Organ transplantation has significant survival and quality of life benefits compared to bestmedical (non-transplant) management. One of the most important factors that has allowed for prolonged allograft survival has been the advances in immunosuppressive regimens. Although de novomalignancies are known long-term complications of organ transplantation, breast cancer is not increased in the transplant population when compared against age-matched SEER general population data. Incidentrates in published literature show age-specific breast cancer incidence after 50 years old in those withliver transplantation similar to that of the general population. Our sample size is small when compared tothe overall incidence in the literature of de novo breast cancers in those with liver transplants. Nonetheless, after weighting, our results reflect a realistic appraisal of patients with breast cancer and liver transplantation.
The care of the liver transplant recipient requires a lifelong multidisciplinary effort by a wide range of specialists. Clinicians must not only consider all of the transplant-related complications, but alsotypical age-related comorbidities. Moreover, chronic immunosuppressive therapy can induce or accelerate some conditions that the non-transplant patient may not be routinely monitored for, specificallymalignancy.
Centralized and specialized management of breast cancer in the liver transplant recipient is paramount. On univariate analysis, the complication rate, especially in acute renal failure was higher in LTR group. Currently most of breast surgery was performed in the outpatient setting. LTR might show the elevation of creatinine in perioperative workup since LTR require immunosuppression drugs and adjustment of the doses frequently according to serum creatinine levels.However, after adjustment and on multivariate analysis, LTR was not an independent risk factor for developing a post-operative complication (OR 1.223 p 0.480) (Table IV). This suggests that factors other than liver transplantation are associated with development of post-operative complications.
A significantly higher proportion of LTR had an Elixhauser comorbidity score of ≥ 3 (69.7% vs.21.5%, p<0.001, Table I), indicating that LT patients suffered from a higher degree of co-morbidity.However, our data shows that despite the LTR having significantly more comorbidities, there were nodifferences in mortality, complication rate, total charge, or length of stay when these patients were managed at a transplant center (Table IV). Breast cancer management in LTR at non-transplant centers incurred higher charges but nodifference in complication rate nor LOS when compared to breast cancer management in LTR at transplant centers.
Of women who received a liver transplant, length of stay following breast cancer surgery wassignificantly shorter in the group which underwent breast reconstruction. (OR <1, p 0.002) (Table IV). This may be due to the fact that, in general, immediate breast reconstruction is performed by careful selection of those patients who are possibly overall healthier. We do not have knowledge of pre- and posttransplant performance status, immunosuppressive regimens, or pretransplant health that may overall lend to healthier LTR and thus ability to withstand an immediate breast reconstruction with acceptable outcomes and LOS.We have found a significantly shorter LOS after reconstruction in the liver transplant cohort compared to the non-liver transplant cohort most likely explained by better selection of appropriate candidates. The liver transplant patients underwent probably simpler implant-based reconstruction as opposed to non-liver transplant patients who underwent autologous tissue based reconstructions usually associated with more than double the LOS.
Our analyses revealed no statistical difference when comparing the overall survival of the two cohorts. This mirrors previous reports. Jeong et al. compared the prognosis of post-transplant breast cancer patients receiving immunosuppressants to general breast cancer survivors. All individuals had previously undergone either a liver or kidney transplant. They discovered that after matching by tumor size, lymph node metastasis, and age, disease-free survival, breast-cancer specific survival, and overallsurvival were not significantly different between the two cohorts.
A final, notable point is the fact that total hospital charges for breast cancer surgery were higher in the liver transplant group, even after controlling for other variables (OR 2.621, p <0.001) (Table IV). This may be explained by LTR suffer from a higher degree of co-morbidity. An analysis of 126,664 individuals with breast cancer, revealed the average medical cost per patient with comorbidity was higher compared to the average medical cost per person without comorbidity (p<0.05). We hypothesize that increased comorbidities in the LT cohort may have played a role in these women incurring higher costs for breast cancer surgery.
This analysis is not without limitations, as there is inherent weakness of large database analysis. Time between liver transplantation and breast cancer surgery was not known. Prolonged periods of immunosuppressive treatment may induce DNA damage and inhibit immune surveillance mechanisms, thus increasing risk of lymph node metastases which would require more extensive BC surgery, possibly axillary node dissection, with locally advanced disease at presentation24. Additionally, immunosuppressive medications are unknown. This prevented us from stratifying outcomes based on type of immunosuppressive agent. Further, information on the breast cancer stage and neoadjuvant chemotherapy treatment prior to surgery is unknown. Thus, we were unable to assess outcomes on early versus advanced disease. Similarly, long term patient outcomes are not available due to database limitations, and could not be assessed, and may differ from the reported short-term outcomes in our analyses. Further, there is no data available on cancer stage distribution or method of breast cancer detection or screening rates in those with liver transplantation.
Additional research is needed to more comprehensively understand the difficulties that post-livertransplant breast cancer survivors face following breast cancer surgery compared to the general breast cancer population. Future analyses should consider factors such as breast cancer stage, type of immunosuppressive therapy, and time since LT.
The strengths of this manuscript are reflected in this being the largest and first reported analysesthat determines that prior liver transplantation does not increase morbidity nor mortality in womenundergoing surgery for breast cancer. However, we found total hospital charges for breast surgery were significantly higher in LTR. These results may be used to guide clinical practice when treating women forbreast cancer who have undergone a liver transplant.