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It is difficult to cure recurrent or metastatic breast cancer (MBC). Therefore, it is important to continue treatment for MBC with maintenance of quality of life (QOL). Gemcitabine has been approved for MBC since February 2010. We administered gemcitabine to 39 patients with MBC between February 1, 2010 and March 31, 2012. Depending on the case, taxane or trastuzumab was added. Almost all patients had received prior chemotherapy or hormonal therapy. The median age of patients was 61 years (range, 33-82 years), and the median number of previous treatment regimens was 3 (range, 0-6). The response rate was 15.4%, the disease control rate was 56.4%, and the clinical benefit rate was 33.3%. The main hematological adverse event was neutropenia, and the main non-hematological adverse event was fatigue. Neutropenia could be managed by reducing the gemcitabine dose or withdrawing treatment. Adverse events requiring hospitalization were not observed. These findings suggest that gemcitabine-based regimens are feasible in terms of efficacy and maintenance of QOL for patients with MBC.

Although the progress in understanding human genetics regarding cancer has been applied to the medical practice of treating hereditary cancers in developed western countries, it is not widely implemented in Japan. We started treating hereditary cancers at NHO Shikoku Cancer Center in November 2000. Our institution has a multidisciplinary team that provides medical care and genetic counseling for patients with hereditary cancers, and their relatives. The team consists of doctors from several related departments, and paramedics including a genetic counselor who participated as of 2009. Medical care of patients with hereditary cancers should not be separated from general oncological practice, but incorporate all medical professionals, including doctors of related departments and paramedic. We have attempted to identify patients with hereditary cancer and their family members and relatives at high risk; we followed them up and provided risk-reducing therapies for them at our cancer center. Here we present the framework of our practice in treating hereditary cancers. We discuss appropriate goals and future perspectives in the field of hereditary cancer in Japan.

Background: Neoadjuvant chemotherapy has been considered the standard care in locally advanced breast cancer. However, about 10-35% of the patients don't benefit from this treatment. This study was designed to evaluate predictive values of biological markers in response of breast cancers treated with docetaxel alone as neoadjuvant chemotherapy., Methods: 36 patients received the planned four courses of preoperative docetaxel(60-75 mg/m(2)) every 3 weeks. We evaluated the relationship between the response rate to neoadjuvant chemotherapy and hormonal receptor, HER2 status or nuclear grades., Results: Clinical response rate was 57.2%. Pathological complete response rate was 5.6%. Clinical response rate by each factors were as follows; 9(50%)in ER-positive tumors, 10(66.7%)in ERnegative( p=0.27), 7(50%)in PgR-positive, 12(63.3%)in PgR-negative(p=0.34), 5(55.6%)in HER2-positive, 14 (58.3%)in HER2-negative(p=0.71), 4(50%)in tumors of low nuclear grade and 13(65%)in ones of high nuclear grade(p=0.38)., Conclusion: The possibility that tumors with negative hormonal receptors or of high nuclear grade tend to respond to neoadjuvant chemotherapy with docetaxel alone more likely was suggested. It is thought breast cancers respond to neoadjuvant chemotherapy of docetaxel alone regardless of HER2 status.

Vinorelbine is a newanti-cancer drug that is available for advanced or metastatic breast cancer, approved by the Japanese Ministry of Health, Labour and Welfare in May 2005. At present, we evaluated the efficacy and safety of vinorelbine in our hospital. 51 patients were treated with vinorelbine since April 1, 2006 to August 20, 2007. Average age was 55.9 years old and period of treatment was 161.9 days. Average number of previous treatments was 2.2, and 37 patients(72.6%)were treated with anthracyclines and taxanes. The response rate was 19.6%, there was one complete responder, and nine partial responders. Especially, the response rate was 16.2% in patients pretreated with anthracyclines and taxanes. The major toxicity was grade 3 or 4 neutropenia(15.7%), and superficial phlebitis(7.8%). Vinorelbine will be a standard treatment agent for patients pretreated with anthracyclines and taxanes.

The Japanese Ministry of Health, Labor and Welfare approved the use of pamidronate in November 2004 at a dose of 90 mg/day/month especially for Japanese breast cancer patients with lytic bone metastasis. But no safety data have been shown for these Japanese patients thus far. Therefore, we evaluated the safety of pamidronate treatment for breast cancer patients with bone metastasis at the dose of 90 mg/day/month since July 1, 2004 until Dec 31, 2004, retrospectively, in our institute, the Shikoku Cancer Center. No definite severe side effects were detected in these patients, including renal dysfunction and thrombocytopenia. In addition, there were no definite alternations in hemoglobin titers, platelet counts, BUN, serum creatinine and potassium levels in one month and 3 months after beginning the treatment except for significant alternations in RBC counts in one month and in the serum calcium level 3 months later (p=0.03). Improvements of clinical symptoms or data due to bone metastases, i.e., bone pain or elevation of tumor markers, were obtained in 91% of patients. As a conclusion, pamidronate administration at the dose of 90 mg/day/month was safe for Japanese breast cancer patients with bone metastasis.

