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Clinical studies have confirmed that nab-paclitaxel(nab-PTX)therapy is effective and safe in patients with metastatic breast cancer. Neoadjuvant chemotherapy(NAC) with nab-PTX has resulted in a pathological complete response (pCR) rate of 29% in all cases and 58% in HER2-positive cases. However, these data were obtained from an overseas study, and the effectiveness and safety of NAC with nab-PTX remain unclear in Japan. Thus, the present study was conducted to investigate these aspects. In patients with T1-3, N0-2, M0 breast cancer, 4 cycles of 260 mg/m2 nab-PTX were administered every 3 weeks after 4 cycles of EC therapy(100 mg/m2 of epirubicin and 600 mg/m2 of cyclophosphamide)as NAC. In HER2- positive patients, trastuzumab was used in combination with nab-PTX. Overall, 14 patients were registered between October 2014 and October 2018. One patient who had requested for another drug after providing informed consent was excluded, and the remaining 13 patients were analyzed. The primary endpoint was pCR rate. The median age of the subjects was 57 years, and the median tumor diameter was 35 mm. There were 7 cases of Stage Ⅱ disease and 6 cases of Stage Ⅲ disease. As for tumor subtype, there were 7 cases of Luminal-type, 2 cases of Luminal- HER2-type, 4 cases of HER2-type, and no triple negative-type tumors(the cut-off values for estrogen receptor [ER] and progesterone receptor were both 1%). The objective response rate to NAC was 77%(10/13 cases), and no PD was observed. The pCR rate was 54%(7/13 cases): 2 patients had Luminal-type tumors, 1 had a Luminal-HER2-type tumor, and 4 had HER2-type tumors. Predictive factors for pCR were ER negativity and HER2 positivity. Common adverse events of chemotherapy were hair loss, pain, malaise, anemia, dysgeusia, constipation, itchiness, and numbness, but their severity was modest, and they were manageable. This study suggests the efficacy and safety of nab-PTX after EC therapy in Japanese patients with operable breast cancer.

A 33-year-old woman became aware of a right breast mass at her 28th week of pregnancy. From the biopsy results, we diagnosed her with right breast cancer. At her 33rd week of pregnancy, she underwent modified radical mastectomy (pT2N3aM0, Stage III C, ER-negative, PR-negative, HER2-positive), and she elected to receive adjuvant therapy after the surgery during her pregnancy. She received the first course of EC (epirubicin plus cyclophosphamide) therapy on the 13th postoperative day (35 weeks of gestation) and gave a natural, vaginal delivery at 36 weeks and 5 days of gestation. On the 4th day after birth, the patient noticed a contralateral left breast mass and was diagnosed with left breast cancer, after core needle biopsy. She received 4 courses of EC therapy and is currently undergoing PTX plus HER (paclitaxel plus trastuzumab) therapy. Regarding chemotherapy during pregnancy, we recommend that there is no need to perform artificial preterm birth, because chemotherapy has little influence on children after their second-trimester. After the second-trimester, chemotherapy can be safely performed.

Background: It has been confirmed by several clinical trials that the fentanyl patch causes less adverse events than sustained-release oral morphine, and after rotation. However, there has been no evidence comparing the fentanyl patch with controlled-release oral oxycodone in terms of adverse events., Purpose: We prospectively investigated the reduced effects of adverse events caused by sustained-release oral morphine and controlled-release oxycodone after rotating to the fentanyl patch in patients with metastatic breast cancer., Method: Metastatic breast cancer patients requiring sustained-release oral morphine or controlled-release oral oxycodone(n=9, 2 taking oral morphine, 7 taking oral oxycodone, mean age, 57. 5 years)were recruited. Those experiencing adverse events from oral morphine or oral oxycodone were administered a fentanyl patch., Results: The pain score was reduced significantly at the 4th week. The fentanyl patch was associated with significantly less nausea, vomiting, constipation, sleepiness and dizziness over the study period., Conclusion: This study suggested that the fentanyl patch can reduce adverse events caused by sustained-release oral morphine as well as controlled-release oral oxycodone.

