Breast cancer diagnosed after age 70 years in Israeli BRCA1/BRCA2 pathogenic sequence variant carriers: a single institution experience.

PURPOSE: A semi-annual surveillance scheme from age 25 to 30 years is offered to BRCA1/BRCA2 pathogenic sequence variants (PSVs) carriers for early detection of breast cancer (BC). There is a paucity of data on the yield of adhering to this scheme beyond 70 years of age. METHODS: Female BRCA1/BRCA2 PSV carriers followed at the Meirav high-risk clinic, Sheba Medical center, Israel were eligible. Type and frequencies if use of Imaging modalities, breast biopsies and histological outcomes for participants after age 70 years were retrieved and analyzed. RESULTS: Overall, the study encompassed 88 consenting participants (46 BRCA1 carriers) mean age ± SD 73.7 ± 3.3 years (range 70-90 years), followed for an average of 3.8 years (range 1-11 years). Ten carriers (11.3%) were diagnosed with BC after age 70 years (mean age at diagnosis 72 ± 2 years) and an additional case was diagnosed with breast lymphoma. The imaging modality that has led to most diagnoses was MRI (8/11 cases). Eight of these ten cases were previously diagnosed with BC prior to age 70 and in six, BC past 70 years was in the contralateral breast. The lesions size averaged 1.29 ± 0.75 cm, with IDC and DCIS diagnosed in five cases each, and none had lymph node involvement. CONCLUSION: In ~10% of BRCA1/BRCA2 PSV carriers BC is diagnosed by breast imaging after age 70 years. If these results are validated in a larger study, the guidelines for the maximum age for BC surveillance in high risk women should be revisited and set at 75 years.

Pregnancy Associated Breast Cancer Among Israeli BRCA1/BRCA2 Carriers in a High-Risk Clinic.

RATIONALE AND OBJECTIVES: Female carriers of pathogenic sequence variants (PSVs) in the BRCA1 /BRCA2 (Breast Cancer gene - BRCA) genes are at a substantially high-risk for developing breast cancer (BC), hence are offered active surveillance scheme based on semiannual breast exam and imaging from age 25 years to facilitate BC early detection (mammography/breast ultrasound depending on the age, and MRI). However, there are not specific guidelines for screening in case of pregnancy or lactation. In the current study, we summarize the experience at the largest high-risk clinic in Israel. MATERIALS AND METHODS: Data of consecutive BRCA-PSV carriers undergoing surveillance as well as diagnostic ultrasound at the Meirav high-risk clinic from January 2014 to 2021 who were pregnant and/or breastfeeding at time of follow-up were identified. Relevant clinical data including results of breast exam, breast ultrasonography, biopsies and histological results were retrieved. Percentage of biopsies with malignancy, cancer detection rate and positive predictive values were calculated. Data is presented in descriptive statistics. RESULTS: A total of 263 BRCA-carriers were included. Of these, 593 breast-ultrasonograms were performed in 263 BRCA-carriers for 292 pregnancies and 409 breast-ultrasonograms for 175 breastfeeding carriers. Of 36 breast biopsies in 292 pregnancies, 4 (PPV = 11%) had BC diagnosed (high grade invasive). Of 175 breastfeeding women, 25 biopsies were performed and 2 (PPV = 8%) were high grade invasive BC. Five of 6 BC were diagnosed in BRCA1 carriers, and 4/6 were screen detected. The rate of pregnancy-associated breast cancer was 6/292 (2.05%). CONCLUSION: The overall detection rate of pregnancy-associated BC in BRCA-carriers is relatively low (2.05%), but still much higher than that in the general population. Two thirds of the BC were detected by screening. Therefore, despite the changes of the glandular breast tissue at time of pregnancy and breastfeeding, screening plays an important role in early detection. Ultrasound should be considered as a screening tool during this period of life of high-risk patients.

Abnormal Findings Detected by Multi-modality Breast Imaging and Biopsy Results in a High-risk Clinic.

BACKGROUND: High-risk BRCA mutation carriers are offered a surveillance scheme aimed at early detection of breast cancer. Although the efficacy of this scheme in breast cancer detection is well-established, the rate of breast cancer diagnosis of radiologically suspicious lesions and the effect of this screening scheme on breast cancer grade and stage are less well-defined. PATIENTS AND METHODS: Female BRCA1 and BRCA2 mutation carriers who were cancer-free at the beginning of follow-up at the Meirav High-risk Clinic, Sheba Medical Center, were eligible. Radiological imaging data (mammography, ultrasound, magnetic resonance imaging, Breast Imaging Reporting and Data System scores), and histopathologic data on breast biopsies were retrieved. RESULTS: Overall, 1055 women participated in the study; 760 (72%) were Ashkenazim, 661 (62.6%) were BRCA1 mutation carriers, the mean age at first visit was 44.1 ± 11.8 years, and there was a mean follow-up of 6.2 years. All participants underwent 6641 breast imaging tests: 2613 magnetic resonance imagings, 2662 breast ultrasounds, and 1366 mammograms. Overall, 295 biopsies were performed on 254 women: 82 (27%) biopsies on 79 women were diagnosed with breast cancer, including ductal carcinoma in situ: invasive breast cancer was diagnosed in 58 (70.7%), of whom 36 (62% of invasive cancer) were grade 3, and all but 10 were stage 1 to 2. Benign findings were noted in 213 biopsies performed on 175 women, with fibrocystic disease (n = 134; 62.9%) or fibroadenoma (n = 60; 28.16%) most commonly diagnosed. CONCLUSIONS: Adherence to a breast cancer surveillance scheme enables breast cancer detection at an early stage but at advanced grade. Most biopsies (72%) performed in this high-risk clinic are benign.