Surgical Management of Hereditary Breast Cancer

Abstract

The identification that breast cancer is hereditary was first described in the nineteenth century. With the identification of the BRCA1 and BRCA 2 breast/ovarian cancer susceptibility genes in the mid-1990s and the introduction of genetic testing, significant advancements have been made in tailoring surveillance, guiding decisions on medical or surgical risk reduction and cancer treatments for genetic variant carriers. This review discusses various medical and surgical management options for hereditary breast cancers.

Surgical Management of Inherited Breast Cancer: Role of Breast-Conserving Surgery

“…Indeed, P or LP variants of other BC susceptibility genes, including high-penetrance genes such as CDH1, PALB2, PTEN, STK11, and TP53, and moderate-penetrance genes such as ATM, CHEK2, NBN, and NF1, also confer an increased BC risk [9,22,23,25,27]. These cancer-predisposing variants of not only high-but also moderate-penetrance genes can be largely detected thanks to improvements in sequencing technology and multigene panel testing [28]. Consequently, further genetic variants associated with an increased risk not only of BC but also of ovarian, fallopian tube, colon, melanoma, prostate, and pancreatic cancer were discovered [28].…”

“…These cancer-predisposing variants of not only high-but also moderate-penetrance genes can be largely detected thanks to improvements in sequencing technology and multigene panel testing [28]. Consequently, further genetic variants associated with an increased risk not only of BC but also of ovarian, fallopian tube, colon, melanoma, prostate, and pancreatic cancer were discovered [28]. In general, high-penetrance variants are correlated with over 40-50% absolute lifetime risk of BC, and moderate-penetrance variants with over 20-25% absolute lifetime risk [9].…”

“…Indeed, identifying a BRCA1 PV in a BC patient provides information on her elevated risk of both contralateral BC and ovarian cancer, with all the implications for how to manage those risks. Studies are underway to determine whether these patients might benefit from the inclusion of PARP inhibitors in their adjuvant therapy [28]. Likewise, the added value of PV genes' identification in the clinical management of BC patients is exemplified by the relative contraindication of radiation in patients with TP53 pathogenic variants (associated with Li-Fraumeni Syndrome), due to their higher risk of developing radiation-induced secondary cancers [30].…”

“…In women with an increased risk of hereditary BC, cancer risk, morbidity, and mortality can be reduced using a variety of possible preventive options that include, in addition to healthy lifestyle choices, intensified imaging screening to detect tumors at an earlier stage, prophylactic surgeries, i.e., risk-reducing mastectomy and risk-reducing salpingooophorectomy, and chemoprevention [28].…”

“…Scientific data suggest that 48-90% of women chose prophylactic surgery versus constant surveillance strategies with MRI [28,53]. Over time, risk-reducing mastectomy in genetic variant carriers has become increasingly conservative.…”