Takashi Hojo

Okayama University, Okayama, Okayama, Japan

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Publications (53)106.55 Total impact

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    ABSTRACT: We investigated whether some mucinous carcinomas (MUCs) are associated with lobular neoplasia (LN) components, and if so, whether this subset has any distinct biological properties. MUC specimens from 41 patients were stratified into pure and mixed types. The LN components adjacent to MUC lesions were examined histopathologically. We also tested immunohistochemically for E-cadherin, β-catenin, and the neuroendocrine markers chromogranin A and synaptophysin; and compared results between MUCs with and without LN. Of 41 patients with MUC, LN was detected in 12 patients (29%); LN alone was the noninvasive component in 8 patients (20%). Decreased E-cadherin and β-catenin expression in the MUC component was detected in 2 (17%) and 7 (58%) cases, respectively, of MUC with LN, compared with 0% (P = 0.080) and 21% (P = 0.018) in MUCs without LN. Neuroendocrine factors were frequently detected in MUCs with LN (42%) and without LN (52%), but tended to be less frequent in MUCs with only LN components (25%) than in other MUCs (55%; P = 0.133). MUCs associated with LN components appear to be a biologically characteristic subset that frequently shows decreased cell–cell adhesion, cell polarity molecules and lack of neuroendocrine differentiation.
    Pathology International 05/2014; 64(5). · 1.72 Impact Factor
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    ABSTRACT: Clinical significance of intraoperative sentinel lymph node (SLN) metastases detection using one-step nucleic acid amplification (OSNA) has not been thoroughly investigated. The aim of this study was to assess the usefulness of using a combination of OSNA and conventional histological examinations. We included 772 consecutive patients with clinical node-negative cTis-cT3 primary breast cancer who underwent SLN biopsy with intraoperative OSNA and multi-section histological examination at our institution. We estimated the concordance rate and compared SLN metastases detection rates between the two methods. We also compared non-SLN metastasis detection rate between patients who tested positive in OSNA and those who tested positive in histology. Among 772 patients, SLN metastases were intraoperatively detected in 211 (26.4%) by either OSNA or histology, in 168 (21.8%) by OSNA, and in 150 (19.4%) by histology. The concordance rate between OSNA and histological examination was 89.2%, but only 123 (58.8%) patients tested positive in both OSNA and histology; 45 were positive in OSNA only and 43 were positive in histology only. SLN status as per both OSNA and histology was significantly correlated with the presence of non-SLN metastases and multivariate analysis-identified independent predictive factors of non-SLN metastases. Intraoperative SLN metastases detection may be more accurate with a combination of OSNA and histological examination than with OSNA or histological examination alone. By using both methods, we can reduce the risk of false negative rate in SLN biopsy, and may prevent physicians from overlooking patients with non-SLN metastases.
    Breast (Edinburgh, Scotland) 09/2013; · 2.09 Impact Factor
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    ABSTRACT: The accurate assessment of the risk of first locoregional recurrence is very important for improving the survival of patients with invasive ductal carcinoma of the breast. The present study investigated which histological factors (both well-known histological factors and factors that we have proposed) were the most capable of accurately predicting first locoregional recurrence among 1042 patients with invasive ductal carcinoma and various tumor statuses (overall, nodal status, UICC pTNM stage, adjuvant therapy status, and adjuvant radiotherapy status) using multivariate analyses by the Cox proportional hazard regression model. The present study clearly demonstrated that the best factor for accurately predicting locoregional recurrence was grade 3 lymph vessel tumor embolus (>4 mitotic figures and >6 apoptotic figures in tumor embolus), followed by type 2 invasive ductal carcinoma (negative for fibrotic foci but positive for atypical tumor-stromal fibroblast), grade 2 lymph vessel tumor embolus (1 to 4 mitotic figures and >0 apoptotic figures in tumor embolus; >0 mitotic figures and 1 to 6 apoptotic figures in tumor embolus), primary invasive tumor cell-related factors (>19 mitotic figures, presence of tumor necrosis, presence of skin invasion) and >5 mitotic figures in metastatic carcinomas to the lymph node. Our proposed factors were superior to well-known histological factors of primary invasive tumors or clinicopathological factors for the accurate prediction of first locoregional recurrence in patients with invasive ductal carcinoma of the breast. This article is protected by copyright. All rights reserved.
