Changes In HER2 And Hormonal Receptors Biomarkers After Neoadjuvant Chemotherapy For Breast Cancer And Impact On Adjuvant Therapy Selection
DOI:
https://doi.org/10.34635/rpc.1027Keywords:
breast cancer, receptor alterations, chemotherapy, target treatmentAbstract
Introduction: Breast cancer biological subtype has an important impact in the definition of the treatment strategy and the prognosis. However, the influence of neoadjuvant chemotherapy in the immunohistochemistry profile of the tumor is not well clarified. This study aims to evaluate the incidence of immunohistochemistry profile changes after neoadjuvant chemotherapy and the impact of these changes in adjuvant therapeutic decisions.
Methods: Retrospective review of all breast cancer patients consecutively treated with neoadjuvant therapy followed by surgery between January 2013 and July 2019. Only patients with complete information on hormone receptors (HR) and human epidermal growth factor 2 (HER2) status on both pre-chemotherapy biopsy and post-chemotherapy surgical specimen were included.
Results: During the study period, a total of 655 patients with 662 carcinomas were submitted to neoadjuvant therapy and surgical treatment. From this original cohort, 37.9% didn’t have a complete immunohistochemistry profile, 22.7% had a complete pathological response and one patient had only neoadjuvant hormonal therapy, and was excluded from the study. From the 260 analyzed tumors, 99.2% of the patients were female, with a median age of 50 years. The majority of tumors were cT2 (38.8%) and cT3 (39.2%), as well as cN+ (71.5%). The most common biological subtype at diagnosis was HR-positive/HER2 negative in 50.8% of cases, followed by HR negative/HER2 negative in 27.3%, HR-positive/HER2 positive in 15.4% and HR negative/HER2 positive in 6.5%. There was a change in biological subtype in 10% of patients, namely 5.7% of changes in HER2 profile and 4.2% changes in HR. The changes in progesterone receptors were the only statistically significant between the biopsy and surgical specimen analysis (p<0.001). From the group where immunohistochemistry markers changed, in 42.3% there was a change in adjuvant treatment. In all cases in which HER2 or RH status changed from negative to positive, there was a modification in adjuvant treatment. In most cases in which HR and/or HER2 status changed from positive to negative, adjuvant therapy was performed according to the pre-chemotherapy biopsy findings.
Conclusion: Immunohistochemistry markers changed in 10% of breast cancer patients after neoadjuvant chemotherapy. The main therapeutic modifications were made when there was a change in receptor status from negative to positive. Therefore, it is important to reconsider the evaluation of biological markers in surgical specimens, mainly in patients with negative receptors at diagnosis, so that adjuvant therapies can be adjusted accordingly.
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References
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38. Perez, E.A., et al., Trastuzumab plus adjuvant chemotherapy for human epidermal growth factor receptor 2-positive breast cancer: planned joint analysis of overall survival from NSABP B-31 and NCCTG N9831. J Clin Oncol, 2014. 32(33): p. 3744-52.
39. Xian, Z., et al., Breast cancer biomarkers before and after neoadjuvant chemotherapy: does repeat testing impact therapeutic management? Hum Pathol, 2017. 62: p. 215-221.
2. Wolmark, N., et al., Preoperative chemotherapy in patients with operable breast cancer: nine-year results from National Surgical Adjuvant Breast and Bowel Project B-18. J Natl Cancer Inst Monogr, 2001(30): p. 96-102.
3. van der Hage, J.A., et al., Preoperative chemotherapy in primary operable breast cancer: results from the European Organization for Research and Treatment of Cancer trial 10902. J Clin Oncol, 2001. 19(22): p. 4224-37.
4. Early Breast Cancer Trialists’ Collaborative, G., Long-term outcomes for neoadjuvant versus adjuvant chemotherapy in early breast cancer: meta-analysis of individual patient data from ten randomised trials. Lancet Oncol, 2018. 19(1): p. 27-39.
5. Esserman, L.J., et al., Pathologic complete response predicts recurrence-free survival more effectively by cancer subset: results from the I-SPY 1 TRIAL--CALGB 150007/150012, ACRIN 6657. J Clin Oncol, 2012. 30(26): p. 3242-9.
6. Perou, C.M., et al., Molecular portraits of human breast tumours. Nature, 2000. 406(6797): p. 747-52.
7. Rouzier, R., et al., Breast cancer molecular subtypes respond differently to preoperative chemotherapy. Clin Cancer Res, 2005. 11(16): p. 5678-85.
8. Chen, S., et al., Prognostic value of a positive-to-negative change in hormone receptor status after neoadjuvant chemotherapy in patients with hormone receptor-positive breast cancer. Ann Surg Oncol, 2012. 19(9): p. 3002-11.
9. Lee, S.H., et al., The effect of neoadjuvant chemotherapy on estrogen and progesterone receptor expression and hormone receptor status in breast cancer. Am J Surg, 2003. 186(4): p. 348-50.
10. Zhang, N., et al., The hormonal receptor status in breast cancer can be altered by neoadjuvant chemotherapy: a meta-analysis. Cancer Invest, 2011. 29(9): p. 594-8.
11. Lim, S.K., et al., Impact of Molecular Subtype Conversion of Breast Cancers after Neoadjuvant Chemotherapy on Clinical Outcome. Cancer Res Treat, 2016. 48(1): p. 133-41.
12. De La Cruz, L.M., et al., Impact of Neoadjuvant Chemotherapy on Breast Cancer Subtype: Does Subtype Change and, if so, How? : IHC Profile and Neoadjuvant Chemotherapy. Ann Surg Oncol, 2018. 25(12): p. 3535-3540.
