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Human and rat umbilical cord matrix mesenchymal stem cells (UCMSC) possess the ability to control the growth of breast carcinoma cells. Comparative analyses of two types of UCMSC suggest that rat UCMSC-dependent growth regulation is significantly stronger than that of human UCMSC. Their different tumoricidal abilities were clarified by analyzing gene expression profiles in the two types of UCMSC. Microarray analysis revealed differential gene expression between untreated naïve UCMSC and those co-cultured with species-matched breast carcinoma cells. The analyses screened 17 differentially expressed genes that are commonly detected in both human and rat UCMSC. The comparison between the two sets of gene expression profiles identified two tumor suppressor genes, adipose-differentiation related protein (ADRP) and follistatin (FST), that were specifically up-regulated in rat UCMSC, but down-regulated in human UCMSC when they were co-cultured with the corresponding species' breast carcinoma cells. Over-expression of FST, but not ADRP, in human UCMSC enhanced their ability to suppress the growth of MDA-231 cells. The growth of MDA-231 cells was also significantly lower when they were cultured in medium conditioned with FST, but not ADRP over-expressing human UCMSC. In the breast carcinoma lung metastasis model generated with MDA-231 cells, systemic treatment with FST-over-expressing human UCMSC significantly attenuated the tumor burden. These results suggest that FST may play an important role in exhibiting stronger tumoricidal ability in rat UCMSC than human UCMSC and also implies that human UCMSC can be transformed into stronger tumoricidal cells by enhancing tumor suppressor gene expression.

We compared surgical cosmetic results in 83 patients who underwent mastectomy with immediate breast reconstruction (MIBR) using a myocutaneous flap with those of 153 patients with breast cancer who underwent mastectomy without breast reconstruction. Cosmetic results were significantly better in patients who underwent MIBR than radical mastectomy or extended MIBR, although no intergroup difference existed in the reconstructive technique. Neither did any difference exist in the incidence of complications between patients undergoing MIBR and mastectomy without breast reconstruction, or between patients undergoing modified mastectomy and radical or extended mastectomy. Finally, MIBR did not appear to adversely effect recurrence or overall survival. We conclude that MIBR using a myocutaneous flap is an acceptable treatment option for patients with breast cancer.

We investigated the relation between Helix pomatia (HPA) staining of primary breast cancer and the presence of axillary (AX) or internal mammary (IM) metastases, and evaluated its predictive value for AX or IM metastases in comparison with the use of clinical variables. There was a significant association between the HPA staining and AX or IM metastases. When HPA staining was regarded as an indicator of AX metastases, a diagnostic accuracy of 72%, a sensitivity of 69% and a specificity of 75% were achieved. As an indicator of IM metastases, these values were 64%, 76% and 62%, respectively. In predicting the presence of AX metastases using a discriminant function with clinical AX status, location of tumour and tumour size, diagnostic accuracy, sensitivity and specificity were 79%, 69% and 87%, respectively. In predicting the presence of IM metastases using the discriminant function with clinical AX status and tumour size, these values were 74%, 71% and 75%, respectively. Therefore, it was concluded that the HPA staining may be useful, but it was equivalent with the discriminant function with clinical variables in prediction of AX or IM metastases.

It is important to know the status of internal mammary lymph node (IMN) in estimating the prognosis in patients with breast cancer and/or planning the treatment. In the first series of this study, the diagnostic value of internal mammary lymphoscintigraphy (IMLS) and that of parasternal sonography (PS) were evaluated in 57 patients. The overall diagnostic accuracy of IMLS was 72% and that of PS, 84%, compared with IMN metastases confirmed on a biopsy. In the second series, 23 patients who underwent extended radical mastectomy and were found to have IMN metastases, were examined for the sizes and locations of metastatic IMN. Minute metastatic lymph nodes not detectable by IMLS or PS were found in 9 (39%) of the patients. However, the incidence of metastases to the first and/or second intercostal spaces was 97% for the patients. We concluded that a biopsy of the first and second intercostal spaces is useful in providing the information of IMN status.

