The relationship between cancer and breast implants has been controversial from the outset. Several studies have attempted to quantify the risks but all have major defects and implant-induced malignancies remain prominent concerns in breast augmentation within mainstream scientific and medical communities. Widespread promotion of breast augmentation by segments of the surgical community and a specialized part of the biomedical industry was based on the assertion that cosmetic surgery of the breast was a lucrative and promotable business without significant risk. In spite of the extensive use of breast augmentation implants and the large number of individuals subjected to the technology over more than 40 years, there is still no firm answer on its long term cancer risks.

Many studies establishing physico-chemical connections between prosthetic by-products and atypia exist and strongly support the probability of such adverse impact with a latency of several decades. More recent studies have attempted to quantify the risks epidemiologically but statistical tools appear inappropriate for the study of problems where there is a dominant background of naturally occurring disease, as is the case for breast cancer. The situation is analogous to receiving weak radio signals in environments where there is very elevated background noise.

The medical and scientific literature supports a connection between atypia and repeated surgery at the same site, proliferative scar tissue accumulation, wound contamination with foreign materials, protracted infections by select micro-organisms and foreign body reactions surrounding solid plastics and some metal objects. Most of this information is based on animal studies supplemented by anecdotal reports on human subjects. Occupational medicine and environmental health studies on chemical carcinogenesis further support the belief of harmful and possibly carcinogenic impact of ill-conceived implants containing aggressive entities.

Elaborate studies claiming absence of excess malignancy amongst users of mammary prosthetic systems can also be found. However, the studies are unconvincing; a cohort of cosmetic surgery subjects is not a typical female population and thus the epidemiology of cancer amongst breast implant users is not easily interpreted. The background of breast cancer is very elevated in North American populations and varies widely with age, economic status and geographic location. Epidemiological studies comparing tumor occurrence amongst different sub-groups can be easily distorted when information on the impact of elective procedures such as breast augmentation is sought. There are problems with reporting patterns and user follow-up. The data can also be vitiated by disregarding the type of implants, the dwell time or age-related and socio-economic factors. Incidents of unethical publication control practices have also been documented in that area and further reduce the credibility of some of the published material.

Augmentation of the breast is sought primarily by younger women. It induces a wide range of grossly evident local injuries, diseases and complications. However, malignancies tend to be late occurrences and are not easily correlated to procedures carried out many years before. The analysis of tumor occurrence amongst implant users is not straightforward.

Epistemology or the study of specific cases of disease such as cancer in a population of implant users would be more convincing in demonstrating oncologic phenomena from the use of breast implants. The characteristics of tumors which develop in the vicinity of implants are frequently unusual and support causative links between cancers and poorly manufactured implants or deficient surgical practices. Devices with large amounts of effluents and bioavailable degradation products emerge as probable injurious vectors. Some of these studies were carried out by the implant industry circa 1960-70 but were only released in the nineties.

There is a biochemical and pharmacological basis for tumor induction by poorly engineered and incorrectly formulated prosthetic systems. Animal studies demonstrate initiation of tumors by bioreactive substances of the same generic type as breast implant impurities. Many of these substances induce free radicals or facilitate cross-reactions between adventitious products and proteins responsible for cell development and repair of tissue. Chemical reactants of this kind have an ability to modify surrounding tissue by random initiation of free radical processes. Similar phenomena occur via exposure to ionizing radiation. Free radical reactions and radiolytic cleavage and reassembly of fragmented biological entities are associated with oncogenic processes. The creation of deviant biological entities which can later become tumor precursors is believed to occur as a result of chemical transformations on proteins. Many substances found in low quality plastic materials have such properties.

The healing process which follows the implantation of foreign systems in living organisms culminates in formation of capsules. These arrays of connective tissue structures normally surround implanted objects. They are thin, elastic membranes of connective tissue when implants are chemically stable, well designed and devoid of grossly bioavailable impurities. Commercial breast implants do not have the same behavior. Whereas capsule formation is deemed to be a normal physiologic repair phenomenon, for breast implants it is a pathological situation.

Capsules form rapidly in the early stages and consist primarily of connective tissue which attempts to insulate the implant and its impurities from the surroundings. As the capsules age, they become thicker in some parts and may resorb totally in other areas. Eventually they remodel according to patterns which suggest that the implant surface and its impurities controls the process and that different parts of the material influence the morphology of the capsule to different degrees. Point-to-point variations in capsule morphology are the rule rather than the exception. Tissue contiguous to shell patches and other heterogeneous surfaces of implants such as fixation fabric and orientation appendages of different composition frequently show drastically different tissue phenomena visible on gross examination of capsules. If capsules can vary from point-to-point on an implant, then variations in the type of cellular activity induced or promoted by implants are also demonstrated. Thus, the probability of finding tumor-inducing sites within implant surfaces is significant.

