Quantitative analysis of microvascular structure and function in the amelanotic melanoma A-Mel-3.

Blood cell velocity, capillary diameter, and capillary length were determined in the microcirculation of the amelanotic hamster melanoma A-Mel-3 as well as in s.c. tissue of tumor-free animals. Studies were carried out using a dorsal skin flap chamber, intravital microscopy, and television techniques after transplantation of a 0.5-cu mm piece of tumor tissue. The tumor revealed a special microvascular configuration of short, thin-walled, sometimes dilated capillaries running around the edge of the tumor. Large avascular areas appeared in the center part approximately 5 days after tumor transplantation. Although mean capillary blood cell velocity was not different in tumor-containing and tumor-free preparations, localized irregularities of blood flow were observed close to points of endothelial sacculations. Huge platelet conglomerates were consistently noted in capillaries of the tumor, blocking the blood stream temporarily. Due to discrepancies in microvascular morphology and lack of visible vascularization, large parts of this tumor seem to be inaccessible to tumor treatment. This implies that better vascularization of these regions might enhance the efficiency of cancer treatment. The chamber technique, intravital microscopy, and television methods combined with the subsequent, quantitative microvascular analysis may provide a unique means for direct evaluation of local therapy, particularly during early melanoma growth.

Characterization of n-butyl alcohol solubilized, breast tumor specific antigens recognized by a human autologous cytotoxic T-cell clone.

We demonstrated previously the establishment of a human cytotoxic T-cell clone, TcHMC-1, under culturing with recombinant interleukin that showed the specific cytotoxicity against an autologous breast tumor cell line, HMC-1-8. In the present study, the autologous tumor specific antigens that could be involved in this cytotoxicity were extracted by using n-butyl alcohol and were analyzed for their biochemical profiles. The cytotoxicity of TcHMC-1 against HMC-1-8 was inhibited by adding OKT3 and OKT8 monoclonal antibodies into the cultures, or by pre-sensitizing HMC-1-8 target cells by anti-major histocompatibility complex class I monoclonal antibodies. This suggests that T-cell antigen receptor molecule complexes Ti/T3 on TcHMC-1 and corresponding specific tumor antigens on HMC-1-8 are involved in the cytotoxicity under the restriction of major histocompatibility complex class I products. Precultures of TcHMC-1 with crude n-butyl alcohol extracts from HMC-1-8 cells enhanced the cytotoxic potentials of this clone as seen as mixed lymphocyte tumor cell cultures. This enhancement was dependent on dosage of crude n-butyl alcohol extracts and these TcHMC-1 cells were still cytotoxic specifically for HMC-1-8 targets, but not for other allogenic tumor lines including K562. However, HMC-1-8 crude n-butyl alcohol extracts could not enhance DNA synthesis of TcHMC-1 as assessed by incorporation of [3H]thymidine in the cells. Biochemical purification studies demonstrated that the HMC-1-8 tumor specific antigens were eluted into fractions containing molecules with molecular weights of approximately 200,000 on Sephadex G-200 column chromatography. The antigens were further separated into the fraction that was eluted with 0.4-0.5 M NaCl in an ionic strength on Mono Q fast protein liquid chromatography. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of this fraction demonstrated three molecules with molecular weights of 26,000, 30,000, and 32,000 under reduced molecular conditions. The data suggest that these molecules could be tumor specific antigens that are involved in the cytotoxicity of cytotoxic T-cells against a human autologous tumor.

Identification by monoclonal antibody of the tumor antigen of a human autologous breast cancer cell that is involved in cytotoxicity by a cytotoxic T-cell clone.

We have already established a pair of human autologous clones, tumor-specific cytotoxic T-lymphocyte clone TcHMC-1 and tumor target clone HMC-1-8, that were derived from the metastatic pleural effusion of a patient with mammary carcinoma. In this paper, we describe the target antigen that was defined by monoclonal antibody 3A2. This monoclonal antibody selectively inhibited the cytotoxic action of TcHMC-1 against HMC1-8 autologous tumor target cells, but not the cytotoxicity of lymphokine-activated killer and possibly natural killer cells against HMC-1-8 cells. Western blot analysis using the 3A2 monoclonal antibody identified a molecule with an approximate molecular weight of 92,000. This antigen was highly expressed on autologous primary cancer cells of breast carcinoma tissue, but not on the normal mammary gland in the same patient. Moreover, this antigen can be detected on approximately 50% of human allogeneic breast carcinomas, but not on other neoplastic tissues such as gastric and colonic carcinomas except for one out of 10 prostatic carcinomas. Nonneoplastic normal cells did not express this antigen. It was also suggested that the antigen is not murine mammary tumor virus-related products. These data suggest that 3A2-defined antigen could participate in the cytotoxicity by human autologous cytotoxic T-lymphocytes as the target molecule expressed on tumor cells.

