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Biomedical subjects

J Horiguchi

Publications and source records attributed to J Horiguchi.

At least 127 records · Page 7Linked to original sources

The effect of mass screening by physical examination combined with regular breast self-examination on clinical stage and course of Japanese women with breast cancer.

A mass screening program for breast cancer in Japan consists of physical examination (PE) and education on regular breast self-examination (BSE). The effect of PE with BSE on clinical stages and courses of breast cancer patients were retrospectively analyzed. Clinical stages and courses were compared between; i) patients who were examined in outpatient clinics (OPC, n=587), ii) patients who were detected by mass screening with regular BSE [BSE(+), n=68], and iii) without BSE [BSE(-), n=178]. Clinical stage in BSE(+) was significantly earlier than that in BSE(-) or OPC. As early stage cancer was most common in BSE(+), conservative surgery was mostly selected. Survival curve in BSE(+) was significantly better than those in BSE(-) or OPC. BSE complements the role of mass screening by PE for early detection and a more favorable clinical course.

Breast Neoplasms↗

Long-term prognostic value of PCNA labeling index in primary operable breast cancer.

Cell proliferation was evaluated in 167 tissue specimens obtained from primary breast cancer patients who had undergone radical surgery between 1984 and 1988. Formalin-fixed and paraffin-embedded tissue specimens were used in the immunohistochemical study. The immunohistochemical method was carried out using the avidin-biotin immunoperoxidase technique, and anti-proliferating cell nuclear antigen (PCNA) monoclonal antibody was used for primary antibody. Based upon the PCNA labeling index (LI), the patients were divided into two groups: low PCNA, <25% and high PCNA, >/= 25%. The PCNA LI ranged from 1% to 76% (mean, 23.9%). Patients aged </= 50 showed significantly higher PCNA LI than those of > 50 years. There was no relationship between the PCNA LI and tumor size, lymph node involvement and hormone receptors. The survival curves of 146 invasive breast cancer patients showed that the high PCNA group had poor overall survival compared with the low PCNA group. A significant difference in the overall survival between the high and low PCNA groups was observed in lymph node-positive patients, however, no significant difference was found between the two groups in lymph node-negative patients. PCNA LI was identified as an independent predictor in primary breast cancer patients.

Adult↗

Local resection after breast-conserving therapy.

We analyzed the results of local re-excision after radiation therapy on seven patients with positive surgical margins at the initial breast-conserving surgery. The age of the patients ranged from 30 to 55 years, and the tumor sizes from 1.1 to 4.7 cm. Both estrogen receptor and progesterone receptor status were positive in two patients, negative in four, and unknown in one. Pathological examination revealed residual carcinoma in one (14.3%) of seven patients. The immunohistochemical results of the initial specimen were estrogen receptor-positive, c-erbB-2-positive, and Bax-negative. We performed local re-excision after radiation therapy and found only one incidence of residual carcinoma in the conserved breast.

Adult↗

Clinical significance of immunohistochemical Bcl-2 expression in invasive breast carcinoma.

The immunohistochemical expression of bcl-2 protein, and its correlations with clinicopathological features and prognosis were studied in patients with invasive breast carcinoma. Bcl-2 positive expression significantly correlated with hormone receptor positivity and histological tumor differentiation, and inversely correlated with p53 overaccumulation. No correlation was observed between bcl-2 expression and patient age, menopausal status, tumor size, and lymph node metastasis. Survivals of stage I to III patients who had not received adjuvant hormonal therapy showed no difference between bcl-2-positive and -negative tumors, even if patients were divided as with or without adjuvant chemotherapy, or with or without nodal involvement. In consequence, immunohistochemical bcl-2-positivity correlates with positive hormone receptors and well differentiated phenotypes in invasive breast carcinoma, however, it might not predict response to adjuvant chemotherapy and not be a favorable predictive value in patients treated without adjuvant hormonal therapy.

Adult↗

Regulation of estrogen receptor and epidermal growth factor receptor by tamoxifen under high and low estrogen environments in MCF-7 cells grown in athymic mice.

