Hiroyuki Takei - Academia.edu (original) (raw)
Papers by Hiroyuki Takei
Nippon Geka Gakkai zasshi
Anticancer research
The aim of this study was to compare the survival and recurrence rates of patients undergoing bre... more The aim of this study was to compare the survival and recurrence rates of patients undergoing breast-conserving therapy with the rates of those undergoing mastectomy. Between August 1991 and June 1994, 229 patients were enrolled in this study, although one was later excluded because the tumor was histologically diagnosed as benign. A total of 119 patients with clinical stage TIS, I or II underwent breast-conserving therapy and 109 patients received mastectomy. Mastectomy was utilized more than breast-conserving therapy in the case of clinical stage II, greater age, larger tumor size or shorter distance between the tumor and the nipple. Twenty-seven patients (23.1%) of the 117 receiving breast-conserving surgery were surgical margin positive. There was no significant difference in the distance between the tumor and the nipple, tumor size or clinical stage in the incidence of surgical margin positive cases. Mean follow-up time of the breast-conserving therapy group and the mastectomy group was 42.4 and 39.7 months, respectively. There was no significant difference in the overall survival and disease-free survival between breast-conserving therapy and mastectomy. After adjustment for the clinical stage, there was no significant difference in the prognosis between breast-conserving therapy and mastectomy.
Anticancer research
Thirty-seven patients with nonpalpable breast cancer treated between 1981 and 1992 were analysed.... more 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.
Anticancer research
In our previous study, oral adjuvant combination chemotherapy of 5-fluorouracil, cyclophosphamide... more 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.
Nihon Nyugan Kenshin Gakkaishi (Journal of Japan Association of Breast Cancer Screening)
Anticancer research
Cytokeratin #8 (CK8) was analysed by immunohistochemistry using a monoclonal antibody in 101 oper... more 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.
Anticancer research
ABSTRACT
Japanese Journal of Clinical Oncology
The expression of c-erbB-2 oncoprotein was studied in relation to the histological type of invasi... more The expression of c-erbB-2 oncoprotein was studied in relation to the histological type of invasive ductal carcinoma. The expression of c-erbB-2 was found in 26 (17.6%) of 148 cases, and was a significant prognostic indicator in patients with lymph node metastasis, but not in those without. The patients were divided into a scirrhous group and a non-scirrhous group on the basis of histological type. There was no significant difference between the two groups in age, clinical stage, lymph node status, estrogen receptor status, operation method or c-erbB-2 expression. The expression of c-erbB-2 was a significant prognostic indicator in the scirrhous group, irrespective of lymph node metastasis, but not in the non-scirrhous group. We conclude that the prognostic significance of c-erbB-2 expression differs among histological types of invasive ductal carcinoma, and that c-erbB-2 expression is a prognostic indicator in patients with scirrhous carcinoma.
Anticancer research
ABSTRACT
Anticancer research
Breast conserving surgery with nipple resection was carried out on 4 patients with early breast c... more Breast conserving surgery with nipple resection was carried out on 4 patients with early breast cancer because location of each tumor was very close to nipple. These consisted of 3 patients with state I invasive ductal carcinoma and 1 patient with stage II invasive ductal carcinoma. Cancer cells were not recognized histopathologically in the resection margins of each case and all cases underwent a curative resection with axillary dissection (up to level III). The rested areola in each case was made to be round-shaped by skin suture and the edge of the wound located in the center of areola looked like a small nipple. The cosmetic result of this operation were excellent in all patients. This operation may be effective both for these patients with early breast cancer locating under the nipple or areola and for those whose tumor was very close to nipple.
