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Clinical Trial
. 2025 Feb;10(2):104100.
doi: 10.1016/j.esmoop.2024.104100. Epub 2025 Jan 17.

HER2DX in HER2-positive inflammatory breast cancer: correlative insights and comparative analysis with noninflammatory breast cancers

F Lynce  1 , O Martínez-Sáez  2 , B Walbaum  3 , F Brasó-Maristany  4 , A G Waks  5 , P Villagrasa  6 , G Villacampa Javierre  7 , E Sanfeliu  8 , P Galván  4 , L Paré  6 , L M Anderson  9 , C M Perou  10 , J S Parker  11 , A Vivancos  12 , M K DiLullo  9 , S Pernas  13 , E P Winer  14 , B Overmoyer  5 , E A Mittendorf  15 , C Bueno-Muiño  16 , M Martín  17 , A Prat  18 , S M Tolaney  5
Affiliations
Clinical Trial

HER2DX in HER2-positive inflammatory breast cancer: correlative insights and comparative analysis with noninflammatory breast cancers

F Lynce et al. ESMO Open. 2025 Feb.

Abstract

Background: The HER2DX assay predicts long-term prognosis and pathologic complete response (pCR) in patients with early-stage human epidermal growth factor receptor 2 (HER2)-positive breast cancer receiving neoadjuvant systemic therapy but has not been evaluated in inflammatory breast cancer (IBC).

Patients and methods: HER2DX was analyzed in baseline biopsy tissues from 23 patients with stage III HER2-positive IBC on a phase II trial (NCT01796197) treated with neoadjuvant trastuzumab, pertuzumab, and paclitaxel (THP). To assess the assay's predictive accuracy for pCR in IBC, clinical-pathological features and outcomes from this IBC cohort were compared with 156 patients with stage III HER2-positive non-IBC from four different cohorts. Comparative analyses included HER2DX scores, gene signatures, and expression of individual genes between patients with IBC and non-IBC.

Results: Notable differences in clinicopathological characteristics included higher pertuzumab and chemotherapy usage and lower axillary burden in patients with IBC compared with non-IBC. In the combined cohort (n = 179), HER2DX pCR score and pertuzumab use were significant predictors of pCR, but not IBC status. The pCR rates in patients treated with trastuzumab-based chemotherapy (including IBC and non-IBC) were 68.9%, 58.5%, and 16.3% in the HER2DX pCR-high, -medium, and -low groups, respectively. Comparative gene expression analysis indicated minor differences between IBC and non-IBC affecting individual HER2, immune, and proliferation genes.

Conclusions: The HER2DX pCR score could predict pCR in stage III HER2-positive IBC following treatment with de-escalated neoadjuvant systemic therapy and in stage III HER2-positive non-IBC. Elevated pCR rates in HER2-positive IBC with high HER2DX pCR scores suggest there may be a role for treatment de-escalation in these patients and confirmatory studies are justified.

Keywords: HER2-positive; HER2DX; inflammatory breast cancer; pathologic complete response.

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Figures

Figure 1
Figure 1
Overall pCR rates in each patient group and according to the type of systemic therapy. ChT, chemotherapy; HP, trastuzumab and pertuzumab; IBC, inflammatory breast cancer; pCR, pathologic complete response.
Figure 2
Figure 2
Distribution of HER2DX pCR score groups in patients with IBC and non-IBC. IBC, inflammatory breast cancer; pCR, pathologic complete response.
Figure 3
Figure 3
HER2DX signatures as a continuous variable in patients with IBC and non-IBC. HER2, human epidermal growth factor receptor 2; IBC, inflammatory breast cancer; IGG; immunoglobulin.
Figure 4
Figure 4
HER2DX signatures by groups (high, medium, and low) in patients with IBC and non-IBC. HER2, human epidermal growth factor receptor 2; IBC, inflammatory breast cancer; IGG; immunoglobulin.
Figure 5
Figure 5
Unsupervised clustering of 179 patients with stage III HER2+ breast cancer with IBC (n = 23) and non-IBC (n = 156) (columns) and the expression of the 27 individual genes of HER2DX (rows). HER2, human epidermal growth factor receptor 2; IBC, inflammatory breast cancer; pCR, pathologic complete response.
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References

    1. Chang S., Parker S.L., Pham T., Buzdar A.U., Hursting S.D. Inflammatory breast carcinoma incidence and survival: the surveillance, epidemiology, and end results program of the National Cancer Institute, 1975-1992. Cancer. 1998;82(12):2366–2372. - PubMed
    1. Hance K.W., Anderson W.F., Devesa S.S., Young H.A., Levine P.H. Trends in inflammatory breast carcinoma incidence and survival: the surveillance, epidemiology, and end results program at the National Cancer Institute. J Natl Cancer Inst. 2005;97(13):966–975. - PMC - PubMed
    1. Dawood S., Lei X., Dent R., et al. Survival of women with inflammatory breast cancer: a large population-based study. Ann Oncol. 2014;25(6):1143–1151. - PMC - PubMed
    1. Abraham H.G., Xia Y., Mukherjee B., Merajver S.D. Incidence and survival of inflammatory breast cancer between 1973 and 2015 in the SEER database. Breast Cancer Res Treat. 2021;185(1):229–238. - PubMed
    1. Goldner B., Behrendt C.E., Schoellhammer H.F., Lee B., Chen S.L. Incidence of inflammatory breast cancer in women, 1992-2009, United States. Ann Surg Oncol. 2014;21(4):1267–1270. - PMC - PubMed

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