Newsletter #80–Feb./Mar. 2004

Breast Implant Safety—Will We Ever Know?

by Jane Sprague Zones

We will probably never have a definitive answer to the question of silicone gel-filled breast implant safety. At the FDA hearings in October, advocates for breast implant availability cited an extensive review of the research published by the Institute of Medicine (IOM) to argue for the devices’ safety.1 While the IOM, which serves as a health advisor to the nation, did an admirable job of compiling the accumulated evidence regarding the effects of the silicone breast implants (SBIs), they appear to have accepted the studies at face value. For example, the IOM did not examine the potential impact of conflict of interest in breast implant research.

Much of the research on implants is sponsored and carried out by those with a vested interest in the outcomes. There is a large and expanding literature that shows industry-sponsored studies have a significantly higher likelihood than independent studies of producing outcomes that favor the product or procedure being examined.2

To take a single instance, one of the strongest studies of SBIs reveals considerable conflict of interest. The article, authored by Sánchez-Guerrero3 and colleagues and published in the New England Journal of Medicine in 1995, finds no association between SBIs and connective tissue disease. Disclaimers on the first page of the article indicate that authors Sánchez-Guerrero and Karlson received money from Dow Corning through a grant to Brigham and Women’s Hospital. In addition, Dr. Matthew Liang, the rheumatologist to whom reprint requests are to be addressed, received payments from four legal firms representing Dow Corning or McGhan (a major implant manufacturer, now Inamed) in 1993 and 1994.

A December 21, 1994, Associated Press wire story stated that Dr. Peter H. Schur, one of two main researchers on the study and a professor of rheumatology at Harvard Medical School, earned approximately $30,000 in 1994 working about 100 hours as a consultant to lawyers representing implant manufacturers. He and Dr. Liang were reported to have resigned as principal rheumatologists on the Women’s Health Cohort Study because of “the appearance of a conflict of interest.” Furthermore, at the time of this study, Dr. Schur was the editor of Arthritis and Rheumatism, the official journal of the American College of Rheumatology. Submitting authors had complained because Schur had rejected two articles showing evidence of silicone-related disease that were later published in other journals. A paper which Schur and three colleagues wrote concluding “little or no association” between implants and disease was published in Arthritis and Rheumatism in February 1994. The lead article in that same issue was written by three medical officials from Dow Corning.

The International Committee of Journal Editors’ ethical rules, adopted in January 1993, regard consulting and expert testimony among “the most important conflicts of interest” regardless of whether authors’ judgments are affected.

There are other concerns with this article. The researchers report a mean follow-up after surgery of 9.9±6.4 years, with a range of one month to 40.5 years. It is not clear how this was calculated, since silicone breast implants have been used only since 1963 (fewer than 30 years before the study’s outcome date), and women having non-SGBI forms of breast augmentation were supposedly excluded from this sample. Including even a small number of cases extending to over thirty years could inflate the mean follow-up substantially. Ruptures and other reported health problems that women associate with their breast implants occur with greater frequency as implants age in the body. Long-term follow-up is a crucial variable in examining breast implant safety.

Finally, although the sample size in Sánchez-Guerrero was very large (close to 90,000 women in the on-going Nurses study), the prevalence of connective-tissue disease in the population is very small, such that the number of those with both connective-tissue disease and breast implants, if randomly distributed, is extremely small. The sample would have to be extremely large to have enough power to detect a significant increase in disease outcome. The authors themselves conclude that because of the infrequency of occurrence of connective-tissue diseases, “our study cannot be considered definitively negative” (p. 1669).

A study of all women with implants in Olmstead County, MN (“The Mayo Clinic Study”), which also found no association with connective-tissue disease, “calculated that it would require a sample of 62,000 women with implants and 124,000 women without implants, followed for an average of 10 years each, for a doubling of the relative risk of [systemic sclerosis] to be detected among women with implants, assuming that the annual incidence of systemic sclerosis is 1.6 cases per 100,000 women.”4

These two studies are widely acknowledged to be the most sound research yet carried out on breast implant safety. Both were widely reported in the popular press to show that breast implants do not cause connective tissue diseases, ailments claimed by many of the women who have won legal compensation for health conditions they attribute to their breast implants. Yet both offer disclaimers that their research cannot provide a definitive answer to the long-term health effects of breast implants.

The Sánchez-Guerrero article, despite its considerable conflict of interest flaws, is the foundation for many arguments in favor of SBIs. Today, it is fair to say that the medical establishment generally endorses the use of SBIs. Yet does that mean that SBIs are safe? There have been two major cases in the past several years where the established medical perspective regarding the incidence and treatment of breast cancer have been shown through randomized clinical trials to be completely wrong. In the first case, the community of physicians was so certain of the benefits of high dose chemotherapy with autologous bone-marrow transplant that they encouraged their patients not to enter NIH-sponsored clinical trials and risk being randomized to conventional treatment. This delayed the conclusion of clinical trials for years. By the time the NIH finally cut the studies short because of the lack of benefit compared to conventional treatment and the greatly increased comparative risk, thousands of women had been unnecessarily harmed.

In the second example, from 2002, the Women’s Health Initiative (WHI) began reporting the outcomes of their large randomized trials of the health impact of hormone replacement therapy (HRT). The WHI was carried out in the face of massive opposition by organized medicine, which so strongly believed in the benefits of HRT that they argued that randomization to placebo was unethical. The WHI, however, showed that not only was HRT not beneficial in alleviating heart disease and other chronic conditions of aging for which it was widely prescribed, it significantly increased the risk of the events which it had been purported to prevent. And the research substantiated the elevated incidence of breast cancer in women who took these drugs for even a few years.

For both high dose chemotherapy and HRT, women’s health advocates, including Breast Cancer Action, had questioned the amassed body of correlational research, its conclusions, and the conflict of interest inherent in the conduct of many of the studies. We were heavily attacked for our point of view. And we are still waiting to be thanked—or even acknowledged by the medical community for our prescience.

It is unlikely that we will ever again get the research opportunity we had—and missed—twenty years ago, before all the controversy arose about breast implants’ long term effects. Only sound and independent trials with long enough follow-up of very large samples of women could answer the questions we continue to have about silicone breast implant safety. For this reason, Breast Cancer Action urges the FDA to proceed cautiously with marketing approval for the silicone gel-filled breast implants and require Inamed’s planned ten-year follow up prior to making the implants freely available.

Former BCA Board President Jane Sprague Zones traveled to the Washington, DC, area last fall to represent BCA at the SBI hearings. Jane is a medical sociologist who has served on several scientific advisory panels of the FDA.

1 Stuart Bondurant, Virginia Ernster, and Roger Herdman, Editors, Safety of Silicone Breast Implants, National Academy Press, Washington, DC, 2000.

2 Joel Lexchin, Lisa A. Bero, Benjamin Djulbegovic, and Otavio Clark, “Pharmaceutical Industry Sponsorship and Research Outcome and Quality: Systematic Review,” BMJ (British Journal of Medicine) 326, May 31, 2003, pp. 1167-1176.

3 Jorge Sánchez-Guerrero, Graham A. Colditz, Elizabeth W. Karlson, David J. Hunter, Frank E. Speizer, and Matthew H. Liang, “Silicone Breast Implants and the Risk of Connective-Tissue Diseases and Symptoms.” New England Journal of Medicine 332(25): 1666-70, June 22, 1995.

4 S.E.Gabriel, et al., “Risk of Connective-Tissue Diseases and other Disorders after Breast Implantation,” New England Journal of Medicine, 330(24): 1701, 1994.