title: Molecular Heterogeneity and Response to Neoadjuvant Human Epidermal Growth Factor Receptor 2 Targeting in CALGB 40601, a Randomized Phase III Trial of Paclitaxel Plus Trastuzumab With or Without Lapatinib.
abstract: OBJECTIVE
  Dual human epidermal growth factor receptor 2 (HER2) targeting can increase pathologic complete response rates (pCRs) to neoadjuvant therapy and improve progression-free survival in metastatic disease. CALGB 40601 examined the impact of dual HER2 blockade consisting of trastuzumab and lapatinib added to paclitaxel, considering tumor and microenvironment molecular features.
  
  
  METHODS
  Patients with stage II to III HER2-positive breast cancer underwent tumor biopsy followed by random assignment to paclitaxel plus trastuzumab alone (TH) or with the addition of lapatinib (THL) for 16 weeks before surgery. An investigational arm of paclitaxel plus lapatinib (TL) was closed early. The primary end point was pCR in the breast; correlative end points focused on molecular features identified by gene expression-based assays.
  
  
  RESULTS
  Among 305 randomly assigned patients (THL, n = 118; TH, n = 120; TL, n = 67), the pCR rate was 56% (95% CI, 47% to 65%) with THL and 46% (95% CI, 37% to 55%) with TH (P = .13), with no effect of dual therapy in the hormone receptor-positive subset but a significant increase in pCR with dual therapy in those with hormone receptor-negative disease (P = .01). The tumors were molecularly heterogeneous by gene expression analysis using mRNA sequencing (mRNAseq). pCR rates significantly differed by intrinsic subtype (HER2 enriched, 70%; luminal A, 34%; luminal B, 36%; P < .001). In multivariable analysis treatment arm, intrinsic subtype, HER2 amplicon gene expression, p53 mutation signature, and immune cell signatures were independently associated with pCR. Post-treatment residual disease was largely luminal A (69%).
  
  
  CONCLUSIONS
  pCR to dual HER2-targeted therapy was not significantly higher than single HER2 targeting. Tissue analysis demonstrated a high degree of intertumoral heterogeneity with respect to both tumor genomics and tumor microenvironment that significantly affected pCR rates. These factors should be considered when interpreting and designing trials in HER2-positive disease.
authors.affiliation: Lisa A. Carey, David W. Ollila, Carey K. Anders, Katherine A. Hoadley, Michael Iglesia, and Charles M. Perou, University of North Carolina Chapel Hill, Chapel Hill; Constance T. Cirrincione and Brandelyn N. Pitcher, Alliance Statistics and Data Center, Duke University, Durham, NC; Donald A. Berry, Alliance Statistics and Data Center, MD Anderson, Houston, TX; William T. Barry, Alliance Statistics and Data Center, Dana-Farber Cancer Institute; Ian E. Krop and Eric P. Winer, Dana-Farber Cancer Institute, Boston, MA; Lyndsay N. Harris, University Hospitals of Cleveland, Cleveland, OH; Norah Lynn Henry, University of Michigan, Ann Arbor, MI; Douglas J. Weckstein, New Hampshire Hematology-Oncology, Hooksett, NH; Baljit Singh, New York University; Clifford A. Hudis, Memorial Sloan-Kettering Cancer Center, New York, NY; and Maggie Chon U. Cheang, Clinical Trials and Statistics Unit, Institute of Cancer Research, Belmont, United Kingdom. lisa_carey@med.unc.edu.
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Carey
authors.affiliation: Lisa A. Carey, David W. Ollila, Carey K. Anders, Katherine A. Hoadley, Michael Iglesia, and Charles M. Perou, University of North Carolina Chapel Hill, Chapel Hill; Constance T. Cirrincione and Brandelyn N. Pitcher, Alliance Statistics and Data Center, Duke University, Durham, NC; Donald A. Berry, Alliance Statistics and Data Center, MD Anderson, Houston, TX; William T. Barry, Alliance Statistics and Data Center, Dana-Farber Cancer Institute; Ian E. Krop and Eric P. Winer, Dana-Farber Cancer Institute, Boston, MA; Lyndsay N. Harris, University Hospitals of Cleveland, Cleveland, OH; Norah Lynn Henry, University of Michigan, Ann Arbor, MI; Douglas J. Weckstein, New Hampshire Hematology-Oncology, Hooksett, NH; Baljit Singh, New York University; Clifford A. Hudis, Memorial Sloan-Kettering Cancer Center, New York, NY; and Maggie Chon U. Cheang, Clinical Trials and Statistics Unit, Institute of Cancer Research, Belmont, United Kingdom.
