Content » Vol 92, Issue 6

Letter to the Editor

Successful Treatment of HER-2-Positive Metastatic Apocrine Carcinoma of the Skin with Lapatinib and Capecitabine

Takanori Hidaka, Taku Fujimura*, Akiko Watabe, Akira Hashimoto, Tahahiro Haga, Kaoru Onami, Masato Mizuashi and Setsuya Aiba

Department of Dermatology, Tohoku University, Graduate School of Medicine, Seiryo-machi 1-1, Aobaku, Sendai, 980-8574, Japan. *E-mail:

Accepted January 12, 2012.

Primary cutaneous apocrine carcinoma (AC) is a rare and highly aggressive cutaneous adenocarcinoma. In general, most cutaneous AC occurs in the axilla and it is more common in middle-age women (1). Complete remission by chemotherapy is uncommon and median survival was only 2 years for patients with Bloom-Richardson grade 3 tumours (2).

HER-2 is a 1260-amino-acid transmembrane protein with tyrosine kinase that plays a central role in cell differentiation, adhesion and motility (3). In the treatment of breast cancer, HER-2 signal inhibitors, such as the humanized monoclonal antibody trastuzumab and the small molecule tyrosine kinase inhibitor lapatinib, have been used as a standard therapy for HER-2 overexpressing metastatic tumour (4). Moreover, several reports have indicated that the apocrine subtype of breast cancer consistently overexpressed HER-2 (5). Interestingly, AC has a marked histological similarity to the apocrine subtype of breast cancer, including immunohistochemistry (6). Therefore, we hypothesized that a HER-2 signal inhibitor, such as lapatinib, can be effective for HER-2 overexpressing metastatic AC.

We report here a patient with a metastatic AC showing a complete remission following the administration of lapatinib with capecitabine. To our knowledge, this is the first case report describing the successful treatment of metastatic AC with HER-2 signal inhibitors.


A 62-year-old Japanese man visited our outpatient clinic with a 3-year history of a bleeding nodule on his scalp. Physical examination revealed a dome-shaped, 45 × 40 mm, ulcerated nodule on the left side of his scalp (Fig. 1) and bilateral cervical lymph node swelling. Biopsy revealed that tumour cells proliferated mainly in the dermis, forming solid pattern nests and pagetoid epidermal upward migration, especially at the hair follicle (Fig. 2a). The tumour consisted mainly of neoplastic cells with abundant eosinophilic cytoplasm, large nuclei containing prominent macronucleoli and cytological pleomorphism (Fig. 2b). Immunohistochemically, these tumour cells were positive for cytokeratin (CK) 7, CK8, CK18, CK19, gross cystic disease fluid protein (GCDFP)-15, a1-AT, androgen receptors and HER-2 (immunohistochemistry (IHC) score of 3+), and negative for CK10, CK14, CK20, p63, CEA, CA19-9, HER-par-1, a FP and oestrogen receptor. Moreover, the cytoplasm contained periodic acid-Schiff diastase resistant granules. From these data, we diagnosed his tumour as an AC. Computed tomography (CT) scan from neck to abdomen revealed significant enlargement of cervical lymph nodes. There was no sign of distant metastasis. A cranial magnetic resonance scan did not show any sign of intracranial involvement. There was no evidence of an internal malignancy on screening CT scan.

Fig. 1. A dome-shaped, 45 × 40 mm, easy-bleeding nodule on the left side of the scalp.


Fig. 2. (a) Tumour cells proliferate mainly in the dermis, forming solid pattern nests and pagetoid epidermal upward migration, especially at hair follicle (H&E). (b) The tumour consists mainly of neoplastic cells with abundant eosinophilic cytoplasm, large nuclei containing prominent macronucleoli and cytological pleomorphism (H&E). Immunohistochemical staining for the primary tumour reveals that this tumour was positive for (c) gross cystic disease fluid protein 15 and (d) HER-2. a, c, d: × 100, b: × 400.

The tumour was excised with a 3-cm margin. Additional radiotherapy after surgical treatment was performed on left parietal and cervical regions, with a total dose of 70 Gy. One month after the surgical treatment, cisplatin (80 mg/m2 every 4 weeks) was administered combined with 5-fluorouracil (800 mg/m2 for 5 days for 2 cycles).

Five months after the tumour excision, the CT scan disclosed multiple liver nodules, which were suspicious of AC metastasis. Since the metastatic lesions appeared during the course of the chemotherapy, we considered that these metastatic lesions were resistant to both cisplatin or 5-fluorouracil. Therefore, considering that the tumour cells express HER-2 strongly, with an IHC score of 3+, we administrated trastuzumab, 2 mg/m2 every week. Three months after the administration of trastuzumab, the CT scan showed complete regression of all metastatic tumours. Nevertheless, liver metastasis reappeared 7 months after the administration of trastuzumab (Fig. 3a). We considered that his tumour had become resistant to trastuzumab. Therefore, we next administrated lapatinib, 1,250 mg once daily, combined with capecitabine 1,000 mg/m2 twice daily for 14 of every 28 days. No side-effects were observed, except for slightly general fatigue. Four months after the administration of this combination therapy, all the metastatic tumours disappeared, as observed on the CT scan (Fig. 3b). Six months after the remission of liver metastasis, his AC was still under remission.