A 53-year-old woman with left breast tumor was diagnosed as bilateral breast cancer(left; T3N3M0, Stage III C/right; T2N0M0, Stage II )in our hospital, both of which were revealed as invasive ductal carcinoma shown to be ER-negative, PgR negative and HER2-positive by core needle biopsy. In December 2004, paclitaxel and trastuzumab combination therapy was tried, but she went into shock just during administration of paclitaxel, and this therapy was discontinued. After that the triweekly CTF therapy was tried as an anthracycline containing regimen, and the lymph node metastases obtained a complete response after a month and a 38. 5% reduction of left primary breast tumor, which was the best response observed after three months. Time to progression was prolonged to 7 months(9 cycles). Although febrile neutropenia occurred in the first cycle, the therapy could be continued safely thereafter as an outpatient. Anthracycline-containing regimens are likely to be avoided because of the difficulty of combining with trastuzumab in the treatment of HER2 overexpressing advanced/metastatic breast cancer. But the CTF therapy of less cardiotoxicity and less alopecia, can expect longer use and better QOL as an alternative for HER2 overexpressing advanced/metastatic breast cancer patients.

Background: Though irinotecan hydrochloride(CPT-11)was approved in Japan in 1994, there have been few reports since that evaluated the efficacy of CPT-11. The position of this agent in the treatment of patients with metastatic breast cancer(MBC)is not definite. In addition, no report has been published to date about CPT-11 and trastuzumab combination therapy., Purpose: To evaluate retrospectively the efficacy of CPT-11 and trastuzumab combination therapy as salvage treatment in patients with human epidermal growth factor receptor 2 (HER2)overexpressing MBC., Patients and Method: We examined ten cases who received this therapy against MBC since February 2002 till March 2007 in our hospital. Overall response rate, change of tumor markers, time to treatment failure (TTF), time to progression( TTP), overall survival (OS)after start of CPT-11 and adverse events were examined for efficacy and tolerability., Results: Median age was 57 (40-67)and median number of prior chemotherapies was 5(2-9). Though the overall response rate was 20%, some tumor reduction was observed totally in seven cases. CEA and CA15-3 were decreased in 78%(7/9)and 63%(5/8) of cases, respectively. Median TTF, TTP and OS were 3, 4, and 6 months, respectively. Adverse events included three cases of severe neutropenia, one of whom died of treatment-related sepsis. Slight diarrhea occurred in seven and severe nausea occurred in two cases. Dose modification of CPT-11 was necessary in 5 cases, and three discontinued CPT-11 administration, mainly due to easy fatigability, nausea and neutropenia. During the therapy, four cases were all inpatients, and 6 eventually became outpatients., Discussion: This therapy for patients with HER2 overexpressing metastatic cancer resistant to multi-agents demonstrated a good result in terms of antitumor effect. But high tolerability could not be documented by our experience with this therapy. It was supposed that the risk management with prediction of adverse events and preparation of better supportive therapy could make for the higher tolerability of this therapy for more effective clinical use.

We experienced a case of paclitaxel- and trastuzumab-resistant recurrent breast cancer with liver metastases showing significant improvement by S-1. A 76-year-old woman was diagnosed with left breast cancer (T2N1M0, Stage II B). She received total mastectomy and CEF (cyclophosphamide 500 mg/m(2), epirubicin 60 mg/m(2), 5-FU 750 mg/m(2)) as adjuvant chemotherapy in March 2004. But twelve months later, she was referred to our clinic for management of lung and left supraclavicular lymph node metastases. Then weekly paclitaxel (80 mg/m(2)) and trastuzumab were started. After 2 cycles of weekly paclitaxel and trastuzumab treatment, lung and lymph node metastases were reduced and the patient showed a clinical response (CR), so she was treated by trastuzumab only. But seven months later, she was diagnosed as a recurrence of liver metastases. She was treated by combined paclitaxel and trastuzumab again, but liver metastases and tumor marker were progressive. S-1 was administered orally 100 mg/day every day for 4 weeks, followed by a 2-week rest interval as 1 cycle, and trastuzumab was injected at 2 mg/kg/week for every weeks. After 2 courses of the treatment, the level of tumor marker and tumor size of liver metastases were reduced. Only rash (grade 1) was observed during treatment. The treatment of S-1 is thought to be effective for taxane-resistant recurrent breast cancer.

