Organ transplants and breast cancer: A dangerous connection

By Alpana Mohta, MD, DNB, FEADV, FIADVL, IFAAD | Medically reviewed by Jeffrey A. Bubis, DO, FACOI, FACP
Published March 27, 2023

Key Takeaways

  • Three types of cancer occur in organ transplant recipients: cancer transmitted by the donor, or donor-transmitted cancer (DTC); cancer that develops from the graft, or donor-derived cancer (DDC); and de-novo cancer, which can be caused by genetic factors and immunosuppressive treatment. 

  • Organ transplant recipients carry a higher risk of developing breast cancer than the general population, with a two-fold higher mortality rate.

  • Guidelines suggest a 10-year remission period for breast cancer in donors and 2-5 years for recipients before organ transplant to lower the risk of post-transplant breast cancer.

In a heartening sign of progress, the Organ Procurement and Transplantation Network (OPTN) has reported that in 2022, more than 21,000 individuals in the United States donated their organs—a staggering 52.5% increase from just a decade ago in 2012.[]

However, despite the significant strides in organ donation, over 100,00 patients are still waiting for transplants, highlighting a major backlog that needs to be addressed.

The safety of donations needs to be assured, nonetheless. Breast cancer is one disease that can be transmitted from a donor and that can develop post-transplant in recipients who are at risk.

Unforeseen risk of organ transplant

In the United States, a woman has a 12.9% chance of developing breast cancer in her lifetime.[] This is an age-dependent statistic; there's an 87.1% likelihood a woman won't have breast cancer, and the risk declines after menopause. Nonetheless, given the current rise in incidence rate with rising age, potential donors' breast cancer risk must be considered.

The likelihood of cancer being transmitted by the donor is low, at around 0.05%, although breast cancer poses a higher risk of transmission than other cancers, according to a recently published meta-analysis by French researchers.[]

A group of researchers from the Mayo Clinic observed that female patients who underwent organ transplants had a higher risk of developing breast cancer than the national average for women in the United States.[]

Donor-originating cancer

The transfer of cancer from a donor to a transplant recipient can occur in two ways: Either the cancer cells are already present in the donor's organ and become transmitted to the recipient (referred to as donor-transmitted cancer, or DTC), or the tumor develops in the recipient after receiving the graft (known as donor-derived cancer, or DDC).

According to researchers publishing in Transplantation, the factors contributing to cancer transmission during organ transplantation include older age of the donor (over 45 years) and organ donation after circulatory death.[]

A 2018 Dutch report discussed a rare case in which one donor was linked to breast cancer in four transplant recipients.[] In commenting on the case, the authors stated that the value of pre-donation CT scans to detect malignancy was uncertain, and they noted that routine post-mortem scans that revealed clinically irrelevant findings might increase the number of rejections.

To mitigate the risk of DTC or DDC, the United Network for Organ Sharing (UNOS) employs the DonorNet® traceability system. If a cancer is deemed to be transmitted by the donor, the medical teams in charge of recipients receiving any organs from the same donor are alerted.

De-novo cancer in recipient

De-novo breast cancer can also develop in organ recipients due to an inherited predisposition or long-term immunosuppression.

A research group from Stanford University has reported on predispositions in certain populations.[] For instance, Ashkenazi Jews have a higher chance of inheriting mutations linked to both hereditary breast/ovarian cancer syndrome (BRCA1/2 mutation) and cystic fibrosis (CFTR mutation). The resultant respiratory insufficiency accounts for around 15% of adult lung transplants.

Outcomes after organ transplantation

Breast cancer prognosis in patients with solid organ transplants is poorer than anticipated.

Researchers publishing in the American Journal of Transplantation stated that women with kidney transplants have an increased risk of death from breast cancer by at least two-fold compared to women in the general population.[]

These recipients are also more likely to present with advanced-stage breast cancer at a younger age (median age of 51 years) than the general population (median age of 60 years). Similarly, a two-fold rise in mortality is also reported for all cancer-related deaths in liver and cardiothoracic transplant recipients.

The reasons behind the escalated mortality rate are partly due to the use of immunosuppressive drugs which promote chronic opportunistic viral infections, according to researchers writing in The New England Journal of Medicine.[] The type, duration, and extent of immunosuppressive drugs used also affect the risk and type of cancer that may develop. Calcineurin inhibitors like cyclosporine and tacrolimus may promote tumor growth by producing growth factors that enhance angiogenesis, tumor growth, and metastasis.

Other causes include cancer's intensified biological aggressiveness, invasiveness facilitated by immunosuppression, and end-organ disease in recipients.[] Another reason is clinicians' reluctance to introduce new interventions for these patients—because of the risk of rejection of transplant organs.

Criteria for donors

Several factors must be evaluated when considering organ transplants from a donor previously treated for breast cancer. These include the initial clinical and histopathological staging of cancer, the treatments received, and the duration of remission.

Expert groups, including the UNOS and the European Directorate for the Quality of Medicines and Healthcare (EDQM), have developed guidelines for assessing the risk of transmitting breast cancer through donor organs. As discussed by the French researchers, the goal is to widen the pool of potential donors while ensuring the recipient's safety.

For patients with a history of ductal carcinoma in situ of the breast—regardless of grade or time to remission—removal for organ donation may be considered, as there is theoretically no risk of metastasis, and the prognosis is generally favorable. However, the risk of transmitting breast cancer through transplantation is relatively high for infiltrating lesions, as late secondary lesions can occur. Therefore, organ removal should be avoided unless absolutely essential.

The American Society of Transplant Surgeons recommends organ removal from patients with a history of breast cancer only for those with lesions under 1 cm after a minimum of 10 years in remission.[]

However, these recommendations do not always consider the risk of occult cancer in the donor organ.

Transplant eligibility

Patients with a prior cancer history can be considered for the transplant wait list, but with caution.

The risk of recurrence is highest in the first 12 months post-transplant, according to the authors writing in the American Journal of Transplantation. Breast and urinary tract cancers have the greatest likelihood of recurrence.

Therefore, clinical guidelines suggest waiting 2 to 5 years for most cancer types to reduce the risk of cancer recurrence.[]

Cancer screening in recipients

Regular cancer screening in individuals with a low life expectancy, such as transplant patients, may result in needless diagnostic tests (eg, core biopsy), overdiagnosis, and overtreatment.

Genomic profile is a better approach for predicting the risk of breast cancer recurrence in potential recipients. Examples of tools with potential utility include the Oncotype DX Breast Recurrence Score, MammaPrint, and PAM50.[]

What this means for you

A collaborative approach to data sharing between solid organ transplant registries worldwide is needed for better screening of donors and increased understanding of the natural history of breast cancer in recipients. The benefits of screening include reduced cancer-related mortality in high-risk persons. To optimize the benefits while minimizing the downsides, a conceptual model is required that would provide for avoiding unnecessary tests in low-risk individuals. If your patient is considering becoming an organ donor, it is important to discuss the OPTN guidelines, which recommend a comprehensive medical examination, including a breast examination.

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