Sequential somatic mutations upon secondary anti-HER2 treatment resistance in metastatic ERBB2S310F mutated extramammary Paget’s disease

Nordmann, Thierry M.; Messerli-Odermatt, Olivia; Meier, Larissa; Micaletto, Sara; Coppetti, Thomas; Nägeli, Mirjam; Kamarachev, Jivko; Kudura, Ken; Freiberger, Sandra N.; Rordorf, Tamara; Mangana, Joanna; Braun, Ralph; Dummer, Reinhard

doi:10.18632/oncotarget.27272

Cited by 10 publications

(11 citation statements)

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“…In 2019, Nordmann TM reported a case with EMPD harboring HER2 S310F mutation, who achieved near-complete response after treatment with trastuzumab and carboplatin. 17 In the present study, we reported a novel HER2 gene alteration that these EMPD patients harbored triple uncommon HER2 mutations (R678Q/S310Y/S310F). Meanwhile, this patient showed a partial response to pyrotinib.…”

Section: Discussionmentioning

confidence: 52%

<p>Response to Pyrotinib in a Chinese Patient with Bone-Metastatic Scrotal Paget’s Disease Harboring Triple Uncommon HER2 Mutation: A Case Report</p>

Guo¹,

Jiao²,

Wu³

et al. 2020

OTT

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Background: Previous studies have suggested the efficacy of HER2 antibody (trastuzumab) in scrotal Paget's disease with HER2 amplification or overexpression. However, no report about the effectiveness of HER2 inhibitor (pyrotinib) in those patients has been provided until now. Case Presentation: We present a case of a Chinese patient with bone-metastatic scrotal Paget's disease harboring triple uncommon HER2 mutations (R678Q/S310Y/S310F). Due to poor conditions (severe anemia, thrombocytopenia, ECOG PS3), this patient could not tolerate traditional chemotherapy and radiotherapy. Then, the patient participated in a registered clinical trial (NCT03239015) about basket trial for intractable cancer. The patient received pyrotinib (400 mg po qd) and achieved a partial response for 4.0 months. Conclusion: This is the first report describing a patient with scrotal Paget's disease harboring triple uncommon HER2 mutation who responds well to pyrotinib. This case suggested that HER2 mutation is also a potential biomarker for treatment in extramammary Paget's disease and pyrotinib may be an ideal choice for these patients.

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Section: Discussionmentioning

confidence: 52%

<p>Response to Pyrotinib in a Chinese Patient with Bone-Metastatic Scrotal Paget’s Disease Harboring Triple Uncommon HER2 Mutation: A Case Report</p>

Guo¹,

Jiao²,

Wu³

et al. 2020

OTT

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“…8 This report describes three cases of metastatic and one case of recurrent HER2-positive vulvar Paget's disease effectively treated with weekly paclitaxel and trastuzumab. In addition to case reports of patients with HER2 positive, non-vulvar extramammary Paget's disease treated with anti-HER2 agents, [9][10][11][12][13][14] there are four separate case reports of women with metastatic HER2 positive vulvar Paget's disease treated similarly (online supplemental table). Our series, therefore, represents the largest number of reported cases of vulvar Paget's treated with these agents.…”

Section: Discussionmentioning

confidence: 99%

Human epidermal growth factor receptor-2 (HER2) is a potential therapeutic target in extramammary Paget’s disease of the vulva

