The Breast Tumor Microenvironment: Could Silicone Breast Implant Elicit Breast Carcinoma?

Abstract

Complications related to breast implants have received much attention recently. Breast implant-associated anaplastic large cell lymphoma, silicone-induced granuloma of breast implant capsule, and breast implant illness are the main complications reported in the medical literature. However, the literature contains limited evidence regarding the possibility of silicone implants eliciting breast carcinoma. In this manuscript, we propose a theory in which the immune response to silicone breast implant gel bleeding acts as a triggering point for tumor oncogenesis in breast tissue. This hypothesis is derived from our findings of a case of invasive and undifferentiated medullary carcinoma in a patient with a silicone breast implant. The following concepts have been used to support this theory: 1) silicone bleeding from intact breast implants; 2) metaplasia: an adaptation to injury and precursor to dysplasia and cancer; 3) T-cell dysfunction in cancer immunity; 4) inhibitory cells in the tumor microenvironment (TME); 5) morphogenesis and bauplan; and 6) concepts underlying medullary carcinoma. We propose that the inflammatory process in response to silicone particles in the pericapsular glandular tissue favors the development of cellular mutations in specialized epithelial cells. This reverse morphogenesis could have resulted in breast carcinoma of the medullary type in the present case.

Keywords:

• breast implant-associated anaplastic large cell lymphoma
• BIA-ALCL
• breast implant illness
• BII
• silicone granuloma
• breast cancer
• breast implant

Future Perspectives

We hope that this theory will lead to further studies correlating breast implants with breast carcinomas. For this, it would be necessary to identify SIGBIC findings in preoperative examinations to investigate the presence of foamy histiocytes on microscopy by pathologists and the microscopic evaluation of the integrity of the silicone implant surface in patients with suspicious lesions in the pericapsular implant space.

Our theory proposed that free silicone could elicit epithelial metaplasia/dysplasia, which could vary in the host response to an external antigen, from more differentiated to undifferentiated tumors. Since this tumor is probably antigen dependent, its treatment can be personalized. Considering these findings, the safety of breast implants must be questioned, given the complexity of the triggered immune response’s complications.

Abbreviations

BIA-ALCL, breast implant-associated anaplastic large cell lymphoma; BMRI, breast magnetic resonance; SIGBIC, silicone-induced granuloma of breast implant capsule; BII, breast implant illness; FDA, Food and Drug Administration; PET-CT, positron-emission tomography; US, ultrasonography; ADM, acinar-ductal metaplasia; PanIN, pancreatic intraepithelial neoplasia; IL, interleukin; STAT3, signal transducers and activators of transcription 3; TNF, tumor necrosis factor; CCL5, CC motif chemokine 5; MMPs, macrophage-released matrix metalloproteinases; SHH, sonic hedgehog; Teff, stroma in the transcription factor ETS2 T cells; TCR, T cell receptor; NFAT, nuclear factor f activated T cells; SPRY2, sprouty homolog 2; PD-1, programmed cell death protein; Tex, T cell exhaustion; TME, tumor microenvironment; Treg cells, regulatory T cell; TAMs, tumor-associated macrophages; MDSCs, myeloid-derived suppressor cells; TGF-B, transforming growth factor-BETA; TIGIT, T cell immunoreceptor with Ig and ITIM domains; MC, medullary carcinoma; ASIA, autoimmune/inflammatory syndrome induced by adjuvants.

Disclosure

The authors report no conflicts of interest in this work.