Abstract 61: Optimizing Breast Cancer Subtyping in Kenya: Concordance Between Immunohistochemistry and PAM50 Molecular Classification and Strategies for Resource-Limited Settings

Abstract Purpose: Accounting for over 25% of cancer incidence, breast cancer is the second most common cause of cancer mortality among females in Kenya. Over 80% of Kenyan women diagnosed with breast cancer are unlikely to survive more than 5 years. Multiple barriers exist to early diagnosis, including access to specialist services and affordability of ancillary testing such as immunohistochemistry (IHC). The aims of our study were to evaluate the performance of IHC for estrogen (ER), progesterone (PR), HER2, and Ki67 in subtyping of breast cancer tissue by comparing them against the gold standard PAM50 intrinsic subtypes and to establish an optimal strategy for biomarker testing in a resource-limited setting such as Kenya. Methods: A total of 467 formalin-fixed paraffin-embedded (FFPE) breast tumor tissues from newly diagnosed Kenyan women with breast cancer were analyzed using NanoString nCounter (fifty PAM50 genes within a ∼ 600 gene panel) for transcriptome-based subtyping according to PAM50 classification. IHC-based subtypes were assigned to the same tumors following the ASCO/CAP guidelines for ER/PR/HER2 and Ki67 when available (with a cutoff of >/= 20%) and compared to PAM50 subtypes using Kappa statistics as well as subtype-specific sensitivity and specificity. Results: Overall, the cohort mean age was 50.57 years (SD = 12.44), with 50% of tumors classified as grade 3 and 42% at advanced stages (III/IV). The intrinsic subtype classification by PAM50 categorized 205 (43.9%), 83 (17.8%), 51 (10.9%), 99 (21.2%), and 29 (6.2%) as Luminal A, Luminal B, HER2-enriched, basal-like, and normal-like, respectively. The highest concordance between IHC-based and PAM50 transcriptome-based subtyping was observed when Ki67 was added to distinguish Luminal A from Luminal B. This improvement with Ki67 was sustained even when PR was excluded. The proportion of Luminal B subtypes increased by 28.41%, with 77 additional cases reclassified from Luminal A to Luminal B out of 271 Luminal patients, incorporating the proliferation marker Ki-67, or Grade, as a surrogate if Ki-67 was unavailable. Conclusion: Overall, there was a good concordance of IHC and PAM50 for Luminal A and Basal-like breast cancer based on ER, PR, Her2. The incorporation of Ki67 and/or grade can improve the diagnosis of Luminal B patients who may benefit from therapy in addition to endocrine therapy. We note that PR could potentially be replaced by Ki67 where resources are limited. Citation Format: Shahin Sayed, Li Feng, Hela Koka, Difei Wang, Maria Brown, Kristine Jones, Margaret Maina, Veronica Ngundo, Alfred M. Githuka, Zaitun Ajuoga, Shaoqi Fan, Amber Hurson, Xing Hua, Petra Lenz, Rosemary W. Kamau, Beryl A. Ooro, Francis Makokha, Stefan Ambs, Aaron M. Rozeboom, Amy Hutchinson, Belynda Hicks, Mustapha Abubakar, Jonine Figueroa, Xiaohong R. Yang. Optimizing Breast Cancer Subtyping in Kenya: Concordance Between Immunohistochemistry and PAM50 Molecular Classification and Strategies for Resource-Limited Settings [abstract]. In: Proceedings of the 13th Annual Symposium on Global Cancer Research; 2025 Sep 16. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2025;34(12_Suppl):Abstract nr 61.