Bartoletti

Mazzeo

Scordilli

et al. 2020

Int J Gynecol Cancer

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BackgroundInvasive vulvar Paget’s disease with over-expression of the human epidermal growth factor receptor 2 (HER2) protein is potentially suitable for targeted therapy, especially in a metastatic setting where no effective treatments are available.MethodsFour consecutive patients with HER2 positive advanced vulvar Paget’s disease, treated with weekly trastuzumab (loading dose 4 mg/kg, then 2 mg/kg) and paclitaxel (80 mg/m2) followed by 3-weekly trastuzumab maintenance (6 mg/kg), are reported.ResultsMedian age and follow-up of patients were 62.5 years (45–74) and 16 months (6-54), respectively. Complete or partial responses were observed in all patients. Median time to response was 3 months (range 2–4), while median duration of response was 10 months (range 2–34). Case 1 presented with pulmonary and lymph nodes involvement. She experienced a radiological complete response after 24 treatment administrations, and a progression-free survival of 36 months. At disease progression, treatment re-challenge achieved partial response. She is currently receiving treatment with trastuzumab–emtansine. Case 2 was a 74-year-old woman who developed pulmonary metastasis after first-line cisplatin treatment. She had a partial response and a progression-free survival of 10 months. Case 3 had inguinal and para-aortic lymphadenopathy in complete response after 18 treatment administrations. She developed brain metastasis while receiving trastuzumab maintenance. Case 4 was treated for locally advanced disease and experienced a subjective benefit with relief in perineal pain and itching. No unexpected treatment-related side effects were reported.ConclusionsAdvanced vulvar Paget’s disease is a rare disorder and no standard treatment is available. In the sub-group of HER2 positive disease, weekly paclitaxel–trastuzumab appears to be active and safe, and may be considered a therapeutic option in these patients.

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“…As described above, HER2 overexpression is frequently found in EMPD lesions, and HER2 may play crucial roles in the development and progression of EMPD in cases of HER2-positive tumors. Indeed, multiple cases of HER2-positive advanced EMPD have been reported that have shown the antitumor effects of anti-HER2 antibody, trastuzumab, monotherapy, or trastuzumab combined with other chemotherapies, such as paclitaxel or carboplatin [57,[143][144][145][146][147][148]. Most of these cases showed PFS of longer than 12 months, suggesting that anti-HER2 antibody is a promising therapy for advanced EMPD.…”

Section: Anti-her2 Antibody Therapymentioning

confidence: 99%

Extramammary Paget’s Disease: Diagnosis, Pathogenesis, and Treatment with Focus on Recent Developments

Ishizuki

Nakamura

2021

Current Oncology

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Extramammary Paget’s disease (EMPD) is a rare neoplasm that usually develops in apocrine gland-bearing areas, such as the vulva, scrotum, and penis. EMPD may present with a focal, multifocal, or an ectopic lesion. Clinically, EMPD lesions often exhibit infiltrative erythema, which is sometimes similar to other skin disorders such as eczema. While primary EMPD arises as intraepithelial neoplasm of the epidermis, EMPD-like lesions may occur from epidermotropic spread of malignant cells or direct extension from an underlying internal neoplasm, known as secondary EMPD. Because treatment strategies differ for primary EMPD and secondary EMPD, accurate diagnosis based on detailed histopathological evaluation is required. In the early stages, EMPD usually shows indolent growth, and most cases are diagnosed as carcinoma in situ. However, invasive lesions may result in metastases, and deep invasion is associated with high incidence of metastases. Conventional chemotherapies have been used for EMPD treatment in patients with distant metastases, but the efficacy is not satisfactory, and the prognosis for such patients remains poor. Recent studies have provided various insights into the molecular pathogenesis of the development and advancement of EMPD, which may lead to novel treatment approaches for metastatic EMPD. This review addresses the diagnosis, pathogenesis, and treatment of EMPD with focus on recent progress in understanding this disease.

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Sequential somatic mutations upon secondary anti-HER2 treatment resistance in metastatic ERBB2S310F mutated extramammary Paget’s disease

Cited by 10 publications

References 11 publications

<p>Response to Pyrotinib in a Chinese Patient with Bone-Metastatic Scrotal Paget’s Disease Harboring Triple Uncommon HER2 Mutation: A Case Report</p>

<p>Response to Pyrotinib in a Chinese Patient with Bone-Metastatic Scrotal Paget’s Disease Harboring Triple Uncommon HER2 Mutation: A Case Report</p>

Human epidermal growth factor receptor-2 (HER2) is a potential therapeutic target in extramammary Paget’s disease of the vulva

Extramammary Paget’s Disease: Diagnosis, Pathogenesis, and Treatment with Focus on Recent Developments

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