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

Shay Shraga; Albert Grinshpun; Aviad Zick; Luna Kadouri; Yogev Cohen; Ofra Maimon; Yael Adler-Levy; Galina Zeltzer; Avital Granit; Bella Maly; Einat Carmon; Vardiella Meiner; Tamar Sella; Tamar Hamburger; Tamar Peretz

doi:10.3389/fonc.2021.683656

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

Front Oncol. 2021 Sep 2:11:683656. doi: 10.3389/fonc.2021.683656. eCollection 2021.

Authors

Shay Shraga^{1

2}, Albert Grinshpun^{1

2}, Aviad Zick^{1

2}, Luna Kadouri^{1

2}, Yogev Cohen^{1

2}, Ofra Maimon^{1

2}, Yael Adler-Levy^{2

3}, Galina Zeltzer^{2

3}, Avital Granit^{1

2}, Bella Maly^{2

4}, Einat Carmon^{2

5}, Vardiella Meiner^{2

6}, Tamar Sella^{2

3}, Tamar Hamburger¹, Tamar Peretz^{1

2}

Affiliations

¹ Sharett Institute of Oncology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
² Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel.
³ Radiology Department, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
⁴ Pathology Department, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
⁵ Surgery Department, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
⁶ Department of Genetic and Metabolic Diseases, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.

Abstract

Background: Germline 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 methods: Retrospectively, 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.

Results: Median 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).

Conclusions: High-risk screening might facilitate downstaging of detected breast tumor among BRCA1/2 carrier population.

Keywords: BRCA1/2; breast cancer; downstaging; high-risk; screening; survival.