A recent study has shed new light on the potential treatment options for patients suffering from HER2-positive extramammary Paget disease (EMPD), a rare and challenging type of skin cancer. The research delves into the role of the human epidermal growth factor receptor 2 (HER2) in EMPD and introduces disitamab vedotin (DV), a novel humanized anti-HER2 antibody-drug conjugate (ADC), as a promising therapeutic candidate.
EMPD primarily affects areas of the skin rich in apocrine glands and can present either as a primary condition or as secondary to an underlying visceral carcinoma. While surgery remains the standard treatment for intraepithelial EMPD, more advanced cases often require chemotherapy or targeted therapies.
HER2 overexpression has been identified as a poor prognostic marker in various cancers, but its role in EMPD has been understudied due to the rarity of the disease. Previous research on HER2 in EMPD has been limited by small sample sizes, leading to inconsistent findings regarding the prevalence of HER2 overexpression in these patients. The current study seeks to address this gap by analyzing HER2 status in a larger cohort of 129 EMPD patients from three medical centers, using immunohistochemical (IHC) staining and fluorescence in-situ hybridization (FISH) analysis.
The findings reveal that HER2 protein is expressed in a significant number of EMPD cases, with varying levels of intensity. In particular, higher HER2 expression levels (scored as 2+ or 3+) were more commonly observed in invasive forms of EMPD compared to intraepithelial cases. Moreover, the study found a correlation between higher HER2 expression and an increased likelihood of lymph node metastasis, suggesting that HER2 may play a role in the disease’s progression.
Notably, the study also explored the use of DV in two patients with advanced EMPD who had not responded to prior chemotherapy treatments. Both patients showed partial responses to DV, according to the modified RECIST 1.1 criteria, indicating that even patients with lower levels of HER2 expression could potentially benefit from HER2-targeted therapies.
The research highlights the potential of HER2 as a therapeutic target in EMPD and underscores the need for further exploration of HER2-targeted ADC therapies, particularly DV. The study’s multicenter approach and its focus on low HER2 expression levels in EMPD add to its significance, providing new insights that could expand treatment options for this rare malignancy.
In conclusion, this study offers a new perspective on the management of HER2-positive EMPD, suggesting that even patients with low HER2 expression may respond to targeted therapies like DV. Further clinical trials and research are necessary to validate these findings and to better understand the efficacy and safety of ADC therapies in a broader population of EMPD patients.
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