Hereditary Susceptibility for Triple Negative Breast Cancer Associated With Western Sub-Saharan African Ancestry: Results From an International Surgical Breast Cancer Collaborative.

OBJECTIVE: To investigate subtype-specific risk of germline alleles associated with triple negative breast cancer (TNBC) in African ancestry populations. BACKGROUND: Breast cancer (BC) mortality is higher in African American (AA) compared to White American (WA) women; this disparity is partly explained by 2-fold higher TNBC incidence. METHODS: We used a surgically maintained biospecimen cohort of 2884 BC cases. Subsets of the total (760 AA; 962 WA; 910 West African/Ghanaian; 252 East African/Ethiopian) were analyzed for genotypes of candidate alleles. A subset of 417 healthy controls were also genotyped, to measure associations with overall BC risk and TNBC. RESULTS: TNBC frequency was highest in Ghanaian and AA cases (49% and 44% respectively; P < 0.0001) and lowest in Ethiopian and WA cases (17% and 24% respectively; P < 0.0001). TNBC cases had higher West African ancestry than non-TNBC (P < 0.0001). Frequency of the Duffy-null allele (rs2814778; an African ancestral variant adopted under selective pressure as protection against malaria) was associated with TNBC-specific risk (P < 0.0001), quantified West African Ancestry (P < 0.0001) and was more common in AA, Ghanaians, and TNBC cases. Additionally, rs4849887 was significantly associated with overall BC risk, and both rs2363956 and rs13000023 were associated with TNBC-specific risk, although none as strongly as the Duffy-null variant. CONCLUSIONS: West African ancestry is strongly correlated with TNBC status, as well as germline variants related to BC risk. The Duffy-null allele was associated with TNBC risk in our cohort.

African Ancestry-Associated Gene Expression Profiles in Triple-Negative Breast Cancer Underlie Altered Tumor Biology and Clinical Outcome in Women of African Descent.

Women of sub-Saharan African descent have disproportionately higher incidence of triple-negative breast cancer (TNBC) and TNBC-specific mortality across all populations. Population studies show racial differences in TNBC biology, including higher prevalence of basal-like and quadruple-negative subtypes in African Americans (AA). However, previous investigations relied on self-reported race (SRR) of primarily U.S. populations. Due to heterogeneous genetic admixture and biological consequences of social determinants, the true association of African ancestry with TNBC biology is unclear. To address this, we conducted RNA sequencing on an international cohort of AAs, as well as West and East Africans with TNBC. Using comprehensive genetic ancestry estimation in this African-enriched cohort, we found expression of 613 genes associated with African ancestry and 2,000+ associated with regional African ancestry. A subset of African-associated genes also showed differences in normal breast tissue. Pathway enrichment and deconvolution of tumor cellular composition revealed that tumor-associated immunologic profiles are distinct in patients of African descent. SIGNIFICANCE: Our comprehensive ancestry quantification process revealed that ancestry-associated gene expression profiles in TNBC include population-level distinctions in immunologic landscapes. These differences may explain some differences in race-group clinical outcomes. This study shows the first definitive link between African ancestry and the TNBC immunologic landscape, from an African-enriched international multiethnic cohort. See related commentary by Hamilton et al., p. 2496. This article is highlighted in the In This Issue feature, p. 2483.

Investigation of triple-negative breast cancer risk alleles in an International African-enriched cohort.

Large-scale efforts to identify breast cancer (BC) risk alleles have historically taken place among women of European ancestry. Recently, there are new efforts to verify if these alleles increase risk in African American (AA) women as well. We investigated the effect of previously reported AA breast cancer and triple-negative breast cancer (TNBC) risk alleles in our African-enriched International Center for the Study of Breast Cancer Subtypes (ICSBCS) cohort. Using case-control, case-series and race-nested approaches, we report that the Duffy-null allele (rs2814778) is associated with TNBC risk (OR = 3.814, p = 0.001), specifically among AA individuals, after adjusting for self-indicated race and west African ancestry (OR = 3.368, p = 0.007). We have also validated the protective effect of the minor allele of the ANKLE1 missense variant rs2363956 among AA for TNBC (OR = 0.420, p = 0.005). Our results suggest that an ancestry-specific Duffy-null allele and differential prevalence of a polymorphic gene variant of ANKLE1 may play a role in TNBC breast cancer outcomes. These findings present opportunities for therapeutic potential and future studies to address race-specific differences in TNBC risk and disease outcome.

Internal hernia and small bowel obstruction caused by a linear cutter staple at appendiceal stump following laparoscopic appendectomy.

Commonly linear staplers are used to perform laparoscopic appendectomies. We report a case of a small bowel obstruction caused by a staple on the appendiceal stump creating an internal hernia <1 week after laparoscopic appendectomy. We discuss the available literature on bowel obstructions caused by staples. Most of the discussed complications were caused by staples free in the abdomen, which were remote from the staple line. Generally, loose staples do not cause problems, but if noted during the operation, we recommend removal to prevent future obstruction.

Permanent mesh results in long-term symptom improvement and patient satisfaction without increasing adverse outcomes in hiatal hernia repair.

BACKGROUND: The purpose of this study is to evaluate symptom relief, patient satisfaction, and safety of permanent mesh following Nissen fundoplication and hiatal hernia repair. METHODS: Patients who underwent Nissen fundoplication and hiatal hernia repair with permanent mesh (Crurasoft; Davol, Inc, Bard, Warwick, RI) between 2005 and 2011 were identified. A retrospective chart review was conducted. Long-term follow-up data were obtained via telephone interviews using a modified 5-point Likert scale. RESULTS: Forty-one patients were identified. Twenty-six patients (63%) had complete follow-up data. Mean follow-up period was 65 months (14 to 96 months). Symptomatic improvement occurred in 23 patients (88%). Twenty-three patients (88%) reported overall satisfaction with the procedure as either excellent or good, and 23 of 26 patients (89%) would undergo surgery again. Three patients (12%) reported hernia recurrence. There were no mesh erosions. CONCLUSION: The use of permanent (Crurasoft; Davol, Inc) mesh resulted in symptom improvement as well as patient satisfaction, and no mesh erosions were seen.