Many prosthetic substances found in breast implants are demonstrably inimical to living tissue. Some are outright necrotic. Their release is associated with proximal and frequently distal destruction of tissue. There is secondary redeposition of necrotic by-products and mineralization of the implant-tissue interface. Capsules may be similar to scar tissue in structure and may have analogous properties to repair tissue but after many years in situ, implants acquire the ability to subject the tissue interface to repeated chemical and mechanical injury, a situation empirically connected with certain classes of atypia.

The capsules eventually lose their water permeability as the implant site matures. They acquire the capacity to concentrate reactive impurities released by defective implants in the immediate vicinity of tumor-vulnerable, chronically injured scar tissue. The capsules impede irrigation of the tissue and minimize the transport of soluble toxic metabolites from the necrotic tissue. They also limit the free movement of biological entities responsible for identification and catabolysis of deviant cells.

These factors are expected to militate strongly towards development of atypical tissue over the long term. There is thus a strong basis to expect the occurrence of tumors in the vicinity of implants. The poor quality and the high levels of reactive impurities, including carcinogenic and necrotic entities encountered in commercial breast implants significantly magnify such risks and the risks are expected to increase with dwell time, in particular amongst the more vulnerable users of such implants, some of whom would have been subjected to prophylactic mastectomies because of familial factors.

Type and Role of Impurities:

It is generally believed that most adverse reactions from implants at the cellular level occur through soluble intermediates. Thus, solubility ensures bioavailability and enhances the range of effect well beyond the implant boundary. Simple chemical analysis of implant released entities document hundreds of compounds in significant quantities. These compounds may be in small quantities when referenced to the total body weight of the user. At the implant interface, they exist in extremely concentrated forms. Thus, the risks from solubles released by a prosthetic system cannot be based on gross mass transfer equations which assume dilution of the substances throughout the organism. Calculation of risks further requires knowledge on the type and amounts of solubles in the vicinity of implants and the metabolic route. The pharmacokinetics of injury is expected to be dominated by low molecular weight entities which are habitually more bioavailable. Substances formed in situ through degradation and cross-reactions are even more of concern as these products tend to be more reactive.

Orally ingested compounds do not behave in the same way. The substances are instantly diluted by fluid media in the digestive tract and their absorption is further limited by the permeability of the digestive organs. Nevertheless and with few rare exceptions, it is generally believed that soluble intermediates are the responsible vectors for injury from oral intake of injurious substances. Keynote factors include the large dilution of the dose and the absence of mechanical effects which would alter the pattern of absorption.

Focal toxicological and mechano-pharmacologic effects dominate injury from implant-borne substances. The concentration of these substances at cellular interfaces is expected to promote proliferation of aberrant cells. Disaggregation and dispersion of implant surfaces into finely divided solids further potentiate the role of solubles at the interface by stimulating phagocytotic activity which is associated with aggressive metabolites of their own. Chronic effects taking place over many years suggest longer latencies for observable adverse effects.

Commercial plastics used for breast implants are not pure compounds. They are mixtures of high and low molecular weight solids and liquids. Their synthesis requires free radical initiators and highly reactive catalytic systems. For many commercial products, the technology of fabrication is also defective. It precludes exhaustive purification of the materials used at the surface of the prosthesis and in the core. Even long after the devices are finished, the reactions continue and residual reactants interact to form a rising background of impurities.

Composite and assembled prostheses made of different, frequently incompatible materials using coarse technologies make matters worse. Biodegradable coatings frequently created by design or by accident on the surface of implants have other families of residuals associated with substances which are frequently unsuited for human implantation. Impurities from formulated plastics used in breast implants have consistently been a concern with reference to induction of atypical tissue because many of these substances are inherently atypia-inducing. Low molecular weight entities present in prosthetic systems or formed incidental to storage or degradation in vivo fit this category.

Conventional silicone-based breast prostheses include reactants with biologically aggressive properties such as platinum-based organo-metallics and peroxides. The mixtures can incorporate cyclic silicon-containing intermediates such as cyclosiloxanes with a capacity to interact with biological substances. These intermediates are almost universally used in prosthetic silicones and are not completely removed by the processing conditions. Other impurities arising from the synthesis of silicone-based materials are lipid soluble and have estrogen-like activity with indirect roles in modifying the behavior of cells in proximity with the implant. Thus, they are deemed to have potential for modulating atypical cell behavior within tissue. These substances constitute a substantial fraction of gel-based prostheses and can be present on the surface of elastomeric materials used in breast prostheses.

Polyurethane foam core and foam-coated implants constitute a special sub-class of devices where effluents are produced in large quantities and where the composition of such effluents is modified by the capsule environment. Solubles include aromatic amines and metabolic derivatives such as acetylated aminotoluenes, some of which are documented mutagens and suspected carcinogens under conditions of chronic exposure. Residues also include unreacted isocyanates and adducts from acidic components of silicone-based adhesives catalyzed with peroxides. Other impurities include oils, detergents, acidic substances from adhesives and adipate esters. These reactive intermediates are largely formed in situ. Thus, they are ‘nascent’ and are at their most reactive state within the biological environment where the implant is expected to function.