.

I will not go into details about the statistics, because that does not seem necessary. Anyone who knows anything about research, and even many who know nothing about research, know that you can’t lose 95% of your sample and still have a meaningful study. When Mentor Corp analyzed their five-year follow-up data on only 60 of the more than 1200 women who were enrolled in their augmentation study, they did a disservice to the more than 400,000 women who underwent augmentation surgery since saline implants were approved in 2000, to you as FDA Advisory Committee members, and to the FDA. There is no excuse for that kind of shoddy research — in fact, it does not deserve to be called research. It is meaningless data. The fact that Mentor improved their follow-up to 24 percent at the six-year mark shows how little attention went into their 5-year study, but even a 24 percent response rate is much too low to be meaningful.

A response rate under 50 percent raises more questions than it can answer: are the other women dead or alive? Are they healthy and happy or sick and seeking medical care elsewhere? We don’t know the answers to those questions, so the data can’t really tell us about the safety of implants.

The McGhan data are little better. Like the Mentor study, they manipulate the data to make it seem that saline implants are safer than they really are. Both Mentor and McGhan made note of the women who had both their implants removed, but they are not included in the complication rate data. Instead, they are apparently excluded from the study as if they never existed — or worse, as if they were satisfied with their implants or had the same complication rate as everyone else. Even with this highly inappropriate data manipulation, approximately one out of every three McGhan augmentation patients is described as undergoing 463 additional surgical procedures — an average of more than two additional surgeries per patient

Consumers deserve an FDA that keeps unsafe or ineffective medical devices off the market. They also deserve accurate information about the long-term safety of medical implants that are intended for long-term use. In the case of breast implants, the manufacturers have failed to conduct meaningful long-term safety studies and as a result consumers are continuing to buy implants that are FDA-approved but are not necessarily safe. All we do know is breast implants have an extremely high complication rate — higher than any medical product I can think of, with the exception of a small number of life-saving products used by patients who have no other choices. Even the misrepresentation of data does not hide that fact.

On behalf of the National Women’s Health Network, I strongly urge this Advisory Committee to speak on behalf of the millions of consumers who are not able to come to this meeting, but who look to the FDA to protect them from harmful products. If this Advisory Committee does not vehemently criticize these studies, and the manufacturers’ misrepresentation of their own research, and urge the FDA to take a stronger watchdog role, breast implants will never be improved, and accurate and informative research will probably never be conducted.

Third, the cost of reoperations and local complications associated with breast implants can be significant for both the patient and society. Many health plans do not cover the medical costs associated with cosmetic breast implant complications — forcing many patients to cover these costs out-of-pocket. For example, Aetna — one of the nation’s largest health insurers — does not cover the cost of removing ruptured saline implants in patients who have previously undergone cosmetic breast augmentation. It should be noted that in 2001, more than 62,000 breast implant removal procedures were performed in the U.S.

This statement was read by Tonia Bair, because Ms. Pearson was unable to attend the meeting.

Audrey Sheppard, April 2005

I have no financial conflicts.

For four years, 1996 through ’99, I directed the FDA Office of Women’s Health. As a result of my professional involvement with silicone breast implants, I regard sharing my perspective an ongoing responsibility. I hold the agency and you in high regard and am optimistic about your making scientifically sound judgments.

My role at OWH, nearly a decade ago, requested by and partnering with the Center for Device Leaders, was to champion and obtain full funding to conduct what became the critically important FDA rupture study. Its findings have resulted in a better understanding of the frequency of these devices rupturing over time.

You will be briefed — and there has been reference to it already — on the results. Suffice it to say that over time more than 65 percent of women in the study were found to have at least one ruptured implant and over 21 percent had silicone gel outside the capsule in one or both breasts. The latter finding is particularly concerning since the effect of silicone on the tissues and in development or progression of disease remains unknown.

After leaving the agency five years ago, I have advised and assisted women’s health and other women’s nonprofits and projects and from this vantage point will share three requests. One, follow the science.

Even the company’s data, which you know will put on the best face, will not dispute a significant rupture rate nor other consequences of having these devices for years. These are not lifetime devices and, as such, without regular and too frequent resurgeries are not safe and effective, as intended.