Antioxidant enzyme activities and oxidative stress in human breast cancer.

We have analysed products of lipid peroxidation reactions and activities of antioxidant enzymes in cancerous breast tissue and in corresponding reference tissue. In addition, the serum lipid peroxidation and peroxyl-radical-trapping capacity of breast cancer patients were compared to those of healthy subjects. A total of 23 patients with breast cancer participated in this study. In the cancerous tissue, catalase activity was lower than in the reference tissue, while the activities of superoxide dismutase, glutathione peroxidase and the hexose monophosphate shunt were elevated. The content of thiobarbituric-acid-reactive material was slightly lower in the cancerous tissues, but the levels in serum were found to be elevated in patients with breast cancer. The amounts of conjugated diene double bonds were essentially equal both in the cancerous and in the reference tissue. Moreover, in breast cancer patients the serum levels of diene conjugation and the peroxyl-radical-scavenging capacity did not differ from those measured in healthy subjects. This study indicates that the antioxidant defence system is altered in cancerous breast tissues, but does not support the hypothesis suggesting that formation of lipid peroxides in the tumour tissue itself is of primary importance in the carcinogenesis.

Correlation of heat shock protein 70 expression with estrogen receptor levels in invasive human breast cancer.

The authors studied the role of 70-Kd heat shock protein (HSP70) in the progression of breast cancer by examining the correlation between the expression of HSP70 and epidermal growth factor receptor, c-erbB-2, p53, and estrogen receptor in 124 cases of invasive primary human breast cancers. Positivity of an anti-HSP70 monoclonal antibody, C92, was closely associated with the elevation of estrogen receptor (P < .008), whereas it inversely correlated with the expression of p53 (P < .01). In addition, the expression of HSP70 correlated inversely with the expression of epidermal growth factor receptor, although the correlation was not statistically significant (P = .06). These results suggest that the expression of HSP70 plays a role in the progression of human breast cancer.

UFT and mitomycin plus tamoxifen for stage II, ER-positive breast cancer. Hokkaido ACETBC Study Group.

A trial was designed to examine the combination of UFT and mitomycin (Mutamycin) plus tamoxifen (Nolvadex) as postoperative adjuvant therapy in the treatment of patients with stage II, estrogen receptor (ER)-positive primary breast cancer. Mitomycin was administered intravenously at 13 mg/m2 on the day of surgery. Patients judged to be ER-positive were randomly allocated to either group A, which received oral tamoxifen 20 mg/day 14 days after surgery for 2 years, or group B, receiving oral UFT 400 mg/day plus tamoxifen 20 mg/day. A total of 219 patients were enrolled in group A, of which 213 (97.3%) were determined to be eligible; 225 patients enrolled in group B and 223 (99.1%) were eligible. The 5-year survival rates were 93.0% for group A and 95.4% for group B, with no significant difference between groups. The 5-year relapse-free survival rates were 83.1% for group A and 90.7% for group B, a significant advantage (P = .020) for the UFT plus tamoxifen group. Combination therapy with mitomycin, tamoxifen, and UFT proved to be an effective postoperative chemoendocrine therapy for stage II, ER-positive breast cancer.

Mammary involvement in a patient with sarcoidosis.

Sarcoidosis is a systemic granulomatous disease of unknown etiology. Sarcoidosis affects multiple organs; the lungs, lymphoid system, eyes and skin are usually involved. Commonly, any organ system may be affected. Sarcoid involvement in the nervous system, locomotor system, lacrimal and salivary glands, heart, kidney and liver has been recognized in patients with sarcoidosis. However, sarcoid involvement of the breast parenchyma has been extremely rare in patients with sarcoidosis. Herein, we report a patient with a sarcoid breast mass who had bilateral hilar lymphadenopathy and lymphocytosis in bronchoalveolar lavage analysis.

[A case of Hurthle cell carcinoma in the superior mediastinum].

