Differences in Natural History between Breast Cancers in BRCA1 and BRCA2 Mutation Carriers and Effects of MRI Screening-MRISC, MARIBS, and Canadian Studies Combined

Abstract

Background: It is recommended that BRCA1/2 mutation carriers undergo breast cancer screening using MRI because of their very high cancer risk and the high sensitivity of MRI in detecting invasive cancers. Clinical observations suggest important differences in the natural history between breast cancers due to mutations in BRCA1 and BRCA2, potentially requiring different screening guidelines.Methods: Three studies of mutation carriers using annual MRI and mammography were analyzed. Separate natural history models for BRCA1 and BRCA2 were calibrated to the results of these studies and used to predict the impact of various screening protocols on detection characteristics and mortality.Results: BRCA1/2 mutation carriers (N ¼ 1,275) participated in the studies and 124 cancers (99 invasive) were diagnosed. Cancers detected in BRCA2 mutation carriers were smaller [80% ductal carcinoma in situ (DCIS) or 10 mm vs. 49% for BRCA1, P < 0.001]. Below the age of 40, one (invasive) cancer of the 25 screen-detected cancers in BRCA1 mutation carriers was detected by mammography alone, compared with seven (three invasive) of 11 screen-detected cancers in BRCA2 (P < 0.0001). In the model, the preclinical period during which cancer is screen-detectable was 1 to 4 years for BRCA1 and 2 to 7 years for BRCA2. The model predicted breast cancer mortality reductions of 42% to 47% for mammography, 48% to 61% for MRI, and 50% to 62% for combined screening.Conclusions: Our studies suggest substantial mortality benefits in using MRI to screen BRCA1/2 mutation carriers aged 25 to 60 years but show important clinical differences in natural history.Impact: BRCA1 and BRCA2 mutation carriers may benefit from different screening protocols, for example, below the age of 40. Cancer Epidemiol Biomarkers Prev; 21(9); 1458-68. Ó2012 AACR.

The INTRABEAM® Photon Radiotherapy System for the adjuvant treatment of early breast cancer: a systematic review and economic evaluation

“…It is also possible for tumour cells to metastasise via the vascular system directly to systemic sites; 25 however, not all breast cancers metastasise. Evidence from screening studies suggests that some screen-detected breast cancers may regress spontaneously 27 and natural history may vary according to a variety of factors, for example genotype, 28 hormone receptor status 29 and race. 30 The heterogeneous nature of breast cancer natural history has an impact when trying to provide a prognosis and tools have been developed which aim to predict invasive breast cancer outcome.…”

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

“…Genetic changes in high-risk women do not only influence the frequency and age at which breast cancer is likely to occur [1], but also the histological type and imaging presentation of breast cancers differ depending on the underlying genetic abnormality [60,61]. Knowledge of the genetic status of a particular patient is, therefore, crucial for choosing the optimal individualized surveillance strategy in high-risk patients.…”

“…Unfortunately, several of the older studies on the imaging features of BRCA1-associated cancers did not differentiate between TNBCs and other cancers in BRCA1 carriers, although it can be assumed that the majority of the BRCA1-associated cancers in these studies would have been TNBCs. Imaging findings in BRCA2-associated breast cancers are much more similar to sporadic breast cancers, including a significantly higher proportion of in situ cancers with typical microcalcifications on mammography [61]. Another example of an association between immunohistological tumor properties and imaging features is the observation that estrogen receptor-negative and HER2-positive cancers, which are rare in both BRCA1 and BRCA2 carriers [70], are often associated with typical malignant mammographic features, such as spiculated margins and pleomorphic microcalcifications [63].…”

“…In addition, comparison with historical cohorts is difficult due to the substantial advances in targeted treatment and an increasing frequency of risk-reducing surgeries in high-risk women. Several prospective observational studies have shown a very favorable stage distribution of cancers detected by intensified multimodal surveillance programs [17,23,61,75,76,77], which can be used as surrogate parameter for the reduction in breast cancer mortality. …”

Cost-Effectiveness of a Genetic Test for Breast Cancer Risk—Letter

“…Such benefits may be very different if the expected cancers occur later and are less aggressive. Indeed, MRI currently shows little added value after the age of 60 to 70 years, even in BRCA carriers (2), and the value of MRI was previously documented in addition to current strategies, including mammography. The assumption made in this article that MRI may lead to the elimination of mammography, remains a hypothesis and is the object of currently ongoing trials (3).…”