{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T15:50:52Z","timestamp":1791820252070,"version":"4.3.4"},"reference-count":28,"publisher":"American Medical Association (AMA)","issue":"10","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Netw Open"],"abstract":"\n Importance<\/jats:title>\n Breast cancer subtyping based on immunohistochemistry (IHC) guides systemic therapy where gene expression profiling assays are unavailable, yet its validity against molecular reference standards remains poorly characterized in African populations, where laboratory infrastructure and access to pathology services are limited.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n To evaluate concordance between IHC-based breast cancer subtyping and PAM50 intrinsic subtypes in East and West African populations and identify resource-appropriate strategies to improve classification.<\/jats:p>\n <\/jats:sec>\n \n Design, Setting, and Participants<\/jats:title>\n This cross-sectional study included Kenyan (diagnosed 2012-2022) and Ghanaian women (diagnosed 2013-2015) with invasive breast cancer, from whom formalin-fixed, paraffin-embedded tumor specimens were collected during the same periods. Gene expression profiling and data analyses were performed between April 2020 and August 2026 for both cohorts.<\/jats:p>\n <\/jats:sec>\n \n Exposures<\/jats:title>\n \n Tumor subtyping using standard IHC markers (estrogen receptor [ER], progesterone receptor [PR], and\n ERBB2<\/jats:italic>\n status and Ki-67) and histologic grade vs PAM50 intrinsic subtyping derived from a gene expression panel.\n <\/jats:p>\n <\/jats:sec>\n \n Main Outcomes and Measures<\/jats:title>\n Concordance between IHC-based and PAM50 intrinsic subtypes was assessed using Cohen \u03ba statistics, with sensitivity and specificity calculated against PAM50.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Among 460 women in Kenya with breast cancer (mean [SD] age at diagnosis, 50.3 [12.5] years), 224 (49.4%) had grade 3 disease and 148 (42.3%) had stage III or IV tumors. A total of 451 women in Ghana with breast cancer (mean [SD] age, 49.9 [12.0] years; 317 [75.1%] with grade 3 disease) were enrolled as a validation cohort. PAM50 classified patients\u2019 tumors as luminal A (201 tumors [43.7%]), luminal B (82 tumors [17.8%]),\n ERBB2<\/jats:italic>\n -enriched (50 tumors [10.9%]), basal-like (99 tumors [21.5%]), and normal-like (28 tumors [6.1%]). Concordance between IHC and PAM50 was highest for basal-like tumors (sensitivity ranging from 73.3% [95% CI, 61.9%-82.9%] to 79.6% [95% CI, 70.3%-87.1%]; specificity ranging from 96.9% [95% CI, 93.9%-98.6%] to 97.3% [95% CI, 94.9%-98.7%]) and moderate for\n ERBB2<\/jats:italic>\n -enriched tumors (sensitivity was 50.0% across all schemes, with 95% CIs ranging from 33.8%-66.2% to 35.5%-64.5%; specificity ranging from 97.6% [95% CI, 95.6%-98.9%] to 97.9% [95% CI, 95.6%-99.2%]). Luminal subtypes showed substantial misclassification using ER, PR, and\n ERBB2<\/jats:italic>\n status alone. Incorporation of Ki-67 (\u226520%) or histologic grade improved discrimination between luminal A and luminal B tumors, increasing luminal B classification from 12.2% (95% CI, 8.5%-16.7%) to 41.2% (95% CI, 35.2%-47.4%), even when PR status was excluded from the panel. Findings were independently validated in women with breast cancer from Ghana.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions and Relevance<\/jats:title>\n In this cross-sectional study of African breast cancer populations, standard IHC markers performed well for basal-like tumors but frequently misclassified luminal subtypes without proliferation markers. When testing was constrained, proliferation markers contributed more to molecular approximation than PR, with histologic grade providing useful information when Ki-67 was unavailable. These findings support tiered, resource-adapted classification where molecular assays are inaccessible.