EDITORIALS * EDITORIAUX
Breast implants: Quo vadis? Hans J. Berkel, MD, PhD reast augmentation was introduced into clinical practice in the early 1 960s and until recently was considered an accepted and safe procedure. In certain areas it was even an approved procedure and therefore payable through health care insurance. Millions of women worldwide have had breast augmentation for cosmetic or reconstructive reasons. No exact data are available for Canada, but, assuming the same frequency in Alberta as in the other provinces, it can be estimated that 150 000 to 200 000 women in this country have received breast implants. Recently major public concerns have arisen about the safety and efficacy of these devices. The media have published numerous articles about the alleged side effects of breast implants. Women's advocacy groups both for and against implants have mushroomed. The US Food and Drug Administration (FDA) held hearings and came out with some ambiguous statements. In the United States a moratorium was imposed on the use of implants early in January 1992. Canada followed suit a few days later. The minister of national health and welfare (DNHW) struck an independent advisory committee to advise him of what action to take regarding the implant controversy. A summary of the committee's report is in this issue (starting on page 1141). If implants prove to have deleterious long-term effects on the health of women, we could face a major public health problem. For example, the lifetime probability of breast cancer for women is 10%.' Assuming a 25% increase in this risk due to implants, breast cancer would develop in 3750 more women in Canada! The concerns thus seem quite justified. What, however, are the scientific facts? The discussions around breast augmentation focus mainly on the long-term health effects. Shortterm complications such as capsular contraction, B
pain, infection and rupture or dislocation of the implant are well known. No firm data exist, however, on either the frequency or the health impact of these problems. In regard to the long-term health effects two issues arise: first, the concern for an increased risk of cancer (specifically breast cancer) and, second, the alleged association between connective tissue disorders (specifically scleroderma) and implants. Although various implant types have been on the market, the main components of all types are silicone (polydimethylsiloxane) polymers as elastomers and gels. Most frequently gel-filled implants are used. The "envelope" surrounding the implant is a silicone elastomer, and the gel is mainly polydimethylsiloxane oil, which is classified as a nonreactive substance. Saline-filled implants have also been used. These consist of a silicone elastomer envelope that can be inflated with the desired volume of sterile saline. To overcome capsular contraction, a well-known complication of silicone implants, an implant covered with polyurethane foam (the Meme implant) was developed. This implant is no longer available in Canada: the manufacturer voluntarily withdrew it from the market because of allegations of carcinogenicity of the breakdown products of polyurethane. These products (2,4- and 2,6-toluenediisocyanate diamines) were discovered in the urine of a patient with Meme implants.2 However, an expert panel coordinated by the CMA, at the request of the DNHW, after reviewing all the evidence concluded that "surgical removal of polyurethane-foam-covered breast implants solely for reasons of potential risk of cancer does not appear to be indicated."3 It will be at least another 5 to 10 years before the issue of increased risk of cancer in
with Meme implants can be resolved, given the long latency period of the carcinogenic process. I
women
Reprint requests to: Dr. Hans J. Berkel, Director, Division of Epidemiology and Preventive Oncology, Alberta Cancer Board, 6th floor, 9707-1 10 St., Edmonton, AB T5K 2L9 OCTOBER 15, 1992
CAN MED ASSOC J 1992; 147 (8)
1127
will thus focus on silicone implants only in the remainder of this article. The first concern is whether there is an association between cancer (specifically breast cancer) and breast augmentation. Few studies have tried to evaluate this question, although some case reports have been published.46 We are aware of five studies, three involving mail surveys of plastic surgeons.7'9 Although no excess risk of breast cancer was found the strength of the evidence from this type of survey is limited. Two properly conducted large-scale cohort studies have been reported.'0-'2 Both were nonconcurrent linkage studies, and together they accounted for approximately 15 000 women with cosmetic breast augmentation, who were followed for an average of more than 10 years. No excess risk of breast cancer in these women compared with the general population could be demonstrated. In fact the standardized incidence ratios were well below 100%, indicating a deficit of breast cancer among women with implants. This apparent deficit can probably be explained by an a priori lower risk for breast cancer among women who have undergone cosmetic breast augmentation. This would make the comparison with the general population less adequate. Several studies in the United States are under way to address this question, and in Canada the DNHW is planning a