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. 2023 Jun 2;9(1):50.
doi: 10.1038/s41523-023-00555-w.

Clinical outcomes of de novo metastatic HER2-positive inflammatory breast cancer

Ana C Garrido-Castro  1   2   3 , Meredith M Regan  3   4 , Samuel M Niman  4 , Faina Nakhlis  2   3   5 , Claire Remolano  1 , Jennifer M Rosenbluth  1   2   3   6 , Caroline Block  1   2   3 , Laura E Warren  2   3   7 , Jennifer R Bellon  2   3   7 , Eren Yeh  3   8 , Beth T Harrison  3   9 , Elizabeth Troll  1 , Nancy U Lin  1   2   3 , Sara M Tolaney  1   2   3 , Beth Overmoyer  1   2   3 , Filipa Lynce  10   11   12
Affiliations

Clinical outcomes of de novo metastatic HER2-positive inflammatory breast cancer

Ana C Garrido-Castro et al. NPJ Breast Cancer. .

Abstract

Inflammatory breast cancer (IBC) is a rare, aggressive form of breast cancer that presents as de novo metastatic disease in 20-30% of cases, with one-third of cases demonstrating HER2-positivity. There has been limited investigation into locoregional therapy utilization following HER2-directed systemic therapy for these patients, and their locoregional progression or recurrence (LRPR) and survival outcomes. Patients with de novo HER2-positive metastatic IBC (mIBC) were identified from an IRB-approved IBC registry at Dana-Farber Cancer Institute. Clinical, pathology, and treatment data were abstracted. Rates of LRPR, progression-free survival (PFS), overall survival (OS), and pathologic complete response (pCR) were determined. Seventy-eight patients diagnosed between 1998 and 2019 were identified. First-line systemic therapy comprised chemotherapy for most patients (97.4%) and HER2-directed therapy for all patients (trastuzumab [47.4%]; trastuzumab+pertuzumab [51.3%]; or trastuzumab emtansine [1.3%]). At a median follow-up of 2.7 years, the median PFS was 1.0 year, and the median OS was 4.6 years. The 1- and 2-year cumulative incidence of LRPR was 20.7% and 29.0%, respectively. Mastectomy was performed after systemic therapy in 41/78 patients (52.6%); 10 had a pCR (24.4%) and all were alive at last follow-up (1.3-8.9 years after surgery). Among 56 patients who were alive and LRPR-free at one year, 10 developed LRPR (surgery group = 1; no-surgery group = 9). In conclusion, patients with de novo HER2-positive mIBC who undergo surgery have favorable outcomes. More than half of patients received systemic and local therapy with good locoregional control and prolonged survival, suggesting a potential role for local therapy.

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Conflict of interest statement

The authors report the following potential financial competing interests: Consulting/Advising Role: Novartis (S.M.T.), Pfizer (S.M.T., F.L.), Merck (S.M.T.), Eli Lilly and Company (S.M.T.), Nektar Therapeutics (S.M.T.), NanoString Technologies (S.M.T.), AstraZeneca (S.M.T., M.M.R., N.U.L., F.L.), Puma Biotechnology (S.M.T., N.U.L.), Genentech/Roche (S.M.T.), Eisai (S.M.T.), Sanofi (S.M.T.), Bristol Myers Squibb (S.M.T., M.M.R.), Seattle Genetics (S.M.T., N.U.L.), Odonate Therapeutics (S.M.T.), OncoPep (S.M.T.), Kyowa Hakko Kirin (S.M.T.), Samsung Bioepis (S.M.T.), CytomX Therapeutics (S.M.T., F.L.), Daiichi Sankyo (S.M.T., N.U.L., F.L.), Athenex (S.M.T.), Gilead Sciences (S.M.T.), Mersana (S.M.T.), Certara (S.M.T.), Chugai Pharma (S.M.T.), Ellipses Pharma (S.M.T.), Infinity (S.M.T.), 4D Pharma (S.M.T.), OncoSec Medical Inc. (S.M.T.), BeyondSpring Pharmaceuticals (S.M.T.), OncXerna (S.M.T.), Zymeworks (S.M.T.), Zentalis (S.M.T.), Blueprint Medicines (S.M.T.), Reveal Genomics (S.M.T.), ARC Therapeutics (S.M.T.), Ipsen Biopharmaceuticals (M.M.R.), DebioPharm (M.M.R.), Tolmar Pharmaceuticals (M.M.R.), Denali Therapeutics (N.U.L.), Prelude Therapeutics (N.U.L.), Olema Pharmaceuticals (N.U.L.), Aleta BioPharma (N.U.L.), Affinia Therapeutics (N.U.L.), Voyager Therapeutics (N.U.L.), Janssen (N.U.L.), Blueprint Medicines (N.U.L.), OncoSec Medical, Inc. (FL). Institutional Research Funding: Genentech/Roche (S.M.T., N.U.L.), Merck (S.M.T., ACG-C, N.U.L.), Exelixis (S.M.T.), Pfizer (S.M.T., M.M.R., N.U.L.), Eli Lilly and Company (S.M.T.), Novartis (S.M.T.), Bristol Myers Squibb (S.M.T., M.M.R.), Eisai (S.M.T., FL), AstraZeneca (S.M.T., A.C.G.C., M.M.R., N.U.L., FL), NanoString Technologies (S.M.T.), Cyclacel Pharmaceuticals (S.M.T.), Nektar Therapeutics (S.M.T.), Gilead Sciences (S.M.T., A.C.G.C., FL), Odonate Therapeutics (S.M.T.), Sanofi (S.M.T.), Seattle Genetics (S.M.T., N.U.L.), Ipsen Biopharmaceuticals (M.M.R.), TerSera Therapeutics (M.M.R.), DebioPharm (M.M.R.), Pierre Fabre (M.M.R.), Roche (M.M.R.), Bayer (M.M.R.), Zion Pharmaceuticals (N.U.L.), Olema Pharmaceuticals (N.U.L.), Daiichi-Sankyo (A.C.G.C.), Zenith Epigenetics (A.C.G.C.). Stock and Ownership Interests: Artera, Inc. <$50,000 and <5% as it relates to consulting activities; options are not currently valued or in-hand (N.U.L.). Speaker Honorarium: Varian (J.R.B.). Royalties: UpToDate, Inc. (N.U.L.). Travel support: Roche/Genentech (A.C.G.C.). The authors have no non-financial competing interests to declare.