We evaluated the toxicity of 4 cycles of doxorubicin (60 mg/m2) and cyclophosphamide (600 mg/m2) every 3 weeks (AC 60/600) in adjuvant chemotherapy for breast cancer. Between 1994 and 2003, 62 patients received 6 cycles of doxorubicin (40 mg/m2) and cyclophosphamide (500 mg/m2) every 3 weeks (AC 40/500), and 106 patients received AC 60/600 as adjuvant chemotherapy for breast cancer. The performance status of all patients was 0 or 1. Toxicity was determined using the National Cancer Institute Common Toxicity Criteria (NCI-CTC) ver. 2. Grade 3/4 neutropenia was frequent in AC 60/600 (6.5% vs 24.3%, p < 0.001). However, febrile neutropenia was not significant in either group (1.6% vs 3.8%, p = 0.39). There was also no statistical difference in the toxicity greater than grade 3 of anemia, nausea, vomiting, fatigue, diarrhea and cardiotoxicity. There was no treatment-related death in both groups. The number of patients who completed chemotherapy was higher in those receiving AC 60/600 than in those receiving AC 40/500 (91.9% vs 99.1%, p = 0.026). AC 60/600 is tolerated and feasible in adjuvant chemotherapy of breast cancer in Japanese patients from the viewpoint of toxicities.

We examined the efficacy, toxicity, and survival rate of patients treated with local administration of adriamycin (ADM) for malignant pleural effusion and pericardial effusion in breast cancer. From May 1996 to December 2002, we injected ADM into the pleural cavity for 21 courses and into the pericardial cavity for 2 courses in 18 patients. Thirteen patients showed CR (including 2 cases were injected into pericardial cavity), 2 PR, and 4 PD, and the overall response rate was 78.9%. Toxicities included nausea/vomiting, elevated fever, chest pain, and so on in 15 patients (83.3%). No severe toxicities, however, were observed. The overall survival rate after the removal of the drainage tube was 42.5% at 1 year and 16.5% at 2 years. The survival in patients with a first recurrence, and CR or PR was significantly better than other patients. We conclude that local administration of ADM is useful for treatment, without severe toxicities, of malignant pleural effusion and pericardial effusion in breast cancer.

Breast cancer is relatively sensitive to chemotherapy. However, although response rate to chemotherapy is reported to be from 50 to 70% in metastatic breast cancer, it is incurable. Current standard chemotherapeutic regimens do not provide a large survival benefit according to the evidence obtained from clinical studies. Before developing a treatment program, we should therefore realize that the aims of chemotherapy for metastatic breast cancer are improvement of quality of life through relief of symptoms, and prolonging survival.

CDDP is one of the most effective drugs in chemotherapy for gastric cancer. We compared the antiemetic effect of a combination of granisetron and methylprednisolone with that of granisetron administered alone. Twenty postgastrectomy-patients who were to receive moderately emetogenic chemotherapy, including CDDP, were enrolled in randomized fashion to evaluate the efficacy and toxicity of two antiemetic regimens. The following antiemetic regimens were used: 3 mg of granisetron given intravenously before chemotherapy (11 patients) or a combination of granisetron and 250 mg of methylprednisolone in the same manner (9 patients). Granisetron combined with methylprednisolone tender to be more effective than granisetron alone. The adverse effects were very mild. Their efficacy against delayed emesis is still not entirely satisfactory.

Reported is the case of a 70-year-old woman who, on diagnosis, was found to have a papillary carcinoma of the thyroid gland that showed an anaplastic transformation of a metastatic lesion of the right cervical lymph node. The primary lesion, however, contained no anaplastic areas. Simultaneously, she also was found to have a primary carcinoma of the left breast, an invasive ductal carcinoma. She thus received a total thyroidectomy with a right cervical node dissection, a modified radical mastectomy, and irradiation of the right cervical area, but no intensive chemotherapy was performed. Six months after the thyroidectomy, the anaplastic carcinoma caused her death. On autopsy, it was found to have involved the right cervical area, the lungs, the mediastinum, the right axilla, and the right kidney.

A case of a breast tumor which showed the appearance of invasive ductal carcinoma and chondrosarcoma is reported. The patient was a 36-year-old female. Simple mastectomy and lymph node dissection were performed for the tumor. Local recurrence and metastases to the contralateral breast, lymph nodes, subcutaneous tissue, and bones arose after the operation. She died of the disease 2 years and 3 months after the operation. It is thought that this tumor had formed as a result of metaplasia of the carcinomatous tissue, since a histological transition between the carcinoma and sarcoma was demonstrated.