This is a report for an unusual case of oxyphilic cell adenocarcinoma originating from anterior mediastinum in a 36-year-old male who complained of his neck lymphoadenopathy. 201Tl whole body scanning showed increased uptake of the left supraclavicular and upper mediastinal regions. There was no history of prior operation nor irradiation to the thyroid or neck region. Chest CT scanning also demonstrated the tumor in the superior mediastinum, but the mass has no increased 67Ga uptake. No tumor in the thyroid lobes was apparent on thyroid scintiscanning, ultrasonography and neck CT. The mediastinal tumor resection, the right and left thyroid lobectomy and the neck lymphonodectomy were completed. Serial sectioning of the resected thyroid lobes failed to show any tumorous tissue. The light microscopic features of a Hurthle-cell tumor arising in the mediastinal ectopic thyroid and diagnosed by neck lymph node biopsy were presented. The tumor was clinically malignant, having metastasized to the bone and the neck lymph nodes. Non surgical treatment including radioactive iodine (131I) therapy and combination chemotherapy were disappointing. The patient deteriorated progressively and died 16 months after thyroidectomy. We describe here an unusual case of a papillary growing and thyroglobulin producing tumor in the superior mediastinal region without evidence of a primary thyroid gland tumor.

[Clinical evaluation of the hot nodule on 99mTcO4- and 123I thyroid scintigraphy: correlation of scan appearance and histopathology].

Histopathology and scan findings of hot nodule on 99mTcO4- and/or 123I were correlated in 34 patients with thyroid nodules. In a series of 30 hot nodular lesions, 29 were either adenomas or benign nodules; however, one was proved follicular carcinomas histopathologically. And four patients were chronic thyroiditis without nodular lesions in the thyroid lobes, which were diagnosed pathologically and clinically. In 6 patients with palpable thyroid nodules, thyroid scans performed with both 99mTcO4- and 123I were compared. A discrepancy of the two types of scan existed in only one case. Subsequent surgery revealed no malignancy in this patient. From the results of 201T1 imaging of the thyroid gland in 30 patients with cold or hot nodules on either 99mTcO4- or 123I thyroid scanning, we found no distinct difference between the degrees of 201T1 malignant and nonmalignant tumors. It appears that 201T1 accumulation demonstrates only tumor volume and tumor cell viability in these subjects. From these results, it is confirmed that the functional heterogeneities exist in thyroid adenoma tissues as well as in thyroid cancerous tissues. Therefore, the development of the reliable techniques used to distinguish a benign from malignant lesion is indispensable.

[Local treatment of locally recurrent breast cancers].

For the treatment of recurrent breast cancer, surgical treatment of the local lesion is only of limited significance, leaving a major role for systemic treatment such as chemotherapy and endocrine therapy. Therefore, a new method of local treatment other than surgical removal alone, or systemic treatment of these locally recurrent breast cancers is required. For the treatment of locally recurrent breast cancer, intra-arterial infusion chemotherapy was performed through both the internal mammary artery and subclavian artery or individually. Fourteen cases of locally recurrent breast cancer in our hospital were treated with this therapy. Continuous infusion of 5-fluorouracil and intermittent injections of mitomycin, adriamycin or 4'-epi-adriamycin were jointly or individually done into each artery. Regression of the locally recurrent mass was periodically measured from 4 to 6 weeks after infusion. The percentage of patients with PR was 35.7%. Intra-arterial infusion chemotherapy is a useful preliminary procedure for systemic treatment of local lymph node recurrence from breast cancer. A treatment involving local infusion of the non-specific immuno-activators, OK-432 and PSK, has also been performed for local recurrent lesions of breast cancers. We injected OK-432 and 5% PSK solution into patients with locally recurrent breast cancers and studied their suppressive effect on tumor proliferation. Macroscopically, PR was noted in 3 of 12 patients given OK-432. CR+PR were obtained in 9 of 12 patients given PSK. These results suggest that local injection of OK-432 and PSK solution is beneficial in the management of nodular or scattered-type locally recurrent tumors except for infiltrating type.

[Efficacy and safety of high dose NK 622 (toremifene citrate) in tamoxifen failed patients with breast cancer].

