Liver Transplantation Worldwide
Syndromic incidence of ovarian cancer after liver transplantation: Is breast cancer an antecedent risk?
Joseph F. Buell, MD, E. Steve Woodle, MD
Israel Penn International Transplant Tumor Registry Division of Transplantation Department of Surgery University of Cincinnati School of Medicine Cincinnati, OH
Ovarian cancer is the gynecologic malignancy with the highest number of deaths in the United States. Previous studies had found a decreased incidence of female gynecological malignancies after liver transplantation. In order to estimate the incidence of ovarian carcinoma after liver transplantation, we evaluated 1,708 consecutive liver transplant recipients from 1984 to 2001. Of them, 770 (43%) were female. Routine follow-ups were performed at 1, 2, 5, and 10 years after transplantation. There were two cases of ovarian carcinoma. Both occurred in recipients with a previous history of breast cancer. Based on these data, we conclude that the incidence of ovarian cancer is 1:385 among all female liver transplant recipients, and 1:6.5 among those with a history of pretransplant breast cancer. We recommend that regular checkups be undertaken, especially in the population at highest risk. (Dig Dis and Sci 2003;48:187-189.)
IPITTR, Israel Penn International Transplant Tumor Registry; BUMC, Baylor University Medical Center; SEER, Surveillance, Epidemiology and End Results.
Chronic immunosuppression is an established risk factor linked to the development of malignancy in transplant recipients.[1-4] Multiple series have estimated the incidence of de novo malignancies to vary between 20 and 80% at 10 years posttransplant, based on hereditary and environmental factors, with the highest incidence of malignancies being observed in patients residing in the Sunbelt.[1-3] Most malignancies common to both the transplant recipient and general populations occur more frequently in immunosuppressed transplant recipients. However, a recent report from the Israel Penn International Transplant Tumor Registry (IPITTR) found ovarian cancer to occur at a lower incidence than observed in the general population. For this reason, we found the report from the Baylor group of particular interest.
A recent report from Molmenti et al. at Baylor University Medical Center (BUMC) confirmed a low incidence of ovarian cancer in their series of 1,708 liver transplant recipients, establishing an incidence of ovarian cancer for their liver transplant recipient population of 1 in 385. Molmenti et al. suggested an association between the development of ovarian cancer and an antecedent history of breast cancer, with the incidence of ovarian cancer being 1 in 6.5 for patients with antecedent breast cancer. Molmenti et al. subsequently advocate the use of intensive screening in all patients with antecedent breast cancer.
In the United States, ovarian cancer accounts for more deaths than cervical and endometrial cancer combined. Over 21,000 new cases of ovarian cancer are diagnosed each year, resulting in more than 13,000 deaths. Three forms of familial ovarian cancer have been described in the literature. Two of these, Lynch Syndrome II and breast-ovarian syndrome, show an autosomal dominant pattern of inheritance with a link to breast cancer. Lynch syndrome II describes a familial predisposition to the development of ovarian, endometrial, and colon cancer. The increased lifetime risk for the development of ovarian cancer in these patients has been reported to range between threefold and tenfold. Breast-ovarian cancer syndrome, associated with the BRCA1 (chromosome locus17q21) and BRCA2 (chromosome locus 13q12.3), carries a stronger association between the two malignancies, with relative risk predictions for the development of ovarian cancer varying widely (27-63%) and increasing with the age of the patient.
The report by Boardman et al. examined all cases of ovarian cancer reported to the IPITTR from United States transplant centers. The estimated incidence of ovarian cancer within this population was 2%, which was significantly lower than the 4% of all female malignancies diagnosed in the general population. While registries in general suffer from underreporting, it has been suggested that the IPITTR, being of a voluntary nature, may suffer from an overreporting, receiving primarily those cases deemed noteworthy. For this reason, we found these results to be of particular interest. A lower incidence of ovarian cancer in transplant recipients was also reported in a recent finding from Yakupoglu et al., which failed to identify a single case of ovarian cancer in 409 rapamycin-treated women. Further examination of the IPITTR series revealed that the incidence of ovarian cancer was 2.6% (41/1,553), highest in the kidney recipients (3.0%; n = 34/1,127), followed by heart recipients (2.0%; n = 4/199), and liver allograft recipients (1.6%; n = 3/178). Notably, Boardman et al. found that ovarian cancer in transplant recipients occurred at a younger age; had a higher percentage of stage II and III malignancies; was more biologically aggressive; and had significantly poorer survival rates than that which occurred in the general population reported to the National Cancer Institute's Surveillance, Epidemiology and End Results (SEER) registry. There was only one case of ovarian cancer with antecedent breast cancer identified in the series.
