Breast Cancer Screening in Women with Hereditary or Familial Risk

Abstract

We estimated influence of tumor size and number of positive lymph nodes at breast cancer detection on survival in the current era of new system (neo) adjuvant therapies. We showed that early breast cancer detection remains of great influence. Relative 5-year survival was 96%.

Early breast cancer detection is accomplished by screening. For women with BRCA1/2 mutation or familial risk breast cancer screening is a widely used and generally accepted effective secondary preventive measure. However, what the most optimal screening strategy is; method and frequency of screening, and appropriate age group, is under discussion. Furthermore, whether earlier breast cancer detection by screening translates in actual survival benefit in these women is until now unknown for this specific group.

The Dutch multicenter MRI Screening Study (MRISC), that ran from 1999-2007, screened women with a familial risk or BRCA1/2 mutation with annual mammography and MRI. With 10 years of follow-up we have shown that early detection by mammography and MRI screening improves breast cancer specific distant metastasis free survival significantly. However, for women with familial MRI screening was not cost-effective because of the lower breast cancer incidence rate in these women.

MRI screening is cost-effective for BRCA1/2 mutation carriers and is advised by most guidelines from 25-60 years. Sensitivity of MRI is much higher than of mammography and mammography at young ages can induce breast cancer, therefore there are growing doubts about the additional value of mammography screening next to MRI. In an international meta-analyses we demonstrated that additional mammography screening adds little for BRCA1 mutation carrier, but may still have an important role in breast cancer detection in BRCA2 mutation carriers.

Above the age of 60 years less intensive screening is advised for BRCA1/2 mutation carriers in some guidelines worldwide, amongst which the Dutch guidelines. We show that more than 70% of 60 year old BRCA1/2 mutation carriers still has one or both breasts at risk, i.e. had not undergone therapeutic or risk-reducing bilateral mastectomy, with still a 20-30% risk of breast cancer. With biennial mammography twice as much breast cancers were detected in unfavorable stage (53%) in comparison with annual mammography screening. Therefore continuation of annual breast cancer screening of BRCA1/2 mutation carriers ≥60 is worthwhile, when life expectancy is good.

The MRISC was a non-randomized trial. Furthermore, effect of breast density, that increases risk of breast cancer and decreases mammography sensitivity, was not taken into consideration. We describe the study protocol of the Dutch Familial MRI Screening Study (FaMRIsc), a randomized controlled trial with 12 participating hospitals, in which mammography and MRI screening are compared and influence of breast density is assessed. Results are expected in 2017.