The influence of estrogens and tamoxifen on estrogen receptor (ER)-positive human breast cancer (MCF-7) cells transplanted into athymic nude mice was investigated. The mice were divided into the following three groups: (1) an E2 group with mice receiving 17 beta-estradiol dipropionate; (2) a TAM group with mice receiving tamoxifen; (3) a control group with mice given no hormone. (1) Tumor growth was significantly increased in the E2 group, but significantly decreased in the TAM group compared to control; (2) the tumor contents of insulin-like growth factor-I (IGF-I) and the rate of IGF-I-positive cells were significantly lower in the E2 group, but significantly higher in the TAM groups compared to control; (3) the IGF-I-positive cell rates were in significant inverse correlation with the [3H]thymidine-labeled cell rates in the E2, TAM and control groups. Thus, the tumor contents of IGF-I and the rate of IGF-I-positive cells were inversely correlated to the tumor growth and the [3H]thymidine-labeled cell rate in this in vivo study, although IGF-I is known to be a mitogen for breast cancer cells in vitro. Further studies are necessary to answer the questions as to the in vivo roles of immunoreactive IGF-I in ER-positive breast cancer.

We evaluated the relationship among DNA ploidy, c-erb B-2 oncoprotein expression, and clinicopathologic prognostic factors, especially axillary and internal mammary node metastases, and their value in estimating the prognosis in 128 patients with operable breast cancer. There were significant correlations between DNA ploidy and clinical stage, tumor size, or axillary or internal mammary lymph node metastases, and between c-erb B-2 expression and clinical stage or axillary lymph node metastases. In a univariate study, overall or disease-free survival was significantly correlated to clinical stage, tumor size, DNA ploidy, c-erb B-2 expression, and axillary and internal mammary node metastases. In a multivariate study, however, only axillary and internal mammary node metastases were recognized as independent factors on overall survival, whereas on disease-free survival, only axillary lymph node metastases were identified as an independent indicator. Since the DNA ploidy status and c-erb B-2 expression were closely correlated with the axillary and/or internal mammary lymph node metastases, they did not appear as independent prognostic factors in this small series.

If axillary lymph node metastases were able to be accurately predicted, dissection could be avoided in some patients with breast cancer whose axillary nodes are clinically negative. In this study, we assessed the relationships between histological axillary lymph node metastases and clinical axillary nodal status, tumor size, DNA-ploidy, c-erbB-2 expression, and the score of the argyrophilic nucleolar organizer region. We then attempted to evaluate their predictive values for axillary lymph node metastasis in 173 patients with invasive breast cancer, retrospectively. The clinical and biological variables were significantly correlated with the presence and degree of axillary lymph node metastases. A metastatic index, calculated from the clinical and biological variables, proved especially useful for predicting axillary lymph node metastases in patients whose axillary nodes were clinically negative. However, the predictive abilities were still limited and thus it was concluded that as yet, only axillary dissection can provide accurate information on axillary lymph node metastases.

We evaluated the results of a mass screening study on breast cancer detection by physical examination alone conducted in Ishikawa Prefecture from 1978 to 1990. The number of cases of breast cancer detected by mass screening was then compared with that found in out-patient clinics during the same period. Breast cancer was detected in 88 of 152,969 women by mass screening, the detection rate being 0.06% for the total study: 0.08% at the initial screening and 0.04% at periodic screenings. Early stage breast cancer was more frequently detected during periodic screenings than at the initial screening or in out-patient clinics. Moreover, although the initial screenings may have identified patients with breast cancer at more advanced stages, the survival was not significantly different. The results of this series led us to conclude that mass screening by physical examination alone may have no impact on the mortality rate of breast cancer.

We assessed the relationships among histological axillary (AX) or internal mammary (IM) metastases and clinical and biological variables, and then attempted to evaluate their predictive values for AX and IM metastases in 128 patients with invasive breast cancer. As the results, these clinical and biological variables were significantly correlated with AX and IM metastases. However, a metastatic index calculated from clinical and biological variables was not much better in prediction of the AX metastases than axillary nodal status, whereas it was useful to predict the IM metastases. Thus, the predictive ability was still limited. Since accurate prediction of AX and IM metastases is critical to therapeutic choice, however, further study would be required.

