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 pathogenic variant in a breast cancer predisposition gene, the exact levels of risk are difficult to determine. Risk models such as iPrevent, IBIS and BOADICEA can calculate individual cancer risks.
Additional high risk genes have been identified, such as PALB2 and a specific ATM pathogenic variant (7271T>G). Pathogenic variants in these genes are rare in high risk breast cancer families, however detection of a heritable pathogenic variant would allow predictive testing to guide care of relatives. Moderate risk breast cancer genes (e.g. CHEK2) have been identified, but their presence alone may not explain strong family histories of breast cancer. Predictive testing for these genes at present does not allow targeted breast cancer screening in high risk families.
Breast cancer risks can be low under age 40, even with family history, for women who do NOT carry a BRCA1 or BRCA2 pathogenic variant. Potential harms of screening may outweigh benefits at this age, and an individual discussion is advised, based on the woman’s 10-year breast cancer risk assessment.
Bilateral risk reducing mastectomy reduces absolute breast cancer risk to <2%.
Mammography has been shown to reduce mortality for women at population risk of developing breast cancer. 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 program and 80% of cancers were screen detected. Projected mortality reduction was 20% at 10 years.
Screening with use of MRI in addition to mammography improved detection of breast cancer for women with a high risk of breast cancer based on their family history. Sensitivity with mammography alone was 55% increasing to 98% with the addition of MRI. False positive findings increased with decreased specificity with use of MRI.r
MRISC, a prospective cohort screening trial with annual mammography and breast MRI for women 25-70 years was compared to controls following the national screening recommendations.r A benefit for more intensive screening was found for those with familial risk of breast cancer, as cancers detected were earlier stage, required less adjuvant therapy and lower rate of metastatic disease.
The sensitivity of mammography has been reported to be lower (50%) for women with high breast density, and limited evidence supports adding breast MRI, breast ultrasound or tomosynthesis to increase sensitivity. Screening plans should be individualised for high risk women.
A systematic review of mammography with digital breast tomosynthesis use for breast cancer screening found lower false positive rates, recall rates and increased cancer detection when compared to standard 2D mammography, adding support for its use in screening.rr
Tamoxifen and raloxifene have been shown to reduce the risk of breast cancer in high risk women. Five years of tamoxifen (20mg daily) 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. Tamoxifen 5mg daily (or 10mg on alternate days, given lack of availability of 5mg tablet) for 3 years may be a reasonable alternative to 20mg daily for women who do not tolerate the higher dose.r
For postmenopausal women, 5 years of raloxifene has lower efficacy than tamoxifen but fewer side effects. Alternatives in postmenopausal women include anastrozole and exemestane which also reduce the risk of invasive ER-positive breast cancer (reduced 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 balance of relevant risks and benefits of each in an individual. The iPrevent breast cancer risk management tool may be useful for collaborative decision making.