Phase II clinical study of eribulin monotherapy in Japanese patients with metastatic breast cancer who had well-defined taxane resistance.

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/m(2) (equivalent to eribulin 1.23 mg/m(2) [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.

Efficacy of octreotide against chylothorax following lateral neck dissection for thyroid cancer: A case report.

INTRODUCTION: Postsurgical chylothorax is a rare complication of cervical dissection for thyroid cancer. We report that octreotide, a synthetic analog of somatostatin, is effective in treating chylothorax after thyroid carcinoma surgery. PRESENTATION OF CASE: The patient was a 48-year-old woman who presented to our institution complaining of a left anterior cervical mass. We diagnosed this as thyroid papillary carcinoma and performed a subtotal excision of the thyroid gland with left cervical lymph node dissection. The patient developed dyspnea, and a chest X-ray revealed bilateral chylothorax on Day 4 post-surgery. Octreotide was administered since bilateral chylothorax was noted. A marked decrease in chyle effusion was noted just 3 days after starting octreotide, and after a total of 9 days of treatment, there were no further signs of chylous effusion. DISCUSSION: Octreotide is effective against postsurgical chylothorax; however, if there are no signs of improvement, we believe surgical treatment should be considered. CONCLUSION: Octreotide should be administered first to treat postsurgical chylothorax before surgical treatment is considered.

A case of femoral diaphyseal fracture after long-term treatment with zoledronic acid.

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.

Hepatotoxicity induced by trastuzumab used for breast cancer adjuvant therapy: a case report.

INTRODUCTION: Trastuzumab 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 PRESENTATION: The 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 43 U/L, alanine aminotransferase 104 U/L, alkaline phosphatase 634 U/L, and γ-glutamyl transpeptidase 383 U/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 (4 mg/kg) at the second cycle. However, hepatotoxicity (aspartate aminotransferase 267 U/L, alanine aminotransferase 246 U/L, alkaline phosphatase 553 U/L, and γ-glutamyl transpeptidase 240 U/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, 50 Gy), she received trastuzumab administration (4 mg/kg) but hepatotoxicity (aspartate aminotransferase 47 U/L, alanine aminotransferase 102 U/L, alkaline phosphatase 377 U/L, and γ-glutamyl transpeptidase 91 U/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. CONCLUSIONS: Although 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.

Efficacy of high-dose toremifene therapy in postmenopausal patients with metastatic breast cancer resistant to aromatase inhibitors:a retrospective, single-institution study.

BACKGROUND: Aromatase inhibitors(AI)have established efficacy as first-line therapy in postmenopausal patients with hormone-sensitive metastatic breast cancer(MBC). However,the use of endocrine therapy has not yet been established for second-line and later therapy. Our study examined the efficacy of high-dose toremifene therapy(HD-TOR)in patients with MBC resistant to AIs. PATIENTS AND METHODS: A retrospective analysis was carried out to determine outcomes in 85 postmenopausal patients with MBC resistant to AIs who began HD-TOR between May 2001 and October 2011. The patients received toremifene 120 mg once daily on consecutive days. RESULTS: The objective response rate(ORR)was 21.2%,the clinical benefit rate(CBR)was 41.2%,and the median time to treatment failure(TTF)was 7.3 months. The CBR was high in patients with ER-positive status(p=0.045),no visceral metastasis(p=0.037),HD -TOR as first- or second-line therapy(p=0.007),no history of tamoxifen(TAM)therapy(p=0.019),and no history of chemotherapy(p=0.017). Multivariate analysis showed that ER-positive status(p=0.005, odds ratio: 0.064)and no visceral metastasis(p=0.034, odds ratio: 0.323)were independent predictors of efficacy. The TTF was significantly longer in patients with ER-positive status(p=0.019)and no history of TAM therapy(p=0.015). Multivariate analysis showed that ER-positive status(p=0.025, hazard ratio: 0.377)and no history of TAM therapy(p=0.002, hazard ratio: 0.422)were independent predictors of efficacy. No patient discontinued HDTOR therapy due to adverse events. CONCLUSION: HD-TOR is an effective endocrine therapy for patients with MBC who have failed AIs.

Locally advanced breast cancer with bleeding - two cases effectively treated with bevacizumab plus weekly paclitaxel.

Bleeding is one of the serious adverse events of bevacizumab (BV). In our report, two patients had locally advanced breast cancer with bleeding. They received BV plus weekly paclitaxel (PTX), and good local control was observed. Case 1: The patient was a 50-year-old postmenopausal woman. She had left-sided breast cancer (T4cN2cM1 [bone]-stageIV) that was negative for estrogen receptor (ER), negative for progesterone receptor(PgR), and 1+for human epidermal growth factor receptor 2 (HER2). The patient began receiving different regimens of chemotherapy: 5-fluorouracil (5-FU), epirubicin (EPI), and cyclophosphamide(CPA), (FEC); PTX; docetaxel (DTX); and gemcitabine (GEM) plus PTX. Subsequently, she received BV plus PTX. The tumor was markedly reduced in size at the completion of 2 cycles. Bleeding and exudate were also reduced. The patient had a partial response until the sixth cycle, and good local control was obtained. However, the patient had progressive disease at the completion of 8 cycles. Therefore, therapy was changed to capecitabine(CAP)plus CPA, but the patient died one year after she began treatment with BV plus PTX. Case 2: The patient was a 76-year-old postmenopausal woman. She had right-sided breast cancer (T4bN3bM1[lung]-stageIV) that was negative for ER, negative for PgR, and 0 for HER2. The patient began receiving different regimens of chemotherapy: EPI and CPA (EC); and PTX. Subsequently, she received BV plus PTX. The tumor was markedly reduced in size at the completion of 2 cycles. Bleeding and exudate were also reduced. The patient had a partial response until the third cycle, and good local control was obtained. However, the patient had progressive disease at the completion of 4 cycles. Therefore, therapy was changed to CAP and DTX, but the patient died six months after she began treatment with BV plus PTX.

