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K Kuroi

Publications and source records attributed to K Kuroi.

At least 19 recordsLinked to original sources
PubMed2005

Update results of FEC followed by docetaxel neoadjuvant trials for primary breast cancer.

This study has been initiated to evaluate the safety, clinical and pathologic response as well as the relation of response (pCR or non-pCR) and survival (overall and relapse-free) of fluorouracil, epirubicin and cyclophosphamide (FEC) followed by docetaxel (DOC) as preoperative chemotherapy in patients with operable breast cancer. Japanese patients with primary breast cancer, Tlc-3N0M0 or T1-3NIM0, age 20-60, PS 0-1 were included in this study. Preoperative chemotherapy consisted of 4 cycles of FEC (500 mg/m(2), 100 mg/m(2), 500 mg/m(2)) every 3 weeks followed by 4 cycles of DOC (75 mg/m(2)) every 3 weeks. Since June 2002, 200 patients were enrolled in this study, and the time of this interim analysis, 80 patients were evaluable for safety and clinical efficacy. The overall clinical response rate was 71.4% (14% CR, 44% PR, 42% SD/PD), and the only G3,4 toxicities, neutropenia and febrile neutropenia were observed in 54% and 14% of patients, respectively. Eighty nine patients were evaluable for pathologic response by central review. Pathologic response was evaluated among invasive tumors on multiple cross-section specimens based on a modified version of the Japanese grading system for Japanese Breast Cancer Society. The pathologic response rate was 17%. In this ongoing trial, FEC followed by DOC was active and well tolerated.

Antineoplastic Agents, Phytogenic↗
PubMed2005

Unargued issues on the pathological assessment of response in primary systemic therapy for breast cancer.

PURPOSE: The role of primary systemic therapy (PST) in the treatment of operable breast cancer is currently under intensive investigation in the hope of allowing greater conservation of the breast, and emerging evidence suggests that induction of a pathological complete response (pCR) is at least, to some extent, predictive of long-term clinical response. In this review, we highlight the issues of pathologic evaluation after PST. METHODS: We performed a computer-assisted MEDLINE search, and additional references were found in the bibliographies of these articles. RESULTS: So far, several grading classifications are used to assess pathologic responses after PST, and pCR rates vary from 1% to 54.7% according to the PST regimens employed. However, the term "pCR" has not been applied in a consistent, standardized manner, and the pCR rates appear to depend not only on the differences in the definition of pCR, but also on the extent of tissue sampling and the techniques used for pathologic examination. So far, only limited information is available about the reliability and validity of the definition of pathologic responses. CONCLUSION: Assessment of pCR needs to be standardized, and each grading system should be verified for reliability and validity. As a lack of standard for tumor processing and evaluation may result in considerable fluctuation of pCR rates between trials, we should take into account the differences in the definition of pathologic response when comparing the results of PST.

Breast Neoplasms↗
PubMed2001

Clinical significance of plasma nucleosome levels in cancer patients.

The nucleosome is the primary repeating unit of DNA organization in chromatin, and cell death may lead to increased levels of circulating nucleosomes in plasma (PNLs) in various circumstances such as inflammation, pulmonary embolism, autoimmune disease, and cancer. Cell death can also be induced by chemotherapeutic agents. We investigated PNLs in 99 patients with primary breast cancer, 26 with recurrent disease, 11 with benign breast disease, and 27 with other histological types of cancer. In 18 patients with recurrent breast cancer who received docetaxel (D, 60 mg/m2) every 3 weeks as second line therapy after an anthracycline-based regimen, PNLs were investigated before and during the administration of D. One hundred and seventy-four healthy controls (111 females, 63 males) without any evidence of disease were also investigated. PNLs were detected using the cell death detection ELISAplus kit. PNLs were significantly higher in patients with primary breast cancer (mean +/- SD: 0.135 +/- 0.213) and in recurrent breast cancer (0.182 +/- 0.196) as compared with healthy female controls (0.010 +/- 0.012) (p < 0.01). In patients with primary breast cancer, no correlation was found between PNLs and clinicopathological characteristics. On the other hand, PNLs were decreased after mastectomy (p < 0.05). Patients with other histological types of cancer (0.244+/-0.383) also showed significantly higher PNLs as compared to healthy controls (p < 0.01), and PNLs were elevated independently of the histological type of cancer. In patients with recurrent breast cancer, PNLs showed a transient increase 24 h after the administration of D, and these increases correlated with the degree of subsequent leukopenia. In a follow-up study, pretreatment baseline PNLs decreased markedly when a response was obtained, whereas there was no decrease in either stable disease or progressive disease. Thus, increased PNLs were found in cancer patients, and PNLs seem to be a sensitive marker of cell death that could be predictive of both leukopenia and response to chemotherapy.

