Illness perceptions and quality of life in Japanese and Dutch women with breast cancer.

Knowledge on cross-cultural quality of life (QOL) and illness perceptions may help women with breast cancer cope more effectively. The self regulation model (SRM) guided the current exploratory longitudinal pilot-study. Central to SRM is the perception of health threats and their effects on QOL. Illness perceptions and QOL were assessed in 22 Dutch and 21 Japanese patients with breast cancer who filled out questionnaires before, 1 week, and 8 weeks after the first chemotherapy course. The questionnaires assessed QOL and illness perceptions. Patients' scores were compared with groups of patients with other chronic somatic illnesses (asthma, diabetes). Patients in both samples reported major impact of chemotherapy on global health status, physical functioning, role functioning, emotional functioning, constipation and diarrhea. Differences between Japanese and Dutch patients were limited to social functioning and financial problems. Japanese patients expressed stronger concerns about their illness than Dutch patients. Results of the Japanese and Dutch patients with breast cancer differed from data in patients with asthma on consequences, timeline, concern and emotional response. Results of Japanese patients differed from patients with type 2 diabetes on timeline and concern, whereas Dutch patients differed on timeline and consequences. Japanese and Dutch breast cancer patients have-overall-similar illness perceptions and QOL responses and are aware of the typical characteristics of their disease. The results support the feasibility of cross-cultural psychosocial research in oncology and offer implications for clinical interventions which impact on self-efficacy to empower patients with breast cancer.

Phase III trial of doxorubicin plus cyclophosphamide (AC), docetaxel, and alternating AC and docetaxel as front-line chemotherapy for metastatic breast cancer: Japan Clinical Oncology Group trial (JCOG9802).

BACKGROUND: This randomized, multicenter, phase III trial compared doxorubicin plus cyclophosphamide (AC), single-agent docetaxel (D), and an alternating regimen of AC and docetaxel (AC-D) as first-line chemotherapy in metastatic breast cancer (MBC). PATIENTS AND METHODS: Patients with MBC resistant to endocrine therapy were entered in a randomized study to receive either six cycles of AC (doxorubicin 40 mg/m2 plus cyclophosphamide 500 mg/m2), D (60 mg/m2), or alternating treatment with AC-D (i.e. three cycles of AC and three cycles of D). Treatment was administered every 3 weeks. RESULTS: A total of 441 patients were entered in a randomized study. Response rates were 30% for AC, 41% for D, and 35% for AC-D. The median times to treatment failure (TTFs) were 6.4, 6.4, and 6.7 months (one-sided log-rank test, P = 0.13 for AC versus D, P = 0.14 for AC versus AC-D) and median overall survival (OS) was 22.6, 25.7, and 25.0 months (P = 0.09 for AC versus D, P = 0.13 for AC versus AC-D) in the AC, D, and AC-D, respectively. CONCLUSION: There was no difference in the TTF among the three arms. However, there was a trend toward a better response and better OS in the D than in the AC.

Evaluation of the safety and tolerability of oral TAS-108 in postmenopausal patients with metastatic breast cancer.

BACKGROUND: The potential of TAS-108 for the treatment of breast cancer has been shown by preclinical studies. We therefore investigated the safe dosage, tolerability, and effectiveness on hormone levels and bone metabolism markers and the pharmacokinetics of TAS-108 administered in postmenopausal Japanese women with metastatic breast cancer. PATIENTS AND METHODS: The subjects had previously undergone standard endocrine therapeutic modalities. TAS-108 was given repeatedly to five patients each, at three dose levels (40, 80, and 120 mg p.o.) once a day after the first daily meal for a scheduled 8 weeks. Plasma concentrations of TAS-108 and its metabolites were measured at the scheduled time points. RESULTS: Fifteen patients received TAS-108 treatment. Orally administered TAS-108 was well tolerated at doses up to 120 mg and did not cause notable changes either in hormone levels or bone metabolism markers. Pharmacokinetic results indicated dose-dependent increases in plasma levels of TAS-108 and its metabolites. A steady state was achieved by 2 weeks at all dose levels, suggesting no marked accumulation. Clinical benefits were confirmed in 5 of 15 patients. CONCLUSIONS: Repeated oral administration of TAS-108 at doses up to 120 mg was well tolerated, and the plasma level of this compound increased dose-dependently.

