Breast implants and cancer: causation, delayed detection, and survival

Concern for many women with breast implants has been focused on three topics: cancer (both breast and other cancers), delayed detection of breast cancer, and increased breast cancer recurrence or decreased length of survival. In this study, a qualitative review of the literature on these subjects was conducted, coupled with a meta-analysis of the risk for breast cancer or other cancers (excluding that of the breast). Researchers have consistently found no persuasive evidence of a causal association between breast implants and any type of cancer. The meta-analysis results obtained by combining the epidemiology studies support the overall conclusion that breast implants do not pose any additional risk for breast cancer (relative risk, 0.72; 95% confidence interval, 0.61 to 0.85) or for other cancers (relative risk, 1.03; 95% confidence interval, 0.87 to 1.24). This analysis suggests that breast implants may confer a protective effect against breast cancer. Women with implants should be reassured by the consistency of scientific studies which have uniformly determined that, compared with women without implants, they are not at increased risk for cancer, are not diagnosed with later-stage breast malignancies, are not at increased risk for breast cancer recurrence, and do not have a decreased length of survival.     

Characteristics of a population of women with breast implants compared with women seeking other types of plastic surgery

Several previous studies have shown that breast implant patients demonstrate a number of differences compared with the general population. However, studies have not compared patients with breast implants with women receiving other types of plastic surgery, of interest because this latter group has been proposed as a comparison group for assessing the long-term health effects experienced by breast implant patients. Questionnaire data obtained from 7447 breast implant patients and 2203 patients with other types plastic surgery were collected during the course of a retrospective cohort study, to determine whether implant patients demonstrate different characteristics compared with a more restricted group of patients. In contrast to previous investigations that compared implant patients with the general population, distinctive differences with respect to family income, number of pregnancies, alcohol consumption, cigarette smoking, or histories of previous gynecologic operations or operations for benign breast disease were not found. However, implant patients were significantly more likely than other plastic surgery patients to be white, have low levels of education, have early ages at first birth, be thin, and be screened frequently for breast disease. Furthermore, implant patients reported somewhat greater use of exogenous hormones and familial histories of rheumatoid arthritis. These results support the notion that other plastic surgery patients are a more appropriate comparison group than women in the general population for studies of the health effects of breast implants; however, there continue to be distinctive characteristics possessed by breast implant patients, which need to be taken into account in an assessment of what disease effects can be uniquely attributed to silicone breast implants.     

A review of psychological outcomes and suicide in aesthetic breast augmentation

Aesthetic surgery is an essential component of plastic surgery and has become increasingly popular in American society. In 2002, 1.8 million surgical cosmetic procedures were performed in the United States, representing a 294 percent increase from 1992. The 1992 U.S. Food and Drug Administration moratorium on silicone breast implants arose in response to numerous reports of connective tissue disease associated with silicone gel breast augmentation and has led to a decade-long battle over the safety of silicone breast implants that continues today. Numerous scientific and epidemiologic studies of the past decade have established that there is no association between silicone breast prostheses and systemic disease. Recently, a new front has opened in the conflict regarding the safety of breast augmentation: the psychological impact of breast augmentation. Quality studies assessing the psychological characteristics of breast augmentation patients and the psychological impact of breast augmentation surgery are few and most studies are flawed in their methods. Recent reports have provided corroborating evidence to support the psychological benefits of cosmetic surgery and breast augmentation. New reports citing an increased risk for suicide among women with breast implants have brought renewed concerns but are unable to demonstrate a cause-and-effect relationship between breast implants and suicide. The present challenge is to determine whether the increased risk reported in epidemiologic studies is falsely associated with breast implants or whether it represents underlying risk factors or psychopathology in women undergoing breast augmentation that puts them at increased risk for suicide. The purpose of this article is to review the literature regarding the psychological impact of breast augmentation and assesses current scientific findings, with emphasis on the validity of suicide risk in breast augmentation patients.     

Comparative experience with smooth and polyurethane breast implants using the Kaplan-Meier method of survival analysis.

