HER2-low — nowy podtyp raka piersi?
Streszczenie
W ostatnich latach trwają intensywne badania nad możliwościami stosowania leczenia anty-HER2 u chorych, u których obecnie rozpoznawany jest HER2-ujemny rak piersi. Pierwsze wyniki badań z koniugatami nowej generacji są obiecujące w grupie chorych z niską ekspresją HER2 (HER2-low), co oznacza ekspresję HER2 1+ lub 2+ w badaniu immunohistochemicznym z negatywnym wynikiem badania FISH (fluorescence in situ hybridisation). W obecnym artykule podsumowano dostępne informacje na temat potencjalnie nowej grupy raków piersi, które obecnie stanowią część raków luminalnych i potrójnie ujemnych. Omówiono doniesienia na temat cech klinicznych raków HER2-low oraz podsumowano wyniki przeprowadzonych badań z użyciem leków anty-HER2 u wymienionych chorych. Zwrócono uwagę na skuteczność koniugatów nowej generacji. Wyniki trwających badań z użyciem koniugatów być może pozwolą na stosowanie leczenia anty-HER2 w szerszej grupie chorych (w tym w rakach o niskiej ekspresji HER2). Nowa koncepcja raka piersi „HER2-low” wymusi rewizję dotychczasowego podziału raka piersi w zależności od ekspresji HER2 tylko na dwie grupy, wprowadzając grupę pośrednią o niskiej ekspresji HER2.
Słowa kluczowe: HER2rak piersi z niską ekspresją HER2koniugatpodtypy raka piersi
Referencje
- Perou CM, Sørlie T, Eisen MB, et al. Molecular portraits of human breast tumours. Nature. 2000; 406(6797): 747–752.
- Burstein HJ, Curigliano G, Thürlimann B, et al. Panelists of the St Gallen Consensus Conference. Customizing local and systemic therapies for women with early breast cancer: the St. Gallen International Consensus Guidelines for treatment of early breast cancer 2021. Ann Oncol. 2021; 32(10): 1216–1235.
- Schechter AL, Stern DF, Vaidyanathan L, et al. The neu oncogene: an erb-B-related gene encoding a 185,000-Mr tumour antigen. Nature. 1984; 312(5994): 513–516.
- Ross JS, Fletcher JA, Linette GP, et al. The Her-2/neu gene and protein in breast cancer 2003: biomarker and target of therapy. Oncologist. 2003; 8(4): 307–325.
- Slamon DJ, Clark GM, Wong SG, et al. Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science. 1987; 235(4785): 177–182.
- Gennari A, André F, Barrios CH, et al. ESMO Guidelines Committee. Electronic address: clinicalguidelines@esmo.org. ESMO Clinical Practice Guideline for the diagnosis, staging and treatment of patients with metastatic breast cancer. Ann Oncol. 2021; 32(12): 1475–1495.
- Murthy RK, Loi S, Okines A, et al. Tucatinib, Trastuzumab, and Capecitabine for HER2-Positive Metastatic Breast Cancer. N Engl J Med. 2020; 382(7): 597–609.
- Modi S, Saura C, Yamashita T, et al. DESTINY-Breast01 Investigators. Trastuzumab Deruxtecan in Previously Treated HER2-Positive Breast Cancer. N Engl J Med. 2020; 382(7): 610–621.
- Cortés J, Kim SB, Chung WP, et al. LBA1 Trastuzumab deruxtecan (T-DXd) vs trastuzumab emtansine (T-DM1) in patients (Pts) with HER2+ metastatic breast cancer (mBC): Results of the randomized phase III DESTINY-Breast03 study. Annals of Oncology. 2021; 32: S1287–S1288.
- Wolff AC, Hammond ME, 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.
- Tarantino P, Hamilton E, Tolaney SM, et al. HER2-Low Breast Cancer: Pathological and Clinical Landscape. J Clin Oncol. 2020; 38(17): 1951–1962.
- Lambein K, Van Bockstal M, Vandemaele L, et al. Distinguishing score 0 from score 1+ in HER2 immunohistochemistry-negative breast cancer: clinical and pathobiological relevance. Am J Clin Pathol. 2013; 140(4): 561–566.
- Schettini F, Chic N, Brasó-Maristany F, et al. Clinical, pathological, and PAM50 gene expression features of HER2-low breast cancer. NPJ Breast Cancer. 2021; 7(1): 1.
- 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.
- Mutai R, Barkan T, Moore A, et al. Prognostic impact of HER2-low expression in hormone receptor positive early breast cancer. Breast. 2021; 60: 62–69.
- Guven DC, Kaya MB, Fedai B, et al. HER2-low breast cancer could be associated with an increased risk of brain metastasis. Int J Clin Oncol. 2021 [Epub ahead of print].
- Paik S, Kim C, Wolmark N. HER2 status and benefit from adjuvant trastuzumab in breast cancer. N Engl J Med. 2008; 358(13): 1409–1411.
- Perez EA, Reinholz MM, Hillman DW, et al. HER2 and chromosome 17 effect on patient outcome in the N9831 adjuvant trastuzumab trial. J Clin Oncol. 2010; 28(28): 4307–4315.
- Fehrenbacher L, Cecchini R, Jr CG, et al. NSABP B-47/NRG Oncology Phase III Randomized Trial Comparing Adjuvant Chemotherapy With or Without Trastuzumab in High-Risk Invasive Breast Cancer Negative for HER2 by FISH and With IHC 1+ or 2+. J Clin Oncol. 2020; 38(5): 444–453.
- Burris HA, Rugo HS, Vukelja SJ, et al. Phase II study of the antibody drug conjugate trastuzumab-DM1 for the treatment of human epidermal growth factor receptor 2 (HER2)-positive breast cancer after prior HER2-directed therapy. J Clin Oncol. 2011; 29(4): 398–405.
- Krop IE, LoRusso P, Miller KD, et al. A phase II study of trastuzumab emtansine in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer who were previously treated with trastuzumab, lapatinib, an anthracycline, a taxane, and capecitabine. J Clin Oncol. 2012; 30(26): 3234–3241.
- Manich CS, O'Shaughnessy J, Aftimos PG, et al. LBA15 Primary outcome of the phase III SYD985.002/TULIP trial comparing [vic-]trastuzumab duocarmazine to physician’s choice treatment in patients with pre-treated HER2-positive locally advanced or metastatic breast cancer. Ann Oncol. 2021; 32: S1288.
- Banerji U, van Herpen CML, Saura C, et al. Trastuzumab duocarmazine in locally advanced and metastatic solid tumours and HER2-expressing breast cancer: a phase 1 dose-escalation and dose-expansion study. Lancet Oncol. 2019; 20(8): 1124–1135.
- Modi S, Park H, Murthy RK, et al. Antitumor Activity and Safety of Trastuzumab Deruxtecan in Patients With HER2-Low-Expressing Advanced Breast Cancer: Results From a Phase Ib Study. J Clin Oncol. 2020; 38(17): 1887–1896.