authors.forename: Donald A
authors.initials: DA
authors.lastname: Berry
authors.affiliation: Lisa A. Carey, David W. Ollila, Carey K. Anders, Katherine A. Hoadley, Michael Iglesia, and Charles M. Perou, University of North Carolina Chapel Hill, Chapel Hill; Constance T. Cirrincione and Brandelyn N. Pitcher, Alliance Statistics and Data Center, Duke University, Durham, NC; Donald A. Berry, Alliance Statistics and Data Center, MD Anderson, Houston, TX; William T. Barry, Alliance Statistics and Data Center, Dana-Farber Cancer Institute; Ian E. Krop and Eric P. Winer, Dana-Farber Cancer Institute, Boston, MA; Lyndsay N. Harris, University Hospitals of Cleveland, Cleveland, OH; Norah Lynn Henry, University of Michigan, Ann Arbor, MI; Douglas J. Weckstein, New Hampshire Hematology-Oncology, Hooksett, NH; Baljit Singh, New York University; Clifford A. Hudis, Memorial Sloan-Kettering Cancer Center, New York, NY; and Maggie Chon U. Cheang, Clinical Trials and Statistics Unit, Institute of Cancer Research, Belmont, United Kingdom.
authors.forename: Constance T
authors.initials: CT
authors.lastname: Cirrincione
authors.affiliation: Lisa A. Carey, David W. Ollila, Carey K. Anders, Katherine A. Hoadley, Michael Iglesia, and Charles M. Perou, University of North Carolina Chapel Hill, Chapel Hill; Constance T. Cirrincione and Brandelyn N. Pitcher, Alliance Statistics and Data Center, Duke University, Durham, NC; Donald A. Berry, Alliance Statistics and Data Center, MD Anderson, Houston, TX; William T. Barry, Alliance Statistics and Data Center, Dana-Farber Cancer Institute; Ian E. Krop and Eric P. Winer, Dana-Farber Cancer Institute, Boston, MA; Lyndsay N. Harris, University Hospitals of Cleveland, Cleveland, OH; Norah Lynn Henry, University of Michigan, Ann Arbor, MI; Douglas J. Weckstein, New Hampshire Hematology-Oncology, Hooksett, NH; Baljit Singh, New York University; Clifford A. Hudis, Memorial Sloan-Kettering Cancer Center, New York, NY; and Maggie Chon U. Cheang, Clinical Trials and Statistics Unit, Institute of Cancer Research, Belmont, United Kingdom.
authors.forename: William T
authors.initials: WT
authors.lastname: Barry
authors.affiliation: Lisa A. Carey, David W. Ollila, Carey K. Anders, Katherine A. Hoadley, Michael Iglesia, and Charles M. Perou, University of North Carolina Chapel Hill, Chapel Hill; Constance T. Cirrincione and Brandelyn N. Pitcher, Alliance Statistics and Data Center, Duke University, Durham, NC; Donald A. Berry, Alliance Statistics and Data Center, MD Anderson, Houston, TX; William T. Barry, Alliance Statistics and Data Center, Dana-Farber Cancer Institute; Ian E. Krop and Eric P. Winer, Dana-Farber Cancer Institute, Boston, MA; Lyndsay N. Harris, University Hospitals of Cleveland, Cleveland, OH; Norah Lynn Henry, University of Michigan, Ann Arbor, MI; Douglas J. Weckstein, New Hampshire Hematology-Oncology, Hooksett, NH; Baljit Singh, New York University; Clifford A. Hudis, Memorial Sloan-Kettering Cancer Center, New York, NY; and Maggie Chon U. Cheang, Clinical Trials and Statistics Unit, Institute of Cancer Research, Belmont, United Kingdom.
