Chemoprevention in breast cancer represents one of the most important therapeutic regimens in an effort to optimize survival and prevent breast cancer recurrence. The chapter aims to analyze below all potential medical regimens used in breast cancer chemoprevention, along with explaining the reasons why those are the ones selected: their characteristics, their mechanism of action, and their side effects. Among these, we may report tamoxifen, raloxifen, aromatase inhibitors, and new therapeutic regimens such as polyphenoles.
TopIntroduction
Below will be analyzed all of the medicine used in breast cancer chemoprevention, the reasons why those are the ones selected, their characteristics, their mechanism of action and their side effects.
SERM (Selective Estrogen Receptor Modulator)
Estrogen administration is associated with the reduction in menopausal symptoms as well as the reduction of the risk of various conditions affecting postmenopausal women. Since estrogen administration also increases the risk for breast cancer, a common dilemma faced by many women and their doctors is whether they will use estrogen replacement therapy (ERT), a selective estrogen receptor modulator (SERM) - (which competes with estrogen effects on the breast tissue but maintains some estrogenic functional properties in other organs or none)(Gabriel & Jatoi, 2012).
For women of very high risk (> 1% per year) with menopausal symptoms, alternatives should be offered and tested. Diagnosis of in situ carcinoma or invasive breast cancer within the last 2 to 5 years should be considered a relative contraindication for ERT unless the tumor was estrogen receptor negative (Fabian & Kimler, 2012).
SERMs were evaluated in phase III clinical trials in women with osteoporosis. The test compared 2 doses of lazofixin with placebo and there was a significant reduction in the incidence of breast cancer with a higher dose of lazofixin 0.5 mg but not at a dose of 0.25 mg. Although the highest dose also reduced the risk of coronary artery disease and stroke, there was an inclination towards more death in a lower dose group compared to placebo (65 deaths vs. 90 deaths, P = 0.05), decreasing overall excitement for this factor and the request for regulatory approval was withdrawn (Chlebowski, 2014).
Below are analyzed the most widely used SERMs worldwide:
Tamoxifen
Chemoprevention is based on the use of pharmacological or physical agents to inhibit the development of invasive cancer (Gabriel & Jatoi, 2012). Risk factors for women at least 35 years of age are necessary. Tamoxifen is the oldest and most studied drug in the prevention of breast cancer, which has been studied in many great tests, some of which (as well as their results) are reported as follows: Royal Marsden, NSABP P-1, and of IBIS I, which have been published with subsequent long-term follow-up.
A recent meta-analysis by Cuzick et al. showed an overall risk reduction of 33%. This decrease is mainly due to a large effect on invasive breast cancer, for which the rate of reduction is 44 (p = 0.0001) and a significant decrease in in situ carcinoma (DCIS) (p = 0.009).The effect largely reflects the effect on estrogen-receptor-positive breast cancers with a much lower, non-significant increase in estroge- negative breast cancer. However, according to these studies, women taking tamoxifen had a higher rate of endometrial cancer than patients receiving placebo (OR 2.18, CI 1.39-3.42, p = 0.001) and in addition, thromboembolic events (OR 1.60, CI 1.21-2.12, p = 0.001) (Sismondi et al,. 2015). and moderate cataracts (Reimers et al., 2015).. Regarding the risk for endometrial cancer, it has been shown that the increase in risk is statistically significant for women aged 50 years and above (RR, 4.01 [CI, 1.70 to 10.90]). Women aged less than 50 years who received tamoxifen in several clinical trials have not been at increased risk. All cases of endometrial cancer in the tamoxifen group were stage 1 and no woman died of endometrial cancer. (Victor G, 2002).