<\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jamanetworkopen.2026.38664","type":"journal-article","created":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T15:30:24Z","timestamp":1791819024000},"page":"e2638664","source":"Crossref","is-referenced-by-count":0,"title":["Immunohistochemistry vs Molecular Breast Cancer Subtyping Among African Populations"],"prefix":"10.1001","volume":"9","author":[{"given":"Shahin","family":"Sayed","sequence":"first","affiliation":[{"name":"Aga Khan University Hospital, Nairobi, Kenya"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Feng","sequence":"additional","affiliation":[{"name":"Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hela","family":"Koka","sequence":"additional","affiliation":[{"name":"Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manel Haj","family":"Mansour","sequence":"additional","affiliation":[{"name":"Aga Khan University Hospital, Nairobi, Kenya"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Difei","family":"Wang","sequence":"additional","affiliation":[{"name":"Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland"},{"name":"Cancer Genomics Research Laboratory, Leidos Biomedical Research, Inc, Frederick, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Brown","sequence":"additional","affiliation":[{"name":"Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland"},{"name":"Cancer Genomics Research Laboratory, Leidos Biomedical Research, Inc, Frederick, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristine","family":"Jones","sequence":"additional","affiliation":[{"name":"Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland"},{"name":"Cancer Genomics Research Laboratory, Leidos Biomedical Research, Inc, Frederick, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret","family":"Maina","sequence":"additional","affiliation":[{"name":"Aga Khan University Hospital, Nairobi, Kenya"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronica","family":"Ngundo","sequence":"additional","affiliation":[{"name":"Aga Khan University Hospital, Nairobi, Kenya"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfred Mburu","family":"Githuka","sequence":"additional","affiliation":[{"name":"Aga Khan University Hospital, Nairobi, Kenya"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zaitun","family":"Ajuoga","sequence":"additional","affiliation":[{"name":"Aga Khan University Hospital, Nairobi, Kenya"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaoqi","family":"Fan","sequence":"additional","affiliation":[{"name":"Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amber N.","family":"Hurson","sequence":"additional","affiliation":[{"name":"Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xing","family":"Hua","sequence":"additional","affiliation":[{"name":"Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland"},{"name":"Cancer Genomics Research Laboratory, Leidos Biomedical Research, Inc, Frederick, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petra","family":"Lenz","sequence":"additional","affiliation":[{"name":"Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland"},{"name":"Cancer Genomics Research Laboratory, Leidos Biomedical Research, Inc, Frederick, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosemary Wangari","family":"Kamau","sequence":"additional","affiliation":[{"name":"AIC Kijabe Hospital, Kijabe, Kenya"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beryl Akinyi","family":"Ooro","sequence":"additional","affiliation":[{"name":"AIC Kijabe Hospital, Kijabe, Kenya"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francis","family":"Makokha","sequence":"additional","affiliation":[{"name":"Mount Kenya University, Nairobi, Kenya"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Ambs","sequence":"additional","affiliation":[{"name":"Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaron M.","family":"Rozeboom","sequence":"additional","affiliation":[{"name":"Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland"},{"name":"Cancer Genomics Research Laboratory, Leidos Biomedical Research, Inc, Frederick, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy","family":"Hutchinson","sequence":"additional","affiliation":[{"name":"Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland"},{"name":"Cancer Genomics Research Laboratory, Leidos Biomedical Research, Inc, Frederick, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Belynda","family":"Hicks","sequence":"additional","affiliation":[{"name":"Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland"},{"name":"Cancer Genomics Research Laboratory, Leidos Biomedical Research, Inc, Frederick, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mustapha","family":"Abubakar","sequence":"additional","affiliation":[{"name":"Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohong R.","family":"Yang","sequence":"additional","affiliation":[{"name":"Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"10","published-online":{"date-parts":[[2026,10,12]]},"reference":[{"issue":"4","key":"zoi261037r1","doi-asserted-by":"publisher","first-page":"1154","DOI":"10.1038\/s41591-025-03502-3","article-title":"Global patterns and trends in breast cancer incidence and mortality across 185 countries.","volume":"31","author":"Kim","year":"2025","journal-title":"Nat