Preventive drug therapy and contralateral breast cancer: summary of the evidence of clinical trials and observational studies

Abstract

Background: Breast cancer patients have a lifelong 2-4-fold increased risk of developing a second primary tumor in the contralateral breast compared with the risk for a first primary breast cancer in the general female population. Prevention of contralateral breast cancer (CBC) has received increased attention during recent decades. Here, we summarize and discuss the available literature on drug preventive therapy and CBC. Results: The endocrine-targetting drugs, tamoxifen and aromatase inhibitors are used as standard adjuvant treatment for estrogen receptor (ER)-positive breast cancer. Both are associated with relative risk reductions of CBC of up to 50%, but incur serious side effects. Several prescription drugs originally developed for other purposes, including bisphosphonates, statins, non-steroidal anti-inflammatory drugs, metformin, anti-hypertensives and retinoids, have shown anti-cancer activity in preclinical models. However, results of observational studies on CBC are sparse and inconsistent, with only statins demonstrating promise as preventive agents and a potential treatment option for ER-negative breast cancer patients. Conclusion: Future studies are needed to assess the effect of statins in risk reduction and to identify other drugs with chemopreventive potential against CBC. Eventually, efforts must be directed towards identifying those breast cancer patients likely to benefit most from specific preventive therapies.

Obesity and endocrine therapy resistance in breast cancer: Mechanistic insights and perspectives

“…It is important to highlight that endocrine agents are also used in the breast cancer prevention setting. High quality evidence from observational studies and clinical trials has shown a reduced rate of breast cancer development in women at high‐risk by 40%–53% and a continued significant effect in the posttreatment follow‐up period 87–94 . However, utilization of preventive therapy remains poor mainly due to lack of physician and patient awareness, concerns about side effects (i.e., nausea, vomiting, hot flushes, musculoskeletal discomfort, fatigue and headaches for AIs, or vaginal bleeding, endometrial cancer and thromboembolism for tamoxifen) as well as other issues related to the need to improve our risk prediction models and develop surrogate biomarkers of response.…”

“…High quality evidence from observational studies and clinical trials has shown a reduced rate of breast cancer development in women at high‐risk by 40%–53% and a continued significant effect in the posttreatment follow‐up period. 87 , 88 , 89 , 90 , 91 , 92 , 93 , 94 However, utilization of preventive therapy remains poor mainly due to lack of physician and patient awareness, concerns about side effects (i.e., nausea, vomiting, hot flushes, musculoskeletal discomfort, fatigue and headaches for AIs, or vaginal bleeding, endometrial cancer and thromboembolism for tamoxifen) as well as other issues related to the need to improve our risk prediction models and develop surrogate biomarkers of response. For instance, evaluation of anthropometric parameters to identify women at high‐risk with greater accuracy and/or to predict sensitivity to breast cancer prevention are awaited with interest.…”

Clonal Evolution Characteristics and Reduced Dimension Prognostic Model for Non-Metastatic Metachronous Bilateral Breast Cancer

“…Owing to the increasing morbidity of BC, prolongation of survival time and improvement of detection rate, a growing number of patients with BC are diagnosed as contralateral disease (2,3). Recently, majority of studies focused on risk factors for the formation of contralateral breast cancer (CBC) in patients with primary breast cancer (PBC) (4,(35)(36)(37)(38)(39)(40)(41)(42), and expected to prevent the occurrence of CBC via bilateral mastectomy (5,6). While for clinical practice, it is not yet clear whether patients would benefit from bilateral mastectomy in terms of mortality (5).…”