Breast reconstruction with biological graft : clinical outcomes in the setting of breast cancer treatment

The overall aim of this thesis was to investigate the use of acellular dermal matrix (ADM) in implant-based breast reconstructions (IBBR) in the setting of breast cancer treatment. ADM refers to a surgical mesh developed from human or animal skin, and was initially applied in surgeries where soft tissue was deficient (e.g., hernia repair and treatment of burns). In the past few years, there has been a substantial increase in demand of ADM products for use in IBBR, and in many institutions ADM is a cornerstone in these procedures. The rationale for applying ADM in IBBR was initially two-fold: provide soft tissue coverage with implant support, and convert two-stage surgeries into one-stage procedures. In doing so, aesthetic outcomes after IBBR were said to improve, and breast reconstructions with implants would potentially require fewer overall procedures. In this context, the randomized trial this thesis is based upon, was initiated to evaluate the use of a biological mesh (xenograft) in IBBR. In the trial, women with breast cancer planned for mastectomy and immediate IBBR, were randomly allocated to either IBBR with ADM or to IBBR without ADM.

Due to emerging reports concerning a potential relationship between ADM and harm, the shortterm (complications within six months) safety of ADM-assisted IBBR was investigated. In study I, we found ADM not to be associated with an increased risk of reconstructive failure, compared to conventional IBBR without ADM, but linked to more surgical adverse events requiring reoperations. We further explored whether using ADM would translate into improved health-related quality of life (HRQOL), by means of superior aesthetic outcomes as viewed by the patient, compared to conventional IBBR without ADM. In study II, we found a tendency of improved aesthetic outcomes favoring ADM-assisted IBBR, compared to conventional IBBR without ADM, measured at six months after reconstruction. However, the differences were minor, and we were unable to confirm any advantages of ADM with respect to HRQOL and self-perceived aesthetics. In study III, HRQOL and patient-reported aesthetic outcomes were also assessed, but with a two-year follow-up. Again, we failed to find an advantage of ADM-augmented IBBR with regard to patient-perceived aesthetics or HRQOL. With implant-based breast reconstructions regularly involving additional surgeries, the primary trial endpoint was presented in study III, i.e., comparing reoperation rates between IBBR with and without ADM. The outcome of this study revealed that ADM-assisted IBBR, compared to conventional IBBR without ADM, did not reduce the number of reoperations within a followup time of two years. In study IV, we evaluated whether IBBR augmented with ADM would improve aesthetics, measured as physician-reported scores at two years. Results from this study did not support a benefit of using ADM in IBBR.

In summary, outcomes from this randomized trial performed in a breast cancer setting indicated ADM being associated with increased risk for complications compared to IBBR without ADM. We were unable to confirm the proposed benefit for acellular dermal matrix in reducing the number of surgical procedures, or improving health-related quality of life and patient-reported aesthetic outcomes, when used in immediate implant-based breast reconstructions.

List of scientific papers

I. Lohmander F, Lagergren J, Roy PG, Johansson H, Brandberg Y, Eriksen C, Jan Frisell. Implant Based Breast Reconstruction With Acellular Dermal Matrix: Safety Data From an Open-label, Multicenter, Randomized, Controlled Trial in the Setting of Breast Cancer Treatment. Annals of Surgery. 2019;269(5):836-41.
https://doi.org/10.1097/SLA.0000000000003054

II. Lohmander F, Lagergren J, Johansson H, Roy PG, Frisell J, Brandberg Y. Quality of life and patient satisfaction after implant-based breast reconstruction with or without acellular dermal matrix: randomized clinical trial. British Journal of Surgery Open. 2020;4(5):811-20.
https://doi.org/10.1002/bjs5.50324

III. Lohmander F, Lagergren J, Johansson H, Roy PG, Brandberg Y, Frisell J. Effect of immediate implant-based breast reconstruction after Mastectomy With and Without Acellular Dermal Matrix Among Women With Breast Cancer: A Randomized Clinical Trial. JAMA Netw Open. 2021;4(10):e2127806.
https://doi.org/10.1001/jamanetworkopen.2021.27806

IV. Lohmander F, Johansson H, Roy PG, Brandberg Y, Frisell J, Lagergren J. Aesthetic outcomes following implant-based immediate breast reconstruction with biological graft – Physician-reported results from a randomized study. [Manuscript]