Background: There are three third-generation aromatase inhibitors (AI) available in Japan. Though it is supposed that they can be administered sequentially because of their little cross-resistant effect, it is not definite which sequential treatment is best., Purpose: To examine retrospectively the difference in efficacy by the AI sequence when anastrozole ( ANA) and exemestane (EXE) are clinically administered sequentially for patients with metastatic breast cancer., Patients: We examined 22 patients with metastatic breast cancer administered ANA alone as first-line AI treatment, EXE alone as second-line (A--> E group), and 13 patients given EXE alone as first-line AI treatment (E --> A group) since December 2002 in our hospital., Method: In the A --> E and E --> A group, we examined overall response rate, clinical benefit (CB) rate, time to progression (TTP) for the first- and second-line treatment, respectively, overall survival (OS) after starting AI and successive efficacy of the two AIs., Results: There were no significant differences between the two groups in patient characteristics and history of prior treatments. Overall response rate of the first-line treatment in the A--> E and the E--> A group was 31.8% and 38.5%, and the CB rate was 68.2% and 53.8%, respectively. Overall response rate of the second-line treatment in the A --> E (22 cases) and the E --> A (3 cases) group was 13.6% and 0%, and the CB rate was 36.4% and 33.3%, respectively, reflecting no particular differences. In the A --> E group, five (33.3%) among 15 cases obtained CB by EXE and three (42.6%) among 7 cases who did not obtain CB by ANA did so by EXE. Also, in the E--> A group, one among 3 cases who did not obtain CB by EXE did so by ANA. No significant differences were observed in TTP and OS between the two groups., Conclusion: When ANA and EXE are administered sequentially, no particular difference in efficacy occurs due to the sequence. In some cases, 2 agents become effective successively, and cases resistant to first-line treatment can expect efficacy from second-line treatment. Sequential treatment with the two agents seems to provide very significant efficacy in clinical practice regardless of the order of administration.

We report three radioiodine-resistant patients with metastatic papillary thyroid carcinoma administered docetaxel. Patient 1: Bi-weekly docetaxel was administered to a 67-year-old woman with clavicle, cervical lymph node and lung metastases that had progressed after external irradiation and radioiodine therapy. Stable disease was maintained for 18 months without elevation of serum thyroglobulin. Patient 2: Bi-weekly docetaxel was administered to a 72-year-old man with lung metastases that had progressed after radioiodine therapy. Stable disease was maintained for 14 months. Patient 3: Bi-weekly docetaxel was administered to a 58-year-old woman with lung metastases that had progressed after radioiodine therapy. Stable disease was maintained for 18 months with slight reduction of serum thyroglobulin. In all three patients, doubling time of tumor growth was revealed to be far prolonged after docetaxel administration without distinct adverse events. Since no effective systemic treatment has been established for radioiodine-resistant patients with metastatic papillary thyroid carcinoma,docetaxel therapy was supposed to be a viable alternative for them.

We investigated 29 patients with advanced and recurrent breast cancers who underwent capecitabine therapy in the department. Patients'backgrounds: 41-89 years of age (median, 57 years of age). Advanced breast cancers, 5; recurrent breast cancers, 24. PS< or =2 in 18 cases and PS 3< or =in 11 cases. Eighty-six percent of patients were positive for ER and/or PgR. Multiorgan metastases occurred in 22 cases; bone metastases, 22 cases; lymph node metastases, 12 cases; skin metastases, 11 cases; lung metastases, 10 cases. The rate of patients who received chemotherapy was 93%, and the rate of those who received endocrinotherapy was 90%. Therapeutic response rate was CR in 1 case, PR in 5 cases, long SD in 5 cases, SD in 10 cases and PD in 8 cases, indicating a response rate of 20.7% and a clinical benefit rate of 37.9%. Time to progression (TTP) was 1-15 months (the median time, 4 months). Overall survival time (OS) was 2-23 months (median length, 12 months). OS was significantly longer in patients who had therapeutic effects than in patients with no such effects. TTP was significantly longer in patients who had therapeutic effects and in those who had longer SD than in patients with no such effects. OS was significantly longer in patients who had TTP of 6 months or longer. Clinical benefit (presence vs. absence) and PS (< or =2 vs. 3< or =) were independent factors affecting TTP. Capecitabine is expected to prolong the length of survival in patients who are able to continue treatment for 6 months or longer.