The purpose of this study was to investigate whether tamoxifen (TAM) treatment causes a downregulation of estrogen receptor (ER) and whether TAM induces epidermal growth factor receptor-1 (EGFR). We investigated the expression of ER and EGFR after the treatment of TAM in MCF-7 tumors grown in athymic mice under high and low estrogen environments. MCF-7 tumors were grown in ovariectomized athymic mice by implanting a sustained release 17beta-estradiol (E2) pellet. The E2 pellets were removed after 3 weeks of E2 treatment. Animals were then divided into the following 4 groups: i) an E2 (0. 72 mg/pellet) pellet [E2(+)]; ii) an E2 and a TAM (5 mg/pellet) pellets [E2(+)TAM]; iii) no treatment [E2(-)]; iv) a TAM pellet [E2(-)TAM]. A significant reduction in tumor size was observed in the estrogen-depleted group [E2(-) and E2(-)TAM] compared with the estrogen-completed group [E2(+) and E2(+)TAM]. TAM inhibited estrogen-stimulated growth in the estrogen-completed mice. No additional reduction of the tumor by TAM was observed in the estrogen-depleted mice. Both ER and EGFR protein levels in the tumors of the estrogen-depleted mice were higher than in the estrogen-completed mice. Expression of ER and EGFR protein was increased by TAM in the estrogen-completed mice, however it was decreased by TAM in the estrogen-depleted mice. Changes of ER and EGFR protein levels were similar in all treatments. Transforming growth factor-alpha (TGF-alpha) in tumors, which is known as a ligand of EGFR and as an estrogen-inducible protein in ER positive MCF-7 cells, was decreased by TAM in the estrogen-completed mice, by contrast, it was increased by TAM in the estrogen-depleted mice. Downregulation of ER was observed in TAM-treated mice in an estrogen-depleted environment, this action of TAM was similar to E2. These results suggest that increase of EGFR expression does not lead to a loss of ER after short-term TAM treatment in MCF-7 tumors.

Animals↗

Immunohistochemical study on primary and recurrent tumors in patients with local recurrence in the conserved breast.

One hundred and seventy patients received breast-conserving therapy in the Second Department of Surgery, Gunma University School of Medicine. Six (3.5%) out of the 170 patients showed breast recurrence. We investigated the breast recurrent cases clinicopathologically. The age at the initial operation ranged from 38 to 78 (mean 57) years. One patient was clinical stage I and the others were clinical stage II. Surgical margin at the initial operation was negative in two patients and positive in four. Histological type was invasive ductal cancer in all cases. Three patients had lymph node involvement. The interval from the initial operation to breast recurrence ranged from 19 to 68 months. Five cases were nodular type and one was diffuse type of breast recurrence. Histological type of breast recurrence was the same as the initial one. We performed salvage surgery for all breast recurrent patients, mastectomy for four patients and local resection for two. One patient who showed diffuse type of recurrence could not be controlled with any surgical treatment, and later died of breast cancer. We investigated the expression of estrogen receptor, progesterone receptor, pS2, c-erbB-2 and p53 on both initial and recurrent specimens of the six patients. The expression of each protein on the recurrent specimens was the same as the initial one. We conclude that breast recurrence after breast-conserving therapy has its origin in the residue of cancer cells at the initial operation, even if surgical margins are histopathologically negative.

Adult↗

Serum concentration of pyridinoline cross-linked carboxyterminal telopeptide of type I collagen in patients with metastatic breast cancer.

The serum concentration of pyridinoline cross-linked carboxyterminal telopeptide of type I collagen (ICTP) was examined in 83 patients with metastatic breast cancer. ICTP levels were significantly higher in patients with bone metastases than in those without bone metastasis. In patients with bone metastasis, significantly higher ICTP levels were observed in those with multiple lesions than in those with a solitary lesion and these levels reflected therapeutic response. Sequential monitoring of ICTP revealed that this elevation was correlated with disease progression. Combined with imaging studies, monitoring of ICTP appears to offer additional information for detection of bone metastasis and evaluation of therapeutic response to bone metastasis.

Adult↗

Antitumor effect of 22-oxacalcitriol on estrogen receptor-negative MDA-MB-231 tumors in athymic mice.

