“High-Risk Breast Cancer Screening in BRCA1/2 Carriers Leads to Early Detection and Improved Survival After a Breast Cancer Diagnosis”

Abstract

BackgroundGermline BRCA1/2 pathogenic variant (PV) carriers have high lifetime risk of developing breast cancer and therefore subjected to intense lifetime screening. However, solid data on the effectiveness of high-risk screening of the BRCA1/2 carrier population is limited.Patients and MethodsRetrospectively, we analyzed 346 women diagnosed with breast tumors. Patients were divided according to the timing of BRCA1/2 PVrecognition, before (BRCA-preDx awareness, N = 62) or after (BRCA-postDx awareness group, N = 284) cancer diagnosis.ResultsMedian follow-up times were 131.42 and 93.77 months in the BRCA-preDx awareness and BRCA-postDx awareness groups, respectively. In the BRCA-preDx awareness group, 78.7% of the patients had invasive tumors and 21.3% were diagnosed with pure ductal carcinoma in situ. In contrast, in the BRCA-postDx awareness group over 93% of women were diagnosed with invasive cancer and only 6.4% had in situ disease. The mode of tumor detection differed significantly between the groups: 71.9% in the BRCA-postDx awareness group and 26.2% in the BRCA-preDx awareness group were diagnosed after personally palpating a lump. Tumor size and nodal involvement were significantly more favorable in the BRCA-preDx awareness group. T stage was significantly lower in the BRCA-preDx awareness group: 54.84% at T1 and 20.96% at Tis. In the BRCA-postDx awareness group, only 37.54% were at T1 and 6.49% at Tis. The N stage was also significantly lower in the BRCA-preDx awareness group: 71% had no lymph node metastases, compared with 56.1% in the BRCA-postDx awareness group. Additionally, therapeutic procedures varied between the groups: BRCA-preDx awareness group patients underwent more breast conserving surgeries. Axillary lymph node dissection was done in 38% of women in the BRCA-postDx awareness group and in only 8.7% of the BRCA-preDx awareness group patients. Interestingly, improved survival was found among patients who underwent high-risk screening (hazard ratio=0.34).ConclusionsHigh-risk screening might facilitate downstaging of detected breast tumor among BRCA1/2 carrier population.

Nonsurgical Options for Risk Reduction of Contralateral Breast Cancer in BRCA Mutation Carriers With Early-Stage Breast Cancer

“…6 For those who forgo mastectomy, intensive follow-up with annual MRI alternating with mammography and breast ultrasound allows early detection and curative treatment of BC 37 and may improve survival. 38 Nevertheless, nonsurgical prevention seems highly desirable and could alleviate morbidity and suffering.…”

Is it Time to Retire the Term of Low-Grade Ductal Carcinoma in Situ and Replace it With Ductal Neoplasia?

“…The role of BRCA1 & BRCA2 gene as important risk factors for the development of breast cancer is well-established; however, this association has been mostly directed to invasive breast cancers 65 . Nevertheless, it appears that with increased emphasis on early breast cancer screening and the recommendation for the use of MRI in carriers of breast cancer genes, carcinoma in situ lesions are now being more frequently identified 66 . It appears that BRCA1-related DCIS is diagnosed earlier, more likely to be estrogen receptor-negative and of higher grade than BRCA2-related DCIS.…”

“…65 Nevertheless, it appears that with increased emphasis on early breast cancer screening and the recommendation for the use of MRI in carriers of breast cancer genes, carcinoma in situ lesions are now being more frequently identified. 66 It appears that BRCA1-related DCIS is diagnosed earlier, more likely to be estrogen receptor-negative and of higher grade than BRCA2-related DCIS. More studies are required to better identify the relationship between breast cancer genes and low-grade DCIS.…”

‘Earlier than Early’ Detection of Breast Cancer in Israeli BRCA Mutation Carriers Applying AI-Based Analysis to Consecutive MRI Scans

“…The current screening guidelines for female BRCA PVs carriers, including bi-annual breast imaging [ 7 ], have been shown to increase the rate of early diagnosis with more in-situ pathology, smaller tumors, and less axillary involvement compared with carriers who do not adhere to the suggested surveillance scheme [ 7 , 8 , 9 , 10 ]. MRI is considered the most sensitive modality for BC detection in BRCA PV carriers, with sensitivity rates of up to 96% [ 10 , 11 , 12 , 13 ].…”

“…The current screening guidelines for female BRCA PVs carriers, including bi-annual breast imaging [ 7 ], have been shown to increase the rate of early diagnosis with more in-situ pathology, smaller tumors, and less axillary involvement compared with carriers who do not adhere to the suggested surveillance scheme [ 7 , 8 , 9 , 10 ]. MRI is considered the most sensitive modality for BC detection in BRCA PV carriers, with sensitivity rates of up to 96% [ 10 , 11 , 12 , 13 ]. Yet several studies have shown that, in retrospective analyses, in a significant number of MRI detected BCs (50–74%), localized radiological abnormalities were present in the prior MRI, which was performed approximately one year before actual BC diagnosis [ 12 , 14 , 15 , 16 , 17 ].…”