authors.forename: Brandelyn N
authors.initials: BN
authors.lastname: Pitcher
authors.affiliation: Lisa A. Carey, David W. Ollila, Carey K. Anders, Katherine A. Hoadley, Michael Iglesia, and Charles M. Perou, University of North Carolina Chapel Hill, Chapel Hill; Constance T. Cirrincione and Brandelyn N. Pitcher, Alliance Statistics and Data Center, Duke University, Durham, NC; Donald A. Berry, Alliance Statistics and Data Center, MD Anderson, Houston, TX; William T. Barry, Alliance Statistics and Data Center, Dana-Farber Cancer Institute; Ian E. Krop and Eric P. Winer, Dana-Farber Cancer Institute, Boston, MA; Lyndsay N. Harris, University Hospitals of Cleveland, Cleveland, OH; Norah Lynn Henry, University of Michigan, Ann Arbor, MI; Douglas J. Weckstein, New Hampshire Hematology-Oncology, Hooksett, NH; Baljit Singh, New York University; Clifford A. Hudis, Memorial Sloan-Kettering Cancer Center, New York, NY; and Maggie Chon U. Cheang, Clinical Trials and Statistics Unit, Institute of Cancer Research, Belmont, United Kingdom.
authors.forename: Lyndsay N
authors.initials: LN
authors.lastname: Harris
authors.affiliation: Lisa A. Carey, David W. Ollila, Carey K. Anders, Katherine A. Hoadley, Michael Iglesia, and Charles M. Perou, University of North Carolina Chapel Hill, Chapel Hill; Constance T. Cirrincione and Brandelyn N. Pitcher, Alliance Statistics and Data Center, Duke University, Durham, NC; Donald A. Berry, Alliance Statistics and Data Center, MD Anderson, Houston, TX; William T. Barry, Alliance Statistics and Data Center, Dana-Farber Cancer Institute; Ian E. Krop and Eric P. Winer, Dana-Farber Cancer Institute, Boston, MA; Lyndsay N. Harris, University Hospitals of Cleveland, Cleveland, OH; Norah Lynn Henry, University of Michigan, Ann Arbor, MI; Douglas J. Weckstein, New Hampshire Hematology-Oncology, Hooksett, NH; Baljit Singh, New York University; Clifford A. Hudis, Memorial Sloan-Kettering Cancer Center, New York, NY; and Maggie Chon U. Cheang, Clinical Trials and Statistics Unit, Institute of Cancer Research, Belmont, United Kingdom.
authors.forename: David W
authors.initials: DW
authors.lastname: Ollila
authors.affiliation: Lisa A. Carey, David W. Ollila, Carey K. Anders, Katherine A. Hoadley, Michael Iglesia, and Charles M. Perou, University of North Carolina Chapel Hill, Chapel Hill; Constance T. Cirrincione and Brandelyn N. Pitcher, Alliance Statistics and Data Center, Duke University, Durham, NC; Donald A. Berry, Alliance Statistics and Data Center, MD Anderson, Houston, TX; William T. Barry, Alliance Statistics and Data Center, Dana-Farber Cancer Institute; Ian E. Krop and Eric P. Winer, Dana-Farber Cancer Institute, Boston, MA; Lyndsay N. Harris, University Hospitals of Cleveland, Cleveland, OH; Norah Lynn Henry, University of Michigan, Ann Arbor, MI; Douglas J. Weckstein, New Hampshire Hematology-Oncology, Hooksett, NH; Baljit Singh, New York University; Clifford A. Hudis, Memorial Sloan-Kettering Cancer Center, New York, NY; and Maggie Chon U. Cheang, Clinical Trials and Statistics Unit, Institute of Cancer Research, Belmont, United Kingdom.
authors.forename: Ian E
authors.initials: IE
authors.lastname: Krop
authors.affiliation: Lisa A. Carey, David W. Ollila, Carey K. Anders, Katherine A. Hoadley, Michael Iglesia, and Charles M. Perou, University of North Carolina Chapel Hill, Chapel Hill; Constance T. Cirrincione and Brandelyn N. Pitcher, Alliance Statistics and Data Center, Duke University, Durham, NC; Donald A. Berry, Alliance Statistics and Data Center, MD Anderson, Houston, TX; William T. Barry, Alliance Statistics and Data Center, Dana-Farber Cancer Institute; Ian E. Krop and Eric P. Winer, Dana-Farber Cancer Institute, Boston, MA; Lyndsay N. Harris, University Hospitals of Cleveland, Cleveland, OH; Norah Lynn Henry, University of Michigan, Ann Arbor, MI; Douglas J. Weckstein, New Hampshire Hematology-Oncology, Hooksett, NH; Baljit Singh, New York University; Clifford A. Hudis, Memorial Sloan-Kettering Cancer Center, New York, NY; and Maggie Chon U. Cheang, Clinical Trials and Statistics Unit, Institute of Cancer Research, Belmont, United Kingdom.
