Evaluating the role of HER2-low versus HER2-0 status in predicting response to neoadjuvant chemotherapy in hormone receptor-positive breast cancer

Alper Topal; Mustafa Başak

doi:10.18621/eurj.1704067

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Kaynak Göster

Yıl 2025, EARLY ONLINE, 1 - 10

Alper Topal , Mustafa Başak

https://doi.org/10.18621/eurj.1704067

Öz

Kaynakça

1. Siegel RL, Kratzer TB, Giaquinto AN, Sung H, Jemal A. Cancer statistics, 2025. CA Cancer J Clin. 2025;75(1):10-45. Epub 20250116. doi: 10.3322/caac.21871.
2. Trapani D, Ginsburg O, Fadelu T, et al. Global challenges and policy solutions in breast cancer control. Cancer Treat Rev. 2022;104:102339. doi: 10.1016/j.ctrv.2022.102339.
3. Schettini F, Martínez-Sáez O, Falato C, et al. Prognostic value of intrinsic subtypes in hormone-receptor-positive metastatic breast cancer: systematic review and meta-analysis. ESMO Open. 2023;8(3):101214. doi: 10.1016/j.esmoop.2023.101214.
4. Cejalvo JM, Martínez de Dueñas E, Galván P, et al. Intrinsic Subtypes and Gene Expression Profiles in Primary and Metastatic Breast Cancer. Cancer Res. 2017;77(9):2213-2221. doi: 10.1158/0008-5472.CAN-16-2717.
5. Akdag G, Yildirim S, Dogan A, et alNeoadjuvant Chemotherapy and Pathologic Complete Response in HR+/HER2- Breast Cancer: Impact of Tumor Ki67 and ER Status. Chemotherapy. 2024;69(3):141-149. doi: 10.1159/000537874.
6. Yau C, Osdoit M, van der Noordaa M, et al. Residual cancer burden after neoadjuvant chemotherapy and long-term survival outcomes in breast cancer: a multicentre pooled analysis of 5161 patients. Lancet Oncol. 2022;23(1):149-160. doi: 10.1016/s1470-2045(21)00589-1.
7. Boughey JC, Ballman KV, McCall LM, et al. Tumor Biology and Response to Chemotherapy Impact Breast Cancer-specific Survival in Node-positive Breast Cancer Patients Treated With Neoadjuvant Chemotherapy: Long-term Follow-up From ACOSOG Z1071 (Alliance). Ann Surg. 2017;266(4):667-676. doi: 10.1097/sla.0000000000002373.
8. Tarantino P, Viale G, Press MF, et al. ESMO expert consensus statements (ECS) on the definition, diagnosis, and management of HER2-low breast cancer. Ann Oncol. 2023;34(8):645-59. doi: 10.1016/j.annonc.2023.05.008.
9. Modi S, Jacot W, Yamashita T, et al.; DESTINY-Breast04 Trial Investigators. Trastuzumab Deruxtecan in Previously Treated HER2-Low Advanced Breast Cancer. N Engl J Med. 2022;387(1):9-20. doi: 10.1056/NEJMoa2203690.
10. Corti C, Giugliano F, Nicolò E, Tarantino P, Criscitiello C, Curigliano G. HER2-Low Breast Cancer: a New Subtype? Curr Treat Options Oncol. 2023;24(5):468-478.. doi: 10.1007/s11864-023-01068-1.
11. Zhang H, Katerji H, Turner BM, Hicks DG. HER2-Low Breast Cancers. Am J Clin Pathol. 2022;157(3):328-336. doi: 10.1093/ajcp/aqab117.
12. Ogston KN, Miller ID, Payne S, et al. A new histological grading system to assess response of breast cancers to primary chemotherapy: prognostic significance and survival. Breast. 2003;12(5):320-327. doi: 10.1016/s0960-9776(03)00106-1.
13. Guarneri V, Broglio K, Kau SW, et al. Prognostic value of pathologic complete response after primary chemotherapy in relation to hormone receptor status and other factors. J Clin Oncol. 2006;24(7):1037-1044. doi: 10.1200/jco.2005.02.6914.
14. Zhou S, Liu T, Kuang X, et al. Comparison of clinicopathological characteristics and response to neoadjuvant chemotherapy between HER2-low and HER2-zero breast cancer. Breast. 2023;67:1-7. doi: 10.1016/j.breast.2022.12.006.
15. de Moura Leite L, Cesca MG, Tavares MC, et al. HER2-low status and response to neoadjuvant chemotherapy in HER2 negative early breast cancer. Breast Cancer Res Treat. 2021;190(1):155-163. doi: 10.1007/s10549-021-06365-7.
