Intensified Surveillance for Early Detection of Breast Cancer in High-Risk Patients

Abstract

Efforts for early detection of breast cancer play an important role in the care of high-risk women. This will include both women with a pathological mutation in one of the known breast cancer susceptibility genes as well as women with a high breast cancer risk based on family history only. Due to the much higher incidence of breast cancer in premenopausal women with a genetic predisposition or a familial background, to be most effective, imaging-based breast surveillance should start at an age as early as 25-30 years. There is now ample evidence that magnetic resonance imaging (MRI) is by far the most sensitive imaging modality in young high-risk women. With high-risk multimodality screening at least 30% of breast cancers will be detected primarily by MRI and would have been missed at regular screening without MRI. Therefore, most high-risk breast surveillance programs now offer annual MRI to eligible high-risk women from age 25 to 30, usually supplemented by regular mammography starting at least from age 40. The inclusion of clinical breast exam (CBE) and/or ultrasound in the high-risk surveillance has little impact on the detection of additional cancers, but may improve compliance and reduce unnecessary call-backs for nonspecific findings on MRI. To reduce advanced stage interval cancers, especially in BRCA1/2 mutation carriers, some programs offer additional semiannual CBE and/or ultrasound or alternate MRI and mammography every 6 months. How long regular MRI should be continued in high-risk women is a matter of considerable debate. It appears feasible that MRI can safely be discontinued even in BRCA1/2 mutation carriers between the age of 60 and 70, especially if mammographic breast density is low. Even though several cohort studies have now demonstrated a very favorable stage distribution of breast cancers found in women undergoing high-risk surveillance with MRI, data on long-term survival and mortality in these patients is still rare.

Breast cancer risk in BRCA1/2 mutation carriers and noncarriers under prospective intensified surveillance

“…32,33 In January 2005, a structured prospective multimodality BC surveillance program was initiated in 12 GC-HBOC centers, which comprises imaging examinations with mammography and magnetic resonance imaging (MRI) at annual intervals, and sonography every 6 months. 28,29 This surveillance program is offered in an identical manner to all women with a deleterious BRCA1/2 mutation as well as to women from families in which the index case was tested negative for BRCA mutations but who have a predicted mutation risk of at least 20% and/or a remaining BC lifetime risk of at least 30% based on the extended Claus model (as implemented in the commercial pedigree drawing software Cyrillic 2.1.3, Cherwell Scientific, London, UK). 34,35 Written informed consent was obtained from all individuals undergoing genetic testing and/or participating in the prospective surveillance study.…”

“…19,21,26,27 There is a debate, however, whether these women should undergo specific surveillance programs and how these programs should be designed, for example, regarding ages at entry and exit and examination intervals. 28 In 2005, the German Consortium for Hereditary Breast and Ovarian Cancer (GC-HBOC) initiated a prospective multimodality breast imaging surveillance program in 12 university centers across Germany, which is offered to BRCA1/2 mutation carriers, but explicitly also to those women from BRCA1/2 negative families, who are predicted to have an elevated BC risk based on risk modeling. Using the prospective follow-up data from this surveillance program, we characterized and compared the risk of FBC and CBC in BRCA1/2 noncarriers and carriers.…”

Screening of populations at high risk for breast cancer

“…Recommendations for discontinuation of MRI screening in high‐risk patients varies from after age 50 years except for patients with dense breasts, to after age 75 years regardless, to discontinuation of all screening once life expectancy is less than 10 years . As the incidence rates of breast cancer in those with BRCA pathogenic variants and the benefits of MRI sensitivity compared with mammography in this population are relatively independent of age, it appears reasonable to continue MRI screening in select high‐risk women until breast parenchymal density decreases to optimal mammography conditions …”

BRCA1/2 associated cancer susceptibility: a clinical overview

“…Notably, in relevant studies, despite the higher detection rate, a benefit in survival with the adoption MRM has not been apparent [18,19]. The risks of frequent screening, especially with MRM, include false-positive diagnoses, leading to unnecessary biopsies and/or surgeries, adding in financial and psychological costs, although there is evidence supporting a sharp reduction of false-positives after the first three to five MRMs [20,21]. Concerns have also been voiced on the impact of radiation administered during mammograms.…”