title: Systemic therapy for patients with advanced human epidermal growth factor receptor 2-positive breast cancer: American Society of Clinical Oncology clinical practice guideline.
abstract: OBJECTIVE
  To provide evidence-based recommendations to practicing oncologists and others on systemic therapy for patients with human epidermal growth factor receptor 2 (HER2) -positive advanced breast cancer.
  
  
  METHODS
  The American Society of Clinical Oncology convened a panel of medical oncology, radiation oncology, guideline implementation, and advocacy experts and conducted a systematic literature review from January 2009 to October 2012. Outcomes of interest included overall survival, progression-free survival (PFS), and adverse events.
  
  
  RESULTS
  A total of 16 trials met the systematic review criteria. The CLEOPATRA trial found survival and PFS benefits for docetaxel, trastuzumab, and pertuzumab in first-line treatment, and the EMILIA trial found survival and PFS benefits for trastuzumab emtansine (T-DM1) in second-line treatment. T-DM1 also showed a third-line PFS benefit. One trial reported on duration of HER2-targeted therapy, and three others reported on endocrine therapy for patients with HER-positive advanced breast cancer.
  
  
  CONCLUSIONS
  HER2-targeted therapy is recommended for patients with HER2-positive advanced breast cancer, except for those with clinical congestive heart failure or significantly compromised left ventricular ejection fraction, who should be evaluated on a case-by-case basis. Trastuzumab, pertuzumab, and taxane for first-line treatment and T-DM1 for second-line treatment are recommended. In the third-line setting, clinicians should offer other HER2-targeted therapy combinations or T-DM1 (if not previously administered) and may offer pertuzumab, if the patient has not previously received it. Optimal duration of chemotherapy is at least 4 to 6 months or until maximum response, depending on toxicity and in the absence of progression. HER2-targeted therapy can continue until time of progression or unacceptable toxicities. For patients with HER2-positive and estrogen receptor-positive/progesterone receptor-positive breast cancer, clinicians may recommend either standard first-line therapy or, for selected patients, endocrine therapy plus HER2-targeted therapy or endocrine therapy alone.
authors.affiliation: Sharon H. Giordano and Ana M. Gonzalez-Angulo, University of Texas MD Anderson Cancer Center, Houston; Debra A. Patt, Texas Oncology, Austin, TX; Sarah Temin, American Society of Clinical Oncology, Alexandria, VA; Jeffrey J. Kirshner, Hematology/Oncology Associates of Central New York, East Syracuse; Sarat Chandarlapaty and Shanu Modi, Memorial Sloan Kettering Cancer Center; Francisco J. Esteva, New York University Cancer Institute, New York, NY; Jennie R. Crews, PeaceHealth St Joseph Cancer Center, Bellingham, WA; Nancy E. Davidson, University of Pittsburgh Cancer Institute and University of Pittsburgh Medical Center Cancer Center, Pittsburgh, PA; Ian Krop, Nancy U. Lin, and Eric P. Winer, Dana-Farber Cancer Institute, Boston, MA; Jennifer Levinson, Ponte Vedra Beach; Edith A. Perez, Mayo Clinic, Jacksonville; Naren Ramakrishna, University of Florida Health Cancer Center at Orlando Health, Orlando, FL; and Jane Perlmutter, Ann Arbor, MI.
authors.forename: Sharon H
authors.initials: SH
authors.lastname: Giordano
authors.affiliation: Sharon H. Giordano and Ana M. Gonzalez-Angulo, University of Texas MD Anderson Cancer Center, Houston; Debra A. Patt, Texas Oncology, Austin, TX; Sarah Temin, American Society of Clinical Oncology, Alexandria, VA; Jeffrey J. Kirshner, Hematology/Oncology Associates of Central New York, East Syracuse; Sarat Chandarlapaty and Shanu Modi, Memorial Sloan Kettering Cancer Center; Francisco J. Esteva, New York University Cancer Institute, New York, NY; Jennie R. Crews, PeaceHealth St Joseph Cancer Center, Bellingham, WA; Nancy E. Davidson, University of Pittsburgh Cancer Institute and University of Pittsburgh Medical Center Cancer Center, Pittsburgh, PA; Ian Krop, Nancy U. Lin, and Eric P. Winer, Dana-Farber Cancer Institute, Boston, MA; Jennifer Levinson, Ponte Vedra Beach; Edith A. Perez, Mayo Clinic, Jacksonville; Naren Ramakrishna, University of Florida Health Cancer Center at Orlando Health, Orlando, FL; and Jane Perlmutter, Ann Arbor, MI.
