{
  "abstract": "The integration of anthracyclines with HER2-targeted agents in neoadjuvant therapy for HER2-positive breast cancer has been limited by cardiotoxicity concerns. This randomized phase II METIS trial (NCT04172259) assessed whether concurrent pegylated liposomal doxorubicin (PLD)-containing chemotherapy plus dual HER2 blockade (trastuzumab/pertuzumab) could improve efficacy without increasing cardiac risk. A total of 156 patients with stage II-III HER2-positive breast cancer were randomized to a PLD-based concurrent regimen or an epirubicin and cyclophosphamide (EC)-based sequential regimen. The PLD-based concurrent group achieved a higher pathological complete response (pCR) rate (67.5% vs. 48.7%; difference, 18.8%; 95% confidence interval [CI], 3.6-34.0; P = 0.033) compared with the EC-based sequential group, with greater benefit in hormone receptor-positive disease (58.7% vs. 36.7%) and stage II tumors (82.1% vs. 48.0%). After a median follow-up of 37.5 months, fewer event-free survival (EFS) events occurred in the PLD-based concurrent group (3 vs. 8), yielding a hazard ratio (HR) of 0.35 (95% CI, 0.09-1.32; P = 0.105). The estimated 3-year EFS rates were 96.0% (95% CI, 88.1-98.7) versus 90.7% (95% CI, 81.5-95.6). Achieving pCR was significantly associated with improved EFS (HR = 0.15; 95% CI, 0.03-0.71; P = 0.006). Cardiac safety was comparable, with no symptomatic cardiac dysfunction and only one grade ≥3 cardiotoxicity in the EC-based sequential group. These findings support PLD-based concurrent therapy with trastuzumab and pertuzumab as an effective and safe neoadjuvant option for high-risk HER2-positive breast cancer, warranting further evaluation in phase III trials.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Medical Oncology, Sun Yat-sen University Cancer Centre, State Key Laboratory of Oncology in South China, Collaborative Innovation Centre for Cancer Medicine, Guangzhou, China.",
    "Department of Breast Oncology, Shantou Central Hospital, Shantou, China.",
    "Department of Breast Surgery, The Tenth Affiliated Hospital of Southern Medical University (Dongguan People's Hospital), Dongguan, China.",
    "Department of Breast Surgery, Zhongshan City People's Hospital, Zhongshan, China.",
    "Department of Breast Surgery, The Affiliated Hospital of Guangdong Medical University, Zhanjiang, China.",
    "Department of Breast Surgery, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.",
    "Department of Medical Oncology, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou, China.",
    "Department of Breast Surgery, Lianjiang People's Hospital, Lianjiang, China.",
    "Department of Breast Oncology, Anhui Provincial Hospital, Hefei, China.",
    "Department of Breast Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.",
    "Department of Breast Surgery, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.",
    "Department of Medical Oncology, Sun Yat-sen University Cancer Centre, State Key Laboratory of Oncology in South China, Collaborative Innovation Centre for Cancer Medicine, Guangzhou, China. yuanzhy@sysucc.org.cn.",
    "Department of Medical Oncology, Sun Yat-sen University Cancer Centre, State Key Laboratory of Oncology in South China, Collaborative Innovation Centre for Cancer Medicine, Guangzhou, China. xiawen@sysucc.org.cn."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 25,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Qiufan Zheng",
      "orcid": "0000-0003-3752-8506"
    },
    {
      "affs": [
        0
      ],
      "name": "Shusen Wang",
      "orcid": "0000-0003-0139-5780"
    },
    {
      "affs": [
        1
      ],
      "name": "Zhiyong Wu"
    },
    {
      "affs": [
        2
      ],
      "name": "Muyi Zhong"
    },
    {
      "affs": [
        0
      ],
      "name": "Fei Xu",
      "orcid": "0000-0001-8543-6636"
    },
    {
      "affs": [
        3
      ],
      "name": "Shihui Ma"
    },
    {
      "affs": [
        4
      ],
      "name": "Yuanqi Zhang"
    },
    {
      "affs": [
        5
      ],
      "name": "Lehong Zhang"
    },
    {
      "affs": [
        0
      ],
      "name": "Yanxia Shi"
    },
    {
      "affs": [
        6
      ],
      "name": "Ying Wang"
    },
    {
      "affs": [
        7
      ],
      "name": "Heng Huang"
    },
    {
      "affs": [
        8
      ],
      "name": "Xiaopeng Ma"
    },
    {
      "affs": [
        9
      ],
      "name": "Xiangdong Xu"
    },
    {
      "affs": [
        10
      ],
      "name": "Haiyan Li"
    },
    {
      "affs": [
        0
      ],
      "name": "Jibin Li",
      "orcid": "0000-0001-7632-3648"
    },
    {
      "affs": [
        0
      ],
      "name": "Xiwen Bi"
    },
    {
      "affs": [
        0
      ],
      "name": "Jiajia Huang"
    },
    {
      "affs": [
        0
      ],
      "name": "Kuikui Jiang"
    },
    {
      "affs": [
        0
      ],
      "name": "Xin An"
    },
    {
      "affs": [
        0
      ],
      "name": "Ruoxi Hong"
    },
    {
      "affs": [
        0
      ],
      "name": "Meiting Chen"
    },
    {
      "affs": [
        0
      ],
      "name": "Cong Xue"
    },
    {
      "affs": [
        0
      ],
      "name": "Yongyi Zhong"
    },
    {
      "affs": [
        11
      ],
      "name": "Zhongyu Yuan"
    },
    {
      "affs": [
        12
      ],
      "name": "Wen Xia"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/a72zv0mpeawa9.bib",
  "cited_by": 0,
  "doi": "10.1038/s41392-026-02834-x",
  "fulltext_url": "https://europepmc.org/articles/PMC13724669",
  "id": "a72zv0mpeawa9",
  "issns": [
    "2095-9907",
    "2059-3635"
  ],
  "landing_url": "https://europepmc.org/article/MED/42967914",
  "language": "eng",
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Article"
    ],
    [
      "openalex",
      "2730|HER2/EGFR in Cancer Research"
    ]
  ],
  "openalex": "W7225035260",
  "pdf_url": "https://europepmc.org/articles/PMC13724669?pdf=render",
  "pmcid": "PMC13724669",
  "pmid": "42967914",
  "published": "2026-11-02",
  "publisher": "Nature Publishing Group",
  "ris": "https://research.draconitic.com/paper/a72zv0mpeawa9.ris",
  "sources": [
    {
      "first_seen": "2026-11-03T15:20:53Z",
      "native_id": "MED:42967914",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42967914"
    },
    {
      "first_seen": "2026-11-04T12:23:12Z",
      "native_id": "PMC13724669",
      "source": "pmc",
      "url": "https://doi.org/10.1038/s41392-026-02834-x"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2730|HER2/EGFR in Cancer Research",
      "subfield": "oncology"
    }
  ],
  "title": "Neoadjuvant concurrent or sequential anthracycline-containing chemotherapy and HER2-targeted agents for HER2-positive breast cancer: a randomized phase 2 study (METIS).",
  "title_text": "Neoadjuvant concurrent or sequential anthracycline-containing chemotherapy and HER2-targeted agents for HER2-positive breast cancer: a randomized phase 2 study (METIS).",
  "type": "peer-reviewed",
  "updated_at": "2026-11-06T12:21:05Z",
  "url": "https://research.draconitic.com/paper/a72zv0mpeawa9",
  "venue": "Signal transduction and targeted therapy",
  "versions": []
}