Browsing by Author "Vuhahula,Edda A.M."

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    FNAB samples with the STRAT4 assay for breast cancer diagnosis – Authors' reply
    (The Lancet. Oncology, 2025-01-26) Vuhahula,Edda A.M.
    We thank Liqi Li for noting the myriad challenges of implementing leapfrog technologies in a resource-constrained setting. To clarify, our expectation in this pilot study,1 was not to demonstrate high levels of concordance for all biomarkers across all lysate preparation conditions. Our aims were: (1) to test different lysate preparation conditions to identify the optimal method that would facilitate use of off-label fine-needle aspiration biopsy (FNAB) specimens with the Xpert Breast Cancer STRAT4 Assay (STRAT4; Cepheid, Sunnyvale, CA, USA) in a resource-constrained setting; and (2) to assess whether similar concordance levels between results using FNAB specimens and previous results using formalin-fixed paraffin embedded specimens could be achieved.2 Previous studies of STRAT4 in sub-Saharan Africa have also explored multiple preparation methods to establish whether alternative, more reagent-efficient methods could be used.3,4 Although the inability to test all the samples using all sample preparation methods limited the ability to directly compare each method's performance, a sufficient number of samples were collected to assess each sample type independently. The College of American Pathologists (CAP) provides rigorous guidelines on anatomic pathology test validation.5 Using immunohistochemistry and fluorescence in-situ hybridisation results from another accredited laboratory as a reference standard during assay validation is a CAP-recommended practice. We also previously acknowledged that convenience sampling can introduce bias. Random sampling would not have been feasible in our study while ensuring the prospective collection of enough samples in a timely manner. The robust performance of STRAT4 for oestrogen receptor alone has the potential to markedly increase access to life-prolonging endocrine therapies in resource-constrained settings. However, the more modest performance of the other biomarkers reflect the need for additional FNAB lysis method optimisation before broader implementation. Additional studies evaluating real-world performance in resource-constrained settings will also be an essential next step. Our study provides an example of how leapfrog technologies for cancer diagnosis can be successfully investigated, using rigorous methodology, within a resource-constrained setting.
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    Xpert Breast Cancer STRAT4 Assay using fine-needle aspiration biopsy samples in a resource-constrained setting: a prospective diagnostic accuracy study
    (The Lancet Oncology, 2024-10-03) Vuhahula,Edda A.M.
    Summary Background Use of fine-needle aspiration biopsy (FNAB) specimens on Xpert Breast Cancer STRAT4 Assay (STRAT4; Cepheid, Sunnyvale, CA, USA), a CE-marked in-vitro diagnostic medical device, could potentially increase access to breast cancer biomarker testing in resource-constrained settings. We aimed to assess the performance of a research use-only version of STRAT4 using FNAB specimens in Tanzania. Methods In this prospective diagnostic accuracy study, patients aged 18 years or older with palpable breast masses presenting to the FNAB Clinic at Muhimbili National Hospital (Dar es Salaam, Tanzania) were recruited consecutively. Patients who were pregnant, lactating, or had a previous diagnosis of breast cancer were excluded. STRAT4 testing was performed on off-label FNAB samples using four protocols: the 1 × protocol (using the standard lysate method) on FNAB smears (1 × FNAB), quick lysis and Maui protocols (both on FNAB smears), and the 1 × protocol on formalin-fixed paraffin-embedded (FFPE) cell block material (1 × cell block). For 1 × FNAB and 1 × cell block, tissue was processed using FFPE lysis reagent, incubated at 80°C with proteinase K, and followed by addition of 95% or higher ethanol. Quick lysis was processed using FFPE lysis reagent and 95% or higher ethanol, whereas Maui was processed using a proprietary research-use only lysis reagent. The primary outcomes were overall concordance, sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) of STRAT4 as compared with immunohistochemistry or immunohistochemistry plus fluorescence in-situ hybridisation performed on cell blocks using clinically validated protocols in a Clinical Laboratory Improvement Amendments-accredited laboratory at the University of California, San Francisco (San Francisco, CA, USA). Findings Between Nov 29, 2017, and Dec 17, 2020, 208 patients were enrolled. Of 208 cases, 51 (25%) were excluded from analysis because of insufficient tissue in the cell block or absent cell blocks, leaving 157 participants (all female) for analysis. For oestrogen receptor, 1 × FNAB had the best performance, with an overall concordance of 95% (95% CI 90–100), sensitivity of 94% (85–100), specificity of 97% (90–100), and AUC of 0·96 (0·81−1·00). For progesterone receptor, 1 × cell block had the best overall performance (overall concordance 89% [95% CI 84–95], sensitivity 91% [82–99], and specificity 89% [81–97], with an AUC of 0·93 [0·89−0·99]) and 1 × FNAB performed the best among the smear protocols, with a concordance of 84% (95% CI 74–93), sensitivity of 63% (43–82), specificity of 97% (92–100), and AUC of 0·91 (0·72−0·97). For HER2, Maui had the highest agreement, with an overall concordance of 93% (95% CI 89–98), sensitivity of 96% (88–100), specificity of 92% (87–98), and AUC of 0·95 (0·98–1·00). For Ki67, Maui had the best performance of smear protocols, with a concordance of 73% (95% CI 64–82), sensitivity of 70% (58–81), specificity of 81% (66–96), and AUC of 0·80 (0·54−0·82). Interpretation Processing FNAB samples with STRAT4 is feasible in Tanzania, and performance for the oestrogen receptor is robust. Further optimisation of STRAT4 for FNAB has the potential to improve timely access to breast cancer diagnostics in resource-constrained settings. Funding US National Institutes of Health; UCSF Global Cancer Program, Helen Diller Family Comprehensive Cancer Center; UCSF Department of Pathology; and Cepheid.