HER2 in Uterine Serous Carcinoma: Testing platforms and implications for targeted therapy.

OBJECTIVE: HER2 is an important prognostic and therapeutic target in uterine serous carcinoma (USC). Optimal HER2 testing platforms have not been defined and guidelines for testing have changed over time. Our objective is to assess the concordance of HER2 positivity based on chromogenic in situ hybridization (CISH), immunohistochemistry (IHC), and next generation sequencing (NGS) and to determine the rate of downstream mutations that may affect response to HER2 directed therapy. METHODS: Utilizing the Caris tumor registry, 2192 USC tumors were identified and analyzed using NGS (NextSeq, 592 Genes and WES, NovaSEQ), IHC, and CISH. PD-L1 expression was tested by IHC. Microsatellite instability was tested by fragment analysis, IHC, and NGS. Tumor mutational burden (TMB) was measured by totaling somatic mutations per tumor. HER2 positivity through IHC and CISH was determined based on 2007 and 2018 ASCO/CAP HER2 breast cancer guidelines. RESULTS: There was a higher rate of HER2 positivity by IHC when using the 2018 guidelines compared to the 2007 guidelines (16.3% vs 12.3%). Concordance between IHC and CISH was 98.9%. ERBB2 amplification was identified by NGS in 10.5% of tumors. Compared to CISH results, this corresponds to a concordance rate of 91.6% and a positive predictive value (PPV) of 60.3%. Single gene alterations in HER2 amplified tumors that may implicate HER2 therapy resistance included PI3K (33.1%), KRAS (2.5%), and PTEN (1.3%). CONCLUSIONS: There was high concordance between HER2 positivity based on CISH and IHC. Rate of HER2 positivity is the lowest by NGS. Ultimately these testing platforms need to be validated by response to targeted therapy.

Abortion in rural Ghana: Cultural norms, knowledge and attitudes.

Using qualitative methodology, semi-structured questionnaires were administered to participants in the Barakese subdistrict of Ghana in order to understand the extent to which men and women have knowledge of family planning services and in what ways cultural norms, practices, and attitudes toward abortion affect the decision to abort. Women in the community pursue abortion using unsafe methods, despite fear of shame, bleeding, infection, or death, as the perceived cost of maintaining the pregnancy is greater. Protective factors that were reported to dissuade women from pursuing unsafe abortion include fear of social disgrace, divine retribution, and death. Women reported the inability to control the timing of their pregnancies, despite harboring knowledge of family planning. Concerned about perceived side effects of modern family planning methods, respondents chose to use fertility awareness methods or to use no contraception. There remains a gap between knowledge of the benefits of and the actual use of family planning methods, leading to unwanted pregnancy and seeking unsafe abortion. Intensified health promotion and education regarding side effects to combat misconceptions related to contraception, as well as expanding alternative contraceptive options to all regions of Ghana, are critical to improve uptake.