Assessment of ERBB2 and HER2 expression in metastatic breast cancer using the nCounter® system and a 100-gene scale

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Abstract

Background. Individual molecular characteristics of a tumor can serve as a basis for a tailored approach to therapy, prediction of the disease course and outcome, and timely treatment correction in cancer patients. Tumor genomic profiling allows for a more precise tumor assessment in an individual manner. Accurate identification of the HER2 status of a breast tumor is crucial for clinical decisions and appropriate treatment strategy.

Aim. To increase the efficacy of systemic therapy for breast cancer, reduce inappropriate prescribing, and ensure a tailored approach to systemic breast cancer therapy using the information on individual molecular characteristics of the tumor.

Materials and methods. We explored the expression of 100 genes involved in breast cancer development in 106 tumor samples from patients with metastatic breast cancer. We used the nCounter technology based on direct digital target detection using color-coded molecular barcodes. We analyzed the expression of 28 genes with a high predictive value for breast cancer.

Results. The nCounter technology allowed us to perform semiquantitative assessment of the expression of 28 genes in tumor tissue samples. We compared the expression of ERBB2 and HER2. The HER2 expression between 252.32 and 6000 barcodes was equivalent to HER2 (0) status; between 6000 and 9196.25 barcodes, to HER2 (1+); between 9196.25 and 15022.46, to HER2 (2+/ISH±); and 15022.46 barcodes, to HER2 (3+). In case of HER2 (3+) and ERBB2 below 6000 barcodes, the result was considered false positive. In case of HER2 (0) or (1+) and ERBB2 above 15 000 barcodes, the result was considered false negative. In 18 tumors, the discrepancies in the results meant two principally different breast cancer subtypes requiring different treatments; in 2 cases, the discrepancies were in the level of HER2 expression.

Conclusion. HER2 testing should be performed on an excision sample (ideally on the same block that was used for genomic testing). Despite the correlation between the HER2-enriched molecular class and the response to anti-HER2 therapy, the final result on HER2 status in discordant cases should be based on currently approved assays after results validation.

About the authors

R.  M.  Paltuev

Public organization «Russian Society of Oncomammologists»; N.N. Petrov National Medical Research Oncology Center, Ministry of Health of Russia

Author for correspondence.
Email: paltuev@mail.ru
ORCID iD: 0000-0002-0871-9453

Ruslan Malikovich Paltuev

56 Prospekt Veteranov, Saint Petersburg 198255;
68 Leningradskaya St., Pesochnyy Settlement, Saint Petersburg 197758

Russian Federation

 O.  A.  Volynshchikova

N.N. Petrov National Medical Research Oncology Center, Ministry of Health of Russia

ORCID iD: 0009-0001-9454-1320

68 Leningradskaya St., Pesochnyy Settlement, Saint Petersburg 197758

Russian Federation

 Sh.  R.  Abdullaeva

N.N. Petrov National Medical Research Oncology Center, Ministry of Health of Russia

ORCID iD: 0000-0002-6601-2528

68 Leningradskaya St., Pesochnyy Settlement, Saint Petersburg 197758

Russian Federation

S.  N.  Aleksakhina

N.N. Petrov National Medical Research Oncology Center, Ministry of Health of Russia

ORCID iD: 0000-0002-2149-7728

68 Leningradskaya St., Pesochnyy Settlement, Saint Petersburg 197758

Russian Federation

 A.  S.  Artemyeva

N.N. Petrov National Medical Research Oncology Center, Ministry of Health of Russia

ORCID iD: 0000-0002-2948-397X

68 Leningradskaya St., Pesochnyy Settlement, Saint Petersburg 197758

Russian Federation

 E.  A.  Baychorov

Stavropol Regional Clinical Oncology Dispensary

ORCID iD: 0000-0002-6292-1775

82а Oktyabrskaya St., Stavropol 355047

Russian Federation

S.  Yu.  Bakharev

Altai Regional Oncology Dispensary

110k Zmeinogorskiy Trakt, Barnaul 656045

Russian Federation

Yu.  A.  Belaya

District Clinical Hospital

ORCID iD: 0009-0006-0709-3686

40 Kalina St., Khanty-Mansiysk 628011

Russian Federation

 A.  A.  Bozhok

Saint Petersburg State Pediatric Medical University, Ministry of Health of Russia

2 Litovskaya St., Saint Petersburg 194100

Russian Federation

 V.  A.  Vasin

Ivanovo Regional Oncology Dispensary

5 Lyubimova St., Ivanovo 153040

Russian Federation

V.  I.  Vladimirov

Pyatigorsk Regional Oncology Dispensary

31 Prospekt Kalinina, Pyatigorsk 357502

Russian Federation

A.  Yu.  Vorontsov

Nizhny Novgorod Regional Clinical Oncology Dispensary

11 / 1 Delovaya St., Nizhny Novgorod 603093

Russian Federation

E.  A.  Gaysina

Multidisciplinary Clinical Medical Center «Medical City»

32 Barnaulskaya St., Tyumen 625041 

Russian Federation

A.  A.  Gofman

Altai Regional Oncology Dispensary

110k Zmeinogorskiy Trakt, Barnaul 656045

Russian Federation

 V.  N.  Dmitriev

Belgorod Regional Oncology Dispensary

ORCID iD: 0000-0002-5523-5718

1 Kuybysheva St., Belgorod 308010

Russian Federation

 E.  N.  Imyanitov

N.N. Petrov National Medical Research Oncology Center, Ministry of Health of Russia

ORCID iD: 0000-0003-4529-7891

68 Leningradskaya St., Pesochnyy Settlement, Saint Petersburg 197758

Russian Federation

 V.  V.  Klimenko

N.N. Petrov National Medical Research Oncology Center, Ministry of Health of Russia

