Introduction Sample — Sandra Munro, Scientific/Medical Writer

An Introduction was needed for a manuscript on the prevalence of pathogenic variants in genes other than the traditional breast cancer risk genes (BRCA1 and BRCA2) in male breast cancer. (This is a mock study and not part of a real manuscript.)

Introduction

Breast cancer in males is uncommon, comprising less than 1 out of 100 of all diagnosed cases of breast cancer in the United States.[1] Despite this low prevalence, male breast cancer (MBC) can be more deadly than other rare cancers, as it is more likely to be diagnosed at a more advanced stage when treatment options are limited.[2] Pathogenic variants (PVs) in the hereditary breast and ovarian cancer (HBOC) syndrome genes BRCA1 and BRCA2 (BRCA1/2) account for approximately 2% and 10% of MBC cases, respectively.[3] According to the current National Comprehensive Cancer Network guidelines, genetic testing for BRCA1/2 and other high-penetrance breast cancer predisposition genes, including CDH1, PALB2, PTEN, and TP53, is recommended for those with a personal or family history of MBC.[4]

Evaluation of PV prevalence in cancer-related genes other than BRCA1/2 has important implications for breast cancer patients, including evidence-based clinical management, risk-reducing interventions, cancer screenings, and clinical trial eligibility.[5,6] The use of multi-gene panels has identified PVs in non-BRCA1/2 cancer-associated genes in 5–15% of HBOC patients. These include established breast cancer predisposition genes ATM, CHEK2, and PALB2, which, like BRCA1/2, are involved in DNA damage repair (DDR).[7,8] Advances in the understanding of DDR pathways have led to the development of targeted therapies such as poly(ADP-ribose) polymerase (PARP) inhibitors. The OlympIA trial demonstrated the efficacy of the PARP inhibitor olaparib in improving overall and progression-free survival in female patients with BRCA1/2-associated early-stage breast cancer.[9] Olaparib is currently being investigated in clinical trials for breast cancer patients with PVs in non-BRCA1/2 DDR genes.[10]

Due to the limited number of studies that have tested for PVs beyond those in BRCA1/2 in MBC patients, there remains a lack of data regarding potential MBC-associated PVs in cancer predisposition genes.[11] In this study, we sought to comprehensively evaluate the germline genetic predisposition to MBC using a hereditary cancer multi-gene panel.

References

1. Konduri S, Singh M, Bobustuc G, Rovin R, Kassam A. Epidemiology of male breast cancer. Breast. 2020;54:8-14.

2. Yalaza M, İnan A, Bozer M. Male breast cancer. J Breast Health. 2016;12(1):1-8.

3. Campos FAB, Rouleau E, Torrezan GT, et al. Genetic landscape of male breast cancer. Cancers. 2021;13(14).

4. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic. Published August 11, 2021. Accessed August 14, 2022. https://www.nccn.org/

5. O’Leary E, Iacoboni D, Holle J, et al. Expanded gene panel use for women with breast cancer: identification and intervention beyond breast cancer risk. Ann Surg Oncol. 2017;24(10):3060-3066.

6. Abdel-Razeq H. Expanding the search for germline pathogenic variants for breast cancer. How far should we go and how high should we jump? The missed opportunity! Oncol Rev. 2021;15(1):544.

7. Kurian AW, Hughes E, Handorf EA, et al. Breast and ovarian cancer penetrance estimates derived from germline multiple-gene sequencing results in women. JCO Precis Oncol. 2017;(1):1-12.

8. Hu C, Hart SN, Gnanaolivu R, et al. A population-based study of genes previously implicated in breast cancer. N Engl J Med. 2021;384(5):440-451.

9. Tutt ANJ, Garber JE, Kaufman B, et al. Adjuvant olaparib for patients with BRCA1- or BRCA2-mutated breast cancer. N Engl J Med. 2021;384(25):2394-2405.

10. Olaparib in metastatic breast cancer. ClinicalTrials.gov. Published March 18, 2022. Accessed August 12, 2022. https://clinicaltrials.gov/ct2/show/NCT03344965

11. Rolfes M, Borde J, Möllenhoff K, et al. Prevalence of cancer predisposition germline variants in male breast cancer patients: results of the German Consortium for Hereditary Breast and Ovarian Cancer. Cancers. 2022;14(13).