Search

Immunohistochemical (IHC) expression of Ki67 has a prognostic and predictive value for breast cancer, and the IHC Ki67 labeling index is estimated by counting the number of positive and negative cells. It has not been clarified whether IHC Ki67 estimated using a semiquantitative scoring system has a prognostic value. We aimed to estimate the usefulness of scoring categories of IHC Ki67 as a prognostic factor for breast cancer subgroups.We retrospectively identified patients in the Tokai University breast cancer database for whom IHC Ki67 data were available between January 1, 2000 and December 31, 2010. Survival curves were calculated using the Kaplan-Meier method and compared using the log-rank test.Of the 1331 primary breast cancer patients included in the study, In patients with estrogen receptor (ER)-positive and HER2-negative tumors (n = 971), high and intermediate Ki67 scores were associated with poorer relapse-free survival than low Ki67 scores (P.001 and P = .002, respectively). Furthermore, in the multivariate analyses of this subgroup, progression-free survival (PFS) was significantly longer in patients with low Ki67 scores than in patients with high Ki67 scores (hazard ratio, 0.387; 95% confidence interval, 0.233-0.643; P.001). In the multivariate analyses, the Ki67 score was not significantly associated with PFS in the ER-positive and HER2-positive, ER-negative and HER2-positive, or ER-negative and HER2-negative subgroups.Our data demonstrated that low, intermediate, and high Ki67 scores have a prognostic value in breast cancer patients with ER-positive and HER2-negative tumors.

Aim: Brain metastases (BM) are associated with impaired quality of life and have an increasing problem in the management because of progressive neurological impairments. Although BM are less common in patients (pts) with breast cancer, they are associated with considerably poorer prognosis and are less responsive to systemic therapies. Recently, a trend of increased incidence of BM has been noted. To define prognostic factors for BM, compare their clinical courses and prognoses according to the subtypes, and analyze the causes of death. Methods: We retrospectively collected cohort data for 1466 pts diagnosed with BM between 2001 April and 2012 December from 24 institutions of the breast division of the Japan Clinical Oncology Group (JCOG). Results: After exclusion 210 pts' data due to the lack of enough data, overall 1256 pts with BM were evaluated. The median overall survival (OS) was 8.7 months (m) (95% CI, 7.8–9.6). Univariate and multivariate analyses revealed that pts with BM within 6 m of metastatic breast cancer diagnoses, asymptomatic brain disease, or HER2-positive/ER-positive tumors had increased OS. Median OS after BM was 9.3 m (95% CI, 7.2–11.3) for the luminal type, 16.5 m (11.9–21.1) for the luminal-HER2 type, 11.5 m (9.1–13.8) for the HER2 type, and 4.9 m (3.9–5.9) for the triple-negative type. The duration from MBC diagnosis until BM was longer in pts with luminal-type tumors than in pts with luminal-HER2 (HR = 1.24, P= 0.03), HER2 (HR = 1.83, P Conclusions: The prognosis and clinical course of pts before and after developing BM vary according to the subtype. Good prognostic factors for OS included the early detection of BM, asymptomatic brain disease, and HER2/ER-positive status. Focusing on the subtypes can optimize the prevention, early detection, and improved treatment of BM. Disclosure: All authors have declared no conflicts of interest.

In previous decades, numerous attempts have been made to develop therapeutic peptide vaccines for cancer. However, the HLA (Human Leukocyte Antigen) types are limited because most peptide vaccines are specific to the major HLA types of the area. Peptide vaccines specific for Caucasians thus may not be specific to Japanese. Moreover, they are not designed to stimulate both helper and killer T cells. We are trying to make a peptide vaccine specific to the MHC of Japanese patients that stimulates both helper and killer T cells. We selected a new-HER2 peptide including a B-cell epitope which has anti-tumor effects in a mouse system. The B-cell epitope was determined for a H401 monoclonal antibody (mAb) specific for HER2. As for epitope mapping of the chimera mAb CH401, enzyme-linked immunosorbent assay was employed with 20mer MAPs carrying a partial HER2 sequence. The CH401 epitope was determined as N:163-182, and the CH401MAP including the epitope induced anti-tumor effects in HER2-overexpressing tumor cells in a mouse system. We predicted the peptide MHC affinity and examined the in vitro reaction of PBMCs from Japanese breast cancer patients. The study enrolled 173 female breast cancer patients who underwent surgery between October 2010 and July 2012 at Tokai University Hospital. We used SYFPEITHI, BIMAS and IEDB algorithms to estimate peptide and HLA affinity. Lymphocyte proliferation ability, cell surface marker expression, cytokine (interleukin (IL)-2, IL-4 and interferon (IFN)-g) secretion and specific antibody production were analyzed in vitro. According to the algorithms, 97.1% of patients showed high to intermediate affinity of the CH401 epitope peptide to Japanese major HLA class I. Similarly, 34.5% of patients showed high to moderate affinity to HLA class II. The proliferative ability of patient groups was significantly higher than that of the HD group (HER2 0 group, p Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P5-01-11.