Efficacy and safety of high dose administration of NK 622 (toremifene citrate) were studied in tamoxifen (TAM)--failed patients with breast cancer. The patients included in the study were the following failure cases in TAM therapy: unresponded cases in TAM therapy (TAM unresponded cases), temporary responded (CR, PR) but progressed cases in TAM therapy (TAM temporary responded cases), and those relapsing during TAM adjuvant therapy or within 6 months after the adjuvant therapy (TAM adjuvant failed cases). NK 622 of a 120 mg/day dose were orally given daily once at least for 8 weeks. The response rates in evaluable cases were 6.3% (1/16) in TAM unresponded cases, 11.1% (1/9) in TAM temporary responded cases, 15.4% (4/26) in TAM adjuvant failed cases, and 11.8% (6/51) in total cases including 1 CR and 5 PR cases. Long NC in which duration of NC maintained for more than 6 months was observed in 18.8% (3/16) of TAM unresponded cases, 22.2% (2/9) of TAM temporary responded cases, 11.5% (3/26) of TAM adjuvant failed cases, and 15.7% (8/51) of total cases. Rates of response and long NC were 14.3 and 19.0% in postmenopausal patients with estrogen receptor positive cancer, respectively. A median value of duration to the onset of response was 34 days (15-137). Median duration of response and long NC were 127 days (39-381) and 238.5 days (178-281), respectively. Adverse effects were experienced in 3 (5.1%) of 59 patients: nausea in 1, vertigo in 1 and increase of GOT, GPT, LDH and gamma-GTP in another 1. The side effects were moderate and reversible. From these results, NK 622 seems to become a safe and effective drug for TAM-failed patients with breast cancer by using a 120 mg/day dose.

[Nuclear DNA ploidy pattern and cytological atypia in aspiration cytology of breast cancer].

The relationship between nuclear DNA ploidy pattern and cytological atypia in aspiration cytology of breast cancer was studied in 40 cases of primary breast cancers (T1: 14 cases; T2: 26 cases). They were divided into two groups, according to cytological specimens, high degree (H group) and low degree (L group). Twelve of 40 cases were classified into H group and 28 cases into L group. Fresh frozen materials were obtained from mastectomy specimens and nuclear DNA analysis was carried out by flow cytometry (FCM). Estrogen receptor (ER) and progesterone receptor were measured with the DCC method. Lymph node metastases were histologically seen in 17 cases; the ER positive rate was 55.0%, and the PgR positive rate was 42.5%. FCM revealed 21 cases (52.5%) with diploidy pattern and 19 cases (47.5%) with aneuploidy pattern. S-phase fraction in 17 cases (48.6%) exceeded 20%. L group had more diploid cases and ER positive cases than H group (p < 0.05, p < 0.01). No differences in other factors were seen between the two groups. In diploid cases, L group had more ER positive cases than H group (p < 0.02).

[The significance of intra-arterial infusion therapy for neoadjuvant chemotherapy].

Arterial infusion therapy with anticancer drugs is now attracting attention as a valuable modality for locally advanced breast cancer. Since 1977, we have used this therapy in 122 patients with primary breast cancer. The present report mainly discusses the clinical and histological response as well as the prognosis. The anticancer drugs were mainly given by two routes, infusion into the internal mammary artery and the subclavian artery. Continuous infusion of 5-FU and intermittent injections of MMC, ADR, 4'-epi-ADR and THP-ADR were jointly or individually made in each artery. Clinical response, defined as CR + PR, was noted in 48.4% of 5-FU group and 72.7% of ADR-MMC group. Histological response according to Shimosato Criteria, defined as grade IIb or better, appeared in 45.2% of main tumors and 25.4% of metastatic lymph nodes in the 5-FU group, and 70.9% main tumors and 46.3% of metastatic lymph nodes in the ADR-MMC group. The non-infusion group contained 27.7% of stage IIIb, against 72.2% in the infusion group. The 5-year overall survival rates were non-infusion group 62%, 5-FU group 34.1% and ADR-MMC group 66.2%. A significant difference was seen between the 5-FU infusion group and the ADR-MMC group (p = 0.03). Administration of high dose medroxy progesterone acetate for two weeks and 4'-epi-ADR infusion chemotherapy resulted in an excellent histological response. This combination therapy is a promising neoadjuvant chemo-endocrine therapy for advanced breast cancer.

[Therapeutic effect of stage III breast cancer--comparative study of preoperative intra-arterial infusion chemotherapy and non-infusion therapy].