16. Denkert C, Seither F, Schneeweiss A, et al. Clinical and molecular characteristics of HER2-low-positive breast cancer: pooled analysis of individual patient data from four prospective, neoadjuvant clinical trials. Lancet Oncol. 2021;22(8):1151-1161. doi: 10.1016/S1470-2045(21)00301-6.
17. Baez-Navarro X, van Bockstal MR, Jager A, van Deurzen CHM. HER2-low breast cancer and response to neoadjuvant chemotherapy: a population-based cohort study. Pathology. 2024;56(3):334-342. doi: 10.1016/j.pathol.2023.10.022.
18. de Moraes FCA, de Castro Ribeiro CHD, Pessôa FDDL, et al. Pathologic response rates in HER2-low versus HER2-zero early breast cancer patients receiving neoadjuvant therapy: a systematic review and meta-analysis. Breast Cancer Res. 2025;27(1):39. doi: 10.1186/s13058-025-01989-9.
19. Yang M, Sun J, Liu L, et al. Clinicopathological characteristics of HER2-low breast cancer: a retrospective study. Sci Rep. 2023;13(1):12382. doi: 10.1038/s41598-023-39372-3.
20. Ilie SM, Briot N, Constantin G, et al. Pathologic complete response and survival in HER2-low and HER2-zero early breast cancer treated with neoadjuvant chemotherapy. Breast Cancer. 2023;30(6):997-1007. doi: 10.1007/s12282-023-01490-1.
21. Ring AE, Smith IE, Ashley S, Fulford LG, Lakhani SR. Oestrogen receptor status, pathological complete response and prognosis in patients receiving neoadjuvant chemotherapy for early breast cancer. Br J Cancer. 2004;91(12):2012-2017. doi: 10.1038/sj.bjc.6602235.
22. Jones RL, Salter J, A'Hern R, et al. Relationship between oestrogen receptor status and proliferation in predicting response and long-term outcome to neoadjuvant chemotherapy for breast cancer. Breast Cancer Res Treat. 2010;119(2):315-323. doi: 10.1007/s10549-009-0329-x.
23. Dieci MV, Griguolo G, Bottosso M, et al. Impact of estrogen receptor levels on outcome in non-metastatic triple negative breast cancer patients treated with neoadjuvant/adjuvant chemotherapy. NPJ Breast Cancer. 2021;7(1):101. doi: 10.1038/s41523-021-00308-7.
24. Gloyeske NC, Dabbs DJ, Bhargava R. Low ER+ breast cancer: Is this a distinct group? Am J Clin Pathol. 2014;141(5):697-701. doi: 10.1309/AJCP34CYSATWFDPQ.
25. Fujii T, Kogawa T, Dong W, et al. Revisiting the definition of estrogen receptor positivity in HER2-negative primary breast cancer. Ann Oncol. 2017;28(10):2420-2428. doi: 10.1093/annonc/mdx397.
26. Ohara AM, Naoi Y, Shimazu K, et al. PAM50 for prediction of response to neoadjuvant chemotherapy for ER-positive breast cancer. Breast Cancer Res Treat. 2019;173(3):533-543. doi: 10.1007/s10549-018-5020-7.
27. Rapoport BL, Barnard-Tidy J, Van Eeden RI, Smit T, Nayler S, Benn C. Pathological complete response in early breast cancer patients undergoing neoadjuvant chemotherapy: Focus on Ki-67 and molecular subtypes. Ann Oncol. 2019;30(Supplement 3):iii37. doi: 10.1093/annonc/mdz097.012.
28. Fasching PA, Heusinger K, Haeberle L, et al. Ki67, chemotherapy response, and prognosis in breast cancer patients receiving neoadjuvant treatment. BMC Cancer. 2011;11:486. doi: 10.1186/1471-2407-11-486.
29. Fisher ER, Wang J, Bryant J, Fisher B, Mamounas E, Wolmark N. Pathobiology of preoperative chemotherapy: findings from the National Surgical Adjuvant Breast and Bowel (NSABP) protocol B-18. Cancer. 2002;95(4):681-695. doi: 10.1002/cncr.10741.
30. Spring LM, Fell G, Arfe A, et al. Pathologic Complete Response after Neoadjuvant Chemotherapy and Impact on Breast Cancer Recurrence and Survival: A Comprehensive Meta-analysis. Clin Cancer Res. 2020;26(12):2838-2848. doi: 10.1158/1078-0432.CCR-19-3492.