authors.forename: Sarah
authors.initials: S
authors.lastname: Temin
authors.affiliation: Sharon H. Giordano and Ana M. Gonzalez-Angulo, University of Texas MD Anderson Cancer Center, Houston; Debra A. Patt, Texas Oncology, Austin, TX; Sarah Temin, American Society of Clinical Oncology, Alexandria, VA; Jeffrey J. Kirshner, Hematology/Oncology Associates of Central New York, East Syracuse; Sarat Chandarlapaty and Shanu Modi, Memorial Sloan Kettering Cancer Center; Francisco J. Esteva, New York University Cancer Institute, New York, NY; Jennie R. Crews, PeaceHealth St Joseph Cancer Center, Bellingham, WA; Nancy E. Davidson, University of Pittsburgh Cancer Institute and University of Pittsburgh Medical Center Cancer Center, Pittsburgh, PA; Ian Krop, Nancy U. Lin, and Eric P. Winer, Dana-Farber Cancer Institute, Boston, MA; Jennifer Levinson, Ponte Vedra Beach; Edith A. Perez, Mayo Clinic, Jacksonville; Naren Ramakrishna, University of Florida Health Cancer Center at Orlando Health, Orlando, FL; and Jane Perlmutter, Ann Arbor, MI.
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Kirshner
authors.affiliation: Sharon H. Giordano and Ana M. Gonzalez-Angulo, University of Texas MD Anderson Cancer Center, Houston; Debra A. Patt, Texas Oncology, Austin, TX; Sarah Temin, American Society of Clinical Oncology, Alexandria, VA; Jeffrey J. Kirshner, Hematology/Oncology Associates of Central New York, East Syracuse; Sarat Chandarlapaty and Shanu Modi, Memorial Sloan Kettering Cancer Center; Francisco J. Esteva, New York University Cancer Institute, New York, NY; Jennie R. Crews, PeaceHealth St Joseph Cancer Center, Bellingham, WA; Nancy E. Davidson, University of Pittsburgh Cancer Institute and University of Pittsburgh Medical Center Cancer Center, Pittsburgh, PA; Ian Krop, Nancy U. Lin, and Eric P. Winer, Dana-Farber Cancer Institute, Boston, MA; Jennifer Levinson, Ponte Vedra Beach; Edith A. Perez, Mayo Clinic, Jacksonville; Naren Ramakrishna, University of Florida Health Cancer Center at Orlando Health, Orlando, FL; and Jane Perlmutter, Ann Arbor, MI.
authors.forename: Sarat
authors.initials: S
authors.lastname: Chandarlapaty
authors.affiliation: Sharon H. Giordano and Ana M. Gonzalez-Angulo, University of Texas MD Anderson Cancer Center, Houston; Debra A. Patt, Texas Oncology, Austin, TX; Sarah Temin, American Society of Clinical Oncology, Alexandria, VA; Jeffrey J. Kirshner, Hematology/Oncology Associates of Central New York, East Syracuse; Sarat Chandarlapaty and Shanu Modi, Memorial Sloan Kettering Cancer Center; Francisco J. Esteva, New York University Cancer Institute, New York, NY; Jennie R. Crews, PeaceHealth St Joseph Cancer Center, Bellingham, WA; Nancy E. Davidson, University of Pittsburgh Cancer Institute and University of Pittsburgh Medical Center Cancer Center, Pittsburgh, PA; Ian Krop, Nancy U. Lin, and Eric P. Winer, Dana-Farber Cancer Institute, Boston, MA; Jennifer Levinson, Ponte Vedra Beach; Edith A. Perez, Mayo Clinic, Jacksonville; Naren Ramakrishna, University of Florida Health Cancer Center at Orlando Health, Orlando, FL; and Jane Perlmutter, Ann Arbor, MI.
authors.forename: Jennie R
authors.initials: JR
authors.lastname: Crews
authors.affiliation: Sharon H. Giordano and Ana M. Gonzalez-Angulo, University of Texas MD Anderson Cancer Center, Houston; Debra A. Patt, Texas Oncology, Austin, TX; Sarah Temin, American Society of Clinical Oncology, Alexandria, VA; Jeffrey J. Kirshner, Hematology/Oncology Associates of Central New York, East Syracuse; Sarat Chandarlapaty and Shanu Modi, Memorial Sloan Kettering Cancer Center; Francisco J. Esteva, New York University Cancer Institute, New York, NY; Jennie R. Crews, PeaceHealth St Joseph Cancer Center, Bellingham, WA; Nancy E. Davidson, University of Pittsburgh Cancer Institute and University of Pittsburgh Medical Center Cancer Center, Pittsburgh, PA; Ian Krop, Nancy U. Lin, and Eric P. Winer, Dana-Farber Cancer Institute, Boston, MA; Jennifer Levinson, Ponte Vedra Beach; Edith A. Perez, Mayo Clinic, Jacksonville; Naren Ramakrishna, University of Florida Health Cancer Center at Orlando Health, Orlando, FL; and Jane Perlmutter, Ann Arbor, MI.