Breath alcohol concentrations in Japanese outpatients following paclitaxel and docetaxel infusion.

Patients receiving paclitaxel or docetaxel also receive a significant amount of ethanol, as both products contain ethanol as solvent. Patients in our clinics have occasionally exhibited signs of alcohol intoxication immediately after paclitaxel infusion. In 2002, the Japanese government lowered the minimum ethanol concentration for the definition of drunk driving, with the threshold breath alcohol concentration (BRAC) of 0.15 mg/l. The aim of this study was to measure BRAC in Japanese outpatients treated with paclitaxel or docetaxel and to assess intoxication according to this standard. Fifty-two Japanese patients were enrolled from October 2003 to February 2004. Patient characteristics were as follows: male/female, 13/39: median age, 71 (range: 34-78); breast/lung/ovarian cancer 24/16/12; and paclitaxel/docetaxel treatment: 36/16, respectively. The mean total doses of paclitaxel or docetaxel were 178 mg (range: 107-300) and 53 mg (30-100), respectively. Breath samples were measured three times immediately following the infusion of paclitaxel or docetaxel via ethyl alcohol detector and the mean value was recorded. BRAC was detected in 20 patients (56%) with paclitaxel and in none of the docetaxel patients. BRAC was measured again 30 min after the initial measurement in BRAC-detected cases with the patients' permission. In four of six BRAC-remeasured patients, BRAC became undetectable after 30 min. There was no correlation between the total doses of paclitaxel and BRAC or between the infusion rates of paclitaxel and BRAC. In conclusion, clinicians should recognize the potential for alcohol intoxication with paclitaxel administration. Patients should be instructed to avoid driving on the day of paclitaxel administration.

Relaxant effects of different fractions of essential oil from Carum copticum on guinea pig tracheal chains.

In previous studies, the relaxant and anticholinergic (functional antagonism), histamine(H1) inhibitory, and xanthine-like activity effect of Carum copticum have been demonstrated on guinea pig tracheal chains. To investigate the effective component(s) of this plant, responsible for the observed bronchodilatory effect, fractionation of the essential oil from Carum copticum was carried out and the relaxant effects of different fractions were examined in this study. The bronchodilatory effect of different fractions of essential oil from Carum copticum and theophylline in comparison with ethanol was examined by their relaxant effects on precontracted tracheal chains of guinea pig by 60 mM KCl (group 1) and 10 microM methacholine in two different conditions including: non-incubated tissues (group 2) and incubated tissues with 1 microM propranolol and 1 microM chlorpheniramine (group 3). In addition the relaxant effect of carvacrol was also examined on precontracted tracheal chains of guinea pig by 10 microM methacholine (group 4), (for each group, n = 5). In group 1 experiments, only theophylline and fraction 2 showed significant relaxant effect compared to that of ethanol. Fraction 2 and 3 of essential oil from carum copticum showed potent and volume (concentration) dependent relaxant effects comparable to that of theophylline in groups 2 and 3 experiments. The relaxant effects of different volumes of these two fractions were significantly higher than that of ethanol (p < 0.05 to p < 0.002 ). The volumes of fraction 1 showed relatively small relaxant effects in groups 2 and 3 experiments which were not significantly different from that of ethanol. However, the relaxant effect of different volumes of fractions 2 and 3 obtained in group 2 experiments were not significantly different from those of group 3 experiments. The volumes of fraction 4 did not show any relaxant effects. In addition volumes of carvacrol also showed comparable relaxant effect with those of fraction 2 and theophylline which was significantly greater than that of ethanol. These results indicate that the relaxant effect of essential oil from carum copticum is mainly due to its fraction 2 which is presumably carvacrol and to lesser extent due to fraction 3, and their relaxant effects are not due to anticholinergic or beta-adrenegic stimulatory effects.

Double-blind randomised trial comparing the non-steroidal aromatase inhibitors letrozole and fadrozole in postmenopausal women with advanced breast cancer.