Evaluating the role of HER2-low versus HER2-0 status in predicting response to neoadjuvant chemotherapy in hormone receptor-positive breast cancer

Yıl 2025, EARLY ONLINE, 1 - 10

Alper Topal , Mustafa Başak

https://doi.org/10.18621/eurj.1704067

Öz

Objectives: The classification of human epidermal growth factor receptor 2 (HER2)-low breast cancer has gained clinical relevance following the success of antibody-drug conjugates in this subgroup. However, its prognostic and predictive role, particularly in hormone receptor-positive (HR+) early breast cancer treated with neoadjuvant chemotherapy (NACT), remains unclear. This study aimed to evaluate the impact of HER2-low versus HER2-0 status on pathological complete response (pCR) and disease-free survival (DFS) in HR+ breast cancer patients undergoing NACT.

Methods: A total of 216 HR+ and HER2-negative early breast cancer patients treated with NACT at Tokat Gaziosmanpasa University Hospital between January 2014 and January 2024 were retrospectively analyzed. HER2-low was defined as IHC 1+ or 2+ without gene amplification by FISH. pCR was assessed via the Miller-Payne grading system. Survival analyses were conducted using the Kaplan-Meier method; multivariate analyses were performed using Cox regression.

Results: Of the 216 patients, 30 (13.9%) achieved pCR. There was no statistically significant difference in pCR (P=0.83) or DFS (P=0.12) between HER2-0 and HER2-low groups. However, patients with ER <10% had significantly higher pCR rates (P=0.005). Achieving pCR was associated with longer DFS (P=0.045).

Conclusions: HER2-0 and HER2-low subgroups exhibited similar responses to NACT in HR+ breast cancer. Low ER expression was independently associated with higher pCR. Larger prospective studies are warranted to further define the biological and clinical implications of HER2 expression levels in early-stage HR+ breast cancer.

Anahtar Kelimeler

Neoadjuvant chemotherapy, HER2-low, breast cancer, pathologic complete response

Etik Beyan

This study was approved by the Tokat Gaziosmanpasa University Faculty of Medicine Non-Interventional Scientific Research Ethics Committee (Decision no: 25-MOBAEK-043 and date: 04.02.2025), and it was realized in compliance with the Declaration of Helsinki's enets.

