Clin Cancer Res
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Hormonal manipulation has been used for over 100 years to treat breast cancer. Ovarian ablation/suppression and tamoxifen are currently accepted adjuvant endocrine therapies for premenopausal breast cancer. Methods of permanently ablating ovarian function include surgical oophorectomy and radiation-induced ovarian failure; medical castration with luteinizing hormone-releasing hormone analogues is a reversible approach. ⋯ Thus, ovarian ablation/suppression combined with tamoxifen is a reasonable alternative to chemotherapy for some women with good-risk early-stage breast cancer (high hormone receptor expression, low-grade or lymph node-negative disease), particularly those wishing to preserve fertility. The value of combining ovarian ablation/suppression with chemotherapy, other endocrine therapy, or both and ameliorating the long-term morbidity of estrogen deprivation remain important areas for investigation. With the advent of multiple targeted endocrine therapies with distinct mechanisms of action, there is a unique opportunity to design highly informative clinical trials that can define the optimal combinations and sequencing of hormonal therapies in the treatment of early-stage breast cancer.
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Review Comparative Study
National surgical adjuvant breast and bowel project update: prevention trials and endocrine therapy of ductal carcinoma in situ.
Following up on the results of recent completed trials, several major breast cancer prevention trials are either underway or impending. In the Study of Tamoxifen and Raloxifene trial, eligible women are at least 35 years of age and postmenopausal, with either lobular carcinoma in situ or a 5-year risk of invasive breast cancer of at least 1.67%. The study will compare the ability of 5 years of tamoxifen or raloxifene to reduce the incidence of breast cancer. ⋯ The proposed NSABP B-35 trial will have the same design as NSABP B-24 but will compare tamoxifen with anastrozole in postmenopausal women. Outcomes will include both ipsilateral and contralateral new breast cancer and recurrences, as well as the occurrence of regional and distant disease. Enrollment will begin in early 2003.
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The purpose of our investigation was to evaluate the response and minimal residual disease by quantitative competitive PCR (QC-PCR) studies in patients with chronic myeloid leukemia (CML) treated with imatinib mesylate. ⋯ QC-PCR studies provide a useful tool to monitor patients with CML on imatinib mesylate therapy.
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Our laboratory has shown that the efficacy of bladder cancer intravesical therapy is in part limited by the poor penetration of drugs into the urothelium. We further found that paclitaxel, because of its lipophilicity, shows a higher penetration than other commonly used drugs such as mitomycin C and doxorubicin. However, the commercial formulation of paclitaxel (i.e., Taxol) contains Cremophor, which forms micelles that entrap the drug and reduce its free fraction. ⋯ DMSO also increased the average size of Cremophor micelles from 13 nm to 230 nm at 50% DMSO. A comparison of the tissue penetration data in the presence of Cremophor and/or DMSO indicates the following effects of DMSO: (a). increase in urine production rate and, consequently, a 36% reduction of the final urine concentration; (b). 2-fold increase in paclitaxel penetration across bladder urothelium; (c). increase in drug removal from bladder tissues (30% more rapidly); and (d). a 60% increase of the amount of drug in bladder tissue. These results indicate that DMSO caused rearrangement of Cremophor micelles, reversed the entrapment of paclitaxel in Cremophor micelles and thereby increased the free fraction of paclitaxel in solution, enhanced the urine production rate and enhanced drug removal by the perfusing capillaries, with an overall effect of increasing the bladder tissue delivery of paclitaxel formulated in Cremophor.
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Several studies to date have reported ovarian cancer risk due to inherited BRCA1 and BRCA2 mutations using familial data or population-based series of probands. Familial aggregation associated with both of these methods may result in a substantial ascertainment bias. To address this, we have used a case-control design that does not involve familial aggregation to estimate the lifetime penetrance of ovarian cancer due to BRCA1 and BRCA2 mutations. ⋯ The lifetime penetrances of BRCA1 mutations are lower than estimates obtained using familial data with multiple affected members but larger than estimates from some population-based proband series. The lifetime penetrance estimate of a BRCA2 mutation is in the range reported by some of the studies based on familial data. These results could have implications for clinical counseling, surgical interventions, and screening recommendations in women carrying these founder mutations.