authors.forename: Norah Lynn
authors.initials: NL
authors.lastname: Henry
authors.affiliation: Lisa A. Carey, David W. Ollila, Carey K. Anders, Katherine A. Hoadley, Michael Iglesia, and Charles M. Perou, University of North Carolina Chapel Hill, Chapel Hill; Constance T. Cirrincione and Brandelyn N. Pitcher, Alliance Statistics and Data Center, Duke University, Durham, NC; Donald A. Berry, Alliance Statistics and Data Center, MD Anderson, Houston, TX; William T. Barry, Alliance Statistics and Data Center, Dana-Farber Cancer Institute; Ian E. Krop and Eric P. Winer, Dana-Farber Cancer Institute, Boston, MA; Lyndsay N. Harris, University Hospitals of Cleveland, Cleveland, OH; Norah Lynn Henry, University of Michigan, Ann Arbor, MI; Douglas J. Weckstein, New Hampshire Hematology-Oncology, Hooksett, NH; Baljit Singh, New York University; Clifford A. Hudis, Memorial Sloan-Kettering Cancer Center, New York, NY; and Maggie Chon U. Cheang, Clinical Trials and Statistics Unit, Institute of Cancer Research, Belmont, United Kingdom.
authors.forename: Douglas J
authors.initials: DJ
authors.lastname: Weckstein
authors.affiliation: Lisa A. Carey, David W. Ollila, Carey K. Anders, Katherine A. Hoadley, Michael Iglesia, and Charles M. Perou, University of North Carolina Chapel Hill, Chapel Hill; Constance T. Cirrincione and Brandelyn N. Pitcher, Alliance Statistics and Data Center, Duke University, Durham, NC; Donald A. Berry, Alliance Statistics and Data Center, MD Anderson, Houston, TX; William T. Barry, Alliance Statistics and Data Center, Dana-Farber Cancer Institute; Ian E. Krop and Eric P. Winer, Dana-Farber Cancer Institute, Boston, MA; Lyndsay N. Harris, University Hospitals of Cleveland, Cleveland, OH; Norah Lynn Henry, University of Michigan, Ann Arbor, MI; Douglas J. Weckstein, New Hampshire Hematology-Oncology, Hooksett, NH; Baljit Singh, New York University; Clifford A. Hudis, Memorial Sloan-Kettering Cancer Center, New York, NY; and Maggie Chon U. Cheang, Clinical Trials and Statistics Unit, Institute of Cancer Research, Belmont, United Kingdom.
authors.forename: Carey K
authors.initials: CK
authors.lastname: Anders
authors.affiliation: Lisa A. Carey, David W. Ollila, Carey K. Anders, Katherine A. Hoadley, Michael Iglesia, and Charles M. Perou, University of North Carolina Chapel Hill, Chapel Hill; Constance T. Cirrincione and Brandelyn N. Pitcher, Alliance Statistics and Data Center, Duke University, Durham, NC; Donald A. Berry, Alliance Statistics and Data Center, MD Anderson, Houston, TX; William T. Barry, Alliance Statistics and Data Center, Dana-Farber Cancer Institute; Ian E. Krop and Eric P. Winer, Dana-Farber Cancer Institute, Boston, MA; Lyndsay N. Harris, University Hospitals of Cleveland, Cleveland, OH; Norah Lynn Henry, University of Michigan, Ann Arbor, MI; Douglas J. Weckstein, New Hampshire Hematology-Oncology, Hooksett, NH; Baljit Singh, New York University; Clifford A. Hudis, Memorial Sloan-Kettering Cancer Center, New York, NY; and Maggie Chon U. Cheang, Clinical Trials and Statistics Unit, Institute of Cancer Research, Belmont, United Kingdom.