Smooth-walled silicone implants have been widely used in breast surgery. Capsular contracture, causing undesirable firmness and spherical deformity, has been a common problem. Recent studies suggest that polyurethane-covered breast implants are associated with a lower incidence of capsular contracture. The statistical methodology employed in some of these studies, however, may be subject to criticism. Between July of 1984 and June of 1990 (72 months), 427 polyurethane breast implants were used in 279 patients and 439 smooth prostheses were used in 250 patients for a variety of aesthetic and reconstructive procedures. The occurrence of capsular contracture was carefully monitored and then analyzed using the Kaplan-Meier method of survival analysis. This method is particularly well suited to analysis of these types of clinical data because it allows for the fact that contractures occur at varying intervals after surgery and that follow-up of patients is incomplete. The probability of capsular contracture with smooth-walled prostheses was found to be significantly greater than with polyurethane-covered implants in each group of patients studied (p less than 0.05). Other complications occurred at a similar rate regardless of prosthesis type. This study supports the belief that polyurethane breast implants have a lower contracture rate; furthermore, it introduces the Kaplan-Meier method for analyzing the outcome of alternative plastic surgical therapies.     

Risk of connective tissue disease and related disorders among women with breast implants: a nation-wide retrospective cohort study in Sweden.

OBJECTIVE: To examine the relation between connective tissue disease and related conditions and breast implants. DESIGN: Retrospective cohort study of all women in the Swedish national inpatient registry who underwent breast augmentation surgery with artificial implants during 1964-93, compared with women who underwent breast reduction surgery during the same period. SETTING: Sweden. SUBJECTS: 7442 women with implants for cosmetic reasons or for reconstruction after breast cancer surgery and 3353 women with breast reduction surgery. MAIN OUTCOME MEASURES: Subsequent hospitalisation for definite connective tissue diseases (rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, dermatomyositis, and Sjögren''s syndrome) or related disorders. RESULTS: 29 women with implants were hospitalised for definite connective tissue disease compared with 25.5 expected based on general population rates (standardised hospitalisation ratio 1.1 (95% confidence interval 0.8 to 1.6)). There were no diagnoses of systemic sclerosis, and no significant excess in risk for polymyalgia rheumatica, fibromyalgia, and several related disorders. Among women who underwent breast reduction surgery, 14 were hospitalised for definite connective tissue disease compared with 10.5 expected (standardised hospitalisation ratio 1.3 (0.7 to 2.2)). Compared with the breast reduction group, women with breast implants showed a slight reduction for all definite connective tissue disease (relative risk 0.8 (95% confidence interval 0.5 to 1.4)). CONCLUSIONS: This large nationwide cohort study shows no evidence of association between breast implants and connective tissue disease.     

A prospective analysis of patients undergoing silicone breast implant explantation

Despite the lack of a scientifically proven link between silicone implants and disease, many women have chosen to have their implants removed out of concern for their health. Unfortunately, there are few studies in the literature that have investigated the outcome of explanations, and there are no prospective analyses of the effect explantation has on a patient's general health. The goal of this study was to use a prospective database to determine whether there were any preoperative parameters that could be used to predict which patients would be improved following removal of silicone breast implants and to provide a quantifiable measure of that improvement. A total of 38 patients with silicone breast implants underwent operative removal of their breast implants by faculty at the University of Texas Southwestern Medical Center. They were given questionnaires regarding several personal and medical parameters to be completed preoperatively, at 6 weeks postoperatively, and at 6 months postoperatively. In addition, their physicians completed preoperative and postoperative evaluations of the patient's general health status. A control group of 38 patients was established; they were matched with the experimental group with regard to age and other initial parameters. Their responses to questionnaires were then grouped according to standard subscales to evaluate physical functioning, physical role, bodily pain, general health, vitality, social functioning, emotional role, mental health, appearance evaluation, appearance orientation, illness orientation, and body area satisfaction. When compared with the control group, we found that patients who had undergone explantation showed a temporary decrease in musculoskeletal symptoms and bodily pain, as well as an increase in vitality, mental health, and body area satisfaction. Of the experimental group, those who initially indicated a higher number of musculoskeletal symptoms and a higher appearance evaluation were more likely to indicate a significant improvement in general health since explantation.     