Adolescent↗
PubMed2001

[Efficacy of weekly docetaxel therapy for advanced or recurrent breast cancer].

To evaluate the safety and efficacy of weekly docetaxel (weekly TXT) in cases of advanced or recurrent breast cancer, 31 patients were enrolled in this pilot study of weekly TXT given at 25 mg/m2/w. Each cycle consisted of 3 weeks of therapy followed by a 1-week treatment break in an outpatient setting. Patients received a median of 15 infusions with a median cumulative dose of 680 mg. The median time to treatment failure was 8 months. The overall response rate was 32.3%, and 22.6% of patients had stable disease for at least 6 months. The response rate was consistent regardless of prior chemotherapy with anthracycline. There was no grade 3 or 4 toxicity, and the regimen was generally well tolerated. Although 37.5% of patients had grade 1 or 2 nail change, myelosuppression, fatigue, nausea, vomiting and fluid retention were mild. Weekly TXT seems to be an effective and feasible treatment for advanced or recurrent breast cancer patients.

Adult↗
PubMed2000

The predictive value of angiogenesis for adjuvant therapy in breast cancer.

Recent accumulated data have indicated that angiogenesis is a promising indicator to predict prognosis and response to treatment. In breast cancer, microvessel density (MVD), a semi-quantitative marker of neovascularization grade, has been suggested to provide independent prognostic value. In addition, the expression of both vascular endothelial growth factor (VEGF)and thymidine phosphorylase (TP), two angiogenesis regulatory molecules, were found to be closely associated with MVD, and with the effect of treatments. In particular, VEGF expression seems to be a phenotype resistant to endocrine therapy, whereas TP expression decreases sensitivity to chemotherapy containing fluorouracil. This review summarizes the current topics regarding the prognostic and predictive value of angiogenesis in primary breast cancer, and we discuss future applications of antiangiogenesis treatments in an adjuvant setting.

Angiogenesis Inhibitors↗
PubMed2000

[Antiangiogenesis therapy and hormone therapy--their resemblance and applications of prognostic and predictive factors].

Many new ideas to control tumor angiogenesis are now being tested in clinical trials. In considering strategies for clinical development of antiangiogenesis treatment, that of endocrine therapy might be particularly useful as a model. Endocrine therapy is a unique treatment used only for hormone-dependent tumors; however, its clinical fruits are exceptional in the entire history of cancer therapy. It is now clearly proven that long-term continuous treatment with antihormones brings a magnificent survival benefit for primary breast cancer patients. This benefit is tumor-phenotype oriented, where the hormone receptor is characterized as a potent predictive factor. Antiangiogenesis treatments seem to have several similarities with endocrine therapy, in that both treatments are cytostatic, stroma-targeting, time-dependent and less effective for large tumor burdens. A combination effect with chemotherapy is often observed with both treatments, at least in animal experiments. In a sense, anti-oncogene product therapy follows endocrine therapy in clinical development. Although antiangiogenesis treatments should be developed based on original concepts, the successful experience of endocrine therapy may provide many hints for the development of antiangiogenesis therapy.

Angiogenesis Inhibitors↗
PubMed2000

Significance of macrophage chemoattractant protein-1 in macrophage recruitment, angiogenesis, and survival in human breast cancer.

