HER2 Status in Breast Cancer in Relation to Age and Tumor Histological Type: A Cross-Sectional Study from Karbala Iraq
HER2 Status in Breast Cancer in Karbala Iraq
Abstract
BACKGROUND HER2 overexpression marks out a biologically aggressive targetable subset of breast cancer accounting for 15–20% of cases in Western series Data from Iraq are limited and Karbala Province has not been studied before MATERIALS AND METHODS We reviewed 99 women with confirmed invasive breast cancer at a single Karbala centre grouped into four age bands (28–39 40–49 50–59 60–69 years) HER2 was scored 0 1+ 2+ or 3+ by immunohistochemistry (IHC) using the 2013 ASCOCAP guideline We tested associations with age and histological type using chisquare tests and multivariable logistic regression (HER2 3+ as the dependent variable) reporting odds ratios (OR) and 95% confidence intervals (CI) RESULTS The 40–49year band was largest (333%) Invasive ductal carcinoma was the most common type (566%) followed by locally advanced disease (162%) invasive lobular carcinoma (121%) metastatic carcinoma (81%) and triplenegative breast cancer (71%) Fortyseven tumours (475%) were HER2negative (IHC 0); of the rest 13 (131%) scored 1+ 13 (131%) scored 2+ (equivocal) and 26 (263%) scored 3+ meeting strict ASCOCAP positivity criteria HER2 score was not linked to age (χ² = 782 p = 025) but histology varied significantly with age (χ² = 524 p < 0001) No variable independently predicted HER2 3+ positivity (IDC vs other: OR 175 95% CI 068–452 p = 024) CONCLUSIONS Over half of this cohort showed detectable HER2 expression and the strict HER2positivity rate (263%) is higher than the global benchmark in line with other Arab cohorts Reflex FISH was not available onsite to confirm equivocal (2+) cases pointing to a need for expanded confirmatory testing Histology but not age alone varied meaningfully across age groups which should inform diagnostic planning
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9. Perou CM, Sorlie T, Eisen MB, et al. Molecular portraits of human breast tumours. Nature. 2000;406(6797):747-752. doi:10.1038/35021093
10. Howlader N, Altekruse SF, Li CI, et al. US incidence of breast cancer subtypes defined by joint hormone receptor and HER2 status. J Natl Cancer Inst. 2014;106(5):dju055. doi:10.1093/jnci/dju055
11. World Health Organization. WHO Model List of Essential Medicines – 22nd List (2021). Geneva: WHO; 2021.
12. Hwang J, Shon HS, Lee KH. Barriers to the Use of Trastuzumab for HER2+ Breast Cancer and Biosimilar Replacement Strategies: A Narrative Review. Pharmaceuticals (Basel). 2014;7(9):943-958. doi:10.3390/ph7090943
13. Modi S, Jacot W, Yamashita T, et al. Trastuzumab Deruxtecan in Previously Treated HER2-Low Advanced Breast Cancer (DESTINY-Breast04). N Engl J Med. 2022;387(1):9-20. doi:10.1056/NEJMoa2203690
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15. Wolff AC, Somerfield MR, Dowsett M, et al. Human Epidermal Growth Factor Receptor 2 Testing in Breast Cancer: ASCO/CAP Clinical Practice Guideline Focused Update. J Clin Oncol. 2023;41(28):3867-3872. doi:10.1200/JCO.22.02864
16. Wolff AC, Hammond MEH, Allison KH, et al. Human Epidermal Growth Factor Receptor 2 Testing in Breast Cancer: American Society of Clinical Oncology/College of American Pathologists Clinical Practice Guideline Focused Update. J Clin Oncol. 2018;36(20):2105-2122. doi:10.1200/JCO.2018.77.8738
17. Alwan NAS, Tawfeeq FN, Muallah FH. Breast Cancer Subtypes among Iraqi Patients: Identified By Their ER, PR and HER2 Status. J Fac Med Baghdad. 2018;59(4):303-307. doi:10.32007/jfacmedbaghdad.v59i4.164
18. Alnegheimish NA, Alshatwi AA, Alhudairy SE, et al. Molecular subtypes of breast carcinoma in Saudi Arabia: A retrospective study. Saudi Med J. 2016;37(5):506-512. doi:10.15537/smj.2016.5.15000
19. Saleh BO, Al-Shammari F, Al-Juboori A, et al. Changing Trends in Estrogen Receptors/Progesterone Receptors/Human Epidermal Growth Factor Receptor 2 Prevalence Rates Among Jordanian Patients With Breast Cancer Over the Years. JCO Glob Oncol. 2022;8:e2100359. doi:10.1200/GO.21.00359
20. Chouchane L, Boussen H, Sastry KS. Breast cancer in Arab populations: molecular characteristics and disease management. Lancet Oncol. 2013;14(10):e417-e424. doi:10.1016/S1470-2045(13)70243-7
21. Besharat S, et al. Age at diagnosis of breast cancer in Iranian women: a systematic review and meta-analysis. Iran J Public Health. 2021;50(7):1305-1314.
