Women in families with multiple cases of female breast +/- ovarian cancer are at increased risk of developing breast cancer. In the absence of a known germline mutation in a breast cancer predisposition gene, the exact levels of risk are difficult to determine. Risk models such as BRCAPRO and BOADICEA can calculate individual cancer risks and empirical data from cohort studies can contribute to an estimation of an individual's risk.
Bilateral risk reducing mastectomy reduces absolute breast cancer risk to <2%.
RRBSO for breast cancer risk
Premenopausal RRBSO has been reported to approximately halve breast cancer risk in BRCA mutation carriers although prospective data are still awaited and the impact in other high risk women has not been described. There are competing health risks from surgical menopause particularly before age 45 in women who do not use hormone supplementation. Risk reducing medication is an alternative means of breast cancer risk reduction (see below).
Annual screening for women age 50-69 with a family history of breast cancer detects cancers at an earlier stage than women with a family history having two yearly screening. For women with at least two close relatives with breast cancer where one relative is diagnosed under age 50, the most cost-effective time interval is predicted to be annual screening.
Annual mammography in an observational study of women aged 40-49 with a family history of risk of breast cancer (3% absolute risk during this time period) detected breast cancers at lower stages (smaller, fewer positive lymph nodes and lower grade) than in women who are not involved in a screening programme and 80% of cancers were screen detected. Projected mortality reduction was 20% at 10 years.
For women at increased risk of breast cancer the addition of ultrasound to mammography slightly improves detection of breast cancer but increases the number of false positives so is not recommended.
MRI is more sensitive (62-88%) but less specific (75-99%) than mammography, therefore increases recalls (8-17%) and biopsies (3-15%) compared to mammograms alone. In the prospective EVA trial,r MRI detected all cancers during annual screening; no interval cancer occurred and no cancer was identified during half-yearly ultrasound. Early data suggest cancer detection by MRI alone is not significantly improved by the addition of mammography or ultrasound.r
Further studies on the cost effectiveness of MRI screening in high risk women are needed.
Tamoxifen and raloxifene have been shown to reduce the risk of breast cancer in high risk women. Five years of tamoxifen reduces the risk of ER (oestrogen receptor) positive invasive breast cancer by almost half for high risk women. This equates to a risk reduction of about one third in overall breast cancer risk, with effects lasting for 20 years, although overall mortality benefit is not yet seen.
For post menopausal women, 5 years of raloxifene has lower efficacy that tamoxifen but fewer side effects. Alternatives in postmenopausal women include anastrozole and exemestane which also reduce the risk of invasive ER-positive breast cancer (reducing overall invasive breast cancer risk by half [anastrozole] and two thirds [exemestane] compared to placebo in separate trials). Medications should be discussed with an experienced medical professional to determine the relevant risks and benefits of each in an individual.