We believe syndromic ovarian cancer may be an important clinical entity. Appropriate screening should be performed in high-risk patients, namely those with a familial or personal history of antecedent breast, endometrial, or colon cancer. What the authors of this editorial find equally fascinating is the lower incidence of ovarian cancer in the transplant community. To our knowledge, this is the only malignancy that has demonstrated a lower incidence in the immunosuppressed transplant population than in the general population. A recent multiethnic, population-based, case-control epidemiological study confirmed a direct relationship between ovulation and incidence of ovarian cancer. Ovarian dysfunction is a known sequela of chronic end-stage organ disease. Thus, one might speculate that this phenomenon may contribute to the observed lower incidence of ovarian cancer in transplant recipients. However, further examination of this patient population is required to determine the reason for this decreased incidence and to determine those genetic or environmental factors affecting this phenomenon. Because ovarian cancer is a commonly occurring female malignancy that results in significant mortality, it should be carefully screened for before and after transplantation using the guidelines set forth by the American Cancer Society.[11-12]
1 Penn I. Cancers in renal transplant recipients. Adv Ren Replace Ther 2000; 7: 147-156. Links
2 Penn I. Post-transplant malignancy: The role of immunosuppression. Drug Saf 2000; 23: 101-113. Links
3 Penn I. Occurrence of cancers in immunosuppressed organ transplant recipients. Clin Transpl 1998; 23: 147-148 Links
4 Yarchoan R, Little RF. Immunosuppression-related malignancies. In: DeVita VT , Hellman S , Rosenberg SA , eds. Cancer Principles of Oncology. Philadelphia: Lippincott Williams & Wilkins; 2001: 2575-2996.
5 Boardman RE, Gross TG, Hanaway MJ, First MR, Trofe J, Alloway RR, Beebe TM, Woodle ES, Buell JF. De novo ovarian cancer post solid organ transplantation. Am J Transplant 2003; 3: 188. Links
6 Molmenti EP, Molmenti H, Weinstein J, Elliott EE, Fasola CG, Orr D, et al. Syndromic incidence of ovarian carcinoma after liver transplantation, with special reference to anteceding breast cancer. Dig Dis and Sci 2003; 48: 187-189. Links
7 Sanchez EQ, Marubashi S, Jung G, Levy MF, Goldstein RM, Molmenti EP, et al. De Novo tumors after liver transplantation: A single-institution experience. Liver Transpl 2002; 8: 285-291. Links
8 Ozols RF, Schwartz PE, Eifel PJ. Ovarian cancer, fallopian tube carcinoma, and peritoneal carcinoma. In: DeVita VT , Hellman S , Rosenberg SA , eds. Cancer Principles of Oncology. Philadelphia: Lippincott Williams & Wilkins; 2001: 1597-1632.
9 Yakupoglu YK, Knight RJ, Katz SM, Van Buren CT, Buell JF, Woodle ES, et al. Low incidence of malignancy among sirolimus-cyclosporine treated transplant recipients. Am J Transplant. In press. Links
10 Tung KH, Goodman MT, Wu AH, McDuffie K, Wilkens LR, Kolonel LM, et al. Reproductive factors and epithelial ovarian cancer risk by histologic type: A multiethnic case-control study. Am J Epidemiol 2003; 158: 629-638. Links
11 Kasiske BL, Cangro CB, Hariharan S, et al. The evaluation of renal transplantation candidates: Clinical practice guidelines. Am J Transplant 2002( 1 suppl 2): 1-95. Links
12 Amare D, Buell JF. Management of malignancy after renal transplantation. The Transplant Nephrology Community Outreach Program at the University of Alabama School of Medicine. April 2003.
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