Prognostic value of low HER2 expression in patients with early breast cancer

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Abstract

Background: More than 50% of breast cancer (BC) cases are currently defined with lower levels of HER2 protein expression (HER2-low): HER2–1+ or 2+ with negative ISH. Most of the available retrospective analyses have not found that low HER2 expression has significant prognostic value.

Objective: Comparative analysis of long-term treatment outcomes in patients with early BC depending on the HER2 expression level and HR status, analysis of survival rates in groups of patients with different HER2 expression levels, depending on menopausal status.

Materials and methods: The study included 265 patients with BC (stage II) who received treatment at the N.N. Petrov National Medical Research Center of Oncology from 2011 to 2019. The patients were divided into groups depending on the HER2 expression level and HR status. Then, all patients were divided into 2 groups depending on menopausal status, then into subgroups depending on the HER2 expression level and HR status.

Results: The data of 265 patients with BC were analyzed, including 97 (36.6%) cases with HER2-low, of which 71 were HR+ (73.2%) and 26 (26.8%) patients were HR-. No statistically significant differences were observed in the survival analysis, but the worst 5-year relapse-free survival (RFS) was 73.1% in patients with HR-/HER2-low versus 76% with HR-/HER2-0. Overall survival (OS) rates were 88.5% with HR-/HER2-low and 98%, respectively. Also, in the HR-/HER2+ subgroup, RFS rates were low – 71.4%, OS – 94.3%. In premenopausal patients, 5-year RFS was 74.3% in the HR+/HER2-low subgroup versus HR+/HER2+ – 93.9% (p=0.010). In postmenopausal patients, there were no statistically significant differences in the RFS and OS analysis.

Conclusion: The lowest RFS and OS rates were observed in patients with HR-/HER2-low BC. Premenopausal patients had lower RFS rates with HR+/HER2-low versus HR+/HER2+ (74.3% versus 93.9%). Further studies to assess the relationship between hormone receptors, their levels, and the magnitude of HER2 expression are required.

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About the authors

Nestan B. Bekkeldiyeva

N.N. Petrov National Medical Research Center of Oncology

Author for correspondence.
Email: bekkeldiyeva.n@bk.ru
ORCID iD: 0009-0009-6055-720X

Postgraduate Student, Oncologist

Russian Federation, St. Petersburg

V. F. Semiglazov

N.N. Petrov National Medical Research Center of Oncology

Email: bekkeldiyeva.n@bk.ru
ORCID iD: 0000-0003-0077-9619

Dr. Sci. (Med.), Corr. Member of the RAS, Professor, Head of the Scientific Department of Breast Tumors

Russian Federation, St. Petersburg

A. G. Kudaibergenova

N.N. Petrov National Medical Research Center of Oncology

Email: bekkeldiyeva.n@bk.ru
ORCID iD: 0000-0001-7797-088X

Cand. Sci. (Med.), Pathologist of the Pathological Anatomy Department, SeniorResearcher of the Scientific Laboratory of Tumor Morphology

Russian Federation, St. Petersburg

A. S. Emelyanov

N.N. Petrov National Medical Research Center of Oncology

Email: bekkeldiyeva.n@bk.ru
ORCID iD: 0000-0002-0528-9937

Cand. Sci. (Med.), Oncologist

Russian Federation, St. Petersburg

K. S. Nikolaev

N.N. Petrov National Medical Research Center of Oncology

Email: bekkeldiyeva.n@bk.ru
ORCID iD: 0000-0003-3377-6369

Cand. Sci. (Med.), Oncologist

Russian Federation, St. Petersburg

V. V. Mortada

N.N. Petrov National Medical Research Center of Oncology

Email: bekkeldiyeva.n@bk.ru
ORCID iD: 0000-0002-1982-5710

Cand. Sci. (Med.), Oncologist, Plastic Surgeon

Russian Federation, St. Petersburg

K. Yu. Zernov

N.N. Petrov National Medical Research Center of Oncology

Email: bekkeldiyeva.n@bk.ru
ORCID iD: 0000-0002-2138-3982

Cand. Sci. (Med.), Oncologist, Plastic Surgeon

Russian Federation, St. Petersburg

Ch. A. Raimzhanov

N.N. Petrov National Medical Research Center of Oncology

Email: bekkeldiyeva.n@bk.ru
ORCID iD: 0009-0004-1321-1269

Ultrasound Diagnostics Doctor

Russian Federation, St. Petersburg

T. T. Tabagua

N.N. Petrov National Medical Research Center of Oncology

Email: bekkeldiyeva.n@bk.ru
ORCID iD: 0000-0003-1471-9473

Cand. Sci. (Med.), Oncologist

Russian Federation, St. Petersburg

R. S. Pesotsky

N.N. Petrov National Medical Research Center of Oncology

Email: bekkeldiyeva.n@bk.ru
ORCID iD: 0000-0002-2573-2211

Cand. Sci. (Med.), Oncologist

Russian Federation, St. Petersburg

Ya. I. Bondarchuk

N.N. Petrov National Medical Research Center of Oncology

Email: bekkeldiyeva.n@bk.ru
ORCID iD: 0000-0002-6442-0106

Postgraduate Student, Oncologist

Russian Federation, St. Petersburg

N. S. Amirov

N.N. Petrov National Medical Research Center of Oncology

Email: bekkeldiyeva.n@bk.ru
ORCID iD: 0000-0002-2421-3284

Oncologist

Russian Federation, St. Petersburg

D. A. Enaldieva

N.N. Petrov National Medical Research Center of Oncology

Email: bekkeldiyeva.n@bk.ru
ORCID iD: 0000-0002-2773-3111

Postgraduate Student, Oncologist

Russian Federation, St. Petersburg

D. G. Ulrikh

N.N. Petrov National Medical Research Center of Oncology

Email: bekkeldiyeva.n@bk.ru
ORCID iD: 0000-0002-1346-933X

Oncologist

Russian Federation, St. Petersburg

V. E. Levchenko

N.N. Petrov National Medical Research Center of Oncology

Email: bekkeldiyeva.n@bk.ru
ORCID iD: 0009-0003-6597-376X

Postgraduate Student

Russian Federation, St. Petersburg

P. V. Krivorotko

N.N. Petrov National Medical Research Center of Oncology

Email: bekkeldiyeva.n@bk.ru
ORCID iD: 0000-0002-4898-9159

Dr. Sci. (Med.), Professor, Head of the Department of Breast Tumors

Russian Federation, St. Petersburg

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Supplementary files

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2. Figure. 1. Interpretation of the 2018 ASCO/CAP guidelines and the 2023 ESMO consensus decision on HER2-weak positive breast cancer for each staining sample

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3. Figure. 2. Algorithm for determining НЕR2wеаk positive (HER2-low) status

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4. Figure. 3. Kaplan-Meier RFS curves for HR+/HER2-low versus HR+/HER2-0 (A), HR-/HER2-low versus HR-/HER2-0 (B), HR+/HER2-low versus HR+/HER2+ (C), HR-/HER2-low versus HR-/HER2+ (D)

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5. Figure. 4. Kaplan-Meier OS curves for HR+/HER2-low versus HR+/HER2-0 (A), HR-/HER2-low versus HR-/HER2-0 (B), HR+/HER2-low versus HR+/HER2+ (C), HR-/HER2-low versus HR-/HER2-0 (D)

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