Tumor cells stimulate the formation of stroma that secretes various mediators pivotal for tumor growth, including growth factors, cytokines, and proteases. However, little is known about the local regulation of these soluble mediators in the human tumor microenvironment. In this study, the local expression of cytokines, chemokines, and angiogenic factors was investigated in primary breast cancer tissue. The concentrations of interleukin (IL)-1, IL-4, IL-6, IL-10, IL-12, tumor necrosis factor (TNF)-alpha, IFN-gamma, IL-8, macrophage chemoattractant protein (MCP)-1, epithelial-neutrophil activating peptide-78, vascular endothelial growth factor, and thymidine phosphorylase (TP) were measured in 151 primary breast cancer extracts by ELISA. Tumor-associated macrophages (TAMs) were also examined by immunohistochemistry with anti-CD68 antibodies. The correlation between soluble mediators and the relationship between TAM count and soluble mediators were evaluated. MCP-1 concentration was correlated significantly with the level of vascular endothelial growth factor, TP, TNF-alpha, and IL-8, which are potent angiogenic factors. IL-4 concentration was correlated significantly with IL-8 and IL-10. On the other hand, an inverse association was observed between TP and IL-12. The level of MCP-1 was associated significantly with TAM accumulation. In the immunohistochemical analysis, MCP-1 expression was observed in both infiltrating macrophages and tumor cells. Prognostic analysis revealed that high expression of MCP-1, as well as of VEGF, was a significant indicator of early relapse. These findings indicate that interaction between the immune network system and angiogenesis is important for progression of human breast cancer, and that MCP-1 may play an important role in the regulation of angiogenesis and the immune system.

Adult↗
PubMed1999

Plasma Nucleosome Levels in Node-Negative Breast Cancer Patients.

BACKGROUND: A nucleosome is a primary repeating unit of organized DNA in chromatin, and cell death may lead to increased levels of circulating nucleosomes inplasma (PNLs) in various circumstances such as inflammation, pulmonary embolism, autoimmune disease and cancer. MATERIALS AND METHODS: We investigated PNLs in 96 patients with stage 0-III breast cancer (node-negative, n =57; node-positive, n=39), and in 111 women without any evidence of disease as healthy controls. PNLs were detected using the Cell Death Detection ELISAplus kit (Boehringer Mannheim, Japan). RESULTS: The PNLs in normal controls were 0.010 +/- 0.012 units (mean +/- SD), while PNLs were significantly higher in both node-negative breast cancer (0.153 +/- 0.242) and node-positive breast cancer patients (0.116 +/- 0.172) (p <0.01). When PNLs were classified as high (>0.10) and low( </=0.10), no correlation was found between high PNLs and clinicopathological factors such as tumor size, menopausal status, estrogen receptor status, histological type and lymphatic or venous spread in node-negative breast cancer. The relapse-free survival of patients with high PNLs tended to be better than those with low PNLs in both node-negative and node-positive breast cancer. CONCLUSION: Increased PNLs were found in breast cancer patients, and PNLs seem promising as a new prognostic factor for both node-negative and node-positive breast cancer.

Journal Article↗
PubMed1999

[Docetaxel as a single agent in cases of advanced/recurrent breast cancer previously treated with anthracycline].

Docetaxel 60 mg/m2 was administered via 1-hour intravenous infusion every 3-4 weeks to 20 patients with advanced/recurrent breast cancer who had previously received anthracycline therapy. The overall response rate was 30.0% (6/20), with 1 complete remission and 5 partial remissions. The median response duration was 120 days. Response rates classified by recurrence site were soft tissues 43.0%, liver 33.3%, lung 33.3%, and bone 23.1%, respectively. Stable disease (prolonged NC) which continued more than 6 months was observed in patients with bone metastasis. Grade 3-4 leukocytopenia and neutropenia were observed in 45.0% and 55.0%, respectively. Grade 3-4 leukocytopenia and neutropenia were frequently seen in patients who had received anthracycline of more than 500 mg/body as first-line chemotherapy. Docetaxel thus seems to be effective in patients with advanced/recurrent breast cancer who are refractory to anthracycline therapy.

