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An article in the Annals of Surgery, researchers conclude that their work supports an association between silicone breast implants and a range of conditions. This journal article was accompanied by two editorials in which experts voiced their disagreement with the way the analysis was performed and the conclusions of the authors. (2/21/19)
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The long-term safety of patients with breast implants.
This report was sensationalized in the media and covered in a recent headline hype blog.
Following U.S. FDA approval of silicone breast implants in 2006, the agency ordered manufacturers to conduct post-approval studies involving nearly 100,000 patients. The FDA shared the results from these studies in 2011 and also posted on the FDA post-approval study websites for manufacturers Allergan in 2015 and Mentor in 2018.
In a recent article published in the Annals of Surgery, Coroneos and colleagues report on the long-term outcomes of the 100,000 patients who were enrolled in the FDA-mandated post-approval studies. The authors emphasize that their results implicate silicone implants in an increased risk for certain conditions.
This study has significant problems, including the methods used, potential bias, and inconsistencies in reporting of results. These flaws prohibit any meaningful conclusions that might be drawn from this report’s results regarding silicone implants and health outcomes.
Unfortunately, the conclusions of this study are likely to cause unnecessary alarm to women have or are considering breast implants.
Because this is study was poorly conducted, the following results are untrustworthy.
Compared to the general population, patients with silicone implants had an incidence of specific conditions that was statistically more than double for the following conditions. Oddly, patients with Mentor implants only reported these conditions; none of the physicians of the patients with Allergan reported these conditions:
Compared to the general population, patients with silicone implants also had incidence rates that were statistically significant but less than double for the following conditions:
A variety of patient-reported health conditions, including chronic fatigue, memory problems, rheumatoid arthritis, fibromyalgia, and many others have been referred to as “breast implant illness.” Based on the results of hundreds of studies in different countries, the FDA advises that while implants have inherent problems, no research has ever associated them with the conditions described. The lack of evidence to support or refute a link to rheumatological or connective tissue disorders does not suggest that certain patients who are suffering may not benefit from removal of their implants.
While anecdotal and case reports claim that there is a link between silicone implants and fibromyalgia, this study found that women with silicone implants had lower rates of fibromyalgia, regardless of the manufacturer. They also had lower rates of lung cancer.
Importantly, due to the many limitations of this study, there is not enough evidence to show an association between breast implants and immune or connective tissue diseases.
The many limitations of this study data include:
While many patients with breast implants are satisfied with their results, breast implants are associated with known risks, including capsular contracture (hardening of the breast area around the implant), reoperation, removal, and rupture. Saline and silicone implants are also associated with extremely rare occurrences of breast implant-associated anaplastic large cell lymphoma (BIA-ALCL), a type of non-Hodgkin’s lymphoma. See our XRAYS reviews here and here.
Although newer generations of breast implants are believed to be greatly improved over earlier models, they are not lifetime devices and they are not without problems. They may last 10 to 20 years, or need to be replaced within a year of placement. Although some women do not experience any problems with their implants, the overall incidence of problems, including those that require reoperation and/or replacement is high. The longer a patient has implants the more likely she is to experience rupture, wrinkling, rippling, asymmetry, breast pain and numerous other issues that require medical intervention to resolve.
The FDA held a public meeting of the General and Plastic Surgery Devices Panel at the FDA’s headquarters in Silver Spring, Maryland March 25-26, 2019. FORCE attended and made public comments at the meeting. The FDA and the Plastic Surgery Foundation have developed the Patient Registry and Outcomes For breast Implants and anaplastic large cell Lymphoma (ALCL) etiology and Epidemiology (PROFILE) to collect real world data on patients who have a confirmed diagnosis of BIA-ALCL. The FDA is also creating the National Breast Implant Registry to collect real world data on the safety and performance of breast implants.
Note: FORCE receives funding from industry sponsors, including companies that manufacture implants. All XRAYS articles are reviewed by members of our Scientific Advisory Board prior to publication to assure scientific integrity.
Medical News Today
In the early 1990s, numerous anecdotal and case reports of silicone breast implants causing connective tissue disorders, cancer and autoimmune diseases resulted in a voluntary moratorium of their use. Subsequently, a new generation of silicone implants were approved in 2006.
As a condition of that approval, the FDA ordered breast implant manufacturers Allergan and Mentor to follow implant patients for 10 years to identify common complications and rare events. The FDA shared results of these studies, which involved nearly 100,000 patients in a report published in 2011.
In addition to the FDA’s 2011 report, an extensive literature review in 2016 by Balk and colleagues of more than 5,000 citations concluded that case reports and anecdotes did not conclusively associate breast implants with any health outcomes, including connective tissue disease, cancer, neurological disorders or reproductive problems.
The long-term safety and efficacy of breast implants.
The subset of data used for this study include information from the following patients from the original post-approval studies:
Allergan patients with Natrelle® silicone gel or saline implants were recruited from February 2007 to March 2010 from 873 sites. Mentor patients with saline or MemoryGel® silicone implants were recruited from February 2007 to July 2009 from 2,342 sites. Collected clinical outcome data included deaths, rare adverse events (e.g., connective tissue disease) and local complications. For each manufacturer, participants were assessed at 3 to 4 postoperative visits at predefined intervals, and by annual remote (mail, telephone, internet) patient questionnaires.