    Cancer Science 06/2013; · 3.48 Impact Factor
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    ABSTRACT: While clinical and pathologic responses are important prognostic parameters, biological markers from core needle biopsy (CNB) are needed to predict neoadjuvant chemotherapy (NAC) response, to individualize treatment, and to achieve maximal efficacy. We retrospectively evaluated the cases of 183 patients with primary breast cancer who underwent surgery after NAC (anthracycline and taxane) at the National Cancer Center Hospital (NCCH). We analyzed EGFR, HER2, and p53 expression and common clinicopathological features from the CNB and surgical specimens of these patients. These biological markers were compared between sensitive patients (pathological complete response;pCR) and insensitive patients (clinical no change;cNC and clinical progressinve disease;cPD). In a comparison between the 9 (5%) sensitive patients and 30 (16%) insensitive patients, overexpression of p53 but not overexpression of either HER2 or EGFR was associated with a good response to NAC. p53 (p=0.045) and histological grade 3 (p=0.011) were important and significant predictors of the response to NAC. The correspondence rates for histological type, histological grade 3, ER, PgR, HER2, p53, and EGFR in insensitive patients between CNB and surgical specimens were 70%, 73%, 67%, 70%, 80%, 93%, and 73%. The pathologic response was significantly associated with p53 expression and histological grade 3. The correspondence rate of p53 expression between CNB and surgical specimens was higher than that of other factors. We conclude that the level of p53 expression in the CNB was an effective and reliable predictor of treatment response to NAC.
    Acta medica Okayama 06/2013; 67(3):165-170. · 0.65 Impact Factor
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    ABSTRACT: PURPOSE: The optimal treatment duration time and the causal relationship between neoadjuvant endocrine therapy and clinical response are not clear. Therefore, we conducted the present study to investigate the potential benefits of neoadjuvant exemestane therapy with the goal of identifying the optimal treatment duration. METHODS: This study was conducted at three hospitals, as a multicenter, randomized phase II trial(UMIN000005668) of pre-operative exemestane treatment in post-menopausal women with untreated primary breast cancer. Fifty-one post-menopausal women with ER-positive and/or PgR-positive invasive breast cancer were randomly assigned to exemestane for 4 months or 6 months. Clinical response, pathological response, and decisions regarding breast-conserving surgery were the main outcome measures. RESULTS: Of the 52 patients that enrolled, 51 patients underwent surgery. Of those, 26 and 25 patients had been treated with exemestane for 4 and 6 months, respectively. Treatments were performedat 3 hospitals in Japan between April 2008 and August 2010. The response rates as assessed by clinical examination were 42.3% and 48.0% for 4 and 6 months of treatment, respectively. Pathological responses (minimal response or better) were observed in 19.2% and 32.0% of patients, and breast-conserving surgery was performed on 50.0% and 48.0% of patients from the 4 and 6 month treatment groups, respectively. CONCLUSION: The results of this study demonstrate that responses were equal to 4 or 6 months of exemestane treatment. Therefore, we propose that the rates of breast-conserving surgery could be maximized by 4 months of treatment. Furthermore, in addition to using exemestane as a preoperative treatment in post-menopausal women with ER-positive breast cancer, we envision administering the drug over the long term under careful clinical supervision.
    Breast (Edinburgh, Scotland) 04/2013; · 2.09 Impact Factor
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    ABSTRACT: Although previous studies have reported that onset at young age is associated with poor prognosis in breast cancer, the correlation between reproductive factors, breast cancer characteristics, and prognosis remains unclear. Five hundred and twenty-six premenopausal young women diagnosed with primary invasive breast cancer between January 2000 and December 2007 were included in this study. Patients were classified into four groups according to their reproductive history: women who gave birth within the previous 2 years (group A), women who gave birth between 3 and 5 years previously (group B), women who gave birth more than 5 years previously (group C), and nulliparous women (group N). The correlation between the time since last childbirth to diagnosis, histopathological tumor features, and breast cancer prognosis was evaluated. Breast cancer patients who had given birth more recently had more advanced stage tumors; larger sized tumors; a higher rate of axillary lymph node metastases; a higher histological tumor grade; and increased progesterone receptor (PgR)-, HER2+, and triple negative tumors than patients who had given birth less recently or not at all. Group A patients had significantly shorter survival times than patients in both groups C and N (log rank test; p < 0.001). After adjusting for tumor characteristics, the hazard ratio for death in group A was 2.19 compared with group N (p = 0.036), and the adjusted hazard ratio restricted to patients in group A with hormone-receptor-positive, and HER2- tumors was 3.07 (p = 0.011). Young breast cancer patients who had given birth more recently had tumors with more aggressive features and worse prognoses compared with patients who had given birth less recently or were nulliparous.