authors.forename: Baljit
authors.initials: B
authors.lastname: Singh
authors.affiliation: Lisa A. Carey, David W. Ollila, Carey K. Anders, Katherine A. Hoadley, Michael Iglesia, and Charles M. Perou, University of North Carolina Chapel Hill, Chapel Hill; Constance T. Cirrincione and Brandelyn N. Pitcher, Alliance Statistics and Data Center, Duke University, Durham, NC; Donald A. Berry, Alliance Statistics and Data Center, MD Anderson, Houston, TX; William T. Barry, Alliance Statistics and Data Center, Dana-Farber Cancer Institute; Ian E. Krop and Eric P. Winer, Dana-Farber Cancer Institute, Boston, MA; Lyndsay N. Harris, University Hospitals of Cleveland, Cleveland, OH; Norah Lynn Henry, University of Michigan, Ann Arbor, MI; Douglas J. Weckstein, New Hampshire Hematology-Oncology, Hooksett, NH; Baljit Singh, New York University; Clifford A. Hudis, Memorial Sloan-Kettering Cancer Center, New York, NY; and Maggie Chon U. Cheang, Clinical Trials and Statistics Unit, Institute of Cancer Research, Belmont, United Kingdom.
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Hoadley
authors.affiliation: Lisa A. Carey, David W. Ollila, Carey K. Anders, Katherine A. Hoadley, Michael Iglesia, and Charles M. Perou, University of North Carolina Chapel Hill, Chapel Hill; Constance T. Cirrincione and Brandelyn N. Pitcher, Alliance Statistics and Data Center, Duke University, Durham, NC; Donald A. Berry, Alliance Statistics and Data Center, MD Anderson, Houston, TX; William T. Barry, Alliance Statistics and Data Center, Dana-Farber Cancer Institute; Ian E. Krop and Eric P. Winer, Dana-Farber Cancer Institute, Boston, MA; Lyndsay N. Harris, University Hospitals of Cleveland, Cleveland, OH; Norah Lynn Henry, University of Michigan, Ann Arbor, MI; Douglas J. Weckstein, New Hampshire Hematology-Oncology, Hooksett, NH; Baljit Singh, New York University; Clifford A. Hudis, Memorial Sloan-Kettering Cancer Center, New York, NY; and Maggie Chon U. Cheang, Clinical Trials and Statistics Unit, Institute of Cancer Research, Belmont, United Kingdom.
authors.forename: Michael
authors.initials: M
authors.lastname: Iglesia
authors.affiliation: Lisa A. Carey, David W. Ollila, Carey K. Anders, Katherine A. Hoadley, Michael Iglesia, and Charles M. Perou, University of North Carolina Chapel Hill, Chapel Hill; Constance T. Cirrincione and Brandelyn N. Pitcher, Alliance Statistics and Data Center, Duke University, Durham, NC; Donald A. Berry, Alliance Statistics and Data Center, MD Anderson, Houston, TX; William T. Barry, Alliance Statistics and Data Center, Dana-Farber Cancer Institute; Ian E. Krop and Eric P. Winer, Dana-Farber Cancer Institute, Boston, MA; Lyndsay N. Harris, University Hospitals of Cleveland, Cleveland, OH; Norah Lynn Henry, University of Michigan, Ann Arbor, MI; Douglas J. Weckstein, New Hampshire Hematology-Oncology, Hooksett, NH; Baljit Singh, New York University; Clifford A. Hudis, Memorial Sloan-Kettering Cancer Center, New York, NY; and Maggie Chon U. Cheang, Clinical Trials and Statistics Unit, Institute of Cancer Research, Belmont, United Kingdom.