Adult↗
PubMed1997

A Combination Therapy with Mitomycin C, Etoposide, Doxifluridine and Medroxyprogesterone Acetate as Second Line Therapy for Advanced Breast Cancer Refractory to Combination Chemotherapy of Cyclo-phoshamide, Doxorubicin and 5-Fluorouracil.

Thirty-two patients with advanced breast cancer refractory to combination chemotherapy with cyclophosphamide (CPA), doxorubicin (ADR) and 5-fluorouracil (5-EU) (CAF) were treated with the combination of mitomycin C, etoposide, doxifluridine and medroxyprogesterone acetate as second line therapy. Observed responses included 6 patients (18.7%) with complete response (CR) and 7 (21.9%) with partial response (PR). Two (50%) out of 4 patients who had bone pain due to bone metastasis noted pain relief. CR or PR were obtained in 4 out of 12 patients who had not responded to the previous CAF therapy. While grade III myelosuppression was observed in 3 patients, other adverse effects were minimal. It is suggested that this combination therapy may be recommended for advanced breast cancer patients as a second therapy.

Journal Article↗
PubMed1996

Multicentric Breast Carcinoma: Evaluation of Clinicopathological and Immunohistochemical Characteristics.

Multicentric breast carcinomas not diagnosed clinically, were examined by serial step-cut sectioning of the whole breast, and multicentric carcinoma cases were compared with single carcinoma cases with regard to histological and clinicopathological findings. In 7(3.7%) out of 187 surgically resected breasts, latent carcinomas apart from the main carcinoma were noted. The size of the latent carcinoma varied from 0.2 to 5 cm in diameter. The histological type was noninvasive ductal carcinoma in six cases and invasive ductal carcinoma in one case. When the main carcinoma was small in size (less than 2.5 cm in diameter), and showed papillotubular carcinoma as the histological type or had estrogen receptor (ER) by the dextran-coated charcoal (DCC) method, the incidence of latent carcinoma was high. In 5 of 6 cases with latent carcinoma examined by immunohistochemistry, latent carcinomas showed expression of ER. Concerning Ki-67, proliferating cell nuclear antigen (PCNA) and p53 protein, there was no significant difference between the main and latent carcinomas, as well as with other clinicopathological factors.

Journal Article↗
PubMed1996

Telomerase activity in human breast tumors.

BACKGROUND: The activity of the ribonucleoprotein enzyme telomerase is not detected in normal somatic cells; thus, with each cell division, the ends of chromosomes consisting of the telomeric repeats TTAGGG progressively erode. The current model gaining support is that telomerase activity in germline and immortal cells maintains telomere length and thus compensates for the "end-replication problem." PURPOSE: Our objective was to determine when telomerase activity is reactivated in the progression to malignant breast cancer and if knowledge of telomerase activity may be an indicator for the diagnosis and potential treatment of breast cancer. METHODS: Using a polymerase chain reaction-based telomerase activity assay, we examined telomerase activity in 140 breast cancer specimens (from 140 patients), four phyllodes tumors (from four patients), 38 noncancerous lesions (20 fibroadenomas, 17 fibrocystic diseases, one gynecomastia; from 38 patients), and 55 adjacent noncancerous mammary tissues (from 55 of the 140 breast cancer patients). In addition, 33 fine-needle-aspirated breast samples (from 33 patients) were analyzed. RESULTS: Among surgically resected samples, telomerase activity was detected in 130 (93%) of 140 breast cancers. Telomerase activity was detected in 68% of stage I primary breast cancers, in 73% of cancers smaller than 20 mm, and in 81% of axillary lymph node-negative cancers. Moreover, the activity was detected in more than 95% of advanced stage tumors but in only two (4%) of 55 adjacent noncancerous tissues. While telomerase activity was not detected in any of 17 specimens of fibrocystic disease, surprisingly low levels of telomerase activity were detected in nine (45%) of 20 fibroadenomas. Among samples obtained by fine-needle aspiration, 14 (100%) of 14 patients whose fine-needle-aspirated specimen contained telomerase activity and who subsequently underwent surgery were confirmed to have breast cancer. Multivariate analysis of 125 specimens from patients for whom data were available on age at surgery, stage of disease, tumor size, lymph node status tumor histology, and menopausal status indicated that stage classification exhibited the strongest association with telomerase activity (for stage I versus stages II-IV: odds ratio = 1.0 versus 73.4; 95% confidence interval = 2.0-959.0; P = .02). CONCLUSION: Telomerase activity was detected in more than 95% of advanced stage breast cancers. It was absent in 19%-32% of less advanced cancers. Since a determination of any association between telomerase activity and patient survival is not possible at the present time, it remains to be determined whether lack of telomerase activity predicts for favorable outcome.

