Use of Medications to Reduce Risk for Primary Breast Cancer: A Systematic Review for the U.S. Preventive Services Task Force

Abstract

Background: Medications to reduce risk for primary breast cancer are recommended for women at increased risk; however, use is low. Purpose:To update evidence about the effectiveness and adverse effects of medications to reduce breast cancer risk, patient use of such medications, and methods for identifying women at increased risk for breast cancer.Data Sources: MEDLINE and Cochrane databases (through 5 December 2012), Scopus, Web of Science, clinical trial registries, and reference lists.Study Selection: English-language randomized trials of medication effectiveness and adverse effects, observational studies of adverse effects and patient use, and diagnostic accuracy studies of risk assessment. Data Extraction:Investigators independently extracted data on participants, study design, analysis, follow-up, and results, and a second investigator confirmed key data. Investigators independently dual-rated study quality and applicability using established criteria.Data Synthesis: Seven good-and fair-quality trials indicated that tamoxifen and raloxifene reduced incidence of invasive breast cancer by 7 to 9 cases in 1000 women over 5 years compared with placebo. New results from STAR (Study of Tamoxifen and Raloxifene) showed that tamoxifen reduced breast cancer incidence more than raloxifene by 5 cases in 1000 women. Neither reduced breast cancer-specific or all-cause mortality rates. Both reduced the incidence of fractures, but tamoxifen increased the incidence of thromboembolic events more than raloxifene by 4 cases in 1000 women. Tamoxifen increased the incidence of endometrial cancer and cataracts compared with placebo and raloxifene. Trials provided limited and heterogeneous data on medication adherence and persistence. Many women do not take tamoxifen because of associated harms. Thirteen risk-stratification models were modest predictors of breast cancer.Limitation: Data on mortality and adherence measures and for women who are nonwhite, are premenopausal, or have comorbid conditions were lacking. Conclusion:Medications reduced the incidence of invasive breast cancer and fractures and increased the incidence of thromboembolic events. Tamoxifen was more effective than raloxifene but also increased the incidence of endometrial cancer and cataracts. Use is limited by adverse effects and inaccurate methods to identify candidates. Primary Funding Source: Agency for Healthcare Research and Quality.Ann Intern Med. 2013;158:604-614. www.annals.org For author affiliations, see end of text. In 2002, the U.S. Preventive Services Task Force (USPSTF) recommended that clinicians discuss the potential benefits and harms of tamoxifen and raloxifene for reducing risk for primary breast cancer with women at high risk for breast cancer and low risk for adverse effects (1, 2). The USPSTF also recommended against routine use in women at low or average risk for breast cancer.Clinical trials demonstrate the efficacy of several medications to reduce the risk for invasive breast cancer in women without preexisting cancer (3-8), but onl...

Pomegranate exerts chemoprevention of experimentally induced mammary tumorigenesis by suppression of cell proliferation and induction of apoptosis

“…Nevertheless, the use of the aforementioned medications is limited due to concern about adverse effects, including endometrial cancer, cataract and thromboembolic events, and poor ability to identify women at high risk (12,13). In view of these limitations, discovery and development of newer breast cancer chemopreventive drugs with acceptable efficacy and toxicity is urgently needed (14).…”

Krūties vėžys Lietuvoje

“…Ypač daug apie KV chemoprevenciją kalbama JAV (19)(20)(21) Cochrane collaboration 2009 m. paskelbtais duome nimis, mamografinė patikra sumažino mirš-ta mumą nuo krūties vėžio 15 %, bet padidino nerimą ir nebūtinų chirurginių ekscizijų skaičių. Tačiau dauguma tarptautinių organizacijų rekomenduoja profilaktiškai atlikti mamografiją kas 2 metus 50-74 m. moterims (28).…”

Primary chemoprevention of breast cancer: Are the adverse effects too burdensome?

“…Hot flashes and depression were scored as grade 3 or 4 events (severe enough to limit a person's ability to care for themselves) in more than 7% and 3% of women, respectively. In a pooled analysis, 9 both tamoxifen and raloxifene were found to increase the risk of venous thromboembolism (relative risk 1.93 and 1.60, respectively). In addition, tamoxifen was associated with an increased rate of endometrial cancer (relative risk 2.13).…”

“…In addition, tamoxifen was associated with an increased rate of endometrial cancer (relative risk 2.13). 9 All chemoprevention drugs appear to increase the risk of unpleasant vasomotor effects. In a recent placebo-controlled RCT of exemestane, the drug was associated with worse vasomotor symptoms, bodily pain and sexual domain scores.…”