A recent review paper published in Mayo Clinic Proceedings explores the identification and management of patients at high risk for developing breast cancer (BC). Risk-assessment tools that are available for BC include the Breast Cancer Risk Assessment Tool (BCRAT or Gail Model) and the International Breast Cancer Intervention Study (IBIS) Breast Cancer Risk Evaluation Tool. Although there is no standardized method to assess risk, these tools can be used in shared decision making to determine how to proceed in women who are deemed to be at high risk for disease occurrence. These tools are included in BC guidelines disseminated by the American Society of Clinical Oncology, the National Comprehensive Cancer Network, and the  US Preventative Services Task Force (USPSTF).

Interventions that can be used in women at elevated BC risk include genetic testing, breast imaging surveillance, preventative endocrine therapy (ET), and lifestyle education/modifications.

Even when BC risk-assessment tools are used, there is no consensus on when ET should be initiated. Whereas some clinicians consider a BCRAT 5-year risk of >1.7% as high-risk, signaling the initiation of ET, the USPSTF guidelines consider >3% as “substantial risk” and the point at which ET should be started in women in whom the benefits of ET therapy outweigh the risks. For the IBIS, a 10-year risk estimate of >5% is the signal to consider ET, according to the USPSTF guidelines.

In women aged >35 years who do not have a personal history of ductal carcinoma in situ or invasive BC, high risk is defined by a combination of risk factors including those in the BC risk-assessment models or BC risk-reduction trials, as well as a “strong” family history, which is defined in the article.

A limitation of the BC risk-assessment tools is that atypical ductal hyperplasia confers a risk of BC of 1% to 2% per year (or 25%-30% over 25 years), but it is not accurately evaluated by these risk calculators. Additionally, lobular carcinoma in situ (LCIS) confers a 2% risk per year (20% lifetime risk) of developing BC, and women with LCIS should also be offered ET. Other significant risk factors for which women should consider ET therapy include possessing a known genetic variant such as BRCA 1/2 and having undergone mantle (chest) irradiation between the ages of 10 and 30 years.

Among women aged 40 to 44 years with an estimated relative risk (RR) of at least fourfold the population for their age or those aged 45 to 69 years with an estimated RR of at least twofold the population for their age, risk-reduction counseling should be provided, as these patients are deemed to be at “high risk” for disease occurrence. Put another way, women in the aforementioned groups have a calculated 5-year risk of >3%, a 10-year risk of >5%, and a lifetime risk of >20%. Other factors that increase risk include obesity, older age, early menarche (<10 year), nulliparous or late age of first parity (>30 years), prolonged, combined menopausal hormone therapy (>3 years of use after the expected age for menopause), and increased breast density; these women are eligible for consideration of ET.

Use of ET should be considered in women aged 35 to 70 years who are at high risk for disease, but it may be used earlier, as mentioned previously.

Among the agents that have been used as risk-reducing treatment options are tamoxifen 10 mg every other day for 3 years or tamoxifen 20 mg daily, raloxifene 60 mg daily, exemestane 25 mg daily, or anastrazole 1 mg daily for 5 years. Tamoxifen is approved for BC reduction in premenopausal or postmenopausal women aged >35 years with a BC risk-assessment tool 5-year risk of 1.7%. At a dosagse of 20 mg/day for 5 years, tamoxifen can reduce the risk of invasive estrogen receptor-positive BC by 50% in high-risk women. However, a survival benefit has not been seen with tamoxifen. Raloxifene, exemestane, and anastrazole are indicated only in postmenopausal women at increased BC risk. Adverse effects associated with these medications include hot flashes, vaginal dryness, joint pain, and osteoporosis risk (except for tamoxifen, which does not adversely affect bone).

Pharmacists should take an active role in educating and counseling women at high risk for BC on lifestyle modifications, such as weight loss, and on the benefits and management of adverse events associated with ET therapy.

The content contained in this article is for informational purposes only. The content is not intended to be a substitute for professional advice. Reliance on any information provided in this article is solely at your own risk.

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