Kaynakça

1. Siegel RL, Kratzer TB, Giaquinto AN, Sung H, Jemal A. Cancer statistics, 2025. CA Cancer J Clin. 2025;75(1):10-45. Epub 20250116. doi: 10.3322/caac.21871.
2. Trapani D, Ginsburg O, Fadelu T, et al. Global challenges and policy solutions in breast cancer control. Cancer Treat Rev. 2022;104:102339. doi: 10.1016/j.ctrv.2022.102339.
3. Schettini F, Martínez-Sáez O, Falato C, et al. Prognostic value of intrinsic subtypes in hormone-receptor-positive metastatic breast cancer: systematic review and meta-analysis. ESMO Open. 2023;8(3):101214. doi: 10.1016/j.esmoop.2023.101214.
4. Cejalvo JM, Martínez de Dueñas E, Galván P, et al. Intrinsic Subtypes and Gene Expression Profiles in Primary and Metastatic Breast Cancer. Cancer Res. 2017;77(9):2213-2221. doi: 10.1158/0008-5472.CAN-16-2717.
5. Akdag G, Yildirim S, Dogan A, et alNeoadjuvant Chemotherapy and Pathologic Complete Response in HR+/HER2- Breast Cancer: Impact of Tumor Ki67 and ER Status. Chemotherapy. 2024;69(3):141-149. doi: 10.1159/000537874.
6. Yau C, Osdoit M, van der Noordaa M, et al. Residual cancer burden after neoadjuvant chemotherapy and long-term survival outcomes in breast cancer: a multicentre pooled analysis of 5161 patients. Lancet Oncol. 2022;23(1):149-160. doi: 10.1016/s1470-2045(21)00589-1.
7. Boughey JC, Ballman KV, McCall LM, et al. Tumor Biology and Response to Chemotherapy Impact Breast Cancer-specific Survival in Node-positive Breast Cancer Patients Treated With Neoadjuvant Chemotherapy: Long-term Follow-up From ACOSOG Z1071 (Alliance). Ann Surg. 2017;266(4):667-676. doi: 10.1097/sla.0000000000002373.
8. Tarantino P, Viale G, Press MF, et al. ESMO expert consensus statements (ECS) on the definition, diagnosis, and management of HER2-low breast cancer. Ann Oncol. 2023;34(8):645-59. doi: 10.1016/j.annonc.2023.05.008.
9. Modi S, Jacot W, Yamashita T, et al.; DESTINY-Breast04 Trial Investigators. Trastuzumab Deruxtecan in Previously Treated HER2-Low Advanced Breast Cancer. N Engl J Med. 2022;387(1):9-20. doi: 10.1056/NEJMoa2203690.
10. Corti C, Giugliano F, Nicolò E, Tarantino P, Criscitiello C, Curigliano G. HER2-Low Breast Cancer: a New Subtype? Curr Treat Options Oncol. 2023;24(5):468-478.. doi: 10.1007/s11864-023-01068-1.
11. Zhang H, Katerji H, Turner BM, Hicks DG. HER2-Low Breast Cancers. Am J Clin Pathol. 2022;157(3):328-336. doi: 10.1093/ajcp/aqab117.
12. Ogston KN, Miller ID, Payne S, et al. A new histological grading system to assess response of breast cancers to primary chemotherapy: prognostic significance and survival. Breast. 2003;12(5):320-327. doi: 10.1016/s0960-9776(03)00106-1.
13. Guarneri V, Broglio K, Kau SW, et al. Prognostic value of pathologic complete response after primary chemotherapy in relation to hormone receptor status and other factors. J Clin Oncol. 2006;24(7):1037-1044. doi: 10.1200/jco.2005.02.6914.
14. Zhou S, Liu T, Kuang X, et al. Comparison of clinicopathological characteristics and response to neoadjuvant chemotherapy between HER2-low and HER2-zero breast cancer. Breast. 2023;67:1-7. doi: 10.1016/j.breast.2022.12.006.
15. de Moura Leite L, Cesca MG, Tavares MC, et al. HER2-low status and response to neoadjuvant chemotherapy in HER2 negative early breast cancer. Breast Cancer Res Treat. 2021;190(1):155-163. doi: 10.1007/s10549-021-06365-7.
16. Denkert C, Seither F, Schneeweiss A, et al. Clinical and molecular characteristics of HER2-low-positive breast cancer: pooled analysis of individual patient data from four prospective, neoadjuvant clinical trials. Lancet Oncol. 2021;22(8):1151-1161. doi: 10.1016/S1470-2045(21)00301-6.
17. Baez-Navarro X, van Bockstal MR, Jager A, van Deurzen CHM. HER2-low breast cancer and response to neoadjuvant chemotherapy: a population-based cohort study. Pathology. 2024;56(3):334-342. doi: 10.1016/j.pathol.2023.10.022.