Between January 1977 and March 1988, 111 patients of stage III breast cancer were treated in Sapporo Medical College. The median age was 51.6 years (range, 26-83 years). Menopausal status was 47 cases of premenopausal, 19 cases of perimenopausal and 45 cases of postomenopausal. Fifty-seven of these patients received intra-arterial infusion chemotherapy. The anticancer drugs were mainly given by two routes, infusion into the internal mammary artery and the subclavian artery. Continuous infusion of 5-FU and intermittent injections of MMC, ADR or 4'-epi-ADR were jointly or individually made in each artery. Clinico-histological response was studied in 53 out of 57 patients. Clinical response, defined as CR + PR, was noted in 33 patients (62.3%). Histological response according to Shimosato Criteria, defined as grade IIb or better, appeared in 31 patients (58.5%). Non-infusion group contained 27.7% of stage IIIb, against 72.2% in infusion group. The 5-year overall survival rates were; non-infusion group 62%, 5-FU infusion group 34.1%, and ADR MMC group 66.2%. A significant difference was seen between 5-FU infusion group and ADR-MMC group (p = 0.03). The median disease-free interval was 22.0 months (range, 1-77 months) in infusion group and 28.2 months (range, 1-124 months) in non-infusion group. MMC + ADR combination group revealed the most excellent results in terms of the 5 year survival rate and clinicohistological effect.

[Effect, recurrence and prognosis of intra-arterial infusion chemotherapy with anticancer agents for advanced breast cancer--especially, the significance of tumor blood vessels].

Between January 1977 and March 1991, 86 patients of Stage III and Stage IV breast cancer were treated by intra-arterial infusion chemotherapy (IAIC) in Sapporo Medical College. The 5- and 10-year overall survival rates of Stage III b were: infusion group 53.1% and 53.1%, non infusion group 50.1% and 16.7%, respectively. A significant difference was seen in the 10-year survival rate (p less than 0.05). The 5- and 10-year overall survival rate of Stage III b histologically effective group was 67.3% and non-effective group 31.8%. A significant difference was seen between these two groups (p = 0.0241). A significant difference was seen between n2 positive Stage III b infusion group and non-infusion group in 7-year survival rate (p less than 0.01). The ischemic effect on tumor cells by degeneration changes of the blood vessels was important for the histological effect. Pre-operative angiography helped in the choice of anticancer agents. The sufficient adjuvant chemo-endocrine therapy will assure a good prognosis for IAIC-treated Stage III b breast cancer patients.

[Effect of intra-arterial infusion of adriamycin on locally advanced primary breast cancer--third report. Clinical Study Group of Adriamycin for Breast Cancer in Japan].

The purpose of this study was to define the optimal dose and schedules for intra-arterial administration of adriamycin (ADR) in the treatment of locally advanced breast cancer. ADR was given intra-arterially to 110 patients with locally advanced breast cancer at a dose of 30 mg/time or 50 mg/time twice or once a week, respectively, with a total dose of 150 mg. The local effects and side effects of ADR as well as the prognosis were analysed in 91 evaluable cases. Overall response rates for ADR were as high as 62.2% (63/91) in the primary lesions and 80.0% (40/50) in metastatic lymph nodes. There was no difference in the response rate between cases receiving 30 mg and those receiving 50 mg at each infusion. However, a significantly higher response rate was noted, in patients infused ADR through both the subclavian and internal thoracic arteries (dual route group) in comparison with those infused through the subclavian artery alone (single route group). Histological effects of ADR on the primary lesion were assessed in accordance with the criteria proposed by Shimosato et al. Overall histological response rate (greater than Grade II b) was obtained in 29.4% (16/51), which was lower than the clinical effects. Histological effects were more potent in the 30 mg group than in the 50 mg group, but in relation to the route of administration, there was no significant difference between the groups. As for side effects, signs of systemic toxicity such as alopecia, leukopenia and gastrointestinal disorders were frequently observed, but there was no difference between the dose groups, and these side effects were considered to be tolerable. Prognostically, 50% survival time was 32.6 months, and the patients who received dual-route administration showed better survival.

[Phase I study of NK 622 (toremifene citrate)].