An evaluation of the psychological and cosmetic morbidity of 31 patients who had undergone breast conserving treatment (BCT group) and 71 patients who had undergone radical mastectomy (RM group) revealed that 85% and 73%, respectively, were satisfied with their operative results. BCT appeared superior to RM in relation to body image, with 93% of the BCT group indicating BCT as a future choice of treatment, whereas only 35% of the RM group indicated RM as a future choice of treatment. For 59% of the BCT patients, the results were considered excellent or good by a physician, but fear of recurrence was frequently expressed by both groups even though an early stage of breast cancer had been significantly more common in the BCT group than the RM group. Sexual adjustment was the same in both groups. Body image was thus concluded to have been improved by BCT rather than RM, but psychological morbidity was essentially the same in both groups.

The risk of an internal mammary lymph node (IMN) metastasis and its prognostic value for patients with invasive breast cancer were assessed by evaluating 142 patients who had either a mastectomy with lymph node dissection or a biopsy of the IMN. By univariate analysis, overall survival significantly correlated with the patient's age, clinical axillary node status, tumor size, and DNA ploidy, as well as histologically confirmed axillary and IMN metastases. By multivariate analysis, however, only the presence of axillary and IMN metastases appeared to be an important independent factor affecting survival. However, the incidence of IMN metastases was associated significantly with age, clinical tumor and axillary node status, tumor size, axillary lymph node metastases, and DNA ploidy. Accordingly, the patient's age, tumor size, DNA ploidy, and axillary lymph node metastases proved to be effective variable for discrimination. Consequently, in predicting the presence of IMN metastases, a diagnostic accuracy of 82%, a sensitivity of 84%, and a specificity of 82% can be achieved by a discriminant function. We conclude that the discriminant function with these four variables is effective in assessing the risk of IMN metastases.

In this study, we compared the relapse-free and overall survival of 83 patients who underwent mastectomy with immediate reconstruction (MIBR) using a musculocutaneous flap with or without silicone implant with those of 153 patients with breast cancer who underwent mastectomy without immediate reconstruction. In univariate analysis, the overall and/or relapse-free survival of reconstructed patients with four or more positive axillary lymph nodes or those with menopausal status were significantly inferior compared with those of nonreconstructed patients. In multivariate analysis, however, the immediate breast reconstruction did not appear to have a significant adverse influence on all patients, and on the subgroups stratified by menopausal status or axillary lymph node metastases. Therefore, it was concluded that MIBR using a musculocutaneous flap did not compromise the survival of patients with breast cancer.

The relationship was assessed between c-erbB-2 oncoprotein expression and other prognostic factors in breast cancer, such as axillary and internal mammary node metastases. The value of these indicators was analyzed in estimating prognosis, especially in patients with axillary node-positive breast cancer. These results showed that c-erbB-2 is significantly related to clinical stage and axillary node metastases. A univariate study revealed that disease-free and overall survival were correlated significantly with clinical stage, tumor size, axillary and internal mammary node metastases, and 21N status. Among the patients with axillary node involvement, however, 21N status did not appear to be a significant additional prognostic factor. Internal mammary node metastases were significant. In a multivariate study, only axillary and internal mammary node metastases were significant prognostic factors for either the entire group of patients or those with positive axillary nodes. Therefore, axillary node dissection and biopsy of the internal mammary nodes may provide important prognostic information for patients with breast cancer.

We evaluated the relationship between the regional lymph node metastases and the DNA ploidy status in 207 patients with invasive breast cancer, as well as their prognostic values in estimating the prognosis of breast cancer. A significantly higher incidence of aneuploidy was found in patients with a large T3 or T4 tumor, a positive axillary lymph node status, more than 4 positive axillary lymph nodes or positive internal mammary lymph nodes. In a univariate study, the overall survival was significantly correlated with tumor size, axillary lymph node status, axillary and internal mammary lymph node metastases, and DNA ploidy status. In the multivariate analysis, however, only axillary and internal mammary lymph node metastases were recognized as important independent prognostic factors on survival. In this series, the DNA ploidy status did not appear to be an independent prognostic factor either in the entire series or in negative axillary node patients, since it was closely correlated with the axillary or internal mammary lymph node metastases, and the axillary node negative patients had an extremely favorable prognosis.