large-scale study in Alberta, Ontario and Quebec, which is endorsed by both plastic surgeons and women's interest groups. The conclusion seems justified, however, that implants are not a risk factor for breast cancer in women. Silverstein and associates'3-'5 suggested that implant-related cancers may be more difficult to diagnose and thus be detected at a later stage; this would result in a lower survival rate. This suggestion could not be confirmed by Deapen and Brody"I or by my colleagues and I (unpublished data). The evidence to date suggests that breast implants are not a risk factor for breast cancer and that the survival rate among women with implant-related cancer is not lower than expected. An additional observation supporting the no-association point of view is that no sarcomas were found in all the studies of humans reported to date. The only cancers ever plausibly attributed to silicone were connective tissue sarcomas in rodents susceptible to cancer.'6 Do implants cause an increased risk for other types of cancer? The only published data so far show an increase for lung and vulvar cancers." Preliminary results from the Alberta study (as yet unpublished) do not suggest an increased risk for any type of cancer. Again, this issue will be addressed in several studies that are under way. The second major concern is the potentially increased risk of connective tissue disorders. Diseases such as scleroderma, systemic lupus ery1128
CAN MED ASSOC J 1992; 147 (8)
thematosus, rheumatoid arthritis, Sjogren's syndrome and "human adjuvant disease" have been suggested to be related to silicone breast implants. Unfortunately the literature on this topic is rather ambiguous. No large-scale studies have been done, which are imperative if one wants to evaluate rare disorders. The literature consists of case reports'7'8 and small case series9-2' except for one small, nonconcurrent cohort study.22 The available information provides very little, if any, basis for a causeeffect relation in humans between silicone implants and connective tissue disorders. The DNHW's advisory committee argues that "the reported cases of so-called autoimmune disease in women with implants are far less numerous than would be expected in women without implants. The reported number, even if multiplied 10-fold to account for underreporting of disease, would not equal the expected incidence." Overall, therefore, the conclusion must be that the evidence suggests that no cause-effect relation exists between silicone implants and cancer and that no evidence is available to demonstrate a relation between silicone implants and connective tissue disorders. Does this mean that women who have complaints are hysterical? Certainly not. A small proportion of women will undoubtedly have complaints, and it seems more than likely that these complaints have not been dealt with appropriately in many instances. Do all implants need to be removed? The advisory committee recommends that women without complaints be closely monitored but that implants do not need to be removed. A similar recommendation is made by the FDA. However, it will certainly not be easy to convince the women who have implants that the withdrawal of implants from the market by the FDA does not mean that these devices are dangerous. Explanation is to be offered to women who are seriously concerned or who have complaints or symptoms. This point of view is shared by the FDA, and it seems reasonable. Do breast implants have to be banned completely? Angell23 argued that women should be permitted to continue to receive breast implants, regardless of their participation in studies and the purpose of implantation, as long as they receive the same information as provided to participants in clinical trials. Any medical procedure will have the risk of adverse effects; even an appendectomy has a risk of death, albeit low. Do we therefore ban appendectomies? What we do in these circumstances is weigh the benefits and risks and make a decision. We live with risk.24 If we have to choose between the probability of death from the appendectomy and the risk of septic peritonitis caused by a ruptured appendix, the choice is not very difficult. Similarly, women who consider breast augmentation for whatLE 15 OCTOBRE 1992
ever reason, cosmetic or reconstructive, should be fully informed of the risks and benefits. It is the right of every patient to be fully informed and to fully participate in the decision-making process. If a woman, having evaluated the risks and benefits in her own situation, decides that she wants to have breast augmentation she should be able to. It is reassuring that the DNHW's advisory committee also recommends this, provided several conditions are met. I find it quite disturbing that the FDA allows only women who want an implant for reconstructive reasons the right to an informed decision. This creates the impression that the safety of implants is of less concern to women who already have had breast cancer. Where do we go from here? Several initiatives are under way to collect more information. They should be encouraged, and appropriate resources for such studies should be made available. Until the results of these studies are known, implants should be used with caution, and women should be fully informed about them.