BACKGROUND: To compare the efficacy, safety and tolerability of letrozole, an advanced non-steroidal aromatase inhibitor, and fadrozole hydrochloride, an older-generation drug in this class, we conducted a randomised double-blind trial in postmenopausal women with advanced breast cancer. PATIENTS AND METHODS: One hundred and fifty-seven postmenopausal women with advanced breast cancer were enrolled and randomly assigned to receive letrozole or fadrozole in a multicentre, randomised double-blind trial in Japan. One hundred and fifty-four eligible patients were treated with either letrozole 1.0 mg once daily (n = 77) or fadrozole 1.0 mg twice daily (n = 77), for a minimum of 8 weeks. RESULTS: Letrozole showed a significantly higher overall objective response rate [complete response (CR) + partial response (PR)] than fadrozole (31.2% and 13.0%, respectively; P = 0.011, Fisher's exact test). Clinical benefits defined as CR, PR and stable disease (no change in status for more than 24 weeks) were also higher in patients treated with letrozole (50.6%) than fadrozole (35.1%). Letrozole was significantly superior to fadrozole in terms of the dominant lesion in soft tissue, bone and viscera (P = 0.011, stratified Mantel-Haenszel test). Median time to progression was 211 days in the letrozole group and 113 days in the fadrozole group with no significant difference (P = 0.175, log-rank test). Letrozole markedly reduced the estradiol, estrone and estrone sulfate levels in peripheral blood within 4 weeks. The suppressive effect of fadrozole on these hormone levels was insufficient. Adverse drug reactions were observed in 35.9% of the patients treated with letrozole and in 39.5% of those treated with fadrozole with no significant difference between the two groups (P = 0.74, Fisher's exact test). Most of the adverse drug reactions were rated as grade 1 or 2. CONCLUSIONS: The results show letrozole at a dose of 1.0 mg once daily to be more effective in treating postmenopausal women with advanced breast cancer than fadrozole at 1.0 mg twice daily, with similar safety and tolerability profiles.

Relationship between existence of lymphatic invasion in peritumoral breast tissue and presence of axillary lymph node metastasis in invasive ductal carcinoma of the breast.

Specimens obtained from 92 patients with invasive ductal carcinoma of the breast by quadrantectomy and axillary lymph node dissection were examined to evaluate the relationship between existence of lymphatic invasion in peritumoral breast tissue and presence of axillary lymph node metastasis. The number of lymphatic invasions was classified into 4 groups (ly0-3) by counting the number of peritumoral lymphatic invasions. In addition, immunohistochemistry for cytokeratin was performed to locate micrometastasis in the dissected lymph nodes. Thirty-seven (40.2%) of 92 cases had foci of lymphatic invasion and 29 (31.5%) cases revealed lymph node metastasis on initial routine examination. The rate of diagnosis of lymph node metastasis assessed by the existence of lymphatic invasion had an accuracy of 84.8%, a sensitivity of 89.7% and a specificity of 82.5%. On the other hand, all 3 cases (4.8%) with micrometastasis detected by immunohistochemistry for cytokeratin, showed lymphatic invasion. The rate of diagnosis after detection of micrometastasis increased and exhibited 88.0% accuracy. In addition, the rate of prediction of lymph node metastasis in cases with tumor larger than 15 mm was also high, and its accuracy was 88.2%. These results suggest that the assessment of peritumoral lymphatic invasion is very useful for predicting the presence of axillary lymph node metastasis including micrometastasis. They also suggest that excision specimens should be examined for lymphatic invasion, and that the results of the examination might be necessary to pick up false-negative cases and those at high risk for lymph node metastasis among patients who have not undergone lymph node dissection based on the result of sentinel lymph node biopsy.

[A case of lung and pleural metastases from breast cancer responding to toremifene].

A patient with lung and pleural metastases from breast cancer treated effectively with toremifene is reported. A 62-year-old woman underwent mastectomy for breast cancer, and had high levels of estrogen and progesterone receptor. After 2-years of adjuvant UFT therapy, lung and pleural metastases were seen on a chest x-ray. The patient received a high-dose of toremifene (120 mg/day). After five months with toremifene, a chest x-ray and CT scan showed the disappearance of lung and pleural metastases. No recurrence or metastases have been detected for twenty months to date. No serious side effects were noticed. High-dose toremifene might be an effective therapy for cases of postmenopausal metastatic breast cancer, with high levels of estrogen and progesterone receptor.