Fig. 3. Computed tomography scan disclosed multiple liver metastasis of apocrine carcinoma (arrows) (a) before the administration of HER-2 signal inhibitors, and (b) 4 months after the administration of lapatinib combined with capecitabine.


Apocrine neoplasms are well-known carcinomas in the mammary glands (7) and it is difficult to distinguish breast cancer morphologically from cutaneous AC (6). Several reports suggest that HER-2 signal inhibitors can improve response rates, time to progression, and even survival in only HER-2 overexpressing type breast cancer, so the evaluation of Her-2/neu expression is indispensable for the use of HER-2 signal inhibitors (8–11). Indeed, Slamon et al. (12, 13) mentioned that approximately 25–30% of breast cancers overexpress HER-2, and HER-2 signal inhibitors are administered in the treatment of breast cancer as standard (4). Moreover, HER-2 overexpression is known to associate with an aggressive clinical course and a poor outcome in cases of apocrine subtype of breast cancer (12–14). Previously, Wick et al. (15) reported that approximately 30% of cutaneous ductal sweat gland carcinomas overexpress HER-2. In the present case, trastuzumab was administered to HER-2-positive metastatic AC and achieved complete, but temporal, remission. Furthermore, we achieved complete resolution of recurrent hepatic lesions with lapatinib and capecitabine treatment. This case indicates that HER-2 signal inhibitors are quite effective for HER-2-positive AC.

The authors declare no conflict of interest


  • Chamberlain RS, Huber K, White JC, Travaglino-Parda R. Apocrine gland carcinoma of the axilla: review of the literature and recommendations for treatment. Am J Clin Oncol 1999; 22: 131–135.
  • Robson A, Lazar AJ, Ben Nagi J, Hanby A, Grayson W, Feinmesser M, et al. Primary cutaneous apocrine carcinoma: a clinico-pathologic analysis of 24 cases. Am J Surg Pathol 2008; 32: 682–690.
  • De Potter CR, Schelfhout AM. The neu-protein and breast cancer. Virchows Arch 1995; 426: 107–115.
  • Aebi S, Davidson T, Gruber G, Castiglione M. Primary breast cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2010; 21 Suppl 5: v9–14.
  • Vranic S, Tawfik O, Palazzo J, Bilalovic N, Eyzaguirre E, Lee LM, et al. EGFR and HER-2/neu expression in invasive apocrine carcinoma of the breast. Mod Pathol 2010; 23: 644–653.
  • Wallace ML, Longacre TA, Smoller BR. Estrogen and progesterone receptors and anti-gross cystic disease fluid protein 15 (BRST-2) fail to distinguish metastatic breast carcinoma from eccrine neoplasms. Mod Pathol 1995; 8: 897–901.
  • O’Malley FP, Bane AL. The spectrum of apocrine lesions of the breast. Adv Anat Pathol 2004; 11: 1–9.
  • Cobleigh MA, Vogel CL, Tripathy D, Robert NJ, Scholl S, Fehrenbacher L, et al. Multinational study of the efficacy and safety of humanized anti-HER2 monoclonal antibody in women who have HER2-overexpressing metastatic breast cancer that has progressed after chemotherapy for metastatic disease. J Clin Oncol 1999; 17: 2639–2648.
  • Mass RD, Press MF, Anderson S, Cobleigh MA, Vogel CL, Dybdal N, et al. Evaluation of clinical outcomes according to HER2 detection by fluorescence in situ hybridization in women with metastatic breast cancer treated with trastuzumab. Clin Breast Cancer 2005; 6: 240–246.
  • Press MF, Finn RS, Cameron D, Di Leo A, Geyer CE, Villalobos IE, et al. HER-2 gene amplification, HER-2 and epidermal growth factor receptor mRNA and protein expression, and lapatinib efficacy in women with metastatic breast cancer. Clin Cancer Res 2008; 14: 7861–7870.
  • Slamon DJ, Leyland-Jones B, Shak S, Fuchs H, Paton V, Bajamonde A, et al. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med 2001; 344: 783–792.
  • Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullrich A, McGuire WL. Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science 1987; 235: 177–182.
  • Slamon DJ, Godolphin W, Jones LA, Holt JA, Wong SG, Keith DE, et al. Studies of the HER-2/neu proto-oncogene in human breast and ovarian cancer. Science 1989; 244: 707–712.
  • Seshadri R, Firgaira FA, Horsfall DJ, McCaul K, Setlur V, Kitchen P. Clinical significance of HER-2/neu oncogene amplification in primary breast cancer. The South Australian Breast Cancer Study Group. J Clin Oncol 1993; 11: 1936–1942.
  • Wick MR, Ockner DM, Mills SE, Ritter JH, Swanson PE. Homologous carcinomas of the breasts, skin, and salivary glands. A histologic and immunohistochemical comparison of ductal mammary carcinoma, ductal sweat gland carcinoma, and salivary duct carcinoma. Am J Clin Pathol 1998; 109: 75–84.