EXPERIMENTAL AND CLINICAL TRANSPLANTATION

Long-term immunosuppression can lead to malignant tumors after kidney transplant. In this case study, we report a rare case of breast cancer occurring in a man after 33 years of kidney transplant. This 55-year-old kidney transplant patient presented with a right breast mass. The biopsy showed an infiltrating carcinoma. The immunohistochemical study was positive for estrogen. The patient underwent a right mastectomy with axillary dissection. Chemotherapy based on docetaxel and radiotherapy was started. Adjuvant treatment with tamoxifen and a switch from azathioprine to sirolimus were conducted. Follow-up showed that the patient died 24 months after presentation. Through this case, we emphasize the importance of vigilance about this rare cancer, often diagnosed at a late stage, which can negatively affect prognosis. Screening for risk factors is crucial.

Key words : Neoplasia, Renal transplantation, Risk factors, Therapeutic management

Neoplasms are currently the third leading cause of death in transplant recipients.¹ Mortality linked to cancer posttransplant is high, mainly in advanced stages; hence, screening and early diagnosis are important.² Although the risk of “de novo breast cancer” after solid-organ transplant is comparable to that shown in the general population according to observational studies, the prognosis is poorer among transplant patients because of immunosuppression.³ Breast cancer is the most common cancer in women. In men, breast cancer is a rare condition representing less than 1% of all male cancers.⁴

The patient, a 55-year-old kidney transplant recipient, presented during his periodic nephrology con-sultation (June 2022) with a right breast mass disco-vered on self-examination. History showed that he started dialysis in 1985 and then received a transplant in 1989 from a living related donor (his brother). He was receiving prednisone (10 mg/day) and azathioprine (100 mg/day). Furthermore, he developed de novo posttransplant diabetes that appeared after 30 years and diagnosis of hepatitis C virus infection in 2019, eradicated by antiviral treatment.

Clinical examination revealed a right breast mass measuring approximately 2 cm with skin and nipple retraction associated with centimeter-sized right axillary lymphadenopathy. Breast ultrasonography revealed an eccentric right retro-areolar mass measuring 2 cm in long axis. A biopsy of the nodule revealed a nonspecific invasive carcinoma of SBR (Scarff-Bloom-Richardson) grade 2 (architecture: 3/atypia: 2/mitoses: 1) (Figure 1).

Immunohistochemical studies were positive for estrogen (80%, 3+) and progesterone (20%, 2+/3+) and negative for Her2/Neu (score 1+); the patient’s Ki67 index was 20%. The extension assessment showed bone metastases with multiple suspicious foci with hyperfixation on scintigraphy at left mandible, sternum, rib grill, left scapula, and lumbar spine marked at the lumbar 2 level and the left sacroiliac. A chest scan showed a solid ventromedial retractile pulmonary nodule in a band of nonsuspicious appearance.

The patient underwent a right mastectomy with axillary dissection (Pathey-type surgery) (Figure 2). Chemotherapy was initiated based on docetaxel at a dose of 80 mg/m² combined with bisphosphonate (zoledronate at a dose of 4 mg) with a total of 6 courses. A complement of radiotherapy of the chest wall was proposed at a dose of 40 Gy fractionated into 15 sessions. Maintenance treatment with hormone therapy with tamoxifen (20 mg/day) was initiated in combination with zoledronate. The patient was switched from azathioprine to mammalian target of rapamycin inhibitor (sirolimus). After 10 months of hormone therapy, bone progression was noted with onset of lower back pain requiring a level III analgesic (morphine). A spinal magnetic resonance imaging (MRI) revealed multiple secondary osteo-condensing bone lesions with no signs of compression. Treatment was changed to another hormonal therapy, which was an aromatase inhibitor (letrozole) combined with chemical castration with decapeptyl every 3 months and an oral bisphosphonate.

In April 2024, the patient presented with worse-ning spinal pain with sphincter disorders and circumducted gait when walking. The spinal cord MRI concluded, along with presence of numerous secondary vertebral and pelvic lesions, signs of epiduritis at dorsal 4. The patient was given decom-pressive radiotherapy with a prescription of corti-costeroids. In July 2024, the patient presented with deterioration in his general condition, which included weight loss and a decrease in muscle strength. The evolution was marked by the patient’s death 24 months after discovery of his neoplasia.

