Breast Cancer Detection Among Women With Cosmetic Implants
Breast Cancer Detection Among Women With Cosmetic Implants
This systematic review suggests that women with cosmetic breast implants have later stage tumors at diagnosis of breast cancer. In our second meta-analysis, the results show a higher risk of breast cancer specific mortality among women with breast cancer who have implants compared with women with breast cancer without implants. Nevertheless, the overall estimate should still be interpreted with caution because this meta-analysis included a relatively small number of studies. Of concern, three of five studies had unadjusted hazard ratios (not adjusted for age at diagnosis, or period of diagnosis) and all five studies were unadjusted for other potential confounding factors such as body mass index, which could translate into a biased estimate of the summary hazard ratio. A lack of adjustment for body mass index has previously been shown to lead to underestimation of the association between cosmetic breast implants and breast cancer mortality. Moreover, one study included in this meta-analysis assessed overall mortality rather than breast cancer specific mortality, which could have biased our summary estimate towards the null. The small number of studies and insufficient amount of follow-up time in these studies are suspected to limit statistical power to clearly evaluate survival rate patterns among augmented women. Given the limited evidence, no conclusion regarding breast cancer specific survival can be drawn and continued follow-up to further evaluate this question is particularly relevant.
The finding of later stage tumors at diagnosis of breast cancer in women with implants can be explained by multiple mechanisms, the first being that both silicone and saline implants create radio-opaque shadows on mammograms, which impair the visualization of breast tissue. The amount of parenchymal breast tissue obscured at mammography by the implant is known to be between 22% and 83%. Insufficient compression of the breast to visualize the parenchyma and the production of implant related artifacts on the film can also make interpretation of mammographic examinations difficult in women with augmented breasts. Additionally, capsular contracture, which develops in about 15-20% of women with implants, has been shown to reduce mammographic sensitivity by 30-50%. Furthermore, specific characteristics of breast implants might affect the detection of breast cancer. Specifically, implants placed under the breast glands (subglandular placement), because of their proximity with breast tissue, are suspected to obstruct mammographic visualization of the breast more than those with submuscular placement. However, to date, only one study has been able to evaluate the stage distribution of breast cancer according to implant placement. Results from this study were inconclusive.
Despite the fact that implant displacement techniques are widely used with mammography, studies suggest that breast tissue is still not adequately visualized. Recent reports suggest that magnetic resonance imaging of the breast may be a helpful diagnostic tool for women with breast implants; it allows examination of all breast tissue surrounding the implant, and so has greater sensitivity than mammography. However, insufficient evidence exists to support the use of magnetic resonance imaging in the diagnosis and prognosis of breast cancer, which warrants further research.
Stratification and meta-regression models showed that no potential factors seem to unduly affect the results of the study. When we calculated a summary effect for the three studies that used women who had received other elective cosmetic surgery (chemical peel or dermabrasion, coronal brow lift, otoplasty, rhinoplasty, rhytidectomy, or blepharoplasty) as the comparison group, we observed a stronger association than the one obtained when the general female population was used as the comparison group. Women with other cosmetic surgery are recognized in the scientific literature as being a more appropriate comparison group when studying the health effects associated with cosmetic breast implants, because they tend to be more similar in terms of sociodemographic and lifestyle factors as well as health consciousness than are women in the general population. A previous study conducted in the United States showed no significant differences with respect to family income between women with cosmetic breast implants and women with other cosmetic surgery, which supports the notion that both groups are of similar socioeconomic status. For example, women seeking cosmetic surgeries could have better screening and self examination practices than women in the general female population, which would translate into higher chances of a breast tumor being diagnosed after screening mammography if one is present. This suggests that using other women with cosmetic surgery would be more adequate in terms of controlling for potential confounders. Moreover, studies with adjustment for confounding factors such as the age of breast cancer at diagnosis yielded statistically significant effects that were stronger than those without adjustment. One study showed that a lack of adjustment for the age at which breast cancer was diagnosed underestimates the measure of association. This outlines the importance of providing adjusted estimates. In meta-regression models, we were not able to detect the modifying effect of the type of comparison group and the adjustment for cofactors, but a lack of statistical power due to the small number of studies may explain why the above differences in odds ratios are not statistically significant.