    Breast Cancer Research and Treatment 04/2013; · 4.47 Impact Factor
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    ABSTRACT: BACKGROUND: Triple-negative breast cancer patients are more likely to achieve a pathologic complete response after preoperative chemotherapy but they have still poor prognosis. The aim of this study was to identify prognostic factors in triple-negative breast cancer patients receiving preoperative chemotherapy. PATIENTS AND METHODS: Triple-negative breast cancer patients who underwent preoperative chemotherapy were retrospectively analyzed. Significant prognostic factors among clinical and pathologic variables were investigated with Kaplan-Meier analysis and Cox proportional hazards modeling for disease-free survival and overall survival. RESULTS: Among the 135 triple-negative breast cancer patients, the median age was 54 years, median tumor diameter on palpation was 4.5 cm, and there were 62 clinically node positive patients. The clinical response rate was 76% (103 patients) and pathologic complete response rate was 21% (29 patients). Median disease-free survival was 44.4 months and median overall survival was 49.2 months. Univariate and multivariate analysis showed that that completion of chemotherapy, better clinical response, fewer positive nodes, and lower histologic grades were significant factors associated with both disease-free and overall survival. CONCLUSIONS: Our data demonstrated that clinical response of preoperative systemic chemotherapy is an important independent favorable prognostic factor for triple-negative breast cancer.
    Clinical Breast Cancer 10/2012; · 2.42 Impact Factor
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    ABSTRACT: BACKGROUND: Locoregional recurrence (LRR) after mastectomy reduces the patient's quality of life and survival. There is a consensus that postmastectomy radiotherapy (PMRT) helps achieve locoregional control and reduces LRR. However, in patients with large tumors, the question of which variables affect the likelihood of LRR and the role of PMRT have been subjects of substantial controversy. This study investigated what the risk factors are for LRR and the efficacy of PMRT in this patient population. METHODS: This retrospective study examined 589 cases of invasive breast carcinoma with tumors 5 cm or larger from 1998 to 2008. We divided the study population into 3 groups: patients with negative nodes, 1-3 positive nodes, and ≥4 positive nodes. The relationship between various clinicopathological variables and LRR was examined, and the relationship between LRR and PMRT was estimated. RESULTS: During the median follow-up of 44.2 months, 38 (6.5 %) patients experienced LRR. In the multivariate analysis, independent risk factors for LRR included pectoral invasion in patients with 1-3 positive nodes, severity of lymphatic invasion, estrogen receptor-negative status, and a nodal ratio of positive/excised nodes >0.50 in patients with ≥4 positive nodes. In patients without positive nodes, none of the examined variables were significantly associated with LRR. Although patients treated with PMRT had good outcomes, there was no significant difference. CONCLUSIONS: With systemic therapy and adequate lymph node dissection, PMRT by itself was of limited value in establishing locoregional control. Due to the very low incidence of LRR observed, PMRT was not necessary for patients with large tumors without lymph node metastasis. Further examination and consensus about the indications for PMRT in patients with 1-3 metastatic nodes are needed.
    Breast Cancer 08/2012; · 1.33 Impact Factor
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    ABSTRACT: We assessed the radiological findings and capability of DBT in adjunction to FFDM to predict response to NAC in comparison with other diagnostic modalities. 25 women (ages 29-73, mean age, 53.0 years old) having 26 lesions were recruited for this study and gave informed consent. In accordance with this preliminary study, the adjunction of DBT to FFDM combined with other diagnostic modalities will contribute to more accurate assessment of pathological response to NAC.