The purpose of this study was to evaluate the usefulness of 22-oxacalcitriol (OCT) in the treatment of estrogen receptor (ER)-negative breast cancer. The antitumor effect of this agent and its effect combined with doxifluridine (5'-DFUR) on MDA-MB-231 tumors in female athymic mice were investigated. We also examined the effect of OCT on the expression of vascular endothelial growth factor (VEGF) which had been reported to generate angiogenesis in tumors. OCT significantly suppressed the growth of tumors without inducing hypercalcemia in a dose dependent manner. The effect of OCT combined with 5'-DFUR did not exceed the effect of a single agent therapy. The expressions of VEGF analyzed by enzyme-linked immunosorbent assay were significantly decreased in the OCT-treated group. These results suggest that OCT may partially suppress tumor growth by inhibiting neovascularization and it would likely have positive application as a treatment of ER-negative breast cancer.

Animals↗

Effects of interferon-alpha on cellular proliferation and adhesion of breast carcinoma cells.

We examined the potent inhibitory effects of interferon-alpha (IFN-alpha) on both cellular adhesion and cell proliferation of MCF-7 breast carcinoma cells. When MCF-7 cells were exposed to IFN-alpha at a concentration of 5x10(3) IU/ml for 5 days, cell proliferation was markedly inhibited. Cell attachment assay demonstrated that incubation with IFN-alpha for up to 48 h reduced alpha2beta1 integrin-mediated cellular adhesion. However, fluorescence activated cell sorter (FACS) analysis revealed that incubation with IFN-alpha for 24 h had no effect upon the cell surface expressions of either alpha2 and beta1 integrin on MCF-7 cells. These antiproliferative and antiadhesive actions of IFN-alpha may be applied to treatment for patients with metastatic breast carcinoma.

Breast Neoplasms↗

A comparative study of subcutaneous mastectomy with radical mastectomy.

The purpose of this study was to compare the results of 133 cases (131 patients) of subcutaneous mastectomy with axillary dissection between 1983 and 1999 and 910 cases of radical mastectomy during the same period. The median follow-up period of the subcutaneous mastectomy group and the radical mastectomy group were 66 months and 81 months, respectively. The age at operation was significantly (p<0.01) younger in the subcutaneous mastectomy group than in the radical mastectomy group and the clinical stage was significantly (p<0.01) earlier. Lymph node metastasis was significantly (p<0.01) higher in the radical mastectomy than in the subcutaneous mastectomy group. There was no difference in ER status between the two groups. There was local recurrence in 5 (3.8%) members of the subcutaneous mastectomy group and in 12 (1.3%) members of the radical mastectomy group. There was no difference in disease-free survival and overall survival between the two groups. Divided into two subgroups by lymph node status, there was no difference in disease-free survival and overall survival between the two groups. Local recurrence occurred more frequently (p<0.05) in the subcutaneous mastectomy group, however, than in the radical mastectomy group when no lymph node metastasis was found. Multivariate analysis using the Cox hazard model showed that operation method and lymph node status were independent prognostic factors for local recurrence, whereas, lymph node status and ER status were independent prognostic factors of disease-free survival. In conclusion, subcutaneous mastectomy presents a risk factor for local recurrence, but the survival rate of the subcutaneous mastectomy group is as favourable as the radical mastectomy group.

Adult↗

Predictive value of estrogen receptor status as assessed by ligand-binding assay in patients with early-stage breast cancer treated with breast conserving surgery and radiation therapy.

It is important to determine which factors are predictive for the prognosis of patients treated with breast conserving surgery (BCS) and radiation therapy (RT) in order to make a decision as to the adjuvant treatment. Although estrogen receptor (ER) is known to be a predictive marker for antiestrogens in breast cancer, the prognostic effect of hormone receptors has not been fully analyzed in Japanese breast cancer patients treated with BCS and RT. A total of 153 breast cancer patients having up to three positive nodes in the axilla as identified histologically and treated with both BCS and RT with or without systemic therapy were enrolled in this study. All tumors were measured for ER and progesterone receptor (PR) using ligand-binding assay (LBA). ER was inversely related to patients' age, however, PR was not related to any clinical features. When ER was classified into negative, weakly positive and strongly positive categories, with cut-off levels of zero and 50 fmol/mg protein, the relapse-free survival (RFS) was significantly better in patients with tumors having strongly positive ER than in patients with tumors having negative ER. Multivariate analysis revealed that ER as well as nodal status, was an independent predictive factor for RFS, however, PR was not. As a result, we believe that ER measured by LBA is valuable for predicting prognosis of early-stage breast cancer patients treated with BCS and RT.