5'-deoxy-5-fluorouridine, medroxyprogestrone acetate and mitoxantrone hydrochloride for advanced or recurrent breast cancer.

BACKGROUND: In treating advanced or recurrent breast cancer, anthracycline-containing chemotherapy is used for palliation and to maintain quality of life. However, there are several drawbacks including therapeutic failure and cardiotoxicity. We evaluated the efficacy and toxicity of combination chemotherapy with 5'-deoxy-5-fluorouridine (5'-DFUR), medroxyprogestrone acetate (MPA) and mitoxantrone hydrochloride (MIT). METHODS: Sixteen patients with advanced or recurrent breast cancer were enrolled. Chemotherapy was given in a 28-day cycle, starting with MIT 10 mg/m2 intravenously on day 1, then oral 5'-DFUR 800 mg and MPA 800 mg daily. Two or more cycles were given. RESULTS: Fifteen patients were assessable for response and toxicity. Thirteen patients had been treated previously with an anthracycline containing regimen and 2 with CMF. There were 2 partial response patients (13.3%) and 1 complete response patient (6.7%). There were 11 patients showing no change (NC) (73.3%), one of whom was a minor responder and 7 with a long period of NC. There was only one with progressive disease patient. The overall response rate was 20.0%. Adverse events occurred in 5 patients (33.3%). Myelosuppression was the most common with 5 patients becoming leukopenic (33.3%). Nausea/vomiting was the second most common side effect, affecting 2 patients (13.3%). CONCLUSION: Given its high efficacy and preservation of QOL, the combination of MIT, 5'-DFUR and MPA can be a 2nd or 3rd line therapy for advanced or recurrent breast cancer, especially for anthracycline-resistant cases.

Vegetarian diet ameliorates symptoms of atopic dermatitis through reduction of the number of peripheral eosinophils and of PGE2 synthesis by monocytes.

Many patients with atopic dermatitis are dissatisfied with conventional treatments based on topical steroids and have experienced some traditional remedies and alternative therapies. However, most of such therapies have not been evaluated scientifically and clinically by specialists. This study was designed to assess whether a certain vegetarian diet might be effective for atopic dermatitis and if so, to identify the mechanisms of this remedy through analyses of immunological parameters. An open-trial study was carried out in twenty patients with atopic dermatitis. An improvement of dermatitis was evaluated by SCORAD index and serological and immunological parameters were monitored. After a two-month treatment, the severity of dermatitis was strikingly inhibited, as assessed by SCORAD index and serological parameters including LDH5 activity and a number of peripheral eosinophils. A sharp reduction in eosinophils and neutrophils was observed prior to improvement in the skin inflammation. In addition, PGE2 production by peripheral blood mononuclear cells was reduced by this treatment. In contrast, serum IgE levels did not change during the same period. Although this study is an open-trial one, it suggests that this treatment may be useful for the treatment of adult patients with severe atopic dermatitis.

Enhancement of immunohistochemical reactivity for thymidine phosphorylase in breast carcinoma cells after administration of docetaxel as a neoadjuvant chemotherapy in advanced breast cancer patients.

For the purpose of demonstrating possible effects of docetaxel on thymidine phosphorylase (TP) activity in human breast carcinoma, we examined breast carcinoma tissues pre- and post-administration of docetaxel, by an immunohistochemical method using an anti-TP monoclonal antibody. Eight patients with advanced breast carcinoma were initially treated with 3 cycles of 60 mg/m2 of docetaxel once every 3 weeks after incisional biopsy of tumors, and following 3 cycles of docetaxel, they underwent mastectomy with axillary dissection. Grades of immunohistochemical reactivity for TP of carcinoma cells in pre- and post-treatment specimens were compared. Five biopsy specimens (62.5%) were positive for TP. After administration of docetaxel, 6 of 8 cases (75.0%) revealed significant enhancement of reactivity for TP. Increased reactivity was recognized diffusely as well as focally in carcinoma tissues. From these results, we believe that administration of docetaxel to breast cancer patients evokes enhancement of immunohistochemical reactivity for TP in breast carcinoma cells in situ. Furthermore, we consider that docetaxel treatment might improve efficacy of additional doxifluridine and capecitabine therapy.