References 1. Canadian Cancer Statistics, National Cancer Institute of Canada, Toronto, 1992 2. Chan SC, Birdsell DC, Gradeen CY: Detection of toluenediamines in the urine of a patient with polyurethane-covered breast implants. Clin Chem 1991; 37: 756-758 3. Expert Panel on the Safety of Polyurethane-covered Breast Implants: Safety of polyurethane-covered breast implants. Can Med Assoc J 1991; 145: 1125-1128 4. Bingham HG, Copeland EM, Hackett R et al: Breast cancer in a patient with silicone breast implants after 13 years. Ann
Plast Surg 1988; 20: 236-237 5. Morgenstern L, Gleischman SH, Michel SL et al: Relation of free silicone to human breast carcinoma. Arch Surg 1985; 120: 573-577 6. Hoopes JE, Edgerton MT, Shelley W: Organic synthetics for augmentation mammoplasty: their relation to breast cancer. PlastReconstrSurg 1967; 39: 263-270 7. Snyderman RK, Lizardo JG: Statistical study of malignancies found before, during or after routine breast plastic operations.
OCTOBER 15, 1992
Plast Reconstr Surg 1960; 25: 253-256 8. Harris HI: Survey of breast implants from the point of view of carcinogenesis. Plast Reconstr Surg 1961; 28: 81-83 9. De Cholnoky T: Augmentation mammoplasty, survey of complications in 10,941 patients by 265 surgeons. Plast Reconstr Surg 1970; 45: 573-577 10. Deapen DM, Pike MC, Casagraade JT et al: The relationship between breast cancer and augmentation mammoplasty: an epidemiologic study. Plast Reconstr Surg 1986; 77: 361-367 11. Deapen DM, Brody GS: Augmentation mammoplasty and breast cancer: a 5-year update of the Los Angeles Study. Plast ReconstrSurg 1992; 89: 660-665 12. Berkel J, Birdsell DC, Jenkins H: Breast augmentation: A risk factor for breast cancer? N Engl J Med 1992; 326: 1649-1654 13. Silverstein MJ, Gierson ED, Gamagami P et al: Breast cancer diagnosis and prognosis in women augmented with silicone gel-filled implants. Cancer 1990; 66: 97-101 14. Silverstein MJ, Handel N, Gamagami P et al: Breast cancer in women after augmentation mammoplasty. Arch Surg 1988; 123: 681-685 15. Silverstein MJ, Gamagami P, Handel N: Missed breast cancer in an augmented woman using implant displacement mammography. Ann Plast Surg 1990; 25: 210-213 16. Oppenheimer BS, Oppenheimer ET, Danishefsky I et al: Further studies of polymers as carcinogenic agents in animals. Cancer Res 1955; 15: 333-340 17. Sergott TJ, Limoli JP, Baldwin CM et al: Human adjuvant disease, possible autoimmune disease after silicone implantation: a review of the literature, case studies and speculation for the future. Plast Reconstr Surg 1986; 78: 104-114 18. Seleznick MJ, Martinez-Osuna P, Espinoza LR et al: Is silicone associated with connective tissue disease? J Fla Med Assoc 1991; 78: 85-87 19. Ostermeyer B, Patten BM: Adjuvant breast disease. Ann Neurol 1991; 30: 271 20. Endo LP, Edwards NL, Longley S et al: Silicone and rheumatic diseases. Semin Arthritis Rheum 1987; 17: 112118 21. Kumagai Y, Shiokawa Y, Medsger TA Jr et al: Clinical spectrum of connective tissue disease after cosmetic surgery. Observations on eighteen patients and a review of the Japanese literature. Arthritis Rheum 1984; 27: 1-12 22. Weisman MH, Vecchione TR, Albert D et al: Connective tissue disease following breast augmentation: a preliminary test of the human adjuvant disease hypothesis. Plast Reconstr Surg 1988; 82: 626-630 23. Angell M: Breast implants. Protection or paternalism [E]? N Engl J Med 1992; 326: 1695-1696 24. British Medical Association: Living With Risk, Wiley, Chichester, England, 1987
CAN MED ASSOC J 1992; 147 (8)
1129
Breast implants: Quo vadis? Hans J. Berkel, MD, PhD reast augmentation was introduced into clinical practice in the early 1 960s and until recently was considered an accepted and safe procedure. In certain areas it was even an approved procedure and therefore payable through health care insurance. Millions of women worldwide have had breast augmentation for cosmetic or reconstructive reasons. No exact data are available for Canada, but, assuming the same frequency in Alberta as in the other provinces, it can be estimated that 150 000 to 200 000 women in this country have received breast implants. Recently major public concerns have arisen about the safety and efficacy of these devices. The media have published numerous articles about the alleged side effects of breast implants. Women's advocacy groups both for and against implants have mushroomed. The US Food and Drug Administration (FDA) held hearings and came out with some ambiguous statements. In the United States a moratorium was imposed on the use of implants early in January 1992. Canada followed suit a few days later. The minister of national health and welfare (DNHW) struck an independent advisory committee to advise him of what action to take regarding the implant controversy. A summary of the committee's report is in this issue (starting on page 1141). If implants prove to have deleterious long-term effects on the health of women, we could face a major public health problem. For example, the lifetime probability of breast cancer for women is 10%.' Assuming a 25% increase in this risk due to implants, breast cancer would develop in 3750 more women in Canada! The concerns thus seem quite justified. What, however, are the scientific facts? The discussions around breast augmentation focus mainly on the long-term health effects. Shortterm complications such as capsular contraction, B