Background: A clinical trial of Docetaxel was performed by tri-weekly administration in patients with advanced or recurrent breast cancer. However, careful observation is necessary for outpatients because serious neutropenia often occurs during the therapy. A bi-weekly schedule is recommended since weekly administration requires more visits to the hospital. Docetaxel is proved to express synergistic efficacy in combination with 5'-DFUR by induced dThdPase in vivo. But there are no clinical trials to evaluate efficacy of bi-weekly Docetaxel and 5'-DFUR combination therapy., Purpose: To evaluate safety, the recommended dose of Docetaxel and the efficacy of biweekly Docetaxel and 5'-DFUR combination therapy., Patients and Methods: Patients with advanced or recurrent breast cancer within 1 regimen of prior chemotherapy and without prior use of both Docetaxel and 5'-DFUR were enrolled. 5'-DFUR was orally administered by 600 mg/day. Docetaxel was intravenously given for at least 2 cycles (8 weeks) by 30 mg/m(2) for level 1, 40 mg/m(2) for level 2 and 50 mg/m(2) for level 3. At each level with 3 cases enrolled,the maximum tolerated dose (MTD) level was defined as that in which 2 or 3 cases showed dose limiting toxicity (DLT). The recommended dose was defined as the dose before MTD level. Therapeutic safety was evaluated by analyses of adverse events with the recommended dose., Results: MTD was in level 3 and the recommended dose of Docetaxel was 40 mg/m(2) of level 2. No DLT was observed in level 2, and this combination therapy seemed safe and feasible for outpatients. In addition, all 6 cases for whom therapeutic efficacy was evaluated expressed a clinical response.

The 12 th Oncology Forum discussed the progress and future strategy of cancer prevention in Japan. The National Cancer Center has established a research center for screening focusing on the most common six cancer, stomach, lung, liver, colon, breast and uterus cancer. The program so far had a cumulative detection rate of 3.3%, which is high,and may reflect the selection of subjects. Screening and chemoprevention is also being investigated in prostate cancer, but the issues centre on how to make this widely available. High risk subjects can also be identified for breast cancer. Obesity and family history are especially important. In colorectal cancer studies are evaluating different diets, but general application is not yet possible and the infrastructure to implement any general screening and prevention does not exist. Development of pharmaceutical treatments for prevention is difficult because of the need for very safe treatments, and also because of the length of time needed to carry out studies. Overall, cancer prevention is still in evolution. New approaches are needed, and new infrastructure will be needed at a government level to implement this.

A number of breast cancer-orientated tumor markers have been utilized for various purposes in clinical practice in Japan. Their purposes are as follows: early detection of primary tumors, prediction of disease extent and prognosis, early detection of recurrent diseases, evaluation of therapeutic responses, monitoring patient outcome, and differential diagnosis of metastatic tumors of unknown origin. The clinical significance of the measurement of tumor markers for these purposes is overviewed in this article. In addition, the results are summarized for two clinical studies conducted by the Tumor Marker Study Group of Japanese Breast Cancer Society (Chairperson: Dr. Kurebayashi), a questionnaire survey on the current status of tumor markers in breast cancer in Japan and a multi-institutional study on the utility of tumor markers for evaluation of therapeutic responses. Future directions of clinical and experimental research for breast cancer-orientated tumor markers are also discussed.