Adenocarcinoma↗

Immunohistochemical analysis of cytokeratin #8 as a prognostic factor in invasive breast carcinoma.

Cytokeratin #8 (CK8) was analysed by immunohistochemistry using a monoclonal antibody in 101 operable invasive breast carcinomas (IBCs). The immunohistochemical staining pattern, and its correlations with patient characteristics and prognosis were studied. Sixty-five (65%) out of 101 patients had CK8 positive tumors. The incidence of CK8 positivity in patients with estrogen receptor (ER) positive tumors was significantly higher than that in patients with ER negative tumors. The same tendency was seen between the CK8 positivity and progesterone receptor (PR) status; however, no statistical significance was found. Furthermore, the incidence of CK8 positivity in premenopausal patients was lower than that in postmenopausal patients with no statistical significance. Relapse-free survival (RFS) for patients with CK8 positive tumors was significantly better than that for patients with CK8 negative tumors. The multivariate analysis of factors related to RFS showed that CK8 staining positivity was an independent prognostic indicator of IBCs. These results suggest that CK8 expression may be one of the prognostic factors of IBCs.

Antibodies, Monoclonal↗

Nonpalpable breast cancer.

Thirty-seven patients with nonpalpable breast cancer treated between 1981 and 1992 were analysed. Twenty-five (68%) of the patients were detected by microcalcification of mammogram, 8 by nipple discharge and 4 by other means. Biopsy was carried out in all patients to get a final diagnosis and histopathological examinations were performed using continuous sections (especially the section with microcalcification). The incidence of noninvasive carcinoma was 59% (22 cases) and the remaining invasive carcinomas were 3 minimal lesions less than 0.5 cm, 3 lesions from 0.5 to 1.0 cm, 3 diseases more than 1.0 cm, and 6 invasive carcinomas with noninvasive ductal carcinoma predominant. Modified radical mastectomy was performed in 16 cases, partial glandectomy in 10 and other surgery including subcutaneous mastectomy in 11. All of the patients with nonpalpabl breast cancer showed a good prognosis because of early detection and early treatment. Mammography was useful to detect nonpalpable breast cancers with microcalcification.

Adult↗

Clinical significance of first line treatment in recurrent breast cancer.

From 1962 to 1992, 279 patients with recurrent breast cancer were treated. Of these, the cases with resected lesions, imperfectly evaluated cases and cases where information was lacking were excluded, and 185 recurrent breast cancers were evaluable at the first line or subsequent treatment. Sixty-seven (36.2%) out of 185 cases responded to first line treatment, while the remaining 118 cases did not respond. In the 67 responder cases at the first line treatments, 16 (23.9%) responded to second line or third line, however, in the 118 nonresponder cases, only 13 (11.0%) responded to next or subsequent treatment. The incidence of responder in the second line or third line treatment was significantly higher in the first line responder group than in the first line nonresponder group. Furthermore, overall survival of first line responders was significantly better than that of first line nonresponders. There was no significant difference in the survival after recurrence between responders and nonresponders in the first line chemotherapy, chemoendocrine treatment or radiotherapy, however, a significant difference was seen between the two groups in the first line endocrine treatment. These results suggest that first line treatment may select the treatment sensitive (especially, truly hormone-dependent) recurrent breast cancers which show a better prognosis.

Bone Neoplasms↗

Subcutaneous mastectomy with axillary dissection for early breast cancer.

From 1983 to 1990, subcutaneous mastectomy with axillary dissection was carried out for 46 patients with early breast cancer including three bilateral breast cancer patients (four breasts). Cancer cells were recognized histopathologically in the resection margins of small mammary gland resting under the nipple in four cases, and the remaining 42 cases underwent a curative resection. Multicentric lesions were found out histopathologically by continuous sections in five cases (six breasts). There was no difference in the prognosis using the case-control comparison method between 34 patients with ipsilateral invasive carcinoma who underwent a subcutaneous mastectomy in this study group and 34 patients who underwent a radical or modified radical mastectomy in the control group. Cosmetic results of the subcutaneous mastectomy were evaluated in 37 patients, and 9 were excellent, 17 were good, 9 were not so good and 2 were poor. Subcutaneous mastectomy with axillary dissection was an effective operation for early breast cancer including multicentric lesions and some non-invasive ductal carcinomas from the prognostic and cosmetic standpoints.

