Comparison of the biomarkers for targeted therapies in primary extra-mammary and mammary Paget's disease.

BACKGROUND: Primary Extra-mammary Paget's disease (EMPD) is a very rare cutaneous adenocarcinoma affecting anogenital or axillary regions. It is characterized by a prolonged course with recurrences and eventually distant metastatic spread for which no specific therapy is known. METHODS: Eighteen EMPD (13 vulvar and five scrotal) and ten mammary Paget's disease (MPD) cases were comprehensively profiled for gene mutations, fusions and copy number alterations, and for therapy-relevant protein biomarkers). RESULTS: Mutations in TP53 and PIK3CA were the most frequent in both cohorts: 7/15 and 5/15 in EMPD; 1/6 and 4/7 in MPD HER2 gene amplification was detected in 4/18 EMPD (3 vulvar and 1 scrotal case) in contrast to MPD where it was detected in the majority (7/8) of cases. TOP2A gene amplification was seen in 2/12 EMPD and 1/6 MPD, respectively. Similarly, no difference in estrogen receptor expression was seen between the EMPD (4/15) and MPD (3/10). Androgen receptor was also expressed in the majority of both cohorts (12/16 EMPD) and (7/8 MPD).Here ARv7 splice variant was detected in 1/7 EMPD and 1/4 MPD cases, respectively. PD-L1 expression on immune cells was exclusively observed in three vulvar EMPD. In contrast to MPD, six EMPDs harbored a "high" tumor mutation burden (≥10 mutations/Mb). All tested cases from both cohorts were MSI stable. CONCLUSIONS: EMPD shares some targetable biomarkers with its mammary counterpart (steroid receptors, PIK3CA signaling pathways, TOP2A amplification). HER2 positivity is notably lower in EMPD while biomarkers to immune checkpoint inhibitors (high TMB and PD-L1) were observed in some EMPD. Given that no consistent molecular alteration characterizes EMPD, comprehensive theranostic profiling is required to identify individual patients with targetable molecular alterations.

[Evaluation of hypnosis in pain management during photodynamic therapy: a pilot study]. / Évaluation de l'hypnose à visée antalgique dans la photothérapie dynamique : étude pilote.

BACKGROUND: Pain is the main adverse effect of photodynamic therapy (PDT) and few effective analgesic methods are currently available. Our aim was to evaluate the efficacy of hypnoanalgesia with the use of PDT. PATIENTS AND METHODS: Between August 2011 and February 2013, a hypnoanalgesia session was proposed to patients requiring PTD for the treatment of (pre)carcinomatous lesions. At the end of the hypnosis session, patients evaluated their pain on a numeric pain scale (NPS) of 0 to 10. RESULTS: Twelve patients of average age 74.6 years were included. The indication for PDT was actinic keratosis (AK) in 9 patients, 1 Bowen's disease of the penis, 1 mammary Paget's disease and 1 bowenoid papulosis of the penis. Hypnoanalgesia was effective in 8 patients with a mean pain evaluation score of 2.9/10 on the NPS. Six of these 8 patients had previously undergone treatment by PDT without hypnosis and with an average pain score of 8.3/10. DISCUSSION: Hypnoanalgesia appears to be of value for pain management with PTD. This method is simple, inexpensive and devoid of side effects, and it is active on both pain and anxiety. To improve the use of hypnoanalgesia in PDT, it would be necessary to have better knowledge of the predictive factors for pain in PDT, to determine how to best select patients "sensitive" to hypnosis, and to encourage the training of nurses and doctors in this method.

[A case of pagetoid carcinoma of the breast in nearly complete response by primary systemic therapy].

A 62-year-old female presented with an erosion of the left nipple. At the preoperative examination, it was diagnosed as a Pagetoid carcinoma with an invasive carcinoma. After primary systemic therapy(weekly paclitaxel/trastuzumab), we performed an operation. The only remaining Paget cell was confirmed in the resected specimen, and no other malignant cells were confirmed. There is no report that the preoperative chemotherapy for the Pagetoid carcinoma with an invasive carcinoma. The patient has had no evidence of recurrence 1. 5 years after the operation.

Effectiveness of photodynamic therapy for mammary and extra-mammary Paget's disease: a state of the science review.

