External Quality Assurance Helps Improve Infrastructure for Testing Breast Biomarkers Across a Lower- and Middle-Income Country: Our Experience With Breast Biomarker Testing in the National Cancer Grid External Quality Assurance System in India.

CONTEXT.­: Biomarkers in breast cancer need strict monitoring given their role in patient management. OBJECTIVE.­: To study the impact that regular participation in the National Cancer Grid (NCG) external quality assurance (EQA) system has on concordance rates for biomarkers in breast carcinoma. DESIGN.­: Tissue microarrays (TMAs) containing breast carcinomas were circulated to participating laboratories that performed immunohistochemistry for breast biomarkers. The returned TMAs were then assessed for test concordance. RESULTS.­: A total of 105 laboratories participated in the estrogen receptor (ER) and progesterone receptor (PR) EQA system cycles, and 99 centers participated in the human epidermal growth factor 2 (HER2) EQA system. In the ER EQA in the first cycle only 1 laboratory had a 100% concordance rate, which improved to 59 of 77 (76.6%) and 85 of 97 (87.6%) in the fourth and fifth cycles, respectively. In the PR EQA the 100% pass rate jumped from zero to 52 of 76 (68.4%) in the fourth cycle and 86 of 97 (88.6%) in the last cycle. For HER2 EQA, the 100% pass rates were seen in 7 of 23 laboratories (30.4%) in the first cycle, 49 of 78 laboratories (62.8%) in the fourth cycle, and 48 of 94 laboratories (51.1%) in fifth cycle of EQA. Centers that participated in the NCG EQA system for a longer period often changed testing methodology, with consequent improvement in their laboratory concordance rates. An increasing trend for the use of automated platforms and of the US Food and Drug Administration-approved antibody for HER2 testing was observed. CONCLUSIONS.­: Our experience demonstrates that laboratory performance improves with participation in an EQA system even in less perfect settings, and this drives the placement of more proficient practices across the country.

Yoga to improve maternal mental health and immune function during the COVID-19 crisis (Yoga-M 2 trial): study protocol for a pilot randomized controlled trial.

Background: Mental health of women is adversely affected during pregnancy. A huge proportion of pregnant women suffer from stress and depression which negatively impacts birthweight and neuro-cognitive development of the fetus. The current crisis due to the COVID-19 pandemic further adds to the stressful situation. Yoga practiced during pregnancy has beneficial effects on improving stress and depression and preliminary evidence suggests that yoga-based interventions can improve immunity. This study aims to examine the feasibility, acceptability, and preliminary efficacy of a Yoga-based intervention for maternal Mental health and i Mmunity (Yoga-M 2) in a rural community in India.     Methods: The study design will be a single-blind individual randomized parallel group-controlled pilot trial with 1:1 allocation ratio. Adult pregnant women, with gestational age between 12-24 weeks will be randomly allocated to either the Yoga-M 2 group or the Enhanced Usual Care (EUC) group. Participants in the Yoga-M 2 arm will attend weekly group yoga sessions for 12 weeks and will be encouraged to practice yoga at home. In the EUC arm, participants will receive a single session of health education. Eligibility of the participants, recruitment, retention-in-care, and study completion rates will be estimated and feasibility of delivering Yoga-M 2 and acceptability of this intervention by the participants will be assessed. Change in the scores of the Perceived Stress Scale (PSS), EuroQoL 5 Dimensions Score (EQ-5D-5L), Wisconsin Upper Respiratory Symptom Severity Scale (WURSS-21), and serum C-Reactive Protein at three-months post-randomization will be used to assess preliminary efficacy.   Discussion: The key outputs of this trial will be a structured intervention manual and evidence about the feasibility, acceptability, and preliminary efficacy of the intervention, establishing the foundation to undertake an explanatory randomized controlled trial to assess efficacy and cost-effectiveness of Yoga-M 2 intervention.  Trial registration: CTRI/2022/01/039701. Prospectively registered with the Clinical Trials Registry of India on 25 January 2022.

Dual-color dual-hapten in situ hybridization (D-DISH) - Comparison with fluorescence in situ hybridization (FISH) for HER2/neu testing in breast cancer.

CONTEXT: HER2/neu testing in breast cancer is a mandate due to availability of trastuzumab, a monoclonal antibody targeted against this biomarker. Dual-color dual-hapten in situ hybridization (D-DISH) is a new test for assessment of HER2/neu gene overexpression on light microscopy. AIMS: This was a validation study for D-DISH in our laboratory and was conducted to study the concordance between fluorescence in situ hybridization (FISH) and D-DISH for HER2/neu testing in breast cancer. MATERIALS AND METHODS: In all, 150 cases of invasive breast carcinoma requested for FISH analysis were selected. Immunohistochemistry by Ventana PATHWAY anti-HER2/neu (4B5) antibody, FISH by ZytoLight SPEC ERBB2/CEN17 Dual Color Probe, and D-DISH using the Ventana INFORM HER2 Dual ISH DNA Probe Cocktail Assay was carried out. STATISTICAL ANALYSIS: Cohen's kappa coefficient was used to calculate concordance between FISH and D-DISH assays. The ratios and average number of signals were compared with Lin's concordance correlation coefficient. RESULTS: About 93.1% of the cases showed concordance between FISH and D-DISH results. Cohen's kappa correlation coefficient was 0.836, indicating almost perfect level of agreement. Lin's concordance correlation coefficient (ρc) showed moderate strength of agreement for HER2/chromosome 17 ratios between FISH and D-DISH assays (ρc 0.9452). As per the American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) 2018 updated guidelines, four of the cases that were nonamplified on FISH showed low-level amplification on D-DISH due to counting errors caused by faint signals or background dust. Genomic heterogeneity and larger red chromosome 17 signals on D-DISH led to discordance of the six cases amplified by FISH. D-DISH failure rate was 3.33%. CONCLUSION: Overall, D-DISH showed good concordance with FISH but needs expertise for reporting.