Japanese Journal of Clinical Oncology
To compare proliferating cell nuclear antigen (PCNA) immunoexpression in hyperplastic polyps, ade... more To compare proliferating cell nuclear antigen (PCNA) immunoexpression in hyperplastic polyps, adenomas, and inflammatory cloacogenic polyps of the human colon and rectum using paraffin wax embedded tissue. The monoclonal antibody PC10 was used to demonstrate PCNA immunoreactivity in 88 polypoid lesions from 68 patients. Cases in which immunoexpression was completely absent were excluded, leaving 32 hyperplastic polyps, 31 adenomas, and seven inflammatory cloacogenic polyps for analysis. Labelling indices for the upper and lower third of each lesion and for adjacent normal mucosa were calculated. The upper third labelling indices for adenomas were substantially higher than those for hyperplastic polyps or normal mucosa, whereas those for the upper thirds of hyperplastic polyps and normal mucosa did not differ greatly. The differences between the lower third samples were not significant. In 16 (50%) hyperplastic polyps positive cells persisted onto the luminal surface. Some adenomas showed the most intense staining and the highest labelling indices in the upper third, with strong staining of surface cells; this pattern was not seen in the other lesions. The inflammatory cloacogenic polyps did not show a consistent pattern of immunoexpression. Differences in cell kinetics between adenomas, hyperplastic polyps, and normal mucosa may be shown in formalin fixed, paraffin wax embedded tissue using PC10 as a marker of proliferative activity. PCNA expression also persists into the upper portions of hyperplastic polyps. Assuming that hyperplastic polyps are hypermature lesions with a slower rate of cell migration, this finding suggests that there may be an alteration in PCNA protein metabolism.
Nihon Nyugan Kenshin Gakkaishi (Journal of Japan Association of Breast Cancer Screening)
Anticancer research
ABSTRACT
Anticancer research
The hypothyroid state or nonthyroidal illness is often observed in patients with recurrent cancer... more The hypothyroid state or nonthyroidal illness is often observed in patients with recurrent cancer. High levels of cytokines are frequently observed in critically ill patients. Recent studies have shown that interleukin (IL)-6 may be a cause of nonthyroidal illness. We reported the relationship between thyroid function and the prognosis of the patients with recurrent breast cancer. In this study, we measured the serum level of cytokines (IL-2, IL-6, IL-8) and thyroid function (free T3, free T4, and thyrotropin (TSH)) in 38 patients with recurrent breast cancer. All patients had received three or more different courses of therapy before they were entered the study. The patients were divided into three groups according to their response to therapy. There were 16 partial response (PR), 10 no change (NC) and 11 progressive disease (PD) patients. They did not receive any medication that influenced the thyroid hormone level other than medication for cancer. The IL-2 level was under the detectable limit in all groups. No abnormal levels of cytokines were observed in the PR group. IL-6 and IL-8 levels in the PD group were significantly higher than that in the NC group (p < 0.05). Significant negative correlation was observed between IL-6 and thyroid hormones (free T3, free T4). Patients whose IL-6 level was 20 pg/ml or more died within four months after the beginning of the treatment. We concluded that IL-6 may lead to a hypothyroid state in patients with recurrent breast cancer. A high level of IL-6 and IL-8 means the confusion of the defense system in hosts. Therefore, these cytokines will be predictive indicators of the therapeutic response and the prognosis of the patients with recurrent breast cancer.
European Journal of Cancer
ABSTRACT
Nihon Nyugan Kenshin Gakkaishi (Journal of Japan Association of Breast Cancer Screening)
Gan to kagaku ryoho. Cancer & chemotherapy
A 13-year-old girl and her older sister were referred to our hospital because her father and anot... more A 13-year-old girl and her older sister were referred to our hospital because her father and another older sister and been suffering from medullary thyroid carcinoma (MTC). Physical examinations revealed no thyroid mass. Ultrasonography (US) detected a small hypoechoic lesion in the right thyroid lobe, 3 mm in size. The serum calcitonin level was slightly elevated for their age. One and half year later, US finding showed a slightly larger mass, 7 mm in size, which was not palpable. Genetic testing for ret protooncogene mutation revealed a point mutation at codon 634 (Cys-->Arg) in exon 11. Surgical treatment was recommended, however, the patient wanted to receive it only after the admission to senior high school. Her sister had no mutation in ret protooncogene. The patient underwent total thyroidectomy with modified neck dissection at 16 years of age. At that time, a new mass emerged in the left thyroid lobe and the serum calcitonin level increased to 171 pg/ml. MTC was found in each lobe with positive staining of CEA and carcitonin. No lymph node metasis was found. Her postoperative course was uneventful. Genetic testing for ret mutation is effective for early diagnosis and treatment of patient with FMTC, and is recommended as standard management for hereditary MTC in affected families.
Anticancer research
The purpose of this study was to compare the results of 133 cases (131 patients) of subcutaneous ... more 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.