Adult↗

Immunochemotherapies versus chemotherapy as adjuvant treatment after curative resection of operable breast cancer.

In our previous study, oral adjuvant combination chemotherapy of 5-fluorouracil, cyclophosphamide, mitomycin C, and predonisolone (FEMP) after curative resection of operable breast cancer with vascular invasion in the tumor and/or in the metastatic lymph node was found to be more effective than one course of mitomycin C or cyclic course of mitomycin C. In the present study, we have assessed the efficacy of protein-bound polysaccharide (PSK) or levamisole (LMS) in addition to FEMP. Between January 1980 and December 1990, 227 operable breast cancer patients with vascular invasion in the tumor and/or in the metastatic lymph node were randomized into FEMP, FEMP + LMS, or FEMP + PSK. The risk ratio was lower in the FEMP + PSK group compared to the FEMP group. In disease-free survival or overall survival, there was no significant difference between the three groups, however, the survival curve of the FEMP + PSK group tended to be better than that of the FEMP group(logrank, P = 0.0706; generalized Wilcoxon, P = 0.0739). Side effects were observed at a low incidence, but they were mild and tolerable. Immunochemotherapy using PSK improved the prognosis of patients with operable breast cancer with vascular invasion.

Adjuvants, Immunologic↗

Relationship between thyroid-pituitary function and response to therapy in patients with recurrent breast cancer.

In this study, thyroid (T3, T4, free T3, free T4) and pituitary function (thyrotropin (TSH), growth hormone (GH), prolactin (PRL)) in 38 patients with recurrent breast cancer were examined. The patients were divided into three groups according to their response to the therapy. There were 16 partial response (PR), 10 no change (NC) and 11 progressive disease (PD) patients. The maximum and the minimum value for each hormone throughout the course of treatment were compared between three groups. The PD group showed significantly lower minimum T3 levels than the other two groups (p < 0.05). The maximum TSH level in the PD group was significantly higher than that of the other groups. The minimum TSH level in the PD group was significantly lower than that in the PR group (p < 0.05). The minimum TSH level in the NC group was also lower than that in the PR group. The maximum PRL level in the NC and the PD group was higher than that in the PR group (p < 0.05, p < 0.01, respectively). The tumors of the patients with temporal increase of TSH level were resistant to all subsequent therapies. These five patients died within four months followed by decreasing of the TSH level. It is concluded that thyroid and pituitary function, especially free T4, TSH and PRL, are predictive indicators of therapeutic response and the prognosis of the patients with recurrent breast cancer.

Adult↗

Multidisciplinary treatment with anthracyclines in inflammatory breast cancer.

Twenty-two patients with inflammatory breast cancer treated between 1962 and 1994 were analyzed. Before the introduction of multidisciplinary treatment with anthracycline agents between 1962 and 1981, 11 patients out of 14 were resected, however, a curative operation was performed for only 3 of these patients (29.3%). Ablative endocrine therapy, intraarterial infusion of anticancer drugs (mitomycin C or 5-fluorouracil), and radiation were carried out as the preoperative induction therapy for inflammatory breast cancer. All 14 patients died within 36 months. After the introduction of multi-disciplinary treatment with anthracycline agents between 1981 and 1994, preoperative induction chemotherapy or chemoendocrine therapy using anthracyclines was carried out on 7 out of 8 patients and the remaining patient received radiation. Of the former 7 patients, 6 (85.7%) underwent a curative operation. There was approximately a 35 percent cumulative survival rate observed 60 months after operation, and 3 patients out of the 7 lived for more than 5 years. To conclude, multidisciplinary treatment including systemic induction chemotherapy with anthracyclines was an effective treatment for inflammatory breast cancer.

Adenocarcinoma↗