There is no effective treatment for metastatic cutaneous apocrine carcinoma (CAC). In some cases of CAC, human epidermal growth factor receptor 2 (HER2) is overexpressed.1,2 We report the case of a patient with metastatic CAC for whom a combination of the anti-HER2 humanized monoclonal antibodies with taxane chemotherapy was effective.
A man in his 50s presented with an asymptomatic erythematous tumor and lymph nodes fused with the right chest wall, axillary artery, and vein of the right axilla. (Figure 1A). A skin biopsy performed from a specimen of the axilla revealed that atypical tumor cells had proliferated in the dermis to the subcutis (Figure 2A). Immunohistochemically, these tumor cells were positive for gross cystic disease fluid protein 15 and HER2 (immunohistochemical score of 3+) (Figure 2B and C) and negative for mammaglobin and estrogen and progesterone receptors. From these findings, we diagnosed the tumor as CAC. Computed tomography (CT) revealed fused lymph nodes in the right axilla, which infiltrated the right chest wall, axillary artery, and vein. The CT findings enabled us to determine that there was no surgical indication. Therefore, considering that the tumor cells strongly expressed HER2, we administered the combination of pertuzumab and trastuzumab, which are HER2 inhibitors, with taxane chemotherapy according to the treatment of HER2-positive metastatic breast cancer (MBC).3- 5 These drugs were intravenously administered every 3 weeks. Pertuzumab and trastuzumab were administered at fixed dosages of 420 mg and 6 mg/kg, respectively, and docetaxel was administered at a dosage of 75 mg/m2. After 7 cycles of this combination therapy, erythematous lesions and fused lymph nodes dramatically decreased (Figure 1B). At this point, we determined that it was possible for the patient to undergo surgical treatment. We performed a wide local excision of the primary lesion and regional lymph node dissection, and the defect was reconstructed using the latissimus dorsi musculocutaneous flap (Figure 1C). Pathological results showed that there were viable tumor cells in dissected lymph nodes; however, the accessory mammary gland was not identified. Additional radiotherapy was administered on the right axilla with a total dose of 60 Gy, and subsequent trastuzumab monotherapy was administered. Following 11 cycles of this monotherapy, CT showed complete response (CR). At the last follow-up, 11 months after surgical treatment, the patient was disease free.
A, A 90 × 50-mm, slightly raised erythematous lesion with lymphadenopathy (100 × 100 mm in size) is present at the right axilla. In-transit or satellite metastases are present around the tumor. B, After 7 cycles of the combination therapy of pertuzumab and trastuzumab with docetaxel, right axillary lesions dramatically decreased. C, After 1 month of surgical treatment.
A, A biopsy specimen revealed that atypical tumor cells proliferated in the skin, forming strands or solid pattern nests in collagen fibers (hematoxylin-eosin, original magnification ×100). B, Immunohistochemical staining for gross cystic disease fluid protein 15 (original magnification ×100) revealed positive tumor cells. C, Immunohistochemical staining for human epidermal growth factor receptor protein 2 (HER2) (original magnification ×100) revealed positive tumor cells.
The National Comprehensive Cancer Network guidelines recommend the combination of pertuzumab and trastuzumab with docetaxel as a preferred option for first-line treatment of patients with HER2-positive MBC.3 In general, CAC has a histological similarity to the apocrine subtype of breast cancer. Therefore, if patients with metastatic CAC have overexpression of HER2, HER2 inhibitors, such as pertuzumab and trastuzumab, are expected to be effective for them.
Pertuzumab and trastuzumab are more active in combination than when used alone because these 2 agents bind to different HER2 epitopes and provide a comprehensive signaling blockade.6 According to a randomized clinical trial of patients with HER2-positive MBC,4,5 the combination of pertuzumab and trastuzumab with docetaxel compared with placebo and trastuzumab with docetaxel significantly improved both progression-free and overall survival. Therefore, the addition of pertuzumab plays an important role in the improvement of outcomes for patients with HER2-positive MBC. However, with regard to HER2-positive metastatic CAC, to our knowledge, there are no reports of therapy with pertuzumab. In the present case, the tumor cells dramatically regressed with the combination of pertuzumab and trastuzumab with docetaxel. Because of the effect of this combination therapy, we could perform surgery in this patient; to date, for 11 months after surgical treatment, CR has been maintained by combining subsequent radiation therapy and trastuzumab monotherapy.
This case suggests that the combination of pertuzumab-based targeted therapy with taxane chemotherapy may develop into a new treatment option for patients with HER2-positive metastatic CAC.
Corresponding Author: Masaki Otsuka, MD, Department of Dermatology, Shizuoka Cancer Center Hospital, 1007 Shimonagakubo, Nagaizumi-cho, Shizuoka, Japan (firstname.lastname@example.org).
Published Online: September 16, 2015. doi:10.1001/jamadermatol.2015.2507.
Conflict of Interest Disclosures: None reported.
Otsuka M, Yamasaki O, Kaji T, Shien T, Iwatsuki K. Metastatic Cutaneous Apocrine Adenocarcinoma Treated With a Combination of Pertuzumab-Based Targeted Therapy and Taxane ChemotherapyA Case Report. JAMA Dermatol. 2016;152(1):111-113. doi:10.1001/jamadermatol.2015.2507