Germline breast cancer susceptibility genes, tumor characteristics, and survival.

BACKGROUND: Mutations in certain genes are known to increase breast cancer risk. We study the relevance of rare protein-truncating variants (PTVs) that may result in loss-of-function in breast cancer susceptibility genes on tumor characteristics and survival in 8852 breast cancer patients of Asian descent. METHODS: Gene panel sequencing was performed for 34 known or suspected breast cancer predisposition genes, of which nine genes (ATM, BRCA1, BRCA2, CHEK2, PALB2, BARD1, RAD51C, RAD51D, and TP53) were associated with breast cancer risk. Associations between PTV carriership in one or more genes and tumor characteristics were examined using multinomial logistic regression. Ten-year overall survival was estimated using Cox regression models in 6477 breast cancer patients after excluding older patients (≥75years) and stage 0 and IV disease. RESULTS: PTV9genes carriership (n = 690) was significantly associated (p < 0.001) with more aggressive tumor characteristics including high grade (poorly vs well-differentiated, odds ratio [95% confidence interval] 3.48 [2.35-5.17], moderately vs well-differentiated 2.33 [1.56-3.49]), as well as luminal B [HER-] and triple-negative subtypes (vs luminal A 2.15 [1.58-2.92] and 2.85 [2.17-3.73], respectively), adjusted for age at diagnosis, study, and ethnicity. Associations with grade and luminal B [HER2-] subtype remained significant after excluding BRCA1/2 carriers. PTV25genes carriership (n = 289, excluding carriers of the nine genes associated with breast cancer) was not associated with tumor characteristics. However, PTV25genes carriership, but not PTV9genes carriership, was suggested to be associated with worse 10-year overall survival (hazard ratio [CI] 1.63 [1.16-2.28]). CONCLUSIONS: PTV9genes carriership is associated with more aggressive tumors. Variants in other genes might be associated with the survival of breast cancer patients. The finding that PTV carriership is not just associated with higher breast cancer risk, but also more severe and fatal forms of the disease, suggests that genetic testing has the potential to provide additional health information and help healthy individuals make screening decisions

European polygenic risk score for prediction of breast cancer shows similar performance in Asian women

Abstract: Polygenic risk scores (PRS) have been shown to predict breast cancer risk in European women, but their utility in Asian women is unclear. Here we evaluate the best performing PRSs for European-ancestry women using data from 17,262 breast cancer cases and 17,695 controls of Asian ancestry from 13 case-control studies, and 10,255 Chinese women from a prospective cohort (413 incident breast cancers). Compared to women in the middle quintile of the risk distribution, women in the highest 1% of PRS distribution have a ~2.7-fold risk and women in the lowest 1% of PRS distribution has ~0.4-fold risk of developing breast cancer. There is no evidence of heterogeneity in PRS performance in Chinese, Malay and Indian women. A PRS developed for European-ancestry women is also predictive of breast cancer risk in Asian women and can help in developing risk-stratified screening programmes in Asia

Virtual breast oncoplastic surgery simulator (VBOSS): A novel training tool in breast surgery

10.1016/j.ejso.2018.07.062European Journal of Surgical Oncology44111750-175

Utility preference scores : a demographic analysis

131 p.This research is based on a past Canadian study. The aim of this project is to analyse utility preference scores by race, age, gender, occupation and education level. We present the theory and methodology of the utility system of measuring health status and utilised the recently developed Multi-attribute Health Status Classification System (HUI Mark III System) to describe health status of Singaporeans. We then use the standard gamble method to elicit utility preference scores of various health states from the respondents.ACCOUNTANC

An unusual site for breast clip migration: A case report

Clip migration following breast biopsy is a known complication. However, the migrated clip is usually found within the breast. We describe a rare case of delayed clip migration to the skin, following a magnetic resonance guided biopsy of the breast, highlighting its natural history of presentation and its treatment

Determining the Need for Metastatic Staging in Patients with Bilateral Breast Cancers