We reviewed therapeutic effects and harmful side effects in 33 patients with advanced or recurrent breast cancer who underwent treatment with Anastrozole 1 mg/day in our department. The patients ranged in age from 40 to 83 years old (median, 59). The Performance Status was 0-2, and there was 1 case of advanced breast cancer and 32 cases of recurrent breast cancer. The duration of disease was from 5 to 233 months (median, 50 months). The estrogen and/or progesterone receptor-positive rate was 72.7%. Metastatic sites were in multiple organs in 9 cases, in the lung only in 1 case, in bone only in 12 cases, and in soft tissue only in 10 cases. First-line therapy was used in 10 cases, second-line therapy in 6 cases, and above third-line therapy in 17 cases. There was a complete response in 3 cases, partial response in 5 cases, no long change in 13 cases, no change in 9 cases, and progressive disease in 3 cases. The response rate was 24.3%, The response period ranged from 2 to 22 months (median, 8 months), and clinical benefit was achieved in 63.7%. The clinical benefit rates for first-line were 60%, second-line 83.3% and above third-line therapy 58.8%. The response rate for patients with breast cancer resistant to Anthracyclines and/or Taxanes was 20%. Time-to-progression ranged from 2 to 28 months (median, 11 months), and overall survival ranged from 7 to 30 months (median, 15 months). The most frequent harmful side effects were rise in total cholesterol, general fatigue, hot flashes and arthralgia (9.1%). In this study, we confirmed the availability and safety of Anastrozole, which was suggested to be a useful drug in salvage therapy for patients having resistance to Anthracyclines and/or Taxanes, not only but also useful as a first- or second-line therapy.

Biomarkers are measured in the management of breast cancer patients for the following purposes. (1) Early detection of breast cancer: blood tumor markers such as CA 15-3 are useless for this detection because of a low sensitivity. Proteomics profiling has recently been investigated using blood or nipple aspirate fluid for the detection. Measurement of CEA and HER 2 in abnormal nipple discharge has been approved for diagnosis of breast cancer in Japan. (2) Monitoring of breast cancer patients: serum tumor markers are routinely measured for early detection of recurrent diseases, evaluation of therapeutic response and monitoring outcome of patients by a majority of breast cancer experts in Japan. Study results investigated by the Study Group of the Japanese Breast Cancer Society in 2001 are presented with regard to the questionnaire survey on the present status of tumor marker measurement and the clinical study on usefulness of tumor markers for the evaluation for therapeutic response. (3) Prognostic factors: new biomarkers have been investigated to select patients at high risk for distant metastases, which could not be selected by classic prognostic factors. Three prognostic factors (UPA/PAI-1, cyclin E, gene profiling), which were discussed at the 8th St. Gallen International Consensus Meeting last year, are mainly discussed. (4) Predictive factors for therapeutic response: hormone receptors (HR) have been used as reliable predictive factors for response to endocrine therapy. Other biomarkers have been investigated to select patients with tumors HR-positive but unresponsive to endocrine therapy. Current status, clinical significance, problems and future directions on predictive factors for response to cytotoxic chemotherapy are also discussed.

Our department recently began using paclitaxel in treating patients with breast cancer. Retrospective analysis was conducted to clarify its clinical usefulness. Forty-one patients with metastatic breast cancer were treated with paclitaxel between November 2000 and September 2002. Hospital records of the patients, except for one unsensored patient, were retrospectively reviewed. Characteristics of the patients were as follows: age, 36-81 Y (median, 56); 8 stage IV and 32 recurrent diseases; most frequent dominant site of metastasis was the liver (22 patients, 55%); number with previous chemotherapy was 0-5 (median, 2); anthracycline-based treatment and docetaxel treatment were previously performed in 21 (53%) and 15 (38%) patients, respectively; weekly dose of paclitaxel was 30-150 mg/body (median, 100); and total dose administered was 600-6, 480+ mg/body (median, 1,820). Objective response and clinical benefit rates were 35% and 80%, respectively. Median duration of response, time-to-progression and overall survival were 27+, 33+ and 41.5 weeks, respectively. Common adverse events were sensory neuropathy (45%) and nausea/vomiting (37.5%). Most were graded as 1 or 2. Various agents, such as hormonal agents and trastuzumab, were administered with paclitaxel in 26 patients (65%). No significant difference was observed in efficacy or toxicity among patients treated with paclitaxel alone or paclitaxel plus other agents. Paclitaxel seems to be a feasible, safe and active agent for patients with metastatic breast cancer.

