Background Increasing numbers of women with breast cancer are electing for contralateral prophylactic mastectomy (CPM) to reduce the risk of developing contralateral breast cancer. The objective of this study was to identify factors that may impact a patient’s decision to undergo CPM. Methods We identified 2504 women with stage 0–III unilateral primary breast cancer who underwent breast surgery at our institution from January 2000 to August 2006 from a prospectively maintained database. We performed logistic regression analyses to determine which factors were associated with undergoing CPM. Results Of 2504 breast cancer patients, 1223 (48.8%) underwent total mastectomy. Of the 1223 patients who underwent mastectomy, 284 (23.2%) underwent immediate or delayed CPM. There were 33 patients (1.3%) who had genetic testing before the surgery; with the use of testing increasing in the latter years of the study (0.1% in 2000–2002 vs. 2.0% in 2003–2006, P<0.0001). Multivariable analysis revealed several factors that were associated with a patient undergoing CPM: age younger than 50 years, white ethnicity, family history of breast cancer, BRCA1/2 mutation testing, invasive lobular histology, clinical stage and use of reconstruction. Conclusions We identified specific patient and tumor characteristics associated with the use of CPM. Although genetic testing is increasing, most women undergoing CPM did not have a known genetic predisposition to breast cancer. Evidence-driven models are needed to better inform women of their absolute risk of contralateral breast cancer as well as their competing risk of recurrence from the primary breast cancer to empower them in their active decision making.

Background Germline TP53 mutations predispose to early onset breast cancer (BC) in women and are associated with the Li Fraumeni syndrome. Published data on the pathological characteristics of breast cancer among women with TP53 mutations is limited. Methods We retrospectively reviewed clinical records of women who had genetic testing for suspected germline TP53 mutations and who were diagnosed with BC between 2000 to 2011. The pathological characteristics of the breast tumors from women testing positive (cases) for a mutation were compared to those testing negative (controls). Results Patients who tested positive for germline TP53 mutations (N=30) were compared to (N=79) controls. Human epidermal growth factor receptor 2 (HER2) amplification and/or overexpression was found in 67% of the tumors from the cases, compared to 25% for the controls (p=0.0001). Among patients with a mutation, 70% had estrogen receptor and/or progesterone receptor positive tumors, compared to 68% in the control group (p= 0.87). After adjusting for age at BC diagnosis, having a HER2 positive tumor increased the odds of testing positive for a germline TP53 mutation (OR, 6.9, 95% CI, 2.6 to 18.2). For each yearly increments in age at BC diagnosis, there was decreased likelihood of having a TP53 mutation by 5% (OR=0.95, CI 0.91 to 0.99). Conclusion This study suggests an association between germline TP53 mutations and early onset HER2 positive breast cancer. If confirmed in a larger cohort, these results could guide genetic testing strategies, lead to chemoprevention trials incorporating HER2 targeted therapies, and elucidate some of the molecular pathways involved in breast cancer.

Introduction Preimplantation Genetic Diagnosis (PGD) allows couples to avoid having a child with an inherited condition, potentially reducing cancer burden in families with a hereditary cancer predisposition. This study investigated awareness and acceptance of PGD among patients with hereditary cancer syndromes. Methods Questionnaires were mailed to 984 adults with hereditary breast and ovarian cancer, Lynch syndrome, familial adenomatous polyposis, or multiple endocrine neoplasia type 1 or 2. Associations between clinical, demographic, and psychosocial factors and awareness and acceptance of PGD were examined. Results Of 370 respondents (38% return rate), 28% felt their syndrome impacted family planning, 24% were aware of PGD, 72% felt that PGD should be offered, 43% would consider using PGD, and 29% were uncertain. Family experience and syndrome-specific characteristics, such as disease severity, quality of life and availability of medical interventions as well as gender, family planning stage, and religiosity impact perceptions of the acceptability of PGD, though a high level of uncertainty exists. Conclusion Hereditary cancer patients' opinions about the acceptability of PGD are similar to those of genetics and ethical experts. Patients should be told about PGD given that most had not heard of PGD, but feel that PGD should be offered.

Several genes are associated with hereditary susceptibility to breast cancer. Most notably these include BRCA1 and BRCA2; however, other less common gene mutations which confer elevated breast cancer risk are associated with Cowden syndrome, Li-Fraumeni syndrome, Peutz-Jeghers syndrome, ataxia-telangiectasia heterozygosity and hereditary diffuse gastric cancer. In this article we highlight the genetic epidemiology, gene function, genotype-phenotype correlations, cancer risks and clinicopathologic findings for the cancer susceptibility genes related to these syndromes. We also examine genes, such as CHEK2, which confer a lower penetrance for breast cancer in comparison to these highly penetrant genes.