A 40-year-old woman was diagnosed with cancer of the left breast (cT2NxM0) in June 2010. She received neoadjuvant chemotherapy with four cycles of doxorubicin and cyclophosphamide (AC), followed by four cycles of docetaxel. Afterwards, the patient underwent a total mastectomy and left axillary lymph node dissection (pT3N1M0) in October 2010. The pathology report showed ER and PR negative, but HER2 3+ positive by immunohistochemistry (IHC) and no skin and chest wall involvement with dermal lymphatic invasion. She subsequently started adjuvant radiotherapy and trastuzumab therapy (Fig. 1A).

After four months of adjuvant trastuzumab therapy, we found localized erythematous to purplish patch lesions, with multiple masses measuring 1-2 cm in size on the left anterior chest (Fig. 1B). A punch biopsy of the lesions confirmed metastatic breast cancer.

She enrolled in a clinical trial for pan-HER inhibitor of trastuzumab and failed due to recurrent breast cancer. She received chemotherapy with afatinib, pan-HER inhibitor plus vinorelbine in February 2012. After one cycle of treatment, her skin lesion showed rapid improvement (Fig. 1C). However, the same skin lesion showed progression again after six cycles of treatment. We applied lapatinib, another HER2 targeted, tyrosine kinase inhibitor, plus capecitabine after disease progression. After onlyone cycle of lapatinib treatment, the skin lesion showed improvement again.

A 57-year-old woman was diagnosed with cancer of the left breast (cT4bN2M0) in January 2010. She received neoadjuvant chemotherapy with four cycles of AC. After that, we found that the primary breast mass size had increased and confirmed disease progression by imaging study. She underwent a left modified radical mastectomy (MRM) in April 2010 (T4N2M0). The pathology indicated ER and PR negative, but HER2 3+ positive by IHC and underlying fascia and muscle involvement and dermal lymphatic invasion. She thus started four cycles of adjuvant paclitaxel with trastuzumabin May 2010, followed by adjuvant trastuzumabtherapy until February 2011.

Ten days after the final trastuzumab treatment, she presented with an erythematous, annular, patch-like skin lesion with a central clearing on the left breast and lateral chest wall (Fig. 2A). The result of punch biopsy indicated a metastatic carcinoma in the dermal lymphovascular space of the breast. She received palliative chemotherapy with six cycles of capecitabine combined with lapatinib. After one cycle of capecitabine and lapatinib, the skin lesion showed rapid improvement (Fig. 2B). A complete response was maintained until nine cycles of this regimen. However, the same area of skin lesions showed progression again after nine cycles of lapatinib treatment. We retried trastuzumab therapy with another cytotoxic chemoagent, vinorelbine, combined with radiotherapy. After three cycles of chemotherapy, the skin lesions showed improvement (Fig. 2C).

A 44-year-old woman was diagnosed with cancer of the left breast (cT2N+M0) in August 2011. She received neoadjuvant chemotherapy with four cycles of AC. During treatment, a lymph node in the left supraclavicular fossa became palpable and suspicious for metastatic breast cancer. She underwent a left MRM and left axillary lymph node dissection (pT2N3M0) in December 2011. The pathology indicated triple negative breast cancer by IHC with no skin and chest wall involvement but showed dermal lymphatic invasion. She subsequently received adjuvant chemotherapy with three cycles of docetaxel.

During the fourth cycle of adjuvant docetaxel therapy, she presented with a localized erythematous patch and multiple papules with yellowish crusts near the operation scar on the left chest wall (Fig. 3A). A skin punch biopsy confirmed a metastatic carcinoma of the breast. She received combination therapy of gemcitabine plus cisplatin from April 2012. After four cycles of chemotherapy, the skin lesions showed waxing and waning without definite response (Fig. 3B).

A 44-year-old woman was diagnosed with cancer of the left breast (cT3N+M0) in June 2011. She started neoadjuvant chemotherapy with four cycles of AC followed by docetaxelplus S-1 based on a clinical trial conducted in July 2011. After six cycles of neoadjuvant chemotherapy, the patient was admitted to the hospital due to an atypical pneumonia. Despite receiving treatment for atypical pneumonia, her condition did not show significant improvement. While receiving treatment for pneumonia, we found a skin lesion that was suspicious for a metastatic lesion. She underwent a left MRM for breast cancer, and a wedge resection of her lung via video assisted thoracoscopy for a suspicious lesion of cryptogenic organizing pneumonia in November 2011. The breast pathology indicated triple negative breast cancer by IHC with dermal lymphatic invasion, and the lung pathology showed metastatic breast cancer with the same histology. She started palliative chemotherapy with gemcitabine and cisplatin in February 2012. After three cycles of platinum based chemotherapy, we found that the skin lesions had progressed with localized, erythematous scaly plaques with brown pigmentation on the left chest wall (Fig. 4A). She received palliative radiotherapy for those lesions followed by cytotoxic chemotherapy with paclitaxel plus ifosfamide. The skin lesions subsequently stabilized (Fig. 4B). However, a newly developed liver lesion was found after four cycles of paclitaxel plus ifosfamide.