pain, infection and rupture or dislocation of the implant are well known. No firm data exist, however, on either the frequency or the health impact of these problems. In regard to the long-term health effects two issues arise: first, the concern for an increased risk of cancer (specifically breast cancer) and, second, the alleged association between connective tissue disorders (specifically scleroderma) and implants. Although various implant types have been on the market, the main components of all types are silicone (polydimethylsiloxane) polymers as elastomers and gels. Most frequently gel-filled implants are used. The "envelope" surrounding the implant is a silicone elastomer, and the gel is mainly polydimethylsiloxane oil, which is classified as a nonreactive substance. Saline-filled implants have also been used. These consist of a silicone elastomer envelope that can be inflated with the desired volume of sterile saline. To overcome capsular contraction, a well-known complication of silicone implants, an implant covered with polyurethane foam (the Meme implant) was developed. This implant is no longer available in Canada: the manufacturer voluntarily withdrew it from the market because of allegations of carcinogenicity of the breakdown products of polyurethane. These products (2,4- and 2,6-toluenediisocyanate diamines) were discovered in the urine of a patient with Meme implants.2 However, an expert panel coordinated by the CMA, at the request of the DNHW, after reviewing all the evidence concluded that "surgical removal of polyurethane-foam-covered breast implants solely for reasons of potential risk of cancer does not appear to be indicated."3 It will be at least another 5 to 10 years before the issue of increased risk of cancer in
with Meme implants can be resolved, given the long latency period of the carcinogenic process. I
women
Reprint requests to: Dr. Hans J. Berkel, Director, Division of Epidemiology and Preventive Oncology, Alberta Cancer Board, 6th floor, 9707-1 10 St., Edmonton, AB T5K 2L9 OCTOBER 15, 1992
CAN MED ASSOC J 1992; 147 (8)
1127
will thus focus on silicone implants only in the remainder of this article. The first concern is whether there is an association between cancer (specifically breast cancer) and breast augmentation. Few studies have tried to evaluate this question, although some case reports have been published.46 We are aware of five studies, three involving mail surveys of plastic surgeons.7'9 Although no excess risk of breast cancer was found the strength of the evidence from this type of survey is limited. Two properly conducted large-scale cohort studies have been reported.'0-'2 Both were nonconcurrent linkage studies, and together they accounted for approximately 15 000 women with cosmetic breast augmentation, who were followed for an average of more than 10 years. No excess risk of breast cancer in these women compared with the general population could be demonstrated. In fact the standardized incidence ratios were well below 100%, indicating a deficit of breast cancer among women with implants. This apparent deficit can probably be explained by an a priori lower risk for breast cancer among women who have undergone cosmetic breast augmentation. This would make the comparison with the general population less adequate. Several studies in the United States are under way to address this question, and in Canada the DNHW is planning a large-scale study in Alberta, Ontario and Quebec, which is endorsed by both plastic surgeons and women's interest groups. The conclusion seems justified, however, that implants are not a risk factor for breast cancer in women. Silverstein and associates'3-'5 suggested that implant-related cancers may be more difficult to diagnose and thus be detected at a later stage; this would result in a lower survival rate. This suggestion could not be confirmed by Deapen and Brody"I or by my colleagues and I (unpublished data). The evidence to date suggests that breast implants are not a risk factor for