    Proceedings of the 11th international conference on Breast Imaging; 07/2012
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    ABSTRACT: It is often difficult to make a definitive diagnosis of papillary breast lesions using core needle biopsy (CNB) specimens. We studied loss of heterozygosity (LOH) on chromosome 16q in order to assess its diagnostic use for papillary breast lesions in CNB specimens. Of 25 patients with intraductal papillary breast tumors, we extracted DNA from paired samples of tumor cells from CNB specimens and non-tumor cells from subsequent excision specimens and analyzed LOH at the D16S419 and D16S514 loci on chromosome 16q. LOH analysis results were compared with final diagnoses based on pathological features of the resected specimens. On the CNB specimens, 21 tumors were histologically diagnosed as indeterminate or suspicious for malignancy, while four tumors were unambiguously malignant. Of the 21 indeterminate or suspicious tumors, 11 were finally diagnosed as benign and ten as malignant, and on these, LOH analyses were informative for 8 of the 11 benign tumors and 7 of the 10 malignant tumors. LOH was also informative on two of the four tumors unambiguously malignant on CNB. None of the eight informative benign tumors showed LOH on 16q. Six of the eleven informative malignant tumors showed LOH on 16q. LOH on 16q was significantly different between CNB specimens of benign and malignant intraductal papillary tumors (P = 0.007). Analysis of LOH on 16q may be helpful in making a definitive diagnosis in cases of papillary breast lesions, in both excised and CNB specimens.
    Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin 04/2012; 460(5):497-504. · 2.68 Impact Factor
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    Mammography - Recent Advances, 03/2012; , ISBN: 978-953-51-0285-4
  • The Breast Journal 02/2012; 18(2):195-7. · 1.83 Impact Factor
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    ABSTRACT: Although effective regimens have been established for invasive ductal carcinoma-not otherwise specified (IDC), the efficacy and prognosis of other minor types of breast cancer are unknown because of their rareness. The clinicopathological features and prognosis of other minor types concerning the response to neoadjuvant chemotherapy (NAC) were evaluated in this study. A total of 562 patients were classified according to the Japanese and the World Health Organization (WHO) classifications, and the number of IDC and other special types (SP) was 500 and 62. The SP patients had a significantly poorer clinicopathological response to NAC and less breast-conservative therapy than those with IDC. According to the WHO classification, mucinous carcinoma, metaplastic carcinomas and apocrine carcinoma also responded poorly, and patients with metaplastic carcinomas and invasive lobular carcinoma had a significantly poorer prognosis. Despite the poor response to chemotherapy, patients with mucinous carcinoma and apocrine carcinoma had a good prognosis. The response to NAC and the prognosis vary for each histological type. For some types, the prognosis was not related to the clinicopathological response to NAC. In the treatment of breast cancer, neoadjuvant chemotherapy (NAC) has become the standard treatment modality for downstaging purposes. Although effective regimens have been established for the treatment of invasive ductal carcinoma-not otherwise specified (IDC), the data about the efficacy and prognosis for patients with other minor types of breast cancer are insufficient because of the rareness of these tumors. Defining the relationship between each histological type and the clinicopathological response to NAC is essential to optimizing individualized treatment. We retrospectively evaluated the clinicopathological features and classification of the histological types based on the Japanese and the World Health Organization (WHO) classifications before and after NAC in 562 patients with primary breast cancer who underwent curative treatment after NAC between 1998 and 2008. The prognosis was estimated for each histological type. Of the 562 patients, the number of cases of IDC and other special types (SP) was 500 and 62. In the SP group, the clinicopathological response to NAC was significantly poorer, and the patients underwent breast-conservative therapy less frequently than did the IDC patients. According to the WHO classification, mucinous carcinoma, metaplastic carcinomas and apocrine carcinoma responded poorly to NAC. The disease-free survival and overall survival were significantly worse for patients with metaplastic carcinomas (p<0.001 and p<0.001) and with invasive lobular carcinoma (p=0.03 and p<0.001) than other cancers. Despite their poor response to treatment, patients with mucinous carcinoma and apocrine carcinoma had a good prognosis. The response to standardized NAC and prognosis varies for each histological type. For some types, the prognosis was not associated with the clinicopathological response to NAC. Innovative regimens should therefore be investigated for each histological type to achieve the best response.
