Nobuko Tamura

Metaplastic carcinoma of the breast

The purposes of this study were to investigate whether the biological characteristics or outcomes of patients with metaplastic carcinoma, invasive ductal carcinoma, or invasive lobular carcinoma of the breast differ; to determine whether the metaplastic carcinoma subtypes have similar malignant potentials; and to identify accurate predictors of outcome in patients with metaplastic carcinoma. The subject comprised 6137 invasive ductal carcinoma patients, 301 invasive lobular carcinoma patients, and 46 metaplastic carcinoma patients of the breast. The metaplastic carcinomas were classified according to the World Health Organization classification. Multivariate analyses clearly demonstrated that the metaplastic carcinoma patients had a significantly poorer outcome than the invasive ductal carcinoma patients or the invasive lobular carcinoma patients independent of the nodal status or age not exceeding 39 years, whereas patients with triple-negative metaplastic carcinomas or triple-negative invasive lobular carcinomas had a poorer outcome than those with triple-negative invasive ductal carcinomas. Although no significant differences in clinical outcome were observed among the metaplastic carcinoma subtypes in multivariate analyses, an age not exceeding 39 years, the presence of skin invasion, and the presence of a squamous cell carcinoma component in nodal tumors were significant outcome predictors for metaplastic carcinoma patients. In conclusion, the results of this study clearly demonstrated that metaplastic carcinoma is more aggressive than invasive ductal carcinoma or invasive lobular carcinoma. Although the metaplastic carcinoma subtypes had no prognostic significance, an age not exceeding 39 years, the presence of skin invasion, and the presence of a squamous cell carcinoma component in nodal tumors were significant predictors of outcome among metaplastic carcinoma patients.

p53 expression in tumor-stromal fibroblasts is closely associated with the nodal metastasis and outcome of patients with invasive ductal carcinoma who received neoadjuvant therapy

The purpose of this study was to determine whether p53 immunoreactivity in tumor-stromal fibroblasts assessed by the Allred scoring system in biopsy specimens obtained before neoadjuvant therapy and assessed in surgical specimens obtained after neoadjuvant therapy is significantly associated with nodal metastasis by invasive ductal carcinoma and with the outcome of 318 patients with invasive ductal carcinoma who received neoadjuvant therapy, according to UICC pathologic TNM stage, in multivariate analyses with well-known clinicopathologic factors. The Allred scores for p53 in tumor-stromal fibroblasts in the surgical specimens were significantly associated with the presence of nodal metastasis. The Allred scores for p53 in the tumor-stromal fibroblasts of biopsy and surgical specimens were a very important outcome predictive factor for patients who received neoadjuvant therapy, independent of UICC pathologic TNM status, but the outcome predictive power of the Allred scores for p53 in tumor-stromal fibroblasts assessed in the surgical specimens was superior to that of the Allred scores for p53 in tumor-stromal fibroblasts in the biopsy specimens. The results indicated a close association between p53 protein expression in tumor-stromal fibroblasts, especially in surgical specimens, and both the presence of nodal metastasis and the outcome of invasive ductal carcinoma patients who received neoadjuvant therapy.

p53 expression in tumor stromal fibroblasts is associated with the outcome of patients with invasive ductal carcinoma of the breast

The purpose of this study was to determine whether p53 protein expression in tumor stromal fibroblasts assessed immunohistochemically by the Allred score system is significantly associated with nodal metastasis by invasive ductal carcinoma (IDC), and significantly associated with the outcome of 1042 IDC patients according to adjuvant therapy status, UICC pTNM stage, and triple‐negative IDC status, in multivariate analyses with well‐known clinicopathological factors. The Allred scores for p53 expression in tumor stromal fibroblasts were significantly associated with the number of nodal metastases, and Allred scores of 4–8 for p53 in tumor stromal fibroblasts significantly increased the hazard rate for distant organ metastasis or for tumor death in the triple‐negative IDC patients, and the UICC pTNM stage I, II, and III patients. The results indicated that p53 protein expression in tumor stromal fibroblasts is closely associated with the number of nodal metastases and the outcome of IDC patients. (Cancer Sci 2009; 00: 000–000)