13. Hirata, T., et al., Change in the hormone receptor status following administration of neoadjuvant chemotherapy and its impact on the long-term outcome in patients with primary breast cancer. Br J Cancer, 2009. 101(9): p. 1529-36.
14. Tacca, O., et al., Changes in and prognostic value of hormone receptor status in a series of operable breast cancer patients treated with neoadjuvant chemotherapy. Oncologist, 2007. 12(6): p. 636-43.
15. Burcombe, R.J., et al., Evaluation of ER, PgR, HER-2 and Ki-67 as predictors of response to neoadjuvant anthracycline chemotherapy for operable breast cancer. Br J Cancer, 2005. 92(1): p. 147-55.
16. Jain, V., M. Landry, and E.A. Levine, The stability of estrogen and progesterone receptors in patients receiving preoperative chemotherapy for locally advanced breast carcinoma. Am Surg, 1996. 62(2): p. 162-5.
17. Makris, A., et al., Quantitative changes in cytological molecular markers during primary medical treatment of breast cancer: a pilot study. Breast Cancer Res Treat, 1999. 53(1): p. 51-9.
18. van de Ven, S., et al., Discordances in ER, PR and HER2 receptors after neoadjuvant chemotherapy in breast cancer. Cancer Treat Rev, 2011. 37(6): p. 422-30.
19. Qin, Q., et al., Effect of neoadjuvant chemotherapy on expressions of estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2, and Ki-67 in breast cancer. Chin Med J (Engl), 2014. 127(18): p. 3272-7.
20. Yang, Y.F., et al., Changes in ER, PR and HER2 receptors status after neoadjuvant chemotherapy in breast cancer. Pathol Res Pract, 2013. 209(12): p. 797-802.
21. Niikura, N., et al., Changes in tumor expression of HER2 and hormone receptors status after neoadjuvant chemotherapy in 21,755 patients from the Japanese breast cancer registry. Ann Oncol, 2016. 27(3): p. 480-7.
22. Hurley, J., et al., Docetaxel, cisplatin, and trastuzumab as primary systemic therapy for human epidermal growth factor receptor 2-positive locally advanced breast cancer. J Clin Oncol, 2006. 24(12): p. 1831-8.
23. Mittendorf, E.A., et al., Loss of HER2 amplification following trastuzumab-based neoadjuvant systemic therapy and survival outcomes. Clin Cancer Res, 2009. 15(23): p. 7381-8.
24. Dekker, T.J., et al., Reliability of core needle biopsy for determining ER and HER2 status in breast cancer. Ann Oncol, 2013. 24(4): p. 931-7.
25. Arnedos, M., et al., Discordance between core needle biopsy (CNB) and excisional biopsy (EB) for estrogen receptor (ER), progesterone receptor (PgR) and HER2 status in early breast cancer (EBC). Ann Oncol, 2009. 20(12): p. 1948-52.
26. Gown, A.M., Current issues in ER and HER2 testing by IHC in breast cancer. Mod Pathol, 2008. 21 Suppl 2: p. S8-S15.
27. Bueno-de-Mesquita, J.M., et al., The impact of inter-observer variation in pathological assessment of node-negative breast cancer on clinical risk assessment and patient selection for adjuvant systemic treatment. Ann Oncol, 2010. 21(1): p. 40-7.
28. Parsons, D.W., et al., An integrated genomic analysis of human glioblastoma multiforme. Science, 2008. 321(5897): p. 1807-12.
29. Jones, S., et al., Core signaling pathways in human pancreatic cancers revealed by global genomic analyses. Science, 2008. 321(5897): p. 1801-6.
30. Campbell, P.J., et al., The patterns and dynamics of genomic instability in metastatic pancreatic cancer. Nature, 2010. 467(7319): p. 1109-13.
31. Sjoblom, T., et al., The consensus coding sequences of human breast and colorectal cancers. Science, 2006. 314(5797): p. 268-74.
32. Gerlinger, M., et al., Intratumor heterogeneity and branched evolution revealed by multiregion sequencing. N Engl J Med, 2012. 366(10): p. 883-892.
33. Almendro, V., et al., Inference of tumor evolution during chemotherapy by computational modeling and in situ analysis of genetic and phenotypic cellular diversity. Cell Rep, 2014. 6(3): p. 514-27.
34. Balko, J.M., et al., Molecular profiling of the residual disease of triple-negative breast cancers after neoadjuvant chemotherapy identifies actionable therapeutic targets. Cancer Discov, 2014. 4(2): p. 232-45.
35. Moulder, S., Intrinsic resistance to chemotherapy in breast cancer. Womens Health (Lond), 2010. 6(6): p. 821-30.
36. Early Breast Cancer Trialists’ Collaborative, G., Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet, 2005. 365(9472): p. 1687-717.
37. Coombes, R.C., et al., Survival and safety of exemestane versus tamoxifen after 2-3 years’ tamoxifen treatment (Intergroup Exemestane Study): a randomised controlled trial. Lancet, 2007. 369(9561): p. 559-70.
38. Perez, E.A., et al., Trastuzumab plus adjuvant chemotherapy for human epidermal growth factor receptor 2-positive breast cancer: planned joint analysis of overall survival from NSABP B-31 and NCCTG N9831. J Clin Oncol, 2014. 32(33): p. 3744-52.
39. Xian, Z., et al., Breast cancer biomarkers before and after neoadjuvant chemotherapy: does repeat testing impact therapeutic management? Hum Pathol, 2017. 62: p. 215-221.
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2024-07-29
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