[Combination chemotherapy with vinorelbine and other cytotoxic agents for advanced breast cancer patients--a protocol of vinorelbine plus AC regimens used by the Japan Vinorelbin Study Group].

A new generation type of vinca alkaloid, vinorelbine (VNR), is a promising agent for the treatment of breast cancer patients. As a first line treatment for metastatic breast cancer, combination chemotherapy including anthracyclines plus VNR has demonstrated a high response rate and tolerability. In addition, other VNR containing regimens, such as 5-fluorouracil plus VNR, produced a 64% response rate. This evidence suggests VNR-containing combination chemotherapy may be a promising first-line treatment for breast cancer patients. In Japan, VNR is not registered, but a late phase II study has been completed. An approximately 30% response rate was obtained with its use as a monotherapy. In addition, a phase I/II study of combination VNR plus AC (adriamycin + cyclophosphamide) has been conducted. At the present time, the results are being analyzed.

The role of interleukin-6 in inhibition of lung metastasis in subcutaneous tumor-bearing mice.

Metastasis is the most important factor for prognosis in cancer patients, and its occurrence is largely associated with host immune response. We found that the presence of a growing tumor of colon 26, a mouse colon cancer cell line, completely inhibited lung colony formation in a mouse injected with colon 26 intravenously, whereas depletion of effector cells, such as natural killer and T cell subsets, did not affect antimetastasis of colon 26. Since colon 26 releases large amounts of interleukin-6 (IL-6) spontaneously, we studied the association of IL-6 with lung metastasis. Serum IL-6 level increased gradually and reached 12.6 pg/ml five days after inoculation of colon 26 in the back of mice, while at the same time, lung colony formation was inhibited. Moreover, expression of IL-6 mRNA in lung was observed to be associated with elevated serum IL-6 level. We show the first evidence that inhibition of lung metastases in tumor-bearing mice by colon 26 is closely associated with an increase in serum IL-6, but not in cellular immunity.

Green vegetable juice increases polyunsaturated fatty acid of erythrocyte membrane phospholipid in hypercholesterolaemic patients.

Treatment with green vegetable juice rich in dark-green leafy and cruciferous vegetables, such as cabbage, was tested in 31 hypercholesterolaemic patients for three weeks. Green vegetable juice supplementation significantly increased the content of polyunsaturated fatty acids (PUFA; P); 18:2n-6, 20:3n-6, 20:4n-6, 20:5n-3, 22:4n-6, 22:5n-3 and 22:6n-3 of erythrocyte membrane phospholipid and decreased saturated fatty acids (SFA; S): 14:0 and 18:0, and therefore increased the polyunsaturated fatty acids/saturated fatty acids (P/S) ratio markedly from 0.26 ± 0.01 to 0.49 ± 0.01 (p<0.001). Green vegetable juice supplementation increased both n-6 and n-3 PUFA, but the increase of n-3 PUFA was greater than that of n-6 PUFA. Therefore, the n-6/n-3 ratio decreased significantly from 4.29 ± 0.42 to 3.00 ± 0.16 (p<0.05). Plasma thiobarbituric acid reactive substance production decreased, following the green vegetable juice supplementation. These results suggest that green vegetable juice may protect the erythrocyte membrane from oxidative stress, and the decrease in n-6/n-3 and increase in P/S ratio in the erythrocyte membrane phospholipid may be accompanied by rheological and functional changes in erythrocytes in hypercholesterolaemic patients.

[Therapeutic efficacy of pirarubicin cyclophosphamide and doxifluridine in advanced and metastatic breast cancer].

Twenty-four eligible patients (23 of whom were evaluated) with advanced and metastatic breast cancer were treated at the Saitama Cancer Center every 4 weeks with pirarubicin (30 mg/m2 i.v., day 1 and 8), cyclophosphamide (200 mg/m2 div, day 1 and 8) and doxifluridine (800 mg/day po, day 1-14). The 23 evaluable patients had a median age of 49.7 years (range 35.3-72.1) and underwent a median number of 3 cycles (range 2-5). Grade 4 leukopenia (10/24 patients) was the dose-limiting factor and led to infection in one patient. Four complete responses and 7 partial responses with a median duration of 12.1 months (range 2.6-61.0) were achieved, resulting in an overall response rate of 47.8%. The 50% survival duration was 22.9 months.

