Cyclosporin A and multiple fibroadenomas of the breast

Baildam, A.D.; Higgins, Rob; Hurley, Edward J.; Furlong, A.; Walls, J.; Venning, Mike; Ackrill, P.; Mansel, RE

doi:10.1002/bjs.1800831229

Cited by 45 publications

(28 citation statements)

References 13 publications

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“…The presence of a mouse mammary tumor virus in rodents and published reports of HIV-positive rapidly growing breast cancers suggest a possible viral etiology for some breast cancers (10,16). One study reported multiple and bilateral fibroadenomas in immunosuppressed patients receiving cyclosporin A (17). Isolated studies have investigated the EBV/breast cancer association with contradictory results (2,18,19).…”

Section: Discussionmentioning

confidence: 99%

Detection of Epstein-Barr Virus in Rapidly Growing Fibroadenomas of the Breast in Immunosuppressed Hosts

et al. 2002

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Fibroadenomas are the most common benign tumors of the female breast and are associated with a slight increase in the risk of subsequent breast cancer. Multiple fibroadenomas have been described in patients after renal transplantation and are thought to be secondary to drug-related growth stimulation. Epstein-Barr virus (EBV) has been detected in many neoplasms, including breast cancer. We set out to investigate whether EBV plays a role in the development of rapidly growing fibroadenomas in immunocompromised patients. We studied 19 fibroadenomas and one invasive ductal carcinoma that developed after organ transplantation or treatment for lupus erythematosus. As a control group we included 11 fibroadenomas from non-immunocompromised patients. DNA was amplified using polymerase chain reaction (PCR) of the EBV-encoded small RNA (EBER-2) DNA sequence. EBV latent membrane protein 1 (LMP-1) transcripts were amplified using reverse transcription (RT) PCR. Immunohistochemical (IHC) staining for LMP-1 protein was performed. A total of 9 out of 20 tumors (45%) were concordantly positive by PCR and IHC. IHC stained exclusively the epithelial cells. All the fibroadenomas in non-immunocompromised patients were negative for LMP-1 (Fisher's exact test P ‫؍‬ .0006). These data suggest that EBV is associated with fibroadenomas in this immunosuppressed population and that the infection is specifically localized to epithelial cells. This is the first study suggesting a role for EBV in the pathogenesis of fibroadenomas.

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Section: Discussionmentioning

confidence: 99%

Detection of Epstein-Barr Virus in Rapidly Growing Fibroadenomas of the Breast in Immunosuppressed Hosts

et al. 2002

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“…For example, gingival hypertrophy occurs commonly, and patients frequently require oral surgery to correct it; cyclosporin A is thought to affect the gingival fibroblasts directly to promote both proliferation and collagen production. 12 A positive relationship has been reported between the use of cyclosporin A and the prevalence of multiple giant fibroadenomas of the breast, 8,9 but to our knowledge, no association between the presence of gingival hypertrophy and the presence of fibroadenomas has been reported. This implies that the mechanism of action of cyclosporin A in promoting the development of breast fibroadenomas differs from its action on the gingiva.…”

Section: Discussionmentioning

confidence: 81%

“…Unlike the cases in our study, none of those 12 cases involved giant fibroadenomas. In the study by Baildam et al, 8 fibroadenomas were seen in 13 of 29 women with kidney transplants who had undergone cyclosporin A therapy; 10 of those 13 cases involved multiple lesions and, in 5, the lesions were bilateral. No breast abnormalities were recorded in the 10 women treated with steroids and azathioprine alone.…”

Section: Discussionmentioning

confidence: 96%

“…Those investigators concluded that the pathologic proliferative changes and newly developed multiple fibroadenomas they found were suggestive of an effect of cyclosporin A on the breast. 9 Baildam et al 8 and Rolles and Calne 22 described 12 cases of multiple fibroadenomas that occurred in association with cyclosporin A therapy. Unlike the cases in our study, none of those 12 cases involved giant fibroadenomas.…”