Antinuclear antibodies and breast implants.

Anecdotal reports have linked silicone breast implants to autoimmune diseases, with scleroderma being mentioned most often. In view of other environmental influences--such as silica mining and the toxic oil syndrome--thought to predispose to scleroderma, more systematic immunologic information on women with silicone implants is needed to assess any possible relation to autoimmunity. A cross-sectional survey was carried out with 150 women, of whom 131 had implants. Group 0 consisted of 19 volunteer women without breast implants who felt healthy, group I was 38 volunteer women with breast implants who felt healthy, group II was 82 women with implants who had various symptoms, and group III was 11 women with implants who had autoimmune disease. Scleroderma was overrepresented in group III (6 of 11). Antinuclear antibodies were determined on Hep-2 cells, using serum dilutions of 1:16, 1:64, and 1:256. A positive test was indicated by 1+ or more fluorescence at 1:256. Antinuclear antibody tests were positive in 0% of group 0, 18% of group I (P < .05 versus group 0), 26% of group II, and 64% of group III. There was no correlation between antinuclear antibody positivity and type of implant, indication for implantation, time since first implantation, total number of implants, and report of implant leak or rupture. Women with breast implants may be at risk for the development of antinuclear antibodies. Proof of such an association will require large-scale prospective studies and epidemiologic analyses.     

Phenotypes,genotypes and their contribution to understanding keratin function

A large number of mutations in keratin genes underlie inherited tissue fragility disorders of epithelia. The genotype-phenotype correlations emerging from these studies provide a rich source of information about the function of keratins that would have taken decades to achieve by a purely transgenic approach. Human disease studies are being supplemented by engineered mouse mutant studies, which give access to the effects of genetic alterations unlikely to occur naturally. Evidence is emerging that the great diversity of keratins might be required to enable cells to adapt their structure in response to different signalling pathways.     

Silicone gel-filled breast implant integrity: a retrospective review of 478 consecutively explanted implants

Concern has been expressed over the long-term integrity of silicone gel breast implants. There are no large series representing experience with these implants outside of the United States. A retrospective case note review of explanted silicone breast implants was performed; 478 implants have been explanted during the past 11 years and relate to the use of these devices since 1971. Loss of implant integrity was not simply related to its age in vivo. Failure was more likely with implants of the late 1970s and early 1980s (second generation) and with subpectoral placement. Implant failure was independent of capsular contracture as the indication for removal (p = 0.09). There is no evidence that the currently used textured silicone gel breast implants are subject to the same loss of integrity as previous examples of these devices. The life span of these implants, the first of which are approaching 10 years in vivo, is at present unknown. Information concerning the integrity of silicone gel breast implants is essential in the current climate for counseling of both new and old implant recipients.     

Present clinical applications of osseointegrated percutaneous implants

Altogether, 389 screws of commercially pure titanium have been inserted at various locations in the facial skeleton of 174 patients. The indications for treatment have been stable anchorage of an external hearing aid or a facial episthesis, in the latter case to restore the facial contours after congenital disorders or status after trauma or cancer surgery. All implants have been inserted in a two-stage procedure, the first being anchorage of the titanium elements in the bone, the second, minimally 3 months later, being establishment of a permanent skin penetration. The outcome of every inserted implant has been analyzed. Only six implants failed to become integrated in bone and had to be removed. Five of these failures occurred in previously irradiated bone, where the success rate was estimated to 85.3 percent. In nonirradiated bone, 354 of 355 inserted implants became osseointegrated, i.e., anchored in bone in a stable manner. The soft tissues were without any adverse reactions in 92 percent of the 951 clinical observations, whereas potentially serious skin complications were observed in only 2.8 percent. Presently, the longest clinical follow-up is 8 years, and 37 implants have been followed for more than 5 years. We believe that this clinical material is the first in which an uneventful bone anchorage and skin penetration have been demonstrated in consecutively operated upon clinical cases. The implants used for anchoring an external hearing aid were also successful in the sense that the patients gained 15 dB (average) in hearing threshold and showed a significantly improved discrimination score. The implants inserted to hold facial epistheses resulted in considerably improved retention and a good cosmetic outcome for the patients.     

