Surgery for BRCA, TP53 and PALB2: a literature review

Abstract

IntroductionThe presence of a deleterious mutation, most commonly a BRCA mutation, has a tremendous impact on the management of breast cancer. We review the surgical management of BRCA mutation carriers, and two other potentially high-risk mutations, TP53 and PALB2.MethodologyA search was done on PubMed, limited to reviews and the English language only. The search terms used were ‘BRCA’ or ‘PALB2’ or ‘TP53’ and ‘surgery’. Fifteen articles were identified by searching and one article was obtained from other sources.ResultsBreast-conserving surgery has equivalent survival, but may have an increased risk of local recurrence, compared to mastectomy among BRCA mutation carriers. Contralateral prophylactic mastectomy may not improve overall survival, despite reducing the risk of developing contralateral breast cancer. The use of preoperative genetic testing allows patients to have combined curative and prophylactic surgery. However, preoperative genetic testing may influence patients to make rash decisions. In healthy BRCA mutation carriers, bilateral prophylactic mastectomy is done to prevent breast cancer from occurring. Bilateral prophylactic mastectomy is highly effective in reducing the risk of breast cancer in healthy BRCA mutation-positive women and may have a survival benefit. Prophylactic oophorectomy reduces the risk of ovarian cancer, but may not have an effect on the risk of breast cancer. There is a lack of studies on surgery for non-BRCA mutations. TP53 and PALB2 are potentially high-risk mutations for breast cancer, which may justify the use of prophylactic surgery. Advice should be given on a case-by-case basis.ConclusionA comprehensive approach is needed to provide optimum treatment for breast cancer patients with deleterious mutations.

Heritability of Low ER Staining/HER2-Breast Tumors: Are We Missing an Opportunity for Germline Testing?

“…Since the identification of the BRCA1 and BRCA2 genes over 25 years ago [ 13 , 14 ], the benefits of germline testing have expanded to include not only personal and familial risk assessment, but also treatment choice. For women with BRCA germline mutations, patients may elect contralateral prophylactic mastectomy and oophorectomy [ 15 ]. In patients with TNBC and BRCA mutations, platinum salts and PARP inhibitors, which exploit the genomic instability of cells with defective DNA repair, may be beneficial [ 16 ].…”

Significant random signatures reveals new biomarker for breast cancer

“…Therefore, discovering and controlling the mechanisms that regulate self-renewal and metastasis in tumors before they reach the late stage is essential for personalized patient care [4, 5]. Different cancer driver genes have been described in breast cancer, including TP53, BRCA1 and PALB2 [6]. Cancer genes do not act separately and deregulation of various genes from different pathways can lead to cancer initiation or progression [7, 8].…”

Bioinformatic and experimental findings to indicate anti-cancer targets and mechanisms of calycosin against nasopharyngeal carcinoma

“…TP53, a well-known tumor suppressor, is reportedly studyed in many cancer topics. The molecular mechanism of anti-tumor by TP53 is involved in regulating cell growth, survival, DNA stability, and cytoprotection [26]. Pathologically, abnormal mutation of TP53 is found with many cancer human and cell samples, marked by malignant proliferation, uncontrolled growth, and strong invasiveness [27].…”