Clinical, histologic, and biologic prognostic factors were examined in 144 patients with invasive breast cancer. It was determined whether variable prognostic factors, especially internal mammary lymph node metastases, would serve as a basis for the prognosis of breast cancer. In a univariate study, overall survival was significantly correlated with tumor size, axillary lymph node status, axillary and internal mammary lymph node metastases, and DNA ploidy status. Especially among patients with one to three positive axillary nodes, survival in case of internal mammary involvement were significantly lower than without internal mammary involvement. In a multivariate study, only axillary and internal mammary lymph node metastases were recognized as important, independent prognostic factors of survival, but neither axillary lymph node status nor DNA ploidy status appeared as important prognostic factors. It was concluded that internal mammary lymph node metastases is additional prognostic factor, especially in patients with one to three positive axillary nodes. Because axillary and internal mammary lymph node metastases could not be predicted from their clinical assessment, axillary lymph node dissection and biopsy of internal mammary nodes may be a useful staging procedure for these patients.

In order to evaluate the prognostic importance of clinical and histological node information, we made univariate and multivariate analyses of regional lymph node metastases in 223 patients with operable breast cancer who were surgically treated from 1973 to 1985. Clinical axillary node status, histological involvement of the axillary lymph nodes, their anatomical levels and numbers, and histological involvement of the internal mammary lymph nodes were selected as evaluating prognostic factors. The histological presence or absence of axillary node involvement, especially at the distal level, proved to be the most important prognostic factor. However, neither the anatomical level nor the number of histologically involved axillary lymph nodes appeared to be an important prognostic factor. On the other hand, histological involvement of the internal mammary nodes appeared to be an important and independent prognostic factor. Therefore, we concluded that axillary lymph node dissection with a biopsy of the internal mammary nodes would provide more accurate information about the prognosis of patients with operable breast cancer.

We evaluated the relationship between the DNA ploidy status and other variable prognostic factors, especially regional lymph node metastases, in 121 patients with invasive ductal carcinoma of breast, together with the value of these factors in estimating the prognostic of breast cancer. The ploidy status was diploid in 40% of the patients, and aneuploid in 60%. A significantly higher incidence of aneuploidy was found in patients with more than 4 positive axillary lymph nodes, positive internal mammary lymph nodes, or clinical stage 3 of malignancy. In a univariate study, overall survival and disease-free survival were significantly correlated with axillary and internal mammary lymph node metastases, tumor size, and clinical stage of malignancy. The disease-free survival rates for the diploid group tended to be somewhat higher than those for the aneuploid group of patients without axillary lymph node metastases. In the multivariate analysis, however, only axillary lymph node metastasis was significantly correlated with overall survival and disease-free survival. There was also a trend for the internal mammary lymph node metastases to be correlated with survival. As the DNA ploidy status was closely correlated with the axillary and internal mammary lymph node metastases, it did not appear to be an independent prognostic factor in this small series.

A combination of quadrantectomy, axillary dissection, and radiotherapy (QUART) is the regimen most favored by Japanese surgeons among a variety of breast conserving therapies currently available against breast cancer. Unfortunately, extensive resections such as quadrantectomy often give poor local cosmetic results in patients with small breasts. With the aim of improving the cosmetic aspect after an extensive resection, immediate transposition of the latissimus dorsi muscle (LDM) was carried out in breast conserving surgery. To date, twenty-one patients have been entered in this study. Post-quadrantectomy breast deformity was not corrected in six patients including one with bilateral breast cancers, but was corrected by transposition of a part of LDM in 14 other patients. In the last patient, who also had bilateral breast cancers, the right breast was treated by QUART and the left breast by subcutaneous mastectomy followed by transposition of LDM. The cosmetic outcome for these patients was assessed both subjectively and objectively; the objective assessment used a Moire topography camera. The postoperative appearance and topography revealed a satisfactory symmetry of breasts in the transposed patients, especially those with small breasts, when compared with non-transposed patients. It may be concluded that the transposition of LDM is useful in preventing breast deformity following an extensive resection in breast conserving surgery.