A phase I/II study of continuous intra-arterial chemotherapy using an implantable reservoir for the treatment of liver metastases from breast cancer: a Japan Clinical Oncology Group (JCOG) study 9113. JCOG Breast Cancer Study Group.

BACKGROUND: Liver metastasis from breast cancer has a poor prognosis. While there are some reports of good response rates of hepatic metastasis from breast cancer by hepatic intra-arterial infusion chemotherapy, no phase I study including pharmacokinetic analysis has been reported. We performed a phase I/II study of intra-arterial infusion chemotherapy using adriamycin and 5-fluorouracil to find the maximum tolerated dose and response rate in patients with advanced or recurrent breast cancer. METHODS: A hepatic arterial catheter with an access port was inserted into the proper hepatic artery. Patients received 30 mg/m2 adriamycin on days 1 and 8 and 100 mg/m2 5-fluorouracil at level 1, 200 mg/m2 at level 2,300 mg/m2 at level 3 and 400 mg/m2 at level 4 continuously from day 1 through day 14 every 28 days. At least two cycles were required before evaluation. Twenty-eight patients were entered into this study and 26 patients were evaluable. Seventeen patients had hepatic metastasis only, although nine patients had additional metastasis to other sites. RESULTS: Dose-limiting toxicity of thrombocytopenia and neurotoxicity occurred at level 4. Leukocytopenia (ECOG grade 3-4) was observed in five (19%), thrombocytopenia in three (12%) and anemia in two (8%) patients. There were 11 catheter-related complications which were not dose dependent. Seven out of 13 evaluable patients (54%) responded at level 3. The median duration of response was 5.8 months (range, 1-23+) and median survival was 25.3 months (range, 6.2-54.7+). CONCLUSION: Hepatic arterial infusion therapy appears to be safe and effective but catheter-related complications must be overcome before starting a phase III trial.

Phase II study of paclitaxel (BMS-181339) intravenously infused over 3 hours for advanced or metastatic breast cancer in Japan. BMS-181339 Breast Cancer Study Group.

A Phase II study of paclitaxel in patients with primary advanced or metastatic breast cancer was conducted by a cooperative study group consisting of 16 institutions in Japan. Paclitaxel at a dose of 210 mg/m2 was intravenously infused over 3 hours, along with premedication to prevent hypersensitivity reactions. The course was repeated at 21-day intervals. Of 62 eligible patients, 60 were evaluable for toxicity and 59 were evaluable for efficacy. Forty-five patients were previously treated with anthracyclines. Twenty-one of 59 patients (35.6%) had a major objective response including 2 CRs and 19 PRs (95% confidence interval, 23.6-49.1%). A response rate of 35.5% (CR1, PR10) was observed in 31 patients refractory to the anthracyclines containing prior metastatic chemotherapy. Median (range) time was 41 (6-100) days to onset of and median duration of response was 125 (36-305) days. Toxicities included leukopenia (grade 3, 4: 67%), anemia (grade 1-3: 80%), thrombocytopenia (grade 1: 8%), alopecia (grade 3: 43%), peripheral neuropathy (grade 1-3: 93%), arthralgia (59%), myalgia (46%), nausea and vomiting (40%), fever (33%), allergic reaction (grade 3: 2%) and hypotension (grade 3: 5%). All toxicities were tolerable and manageable. Paclitaxel intravenously infused over 3 hours demonstrated a significant antitumor activity for metastatic breast cancer. Furthermore, paclitaxel exhibited non-cross resistance to anthracycline. Paclitaxel administered as a convenient 3-hour infusion is effective for patients with metastatic breast cancer and has an acceptable toxicity profile.

Multidrug-resistant recurrent breast cancer which responded to medroxyprogesterone acetate showing a remarkable improvement in the quality of life: report of a case and the role of team medical care.

