Immunohistochemical Characterization of Breast Carcinoma: Clinical Correlations, Molecular Subtypes, and Therapeutic Implications Immunohistochemical Characterization of BC

Shaikhali Barodawala (1), Kunjal Lila (2), Kirti Chadha (3), Gauri Pradhan (4), Pooja Parab (5), Raj Jatale (6), Shibani Ramchandran (7)
(1) Metropolis Healthcare LTD, Mumbai, India, India,
(2) Metropolis Healthcare LTD, Mumbai, India, India,
(3) Metropolis Healthcare LTD, Mumbai, India, India,
(4) Metropolis Healthcare LTD, Mumbai, India, India,
(5) Metropolis Healthcare LTD, Mumbai, India, India,
(6) Metropolis Healthcare LTD, Mumbai, India, India,
(7) Metropolis Healthcare LTD, Mumbai, India, India

Abstract

Background: Breast carcinoma exhibits heterogeneity in terms of morphology, molecular, treatment response, and clinical outcomes. The objective of the study was to classify the various malignant breast cancer cases based on their immunohistochemical characteristics and understand their association and behavior, which may be useful for predicting treatment and prognosis.


Methods: In this study, 12808 malignant breast cancer cases were studied based on hormone receptor IHC biomarkers, age, gender, histological type, grade and molecular classifiers.


Results: The mean age of patients was 53.63+13.08 years, around 45.43% were grade 3 tumors and the invasive duct carcinoma of non-specified type (NST) was the most common type seen (93.83%). ER positivity was 83.89% in grade 1, 69.9% in grade 2, and 36.86% in grade 3 tumors, and the overall PR and Her-2 positivity was 47.06% and 18.67%, respectively. A relatively higher percentage of Triple Negative cases was seen (36.58%), followed by 25.43% Luminal A cases. There was a significant association between molecular subtypes with respect to age, gender, Scarff Bloom Richardson (SBR) grade, and histological type (P<0.0001). Overall, grade 3 tumor cases were most common, the majority of which were Triple Negative.  Maximum cases of triple negative tumors were seen among women, being mostly concentrated in younger age group i.e. <40 years.


Conclusion: Immunohistochemistry for hormone receptor positivity remains the mainstay of diagnosis and molecular sub-classification. The hormone response of tumors is important prognostically, in predicting the treatment outcomes. Going further, molecular analysis and gene expression studies can further augment the histopathological diagnosis to assist strategies of targeted therapy and precision medicine resulting in better patient outcomes.

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References

International Agency for Research on Cancer. India Source: Globocan 2020. Available from: https://gco.iarc.fr/today/data/factsheets/populations/356-india-fact-sheets.pdf

DeSantis C, Siegel R, Bandi P, Jemal A. Breast cancer statistics, 2011. CA Cancer J Clin 2011; 61: 409-418. doi: 10.3322/caac.20134

Mehrotra R, Yadav K. Breast cancer in India: Present scenario and the challenges ahead. World J Clin Oncol 2022; 13(3): 209-218

Arpita J, Priyanka G, Ranjana S. A Study of Molecular Subtypes of Carcinoma Breast by Immunohistochemistry at Tertiary Care Center, Jaipur. Asian Pacific Journal of Cancer Biology, 2022:7(3), 219-223. doi:10.31557/apjcb.2022.7.3.219-223.

Nielsen TO, Hsu FD, Jensen K, Cheang M, Karaca G, Hu Z, Hernandez-Boussard T, et al. Immunohistochemical and clinical characterization of the basal-like subtype of invasive breast carcinoma. Clinical Cancer Research: An Official Journal of the American Association for Cancer Research. 2004 08 15;10(16):5367- 5374. doi:10.1158/1078-0432.CCR-04-0220

Yeh IT, Mies C. Application of Immunohistochemistry to Breast Lesions. Arch Pathol Lab Med. 2008;132:349– 358

Achalkar GV. Immunohistochemistry in breast carcinoma. Ind J Pathol Oncol, 2018;5(3):415-417

Mittal, A., & Mani, N. (2021). Molecular classification of breast cancer. Indian Journal of Pathology and Oncology, 8(2), 241–247. doi:10.18231/j.ijpo.2021.047

Sundar S, Khetrapal-Singh P, Frampton J, Trimble E, Rajaraman P, Mehrotra R, et al. Harnessing genomics to improve outcomes for women with cancer in India: key priorities for research. Lancet Oncol 2018; 19: e102-e112. doi: 10.1016/S1470-2045(17)30726-X

Board, W. C. O. T. E. (2019). WHO classification of breast tumours: WHO Classification of Tumours, Volume 2. International Agency for Research on Cancer.

(College of American Pathologists, 2023) https://www.cap.org/protocols-and-guidelines/cap-guidelines/current-cap-guidelines/guideline-recommendations-for-immunohistochemical-testing-of-estrogen-and-progesterone-receptors-in-breast-cancer

Ahmad Fauzi MF, Wan Ahmad WSHM, Jamaluddin MF, Lee JTH, Khor SY, Looi LM, et al. Allred Scoring of ER-IHC Stained Whole-Slide Images for Hormone Receptor Status in Breast Carcinoma. Diagnostics (Basel). 2022 Dec 8;12 (12):3093. doi: 10.3390/diagnostics12123093.

https://www.agilent.com/en/product/pharmdx/herceptest-kits/herceptest-mab-pharmdx-dako-omnis-1324550

https://www.molecular.abbott/int/en/products/oncology/pathvysion-her-2-dna-probe-kit-II

http://www.accessdata.fda.gov/cdrh_docs/pdf6/k061602.pdf BioView Duet approval for PathVysion

http://www.accessdata.fda.gov/cdrh_docs/pdf8/k080909.pdf Ikonisys approval for PathVysion

The molecular subtypes of breast cancer. (n.d.) https://www.breastcancer.org/types/molecular-subtypes

Ambroise M, Ghosh M, Mallikarjuna VS, Kurian A. Immunohistochemical profile of breast cancer patients at a tertiary care hospital in South India. Asian Pac J Cancer Prev. 2011;12(3):625-9.

