24.1.1 History of Breast Implant Safety Surveillance

In the early 1980s, just as third-generation silicone implants were being introduced, rising levels of consumer concern became evident in regard to the safety of silicone breast implants. As this was occurring, the FDA’s new surveillance system began to identify frequent local complications associated with silicone implants. Breast implants became classified as higher-risk devices, which required premarket approval, and in light of this, manufacturers became responsible for providing data that supported the safety of these devices for patient use. ⁴ For more than 60 years there has been controversy as to the safety of these devices, with > 400 reports on various health conditions in association with breast implants. ⁵

Ultimately, in 1992, the FDA determined that silicone implant manufacturers had not provided enough data to address consumer concerns adequately, and silicone implants were removed from the market. During this time the FDA required all breast implant manufactures to conduct core studies to assess overall implant safety profiles. ^{6 ,​ 7 ,​ 8 ,​ 9 ,​ 10} Seven years after the FDA moratorium on silicone implants, the Institute of Medicine (IOM) released a detailed report of the current literature, entitled Safety of Silicone Breast Implants, which ultimately concluded that local complications were of primary concern and, in order to comment definitively on systemic disease such as cancer or autoimmune disorders, further studies were needed, as there was a paucity of significant, well-controlled studies. ⁴

The IOM report was the first step toward the return of silicone breast implants to the market in 2006. This report was instrumental in clarifying the scientific evidence, as well as identifying information gaps on the safety of these devices. Since the return of silicone implants, there has been ongoing research concerning their safety due in part to the FDA’s stipulation that the two manufacturers of silicone breast implants at that time, Allergan Inc. (Dublin, Ireland) and Mentor Corp. (Minneapolis, MN), conduct large post-approval studies to guarantee that these potential long-term risks did not go unmonitored. ^{11 ,​ 12}

24.1.2 Where Are We Now?

The extent of our knowledge on prior safety concerns has expanded since the FDA’s decision to remove silicone breast implants from market. ^{4 ,​ 13} Plastic surgeons must hold industry as well as one another accountable for the care of their patients by increasing awareness of evidence-based practices so that they can best inform their patients and the medical community on the safety of these devices. ^{12 ,​ 14 ,​ 15} Plastic surgeons, like all physicians, take an oath to “do no harm” and have a responsibility to inform their patients best on the safety of these devices and to listen with a kind ear when patients present with symptoms and complaints that have the potential to be associated with silicone breast implants. The information provided in this chapter reviews the current literature regarding the safety of silicone breast implants as well as the concerns that remain about these devices in light of recent consumer concern and social media reports about the possible existence of a “silicone breast implant illness” syndrome—an entity that currently has no clear definition but has been popularized by both health care providers and the media.

24.2.1 Breast Cancer

Because of breast implants’ location, their use in oncologic reconstruction, and their potential to affect breast mammography adversely, the risk of breast cancer development in these patients is of upmost concern. There is extensive data refuting any association between these devices and an increased incidence of breast cancer, as many studies have shown that these patients have a lower incidence of primary breast cancer. ^{12 ,​ 19 ,​ 20 ,​ 21 ,​ 22 ,​ 23 ,​ 24 ,​ 25 ,​ 26 ,​ 27 ,​ 28 ,​ 29 ,​ 30 ,​ 31 ,​ 33 ,​ 34 ,​ 35 ,​ 36 ,​ 37 ,​ 38 ,​ 39} In 1999 the International Agency for Research on Cancer (IARC) published a report stating there was evidence to support a lack of breast carcinogenicity in women with silicone breast implants, and this was later backed by the IOM Committee on the Safety of Silicone Breast Implants. ^{36 ,​ 40} Recent publications examining the incidence of breast cancer in patients with silicone breast implants include a meta-analysis by Noels and coworkers of results from 17 previously published articles. ³⁹ Ultimately the authors found that breast implants are not associated with an increased incidence of breast cancer, and a 2016 review article by Balk and coworkers confirmed these findings. ²³