Two, pay close attention to FDA’s own documents and data. A number of documents on the CDRH Web site, including — and I have the names, but you can find them. These themselves are damning information that is based on scientific research, decades of experience, tens of thousands of adverse event reports. And it also includes disconcerting photographs.

Please don’t discount this body of material with the argument that the devices are much improved today. Make certain there is data to prove it.

And, number three, please believe your own eyes and ears when you see the dozens of sincere women whose health has been compromised standing before you. Of course, you will also hear from those who are highly satisfied. Their experience does not provide reason enough to open implants to wide use for augmentation, even by teenage girls.

To summarize, the health and well-being of some of America’s women and girls will be affected, even if they won’t know it for years to come, by your decisions.

Judy Norsigian, Our Bodies Ourselves, April 2005

I am Judy Norsigian. I am the Executive Director of Our Bodies, Ourselves, also known as the Boston Women’s Health Book Collective, a nonprofit public interest, women’s health, education, and advocacy organization. For 35 years, we have advocated for women’s health from an evidence-based and consumer perspective, most notably through our major publication, Our Bodies, Ourselves. We have no financial ties to either of the manufacturers or their competitors.

Our organization’s interest in breast implants goes back to the mid 1980s, when the late Esther Rome, my coworker, began to work with hundreds of women, both locally and nationally, who believed that breast implants caused some serious problems. Many of these women were initially happy with their implants but later developed debilitating conditions after five or ten years or more. Even today, many women continue to have problems with more recent models. And we still do not have adequate data that would allow women to make informed choices about using these devices.

As we and others have said before, we do want choices, but we want safe choices. Since the October 2003 panel that addressed the safety of silicone gel implants, studies in mammography and platinum suggest new challenges for women with silicone gel implants.

A study published in the January 2004 JAMA issue found that breast implants interfere with mammography, missing 55 percent of breast cancers in women with breast implants, compared to 33 percent in women without implants. This fact alone provides a compelling reason for the FDA to weigh carefully the risk-benefit issues regarding these products.

Silicone breast implants have also been found to contain platinum. A study published in the July 2004 issue of Analytical and Bioanalytical Chemistry found very high levels of platinum in silicone gel as well as the encasing materials, implant elastomer, double lumen, and foam, materials that are in direct contact with the chest wall of patients.

Much media coverage has suggested that there are many studies showing that breast implants are safe, but the largest, best designed studies do show increased risks. Even the Breiting, et al., study of Danish women noted substantial problems that call for further research. When read carefully, this study is anything but a stamp of approval for silicone breast implants.

Scientists at the FDA and NIH are among those who have called for more research to answer many of the key questions that have been raised repeatedly at FDA hearings. You should be joining them.

All assertions to the contrary, we simply do not have adequate data on such conditions as fibromyalgia. Our recent experiences with premature drug and device approval underscore how critical it is to take a cautious approach.

Although saline implants are less ideal for many women, they do provide a reasonable alternative while we await the findings of further research. And such research must include women with implants for a minimum of ten years, not an average of ten years.

Women’s health and lives depend upon a careful assessment of these devices. We urge the panel to require adequate safety data to be collected before any decision to approve their use, especially in light of industry’s current marketing strategy of targeting younger women, whose long-term health status may depend upon your recommendation.

Thank you very much.

Marcy L. Gross, State of Maryland’s Women’s Health Promotion Council, October 14, 2003

General and Plastic Surgery Devices Panel Center for Devices and Radiological Health Food and Drug Administration, DHHS

Good morning.

I am Marcy Gross, a health policy consultant and member of the State of Maryland’s Women’s Health Promotion Council.

I retired last November after 25 plus years at HHS, most recently in the position of Senior Advisor for Women’s Health at the Agency for Healthcare Research and Quality (AHRQ). During part of my tenure at HHS, I also participated in the former Secretary’s ad hoc Working Group on Silicone Breast Implants.

I give you this brief resume to establish my familiarity with the issues you have under consideration today, but am here speaking entirely as a private citizen, and base my remarks on my own personal views and on information available to the general public.