Nippon Geka Gakkai zasshi
Anticancer research
The aim of this study was to compare the survival and recurrence rates of patients undergoing bre... more The aim of this study was to compare the survival and recurrence rates of patients undergoing breast-conserving therapy with the rates of those undergoing mastectomy. Between August 1991 and June 1994, 229 patients were enrolled in this study, although one was later excluded because the tumor was histologically diagnosed as benign. A total of 119 patients with clinical stage TIS, I or II underwent breast-conserving therapy and 109 patients received mastectomy. Mastectomy was utilized more than breast-conserving therapy in the case of clinical stage II, greater age, larger tumor size or shorter distance between the tumor and the nipple. Twenty-seven patients (23.1%) of the 117 receiving breast-conserving surgery were surgical margin positive. There was no significant difference in the distance between the tumor and the nipple, tumor size or clinical stage in the incidence of surgical margin positive cases. Mean follow-up time of the breast-conserving therapy group and the mastectomy group was 42.4 and 39.7 months, respectively. There was no significant difference in the overall survival and disease-free survival between breast-conserving therapy and mastectomy. After adjustment for the clinical stage, there was no significant difference in the prognosis between breast-conserving therapy and mastectomy.
Anticancer research
Thirty-seven patients with nonpalpable breast cancer treated between 1981 and 1992 were analysed.... more 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.
Anticancer research
In our previous study, oral adjuvant combination chemotherapy of 5-fluorouracil, cyclophosphamide... more 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.
Nihon Nyugan Kenshin Gakkaishi (Journal of Japan Association of Breast Cancer Screening)
Anticancer research
Cytokeratin #8 (CK8) was analysed by immunohistochemistry using a monoclonal antibody in 101 oper... more 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.
Anticancer research
ABSTRACT
Japanese Journal of Clinical Oncology
The expression of c-erbB-2 oncoprotein was studied in relation to the histological type of invasi... more The expression of c-erbB-2 oncoprotein was studied in relation to the histological type of invasive ductal carcinoma. The expression of c-erbB-2 was found in 26 (17.6%) of 148 cases, and was a significant prognostic indicator in patients with lymph node metastasis, but not in those without. The patients were divided into a scirrhous group and a non-scirrhous group on the basis of histological type. There was no significant difference between the two groups in age, clinical stage, lymph node status, estrogen receptor status, operation method or c-erbB-2 expression. The expression of c-erbB-2 was a significant prognostic indicator in the scirrhous group, irrespective of lymph node metastasis, but not in the non-scirrhous group. We conclude that the prognostic significance of c-erbB-2 expression differs among histological types of invasive ductal carcinoma, and that c-erbB-2 expression is a prognostic indicator in patients with scirrhous carcinoma.
Anticancer research
ABSTRACT
Anticancer research
Breast conserving surgery with nipple resection was carried out on 4 patients with early breast c... more Breast conserving surgery with nipple resection was carried out on 4 patients with early breast cancer because location of each tumor was very close to nipple. These consisted of 3 patients with state I invasive ductal carcinoma and 1 patient with stage II invasive ductal carcinoma. Cancer cells were not recognized histopathologically in the resection margins of each case and all cases underwent a curative resection with axillary dissection (up to level III). The rested areola in each case was made to be round-shaped by skin suture and the edge of the wound located in the center of areola looked like a small nipple. The cosmetic result of this operation were excellent in all patients. This operation may be effective both for these patients with early breast cancer locating under the nipple or areola and for those whose tumor was very close to nipple.
