No clinical evidence on the efficacy and safety of eribulin monotherapy has been obtained by a prospective clinical study in patients with metastatic breast cancer (MBC) who had well-defined taxane resistance. The present Phase II, multicenter, single-arm, open-label study aimed to obtain the evidence. Japanese female patients, aged 33–74 years who had the metastasis of taxane-resistant and histopathologically confirmed breast cancer, received eribulin mesylate 1.4 mg/m2 (equivalent to eribulin 1.23 mg/m2 [expressed as free base]) as a 2- to 5-min intravenous infusion on days 1 and 8 of each 21-day cycle. The primary endpoint was the clinical benefit rate (CBR) [complete response (CR), partial response (PR), and long-term stable disease (LSD) ≥24 weeks]. A total of 51 patients underwent chemotherapy cycles (median 4; range 1–42 cycles). The CBR was 39.2 % (CR 2.0 %; PR 23.5 %; and LSD 13.7 %), and the rate of progressive disease was 49.0 %. The median progression-free survival and the median overall survival were 3.6 months [95 % confidence interval (CI) 2.6–4.6 months] and 11.7 months (95 % CI 9.2–14.2 months), respectively. Grade 3 or greater adverse events were leukopenia (23.5 %), neutropenia (35.3 %), anemia (5.9 %), and febrile neutropenia (7.8 %). The incidences of grade 3 and 4 peripheral sensory neuropathy were 2.0 and 0 %, respectively. Eribulin showed a clinically manageable tolerability profile by dose adjustments or symptomatic treatment. Eribulin was effective and well tolerated in heavily pretreated patients with MBC who had well-defined taxane resistance, thus providing a potential therapeutic option in the clinical settings.

Herein we report a 62-year-old woman with an excisable breast tumor in whom needle tract seeding was suspected during preoperative ultrasound and magnetic resonance imaging (MRI). A tumor of the right breast was observed during initial examination, and she was referred to our hospital after fine-needle aspiration cytology led to diagnosis of breast cancer, even though core needle biopsy results were negative. Mammography showed a high-density mass with a portion of the margin exhibiting very fine serrations. Ultrasonography revealed a circular mass with a border that was indistinct in some regions, and a hypoechoic band that extended from the tumor toward the skin. A mass was observed on MRI, with a linear enhancement extending on the skin side, and needle tract seeding was suspected. Fine-needle aspiration cytology revealed malignancy, and the histological appearance was consistent with mucinous carcinoma. T1cN0M0 stage I breast cancer was diagnosed, and wide excision and sentinel lymph node biopsy were performed. The skin directly above the tumor was concurrently excised to remove the biopsy puncture site. Histopathological diagnosis confirmed mucinous carcinoma, with the tumor observed to extend linearly into the subcutaneous adipose tissue in a pattern corresponding to the biopsy puncture site. The stump of the excised breast was negative for cancer cells. The possibility of tumor seeding must be considered during fine-needle aspiration cytology and biopsy. As demonstrated in this case, diagnosis of such seeding through preoperative imaging may enable extraction of the entire lesion, including the needle tract.

IntroductionTrastuzumab is generally considered a highly safe drug, but there have been cases of infusion reaction and cardiotoxicity. This report will present a rare case of hepatotoxicity induced by trastuzumab used for adjuvant therapy of human epidermal growth factor receptor type 2-positive breast cancer.Case presentationThe patient was a 60-year-old Japanese postmenopausal woman with a non-contributory past medical history. She presented for detailed examination of an abnormality in her left breast. She had left breast cancer (T2N1M0, stage IIB) that was positive for estrogen receptor and progesterone receptor and was human epidermal growth factor receptor type 2 3+. She began receiving epirubicin and cyclophosphamide therapy but developed hepatotoxicity (aspartate aminotransferase 43U/L, alanine aminotransferase 104U/L, alkaline phosphatase 634U/L, and γ-glutamyl transpeptidase 383U/L). Thus, the therapy was discontinued after two cycles, and a weekly paclitaxel therapy was begun. After the absence of an adverse event was confirmed, she also began receiving trastuzumab (4mg/kg) at the second cycle. However, hepatotoxicity (aspartate aminotransferase 267U/L, alanine aminotransferase 246U/L, alkaline phosphatase 553U/L, and γ-glutamyl transpeptidase 240U/L) developed again, and trastuzumab was discontinued. She received paclitaxel monotherapy for a total of four cycles and subsequently underwent partial mastectomy and axillary dissection. After completing adjuvant radiation therapy (breast, 50Gy), she received trastuzumab administration (4mg/kg) but hepatotoxicity (aspartate aminotransferase 47U/L, alanine aminotransferase 102U/L, alkaline phosphatase 377U/L, and γ-glutamyl transpeptidase 91U/L) recurred. Thus, it was discontinued again. There was no hepatitis B or C virus infection, and a drug-induced lymphocyte stimulation test revealed a positive reaction to trastuzumab (stimulation index: 227%). Thereafter she has used only oral letrozole (2.5mg/day) and no recurrent cancer has been observed.ConclusionsAlthough trastuzumab is a highly safe drug, one must be mindful of its risk for hepatotoxicity. Periodic monitoring of liver functions is necessary during trastuzumab therapy.

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We report here a case of femoral diaphyseal fracture thought to be caused by oversuppression of bone remodeling due to long-term bisphosphonate treatment. The patient was a 63-year-old postmenopausal woman. She had undergone left lumpectomy and sentinel node biopsy for left breast cancer at age 57. The case was diagnosed as pT2N0M0, stage IIA breast cancer. The biopsy sample was positive for hormone receptors and negative for HER2 protein. Postoperatively, exemestane was administered as adjuvant therapy. Right axillary lymph node metastasis was found at age 59, and right axillary lymph node dissection was performed. Postoperatively, epirubicin/cyclophosphamide and paclitaxel were administered. Subsequently, letrozole was administered. However, bone metastases to the first thoracic vertebra and right ilium were found at age 60, and zoledronic acid administration (4 mg/month) for bone metastasis was initiated. The patient developed a transverse fracture in the proximal left femoral diaphysis when she walked on a flat surface after zoledronic acid was administered for 2 years, 10 months. She was treated with an intramedullary nail for left femoral diaphyseal fracture. Cancellous bone of the medullary cavity was histopathologically examined, but there were no metastatic lesions from the breast cancer and no osteoblasts or osteoclasts were observed. Zoledronic acid was immediately discontinued in this patient. In recent years, cases of atypical femoral diaphyseal fractures caused by minor trauma in patients undergoing long-term bisphosphonate treatment have been reported. Thus, careful observation is required for patients who are anticipating bisphosphonate treatment.