Abstract 183P
Background
Women with pathogenic/likely pathogenic (P/LP) variants in inherited breast cancer genes are more likely to develop breast cancer in their lifetime. NCCN guidelines recommend a discussion about contralateral risk reduction mastectomy (RRM) for BRCA1/2 and PALB2 carriers, however there is insufficient evidence to uniformly recommend RRM among women solely based on a P/LP variant in CHEK2 or ATM. Using the Inherited Cancer Registry (ICARE), we compared RRM rates among women with a breast cancer diagnosis and a P/LP variant in BRCA1, BRCA2, PALB2, CHEK2, or ATM.
Methods
Through ICARE, individuals 18+ years were asked to complete a baseline questionnaire and sign a medical record release form to obtain copies of genetic test reports and other relevant clinical records. Women with a breast cancer diagnosis and a P/LP variant in one of the five genes were identified. Relevant self-reported and clinical data were pooled for this analysis. The type of breast cancer surgery (lumpectomy vs. mastectomy vs. RRM) was compared across the five carriers using a chi-squared test.
Results
Data from 684 women with localized breast cancer and a P/LP variant (235 BRCA1, 217 BRCA2, 121 PALB2, 61 CHEK2 and 50 ATM) were included in this study (Table). Notably, rates of RRM were similar across all five genes (p=0.73). Younger women and women with a known P/LP variant prior to surgery were more likely to have RRM. Table: 183P
Characteristics of the Study Population
| Total | BRCA1 | BRCA2 | PALB2 | ATM | CHEK2 | ||||||||
| 684 | N=235 | N=217 | N=121 | N=50 | N=61 | ||||||||
| Age at Diagnosis Mean (Range) | 48 (28-76) | 43 (24-72) | 45 (25-74) | 47 (23-76) | 51 (33-69) | 53 (27-75) | P-value | ||||||
| Surgery | |||||||||||||
| Lumpectomy | 203 | 30% | 72 | 40% | 60 | 36% | 37 | 41% | 10 | 32% | 24 | 45% | 0.73 |
| Mastectomy | 90 | 13% | 33 | 18% | 34 | 20% | 13 | 14% | 4 | 13% | 6 | 11% | |
| RRM | 231 | 34% | 77 | 42% | 73 | 44% | 41 | 45% | 17 | 55% | 23 | 43% | |
| Relatives with Breast Cancer | 0.46 | ||||||||||||
| None | 122 | 18% | 39 | 17% | 32 | 15% | 27 | 22% | 9 | 18% | 15 | 25% | |
| First Degree | 321 | 47% | 105 | 45% | 114 | 53% | 52 | 43% | 26 | 52% | 24 | 39% | |
| Second Degree | 189 | 28% | 69 | 29% | 58 | 27% | 35 | 29% | 12 | 24% | 15 | 25% | |
| Third Degree | 52 | 8% | 22 | 9% | 13 | 6% | 7 | 6% | 3 | 6% | 7 | 11% |
Conclusions
Similar rates of RRM across all carriers regardless of gene is concerning, given that RRM is not recommended solely based on CHEK2 and ATM P/LP variants in breast cancer patients. Our data suggest that known P/LP variant status at the time of surgery influenced the type of breast surgery received in BRCA1, BRCA2, and PALB2 carriers and appeared to also influence surgery in CHEK2 and ATM carriers although the cohort numbers are too small for significance. These findings warrant further evaluation to investigate possible over-treatment among women with CHEK2 and ATM P/LP variants.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.