Breast cancer clinical studies

Tuck, A.B. and Chambers, A.F. 2001. The role of osteopontin in breast cancer Clinical and experimental studies. J. Mammary Gland Biol. Neoplasia 6, 419-429. 

Toremifene (Fareston , chlorotamoxifen Figure 5.15) has been thoroughly investigated in the laboratory [269-272] and has antitumor activity in carcinogen-induced rat mammary cancer, but is less potent than tamoxifen [272-274]. Toremifene has been tested extensively in phase I—III clinical trials [275-278] and has been approved for use in postmenopausal women with metastatic breast cancer [279]. As predicted from the reduced potency in animal studies, the dose required for activity is 60 mg of toremifene daily (tamoxifen is used at 20 mg daily). The side-effects are similar to those of tamoxifen and, as with tamoxifen, the responses are observed in ER-positive tumors. However, because adjuvant therapy with tamoxifen is standard throughout the world, issues of cross-resistance of tamoxifen and toremifene are important considerations for the use of toremifene in recurrent breast cancer. Laboratory studies by Osborne et al. [280] have demonstrated that toremifene-stimulated tumors can develop from MCF-7 breast cancer cells transplanted into athymic mice. Toremifene is cross-resistant with tamoxifen in tamoxifen-stimulated breast cancer in the laboratory [281]. Similarly, cross-over clinical trials demonstrate that there is little possibility of a second response to toremifene after tamoxifen failure [282, 283]. 

Rivera, E., Booser, D., Kuritani, J. and Tsuda, M. (2004) A phase I and pharmacokinetic study of TAS-108 in postmenopausal female patients with locally advanced, locally recurrent inoperable, or progressive metastatic breast cancer. Clinical Cancer Research, 10, 5425-5431. 

Clinical correlation studies between CA 27.29 levels and CA 15-3 levels typically yield correlation coefficients of >0.95. It has been suggested that the epitope mapping studies reflect that the CA 27.29 antigen is essentially the same breast cancer-associated mucinous antigen detected by the two methods. 

In phase I clinical trials 47 patients, all of whom had previously failed standard treatments for solid tumors, received the drug in the UK, Italy, and Switzerland on three different schedules.123,124 Dose-limiting toxicities have been defined as bone marrow depression and diarrhea. The latter is treatable with loperamide. Signs of biological activity were seen. Notably one patient with metastatic pancreatic cancer showed a partial response (for 4 months) and two further patients, one with metastatic melanoma and one with bronchoalveolar carcinoma, also showed partial responses. In a phase I trial in combination with 5-FU, a partial response in breast cancer was observed.125 Furthermore, a reduction in tumor marker levels was observed in two patients, one with ovarian cancer, and one with colon cancer. Phase II studies have shown partial responses in cisplatin-resistant ovarian and nonsmall-cell lung cancer.126,127 The indications are that the profile of clinical activity is different and complementary to the mononuclear platinum agents. 

Mies55 Breast cancer RNAzol (Biotecx, Huston, TX) ER gene (exons 1 and 2) 150 bp amplicon is feasible for clinical and research studies. 

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