Background Immunohistochemical assessment of Ki67 labeling index (IHC Ki67) has been described as a prognostic and predictive marker for breast cancer. On the other hand, several genetic prognostic markers have been described for breast cancer However, few clinical data sets provide information on correlations between genomic markers, mRNA Ki67, and IHC Ki67 in the same cohort of patients with survival data. The objective of this study is to examine the association between immunohistochemical Ki67 labeling index, Ki67 mRNA expression level, and first-generation gene signatures in a cohort of breast cancer patients. Patients and methods We assessed associations between IHC Ki67 and first-generation gene signatures in a panel of 40 tumor samples, using an oligonucleotide microarray. Gene expression analyses included Ki67 alone (MKi67), 21-gene signature, Mitosis Kinome score signature (MKS), and Genomic grade index (GGI). Correlation coefficients were calculated by Spearman's rank correlation test. To assess the relationship between IHC Ki67 and survival outcomes, survival curves were calculated by the Kaplan–Meier method and compared with the log-rank test according to IHC Ki67. Results Median age at diagnosis was 51 years. Treatments included adjuvant chemotherapy (32 patients) and endocrine therapy (21 patients). IHC Ki67, MKi67, and 3 genetic markers were highly correlated in all cases (Rho: 0.71–0.79). Estrogen receptor (ER)-positive cases exhibited strong correlations between IHC Ki67 and other signatures (Rho: 0.79–0.83). ER-negative cases displayed slightly lower correlations (Rho: 0.61–0.74). In ER-positive cases, the low IHC Ki67 group exhibited significantly longer relapse-free survival (RFS) than the high IHC Ki67 group (p = 0.007). This difference was confirmed by multivariate analysis. Conclusions Our data indicate that IHC Ki67 exhibits similar predictive power for proliferation in ER-positive cancers as genomic markers. Further study of IHC Ki67 is needed to define prognostic factors and predictive factors for chemotherapy using central laboratory assessment. Disclosure All authors have declared no conflicts of interest.

545 Background: Studies have suggested that trastuzumab may convert HER2-positive (HER+) primary breast tumors to HER2-negative (HER2–). Whether this conversion happens between primary and metastat...

616 Background: Tyrosine 1248 is one of the autophosphorylation sites of HER2. Our goal was to determine the prognostic value of expression level of tyrosine 1248-phosphorylated HER2 (pHER2) in pat...

Background FDG positron emission tomography/computed tomography (PET/CT) may accurately detect distant metastases during staging of primary breast cancer. However, the evidence is very limited. We retrospectively compared the sensitivity and specificity of PET/CT and conventional imaging (CT, ultrasonography, radiography, and skeletal scintigraphy) for the detection of distant metastases in patients with primary breast cancer. We also retrospectively tested the hypothesis that stage III disease detected by conventional imaging + PET/CT has a better prognosis than that detected by conventional imaging only. Methods To determine sensitivity and specificity, we used a database of 225 patients with primary breast cancer (2000-2009) for which PET/CT data existed. The presence or absence of distant metastases was determined based on histopathologic findings, subsequent imaging findings, or clinical follow-up. To determine prognosis, we studied 935 patients newly diagnosed with stage III breast cancer (2000-2009). In 82 of these patients, stage III disease was detected by conventional imaging + PET/CT. We studied 171 IBC patients newly diagnosed with stage III breast cancer. In 51 of these patients, stage III disease was detected by conventional imaging + PET/CT; we compared their relapse-free survival (RFS) and overall survival (OS) rates with those for 853 patients diagnosed using conventional imaging only. Univariate and multivariate Cox Proportional Hazard regression models were used to assess PEC/CT. Results Among 225 pts with primary breast cancer, the sensitivity and specificity for PET/CT in the detection of distant metastases were 97.4% and 91.2%, respectively; This was significantly higher (p=0.009 and P PET/CT had higher sensitivity and specificity than conventional imaging in the detection of distant metastases of breast cancer. Among patients with stage III disease, there was no difference in OS or RFS between patients diagnosed with conventional imaging + PET/CT and patients diagnosed with conventional imaging only. IBC patients staged with conventional imaging + PET/CT had better prognosis than those staged with conventional imaging only. Based on our results, the use of PET/CT as a staging tool to detect metastasis is not justified in stage III non-IBC. Conversely, the use of conventional imaging + PET/CT in patients with IBC appears promising, but needs prospective confirmation. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P5-01-02.

The prognostic study for the Japanese Breast Cancer Society (JBCS) registry in 2006 was finally published here (Figs. 1, 2, 3, 4, 5, 6, 7, 8, 9, Sup. Table 1–9). The JBCS registry has been started from 1975. To 2003, for 29 years, 188,265 cases have been registered. With the cooperation of the Non-Profit Organization Japan Clinical Research Support Unit (J-CRSU) and the Public Health Research Foundation, we have moved to the new system by the web registration from 2004. In 2006, the number of the registry for institutions was 352 and cases were 22,005. The number of institutions in this prognostic study was 134 and cases were 8788, with 39.9 %. An assessment of 5-year prognosis for cases registered in 2006 has been carried out, and here we report the results thanks to a number of efforts and cooperation. We believe that it is necessary to further promote the registry for contributions to improving breast cancer care and prognosis. Background characteristics of the patients are summarized in Table 1. The 5-year disease-free survival (DFS) was Electronic supplementary material The online version of this article (doi:10.1007/s12282-015-0646-3) contains supplementary material, which is available to authorized users.

Purpose The aim of this study was to investigate whether young age at onset of breast cancer is an independent prognostic factor in patients from the Japanese Breast Cancer Registry, after adjustment of known clinicopathological prognostic factors. Methods Of the 53,670 patients registered between 2004 and 2006 and surveyed after a 5-year follow-up prognosis, 25,898 breast cancer patients (48.3 %), who were obtained prognostic data, were examined. Clinicopathological factors were compared between young adult (YA; 50 years) patients. Five-year disease-free survival (DFS) and overall survival (OS) rates were studied. Results YA patients were associated with an advanced TNM stage and aggressive characteristics (e.g. human epidermal growth factor receptor 2 (HER2)-positive or oestrogen receptor (ER)-negative breast cancers) compared to MA and OA patients (P