Based on presentations on the basic concepts and scientific rationale of anti-angiogenic approaches to cancer therapy and the possible applications in the area of prostate cancer, gastrointestinal cancer, lung cancer and breast cancer it is easy to conclude that development of anti-angiogenic approaches into clinical therapies is extremely challenging. It is now well established that cancer growth is increased by angiogenic factors and that inhibition of angiogenesis decreases growth and metastatic potential. Anti-angiogenic effect can be obtained through interference with multiple targets. Further development of new strategies involving such novel cancer therapies requires wide reaching development of translational research abilities. However, for moving new therapies into the clinic same rigorous criteria need to be applied as is done for traditional therapies. Angiogenesis appear to be a critical factor for development of prostate, gastric, lung and breast cancers. Development of new anti-angiogenic treatment modalities might become very important in these diseases. A critical requirement for the successful clinical development will be the development of imaging techniques that can help evaluate the effect on blood vessel functionality. Such surrogate markers of anti-angiogenic effect will be essential for optimising molecules and doses.

Irinotecan hydrochloride has been administered to patients with breast cancer resistant to anthracyclines and/or taxanes in our department. A retrospective analysis of the efficacy and toxicity of irinotecan therapy was conducted to clarify its clinical usefulness. A total of 35 consecutive patients with advanced or recurrent breast cancer were treated with irinotecan between June 1996 and March 2002. The patients ranged in age from 37 to 66 years old (median, 52). The most frequent metastatic lesion was in the liver. The number of previous chemotherapy was 2 to 7 regimens (median, 3). Ninety-one percent and 97% of the tumors were anthracycline- and taxane-resistant, respectively. The weekly dose of irinotecan was 40-160 mg/body (median, 100), and the total dose was 40-6, 110 mg/body (median, 840). An objective response rate of 6% and a clinical benefit rate of 23% were obtained. The median time-to-progression and overall survival were 3 months and 8 months, respectively. Severe toxicity (grade 3 or 4) was observed in 34% of the patients for a decrease in the white blood count, in 26% for neutropenia, in 17% for nausea/vomiting and in 6% for diarrhea. Although this study suggests that irinotecan is a clinically useful treatment of anthracycline- and/or taxane-resistant breast cancer, its anti-tumor effect was not satisfactory. The activity of first-line irinotecan therapy or the combined use of irinotecan with other agents should be investigated in clinical studies.

Endocrine therapy of advanced or recurrent breast cancer was described. The presence of ER or PgR in primary breast tumors is the best-established marker for response to endocrine therapy. However, ER-positive breast tumors overexpressing EGF-R and/or HER-2 (Erb B2) are resistant to endocrine therapy. Recently it was suggested that an elevated level of the circulating extracellular domain of HER-2 could be a predictor for poor response to endocrine therapy. LH-RH agonist is used as a first-line therapy for premenopausal patients. And LH-RH agonist plus tamoxifen (TAM) has shown a higher response rate and more prolonged survival than LH-RH agonist or TAM alone. As two new aromatase inhibitors, anastrozole (ANA) and letrozole, have shown an equal or higher response rate and a prolonged time to progression than TAM as a first-line therapy, these could be used as a first-line therapy instead of TAM. In a cross-over trial of ANA and TAM, the response rate of ANA after TAM failure was equal to that of TAM after ANA failure. As these drugs showed an equal or higher response rate and longer survival than progestin in TAM resistant cases, these drugs could also used as a second-line therapy. In addition, the trend of recent studies regarding the mechanisms of hormone resistance is also described.

A 67-year-old woman with a left advanced breast cancer was admitted to our hospital. Chest CT revealed a parasternal lymph nodal metastasis invading into the sternum, an axillary lymph nodal metastasis, and a lung metastasis. The clinical stage of the patient was i.v. (T4bN2M1). Laboratory examination showed humoral hypercalcemia. After controlling the hypercalcemia with alendronate, sodium hydrate she received chemoendocrine therapy with medroxyprogesterone acetate (MPA) (800 mg/day) and docetaxel (60 mg/body once every three weeks). A complete response was obtained in the primary and metastatic lesions after 3 cycles of docetaxel. This case suggests the efficacy of the combined therapy with MPA and docetaxel on advanced breast cancers.