BACKGROUND: Paget's disease is a rare skin disorder occurring in the breast (mammary) or in the groin, genital, peri-anal and axillary regions (extra-mammary). Typical treatment involves surgical excision, which in the case of extra-mammary Paget's disease, can lead to significant morbidity. Photodynamic therapy (PDT) which uses a topical or intravenous photosensitizing agent that is activated by a light source to ablate abnormal tissue, offers a minimally invasive alternative. The purpose of this study was to assess the effectiveness of photodynamic therapy in the treatment of Paget's disease. METHODS: Following Cochrane guidelines, a comprehensive systematic review of all clinical studies and reports examining the use of PDT for mammary and extra-mammary Paget's disease was conducted. Study quality was assessed using the Oxford Levels of Evidence Scale. RESULTS: 21 retrospective and 2 prospective non-comparative studies were identified and included in the review: 9 case reports with 1-2 patients and 14 case series with 1-16 patients. These reports totalled 99 patients with 133 extra-mammary Paget's lesions and 3 patients (with 3 lesions) with mammary Paget's disease. Follow-up periods were typically one year or less, with 77/133 extra-mammary lesions exhibiting complete response to PDT. One recurrent mammary skin lesion and two mammary lesions treated concomitantly with surgery also exhibited complete responses. CONCLUSIONS: Evidence of the effectiveness of PDT for Paget's disease is promising, but limited. This may, in part, be explained by the rarity of the condition, making controlled comparative clinical trials challenging.

[A case of mammary Paget's disease with early systemic recurrence after operation].

A 66-year-old woman visited our hospital because of redness and erosion of her right breast, and was diagnosed with mammary Paget's disease by histological examination of erosive skin. The patient had a simple mastectomy. The pathological diagnosis was mammary Paget's disease (8x7.5 cm) showing intraductal spread. The resected skin margin was negative. Partially dermal microinvasion and lymphatic involvement were found. Immunohistochemical analysis of this tumor showed ER negative, PgR negative, and HER2 positive (3+). Eighteen months after the operation, she presented with redness of the chest wall with edema of the right arm. Incisional biopsy on the chest mass revealed a local recurrence of mammary Paget's disease. In addition, she had carcinomatous lymphangiosis in the bilateral lung, nodal metastases in the ipsilateral axillary and mediastinal space, and contralateral breast metastases on CT. She was treated with twelve courses of weekly paclitaxel in combination with trastuzumab. A complete response was obtained eleven months after initiation of chemotherapy. A rare case of early systemic recurrence of mammary Paget's disease after curative operation is reported with a review of the literature.

Treatment of mammary and extramammary Paget's skin disease with topical imiquimod.

BACKGROUND: Paget's disease is an uncommon epidermal cancer, affecting all skin regions wherever apocrine glands are present. It is divided into extramammary (EMPD) and mammary Paget's disease (MPD). It can be confined to the epithelium or may be associated with an underlying adenocarcinoma. The diagnosis is confirmed by skin biopsy and the treatment depends on characteristics of the underlying cancer. Surgery is the first-line treatment. Imiquimod, a topical immunomodulator, approved its efficiency in several skin neoplasms and has been shown as a safe treatment for EMPD. However, it has never been reported for the treatment of MPD. OBSERVATIONS: We report on two cases of EMPD and MPD successfully treated with imiquimod 5% cream. CONCLUSION: This non-surgical method may be considered as a primary treatment when Paget's disease is not associated with an underlying malignancy. The good prognosis with a long-term survival, the anatomic localization and the poor general condition of elderly people may favor imiquimod as an alternative treatment. On the other hand, it will reduce the extent of excision when it anticipates surgery.

Clinical and histopathologic observations of the action of imiquimod in an epithelioid hemangioendothelioma and Paget's mammary disease.

An epithelioid hemangioendothelioma and Paget's disease of the breast were treated with topical imiquimod 5% cream with very impressive results. In both of the tumors complete disappearance of the lesions occurred. In this article, in addition to describing the treatment approach, the findings in biopsy specimens of the epithelioid hemangioendothelioma and the Paget's disease before, during, and after therapy will be described. The histologic findings show ample evidence that there is both a lymphocytic T helper 1-like and T helper 2-like response from imiquimod. Direct evidence of lymphocytotoxicity was found. Furthermore, mast cells appear to be involved in the development of regression in the vascular tumor. Although the study is very limited and reports only two cases, the results are striking. We considered it important to describe these findings because of their possible use in developing strategies for the application of imiquimod in the treatment of other tumors in human beings.

Surgical treatment in Paget's disease of the breast.

The extent of the operation in Paget's disease of the breast depends largely on the degree of clinical advancement of neoplasm as well as counter-indications for breast conserving therapy. Despite the increasing use of breast conserving therapy, rather few such operations of this kind have been performed in our department. We have carried out 29 mastectomies and only 6 breast conserving operations. No matter what type of therapy was applied the percentages of 5-year survivals for the patients with non-invasive component and for the ones with invasive component were respectively 89.76% and 49.32%.

Breast carcinoma associated with Klinefelter syndrome: a case report.

Klinefelter syndrome increases the risk of developing breast cancer to approximately 1/5 that of women and 20 times that of normal men. A case report and the patient's response to hormone manipulation for metastatic disease is described.