Effectiveness and safety of tegafur-gimeracil-oteracil potassium (TS-1) for metastatic breast cancer: a single-center retrospective study.

BACKGROUND: Tegafur-gimeracil-oteracil potassium (TS-1)is a drug that is used mainly as a third-line treatment or beyond for metastatic breast cancer(MBC). However, there is still insufficient evidence on its clinical effectiveness, and there are very few reports on clinical research using TS-1 up front. In this report, we examined the effectiveness and safety of TS-1 therapy for MBC. PATIENTS AND METHODS: The subjects were 46 patients with MBC who were treated with TS-1 between January 2005 and January 2013. These patients were retrospectively examined. RESULTS: The objective response rate to TS-1 therapy was 30.4%, clinical benefit rate (CBR)was 50.0%, and the median time to treatment failure was 10.7 months. When examined by site, the CBR was high locally (46.2%), in the lymph nodes (40.7%), in the bone (42.9%), and in the lungs and pleura (44.8%). However it was low in the liver(30.0%). The relationship was examined between clinicopathological factors and the effectiveness of TS-1 therapy. The objective response rate (ORR) was significantly higher for patients with disease-free interval (DFI) of 2 years or more (p=0.039), TS-1 therapy used as third-line treatment or earlier (p=0.022), negative HER2 status (p=0.020), and no history of capecitabine (CAP)therapy (p=0.049). The CBR was significantly higher for patients with no visceral metastasis (p=0.032), TS-1 used as third-line treatment or earlier (p=0.019), negative HER2 status (p= 0.045), no history of CAP therapy (p=0.006), and no history of tegafur-uracil/doxifluridine therapy (p=0.031). Multivariate analysis showed that DFI of 2 years or more (p=0.035, odds ratio:0.104)was an independent predictor of effectiveness assessed by ORR. There were only 4 patients in whom the treatment was discontinued due to adverse event, and TS-1 was generally well tolerated. CONCLUSION: TS-1 was highly effective and well tolerated by patients with MBC. Its up-front use might enable the maintenance of satisfactory QOL and the enhancement of its clinical effectiveness.

Paclitaxel-resistant advanced recurrent breast cancer: a case of partial response due to addition of bevacizumab to paclitaxel therapy: a case report.

BACKGROUND: Paclitaxel plus bevacizumab have shown a high response rate and prolonged progression-free survival in metastatic breast cancer patients. However, overall survival was not prolonged. Thus, no conclusion has been made on the effectiveness of bevacizumab. In our report, taxane plus bevacizumab were used to treat a metastatic breast cancer patient with taxane resistance, and a good therapeutic result was obtained. CASE PRESENTATION: The patient was a 68-year-old woman with a non-contributory history. In September 2004, she underwent a pectoral muscle-conserving mastectomy with axillary dissection for right-sided breast cancer (pT3N0M0-stage IIB, estrogen receptor positive, progesterone receptor negative, and human epidermal growth factor receptor type 2 negative). Adjuvant therapy consisted of 6 cycles of cyclophosphamide, epirubicin and fluorouracil, and subsequent oral anastrozole. In August 2007, the patient developed a recurrence in the left axillary lymph node. The chemotherapy was changed to high-dose toremifene, and radiation therapy was also performed. The patient achieved a complete response. In April 2009, CT showed left axillary lymph node enlargement once again and multiple lung metastases. Hormone therapy was changed to exemestane and long-term stable disease was achieved. In March 2011, the lung and left axillary lymph node metastases were enlarged and progressive disease was noted. Thus, the tumors were determined to be resistant to hormone therapy, and weekly paclitaxel was begun in May. Since partial response was achieved, this therapy was continued. In December, CT showed that lung and axillary lymph node metastases were enlarged and progressive disease was observed. Therefore, the tumors were determined to be resistant to paclitaxel. In January 2012, bevacizumab and weekly paclitaxel were begun. In April, lung and axillary lymph node metastases were reduced in size, and partial response was achieved. Thereafter the same treatment has been continued, and the patient has been followed up without clinical exacerbation as of January 2013. CONCLUSION: Taxane plus bevacizumab were used to treat a metastatic breast cancer patient with taxane resistance, and a good therapeutic result was obtained. This result is considered important in increasing treatment options for patients with taxane resistance or patients using adjuvant taxane-based therapy and in examining the effectiveness of bevacizumab in metastatic breast cancer patients.

A case of mucinous carcinoma of the breast in which needle tract seeding was diagnosed by preoperative diagnostic imaging.

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.