A phase I study of NK 622 (toremifene citrate), a novel antiestrogen, was conducted in female patients with cancer. Patients received a single oral dosing or daily once oral dosing for five consecutive days. Any adverse effects were not experienced in the single dosing of 40 or 60 mg of NK 622. In the daily administration of 10, 20, 40, 60, 120, 240 and 480 mg/day, one of three patients who received 20 mg/day experienced grade 1 anorexia, three of four patients received 240 mg/day experienced adverse effects: Grade 1 leukopenia in one patient, Grade 1 general hot flush in one patient, and Grade 1 nausea, hot flush in the face and vertigo, Grade 2 anorexia, fatigue, dull headache and general hot flush in another one patient. These symptoms recovered to normal levels after treatment. Serum hormone levels were examined in postmenopausal patients, and a significant increase of the sex hormone binding globulin level was observed in the patients received 120 and 240 mg/day doses. Serum levels of NK 622 determined as free base (TOR) reached the peak levels in 2 to 4 hours after administration on the 1st and 5th day in daily treatment, while a metabolite N-demethyltoremifene (TOR-1) reached the peak level in 4 to 170 hours. Maximum serum levels and area under the concentration versus time curves of TOR and TOR-1 increased dose-dependently. These values also increased by repetition of the treatment. Half-lives of TOR and TOR-1 in serum ranged in 74.5 to 148.9 hours and 154.1 to 653.1 hours, respectively. From these results, it was concluded that safety and efficacy of NK 622 should be assessed by using 240 mg or less doses in clinical phase II studies where breast cancer patients received long term treatment with NK 622.

[Intraarterial chemo-embolization with adriamycin containing albumin microspheres].

For local treatment of inflammatory breast cancer and recurrent breast cancers with liver metastasis, we applied intraarterial infusion chemoembolization therapy utilizing albumin microspheres containing adriamycin (ADM-ms), which was developed by Morimoto. In this study, there were 2 cases of inflammatory breast cancer and 3 cases of recurrent breast cancers with liver metastasis. Arterial canulation of primary breast cancer were made through both arteries, the internal mammary artery and lateral thoracic artery, which were feeding arteries of the breast. ADM-ms was injected into both arteries and its tumor effect was evaluated clinically and histologically. Remarkable reduction in tumor size was recognized. Histologic examination of resected specimens revealed extensive fibrosis in the center of the primary tumors. A few cancer cells, degenerated in various degrees, were found remaining in the periphery of the necrotic mass. Local side effects of the microspheres were skin disturbances such as pain, redness and blistering. ADM-ms was injected into the hepatic artery for the liver metastatic cases, and its antitumor effect was evaluated by CT scan or echography. Effective reduction in tumor size was only recognized in one case. No serious systemic side effects, not recognized in any case. Our report reviews the effectiveness of this therapy as a preliminary procedure for surgical treatment of inoperable inflammatory breast cancer.

[Intra-arterial infusion chemotherapy for advanced or recurrent breast cancers].

Ideally, in preoperative intra-arterial infusion chemotherapy (regarding advanced breast cancer) is to obtain the most significant effects concerning histological features. Intra-arterial infusion chemotherapy using epirubicin (EPI), used in conjunction with daily doses of 1,200 mg medroxyprogesterone acetate (MPA), have recently been performed. This procedure has shown remarkable histological effects in the metastatic lymph nodes as well as in the primary lesions. These results were especially remarkable in the patients who were administered MPA (daily) two weeks prior to EPI infusion. These patients showed a complete disappearance of tumor cells. The results were interesting in view of the mechanism of action. Intra-arterial infusion chemotherapy combined with MPA may also be valuable in treating metastatic liver tumors and recurrent lesions in the regional lymph nodes such as supraclavicular tumors. A high response rate was obtained in the chemo-endocrine therapy when combined with MPA as a pretreatment. Thus, MPA may be expected to be available as a systemic therapy, too. In the future, a new development in the field of intra-arterial infusion chemotherapy may be achieved by utilizing a combination of angiogenesis inhibitors and peripheral blood stem cell transplantation.

[A case of inflammatory breast cancer treated with medroxyprogesterone acetate (MPA) in combination with intra-arterial infusion chemotherapy].

A 55-year-old female with severe inflammatory breast cancer was treated with the combined use of MPA and the intraarterial infusion chemotherapy. One cycle consisted of 4'-epi-adriamycin; 210 mg (day 1, 4 and 8) and daily administration of MPA; 1,200 mg. A marked shrinkage of the tumor was obtained with this treatment. The regressive change was noted not only in the primary lesion but in lymph nodes of the axillary region. Therefore, the combined use of MPA with intra-arterial infusion chemotherapy may well contribute to the treatment of inflammatory breast cancer.