Tumor histology in lymph vessels and lymph nodes for the accurate prediction of outcome among breast cancer patients treated with neoadjuvant chemotherapy

The present study investigated fibrotic foci (FFs), the grading system for lymph vessel tumor emboli (LVTEs), and the histological characteristics of nodal metastatic tumors that were significantly associated with the outcomes of 115 patients with invasive ductal carcinoma (IDC) who had received neoadjuvant chemotherapy. We compared the outcome predictive power of FFs, the grading system for LVTEs, and the histological characteristics of metastatic tumors in lymph nodes with the well‐known clinicopathological characteristics of tumor recurrence and tumor‐related death in multivariate analyses. The presence of FFs, as assessed by a biopsy performed before neoadjuvant chemotherapy, significantly increased the hazard rates (HRs) for tumor‐related death in all the cases and in cases with nodal metastasis. The grading system for LVTEs, which was assessed using surgical specimens obtained after neoadjuvant chemotherapy, was significantly associated with increasing hazard rates (HRs) for tumor recurrence and tumor‐related death in all the cases and in cases with nodal metastasis. Moderate to severe stroma in nodal metastatic tumors and five or more mitotic figures in nodal metastatic tumors were significantly associated with elevated HRs for tumor recurrence and tumor‐related death among all the cases. These results indicated that FFs, the grading system for LVTEs, and the histological characteristics of tumor cells in lymph nodes play important roles in predicting the tumor progression of IDCs of the breast in patients treated with neoadjuvant chemotherapy. (Cancer Sci 2009; 100: 1823–1833)

Feasibility of breast conserving surgery for Paget’s disease

INTRODUCTION The standard treatment for Pagets disease of the breast is mastectomy. Since it is frequently associated with underlying carcinoma, many surgeons are reluctant to choose breast conserving surgery for Pagets disease. PATIENTS AND METHODS We retrospectively analyzed a series of 59 patients with Pagets disease who had undergone mastectomy at the National Cancer Center Hospital between 1963 and 2009. RESULTS 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. CONCLUSION As Pagets disease is frequently accompanied by underlying intraductal and/or invasive carcinoma, patients should be carefully selected for breast conserving surgery.

Grading system for lymph vessel tumor emboli: significant outcome predictor for patients with invasive ductal carcinoma of the breast who received neoadjuvant therapy

The purpose of this study was to confirm that the grades of lymph vessel tumor emboli in biopsy specimens obtained before neoadjuvant therapy and in the surgical specimens obtained after neoadjuvant therapy according to the grading system we devised are significant histological outcome predictor for invasive ductal carcinoma (IDC) patients who received neoadjuvant therapy. The subjects of this study were the 318 consecutive IDC patients who had received neoadjuvant therapy in our institution. The lymph vessel tumor embolus grades in the biopsy specimens and in the surgical specimens were significantly associated with the increases in mean number of nodal metastases. Multivariate analyses with well-known prognostic factors and p53 expression in tumor-stromal fibroblasts clearly showed that the lymph vessel tumor embolus grade based on the biopsy specimens and based on the surgical specimens significantly increased the hazard rates for tumor recurrence and tumor-related death in all the IDC patients as a whole, in the IDC patients who did not have nodal metastasis, and in the IDC patients who had nodal metastasis, and the outcome-predictive power of the lymph vessel tumor embolus grades based on the surgical specimens was superior to that of the lymph vessel tumor embolus grades based on the biopsy specimens. The grades in the grading system for lymph vessel tumor emboli were significantly associated with nodal metastasis, and the histological grading system is an excellent system for accurately predicting the outcome of patients with IDC of the breast who have received neoadjuvant therapy.

