Confounder factors masking a Leydig-cell ovarian tumor in a post-menopausal woman treated for androgen-positive receptor breast cancer

Abstract

Post-menopause hyperandrogenism is a condition that needs careful evaluation. Aromatase inhibitors (AI), which are important in the management of positive estrogen breast cancer, and chronic kidney disease (CKD) can puzzle the evaluation of this condition. A postmenopause female with type-2 diabetes and advanced CKD was attended due to progressive virilization, which has started after the introduction of an AI for breast cancer 5 years earlier. Clinical and radiological investigation has confirmed a pure Leydig cell tumor as source of hyperandrogenism. Re-evaluation of the breast tumor immunohistochemistry has shown positive androgen receptor expression and negative expression for estrogen, progesterone and HER-2 receptors. Even though an ovarian tumor was the source of androgen excess, we discuss that AI could exert a slight contribution to patient’s virilization by reducing estradiol counterbalance. Also, although the onset of hyperandrogenic symptoms was unclear, we could not exclude that the ovarian tumor had produced enough androgens to play a role in breast tumor progression. This case report supports the literature regarding the possible association between Leydig cell tumor and androgen-receptor-positive breast cancer development. Finally, progressive hyperandrogenic symptoms in postmenopause, even under AI therapy or the presence of advanced CKD, impose a more detailed investigation.

Chinese abstract

绝经后雄激素过多是需要仔细评估的一种情况。在雌激素受体阳性乳腺癌的管理中非常重要的芳香酶抑制剂（AI）和慢性肾脏疾病（CKD）使这种评估成为难题。一位绝经后患2型糖尿病和晚期CKD的妇女,因为进行性男性化而住院, 这种情况在5年前进行乳腺癌AI治疗后开始出现的。临床和放射学检查已经证实, 单纯的睾丸间质细胞瘤是雄激素过多的原因。重新评估乳腺肿瘤免疫组化显示:雌激素, 孕激素和HER-2受体均阴性表达,雄激素受体阳性表达。尽管卵巢肿瘤可以引起雄激素过多, 但我们讨论了AI通过降低雌二醇的平衡而致轻度的男性化。此外, 尽管雄激素过多症的发病不清楚, 但我们不能排除卵巢肿瘤产生足够的雄激素在乳腺肿瘤进展中发挥作用。本病例报道支持关于睾丸间质细胞肿瘤与雄激素受体阳性乳腺癌发展之间可能相关的文献。最后, 绝经后进行性雄激素过多症, 即使在AI治疗或晚期CKD的存在下, 必须更详细地研究。

Keywords:

• Aromatase inhibitors
• breast cancer
• hyperandrogenism,chronic kidney disease
• Leydig cell tumor

Acknowledgements

Authors thank to Dr. Gustavo Rubino de Azevedo Focchi at Pathology Department of Universidade Federal de São Paulo for his contribution in histopathological analysis.

Consent for publication

Written informed consent was obtained from the patient for this publication, including authorization to use un-identifying photographs.

Declaration of interest

The author declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the case reported.