Cancer cachexia is a common paraneoplastic syndrome in patients with advanced malignancies. However, the mechanisms of the development of cancer cachexia remain to be elucidated. Interleukin (IL)-6 is known to be involved in the development of cancer cachexia. The KPL-4 human breast cancer cell line, which was recently established in our laboratory, secretes IL-6 into the culture medium. Oral administration of doxifluridine (5'-DFUR, 60 mg/kg or 120 mg/kg) significantly inhibited the growth of KPL-4 tumors, reduced the tissue levels of IL-6, and alleviated body weight loss. Serum IL-6 levels were also lowered by 5'-DFUR in nude mice bearing KPL-4 tumors. Additionally, it is suggested that tumor necrosis factor (TNF)-alpha is involved in the cachexia induced by KPL-4 tumors. We suggest that 5'-DFUR suppresses cancer cachexia by lowering IL-6 levels in the tumor tissues and serum.

Systemic therapy, pain relief and the quality of life (QOL) of breast cancer patients with bone metastasis were described. QOL was measured using a "QOL questionnaire" developed by the Ministry of Welfare in Japan. It was proved objectively that QOL scores in the cases with bone metastasis were significantly low in terms of activity, physical psychological conditions. Chemoendocrine therapy, endocrine therapy and outpatient therapy showed a high QOL score. The cases with bone pain showed a low QOL scores. In the 45 cases whose first metastatic site was bone only, there were no differences between endocrine therapy and chemoendocrine therapy in the rate and period of response or the total QOL score. MPA showed a higher response rate and a higher pain relief rate than TAM. In the cases with bone metastasis but without severe visceral metastasis, MPA monotherapy showed an excellent response when the tumor was ER or PgR positive, or when there was a long disease-free interval of more than three years, or if there was no previous therapy. MPA monotherapy is a suitable firstline therapy in such cases. Radiation therapy was more effective for bone pain (response rate 96.3%), and it was also effective in cases in which systemic therapy was not.

Prospective studies have suggested that postoperative adjuvant chemotherapy for breast cancer resulted in a lower recurrence rate and a better survival rate. However, there have been little experimental data on the chemotherapeutic agents for the suppression of progression of micrometastasis from breast cancer focus. We recently established a spontaneous metastasis model of MKL-4 human breast cancer cells transplanted into nude mice. In the present paper, both antiproliferative and antimetastatic effects of UFT were studied with this metastasis model. Oral administration of UFT (20 mg/kg daily) given 4 weeks inhibited significantly the growth of MKL-4 tumors in mice. Histological examination revealed a massive necrosis in the treated tumors. UFT also seemed to decrease the frequency of lymph node and distant metastases. In particular, no metastasis was observed in tumor-bearing mice in which the volume of tumors after the UFT-treatment was smaller than that before the treatment. It is premature to conclude that UFT has an antimetastatic effect because the volumes of the tumors of the control group and the treatment groups differed, but at least UFT may have an antimetastatic effect.

The characteristics and clinical efficacies of new hormonal drugs and new treatment methods for breast cancer using tamoxifen (TAM) were described. The new anti-estrogens, such as trioxifen, toremifene and droloxifen, have equal or better clinical efficacy than TAM. They showed a high response rate in postmenopausal patients with no previous treatment or estrogen receptor positive tumors. They were occasionally effective for patients who relapsed after TAM treatment. Pure anti-estrogen ICI 164, 384, with fewer estrogenic agonistic properties than TAM, and anti-estrogen TAT-59, which has been developed in Japan, are under clinical investigation. Luteinizing hormone-releasing hormone agonists, such as leuprolide, buserelin, triptrelin and goserelin, are available for premenopausal patients, and showed a 37% response rate on average. The pure aromatase inhibitors, such as 4-hydroxyandrostenedione and CGS 16, 949 A, are available for postmenopausal patients, and showed 30% and 17% response rates on average, respectively. The new pure aromatase inhibitor ZD-1033 is also under clinical investigation. TAM or toremifene as well as the calcium antagonist verapamil were proved to overcome the multiple anticancer drug resistance caused by P-glycoprotein. Clinical studies for breast cancer using high-dose TAM as a potential modulator of drug resistance have already been started in Europe and the United States. Chemoprevention of breast cancer using TAM, which started in the U.S., was described.