Mastectomy and breast reconstruction in the modern era: the role of neoadjuvant therapies and regenerative surgery

Abstract

Complete surgical resection with disease free margins remains the cornerstone of effective breast cancer treatment. Breast cancer management continues to evolve with the development of more sophisticated techniques of mastectomy and breast reconstruction, and more widespread use of adjuvant and neoadjuvant treatments including chemotherapy and radiotherapy. The aim of the work undertaken for this thesis was to investigate the evolving management of breast cancer from a surgical perspective. This includes assessment of factors such as the impact the introduction of neoadjuvant chemotherapy has had on surgical practice and the potential impact that further changes to treatment sequence may have on surgical practice, with a specific focus on mastectomy and breast reconstruction. This work also aimed to investigate novel regenerative approaches to post mastectomy breast reconstruction utilising autologous adipose derived stem cells and tissue engineering strategies. Evolution in surgical practice was examined by reviewing breast cancer cases treated surgically at Galway University Hospital over a ten year period. This revealed an increase in the use of neoadjuvant chemotherapy from 2005 to 2014, with a corresponding increase in the rate of breast conserving surgery. However, mastectomy remains an integral component of surgical treatment in this patient cohort with a mastectomy rate of approximately 55%. The evolution of mastectomy and reconstruction practices at Galway University Hospital from 2004 to 2014 was investigated. The rate of post mastectomy breast reconstruction increased over the study period. Preference for autologous reconstructive procedures at the beginning of the study period changed over time with implant reconstruction becoming the most commonly utilised method of breast reconstruction later in the study. Clinicopathologic and treatment factors also influenced surgical practice in relation to post-mastectomy breast reconstruction. Neoadjuvant chemo-radiation is currently being investigated as a novel treatment sequence in breast cancer. A pilot study was carried out at Galway University Hospital comparing the outcomes of patients being treated with neoadjuvant chemo-radiation to patients being treated with traditional post-mastectomy adjuvant radiotherapy. This study found that neoadjuvant chemo-radiation is a feasible method of delivering breast cancer treatment in shorter treatment times, without increasing surgical complication rates and while sparing the newly reconstructed breast from radiation. Limitations of current methods of breast reconstruction have directed research towards adipose tissue engineering strategies. Adipose derived stem cells (ADSCs) have become the gold standard cell source for tissue engineering. This study investigated the potential for autologous adipose derived stem cells to be harvested from breast cancer patients. A stem cell population was isolated from various adipose tissue sources in patients treated and not treated with neoadjuvant chemotherapy. Cell populations were assessed for their adipogenic potential for suitability for use in adipose tissue engineering. Genetic expression and cytokine secretion analysis was used to assess oncological safety of the isolated ADSCs. ADSCs isolated from breast adipose tissue of breast cancer patients exhibit features which may raise concern relating to their oncological safety for use in breast regeneration. However, breast adipose tissue from patients treated with neoadjuvant chemotherapy is potentially a safer source of autologous ADSCs. Breast adipose tissue engineering strategies require suitable scaffold biomaterials. An injectable hyaluronic acid hydrogel was assessed for its ability to be seeded with abdominal lipoaspirate with or without the stromal vascular fraction of adipose tissue. A hyaluronic acid hydrogel with a concentration of 2% w/v, at a 2x crosslinking density, loaded with 400µl abdominal lipoaspirate, with or without the stromal vascular fraction of adipose tissue, was shown to possess biomechanical properties suitable for breast adipose tissue engineering. Mastectomy remains a mainstay of breast cancer treatment. For patients undergoing mastectomy, breast reconstruction is proven to improve psychosocial and quality of life outcomes. Therefore, optimising methods of breast reconstruction is essential in order to ensure the optimal patient quality of life outcomes. Alterations to systemic and local treatment sequence, along with tissue engineering and regenerative surgery techniques are important developments in the further evolution of breast cancer management.