24.2.2 Other Malignancies

Some reports describe an increased cancer risk among patients with cosmetic breast implants including brain, cervical, vulvar, and lung, in addition to nonmelanoma skin cancer. ^{4 ,​ 12 ,​ 41} However, the data do not support breast implants as being responsible for these findings. ^{4 ,​ 13 ,​ 42} Between 1999 and 2005 multiple independent scientific review boards concluded there is no excess risk of cancer of any type in women with silicone breast implants. ^{13 ,​ 35 ,​ 36 ,​ 37 ,​ 40} Since the release of these advisory reports, numerous studies have been conducted to better quantify the risk of breast and other types of cancer in women with breast implants. ^{12 ,​ 19 ,​ 20 ,​ 21 ,​ 22 ,​ 23 ,​ 28 ,​ 29 ,​ 34 ,​ 35 ,​ 36 ,​ 37 ,​ 38 ,​ 39} Many have definitively concluded that their cancer incidence closely matches that of the general population. ^{19 ,​ 20 ,​ 21 ,​ 22} However, in 2018, the largest study of patient safety and implant-specific outcomes for breast implants found that patients with Mentor Corp. silicone implants were 1.54 (95% CI: 1.42–1.68) times more likely to develop a cancer diagnosis compared to the general population. ¹²

Brinton and coworkers reported a slight excess of cancer in patients with breast implants as a result of statistically significant increased risks for cervical, vulvar, and brain cancer as well as leukemia compared to the general public, but these patients showed no difference when compared to women who had undergone other plastic surgery procedures. It is important to recognize that the authors clearly state that this observed difference is likely due to both selection bias and lack of cancer diagnosis validation. ²⁹ Additionally, multiple epidemiologic studies in the literature have found that women with breast implants have different patient demographics as well as lifestyle and/or reproductive characteristics compared to the general population, which may explain these findings. ^{43 ,​ 44 ,​ 45 ,​ 46}

There is a breadth of literature concerning the risk of brain cancer in patients with breast implants, including a multitude of large-scale incidence studies as well as five mortality studies. ^{12 ,​ 19 ,​ 20 ,​ 21 ,​ 22 ,​ 38 ,​ 47 ,​ 48 ,​ 49 ,​ 50} All but one study consistently failed to show an increased incidence of brain cancer or mortality from brain cancer in patients with breast implants. Such findings were explained by evidence that metastatic disease from distant sites is often not reflected in the diagnostic accuracy of death certificates in patients who die of brain cancer. ⁴⁷

Since McLaughlin’s original paper in 2007, which concluded there is no credible evidence to support a causal relationship between breast implants and cancer, much of the literature on this topic remains consistent. ¹³ This is supported by a large, multicenter observational study published in 2017 that looked at long-term safety of women with Natrelle round silicone gel-filled breast implants. Their study population of 55,279 women, which represented an interim data set that was later fully reported on by Coroneos and coworkers, showed no excess risk for any cancer diagnoses including brain, cervical/vulvar, lung, or breast cancer. ^{12 ,​ 51} Newly published literature found an increased incidence of melanoma in patients with Mentor Corporation breast implants compared to the general population. ¹² However, the authors of that study do not suggest that silicone implants are responsible for these diagnoses of melanoma but rather that patients with breast implants may be more likely to have increased ultraviolet (UV) light exposure secondary to sunbathing or outdoor lifestyles. Because of this, physicians need to be aware of breast implant patients who present with suspicious skin lesions, as they may have placed themselves at risk for the development of such conditions. Despite some reports of an increased incidence of lung cancer in certain populations with breast implants, studies that examined characteristics of these patients found an elevated proportion of smokers in addition to various lifestyle differences as more likely culprits.

24.2.3 Breast Cancer Detection

In a report that looked at the safety of silicone breast implants, the IOM suggested that these devices may obstruct visualization of various parts of the breast and would affect the accuracy of routine screening mammography. ⁴⁰ In response, multiple case series hypothesized that opaque breast implants may interfere with mammographic breast visualization as well as breast physical exam, ultimately delaying breast cancer diagnosis and causing worse prognosis for those affected. ^{52 ,​ 53 ,​ 54 ,​ 55} In addition to the bias presented in most of these reports, many of the women included underwent screening mammography without utilization of the Eklund implant displacement technique. ⁵⁶

In the most recent article published on the effect breast implants have on mammogram outcomes, Kam and coworkers conclude there is no statistically significant difference between women with and without implants in regard to Breast Imaging Recording and Data System 0 score, callback exam, time to resolution of abnormal imaging, or cancer detection rate. ⁵⁷ Additional studies have supported the conclusion that, although the sensitivity of screening mammography may be reduced by the presence of breast implants, this patient population does not present with more advanced stages of breast cancer or suffer from lower survival rates following diagnosis. ^{19 ,​ 21 ,​ 58 ,​ 59 ,​ 60 ,​ 61}