breast cancer and that the survival rate among women with implant-related cancer is not lower than expected. An additional observation supporting the no-association point of view is that no sarcomas were found in all the studies of humans reported to date. The only cancers ever plausibly attributed to silicone were connective tissue sarcomas in rodents susceptible to cancer.'6 Do implants cause an increased risk for other types of cancer? The only published data so far show an increase for lung and vulvar cancers." Preliminary results from the Alberta study (as yet unpublished) do not suggest an increased risk for any type of cancer. Again, this issue will be addressed in several studies that are under way. The second major concern is the potentially increased risk of connective tissue disorders. Diseases such as scleroderma, systemic lupus ery1128
CAN MED ASSOC J 1992; 147 (8)
thematosus, rheumatoid arthritis, Sjogren's syndrome and "human adjuvant disease" have been suggested to be related to silicone breast implants. Unfortunately the literature on this topic is rather ambiguous. No large-scale studies have been done, which are imperative if one wants to evaluate rare disorders. The literature consists of case reports'7'8 and small case series9-2' except for one small, nonconcurrent cohort study.22 The available information provides very little, if any, basis for a causeeffect relation in humans between silicone implants and connective tissue disorders. The DNHW's advisory committee argues that "the reported cases of so-called autoimmune disease in women with implants are far less numerous than would be expected in women without implants. The reported number, even if multiplied 10-fold to account for underreporting of disease, would not equal the expected incidence." Overall, therefore, the conclusion must be that the evidence suggests that no cause-effect relation exists between silicone implants and cancer and that no evidence is available to demonstrate a relation between silicone implants and connective tissue disorders. Does this mean that women who have complaints are hysterical? Certainly not. A small proportion of women will undoubtedly have complaints, and it seems more than likely that these complaints have not been dealt with appropriately in many instances. Do all implants need to be removed? The advisory committee recommends that women without complaints be closely monitored but that implants do not need to be removed. A similar recommendation is made by the FDA. However, it will certainly not be easy to convince the women who have implants that the withdrawal of implants from the market by the FDA does not mean that these devices are dangerous. Explanation is to be offered to women who are seriously concerned or who have complaints or symptoms. This point of view is shared by the FDA, and it seems reasonable. Do breast implants have to be banned completely? Angell23 argued that women should be permitted to continue to receive breast implants, regardless of their participation in studies and the purpose of implantation, as long as they receive the same information as provided to participants in clinical trials. Any medical procedure will have the risk of adverse effects; even an appendectomy has a risk of death, albeit low. Do we therefore ban appendectomies? What we do in these circumstances is weigh the benefits and risks and make a decision. We live with risk.24 If we have to choose between the probability of death from the appendectomy and the risk of septic peritonitis caused by a ruptured appendix, the choice is not very difficult. Similarly, women who consider breast augmentation for whatLE 15 OCTOBRE 1992
ever reason, cosmetic or reconstructive, should be fully informed of the risks and benefits. It is the right of every patient to be fully informed and to fully participate in the decision-making process. If a woman, having evaluated the risks and benefits in her own situation, decides that she wants to have breast augmentation she should be able to. It is reassuring that the DNHW's advisory committee also recommends this, provided several conditions are met. I find it quite disturbing that the FDA allows only women who want an implant for reconstructive reasons the right to an informed decision. This creates the impression that the safety of implants is of less concern to women who already have had breast cancer. Where do we go from here? Several initiatives are under way to collect more information. They should be encouraged, and appropriate resources for such studies should be made available. Until the results of these studies are known, implants should be used with caution, and women should be fully informed about them.