    Breast (Edinburgh, Scotland) 01/2012; 21(3):289-95. · 2.09 Impact Factor
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    ABSTRACT: This is the study which assessed sentinel lymph node biopsy (SNB) using indigo carmine blue dye and the validity of the '10% rule' and '4 nodes rule'. Patients (302) were performed SNB using the combined radioisotope (RI)/indigo carmine dye method. Excised SLNs were confirmed whether they were stained and numbered in order of RI count and the percentage of radioactivity as compared to the hottest node was calculated. The relationship between histological diagnosis, dyeing and RI count was assessed. All the patients were detected SLN. Positive nodes were identified in 84 (27.8%) patients and were identified up to the third degree of hottest. All the hottest positive nodes were stained by indigo carmine. From the results, removing the three most radioactive SLNs identified all cases of nodal metastasis without complications. These stopping rules were valid and useful under indigo carmine use too.
    Breast (Edinburgh, Scotland) 11/2011; 21(4):455-8. · 2.09 Impact Factor
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    ABSTRACT: BACKGROUND: Locoregional recurrence (LRR) after mastectomy reduces the patient's quality of life and survival. There is a consensus that postmastectomy radiotherapy (PMRT) helps establish locoregional control and reduces LRR in patients with ≥4 metastatic nodes. However, in patients with 1-3 metastatic nodes, the incidence of LRR and the role of PMRT have been the subject of substantial controversy. This study assessed the risk factors for LRR and the efficacy of PMRT in Japanese breast cancer patients with metastatic nodes. METHODS: This study analyzed 789 cases of invasive breast carcinoma with metastatic nodes from 1998 to 2008. We divided the study population into 4 groups: 1-3 positive nodes with/without chemotherapy and ≥4 positive nodes with/without chemotherapy. Risk factors for LRR were identified and the relationship between LRR and PMRT was analyzed. RESULTS: During the median follow-up of 59.6 months, 61 (7.7%) patients experienced LRR. In patients who received chemotherapy, independent LRR risk factors were high nuclear grade, severe lymphatic invasion, vascular invasion, and progesterone receptor-negative status in patients with 1-3 positive nodes, and severe lymphatic invasion and estrogen receptor-negative status in patients with ≥4 nodes. Although patients treated with PMRT had good outcomes, there was no significant difference, and PMRT did not significantly improve the outcome of the patients with all risk factors. CONCLUSIONS: With systemic therapy and adequate dissection, PMRT by itself was of limited value in establishing locoregional control. The indication for PMRT in patients with 1-3 positive nodes remains controversial.
    International Journal of Clinical Oncology 11/2011; · 1.41 Impact Factor
  • The Breast Journal 11/2011; 18(1):81-2. · 1.83 Impact Factor
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    ABSTRACT: The pathologic diagnosis is regarded as the final diagnosis of a disease, and pathologic examination based on tumor histology is very important for the accurate assessment of the biological characteristics of tumors. The purpose of this study was to investigate the histologic factors that accurately predict patient outcome among 1042 patients with invasive ductal carcinoma of the breast. Both well-known histologic factors and our proposed histologic factors were examined according to several tumor statuses using multivariate analysis. This study clearly demonstrated that type 4 invasive ductal carcinomas having fibrotic foci and atypical tumor-stromal fibroblasts within the fibrotic foci are significant outcome predictors for lymph node-negative and lymph node-positive, the pathologic UICC-TNM stage II and III, luminal A-subtype, luminal B-subtype, and equivocal HER2 subtype invasive ductal carcinoma patients. Lymph vessel tumor embolus grades 2 and 3 were significant outcome predictors for lymph node-positive, UICC pTNM stages II and III, luminal A-subtype, and triple-negative invasive ductal carcinoma patients (except lymph vessel tumor embolus grade 2 in luminal A-subtype patients). More than 5 mitotic figures in metastatic carcinoma to the lymph nodes was a significant outcome predictor for lymph node-positive, UICC pTNM stage II, and luminal A-subtype invasive ductal carcinoma patients. A fibrotic focus diameter >8 mm was a significant outcome predictor for UICC pTNM stages I and III invasive ductal carcinoma patients. These findings strongly suggest that these histologic factors are very useful for accurately predicting the outcomes of patients with invasive ductal carcinoma of the breast.
