Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Oct 23:16:17588359241290720.
doi: 10.1177/17588359241290720. eCollection 2024.

Deciphering HER2-low breast cancer (BC): insights from real-world data in early stage breast cancer

Anna Pous  1   2   3   4 , Adrià Bernat-Peguera  2   5 , Assumpció López-Paradís  1   2   3 , Beatriz Cirauqui  1   2   3 , Vanesa Quiroga  1   2   3 , Iris Teruel  1   2   3 , Eudald Felip  1   2   5   6 , Angelica Ferrando-Díez  1   2   3 , Milana Bergamino  1   2   3 , Laia Boronat  1   2   3 , Margarita Romeo  1   2   3 , Gemma Soler  1   2   3 , Christian Mariño  1 , Paula Rodríguez-Martínez  3   7 , Laura Pons  3   7 , Ester Ballana  3   6   8 , Anna Martinez-Cardús  9   10 , Mireia Margelí  1   2   3
Affiliations

Deciphering HER2-low breast cancer (BC): insights from real-world data in early stage breast cancer

Anna Pous et al. Ther Adv Med Oncol. .

Abstract

Background: Human epidermal growth factor receptor 2 (HER2)-low has emerged as a potential new entity in breast cancer (BC). Data on this subset are limited, and prognostic results are controversial, evidencing the need of further data in a BC real-world cohort.

Methods: Patients with HER2-negative stage I-III BC diagnosed between 2006 and 2016 were retrospectively reviewed in a single cohort from the Catalan Institute of Oncology Badalona. Demographics and clinicopathological characteristics were examined via medical charts/electronic health records. We aim to describe and compare HER2-0/HER2-low populations through Chi-square or Fisher test, and explore its prognostic impact using Kaplan-Meier curves and Cox regression models.

Results: From a cohort of 1755 BC patients, 1401 invasive HER2-negative, stage I-III cases were evaluated. 87% were hormone receptor (HR)-positive versus 13% triple negative (TNBC). Overall, 43% were HER2-0 and 57% HER2-low (61% immunohistochemistry (IHC) 1+ and 39% IHC 2+). Comparing HER2-low versus HER2-0, HER2-low showed higher proportion of estrogen receptor (ER)-positive (91.6% vs 79.9%, p ⩽ 0.001) and progesterone receptor (PR)-positive (79.8% vs 68.9%, p ⩽ 0.001) cases. HER2-0 exhibited higher proportion of TNBC (20.1% vs 8.4%, p = 0.001), grade III tumors (28.8% vs 23.5%, p = 0.039), and higher Ki67 median value (26.47% vs 23.88%, p = 0.041). HER2-low was associated with longer time to distant recurrence (TTDR) compared to HER2-0 (67.8 vs 54.1 months; p = 0.015) and better BC-related survival (19.2 vs 16.3 years; p = 0.033). In the multivariable analysis, HER2-low was not an independent prognostic factor for TTDR and BC-related survival. ER expression showed a strong association with longer TTDR (Hazard Ratio: 0.425, p ⩽ 0.001) and improved BC-related survival (Hazard Ratio: 0.380, p ⩽ 0.001). PR expression was also associated with longer TTDR (Hazard Ratio: 0.496, p ⩽ 0.001), and improved BC-related survival (Hazard Ratio: 0.488, p ⩽ 0.001). Histological grade III was significantly associated with shorter TTDR (Hazard Ratio: 1.737, p = 0.002). Positive nodal status was the strongest factor correlated with worse BC-related survival (Hazard Ratio: 2.747, p ⩽ 0.001).

Conclusion: HER2-low was significantly associated with HR-positive disease, whereas HER2-0 group had higher incidence of TNBC, histological grade III and higher Ki67%. Although HER2-low group was associated with longer TTDR and improved BC-related survival, these findings could be explained by the greater proportion of favorable prognostic features in this subgroup compared to HER2-0.

Keywords: HER2-low; biomarkers; breast cancer; human epidermal growth factor receptor 2; survival.