Med"},{"key":"zoi261037r2","doi-asserted-by":"publisher","DOI":"10.1016\/j.eclinm.2024.102894","article-title":"An economic evaluation of breast cancer interventions in Kenya.","volume":"77","author":"Hutchinson","year":"2024","journal-title":"EClinicalMedicine"},{"issue":"1","key":"zoi261037r3","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1038\/s41523-022-00423-z","article-title":"PAM50 subtyping and ROR score add long-term prognostic information in premenopausal breast cancer patients.","volume":"8","author":"Lundgren","year":"2022","journal-title":"NPJ Breast Cancer"},{"issue":"1","key":"zoi261037r4","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1186\/s13058-017-0911-9","article-title":"Prognostic value of PAM50 and risk of recurrence score in patients with early-stage breast cancer with long-term follow-up.","volume":"19","author":"Ohnstad","year":"2017","journal-title":"Breast Cancer Res"},{"issue":"8","key":"zoi261037r5","doi-asserted-by":"publisher","first-page":"1160","DOI":"10.1200\/JCO.2008.18.1370","article-title":"Supervised risk predictor of breast cancer based on intrinsic subtypes.","volume":"27","author":"Parker","year":"2009","journal-title":"J Clin Oncol"},{"issue":"5","key":"zoi261037r6","doi-asserted-by":"publisher","first-page":"4518","DOI":"10.1245\/s10434-026-19176-1","article-title":"St. Gallen International Breast Cancer Consensus-based clinical decision validation: concordance assessment between deep large language model outputs and global expert panel recommendations.","volume":"33","author":"Pan","year":"2026","journal-title":"Ann Surg Oncol"},{"issue":"9","key":"zoi261037r7","doi-asserted-by":"publisher","first-page":"2206","DOI":"10.1093\/annonc\/mdt303","article-title":"Personalizing the treatment of women with early breast cancer: highlights of the St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2013.","volume":"24","author":"Goldhirsch","year":"2013","journal-title":"Ann Oncol"},{"issue":"3","key":"zoi261037r8","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1016\/j.clbc.2024.11.024","article-title":"Universal genetic counseling and testing for Black women: a risk-stratified approach to addressing breast cancer disparities.","volume":"25","author":"Pleasant","year":"2025","journal-title":"Clin Breast Cancer"},{"issue":"1","key":"zoi261037r9","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1186\/s13058-021-01446-3","article-title":"Breast cancer risk factors in relation to molecular subtypes in breast cancer patients from Kenya.","volume":"23","author":"Sayed","year":"2021","journal-title":"Breast Cancer Res"},{"issue":"2","key":"zoi261037r10","doi-asserted-by":"publisher","first-page":"425","DOI":"10.1007\/s10549-017-4511-2","article-title":"Ethnicity and breast cancer characteristics in Kenya.","volume":"167","author":"Sayed","year":"2018","journal-title":"Breast Cancer Res Treat"},{"issue":"20","key":"zoi261037r11","doi-asserted-by":"publisher","first-page":"2105","DOI":"10.1200\/JCO.2018.77.8738","article-title":"Human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology\/College of American Pathologists clinical practice guideline focused update.","volume":"36","author":"Wolff","year":"2018","journal-title":"J Clin Oncol"},{"issue":"4","key":"zoi261037r12","doi-asserted-by":"publisher","first-page":"462","DOI":"10.1158\/1055-9965.EPI-24-0390","article-title":"Contribution of Prediagnostic host factors to shaping the stromal microenvironment of breast cancer among Sub-Saharan African women.","volume":"34","author":"Abubakar","year":"2025","journal-title":"Cancer Epidemiol Biomarkers Prev"},{"issue":"6","key":"zoi261037r13","doi-asserted-by":"publisher","first-page":"1535","DOI":"10.1002\/ijc.32929","article-title":"Reproductive factors and risk of breast cancer by tumor subtypes among Ghanaian women: a population-based case-control study.","volume":"147","author":"Figueroa","year":"2020","journal-title":"Int J Cancer"},{"issue":"12","key":"zoi261037r14","doi-asserted-by":"publisher","first-page":"2667","DOI":"10.1002\/ijc.30688","article-title":"Design considerations for identifying breast cancer risk factors in a population-based study in Africa.","volume":"140","author":"Brinton","year":"2017","journal-title":"Int J Cancer"},{"key":"zoi261037r15","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1177\/001316446002000104","article-title":"A coefficient of agreement for nominal scales.","volume":"20","author":"Cohen","year":"1960","journal-title":"Educ Psychol Meas"},{"issue":"4","key":"zoi261037r16","doi-asserted-by":"publisher","first-page":"798","DOI":"10.1158\/1055-9965.EPI-18-0863","article-title":"PAM50 