PO33 Clinical practice guideline for preservation of fertility in breast cancer patients in Japan

HM32 Cognitive coping in young women with breast cancer R. Sachdev, S.M. Rosenberg, K.J. Ruddy, L. Schapira, S. Come, V. Borges, B. Larsen, S. Gelber, R.M. Tamimi, A.H. Partridge. Dana Farber Cancer Institute, Department of Medical Oncology, Boston MA, USA, Mayo Clinic, Department of Medical Oncology, Rochester MN, USA, Massachusetts General Hospital, Department of Medical Oncology, Boston MA, USA, Beth Israel Deaconess Medical Center, Department of Medical Oncology, Boston MA, USA, University of Colorado, Department of Medical Oncology, Aurora CO, USA, Dana Farber Cancer Institute, Department of Biostatistics and Computational Biology, Boston MA, USA, Brigham and Women’s Hospital, Department of Channing Division of Network Medicine, Boston MA, USA

Predictive factors of adjuvant therapy-related amenorrhea for patients with breast cancer.

217 Background: Reproductive age breast cancer patients often experience therapy-related amenorrhea so preserving fertility after treatment is a major concern. Anti-mullerian hormone (AMH) values have been reported useful in predicting menopause for infertility treatment patients, but published information is limited regarding breast cancer patients. If amenorrhea can be predicted before treatment, breast cancer patients hoping to have children in the future can consider this information in choosing treatment. Our aim was to predict patient fertility using AMH values. METHODS Forty breast cancer patients, 25-45 years of age (median, 35.5), who received adjuvant chemotherapy (CT) or endocrine therapy (ET), had AMH values retrospectively assayed from frozen serum before and after treatment. AMH values were then analyzed in relation to clinicopathological factors using logistic analysis. Of 19 adjuvant CT patients whose AMH values could be assayed, Coxs proportional hazard model indicated a correlation in terms of amenorrhea and time to menses resumption between clinicolpathological factors and AMH values. RESULTS The mean pretreatment AMH value for all 40 patients was 21.4pM (range, 3-78) and a correlation was demonstrated with patient age, but not breast cancer intrinsic subtype or stage. AMH values decreased to the lower limit after treatment for all CT patients regardless of age, but there was a difference in degree depending on patient age for ET patients. Of the 19 CT patients, the mean AMH value was 25.6pM (3-78). These patients all underwent a regimen of anthracycline with 11 (58%) also receiving a regimen of taxiane. After starting CT, 17 patients (89%) experienced amenorrhea, but 11 (59%) resumed menstruation within one year of finishing CT and 15 (78%) resumed within two years. There were no significant differences among CT patients in age, pretreatment AMH value, intrinsic subtype or stage, but patients receiving taxiane demonstrated a noteworthy trend. CONCLUSIONS Although we were unable to predict menopause directly using AMH values given the small number of patients in this study, we could estimate the risk of menopause as being either low or high for CT patients based on age and type of regimen.

Locoregional recurrence risk factor and indications for postmastectomy radiotherapy in Japanese patients with tumors 5 cm or larger.

127 Background: Locoregional recurrence (LRR) after mastectomy reduces the patients 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 has been the subject of substantial controversy. This study investigated what are risk factors for LRR and the efficacy of PMRT in this Japanese patient population. METHODS This 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 was 44.2 months, 38 (6.5%) patients experienced LRR. In the multivariate analysis, independent predictors of LRR include pectoral invasion in patients with 1-3 positive nodes, and severity lymphatic invasion, estrogen receptor-negative status, and 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. PMRT did not improve the outcome of the patients at highest risk who had these variables. CONCLUSIONS The efficacy of PMRT in patients with large tumors was not shown. In the context of systemic therapy and adequate lymph node dissection, PMRT by itself had a limited role in providing locoregional control. Due to the very low incidence of LRR observed, PMRT was not necessary for patients with large tumors without lymph node metastasis. The indication for PMRT in patients with metastatic nodes remains controversial.