PubMed Disclaimer

Conflict of interest statement

A.P. declares being invited as speaker for GSK, Eisai, and Lilly, travel expenses and congress assistance from Lilly, Gilead, Dr. Reddys, and Pfizer. Member of GEICAM, SEOM, ESMO, and SOLTI societies. A.B.P. declares no conflicts of interest. A.L. declares being invited as speaker for Eisai, Lilly, and Novartis, and travel expenses from Roche, Gilead, and Novartis. Member of GEICAM, SEOM, ESMO, and SOLTI societies. B.C. declares being invited as speaker for BMS, Merck, and MSD. Training grants from BMS, Merck, and MSD. Advisory board: BMS, Merck, and MSD. Member of GEICAM, SEOM, ESMO, and SOLTI societies, and member of the board of directors from TTCC. V.Q. declares being invited as speaker for AstraZeneca, Novartis, Pfizer, and Roche. Advisory board for Roche. Educational activities from GSK, Lilly, and Pfizer and travel expenses from Pfizer and Roche. Member of GEICAM, SEOM, and SOLTI societies. I.T. declares being invited as speaker for Astra Zeneca. Training grants from Novartis, Lilly, ROCHE, and MSD. Member of GEICAM, SEOM, ESMO, and SOLTI societies. E.F declares travel expenses from Pfizer, Lilly, Novartis, and Roche. Speaking fees from Pfizer and advisory board from Novartis. A.F.D. declares being invited as speaker for MSD and Angelini Pharma; and travel expenses from MSD, Lilly, Roche, Merck, and BMS. M.B. declares advisory funding from Eisai, AstraZeneca, Pfizer, Novartis, and travel expenses from Novartis and AstraZeneca. L.B. declares no conflicts of interest. M.R. declares advisory funding from GSK and AstraZeneca, and travel expenses from MSD and AstraZeneca. G.S. declares no conflicts of interest. C.M. declares no conflicts of interest. P.R.M. declares no conflicts of interest. L.P declares no conflicts of interest. E.B. declares no conflicts of interest. A.M.C. declares no conflicts of interest. M.M. declares being invited as speaker for Pfizer, Novartis, and Lilly. Institution research grants from Pfizer and Gilead. Consultant advisory board from Novartis, Lilly, and Menarini. Travel expenses and congress assistance from Gilead, Pfizer, and Roche.

Figures

Figure 1.
Figure 1.
Flow diagram of the study. FISH: fluorescence in situ hybridization; N: number.
Figure 2.
Figure 2.
Hormone receptor status, HER2-low status, and IHC scores distributions. (a) Percentage IHC scores distribution within the hormone receptor-positive (HR-positive) and negative (TNBC) population. Percentage of HER2-low tumors is shown in each population. (b) Percentage hormone receptor-positive (HR-positive) and negative (TNBC) population distributions within each IHC score (in percentage). Percentage of HER2-low tumors is shown in each population. HR, hormone receptors, IHC, immunohistochemistry, ISH, in situ hybridization (including either fluorescent in situ hybridization (FISH)), chromogenic in situ hybridization (SISH), and silver enhanced in situ hybridization (CISH)).
Figure 3.
Figure 3.
Histological grade and (a) Ki67 score (b) distribution in HER2-0 versus HER2-low tumors. HER2, Human epidermal growth factor receptor 2.
Figure 4.
Figure 4.
Time to recurrence, time to distant recurrence, and time to local recurrence, BC-related survival and OS in the global population. Mean TR in HER2-0 (median not reached) was 191.24 m (184.86–197.61) versus 201.81 (196.5–207.11) in HER2-low (p = 0.094). Mean TTLR in HER2-0 (median not reached) was 102.53 m (86.28–118.78) versus 146.63 m (128.81–164.44) in HER2-low (p = 0.054). Median TTDR in HER2-0 was 54.0 m (34.61–53.39) versus 44.0 m (37.68–70.32) in HER2-low (p = 0.011). Mean cancer-related survival in HER2-0 (median not reached) was 199.43 m (193.47–205.37) versus 235.58 m (227.34–243.82) in HER2-low (p = 0.02). Mean OS in HER2-0 (median not reached) was 174.78 m (167.87–181.70) versus 197.85 m (189.58–206.12) in HER2-low (p = 0.235). HER2, Human epidermal growth factor receptor 2; TTLR, time to local recurrence.
Figure 5.
Figure 5.
Multivariable analysis including major clinicopathological factors for TTDR. ER and PR positive expression were significantly associated with longer TTDR (Hazard Ratio 0.425, p ⩽ 0.001) and (Hazard Ratio 0.469, p ⩽ 0.001), respectively, while histological grade III (Hazard Ratio 1.744, p = 0.002) was associated with worse prognosis. TTDR, time to distant recurrence.
Figure 6.
Figure 6.
Multivariable analysis including major clinicopathological factors for BC-related survival. ER and PR positive expression were significantly associated with improved BC-related survival (Hazard Ratio 0.389, p ⩽ 0.001) and (Hazard Ratio 0.0.488, p ⩽ 0.001), respectively. Positive nodal status (Hazard Ratio 2.747, p ⩽ 0.001) and histological grade III (Hazard Ratio 1.943, p = 0.017) were associated with worse BC-survival. BC, breast cancer; ER, estrogen receptor; PR, progesterone receptor.
See this image and copyright information in PMC

References

    1. Ahn S, Woo JW, Lee K, et al.. HER2 status in breast cancer: changes in guidelines and complicating factors for interpretation. J Pathol Transl Med 2020; 54(1): 34–44. - PMC - PubMed
    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. - PubMed
    1. De Moura Leite L, Cesca MG, Tavares MC, et al.. HER2-low status and response to neoadjuvant chemotherapy in HER2 negative early breast cancer. Breast Cancer Res Treat 2021; 190(1): 155–163. - PubMed
    1. 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. - PMC - PubMed
    1. Agostinetto E, Rediti M, Fimereli D, et al.. HER2-low breast cancer: molecular characteristics and prognosis. Cancers (Basel) 2021; 13(11): 2824. - PMC - PubMed

LinkOut - more resources