The long term presence of cosmetic breast implants has been hypothesized to cause atrophy, thinning, and compression of the breast parenchyma, which may facilitate the detection of palpable breast tumors on physical examination. The breast implants could serve as a base against which the mass may be more likely to be differentiated. This suggests that tumors of equal size may be more easily palpated in patients with implants, especially for implants placed in the subglandular position, and this may compensate somewhat for the potential impairment of mammography. However, very few studies have evaluated this question, providing no conclusive results. Furthermore, the fact that women with implants present more often with palpable tumors could also be because of the smaller native breast volumes making tumors more pronounced with palpation.
Our study has several limitations specific to our analysis and to the different methods used across studies. For instance, certain studies used in both meta-analyses included cases of in situ breast cancer because we were not able to exclude them on the basis of the limited information available in the papers. This could have resulted in a non-differential misclassification bias of the outcome variable. One study, by Clark et al, was responsible for all observed heterogeneity in the analysis of stage distribution of breast cancer at diagnosis. We believe that the results of this publication may be affected by a selection bias, which is supported by the quality assessment scale (supplemental file in web appendix). Moreover, a previous publication also raised the concern that the results of the study by Clark et al may have been influenced by a selection bias. Pooling results from several observational studies has the advantage of increasing statistical power but does not increase internal validity. Misclassification bias, selection bias, and assessment of confounding affecting individual studies will also affect the meta-analyses. Misclassification biases within each study could also be a factor affecting study specific measures of association and consequently our pooled effect. For example, the identification of deaths from breast cancer could be affected by data quality problems such as a misclassification of the cause of death. This could result in biased estimates of breast cancer specific survival, resulting in an underestimation of our pooled effect. Although we have evaluated the quality of the studies with an assessment scale, no threshold scores were available to distinguish between "good" and "poor" quality studies, which could limit our results as we may have included studies of poorer quality in our analyses. Another limitation of our study could be related to the methods used to pool the hazard ratios from available data in each study, which may have underestimated the variance of the estimates.
Our results should be interpreted with caution, considering the current gaps and limitations in the available literature. The accumulating evidence suggests that women with cosmetic breast implants who develop breast cancer have an increased risk of being diagnosed as having non-localized breast tumors more frequently than do women with breast cancer who do not have implants. Moreover, current evidence also suggests that cosmetic breast implants adversely affect breast cancer specific survival following the diagnosis of such disease. Further investigations are warranted into the long term effects of cosmetic breast implants on the detection and prognosis of breast cancer, adjusting for potential confounders.
Discussion
This systematic review suggests that women with cosmetic breast implants have later stage tumors at diagnosis of breast cancer. In our second meta-analysis, the results show a higher risk of breast cancer specific mortality among women with breast cancer who have implants compared with women with breast cancer without implants. Nevertheless, the overall estimate should still be interpreted with caution because this meta-analysis included a relatively small number of studies. Of concern, three of five studies had unadjusted hazard ratios (not adjusted for age at diagnosis, or period of diagnosis) and all five studies were unadjusted for other potential confounding factors such as body mass index, which could translate into a biased estimate of the summary hazard ratio. A lack of adjustment for body mass index has previously been shown to lead to underestimation of the association between cosmetic breast implants and breast cancer mortality. Moreover, one study included in this meta-analysis assessed overall mortality rather than breast cancer specific mortality, which could have biased our summary estimate towards the null. The small number of studies and insufficient amount of follow-up time in these studies are suspected to limit statistical power to clearly evaluate survival rate patterns among augmented women. Given the limited evidence, no conclusion regarding breast cancer specific survival can be drawn and continued follow-up to further evaluate this question is particularly relevant.
Possible Explanations for Findings
The finding of later stage tumors at diagnosis of breast cancer in women with implants can be explained by multiple mechanisms, the first being that both silicone and saline implants create radio-opaque shadows on mammograms, which impair the visualization of breast tissue. The amount of parenchymal breast tissue obscured at mammography by the implant is known to be between 22% and 83%. Insufficient compression of the breast to visualize the parenchyma and the production of implant related artifacts on the film can also make interpretation of mammographic examinations difficult in women with augmented breasts. Additionally, capsular contracture, which develops in about 15-20% of women with implants, has been shown to reduce mammographic sensitivity by 30-50%. Furthermore, specific characteristics of breast implants might affect the detection of breast cancer. Specifically, implants placed under the breast glands (subglandular placement), because of their proximity with breast tissue, are suspected to obstruct mammographic visualization of the breast more than those with submuscular placement. However, to date, only one study has been able to evaluate the stage distribution of breast cancer according to implant placement. Results from this study were inconclusive.