22. Othman RT, et al. Clinicopathological profile of breast cancer in Iraqi Kurdistan. Breast Dis. 2015;35(4):217-222.
23. American Cancer Society. Breast Cancer Facts & Figures 2023-2024. Atlanta: American Cancer Society; 2023.
24. Li CI, Anderson BO, Daling JR, Moe RE. Trends in incidence rates of invasive lobular and ductal breast carcinoma. JAMA. 2003;289(11):1421-1424. doi:10.1001/jama.289.11.1421
25. Surveillance, Epidemiology, and End Results (SEER) Program. Cancer Stat Facts: Female Breast Cancer Subtypes. National Cancer Institute; 2024.
26. Dietze EC, Sistrunk C, Miranda-Carboni G, Seewaldt VL. Triple-negative breast cancer in African-American women: disparities versus biology. Nat Rev Cancer. 2015;15(4):248-254. doi:10.1038/nrc3896
27. Eniu A, Carlson RW, El Saghir NS. Guideline implementation for breast cancer in low- and middle-income countries. J Glob Oncol. 2016;2(1):1-14. doi:10.1200/JGO.2016.006213
28. Knaul FM, Atun R, Arreola-Ornelas H, et al. Access to Cancer Therapeutics in Low- and Middle-Income Countries. Am Soc Clin Oncol Educ Book. 2018;38:521-532. doi:10.1200/EDBK_155975
29. Dent R, Trudeau M, Pritchard KI, et al. Triple-negative breast cancer: clinical features and patterns of recurrence. Clin Cancer Res. 2007;13(15):4429-4434.
30. Al-Azri M, et al. Breast Cancer in the Arabian Gulf: clinical and pathological characteristics. Gulf J Oncolog. 2020;1(33):14-23.
31. Goldhirsch A, Winer EP, Coates AS, et al. 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. Ann Oncol. 2013;24(9):2206-2223. doi:10.1093/annonc/mdt303
32. Cheang MCU, Chia SK, Voduc D, et al. Ki67 Index, HER2 Status, and Prognosis of Patients With Luminal B Breast Cancer. J Natl Cancer Inst. 2009;101(10):736-750. doi:10.1093/jnci/djp082
2. Bray F, Laversanne M, Sung H, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024;74(3):229-263. doi:10.3322/caac.21834
3. World Health Organization. Global Breast Cancer Initiative (GBCI). Geneva: WHO; 2021. Available at: https://www.who.int/initiatives/global-breast-cancer-initiative
4. Anderson BO, Cazap E, El Saghir NS, et al. Optimisation of breast cancer management in low-resource and middle-resource countries: executive summary of a Breast Health Global Initiative consensus, 2010. Lancet Oncol. 2011;12(4):387-398. doi:10.1016/S1470-2045(11)70031-5
5. Abood RA, Al-Jaf J, Al-Mousa A, et al. HealthCare Access Barrier (HCAB) framework for the barriers to cancer care in Iraq. BMJ Oncol. 2024;3(1):e000252. doi:10.1136/bmjonc-2023-000252
6. Al-Hashimi MMY. Trends in Breast Cancer Incidence in Iraq During the Period 2000-2019. Asian Pac J Cancer Prev. 2021;22(12):3889-3896. doi:10.31557/APJCP.2021.22.12.3889
7. Iraqi Cancer Registry. Annual Report. Baghdad: Iraqi Ministry of Health; 2024. Available at: https://moh.gov.iq
8. Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullrich A, McGuire WL. Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science. 1987;235(4785):177-182. doi:10.1126/science.3798106
9. Perou CM, Sorlie T, Eisen MB, et al. Molecular portraits of human breast tumours. Nature. 2000;406(6797):747-752. doi:10.1038/35021093
10. Howlader N, Altekruse SF, Li CI, et al. US incidence of breast cancer subtypes defined by joint hormone receptor and HER2 status. J Natl Cancer Inst. 2014;106(5):dju055. doi:10.1093/jnci/dju055