    The American journal of surgical pathology 08/2011; 35(10):1484-97. · 4.06 Impact Factor
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    ABSTRACT: We previously reported that the primary tumour/vessel tumour/nodal tumour (PVN) classification is significantly superior to the UICC pTNM classification and the Nottingham Prognostic Index for accurately predicting the outcome of patients with invasive ductal carcinoma of the breast in a manner that is independent of the nodal status and the hormone receptor status. The purpose of the present study was to compare the outcome predictive power of a modified PVN classification to that of the newly devised pathological UICC pTNM classification and the reclassified Nottingham Prognostic Index in a different group of patients with invasive ductal carcinoma (n=1042) using multivariate analyses by the Cox proportional hazard regression model. The modified PVN classification clearly exhibited a superior significant power, compared with the other classifications, for the accurate prediction of tumour recurrence and tumour-related death among patients with invasive ductal carcinoma in a manner that was independent of the nodal status, the hormone receptor status, and adjuvant therapy status. The modified PVN classification is a useful classification system for predicting the outcome of invasive ductal carcinoma of the breast.
    British Journal of Cancer 08/2011; 105(5):698-708. · 5.08 Impact Factor
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    ABSTRACT: The standard treatment for Paget's disease of the breast is mastectomy. Since it is frequently associated with underlying carcinoma, many surgeons are reluctant to choose breast conserving surgery for Paget's disease. We retrospectively analyzed a series of 59 patients with Paget's disease who had undergone mastectomy at the National Cancer Center Hospital between 1963 and 2009. In 55 of 59 cases (93%) there was underlying carcinoma in the ipsilateral breast. Clinically, 27 (46%) patients had no evidence of other tumors, but 23 (85%) had underlying histopathologically confirmed carcinoma. Based on the data from this subset, cone excision with a 3-cm radius and a 4-cm radius could completely resect any underlying malignancy in 74% and 85% of patients, respectively. As Paget's disease is frequently accompanied by underlying intraductal and/or invasive carcinoma, patients should be carefully selected for breast conserving surgery.
    Breast (Edinburgh, Scotland) 06/2011; 20(6):515-8. · 2.09 Impact Factor
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    ABSTRACT: We previously reported that the number of mitotic figures in metastatic mammary carcinoma to the lymph nodes accurately predicted the outcome of patients with invasive ductal carcinoma with nodal metastasis. To confirm these previous findings, the present study investigated the number of mitotic figures and other histologic characteristics in metastatic mammary carcinoma to the lymph nodes and their associations with patient outcome according to nodal status and the histologic grade of primary invasive ductal carcinomas in a different series of 1039 patients with invasive ductal carcinoma. Multivariate analyses examining well-known clinicopathologic factors, the number of mitotic figures in the primary invasive ductal carcinomas, the grading system for lymph vessel tumor emboli, the p53 Allred score risk classes of tumor-stromal fibroblasts forming and not forming a fibrotic focus, and 9 histologic features of metastatic mammary carcinoma to the lymph nodes were performed. The presence of 6 or more mitotic figures in metastatic mammary carcinoma to the lymph nodes significantly increased the hazard ratios for tumor recurrence and tumor-related death among patients with invasive ductal carcinoma as a whole, those with nodal metastasis, and those with a histologic grade of 2 or 3. The presence of 6 or more mitotic figures in metastatic mammary carcinoma to the lymph nodes also significantly increased the hazard ratio for tumor recurrence among patients with histologic grade 1 invasive ductal carcinoma. In conclusion, this study clearly confirmed the excellent outcome predictive power of the number of mitotic figures in metastatic mammary carcinoma to the lymph nodes.
    Human pathology 06/2011; 42(12):1823-32. · 3.03 Impact Factor

Publication Stats

244 Citations
106.55 Total Impact Points

Institutions

  • 2008–2013
    • Okayama University
      • • Department of Breast and Endocrine Surgery
      • • Department of Cancer and Thoracic Surgery
      Okayama, Okayama, Japan
    • National Cancer Center
      • Center for Cancer Control and Information Services
      Edo, Tōkyō, Japan
    • National Hospital Organization Kyushu Cancer Center
      Hukuoka, Fukuoka, Japan