Breast cancer early studies

The reversibility of radiation fibrosis in skin and subcutaneous tissues in response to antioxidants is supported by regression of indnration reported in a French non-randomized pilot study involving intramuscnlar administration of bovine liposomal Cu/Zn superoxide dismutase (SOD), 5 mg twice weekly for 3 weeks, to 34 patients with 42 distinct zones of superficial fibrosis. Softening of snbcutaneous induration was noted in 86% of fibrotic zones, with an actuarial response rate of 70% by 5 years. Complete regressions were noted in 7 of 42 (17%) of the fibrotic zones. Supportive data are reported with topical apphcations of SOD over a period of several months in 40 patients with fibrosis after postmastectomy radiotherapy for early breast cancer. These studies were not pursued after bovine spongiform encephalopathy (BSE) was recognized and bovine products withdrawn. 

Dales JP, Garcia S, Meunier-Carpentier S, Andrac-Meyer L, Haddad O, Lavaut MN, Allasia C, Bonnier P, Charpin C. Overexpression of hypoxia-inducible factor HIF-1 alpha predicts early relapse in breast cancer retrospective study in a series of 745 patients. Int J Cancer 2005 116 734-739. 

Hormonal therapies that have been studied in the treatment of primary or early breast cancer include antiestrogens, oophorectomy, ovarian irradiation, luteinizing hormone-releasing hormone (LHRH) agonists, and aromatase inhibitors. 

Hormone therapy has proven highly effective in controlling the menopausal syndrome, especially severe hot flushes (MacLennan et al. 2004), even at doses significantly lower than those used until now (Speroff et al. 2000 Utian et al. 2001). Women s Health Initiative studies found that hormone replacement therapy, when administered as a primary prevention intervention for CVD in older women, increases the risk of heart disease and breast cancer. Even if a protective effect on fracture and colon cancer was observed, the risk-benefit ratio led to a recommendation of this treatment only for the short-term relief of menopausal symptoms (Rossouw et al. 2002 Anderson et al. 2004). The role of early administration of ovarian hormones to young postmenopausal women in the prevention of cardiovascular disease or late dementia remains... 

Given orally at normal therapeutic doses BDZs have little effect on cardiovascular, respiratory or autonomic function. Respiratory depression and reduced systolic blood pressure may occur but this is seen principally with intravenous administration or overdose. Leucopenia and eosinophilia are rare. There was a suggestion in the early 1980s of increased risk of breast cancer but a subsequent large case-control study refuted this. 

Studies from several countries have vindicated early skepticism about the postulated causal role of PCBs and DDE in the development of breast cancer. Dr. Mary Wolff, a coauthor of the two initial studies showing higher levels of PCBs and/or DDE in breast cancer patients, was also involved in several of the later... 

In 147 postmenopausal women with early breast cancer who took exemestane in a placebo-controlled study, exemestane caused modest reductions in high-density lipoprotein cholesterol and apolipoprotein, but had no major effect on lipid profile, homocysteine concentrations, or coagulation (14). 

Aromatase inhibitors increase bone turnover by near complete estrogen depletion, leading to reduced bone mineral density and an increased risk of fractures. Bisphosphonates plus calcium and vitamin D supplementation mitigate this (26). In an open, multicenter, randomized study in 602 women with early-stage breast cancer taking letrozole 2.5 mg/day, zoledronic acid 4 mg every 6 months prevented bone loss (27). 

This study has again confirmed that endometrial problems can be induced by tamoxifen early in the course of treatment and that these problems do not arise with aromatase inhibitors, which may actually reduce the endometrial changes induced by tamoxifen. The idea that the new oral aromatase inhibitors might well replace tamoxifen in breast cancer was tentatively advanced in SEDA-26 (p. 445) and has now been supported by some of the material cited above, as well as by a panel consensus (25). Citing efficacy and safety data on anastrozole, exemestane, and letrozole, the authors concluded that third-generation aromatase inhibitors may be considered first-line therapy of hormone-receptor-positive advanced breast cancer in postmenopausal women and may also be used for preoperative therapy of breast cancer. 

Rutqvist LE, Mattsson AThe Stockholm Breast Cancer Study Group. Cardiac and thromboembolic morbidity among postmenopausal women with early-stage breast cancer in a randomized trial of adjuvant tamoxifen. J Natl Cancer Inst 1993 85(17) 1398 106. 

A 2-year randomized controlled study in 90 women compared the effects of oral tibolone doses of 1.25 mg/day and 2.5 mg/day on bone loss in the early postmenopausal period all took calcium 1000 mg/day. Vertebral and femoral bone density rose in both treated groups but fell in the control group, and bone turnover markers (urinary excretion of hydroxyproline/creatinine and plasma osteocalcin concentrations) were similarly affected favorably in the treated groups, as was the incidence of hot flushes/ flashes (5). Studies such as this still leave open the question of the advisability of continuing tibolone treatment over a longer period. While tibolone has indeed been shown to benefit mineral bone density, few data are available to show whether it lowers fracture incidence nor is it clear whether there is a link between tibolone and breast cancer (6). 

Several reports have described the anticancer activity of curcumin in a variety of cancer cell lines. In vitro studies have established the activity for curcumin against breast, gastric, hepatic, pancreatic, colorectal, urinary bladder, kidney, prostate, cervical, ovarian, uterine, lung, oral, thymic, and skin cancers. Besides these cancer types, curcumin has shown in vitro therapeutic efficacy against hematological cancers including leukemia, lymphoma, and multiple myeloma. One of our early studies established that the antiproliferative effect of curcumin in human breast cancer cell lines, including hormone-dependent, hormone-independent,... 

Battifora, H., Gaffey, M., Esteban, J., Mehta, R, Bailey, A., Faucett, C., and Niland, J. 1991. Immunohistochemical assay of neu/c-erbB-2 oncogene product in paraffin-embedded tissues in early breast cancer Retrospective follow-up study of 245 stage I and II cases. Mod. Pathol. 4 466-414. 

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