Figures

Fig. 1
Fig. 1. Progression-free survival (PFS) and overall survival (OS) from diagnosis in patients with de novo metastatic HER2-positive inflammatory breast cancer (IBC).
Median follow-up in overall cohort: 2.7 years (yrs). a Overall cohort. b According to sites of disease at presentation (CNS ± other [blue color]; visceral ± other [red color]; bone ± LNs [grey color]. c According to initial HER2-directed therapy (trastuzumab [blue color]; trastuzumab+pertuzumab [red color]). CI confidence interval, CNS central nervous system, HER2 human epidermal growth factor receptor 2, LN lymph node, NE not estimable, trastu trastuzumab.
Fig. 2
Fig. 2. Overall survival (OS) from the time of surgery in patients with de novo HER2-positive metastatic inflammatory breast cancer (mIBC) who underwent mastectomy.
Among patients diagnosed with de novo HER2-positive mIBC who underwent mastectomy (n = 41), the median OS from surgery was 5.2 years (95% CI: 3.5–8.4). CI confidence interval, HER2 human epidermal growth factor receptor 2.
Fig. 3
Fig. 3. Cumulative incidence of locoregional progression or recurrence (LRPR), with competing risk of death, among patients with de novo HER2-positive metastatic inflammatory breast cancer (mIBC).
Among patients diagnosed with de novo HER2-positive mIBC (n = 78), the cumulative incidence of LRPR was 20.7% (95% CI: 12.5–30.4) and 29.0% (95% CI: 19.2–39.5) at 1 and 2 years, respectively. Cumulative incidence of LRPR is shown as the blue line; competing risk of death is shown as the dashed black line. CI confidence interval; HER2 human epidermal growth factor receptor 2; yr year.
Fig. 4
Fig. 4. Cumulative incidence of locoregional progression or recurrence (LRPR), with competing risk of death, among patients with de novo HER2-positive metastatic inflammatory breast cancer (mIBC) who were alive and free of LRPR at 12 months since diagnosis, according to receipt of surgery.
Among patients diagnosed with de novo HER2-positive mIBC alive and free of LRPR at 12 months from diagnosis (n = 56), 10 patients subsequently developed LRPR. The cumulative incidence of LRPR over the subsequent 1 and 2 years from the 12-month landmark was 10.8% (95% CI: 4.3–20.6) and 14.8% (95% CI: 6.9–25.7), respectively. Cumulative incidence of LRPR is shown as the blue line; competing risk of death is shown as the dashed black line. CI confidence interval; HER2 human epidermal growth factor receptor 2; yr year.
See this image and copyright information in PMC

References

    1. Anderson WF, Schairer C, Chen BE, Hance KW, Levine PH. Epidemiology of inflammatory breast cancer (IBC) Breast Dis. 2005;22:9–23. doi: 10.3233/BD-2006-22103. - DOI - PMC - PubMed
    1. Hance KW, Anderson WF, Devesa SS, Young HA, Levine PH. 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;97:966–975. doi: 10.1093/jnci/dji172. - DOI - PMC - PubMed
    1. Schlichting JA, Soliman AS, Schairer C, Schottenfeld D, Merajver SD. Inflammatory and non-inflammatory breast cancer survival by socioeconomic position in the Surveillance, Epidemiology, and End Results database, 1990-2008. Breast Cancer Res. Treat. 2012;134:1257–1268. doi: 10.1007/s10549-012-2133-2. - DOI - PMC - PubMed
    1. Dano D, et al. Metastatic inflammatory breast cancer: survival outcomes and prognostic factors in the national, multicentric, and real-life French cohort (ESME) ESMO Open. 2021;6:100220. doi: 10.1016/j.esmoop.2021.100220. - DOI - PMC - PubMed
    1. Wingo PA, Jamison PM, Young JL, Gargiullo P. Population-based statistics for women diagnosed with inflammatory breast cancer (United States) Cancer Causes Control. 2004;15:321–328. doi: 10.1023/B:CACO.0000024222.61114.18. - DOI - PubMed