One legacy of my 6 year tenure at AHRQ is a good appreciation of the need for women and policy makers to have a strong evidence base for making decisions on health care issues. My concern today is that an adequate evidence base for the premarket approval of silicone gel-filled breast prostheses does not exist, and that the short-term assurances drawn from the applicant’s study will override acknowledgment of the troubling gaps in research on long-term risks.

I can see from the information posted on the panel’s web site for the hearing that FDA’s background work has been exhaustive, encompassing extensive literature and statistical reviews, assessment of the toxicology and chemical testing, and extensive consideration of clinical data. All this data and more will come to you again over the next two days.

But, the basic facts are simple, and have not varied in the 12 plus years since silicone implants were pulled from the market:

1. The studies available on the health aspects of silicone gel implants are short-term analyses, often involving mere handfuls of mice studied over the course of a few weeks in the case of toxicology and chemical testing; and, in the case of Inamed’s Core Study, involving patients studied over a two-three year period.

2. Yet, even these short term assessments indicate that the rate of ruptures and other complications which lead to re-operations remains high, unacceptably high in my view: 20 percent plus for patients using implants to augment their figure, and 45 percent plus for reconstruction patients.

Thanks to our longer life span, breast implants will stay in a woman’s body for the rest of her life, which can be 50 years or more, or so many women are told. Even when it is acknowledged that they will have to be replaced, women are given a time line of 10 to 20 years. Thus, a two-three year study simply doesn’t offer the kind of assurance of safety needed to understand the health implications of accepting an implant. It is a set-up for future medical problems for the women who have this type of device implanted, especially when retrospective studies show that by 10 years, most women with silicone gel implants will experience at least one broken implant. At least these women know they have a problem and seek further surgery: Silent ruptures are also a documented and recurring problem.

Sometime in the next few days, I feel certain that you will hear someone say that none of the several important studies of possible health risks of implants has shown that they cause a health problem. You may even hear it said that, well, we use silicone in many other implanted devices such as heart valves, knee joints, etc, so why should silicone from breast implants be different?

My response is that having bubbles or globules of migrating gel floating through a human body, into and around organs, is, on its face, a health risk. As for the silicone in other implanted devices: one doesn’t expect bits of a heart valve to break off and migrate to a patient’s brain, liver, or other organs. Further, patients who get knee or hip joint replacements are routinely warned that a small number of patients will have an immune system reaction to silicone fragments shed by newly implanted joints.

There is no health imperative behind the push to reintroduce silicone breast implants. On the contrary, they are used in an elective, cosmetic procedure that often causes serious health complications associated with ruptures and the surgery itself. Although there are other options available to breast cancer patients that carry fewer risks, for some, access to silicone gel implants is felt as important to their recovery. We know that this will make them more vulnerable to future illness and complications and will obscure future cancer screening procedures. But, again, we lack the kind of long-term studies that would allow their choice to be fully informed.

This FDA panel will be making a decision that affects the lives and pocketbooks of women involved quite substantially. There are substantial, emotional issues involved in the decision and results. Implants are also an expensive procedure, especially when the cost of care for complications, re-operations, infections and other medical side affects are added in. Some 225,000 to 250,000 new procedures were done last year. If costs of surgery are estimated as $5,000 each, the total cost approximates $1.2 billion dollars. While much of this is paid for by the patient, the cost for reconstructive procedures after cancer surgery is most often covered by insurance, as are some of the costs for any follow-up treatments needed.

What is the policy recommendation here? FDA found the middle ground 12 years ago. And while I would still prefer not to see the 4-fold increase in implants that has since occurred, at least the current policy sends a strong cautionary signal to women with choices. That should not change until we are more confident that these implants are safe for long-term use. That will take more time and more research, the kind of research that should have been initiated 10 years ago.

I thank you for your time and attention this morning. I see that your agenda runs well into the evening, and I wish you luck–and stamina.

Marcy Lynn Gross passed away unexpectedly on June 19, 2005. Marcy was an important national advocate for women’s health, and formerly a senior adviser with the U.S. Department of Health and Human Services. She worked closely with the National Research Center for Women & Families to prevent medically-unnecessary mastectomies. The Center is naming an internship in her honor. For more information about Marcy’s national contributions to women’s health, click here.