24.3.1 Implant Rupture and Connective Tissue Disease

Implant rupture has traditionally been thought of as an important risk factor for the development of CTD in patients with breast implants. Two large scale studies published prior to 2007 confirmed that implant rupture does not place patients at increased risk of developing CTD. ^{69 ,​ 70} One earlier study showed an increase in self-reported Raynaud’s syndrome in patients with isolated extracapsular implant rupture (odds ratio = 4.2; 95% CI: 1.1–16.0) and “other CTD” (odds ratio = 2.7; 95% CI: 0.8–8.5). In this study the authors did not discern whether or not onset of symptoms was prior to breast augmentation. ⁷¹

24.3.2 Historical Perspective and Current Evidence on Connective Tissue Disease

In the 1980s and early 1990s, anecdotal reports of CTD in women with breast implants were first published. Through 2004, data from all but one study unanimously concluded that there is no association between breast implants and CTD. ^{40 ,​ 62 ,​ 63 ,​ 66 ,​ 72 ,​ 73 ,​ 74 ,​ 75 ,​ 76}

Prior to recent reports, the only finding of a relationship between CTD and breast implants came from a large cohort study of female health professionals published in 1996. ⁶⁴ Compared to women without breast implants, women with breast implants had a relative risk (RR) of 1.24 (95% CI: 1.08–1.41) for any self-reported combined CTD. For individual connective tissue disorders including rheumatoid arthritis, polymyositis/dermatomyositis, scleroderma, and Sjögren’s syndrome, the relative risk of disease was slightly elevated but did not show statistical significance. Only 22.7% of self-reported CTD was confirmed in patients’ medical records. ⁶⁵ Additional evidence of overreporting and diagnostic biases was also evident in a cohort study that looked at CTD in 7,234 women in the United States with breast implants. ⁷⁷ After examination of the medical record by rheumatologists deemed to be expert, only a minority of self-reports of CTD were declared as “likely,” and the relative risk among women with breast implants was not significant for rheumatoid arthritis, scleroderma, or Sjögren’s syndrome combined when compared to the general population.

Fryzek and coworkers compared 2,761 Danish women with breast implants to 8,807 women who had undergone reduction mammaplasty. ⁷⁸ All outcomes were verified and based on thoroughly reviewed medical records. After a mean follow-up time of 13.4 years, the authors concluded that there was no significant increase in the incidence of any specific CTD or any of the CTDs combined for women with breast implants. Additionally, this study confirmed no difference between the two cohorts as it pertained to the incidence of fibromyalgia. Brinton and coworkers also found that women with breast implants were not at increased risk of developing fibromyalgia compared to those who underwent other types of plastic surgery procedures, although their data were self-reported. ⁷⁷ That study did include a category of conditions termed “other disorders,” for which they reported a risk ratio of 1.4 (95% CI: 0.8–2.6) prior to 1992 and 3.6 (95% CI: 1.9–7.0) for the period that followed, a period marked by widespread litigation in the United States, thereby supporting the authors’ claim that these results were largely due to reporting bias among subjects. Additionally, and most importantly, no saline implant control cohort exists, as the data for these devices has not been released by the implant manufacturers. Therefore, a group that controls for patient demographics in women with saline breast implants cannot be compared to those with silicone implants.

It is important to recognize that, based on the evidence presented at the time, the 1999 IOM report found no “convincing evidence for atypical connective tissue or rheumatic disease or a novel constellation of signs and symptoms in women with silicone breast implants.” ⁴⁰ The authors of this report acknowledged that the study was underpowered and therefore would not have found an association had one existed. Following this report, Tugwell completed a systematic review per the request of a U.S. federal court–appointed national science panel to assist in evaluating expert testimony being presented in lawsuits brought against various breast implant manufacturers. ⁶² It too found no evidence of an association between breast implants and CTD, therefore discrediting the expert testimony that had been presented.

In May 2011, Lipworth, Holmich, and McLaughlin published a paper titled “Silicone Breast Implants and Connective Tissue Disease: No Association,” with the intention of clarifying remaining claims regarding breast implants and CTD. ⁷⁹ Of note, the authors of this editorial were paid consultants of the implant manufacturers and concluded that these claims were a byproduct of “unprecedented large-scale product liability litigation” rather than sound scientific evidence. In it they cite 18 large-scale cohort studies, 11 case-control studies, and 13 additional independent meta-analyses and critical reviews, all of which unequivocally refute an association between breast implants and CTD. It showed a small increased risk of self-reported CTDs in women with breast implants (RR 1.24; 95% CI: 1.08–1.41). The relative risk for each individual CTD, including rheumatoid arthritis, polymyositis/dermatomyositis, scleroderma, or Sjögren’s syndrome were all slightly elevated but not statistically significant. A later study found that only a small fraction of diagnoses could be confirmed. ⁶⁵