Section: Discussionmentioning

confidence: 97%

“…5 Breast tumors, however, have rarely been reported in cyclosporin A-treated transplant recipients, 6,7 and reports of benign breast lesions, such as fibroadenomas, have also been rare. 8,9 Despite the rarity of such lesions, research has indicated a positive association between the use of cyclosporin A for immunosuppression after organ transplantation and the development of multiple fibroadenomas of the breast. 8,9 We undertook this retrospective study to determine the characteristic imaging and histopathologic features of fibroadenomas in kidney-transplant recipients who had been treated long term with cyclosporin A and steroid therapy and to compare these features with those of fibroadenomas in women who had never undergone immunosuppressive therapy or organ transplantation.…”

Section: Received 24 April 2003; Accepted 24 September 2003mentioning

confidence: 98%

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Characteristic imaging features of breast fibroadenomas in women given cyclosporin A after renal transplantation

Son

Kim

et al. 2004

J of Clinical Ultrasound

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The fibroadenomas that developed in kidney-transplant recipients given chronic cyclosporin A and prednisolone immunosuppressive therapy had a tendency to be multiple, bilateral, and larger than those that developed in the control patients. These fibroadenomas also exhibited some imaging features that differed from those of typical fibroadenomas that develop in women who have not undergone organ transplantation or immunosuppressive therapy.

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Cancer incidence and risk factors after solid organ transplantation

Vajdic

Leeuwen

2009

Intl Journal of Cancer

381

253

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Iatrogenic immunosuppression is a unique setting for investigating immune-related mechanisms of carcinogenesis. Solid organ transplant recipients have a 3-fold excess risk of cancer relative to the age-and sex-matched general population. Population-based studies utilizing cancer registry records indicate that a wide range of cancers, mostly those with a viral etiology, occur at excess rates. To date, cancer risk has predominantly been examined in adult kidney transplant recipients in Western countries. It is yet to be established whether a similar incidence profile exists in the longterm for other solid organ, pediatric and non-Western transplant recipients. The cancer incidence profile before and after kidney transplantation strongly suggests a relatively minor contribution by both preexisting cancer risk factors and the conditions underlying end-stage kidney disease, and points to a causal role for immunosuppression. Within-cohort risk factor analyses have largely been performed on cohorts with voluntary cancer notification, and very few have incorporated biomarkers of the level of immunosuppression, the current receipt of immunosuppressive agents, or genetic risk factors. Because of their markedly high risk of certain cancers, findings from comprehensive studies in transplant recipients have the potential to raise new avenues for investigation into causal mechanisms and preventive measures against immunerelated and infectious causes of cancer. ' UICCKey words: cancer; transplantation; immunosuppression; incidence; risk; infection; kidney A wide-ranging excess risk of cancer after solid organ transplantation has been increasingly recognized over recent decades as advances in medicine have extended the life of transplant recipients. Malignancy is now a leading cause of patient death with graft function, 1-3 an outcome that can predominantly be attributed to the iatrogenic immunosuppression required to avoid rejection of the transplanted organ. Solid organ transplantation provides a unique setting for the identification of cancers under immunological control, and for examination of the risk factors for their development. Knowledge of the range of increased cancers and the magnitude of the increased risks is important in developing appropriate prevention and early detection programs for patients undergoing long-term immunosuppression. In addition, comparison of cancer incidence and risk factors between populations with different forms of immune system impairment offers insight into carcinogenic mechanisms that has ramifications for cancer control not only in these populations but also in the general community.This review focuses on the cancer incidence profile in solid organ transplant recipients, and the established and emerging risk factors for 5 cancers that occur at increased rates. Cancer incidence after solid organ transplantationShortly after the widespread introduction of solid organ transplantation, it became apparent that immune suppression was associated with a strikingly increased risk of a few canc...

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Cyclosporin A and multiple fibroadenomas of the breast

Cited by 45 publications

References 13 publications

Detection of Epstein-Barr Virus in Rapidly Growing Fibroadenomas of the Breast in Immunosuppressed Hosts

Detection of Epstein-Barr Virus in Rapidly Growing Fibroadenomas of the Breast in Immunosuppressed Hosts

Characteristic imaging features of breast fibroadenomas in women given cyclosporin A after renal transplantation

Cancer incidence and risk factors after solid organ transplantation

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