Upadhyay AK, Prakash A. Clinicopathological Profile of Breast Cancer at a Tertiary Cancer Center in Jharkhand, India: A Descriptive Cohort Study. Cureus. 2023 Jun 5;15(6):e39990. doi: 10.7759/cureus.39990.

Kim EK, Park SY, Kim SW. Clinicopathological characteristics of BRCA-associated breast cancer in Asian patients. J Pathol Transl Med. 2020 Jul;54(4):265-275. doi: 10.4132/jptm.2020.04.07.

Britta Weigelt, Felipe C. Geyer, Jorge S. Reis-Filho. Histological types of breast cancer: How special are they? Molecular Oncology,Volume 4, Issue 3,2010, Pages 192-208,ISSN 1574-

Clusan L, Ferrière F, Flouriot G, Pakdel F. A Basic Review on Estrogen Receptor Signaling Pathways in Breast Cancer. Int J Mol Sci. 2023 Apr 6;24(7):6834. doi: 10.3390/ijms24076834.

Ditsch N, Kolberg-Liedtke C, Friedrich M, Jackisch C, Albert US, Banys-Paluchowski M, et al. AGO Recommendations for the Diagnosis and Treatment of Patients with Early Breast Cancer: Update 2021. Breast Care (Basel). 2021 Jun;16(3):214-227. doi: 10.1159/000516419.

Mboungou Malanda DM, Magloire Boumba AL, Malonga GA, Mouamb FG, Mambouene FD, Moukassa D, et al. Breast cancer in women: epidemiological, histological, immunohistochemical and molecular sub-types in the Republic of Congo. Int J Health Sci Res. 2021; 11(5): 103-116. doi:10.52403/ijhsr.20210515

Inwald EC, Klinkhammer-Schalke M, Hofstädter F, Zeman F, Koller M, Gerstenhauer M, et al. Ki-67 is a prognostic parameter in breast cancer patients: results of a large population-based cohort of a cancer registry. Breast Cancer Res Treat. 2013 Jun;139(2):539-52. doi: 10.1007/s10549-013-2560-8.

de Azambuja E, Cardoso F, de Castro G, Colozza M, Jr, Mano MS, Durbecq V, et al. Ki-67 as prognostic marker in early breast cancer: a meta-analysis of published studies involving 12,155 patients. Br J Cancer. 2007;96(10):1504–1513. doi: 10.1038/sj.bjc.6603756.

Jonnada PK, Sushma C, Karyampudi M, Dharanikota A. Prevalence of Molecular Subtypes of Breast Cancer in India: a Systematic Review and Meta-analysis. Indian J Surg Oncol. 2021 Apr;12(Suppl 1):152-163. doi: 10.1007/s13193-020-01253-w.

Kumar N, Patni P, Agarwal A, Khan MA, Parashar N. Prevalence of molecular subtypes of invasive breast cancer: A retrospective study. Med J Armed Forces India. 2015 Jul;71(3):254-8. doi: 10.1016/j.mjafi.2015.04.006.

Sotiriou C, Pusztai L. Gene-expression signatures in breast cancer. N Engl J Med. 2009; 360(8): 790- 800.

Hu Z, Fan C, Oh DS, Marron JS, He X, et al. The molecular portraits of breast tumors are conserved across microarray platforms. BMC Genomics. 2006; 7: 96.

Foulkes WD, Smith IE, Reis-Filho JS. Triple-negative breast cancer. The New England Journal of Medicine. 2010 Nov 11;363(20):1938-1948. doi:10.1056/ NEJMra1001389

Almansour NM. Triple-Negative Breast Cancer: A Brief Review About Epidemiology, Risk Factors, Signaling Pathways, Treatment and Role of Artificial Intelligence. Front Mol Biosci. 2022 Jan 25;9:836417. doi: 10.3389/fmolb.2022.836417.

Dent R, Trudeau M, Pritchard KI, Hanna WM, Kahn HK, Sawka CA, et al. Triple-negative Breast Cancer: Clinical Features and Patterns of Recurrence. Clin Cancer Res. 2007:13, 4429–4434. doi:10.1158/1078-0432.ccr-06- 3045.

Akhtar M, Dasgupta S, Rangwala M. Triple negative breast cancer: an Indian perspective. Breast Cancer (Dove Med Press). 2015 Aug 14;7:239-43. doi: 10.2147/BCTT.S85442.

Weigelt B, Baehner FL, Reis-Filho JS. The contribution of gene expression profiling to breast cancer classification, prognostication and prediction: a retrospective of the last decade. J Pathol. 2010:220:263–280.

Authors

Shaikhali Barodawala
Kunjal Lila
Kirti Chadha
Gauri Pradhan
Pooja Parab
Raj Jatale
raj.jatale@metropolisindia.com (Primary Contact)
Shibani Ramchandran
1.
Barodawala S, Lila K, Chadha K, Pradhan G, Parab P, Jatale R, Ramchandran S. Immunohistochemical Characterization of Breast Carcinoma: Clinical Correlations, Molecular Subtypes, and Therapeutic Implications: Immunohistochemical Characterization of BC. Arch Breast Cancer [Internet]. 2024 May 1 [cited 2024 Jun. 16];11(2):108-17. Available from: https://www.archbreastcancer.com/index.php/abc/article/view/901

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