ORCID iD: 0000-0003-1079-4492

68 Leningradskaya St., Pesochnyy Settlement, Saint Petersburg 197758

Russian Federation

A.  V.  Komyakhov

N.N. Petrov National Medical Research Oncology Center, Ministry of Health of Russia

ORCID iD: 0000-0002-6598-1669

68 Leningradskaya St., Pesochnyy Settlement, Saint Petersburg 197758

Russian Federation

M.  M.  Konstantinova

Public organization «Russian Society of Oncomammologists»

56 Prospekt Veteranov, Saint Petersburg 198255

Russian Federation

M. V.  Kopp 

Private Medical University «Reaviz»

ORCID iD: 0000-0002-2783-9493

227 Chapaevskaya St., Samara 443001

Russian Federation

A.  G.  Kudaybergenova

N.N. Petrov National Medical Research Oncology Center, Ministry of Health of Russia

ORCID iD: 0000-0001-7797-088X

68 Leningradskaya St., Pesochnyy Settlement, Saint Petersburg 197758

Russian Federation

 I.  A.  Lalak

Stavropol Regional Clinical Oncology Dispensary

182а Oktyabrskaya St., Stavropol 355047

Russian Federation

D.  L.  Matevosyan

Pyatigorsk Regional Oncology Dispensary

31 Prospekt Kalinina, Pyatigorsk 357502

Russian Federation

N.  M.  Mudzhiri

Research Center of Neurology

ORCID iD: 0000-0002-3835-6622

80 Volokolamskoe Shosse, Moscow 125367

Russian Federation

O.  V.  Poltareva

Ivanovo Regional Oncology Dispensary

5 Lyubimova St., Ivanovo 153040

Russian Federation

 O.  I.  Sevryukova

Stavropol Regional Clinical Oncology Dispensary

182а Oktyabrskaya St., Stavropol 355047

Russian Federation

V.  F.  Semiglazov

N.N. Petrov National Medical Research Oncology Center, Ministry of Health of Russia

ORCID iD: 0000-0003-0077-9619

68 Leningradskaya St., Pesochnyy Settlement, Saint Petersburg 197758

Russian Federation

T.  Yu.  Semiglazova

N.N. Petrov National Medical Research Oncology Center, Ministry of Health of Russia

ORCID iD: 0000-0002-4305-6691

68 Leningradskaya St., Pesochnyy Settlement, Saint Petersburg 197758

Russian Federation

M.  M.  Urezkova

N.N. Petrov National Medical Research Oncology Center, Ministry of Health of Russia

ORCID iD: 0000-0002-4242-2629

68 Leningradskaya St., Pesochnyy Settlement, Saint Petersburg 197758

Russian Federation

A.  S.  Chichkanova

Nizhny Novgorod Regional Clinical Oncology Dispensary

11 / 1 Delovaya St., Nizhny Novgorod 603093

Russian Federation

L.  A.  Churilova

Altai Regional Oncology Dispensary

110k Zmeinogorskiy Trakt, Barnaul 656045

Russian Federation

M.  V.  Shomova

Regional Clinical Oncology Dispensary

ORCID iD: 0000-0002-6235-0925

11 Sportivnaya St., Ryazan 390011

Russian Federation

References

  1. Bertucci F., Finetti P., Cervera N. Gene expression profiling and clinical outcome in breast cancer. J Int Biology 2006;4(10):429–43. doi: 10.1089/omi.2006.10.429
  2. Cowin P.A., Anglesio M., Etemadmoghadam D. Profiling the cancer genome. Ann Rev Gen Hum Genet 2010;11:133–59. doi: 10.1146/annurev-genom-082509-141536
  3. Van de Vijver M.J. Molecular tests as prognostic factors in breast cancer. Virchows Arch 2014;464(3):283–91. doi: 10.1007/s00428-014-1539-0
  4. Hurvitz S.A., Gonçalves A., Rugo H.S. Talazoparib in patients with a germline BRCA-mutated advanced breast cancer: detailed safety analyses from the phase III EMBRACA Trial. Oncologist 2020;25(3):439–50. doi: 10.1634/theoncologist.2019-0493
  5. Paltuev R.M., Aleksakhina S.N., Artemyeva A.S. et al. Predictive multigenic scale. Analysis of own results in metastatic breast cancer. Opukholi zhenskoy reproduktivnoy systemy = Tumors of female reproductive system 2023;19(1):69–81. (In Russ.). doi: 10.17650/1994-4098-2023-19-1-69-81
  6. Modi Sh., Jacot W., Yamashita T. et al. Trastuzumab deruxtecan in previously treated HER2-low advanced breast cancer. N Engl J Med 2022;387(1):9–20. doi: 10.1056/NEJMoa2203690
  7. Schettini F., Chic N., Brasó-Maristany F. et al. Clinical, pathological, and PAM50 gene expression features of HER2-low breast cancer. Breast Cancer 2021;7(1):1. doi: 10.1038/s41523-020-00208-2
  8. Rakha E.A., Tan P.H., Quinn C. et al. UK recommendations for HER2 assessment in breast cancer: an update. J Clin Pathol 2023;76(4):217–27. doi: 10.1136/jcp-2022-20863
  9. Martinez-Sáez O., Chic N., Pascual T. et al. Frequency and spectrum of PIK3CA somatic mutations in breast cancer. Breast Cancer Res 2020;22(1):45. doi: 10.1186/s13058-020-01284-9
  10. Perez-Fidalgo J.A., Criscitiello C., Carrasco E. et al. A phase III trial of alpelisib + trastuzumab ± fulvestrant versus trastuzumab + chemotherapy in HER2+ PIK3CA-mutated breast cancer. Future Oncol 2022;18(19):2339–49. doi: 10.2217/fon-2022-0045

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