Results of FISH study of HER2 in triple-positive breast cancer
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Keywords

breast cancer
FISH HER2
triple-positive breast cancer

How to Cite

Urezkova , M., Semiglazova , T., Artemyeva , A., Kudaybergenova , A., Semiglazov , V., Krivorotko, P., & Semiglazov , V. (2023). Results of FISH study of HER2 in triple-positive breast cancer. Voprosy Onkologii, 69(2), 268–274. https://doi.org/10.37469/0507-3758-2023-69-2-268-274

Abstract

Introduction. It is essential to accurately identify HER2-amplified tumors for effective classification and treatment of breast cancer patients. The most precise method for detecting HER2 gene amplification is fluorescence in situ hybridization (FISH) testing. When tumor status is uncertain in IHC analysis, FISH testing becomes necessary for proper classification into the category of triple-positive carcinomas. Data on the biology of such tumors and their response to therapy are limited and inconsistent, which makes this topic an interesting area for further research.

Aim. To characterize the distribution of HER2 FISH testing results in ER+/PR+ breast cancer.

Materials and methods. 247 samples of ER+/PR+ breast tumors were studied. The HER2 gene amplification was analyzed using the fluorescence in situ hybridization (FISH) method. The average number of signals from the centromere of chromosome 17 (CEN17) and HER2 gene per nucleus, as well as their ratio, were calculated. The results were grouped according to the level of amplification.

Results. In the triple-positive carcinoma group, the distribution of amplification groups was as follows: group 1 (HER2/CEN17 signal ratio ≥ 2.0, HER2 signals/cell nucleus ≥ 4.0) — 91.7 %, group 3 (HER2/CEN17 signal ratio < 2.0, HER2 signals/cell nucleus ≥ 6.0) — 7.3 %, group 4 (HER2/CEN17 signal ratio < 2.0, HER2 signals/cell nucleus 4.0 - 6.0) — 0.91 %. "Non-classical" FISH results were found in 92.8 % of cases. In the ER+/PR+/HER2- carcinoma group, the frequency of "non-classical" results was 30.4 %.

Сonclusion. In the triple-positive breast cancer group, the frequency of "non-classical" FISH results is 9 times higher than the frequency of such results in the general testing cohort (according to literature data) and 2 times higher than the frequency of such results in the ER+/PR+/HER2- cancer group. These results may be due to bidirectional crosstalk between the estrogen receptors and HER2 signaling pathways and may determine the biology of this group of tumors. Limited data on the interpretation and clinical significance of "non-classical" FISH results make it difficult to choose drug therapy for patients with breast cancer and determine the prognosis of the disease.

https://doi.org/10.37469/0507-3758-2023-69-2-268-274
pdf (Русский)

References

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.

Holzschuh MA, Czyz Z, Hauke S, et al. HER2 FISH results in breast cancers with increased CEN17 signals using alternative chromosome 17 probes - reclassifying cases in the equivocal category. Histopathology. 2017;71(4):610625. doi:10.1111/his.13253.

Vanden Bempt I, Van Loo P, Drijkoningen M, et al. Polysomy 17 in breast cancer: clinicopathologic significance and impact on HER-2 testing. J Clin Oncol. 2008;26(30):486974. doi:10.1200/JCO.2007.13.4296.

Sun H, Chen H, Crespo J, et al. Clinicopathological features of breast cancer with polysomy 17 and its response to neoadjuvant chemotherapy. Eur J Breast Health. 2021;17(2):128136. doi:10.4274/ejbh.galenos.2021.2021-2-9.

Varga Z, Tubbs RR, Wang Z, et al. Co-amplification of the HER2 gene and chromosome 17 centromere: a potential diagnostic pitfall in HER2 testing in breast cancer. Breast Cancer Res Treat. 2012;132(3):92535. doi:10.1007/s10549-011-1642-8.

Ballard M, Jalikis F, Krings G, et al. 'Non-classical' HER2 FISH results in breast cancer: a multi-institutional study. Mod Pathol. 2017;30(2):227235. doi:10.1038/modpathol.2016.175.

Fountzilas G, Dafni U, Bobos M, et al. Evaluation of the prognostic role of centromere 17 gain and HER2/topoisomerase II alpha gene status and protein expression in patients with breast cancer treated with anthracycline-containing adjuvant chemotherapy: pooled analysis of two Hellenic Cooperative Oncology Group (HeCOG) phase III trials. BMC Cancer. 2013;13(1). doi:10.1186/1471-2407-13-163.

Vici P, Pizzuti L, Natoli C, et al. Triple positive breast cancer: a distinct subtype? Cancer Treat Rev. 2015;41(2):6976. doi:10.1016/j.ctrv.2014.12.005.

Marchiò C, Lambros MB, Gugliotta P, et al. Does chromosome 17 centromere copy number predict polysomy in breast cancer? A fluorescence in situ hybridization and microarray-based CGH analysis. J Pathol. 2009;219(1):1624. doi:10.1002/path.2574.

Watters AD, Going JJ, Cooke TG, et al. Chromosome 17 aneusomy is associated with poor prognostic factors in invasive breast carcinoma. Breast Cancer Res Treat. 2003;77(2):10914. doi:10.1023/a:1021399923825.

Press MF, Sauter G, Buyse M, et al. HER2 gene amplification testing by fluorescent in situ hybridization (FISH): comparison of the ASCO-College of American Pathologists Guidelines with FISH Scores used for enrollment in Breast Cancer International Research Group clinical trials. J Clin Oncol. 2016;34(29):35183528. doi:10.1200/JCO.2016.66.6693.

Shah MV, Wiktor AE, Meyer RG, et al. Change in pattern of HER2 Fluorescent in Situ Hybridization (FISH) results in breast cancers submitted for FISH testing: experience of a reference laboratory using US Food and Drug Administration criteria and American Society of Clinical Oncology and College of American Pathologists guidelines. J Clin Oncol. 2016;34(29):35023510. doi:10.1200/JCO.2015.61.8983.

Press MF, Villalobos I, Santiago A, et al. Assessing the new American Society of Clinical Oncology/College of American Pathologists Guidelines for HER2 testing by fluorescence in situ hybridization: Experience of an academic consultation practice. Arch Pathol Lab Med. 2016;140(11):12501258. doi:10.5858/arpa.2016-0009-OA.

Sun H, Chen H, Crespo J, et al. Clinicopathological Features of Breast Cancer with Polysomy 17 and Its Response to Neoadjuvant Chemotherapy. Eur J Breast Health. 2021;17(2):128136. doi:10.4274/ejbh.galenos.

Lander EM, Rappazzo KC, Huang LC, et al. Using the HER2/CEP17 FISH ratio to predict pathologic complete response following neoadjuvant anti-HER2 doublet therapy in HER2+ breast cancer. Oncologist. 2023;28(2):123130. doi:10.1093/oncolo/oyac247.

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