The management of anterior chest wall deformity in patients presenting for breast augmentation

Anterior chest wall asymmetry is sometimes encountered in patients presenting for consideration of breast augmentation. The chest wall asymmetry or deficiency may be significant enough to consider reconstruction at the same time as breast augmentation in a small number of cases. Customized and prefabricated chest wall implants have been used in a variety of conditions including Poland syndrome, pectus excavatum, and sunken anterior chest. Careful moulage preparation and on-table implant modification are needed to "seat" these implants on the skeletal chest wall under the pectoralis major muscle. The chest wall implant provides a base for the subsequent breast prostheses and fills up a bony deficit that cannot be camouflaged by the breast prostheses alone.     

Are breast tumours resistant to tamoxifen also resistant to pure antioestrogens?

A substantial proportion of patients with breast cancer are treated with the antioestrogen tamoxifen. As with other endocrine therapies, clinical experience has shown that some tumours in which growth is initially attenuated by tamoxifen treatment become resistant to continued drug treatment and resume growth. The mechanisms underlying the development of tamoxifen resistance have yet to be described but represent an important focus of research with the aim of defining what other therapies might be effective following tamoxifen treatment. Secondly, an understanding of tamoxifen resistance might suggest means to develop more effective agents for primary treatment of the disease. The development of pure antioestrogens, for example ICI 164,384 and ICI 182,780, which differ pharmacologically from tamoxifen in being entirely free of oestrogen partial-agonist activity, together with cell and animal models of tamoxifen resistant human breast cancer, has revealed one mechanism which might be of considerable clinical significance. Pure antioestrogens were shown to inhibit the proliferation of a greater proportion of tumor cells than tamoxifen in vitro, a differential effect that was attributed to the oestrogenic activity of tamoxifen. Subsequently, cell culture studies have shown that breast cancer cell lines selected for resistance to tamoxifen can still remain sensitive to the growth inhibitory action of pure antioestrogens. Similarly, the growth of human breast tumours in nude mice, which is initially attenuated by tamoxifen but then resumes, can be inhibited by pure antioestrogens. Both types of experiment are consistent with the view that tamoxifen resistance in these model systems is due to the oestrogenic action of tamoxifen. Thus, it can be predicted that in some patients whose tumours recur during tamoxifen therapy, a further response to pure antioestrogen treatment might occur. Studies to examine this hypothesis are currently being undertaken with ICI 182,780. One mechanism which might account for the experimental observations is an intrinsic heterogeneity amongst breast tumour cells in their response to tamoxifen, i.e. that there are at least two different populations of cells; one population which responds to tamoxifen as an antioestrogen and one which “reads” tamoxifen as an oestrogen. The growth advantage thus conferred on the latter population would lead to its predominance. If this is what actually happens in a proportion of human tumours, it can be argued that primary treatment of the tumour with a pure antioestrogen, rather than tamoxifen, would be preferred since a more complete and longer-lasting response would be predicted. Recent comparative studies with human breast tumours grown in nude mice support these predictions.     

An analysis of telephone interview data collected in 1992 from 820 women who reported problems with their breast implants to the food and drug administration

How health care providers deal with concerns and feelings of women who have problems with their breast implants affects the women's satisfaction with their breast implants, yet in 1992 little was known about the concerns and feelings of these women. A qualitative analysis of in-depth telephone interviews conducted in 1992 with 820 women from all regions of the United States who reported problems with their breast implants to the Food and Drug Administration and responded to an invitation to be interviewed provided data. Respondents were primarily 40 to 69 years of age at the time of interview, Caucasian, married, and educated beyond high school. The sample was almost equally divided in reason for breast implants, with 65 percent being dissatisfied with their breast implants. Nearly all of the women had heard of problems with silicone gel-filled implants. Their main sources of information were television, newspapers, and magazines rather than their physicians or the breast implant manufacturers. Some women tried to avoid hearing the reports, and many tried to put the reported problems out of their minds. However, a majority (88.7 percent) wanted more information. The women expressed feelings of anger, regret, and worry, and repeatedly said they needed more information. Women who contacted the Food and Drug Administration about breast implant problems needed accurate and honest information from health care professionals. They wanted their physicians to explore their symptoms, fears, and concerns.     