Adult↗
PubMed1994

Modulation of suppressor cell activities by cyclophosphamide in breast cancer patients.

We investigated the immunomodulatory effect of cyclophosphamide on the induction of suppressor cell activities in peripheral blood lymphocytes. The sera from advanced breast cancer patients as well as concanavalin-A (Con-A) induced suppressor cell activities in lymphocytes from healthy volunteers. Pretreatment of these lymphocytes, including CD4+ T cells with 4-hydroperoxycyclophosphamide (4-HC), an active form of cyclophosphamide, abrogated the induction of suppressor cell activities by either cancer sera or Con-A. A decrease in CD4+CD45RA+ suppressor/inducer T cells and reduction of Con-A induced suppressor cell activities were observed in breast cancer patients with metastases that were treated with cyclophosphamide (CPM). These results suggest that cyclophosphamide may modulate the immune responses of breast cancer patients by interference with suppressor/inducer T cells.

Breast Neoplasms↗
PubMed1993

Primary squamous cell carcinoma of the breast after cured Hodgkin's disease.

An unusual case of primary squamous cell carcinoma of the breast occurring after cured Hodgkin's disease is reported herein. A 27-year-old woman developed a left breast mass 2 years after chemotherapy and radiation for nodular sclerosing stage IIB Hodgkin's disease. Excisional biopsy revealed squamous cell carcinoma of the breast and a modified radical mastectomy was performed, however, no metastasis was found in the axillary nodes. She received etoposide, mitomycin-C, and doxifluoridine as adjuvant chemotherapy, and remains well without any evidence of recurrent Hodgkin's disease or breast cancer. To our knowledge, this is the first reported case of primary squamous cell carcinoma of the breast associated with Hodgkin's disease. The risk of patients treated for Hodgkin's disease developing breast cancer as a second malignant neoplasm is discussed following the report of this case.

Adult↗
PubMed1993

Loss of VLA-2 collagen receptor in breast carcinoma, facilitating invasion and metastasis.

The integrin VLA-2 as a collagen receptor and VLA-5 as a fibronectin receptor were detected immunohistochemically in normal, benign tumor and carcinoma tissues of the breast. Both proteins were also detected by Western-blot analysis in some carcinoma cases. Epithelial and myoepithelial cells of both normal breast and benign tumor were in all cases immunoreactive for VLA-2 in the plasma membrane. Carcinoma cells in the invasive component were not immunoreactive for VLA-2 in 31 (46%) of 67 cases. Carcinoma cells in the intraductal components were negative for VLA-2 in only 4 (11%) of 36 cases, while 20 cases (56%) showed weak expression and 12 cases (33%) showed strong expression. Metastatic carcinoma cells in the lymph nodes of 6 cases showed no immunoreactivity except in one case, whereas, again with the exception of one case, the carcinoma cells in the primary tumors did show VLA-2 expression. With regard to VLA-5, there was no difference in its expression in the invasive components and the intraductal components. These findings suggest that the loss of VLA-2 plays a role in the invasion and metastasis of breast carcinoma.

Adult↗