Introduction: Bilateral breast cancers (BBC) diagnosed at an interval apart are uncommon. While metastatic staging guidelines are established in patients with unilateral breast cancer, its role in BBC diagnosed at an interval apart is unclear. We aim to identify the subgroup who would benefit from metastatic staging at contralateral cancer diagnosis. Methods: Eligible patients were divided into three categories: (A) ipsilateral invasive cancer and contralateral ductal carcinoma in situ (DCIS), (B) bilateral invasive cancers and (C) ipsilateral DCIS and contralateral invasive cancer and reviewed retrospectively. We excluded patients with bilateral DCIS, synchronous BBC diagnosed within 6 months from first cancer, patients who were stage IV at first cancer diagnosis and patients with recurrence prior to contralateral cancer. Results: Of 4516 newly diagnosed breast cancer patients, 79 patients were included. Systemic metastasis occurred in 15.6% of patients in Group B. Having nodal positivity of either cancer which were diagnosed ≤30 months apart and nodal positivity of only the contralateral cancer when diagnosed >30 months apart was significantly associated with systemic metastasis (p = 0.0322). Conclusions: Both the nodal status and a 30 months cut-off time interval between the two cancers can be used to identify patients who will benefit from metastatic staging. This finding requires validation in larger studies

Factors influencing the decision to share cancer genetic results among family members : an in-depth interview study of women in an Asian setting

Objective:Reluctance to share hereditary cancer syndrome genetic test results with family is reported among Asian patients. This study aims to explore patient factors influencing result sharing with family, to improve overall testing uptake.Methods:Participants were women with a personal/family history of breast and/or ovarian cancer who received a positive, negative, or variant of uncertain significance test result. In‐depth interviews were conducted to theme saturation to explore facilitators and barriers for sharing results with family. Grounded theory with thematic analysis was applied in analysis and interpretation.Results:Twenty‐four women participated. Three themes representing facilitators emerged for all results categories: family closeness, involvement of families in the testing process, and perception of low emotional impact of results. In the positive result category, 2 facilitator themes emerged: presence of actionable results and perception of family members' acceptance. In the negative and variant of uncertain significance result categories, 2 themes representing barriers to sharing emerged: perception of no genetic or medical implication for family and result ambiguity.Conclusion:Facilitators and barriers for result sharing are similar to those among Western women. A framework to explain Asian patients' decision‐making process identifies optimal counselling opportunities to enhance communication with family

Associations between Pre-Diagnostic Physical Activity with Breast Cancer Characteristics and Survival

Physical activity (PA) is known to reduce breast cancer (BC) risk and improve patient prognosis. However, the association between pre-diagnostic PA and the aggressiveness of BC is unclear. We investigated the associations between PA, BC tumour characteristics, and survival. This retrospective observational study included 7688 BC patients from the Singapore Breast Cancer Cohort (2010&ndash;2016). PA information from the questionnaire included intensity (light/moderate/vigorous) and duration (&lt;1 h/1&ndash;2 h/&gt;2 h per week). A PA score (1&ndash;5) incorporating intensity and duration was calculated. Associations between PA score and tumour characteristics such as stage, histological grade, nodal and hormone receptor status were examined using multinomial regression. Moreover, 10-year overall survival was estimated using Cox regression analysis in 6572 patients after excluding patients with invalid survival data and stage IV disease. Breast tumours associated with higher PA score were more likely to be non-invasive (ORinvasive&nbsp;vs.&nbsp;non-invasive(reference) [95% CI]: 0.71 [0.58&ndash;0.87], p-trend = 0.001), of lower grade (ORpoorly&nbsp;vs.&nbsp;well differentiated(reference): 0.69 [0.52&ndash;0.93], p = 0.014), ER-positive (ORER-negative&nbsp;vs.&nbsp;ER-positive(reference): 0.94 [0.89&ndash;1.00], p-trend = 0.049), PR-positive (ORPR-negative&nbsp;vs.&nbsp;PR-positive(reference): 0.82 [0.67&ndash;0.99], p = 0.041), HER2-negative (ORHER2-negative&nbsp;vs.&nbsp;HER2-positive(reference): 1.29 [1.02&ndash;1.62], p-trend = 0.002), and less likely to be of HER2-overexpressed subtype (ORHER2-overexpressed&nbsp;vs.&nbsp;Luminal A(reference): 0.89 [0.81&ndash;0.98], p-trend = 0.018). These associations (odds ratios) were more pronounced among post-menopausal patients. A higher PA score did not improve survival. Higher levels of pre-diagnostic PA were associated with less aggressive tumours in BC patients. This illustrated another benefit of PA in addition to its known role in BC risk reduction