Early reports of expert evidence reviews including a National Science Panel Report published in 1998, the 1999 IOM report, and a 2011 FDA review all supported that there was no evidence to link silicone breast implants with an increased incidence of connective tissue disease. ^{4 ,​ 40 ,​ 80} They did recognize that there were limitations to the existing evidence and further investigation was warranted. A 2017 article, discussed previously, reported that after looking at 55,279 women with breast implants over a 5-year follow-up period, silicone gel–filled implants had no increased risk of any connective tissue disease compared to national norms or those with saline implants. ⁵¹ All reported instances of adverse events were confirmed with the diagnosing physician to prevent inaccurate diagnoses based solely on patient reported symptoms. However, in the largest and most comprehensive epidemiologic study of patient safety and implant-specific outcomes for breast implants in the literature, studying nearly 100,000 patients (including the 55,279 in the aforementioned study) over a 7-year follow-up period, Coroneos and coworkers found that there were multiple connective tissue disorders for which diagnoses exceeded double that of the general population—conclusions that were contradictory to the interim analysis just discussed. ¹² These included Mentor patients with Sjögren’s syndrome (standardized incidence raio [SIR]: 8.14; 95% CI: 6.24–10.44), scleroderma (SIR: 7.00; 95% CI: 5.12–9.34), and rheumatoid arthritis (SIR: 5.96; 95% CI: 5.35–6.62). Additionally, the large study showed an increased risk of developing multiple sclerosis and myositis, although both at rates less than twice that of the general population. Data for Allergan implants had a 7-year follow-up period, were based on physician-confirmed diagnoses, and had an excellent follow-up rate. Patients who underwent revision of prior breast reconstruction with Allergan implants had incidence ratios greater than 2.0 for scleroderma, Sjögren’s syndrome, and both dermatomyositis and polymyositis at 7-year follow-up. Finally, Coroneos and coworkers reported 500 autoimmune events in the silicone implant cohort compared to five events in those with saline devices. These results are congruent with the largest meta-analysis to date, written by Balk and coworkers, which pooled outcomes from 32 observational studies as well as a recent review article published in 2018 that found a statistically significant association between silicone breast implants and autoimmune/rheumatic disorders, Sjögren’s syndrome, systemic sclerosis, and sarcoidosis. ^{23 ,​ 81}

In response to the media craze that ensued following publication of the study by Coroneos and coworkers, the FDA released a statement to address the findings discussed above. ¹² In it they urge both the public and health care providers to view their conclusions with caution, as the study has major shortcomings. While the author’s analysis was sound, the processes used for data collection were designed by the various implant manufacturers and not without inconsistency and bias; Coroneos and coworkers themselves recognized these conclusions, as do Colwell and Mehrara in a recently published editorial. ⁸² Binita Ashar, of the FDA’s Center for Devices and Radiological Health, reminded readers that the current evidence “does not conclusively demonstrate an association” and that “more evaluation is required.” ⁸³ Colwell and Mehrara highlight that the authors analyze a much smaller group of patients (< 34,000 vs. 99,993) for 7 years despite previous data concerns of poor follow-up and issues with data acquisition. The Mentor reported data had a 2-year follow-up rate of 24% and a 7-year follow-up rate of only 20%, both of which were drastically lower than those of the Allergan data set. Moreover, in addition to poor follow-up, a large subset of data was patient reported and had no physician confirmation. It is not surprising that the patient reported-data provided by Mentor ultimately had the greatest association with rare adverse health events; which were not upheld through the analysis of 25,219 Allergan patients. Outcomes were compared to “normative” populations and thus failed to control for many confounding variables. These methodological flaws prohibit any definitive conclusions to be reached from this article.

In summary, recent data suggest that, although this view was originally refuted, breast implants may have an association with CTD, a fact that must be explicitly communicated to patients interested in pursuing breast reconstruction or augmentation with silicone breast implants. Governing bodies such as the IOM and FDA strongly reaffirm that breast implants are overwhelmingly safe devices with a low overall risk of developing such conditions. We as plastic surgeons have a responsibility to advise our patients judiciously of these potential risks and look proactively for those who may present with symptoms indicating they require further evaluation. We must put our patients’ best interest first, which starts by actively listening to their desires as well as their concerns and working together to ensure patient safety and satisfaction.