Timing of genetic testing in BRCA1/2 and PALB2-Associated breast cancer: Preoperative result disclosure increases uptake of risk-reducing mastectomy and reduces unnecessary exposure to radiotherapy

Eur J Surg Oncol. 2024 Jun;50(6):108324. doi: 10.1016/j.ejso.2024.108324. Epub 2024 Apr 12.

Abstract

Introduction: The impact of timing of genetic testing on uptake of risk reducing mastectomy (RRM) in affected female BRCA1/2 or PALB2 carriers remains an area of evolving interest, particularly with the introduction of mainstream genetic testing initiatives.

Methods: Women with stage I-III breast cancer and a confirmed germline pathogenic variant in BRCA1/2 or PALB2 between 2000 and 2023 were identified from an institutional genetics database. Uptake of RRM was evaluated according to disclosure of genetic testing results before or after index surgery for a first diagnosis of breast cancer.

Results: The cohort included 287 female BRCA1/2 or PALB2 carriers with a median age of 44 years (IQR, 36-52). Overall, 155 (54 %) carriers received genetic testing results before and 132 (46 %) after index breast surgery. Receipt of genetic testing results before surgery was associated with a higher rate of index bilateral mastectomy (58.7 % vs. 7.6 %, p < 0.001) and a commensurate decrease in adjuvant radiation (41.9 % vs. 74.2 %, p < 0.001). At a median follow up of 4.4 years after genetic testing, 219 (76.3 %) affected carriers had undergone bilateral RRM, including 83.9 % with preoperative knowledge and 67.4 % of patients with postoperative knowledge of their germline pathogenic variant (log rank, p < 0.001). On multivariate regression, disclosure of genetic testing results before index breast surgery was independently associated with long-term uptake of bilateral mastectomy (HR 1.69, 95 % CI 1.21-2.38).

Conclusion: Genetic testing results delivered prior to index breast surgery increase uptake of bilateral RRM in affected BRCA1/2 and PALB2 carriers. Efforts to mainstream genetic testing would help optimize surgical decision-making.

Keywords: BRCA1/2; Breast neoplasms; Risk-reducing mastectomy.

MeSH terms

  • Adult
  • BRCA1 Protein / genetics
  • BRCA2 Protein / genetics
  • Breast Neoplasms* / genetics
  • Breast Neoplasms* / radiotherapy
  • Breast Neoplasms* / surgery
  • Disclosure
  • Fanconi Anemia Complementation Group N Protein* / genetics
  • Female
  • Genes, BRCA1
  • Genes, BRCA2
  • Genetic Predisposition to Disease
  • Genetic Testing*
  • Germ-Line Mutation
  • Heterozygote
  • Humans
  • Mastectomy
  • Middle Aged
  • Prophylactic Mastectomy*
  • Time Factors
  • Unnecessary Procedures

Substances

  • Fanconi Anemia Complementation Group N Protein
  • PALB2 protein, human
  • BRCA1 Protein
  • BRCA2 Protein
  • BRCA1 protein, human