We herein report the case of a patient with recurrent breast cancer who showed a remarkable improvement in her quality of life (QOL) as a result of a good response to medroxyprogesterone acetate (MPA). A 43-year-old Japanese woman developed bone metastases 3 years after surgery. Subsequent radiotherapy and chemoendocrine therapy with CAF (cyclophosphamide, adriamycin, 5-fluorouracil) and tamoxifen all failed, and she could not sit up because of bone metastases. The performance status (PS) on admission was grade 4. After admission, delirium accompanied with sensory and visual hallucination caused by intense anxiety occurred, and a continuous consultation by psychiatrists was necessary. MPA treatment at the dose of 1200 mg/day alleviated the bone pain, thus improving her PS to grade 1. Her appetite also improved, while her mental state stabilized. A bone scintigram revealed an improvement of bone metastases, and the tumor markers also returned to normal values. The patient thus showed a pronounced improvement in her QOL due to both MPA treatment and team medical care. The role of the medical staff as well as the importance of their cooperation in achieving an improvement in the QOL of cancer patients is also discussed.

Relationship between grade of intraductal component of breast cancer within main tumor and extent of intraductal spread in surrounding tissue.

Ninety-three specimens obtained by quadrantectomy of invasive ductal carcinoma of the breast were examined to evaluate the correlation between the grade of the intraductal component within the tumor and the extent of intraductal spread in the surrounding tissue. We used immunohistochemistry of a-smooth muscle actin to visualize the contour of intraductal components. The grade of the intraductal component within the tumor was classified into 4 groups (td0 to td3) by counting number of intraductal components; the extent of intraductal spread in the surrounding tissue was also divided into 4 groups (sd0 to sd3) according distance from the tumor margin. Fifty-eight (89.2%) of 65 cases with low-grade td were low-grade sd, and 17 (60.7%) cases of high-grade td were high-grade of sd. The grade of the intraductal component correlated with the extent of intraductal spread in the surrounding tissue, significantly (p < 0.001, Spearman rank correlation test). From these results, we believe that investigation of intraductal components within the tumor is useful for estimating the extent of intraductal spread in the surrounding tissue, and excision specimens from diagnostic lumpectomy should be examined for the extent of the intraductal component, the results being important in estimating the risk of local recurrence.

A phase II study of high-dose epirubicin (EPI) plus cyclophosphamide (CPA) with G-CSF for breast cancer patients with visceral metastases or hormone-independent tumors: a trial of the Japan Clinical Oncology Group.

To evaluate the efficacy and toxicity of high-dose epirubicin (EPI) plus cyclophosphamide (CPA) therapy, a phase II study of EPI, 130 mg/m2, plus CPA, 1000 mg/m2, with G-CSF every 3 weeks was carried out for 51 advanced or recurrent breast cancer patients by the Japan Clinical Oncology Group (JCOG). Fifty out of the 51 patients who were eligible for our criteria were treated with this regimen as first-line chemotherapy for visceral metastases or hormone-independent tumors. In this trial, 203 cycles were administered with an average of four cycles per patients. In 50 patients who were evaluable for response, there were 7 complete (CR) and 25 partial responses (PR) with an overall response rate of 64% (95% confidence interval, 50.1-75.9%). Symptomatic and hematological acute toxicity more than grade 3 occurred frequently; however, no treatment-related death occurred. The incidence of toxicities (> or = grade 3) was as follows: leukopenia 98%, thrombocytopenia 42%, nausea/vomiting 56% and hair loss 12%. In each cycle, daily administration of 2 micrograms/kg G-CSF (granulocyte-colony stimulating factor) was given on days 2-15 subcutaneously. The incidence of cardiotoxicity was low. Arrhythmia (< or = grade 2) was observed in 8% and a slight decrease of ejection fraction index (< or = grade 2) was observed in 2% in this trial. The median follow-up period for patients was 37.2 (24.6-51.5) months and the median survival period was 17.4 months. These data indicate that high-dose EPI + CPA combination chemotherapy was effective and well tolerated for breast cancer patients with visceral metastases or hormone-independent tumors. A randomized trial of high-dose EPI vs conventional chemotherapy is required to ascertain the usefulness of this regimen.