The conclusions of this study cannot be deemed as scientific or reliable, based on the way data was collected, the analysis method, and the overall bias involved.
Compared to the general population, patients with silicone implants had a statistically significant, more than double incidence of the following conditions:
For patients with silicone implants, incidence rates were statistically significant, but less than double that of the general population for the following:
There are important and significant problems with this study.
The data used was inadequate for testing rare events.
The authors of this study performed their analysis on data that was known to be problematic. Although their original post-approval studies enrolled a sufficient number of patients (99,993), other experts warned that using physician-reported or patient-reported data was inadequate, especially for studying rare events, and should not be used to make statistically significant conclusions. The study follow-up was also poorly conducted.
Only a subset of the data was evaluated.
Ethical, accurate study procedure calls for objective analysis of all data in a study. Yet, the authors of this study “cherry-picked” only certain data to include and subsets of the results data to calculate rates of adverse effects. This “picking and choosing” of data skews observations and results. It is unacceptable scientific process without the standard stringent internal validation.
A poorly matched control group was used.
The number of adverse events in this study’s subset of patients was compared to controls. The authors chose the general population rates reported in the literature as controls, rather than control participants who participated in this study. From a scientific perspective, this is highly irregular, since the study test group and the control group from the general population may differ in ways (e.g., environmental exposure to chemicals or differences in ethnicity) that are not related to the presence or absence of breast implants. A more reliable control would be a comparison of rates in the same study of harmful events between women with silicone implants and women with saline implants. In fact, the authors had this data, but they did not use it.
Different data collection methods were used for different test groups.
This study violated another basic rule of scientific methodology: that the method of data collection should be the same among groups that are compared. This study’s comparison of Allergan and Mentor data was highly inappropriate, since they were collected by different methods. Study authors used rates of adverse events that were calculated from physician-reported data in the Allergen study of 25,219 patients. In contrast, rates of adverse events were calculated from patient-reported data (without physician confirmation) for the Mentor study of 8,437 patients. Using patient-reported data for connective tissue diseases or other conditions without clinical confirmation is unreliable. These diseases can vary considerably in presentation and may require physician expertise or laboratory tests to confirm a diagnosis.
Poor follow-up rates increase the likelihood of biased responses.
Rates of patient follow-up were poor. The 2-year follow-up data included 60.5% of Allergan patients, but just 24% of Mentor patients. Even fewer (20%) of women participated in the 7-year follow-up. Poor follow-up rates like these can introduce substantial bias. One reason is that patients without symptoms or concerns are less likely to follow-up, while patients with symptoms or concerns may be more likely to keep their follow-up visits and/or respond to questionnaires. Despite this obvious shortcoming, which was worse with the Mentor study, the authors heavily base their conclusions on that data.
The potential for statistical error exists.
Because large data sets inherently have variations, a subset of data can almost always be randomly found to fit a given pre-formed hypothesis. Objective studies do the opposite: they collect and analyze reliable data and come to objective conclusions.
In one of the two accompanying editorials, Amy S. Colwell, MD, and Babak Mehrara, MD, state that:
“This [type of statistical error] may arise from deliberate academic dishonesty or as an honest mistake. Type I [statistical] errors have a pernicious effect because they cause patient/physician anxiety and lead to medical errors and flawed conclusions.”
Nor did the current analysis evaluate other patient data such as geography, lifestyle, UV light exposure, smoking, alcohol use, cancer history, weight, depression, medications or reproductive history that might impact this study’s outcomes. Failing to control for the potential of statistical and other confounding factors means the statistical conclusions of the current study are untrustworthy.
Results of the study are illogical.
For unknown reasons, the current study emphasizes the patient-reported data from 8,437 Mentor patients, while virtually ignoring the physician-reported data from the larger group of 25,219 Allergan patients:
Binita S. Ashar, MD, FDA Divisional Director and author of the other editorial that accompanied this study, states:
“Unfortunately, as the authors acknowledge, they failed to account for methodological differences between studies, inconsistencies in the data, differential loss to follow-up, confounding and other potential sources of bias.”
Conflicts of interest are not reported
Importantly, the authors report no financial conflicts of interest. Annals of Surgery conforms to the disclosure policy published by the International Committee of Medical Journal Editors, instructing authors to “report all sources of revenue paid (or promised to be paid) directly to you or your institution on your behalf over the 36 months prior to submission of the work.” According to the Propublica online database Dollars for Docs, Mark W. Clemens, MD and senior author of the study received $64,013 from Allergan in 2016 for promoting its Natrelle and Seri products. In 2015, he received $134,782 from Allergan. Awareness of possible bias is essential for proper evaluation of study conclusions.
Social media often amplifies fears about breast implants. As a result, increasing numbers of women see plastic surgeons for evaluation of systemic symptoms of “breast implant illness” that they attribute to their breast implants. However, breast implant illness is not a medical diagnosis. Currently, no simple test confirms the relationship between implants and a patient’s symptoms. Despite the claims of the authors of this scientifically flawed study, no sufficient scientific evidence supports a link between breast implants and autoimmune-related disorders or other diseases. Breast implants (primarily implants with textured surfaces) are linked by evidence to BIA-ALCL, although this is extremely rare. Other known, non-disease risks associated with breast implants include capsular contracture, reoperation, removal, and implant rupture. These remain the most common problems that occur with breast implants.