18. de Moraes FCA, de Castro Ribeiro CHD, Pessôa FDDL, et al. Pathologic response rates in HER2-low versus HER2-zero early breast cancer patients receiving neoadjuvant therapy: a systematic review and meta-analysis. Breast Cancer Res. 2025;27(1):39. doi: 10.1186/s13058-025-01989-9.
19. Yang M, Sun J, Liu L, et al. Clinicopathological characteristics of HER2-low breast cancer: a retrospective study. Sci Rep. 2023;13(1):12382. doi: 10.1038/s41598-023-39372-3.
20. Ilie SM, Briot N, Constantin G, et al. Pathologic complete response and survival in HER2-low and HER2-zero early breast cancer treated with neoadjuvant chemotherapy. Breast Cancer. 2023;30(6):997-1007. doi: 10.1007/s12282-023-01490-1.
21. Ring AE, Smith IE, Ashley S, Fulford LG, Lakhani SR. Oestrogen receptor status, pathological complete response and prognosis in patients receiving neoadjuvant chemotherapy for early breast cancer. Br J Cancer. 2004;91(12):2012-2017. doi: 10.1038/sj.bjc.6602235.
22. Jones RL, Salter J, A'Hern R, et al. Relationship between oestrogen receptor status and proliferation in predicting response and long-term outcome to neoadjuvant chemotherapy for breast cancer. Breast Cancer Res Treat. 2010;119(2):315-323. doi: 10.1007/s10549-009-0329-x.
23. Dieci MV, Griguolo G, Bottosso M, et al. Impact of estrogen receptor levels on outcome in non-metastatic triple negative breast cancer patients treated with neoadjuvant/adjuvant chemotherapy. NPJ Breast Cancer. 2021;7(1):101. doi: 10.1038/s41523-021-00308-7.
24. Gloyeske NC, Dabbs DJ, Bhargava R. Low ER+ breast cancer: Is this a distinct group? Am J Clin Pathol. 2014;141(5):697-701. doi: 10.1309/AJCP34CYSATWFDPQ.
25. Fujii T, Kogawa T, Dong W, et al. Revisiting the definition of estrogen receptor positivity in HER2-negative primary breast cancer. Ann Oncol. 2017;28(10):2420-2428. doi: 10.1093/annonc/mdx397.
26. Ohara AM, Naoi Y, Shimazu K, et al. PAM50 for prediction of response to neoadjuvant chemotherapy for ER-positive breast cancer. Breast Cancer Res Treat. 2019;173(3):533-543. doi: 10.1007/s10549-018-5020-7.
27. Rapoport BL, Barnard-Tidy J, Van Eeden RI, Smit T, Nayler S, Benn C. Pathological complete response in early breast cancer patients undergoing neoadjuvant chemotherapy: Focus on Ki-67 and molecular subtypes. Ann Oncol. 2019;30(Supplement 3):iii37. doi: 10.1093/annonc/mdz097.012.
28. Fasching PA, Heusinger K, Haeberle L, et al. Ki67, chemotherapy response, and prognosis in breast cancer patients receiving neoadjuvant treatment. BMC Cancer. 2011;11:486. doi: 10.1186/1471-2407-11-486.
29. Fisher ER, Wang J, Bryant J, Fisher B, Mamounas E, Wolmark N. Pathobiology of preoperative chemotherapy: findings from the National Surgical Adjuvant Breast and Bowel (NSABP) protocol B-18. Cancer. 2002;95(4):681-695. doi: 10.1002/cncr.10741.
30. Spring LM, Fell G, Arfe A, et al. Pathologic Complete Response after Neoadjuvant Chemotherapy and Impact on Breast Cancer Recurrence and Survival: A Comprehensive Meta-analysis. Clin Cancer Res. 2020;26(12):2838-2848. doi: 10.1158/1078-0432.CCR-19-3492.

Toplam 30 adet kaynakça vardır.

Ayrıntılar

Birincil Dil	İngilizce
Konular	Kemoterapi
Bölüm	Original Article
Yazarlar	Alper Topal 0000-0002-9679-9245 Mustafa Başak 0000-0003-1329-774X
Erken Görünüm Tarihi	6 Ağustos 2025
Yayımlanma Tarihi
Gönderilme Tarihi	22 Mayıs 2025
Kabul Tarihi	1 Ağustos 2025
Yayımlandığı Sayı	Yıl 2025 EARLY ONLINE

Kaynak Göster

AMA	Topal A, Başak M. Evaluating the role of HER2-low versus HER2-0 status in predicting response to neoadjuvant chemotherapy in hormone receptor-positive breast cancer. Eur Res J. Published online 01 Ağustos 2025:1-10. doi:10.18621/eurj.1704067

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