authors.forename: Maggie Chon U
authors.initials: MC
authors.lastname: Cheang
authors.affiliation: Lisa A. Carey, David W. Ollila, Carey K. Anders, Katherine A. Hoadley, Michael Iglesia, and Charles M. Perou, University of North Carolina Chapel Hill, Chapel Hill; Constance T. Cirrincione and Brandelyn N. Pitcher, Alliance Statistics and Data Center, Duke University, Durham, NC; Donald A. Berry, Alliance Statistics and Data Center, MD Anderson, Houston, TX; William T. Barry, Alliance Statistics and Data Center, Dana-Farber Cancer Institute; Ian E. Krop and Eric P. Winer, Dana-Farber Cancer Institute, Boston, MA; Lyndsay N. Harris, University Hospitals of Cleveland, Cleveland, OH; Norah Lynn Henry, University of Michigan, Ann Arbor, MI; Douglas J. Weckstein, New Hampshire Hematology-Oncology, Hooksett, NH; Baljit Singh, New York University; Clifford A. Hudis, Memorial Sloan-Kettering Cancer Center, New York, NY; and Maggie Chon U. Cheang, Clinical Trials and Statistics Unit, Institute of Cancer Research, Belmont, United Kingdom.
authors.forename: Charles M
authors.initials: CM
authors.lastname: Perou
authors.affiliation: Lisa A. Carey, David W. Ollila, Carey K. Anders, Katherine A. Hoadley, Michael Iglesia, and Charles M. Perou, University of North Carolina Chapel Hill, Chapel Hill; Constance T. Cirrincione and Brandelyn N. Pitcher, Alliance Statistics and Data Center, Duke University, Durham, NC; Donald A. Berry, Alliance Statistics and Data Center, MD Anderson, Houston, TX; William T. Barry, Alliance Statistics and Data Center, Dana-Farber Cancer Institute; Ian E. Krop and Eric P. Winer, Dana-Farber Cancer Institute, Boston, MA; Lyndsay N. Harris, University Hospitals of Cleveland, Cleveland, OH; Norah Lynn Henry, University of Michigan, Ann Arbor, MI; Douglas J. Weckstein, New Hampshire Hematology-Oncology, Hooksett, NH; Baljit Singh, New York University; Clifford A. Hudis, Memorial Sloan-Kettering Cancer Center, New York, NY; and Maggie Chon U. Cheang, Clinical Trials and Statistics Unit, Institute of Cancer Research, Belmont, United Kingdom.
authors.forename: Eric P
authors.initials: EP
authors.lastname: Winer
authors.affiliation: Lisa A. Carey, David W. Ollila, Carey K. Anders, Katherine A. Hoadley, Michael Iglesia, and Charles M. Perou, University of North Carolina Chapel Hill, Chapel Hill; Constance T. Cirrincione and Brandelyn N. Pitcher, Alliance Statistics and Data Center, Duke University, Durham, NC; Donald A. Berry, Alliance Statistics and Data Center, MD Anderson, Houston, TX; William T. Barry, Alliance Statistics and Data Center, Dana-Farber Cancer Institute; Ian E. Krop and Eric P. Winer, Dana-Farber Cancer Institute, Boston, MA; Lyndsay N. Harris, University Hospitals of Cleveland, Cleveland, OH; Norah Lynn Henry, University of Michigan, Ann Arbor, MI; Douglas J. Weckstein, New Hampshire Hematology-Oncology, Hooksett, NH; Baljit Singh, New York University; Clifford A. Hudis, Memorial Sloan-Kettering Cancer Center, New York, NY; and Maggie Chon U. Cheang, Clinical Trials and Statistics Unit, Institute of Cancer Research, Belmont, United Kingdom.
authors.forename: Clifford A
authors.initials: CA
authors.lastname: Hudis
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000737:chemistry* / Q000188:drug therapy* / Q000601:surgery; D002277:Carcinoma / Q000737:chemistry* / Q000188:drug therapy* / Q000601:surgery; D047628:Estrogen Receptor alpha / Q000235:genetics; D005260:Female; D015870:Gene Expression; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism; D000077341:Lapatinib; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D018365:Neoplasm, Residual; D017239:Paclitaxel / Q000008:administration & dosage; D011799:Quinazolines / Q000008:administration & dosage; D012333:RNA, Messenger / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis; D000068878:Trastuzumab / Q000008:administration & dosage; D016896:Treatment Outcome; D059016:Tumor Microenvironment; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D055815:Young Adult
chemical_list: D047628:Estrogen Receptor alpha; D007074:Immunoglobulin G; D000077341:Lapatinib; D017239:Paclitaxel; D011799:Quinazolines; D012333:RNA, Messenger; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D000068878:Trastuzumab; D016159:Tumor Suppressor Protein p53; C506487:ESR1 protein, human; C508053:ERBB2 protein, human