References 1. Canadian Cancer Statistics, National Cancer Institute of Canada, Toronto, 1992 2. Chan SC, Birdsell DC, Gradeen CY: Detection of toluenediamines in the urine of a patient with polyurethane-covered breast implants. Clin Chem 1991; 37: 756-758 3. Expert Panel on the Safety of Polyurethane-covered Breast Implants: Safety of polyurethane-covered breast implants. Can Med Assoc J 1991; 145: 1125-1128 4. Bingham HG, Copeland EM, Hackett R et al: Breast cancer in a patient with silicone breast implants after 13 years. Ann
Plast Surg 1988; 20: 236-237 5. Morgenstern L, Gleischman SH, Michel SL et al: Relation of free silicone to human breast carcinoma. Arch Surg 1985; 120: 573-577 6. Hoopes JE, Edgerton MT, Shelley W: Organic synthetics for augmentation mammoplasty: their relation to breast cancer. PlastReconstrSurg 1967; 39: 263-270 7. Snyderman RK, Lizardo JG: Statistical study of malignancies found before, during or after routine breast plastic operations.
OCTOBER 15, 1992
Plast Reconstr Surg 1960; 25: 253-256 8. Harris HI: Survey of breast implants from the point of view of carcinogenesis. Plast Reconstr Surg 1961; 28: 81-83 9. De Cholnoky T: Augmentation mammoplasty, survey of complications in 10,941 patients by 265 surgeons. Plast Reconstr Surg 1970; 45: 573-577 10. Deapen DM, Pike MC, Casagraade JT et al: The relationship between breast cancer and augmentation mammoplasty: an epidemiologic study. Plast Reconstr Surg 1986; 77: 361-367 11. Deapen DM, Brody GS: Augmentation mammoplasty and breast cancer: a 5-year update of the Los Angeles Study. Plast ReconstrSurg 1992; 89: 660-665 12. Berkel J, Birdsell DC, Jenkins H: Breast augmentation: A risk factor for breast cancer? N Engl J Med 1992; 326: 1649-1654 13. Silverstein MJ, Gierson ED, Gamagami P et al: Breast cancer diagnosis and prognosis in women augmented with silicone gel-filled implants. Cancer 1990; 66: 97-101 14. Silverstein MJ, Handel N, Gamagami P et al: Breast cancer in women after augmentation mammoplasty. Arch Surg 1988; 123: 681-685 15. Silverstein MJ, Gamagami P, Handel N: Missed breast cancer in an augmented woman using implant displacement mammography. Ann Plast Surg 1990; 25: 210-213 16. Oppenheimer BS, Oppenheimer ET, Danishefsky I et al: Further studies of polymers as carcinogenic agents in animals. Cancer Res 1955; 15: 333-340 17. Sergott TJ, Limoli JP, Baldwin CM et al: Human adjuvant disease, possible autoimmune disease after silicone implantation: a review of the literature, case studies and speculation for the future. Plast Reconstr Surg 1986; 78: 104-114 18. Seleznick MJ, Martinez-Osuna P, Espinoza LR et al: Is silicone associated with connective tissue disease? J Fla Med Assoc 1991; 78: 85-87 19. Ostermeyer B, Patten BM: Adjuvant breast disease. Ann Neurol 1991; 30: 271 20. Endo LP, Edwards NL, Longley S et al: Silicone and rheumatic diseases. Semin Arthritis Rheum 1987; 17: 112118 21. Kumagai Y, Shiokawa Y, Medsger TA Jr et al: Clinical spectrum of connective tissue disease after cosmetic surgery. Observations on eighteen patients and a review of the Japanese literature. Arthritis Rheum 1984; 27: 1-12 22. Weisman MH, Vecchione TR, Albert D et al: Connective tissue disease following breast augmentation: a preliminary test of the human adjuvant disease hypothesis. Plast Reconstr Surg 1988; 82: 626-630 23. Angell M: Breast implants. Protection or paternalism [E]? N Engl J Med 1992; 326: 1695-1696 24. British Medical Association: Living With Risk, Wiley, Chichester, England, 1987
CAN MED ASSOC J 1992; 147 (8)
1129