Local complications and subsequent symptom reporting among women with cosmetic breast implants

Epidemiologic studies have found no association between breast implants and cancer or well-defined connective tissue diseases. However, women with cosmetic breast implants continue to report specific as well as nonspecific physical and psychological symptoms after receiving their implants. In an attempt to determine whether local complications of implantation may contribute to this excess of symptom reporting, the authors studied a large cohort of women in Sweden with cosmetic breast implants (n = 1280) and a comparison cohort of women who had cosmetic breast reduction surgery (n = 2211). Both groups of women had operations between 1969 and 1996. Medical record reviews of local complications revealed that approximately 31 percent of the women with cosmetic breast implants had an implant change, implant leakage, or a capsulotomy. Capsulotomies occurred more often in women who were age 35 or older at the time of the operation, had ever smoked, and had implants with a smooth surface. On self-administered questionnaires, symptoms were reported more often by the women who had implants regardless of whether they had local complications. Twenty of the 28 symptoms occurred more frequently among women with local complications and breast implants, compared with the women in the breast reduction comparison group or the women with breast implants but no local complications. This study suggests that local complications, particularly capsular contractures as indicated by capsulotomy, may be an important factor to consider when studying symptom reporting among women with breast implants.     

Translational genetic approaches to substance use disorders: bridging the gap between mice and humans

While substance abuse disorders only occur in humans, mice and other model organisms can make valuable contributions to genetic studies of these disorders. In this review, we consider a few specific examples of how model organisms have been used in conjunction with studies in humans to study the role of genetic factors in substance use disorders. In some examples genes that were first discovered in mice were subsequently studied in humans. In other examples genes or specific polymorphisms in genes were first studied in humans and then modeled in mice. Using anatomically and temporally specific genetic, pharmacological and other environmental manipulations in conjunction with histological analyses, mechanistic insights that would be difficult to obtain in humans have been obtained in mice. We hope these examples illustrate how novel biological insights about the effect of genes on substance use disorders can be obtained when mouse and human genetic studies are successfully integrated.     

Alternating Reducing and Enhancing Effect of Pregnancy on Breast Cancer Risk May Reveal Periodic Phenomena which Mask Circannual Rhythms

Although a relationship between reproductive factors and breast cancer risk has been known for long, there are many contradictions between different studies, and a connection with a biological mechanism has not yet been found. Recently, new details have been revealed about different effects of pregnancy on breast cancer risk. During pregnancy breast cancer risk is strongly reduced, while inversely,some years after giving birth the risk is increased. Furthermore, risk is strongly reduced in women whose consecutive births of four or more children occur after short intervals and are terminated before the age of 30. Recently, we have postulated rhythmicity in the occurrence of breast cancer in a subgroup of young women. By analogy with circadian rhythms it may be assumed that circannual rhythms too are influenced by synchronizers and masking effects. In circadian rhythms masking may be by external or internal periodic factors, such as the sleep/wake cycle, meal timing and activity. Over the year pregnancy may be such a periodic factor, with alternation of an empty uterus and one wich gradually enlarges as a consequence of a developing fetus. A masking factor is active only as long as present. Therefore the circannual rhythmicity of breast cancer is attenuated or nullified only during pregnancy. After giving birth, the temporal deficit of the rhythmic increase of tumor growth may be restored, leading to a rebound effect expressed as an increased clinical detection of malignancy some years later. When several consecutive pregnancies occur after short intervals the masking effect continues uninterruptedly, accompanied by a strong reduced breast cancer risk. The same biological mechanism may underly the remission during pregnancy in autoimmune disorders such as rheumatoid arthritis and Graves’ disease. The immune system, crucial in autoimmune disorders, is build up of several constituents which are clearly rhythmic, e.g the lymphocytes. Masking of one or more of these rhythmicities may lead to disease attenuation, followed by relapses as soon as the masking factor has been eliminated.     