Japanese Journal of Clinical Oncology
To compare proliferating cell nuclear antigen (PCNA) immunoexpression in hyperplastic polyps, ade... more To compare proliferating cell nuclear antigen (PCNA) immunoexpression in hyperplastic polyps, adenomas, and inflammatory cloacogenic polyps of the human colon and rectum using paraffin wax embedded tissue. The monoclonal antibody PC10 was used to demonstrate PCNA immunoreactivity in 88 polypoid lesions from 68 patients. Cases in which immunoexpression was completely absent were excluded, leaving 32 hyperplastic polyps, 31 adenomas, and seven inflammatory cloacogenic polyps for analysis. Labelling indices for the upper and lower third of each lesion and for adjacent normal mucosa were calculated. The upper third labelling indices for adenomas were substantially higher than those for hyperplastic polyps or normal mucosa, whereas those for the upper thirds of hyperplastic polyps and normal mucosa did not differ greatly. The differences between the lower third samples were not significant. In 16 (50%) hyperplastic polyps positive cells persisted onto the luminal surface. Some adenomas showed the most intense staining and the highest labelling indices in the upper third, with strong staining of surface cells; this pattern was not seen in the other lesions. The inflammatory cloacogenic polyps did not show a consistent pattern of immunoexpression. Differences in cell kinetics between adenomas, hyperplastic polyps, and normal mucosa may be shown in formalin fixed, paraffin wax embedded tissue using PC10 as a marker of proliferative activity. PCNA expression also persists into the upper portions of hyperplastic polyps. Assuming that hyperplastic polyps are hypermature lesions with a slower rate of cell migration, this finding suggests that there may be an alteration in PCNA protein metabolism.
Nihon Nyugan Kenshin Gakkaishi (Journal of Japan Association of Breast Cancer Screening)
Anticancer research
ABSTRACT
Anticancer research
The hypothyroid state or nonthyroidal illness is often observed in patients with recurrent cancer... more The hypothyroid state or nonthyroidal illness is often observed in patients with recurrent cancer. High levels of cytokines are frequently observed in critically ill patients. Recent studies have shown that interleukin (IL)-6 may be a cause of nonthyroidal illness. We reported the relationship between thyroid function and the prognosis of the patients with recurrent breast cancer. In this study, we measured the serum level of cytokines (IL-2, IL-6, IL-8) and thyroid function (free T3, free T4, and thyrotropin (TSH)) in 38 patients with recurrent breast cancer. All patients had received three or more different courses of therapy before they were entered the study. The patients were divided into three groups according to their response to therapy. There were 16 partial response (PR), 10 no change (NC) and 11 progressive disease (PD) patients. They did not receive any medication that influenced the thyroid hormone level other than medication for cancer. The IL-2 level was under the detectable limit in all groups. No abnormal levels of cytokines were observed in the PR group. IL-6 and IL-8 levels in the PD group were significantly higher than that in the NC group (p < 0.05). Significant negative correlation was observed between IL-6 and thyroid hormones (free T3, free T4). Patients whose IL-6 level was 20 pg/ml or more died within four months after the beginning of the treatment. We concluded that IL-6 may lead to a hypothyroid state in patients with recurrent breast cancer. A high level of IL-6 and IL-8 means the confusion of the defense system in hosts. Therefore, these cytokines will be predictive indicators of the therapeutic response and the prognosis of the patients with recurrent breast cancer.
European Journal of Cancer
ABSTRACT
Nihon Nyugan Kenshin Gakkaishi (Journal of Japan Association of Breast Cancer Screening)
Gan to kagaku ryoho. Cancer & chemotherapy
A 13-year-old girl and her older sister were referred to our hospital because her father and anot... more A 13-year-old girl and her older sister were referred to our hospital because her father and another older sister and been suffering from medullary thyroid carcinoma (MTC). Physical examinations revealed no thyroid mass. Ultrasonography (US) detected a small hypoechoic lesion in the right thyroid lobe, 3 mm in size. The serum calcitonin level was slightly elevated for their age. One and half year later, US finding showed a slightly larger mass, 7 mm in size, which was not palpable. Genetic testing for ret protooncogene mutation revealed a point mutation at codon 634 (Cys-->Arg) in exon 11. Surgical treatment was recommended, however, the patient wanted to receive it only after the admission to senior high school. Her sister had no mutation in ret protooncogene. The patient underwent total thyroidectomy with modified neck dissection at 16 years of age. At that time, a new mass emerged in the left thyroid lobe and the serum calcitonin level increased to 171 pg/ml. MTC was found in each lobe with positive staining of CEA and carcitonin. No lymph node metasis was found. Her postoperative course was uneventful. Genetic testing for ret mutation is effective for early diagnosis and treatment of patient with FMTC, and is recommended as standard management for hereditary MTC in affected families.
Anticancer research
The purpose of this study was to compare the results of 133 cases (131 patients) of subcutaneous ... more 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.