Despite the fact that implant displacement techniques are widely used with mammography, studies suggest that breast tissue is still not adequately visualized. Recent reports suggest that magnetic resonance imaging of the breast may be a helpful diagnostic tool for women with breast implants; it allows examination of all breast tissue surrounding the implant, and so has greater sensitivity than mammography. However, insufficient evidence exists to support the use of magnetic resonance imaging in the diagnosis and prognosis of breast cancer, which warrants further research.
Stratification and meta-regression models showed that no potential factors seem to unduly affect the results of the study. When we calculated a summary effect for the three studies that used women who had received other elective cosmetic surgery (chemical peel or dermabrasion, coronal brow lift, otoplasty, rhinoplasty, rhytidectomy, or blepharoplasty) as the comparison group, we observed a stronger association than the one obtained when the general female population was used as the comparison group. Women with other cosmetic surgery are recognized in the scientific literature as being a more appropriate comparison group when studying the health effects associated with cosmetic breast implants, because they tend to be more similar in terms of sociodemographic and lifestyle factors as well as health consciousness than are women in the general population. A previous study conducted in the United States showed no significant differences with respect to family income between women with cosmetic breast implants and women with other cosmetic surgery, which supports the notion that both groups are of similar socioeconomic status. For example, women seeking cosmetic surgeries could have better screening and self examination practices than women in the general female population, which would translate into higher chances of a breast tumor being diagnosed after screening mammography if one is present. This suggests that using other women with cosmetic surgery would be more adequate in terms of controlling for potential confounders. Moreover, studies with adjustment for confounding factors such as the age of breast cancer at diagnosis yielded statistically significant effects that were stronger than those without adjustment. One study showed that a lack of adjustment for the age at which breast cancer was diagnosed underestimates the measure of association. This outlines the importance of providing adjusted estimates. In meta-regression models, we were not able to detect the modifying effect of the type of comparison group and the adjustment for cofactors, but a lack of statistical power due to the small number of studies may explain why the above differences in odds ratios are not statistically significant.
The long term presence of cosmetic breast implants has been hypothesized to cause atrophy, thinning, and compression of the breast parenchyma, which may facilitate the detection of palpable breast tumors on physical examination. The breast implants could serve as a base against which the mass may be more likely to be differentiated. This suggests that tumors of equal size may be more easily palpated in patients with implants, especially for implants placed in the subglandular position, and this may compensate somewhat for the potential impairment of mammography. However, very few studies have evaluated this question, providing no conclusive results. Furthermore, the fact that women with implants present more often with palpable tumors could also be because of the smaller native breast volumes making tumors more pronounced with palpation.
Limitations of Study
Our study has several limitations specific to our analysis and to the different methods used across studies. For instance, certain studies used in both meta-analyses included cases of in situ breast cancer because we were not able to exclude them on the basis of the limited information available in the papers. This could have resulted in a non-differential misclassification bias of the outcome variable. One study, by Clark et al, was responsible for all observed heterogeneity in the analysis of stage distribution of breast cancer at diagnosis. We believe that the results of this publication may be affected by a selection bias, which is supported by the quality assessment scale (supplemental file in web appendix). Moreover, a previous publication also raised the concern that the results of the study by Clark et al may have been influenced by a selection bias. Pooling results from several observational studies has the advantage of increasing statistical power but does not increase internal validity. Misclassification bias, selection bias, and assessment of confounding affecting individual studies will also affect the meta-analyses. Misclassification biases within each study could also be a factor affecting study specific measures of association and consequently our pooled effect. For example, the identification of deaths from breast cancer could be affected by data quality problems such as a misclassification of the cause of death. This could result in biased estimates of breast cancer specific survival, resulting in an underestimation of our pooled effect. Although we have evaluated the quality of the studies with an assessment scale, no threshold scores were available to distinguish between "good" and "poor" quality studies, which could limit our results as we may have included studies of poorer quality in our analyses. Another limitation of our study could be related to the methods used to pool the hazard ratios from available data in each study, which may have underestimated the variance of the estimates.
Conclusions and Implications
Our results should be interpreted with caution, considering the current gaps and limitations in the available literature. The accumulating evidence suggests that women with cosmetic breast implants who develop breast cancer have an increased risk of being diagnosed as having non-localized breast tumors more frequently than do women with breast cancer who do not have implants. Moreover, current evidence also suggests that cosmetic breast implants adversely affect breast cancer specific survival following the diagnosis of such disease. Further investigations are warranted into the long term effects of cosmetic breast implants on the detection and prognosis of breast cancer, adjusting for potential confounders.
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