11. World Health Organization. WHO Model List of Essential Medicines – 22nd List (2021). Geneva: WHO; 2021.
12. Hwang J, Shon HS, Lee KH. Barriers to the Use of Trastuzumab for HER2+ Breast Cancer and Biosimilar Replacement Strategies: A Narrative Review. Pharmaceuticals (Basel). 2014;7(9):943-958. doi:10.3390/ph7090943
13. Modi S, Jacot W, Yamashita T, et al. Trastuzumab Deruxtecan in Previously Treated HER2-Low Advanced Breast Cancer (DESTINY-Breast04). N Engl J Med. 2022;387(1):9-20. doi:10.1056/NEJMoa2203690
14. Wolff AC, Hammond MEH, Hicks DG, et al. Recommendations for Human Epidermal Growth Factor Receptor 2 Testing in Breast Cancer: American Society of Clinical Oncology/College of American Pathologists Clinical Practice Guideline Update. J Clin Oncol. 2013;31(31):3997-4013. doi:10.1200/JCO.2013.50.9984
15. Wolff AC, Somerfield MR, Dowsett M, et al. Human Epidermal Growth Factor Receptor 2 Testing in Breast Cancer: ASCO/CAP Clinical Practice Guideline Focused Update. J Clin Oncol. 2023;41(28):3867-3872. doi:10.1200/JCO.22.02864
16. Wolff AC, Hammond MEH, Allison KH, et al. Human Epidermal Growth Factor Receptor 2 Testing in Breast Cancer: American Society of Clinical Oncology/College of American Pathologists Clinical Practice Guideline Focused Update. J Clin Oncol. 2018;36(20):2105-2122. doi:10.1200/JCO.2018.77.8738
17. Alwan NAS, Tawfeeq FN, Muallah FH. Breast Cancer Subtypes among Iraqi Patients: Identified By Their ER, PR and HER2 Status. J Fac Med Baghdad. 2018;59(4):303-307. doi:10.32007/jfacmedbaghdad.v59i4.164
18. Alnegheimish NA, Alshatwi AA, Alhudairy SE, et al. Molecular subtypes of breast carcinoma in Saudi Arabia: A retrospective study. Saudi Med J. 2016;37(5):506-512. doi:10.15537/smj.2016.5.15000
19. Saleh BO, Al-Shammari F, Al-Juboori A, et al. Changing Trends in Estrogen Receptors/Progesterone Receptors/Human Epidermal Growth Factor Receptor 2 Prevalence Rates Among Jordanian Patients With Breast Cancer Over the Years. JCO Glob Oncol. 2022;8:e2100359. doi:10.1200/GO.21.00359
20. Chouchane L, Boussen H, Sastry KS. Breast cancer in Arab populations: molecular characteristics and disease management. Lancet Oncol. 2013;14(10):e417-e424. doi:10.1016/S1470-2045(13)70243-7
21. Besharat S, et al. Age at diagnosis of breast cancer in Iranian women: a systematic review and meta-analysis. Iran J Public Health. 2021;50(7):1305-1314.
22. Othman RT, et al. Clinicopathological profile of breast cancer in Iraqi Kurdistan. Breast Dis. 2015;35(4):217-222.
23. American Cancer Society. Breast Cancer Facts & Figures 2023-2024. Atlanta: American Cancer Society; 2023.
24. Li CI, Anderson BO, Daling JR, Moe RE. Trends in incidence rates of invasive lobular and ductal breast carcinoma. JAMA. 2003;289(11):1421-1424. doi:10.1001/jama.289.11.1421
25. Surveillance, Epidemiology, and End Results (SEER) Program. Cancer Stat Facts: Female Breast Cancer Subtypes. National Cancer Institute; 2024.
26. Dietze EC, Sistrunk C, Miranda-Carboni G, Seewaldt VL. Triple-negative breast cancer in African-American women: disparities versus biology. Nat Rev Cancer. 2015;15(4):248-254. doi:10.1038/nrc3896
27. Eniu A, Carlson RW, El Saghir NS. Guideline implementation for breast cancer in low- and middle-income countries. J Glob Oncol. 2016;2(1):1-14. doi:10.1200/JGO.2016.006213
28. Knaul FM, Atun R, Arreola-Ornelas H, et al. Access to Cancer Therapeutics in Low- and Middle-Income Countries. Am Soc Clin Oncol Educ Book. 2018;38:521-532. doi:10.1200/EDBK_155975
29. Dent R, Trudeau M, Pritchard KI, et al. Triple-negative breast cancer: clinical features and patterns of recurrence. Clin Cancer Res. 2007;13(15):4429-4434.
30. Al-Azri M, et al. Breast Cancer in the Arabian Gulf: clinical and pathological characteristics. Gulf J Oncolog. 2020;1(33):14-23.
31. Goldhirsch A, Winer EP, Coates AS, et al. 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. Ann Oncol. 2013;24(9):2206-2223. doi:10.1093/annonc/mdt303
32. Cheang MCU, Chia SK, Voduc D, et al. Ki67 Index, HER2 Status, and Prognosis of Patients With Luminal B Breast Cancer. J Natl Cancer Inst. 2009;101(10):736-750. doi:10.1093/jnci/djp082
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| Issue | Vol 17 No 2 (2025) | |
| Section | Original Articles | |
| Keywords | ||
| breast cancer immunohistochemistry ASCOCAP guideline iraq molecular subtypes | ||
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How to Cite
1.
Kadhim HM, HADI BA. HER2 Status in Breast Cancer in Relation to Age and Tumor Histological Type: A Cross-Sectional Study from Karbala Iraq. Basic Clin Cancer Res. 2026;17(2):54-62.