Male breast cancer after kidney transplant is a rare, if not exceptional, condition. Male breast carcinoma accounts for approximately 1% of all breast cancers.4 The literature shows only 2 case reports of male breast cancer after kidney transplant. The first, reported in 1988 by Showel and colleagues,⁵ and the second, reported in 1990 by Fischer,⁶ occurred 6 years and 2 years, respectively, after transplant. Five cases of male breast cancer were also cited among a large cohort of 114 kidney transplant recipients, reported in 2002 by Buell and colleagues.⁷ In our case report, the age at cancer discovery was 55 years and the time to kidney transplant was 33 years (396 months). Data in the literature varied among the different patient cohorts (Table 1).^5-9

Multiple risk factors from retrospective studies have been identified as contributors to male breast cancer. These can be grouped into hormonal, genetic, environmental, and drug-related factors. For hormo-nal factors, a specific condition of relative hyperes-trogenism in men with low androgen levels increases the risk of developing this cancer. These conditions are encountered in testicular abnormalities (eg, ectopic testis, orchitis), inguinal hernias, infertility, and orchiectomy. Other conditions, such as prostate cancer and its treatment, and gynecomastia have been implicated in male breast cancer. Obesity and liver dysfunction, which promotes the conversion of andro-gens to estrogens, are also potential risk factors.¹⁰ For genetic factors, Klinefelter syndrome (XXY genotype), which combines testicular dysgenesis, gynecomastia, and an imbalance between androgens and estrogens, has been implicated as a robust risk factor for male breast cancer. Furthermore, this cancer is more frequently linked to the BRCA2 mutation (major breast cancer predisposition genes), unlike that in women, which is generally linked to the BRCA1 mutation.¹¹ Environmental risk factors include working in a hot environment and exposure to fumes, electromagnetic fields, and polycyclic aromatic hydrocarbons.¹² Drug-related factors that increase the risk of breast cancer in men include use of estrogen or testosterone medications.¹⁰ As risk factors, our patient presented with gynecomastia and infectious liver damage.

Long delays have been reported between the discovery of symptoms and the consultation of patients. Indeed, men are more alarmed by gyne-comastia than by a breast nodule. Commonly reported functional signs include nipple discharge, pain, or skin ulceration. Bleeding from the nipple may also be observed.¹³

Ductal carcinoma in situ is rare in men. In fact, many male breast cancers are invasive (85%). Most of these cancers are ductal, with less than 2% being lobular. Other subtypes such as papillary (2%), medullary (2%), and mucinous (1%) may be seen.10 Receptor positivity was noted in most cases reported in the literature with absence of HER2 positivity.¹⁰

Because of the rarity of this disease, therapeutic indications in men are often extrapolated from those applied in women. However, unlike female breast cancer, mastectomy combined with ipsilateral axillary curettage remains the standard surgical treatment in men.¹¹ Adjuvant radiotherapy remains controversial. However, observational studies have shown a reduction in local recurrence with radio-therapy, especially for patients with lymph node metastases.¹⁰ Hormone therapy is the most frequently proposed treatment because of the high frequency of positive hormone receptors. Tamoxifen is the most effective molecule in this situation, with duration of treatment of generally 5 years.¹⁴ Data on chemot-herapy are scarce. However, observational studies have suggested decreased mortality and recurrence rates in men who received adjuvant chemotherapy.¹⁰

Breast cancer patients with HER2 positivity are rare in the male population. However, when HER2 is positive, it is a negative prognostic marker compared with HER2-negative counterparts. In these cases, anti-HER agents can be used but unfortunately without clinical evidence.¹⁰ Immunotherapy is among the therapeutic arsenal for advanced breast cancer. However, immunotherapy during organ transplant is not safe given the risk of acute rejection and graft loss.³ Adjuvant treatment with bisphos-phonates leads to a reduction in bone metastases and improves breast cancer mortality, thus qualifying these as novel anticancer agents.¹⁵ However, no consensus has been made on the appropriate action on immunosuppression when cancer is discovered. The lack of knowledge about the therapeutic effect of these changes explains the diversity of treatment. Three therapeutic approaches are generally adopted: continuation of the same immunosuppressive treatment, reduction of immunosuppression, and/or modification of immunosuppressants with a change in therapeutic class.

Male breast cancer is a rare and rather unique condition. A lack of awareness or even neglect of this cancer can lead to delayed diagnosis, complicating treatment and thus impairing prognosis. We empha-size the importance of systematic posttransplant screening, especially in patients with a family history of breast cancer or those with relative hyperes-trogenism.

Volume: 23 Issue: 6 June 2025

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