Takeshi Takeo

Influence of Drinking Green Tea on Breast Cancer Malignancy among Japanese Patients

Inhibitory effects of green tea on carcinogenesis have been investigated in numerous laboratory studies using (–)‐epigallocatechin gallate (EGCG) or crude green tea extract, and there is also some epidemiologic evidence. Further, EGCG has been reported to inhibit the growth of cancer cells, lung metastasis in an animal model, and urokinase activity. In this study, we first examined the association between consumption of green tea prior to clinical cancer onset and various clinical parameters assessed at surgery among 472 patients with stage I, II, and III breast cancer. We found that increased consumption of green tea was closely associated with decreased numbers of axillary lymph node metastases among premenopausal patients with stage I and II breast cancer and with increased expression of progesterone receptor (PgR) and estrogen receptor (ER) among postmenopausal ones. Since these are potential prognostic factors, we then investigated the prognosis of breast cancer with special reference to consumption of green tea, in a follow‐up study of these patients. We found that increased consumption of green tea was correlated with decreased recurrence of stage I and II breast cancer (P<0.05 for crude disease‐free survival); the recurrence rate was 16.7 or 24.3% among those consuming ≥5 cups or ≥4 cups per day, respectively, in a seven‐year follow‐up of stage I and II breast cancer, and the relative risk of recurrence was 0.564 (95% confidence interval, 0.350–0.911) after adjustment for other lifestyle factors. However, no improvement in prognosis was observed in stage III breast cancer. Our results indicate that increased consumption of green tea prior to clinical cancer onset is significantly associated with improved prognosis of stage I and II breast cancer, and this association may be related to a modifying effect of green tea on the clinical characteristics of the cancer.

Effect of toremifene on the growth, hormone receptors and insulin-like growth factor-1 of hormone-dependent MCF-7 tumors in athymic mice

Toremifene given in different sizes of silastic capsules was used to treat MCF-7 tumors in athmic mice. Toremifene inhibited the estradiol-stimulated growth of MCF-7 tumors in athymic mice. Average serum concentrations of toremifene obtained using a sustained-release preparation of the drug (in 0.5-, 1.0-, and 2.0-cm silastic capsules) increased gradually in a capsule-size-dependent fashion. Much higher levels of toremifene orN-demethyltoremifene were detected in tumors(target tissues of estrogen) as compared with muscles (non-target tissues of estrogen). The concentration of toremifene in serum (i.e., 10–30 ng ml−1) was sufficient to inhibit the estrogen-stimulated growth of MCF-7 tumors at physiological (i.e., 200–400 pg ml−1) serum estradiol concentrations in premenopausal women. No significant difference in estrogen receptor (ER) levels was found between the estradiol-alone group and the toremifene-treated groups. However, the ER levels in the toremifene-alone group and the no-treatment group (no toremifene or estradiol) tended to increase as compared with the estradiol-alone group. Toremifene blocked the estradiol-induced increase in progesterone receptor levels in a dose-dependent fashion. Insulin-like growth factor-1 (IGF-1) levels in the MCF-7 tumors significantly decreased in the toremifene-alone group as compared with the estradiol-alone group. These results show the antiestrogenic action of toremifene on hormone-dependent MCF-7 tumors in athymic mice.

Effects of OK-432 (Picibanil) on the Estrogen Receptors of MCF-7 Cells and Potentiation of Antiproliferative Effects of Tamoxifen in Combination with OK-432

OK-432 (picibanil), a streptococcal preparation, has a strong biological response modifier (BRM) function and is expected to produce clinical improvement and prolongation of survival in treated cancer patients in Japan. We were interested in whether OK-432 augments estrogen receptor (ER) levels in breast cancer. To investigate the effect of the BRMs on cellular growth and the characteristics of ER and progesterone receptors (PgR) in the human breast cancer cell line MCF-7, we used OK-432, Krestin (PSK), a protein-bound polysaccharide extracted from Coriolus versicolor, and lentinan, a fungal branched (1...3)-beta-D-glycan. OK432 and PSK dose dependently inhibited DNA synthesis of MCF-7 cells, and the 50% inhibitory concentrations of OK-432 and PSK were 1.2 KE (klinische Einheit, clinical unit)/ml and 200 micrograms/ml, respectively. Lentinan showed no direct anticancer effect in vitro. We found that OK-432 induced a 2-fold increase in ER levels in MCF-7 cells at 0.005 KE/ml, but not in PgR. Lentinan and low-dose PSK did not change ER or PgR levels, but high-dose PSK decreased ER and PgR. We also studied the combined effect of OK-432 and antiestrogens, tamoxifen (TAM) and DP-TAT-59. The combined treatment with OK-432 and TAM showed an additive inhibitory effect on MCF-7 cells. These results suggest that OK-432 may augment the therapeutic effect of TAM in breast cancer.

Fibromatosis of the Breast: A Case Report.

Fibromatosis develops in many anatomic sites, but it rarely arises as a primary lesion in the breast. This lesion is locally invasive and frequently recurs after a local excision, but it has no potential for distant metastasis. In this report, we present a case of mammary fibromatosis which was closely similar to carcinoma in clinical, mammographic and ultrasonographic findings, thus leading us to breast conserving surgery. Despite being a rare disease, fibromatosis should be included in the differential diagnosis of younger patients (the age of the present case was 51, and the mean ages of patients with fibromatosis ranges from37 to 49) with abnormal changes on physical examinations and imaging studies.

Intersite Variation of Estrogen Receptors in Human Breast Cancers and Response to Endocrine Therapy

Estrogen receptor (ER) assays were performed by sucrose gradient centrifugation method at multiple sites in large breast cancers. Intersite variation of ER in a tumor was observed in 24 out of 35 cases. 16 tumors with relatively low ER levels showed different ER status with multiple assays. The results suggest that an assay performed on a small random part of a large tumor may not yield the true ER status. ER value at the largest cross-section was almost the same as the average ER values in each tumor. In addition, 21 cases were examined in relation to ER values at multiple sites in the large tumors and response to endocrine therapy. As the ER value at the largest cross-section was highly correlated with the therapeutic response to endocrine therapy of breast cancer, it would represent true ER status and level. The results suggest that the ER assay at the largest cross-section of a large tumor is an appropriate method to predict response to endocrine therapy.