molecular intrinsic subtypes in the Nurses\u2019 Health Study cohorts.","volume":"28","author":"Kensler","year":"2019","journal-title":"Cancer Epidemiol Biomarkers Prev"},{"issue":"1","key":"zoi261037r17","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1007\/s10549-023-06888-1","article-title":"Reproducibility and intratumoral heterogeneity of the PAM50 breast cancer assay.","volume":"199","author":"Hurson","year":"2023","journal-title":"Breast Cancer Res Treat"},{"issue":"1","key":"zoi261037r18","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s10549-023-06886-3","article-title":"Discordance between PAM50 intrinsic subtyping and immunohistochemistry in South African women with breast cancer.","volume":"199","author":"Dix-Peek","year":"2023","journal-title":"Breast Cancer Res Treat"},{"issue":"21","key":"zoi261037r19","doi-asserted-by":"publisher","first-page":"5222","DOI":"10.1158\/1078-0432.CCR-10-1282","article-title":"A comparison of PAM50 intrinsic subtyping with immunohistochemistry and clinical prognostic factors in tamoxifen-treated estrogen receptor-positive breast cancer.","volume":"16","author":"Nielsen","year":"2010","journal-title":"Clin Cancer Res"},{"key":"zoi261037r20","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1186\/1755-8794-5-44","article-title":"PAM50 breast cancer subtyping by RT-qPCR and concordance with standard clinical molecular markers.","volume":"5","author":"Bastien","year":"2012","journal-title":"BMC Med Genomics"},{"issue":"3","key":"zoi261037r21","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1007\/s10549-022-06769-z","article-title":"Intrinsic subtypes in Ethiopian breast cancer patient.","volume":"196","author":"Desalegn","year":"2022","journal-title":"Breast Cancer Res Treat"},{"issue":"1","key":"zoi261037r22","doi-asserted-by":"publisher","first-page":"1127","DOI":"10.1186\/s12885-024-12867-6","article-title":"PAM50 breast cancer subtypes and survival of patients in rural Ethiopia without adjuvant treatment: a prospective observational study.","volume":"24","author":"Ball\u00e9","year":"2024","journal-title":"BMC Cancer"},{"issue":"10","key":"zoi261037r23","doi-asserted-by":"publisher","first-page":"736","DOI":"10.1093\/jnci\/djp082","article-title":"Ki67 index, HER2 status, and prognosis of patients with luminal B breast cancer.","volume":"101","author":"Cheang","year":"2009","journal-title":"J Natl Cancer Inst"},{"issue":"22","key":"zoi261037r24","doi-asserted-by":"publisher","first-page":"1656","DOI":"10.1093\/jnci\/djr393","article-title":"Assessment of Ki67 in breast cancer: recommendations from the International Ki67 in Breast Cancer working group.","volume":"103","author":"Dowsett","year":"2011","journal-title":"J Natl Cancer Inst"},{"issue":"24","key":"zoi261037r25","doi-asserted-by":"publisher","first-page":"1897","DOI":"10.1093\/jnci\/djt306","article-title":"An international Ki67 reproducibility study.","volume":"105","author":"Polley","year":"2013","journal-title":"J Natl Cancer Inst"},{"issue":"7","key":"zoi261037r26","doi-asserted-by":"publisher","first-page":"808","DOI":"10.1093\/jnci\/djaa201","article-title":"Assessment of Ki67 in breast cancer: updated recommendations from the International Ki67 in Breast Cancer Working Group.","volume":"113","author":"Nielsen","year":"2021","journal-title":"J Natl Cancer Inst"},{"key":"zoi261037r27","doi-asserted-by":"publisher","DOI":"10.1016\/j.humpath.2025.105819","article-title":"Artificial intelligence in breast pathology: overview and recent updates.","volume":"162","author":"Datwani","year":"2025","journal-title":"Hum Pathol"},{"issue":"12","key":"zoi261037r28","doi-asserted-by":"publisher","first-page":"1346","DOI":"10.1200\/JCO.19.02309","article-title":"Estrogen and progesterone receptor testing in breast cancer: ASCO\/CAP guideline update.","volume":"38","author":"Allison","year":"2020","journal-title":"J Clin Oncol"}],"container-title":["JAMA Network Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/jamanetwork.com\/journals\/jamanetworkopen\/articlepdf\/2855218\/sayed_2026_oi_261037_1791317992.12943.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T15:30:25Z","timestamp":1791819025000},"score":1,"resource":{"primary":{"URL":"https:\/\/jamanetwork.com\/journals\/jamanetworkopen\/fullarticle\/2855218"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,12]]},"references-count":28,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2026,10,1]]}},"URL":"https:\/\/doi.org\/10.1001\/jamanetworkopen.2026.38664","relation":{},"ISSN":["2574-3805"],"issn-type":[{"value":"2574-3805","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,12]]}}}