Textured-surface saline-filled silicone breast implants for augmentation mammaplasty

The earliest silicone breast implants were smooth-surface, silicone rubber devices filled with either silicone gel or saline. Because of persistent problems with capsular contracture, polyurethane-covered silicone implants were developed as an alternative. Particularly in the short run, these alternatives proved highly successful at reducing the incidence of capsular contracture. By 1990, polyurethane-covered implants were rapidly becoming the preferred implant choice of many plastic surgeons, but for legal, regulatory, financial, and safety reasons they were withdrawn from the market by Bristol-Myers in 1991. Meanwhile, during the late 1980s, surface texturing and improved materials became available on other silicone breast implants and expanders. Most studies suggest that textured-surface silicone gel-filled implants, saline-filled implants, and tissue expanders have less frequent capsular contracture than their smooth-surface counterparts.     

Alternating Reducing and Enhancing Effect of Pregnancy on Breast Cancer Risk May Reveal Periodic Phenomena which Mask Circannual Rhythms

Although a relationship between reproductive factors and breast cancer risk has been known for long, there are many contradictions between different studies, and a connection with a biological mechanism has not yet been found. Recently, new details have been revealed about different effects of pregnancy on breast cancer risk. During pregnancy breast cancer risk is strongly reduced, while inversely,some years after giving birth the risk is increased. Furthermore, risk is strongly reduced in women whose consecutive births of four or more children occur after short intervals and are terminated before the age of 30. Recently, we have postulated rhythmicity in the occurrence of breast cancer in a subgroup of young women. By analogy with circadian rhythms it may be assumed that circannual rhythms too are influenced by synchronizers and masking effects. In circadian rhythms masking may be by external or internal periodic factors, such as the sleep/wake cycle, meal timing and activity. Over the year pregnancy may be such a periodic factor, with alternation of an empty uterus and one wich gradually enlarges as a consequence of a developing fetus. A masking factor is active only as long as present. Therefore the circannual rhythmicity of breast cancer is attenuated or nullified only during pregnancy. After giving birth, the temporal deficit of the rhythmic increase of tumor growth may be restored, leading to a rebound effect expressed as an increased clinical detection of malignancy some years later. When several consecutive pregnancies occur after short intervals the masking effect continues uninterruptedly, accompanied by a strong reduced breast cancer risk. The same biological mechanism may underly the remission during pregnancy in autoimmune disorders such as rheumatoid arthritis and Graves' disease. The immune system, crucial in autoimmune disorders, is build up of several constituents which are clearly rhythmic, e.g the lymphocytes. Masking of one or more of these rhythmicities may lead to disease attenuation, followed by relapses as soon as the masking factor has been eliminated.     

Towards an integrated cellular and molecular: definition of breast cancers

Breast cancer is a major health problem as well as scientifically poorly understood. Our knowledge of breast cancer is however rapidly progressing in several directions. First, genomic studies are establishing a new molecular classification of breast cancers. Molecular subtypes have been identified and are being associated with the histoclinical forms of breast cancers. Second, genetic alterations are discovered and classified, generating new potential therapeutical targets. Third, mammary stem cells have been identified in the normal mammary epithelium. Their altered counterparts have been identified in tumors and are being characterized. These combined studies allow a new integrated cellular and molecular definition of breast cancers and a conceptual basis that will help the management of the disease.     

Mouse models of triplet repeat diseases

Triplet repeat expansions were first discovered in 1991 and since then have been found to be the mutation underlying a range of neurodegenerative, neuromuscular, and cognitive disorders including fragile X syndrome, myotonic dystrophy, Friedreich's ataxia, and the polyglutamine disorders that include Huntington's disease. The repeats exert their detrimental effects through different molecular mechanisms dependent on whether they are located in coding or noncoding regions of the gene in question. During the past 10 yr, a wide range of strategies have been used to successfully establish mouse models for all of these disorders. This review presents an overview of these mouse models, discusses the insights into the molecular pathogenesis of these disorders that have been gained from their analysis and the strategies that are being used to uncover novel therapeutic options.