Extramammary Paget disease (EMPD) is a rare form of cutaneous,
intraepithelial adenocarcinoma, which typically presents itself as an erythematous plaque originating from apocrine-gland rich regions, such as the vulva, the perianal region, the scrotum, the penis, or the axilla. EMPD patients typically have a good prognosis, with expected 5-year survival of 60%-92%, but it is estimated that about one-third of EMPD patients will develop lymph node or distant
metastases. Treatment approaches for EMPD include locoregional
therapies such as broad surgical resection,
radiotherapy, or topical
imiquimod, when the disease is localized, and
chemotherapy and
biological agents for advanced EMPD. We report the case of a 58-year-old man diagnosed with locally advanced, symptomatic HER2-overexpressing, AR-positive EMPD, who achieved long-term
tumor control with a sequence of several
trastuzumab-based treatments (more than 30 months with second-line
carboplatin plus
paclitaxel plus
trastuzumab followed by
trastuzumab maintenance; 9 months for third-line
vinorelbine plus
trastuzumab). Even if it is reported that AR expression occurs concomitantly with HER2 overexpression in more than half of the cases of EMPD, to the best of our knowledge, this is the first case report describing
androgen receptor blockade
therapy in combination with an anti-HER2 agent. Our patient did not benefit from
androgen receptor blockade in combination with
trastuzumab, thus suggesting that AR expression may simply reflect an intrinsic characteristic of the EMPD cell of origin, rather than
tumor dependence upon AR signaling. Given the reported sensibility to anti-HER2
therapy, also new
antibody drug conjugates targeting HER2 are worth exploring in the management of advanced EMPD.