authors.forename: Nancy E
authors.initials: NE
authors.lastname: Davidson
authors.affiliation: Sharon H. Giordano and Ana M. Gonzalez-Angulo, University of Texas MD Anderson Cancer Center, Houston; Debra A. Patt, Texas Oncology, Austin, TX; Sarah Temin, American Society of Clinical Oncology, Alexandria, VA; Jeffrey J. Kirshner, Hematology/Oncology Associates of Central New York, East Syracuse; Sarat Chandarlapaty and Shanu Modi, Memorial Sloan Kettering Cancer Center; Francisco J. Esteva, New York University Cancer Institute, New York, NY; Jennie R. Crews, PeaceHealth St Joseph Cancer Center, Bellingham, WA; Nancy E. Davidson, University of Pittsburgh Cancer Institute and University of Pittsburgh Medical Center Cancer Center, Pittsburgh, PA; Ian Krop, Nancy U. Lin, and Eric P. Winer, Dana-Farber Cancer Institute, Boston, MA; Jennifer Levinson, Ponte Vedra Beach; Edith A. Perez, Mayo Clinic, Jacksonville; Naren Ramakrishna, University of Florida Health Cancer Center at Orlando Health, Orlando, FL; and Jane Perlmutter, Ann Arbor, MI.
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Esteva
authors.affiliation: Sharon H. Giordano and Ana M. Gonzalez-Angulo, University of Texas MD Anderson Cancer Center, Houston; Debra A. Patt, Texas Oncology, Austin, TX; Sarah Temin, American Society of Clinical Oncology, Alexandria, VA; Jeffrey J. Kirshner, Hematology/Oncology Associates of Central New York, East Syracuse; Sarat Chandarlapaty and Shanu Modi, Memorial Sloan Kettering Cancer Center; Francisco J. Esteva, New York University Cancer Institute, New York, NY; Jennie R. Crews, PeaceHealth St Joseph Cancer Center, Bellingham, WA; Nancy E. Davidson, University of Pittsburgh Cancer Institute and University of Pittsburgh Medical Center Cancer Center, Pittsburgh, PA; Ian Krop, Nancy U. Lin, and Eric P. Winer, Dana-Farber Cancer Institute, Boston, MA; Jennifer Levinson, Ponte Vedra Beach; Edith A. Perez, Mayo Clinic, Jacksonville; Naren Ramakrishna, University of Florida Health Cancer Center at Orlando Health, Orlando, FL; and Jane Perlmutter, Ann Arbor, MI.
authors.forename: Ana M
authors.initials: AM
authors.lastname: Gonzalez-Angulo
authors.affiliation: Sharon H. Giordano and Ana M. Gonzalez-Angulo, University of Texas MD Anderson Cancer Center, Houston; Debra A. Patt, Texas Oncology, Austin, TX; Sarah Temin, American Society of Clinical Oncology, Alexandria, VA; Jeffrey J. Kirshner, Hematology/Oncology Associates of Central New York, East Syracuse; Sarat Chandarlapaty and Shanu Modi, Memorial Sloan Kettering Cancer Center; Francisco J. Esteva, New York University Cancer Institute, New York, NY; Jennie R. Crews, PeaceHealth St Joseph Cancer Center, Bellingham, WA; Nancy E. Davidson, University of Pittsburgh Cancer Institute and University of Pittsburgh Medical Center Cancer Center, Pittsburgh, PA; Ian Krop, Nancy U. Lin, and Eric P. Winer, Dana-Farber Cancer Institute, Boston, MA; Jennifer Levinson, Ponte Vedra Beach; Edith A. Perez, Mayo Clinic, Jacksonville; Naren Ramakrishna, University of Florida Health Cancer Center at Orlando Health, Orlando, FL; and Jane Perlmutter, Ann Arbor, MI.
authors.forename: Ian
authors.initials: I
authors.lastname: Krop
authors.affiliation: Sharon H. Giordano and Ana M. Gonzalez-Angulo, University of Texas MD Anderson Cancer Center, Houston; Debra A. Patt, Texas Oncology, Austin, TX; Sarah Temin, American Society of Clinical Oncology, Alexandria, VA; Jeffrey J. Kirshner, Hematology/Oncology Associates of Central New York, East Syracuse; Sarat Chandarlapaty and Shanu Modi, Memorial Sloan Kettering Cancer Center; Francisco J. Esteva, New York University Cancer Institute, New York, NY; Jennie R. Crews, PeaceHealth St Joseph Cancer Center, Bellingham, WA; Nancy E. Davidson, University of Pittsburgh Cancer Institute and University of Pittsburgh Medical Center Cancer Center, Pittsburgh, PA; Ian Krop, Nancy U. Lin, and Eric P. Winer, Dana-Farber Cancer Institute, Boston, MA; Jennifer Levinson, Ponte Vedra Beach; Edith A. Perez, Mayo Clinic, Jacksonville; Naren Ramakrishna, University of Florida Health Cancer Center at Orlando Health, Orlando, FL; and Jane Perlmutter, Ann Arbor, MI.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Levinson
authors.affiliation: Sharon H. Giordano and Ana M. Gonzalez-Angulo, University of Texas MD Anderson Cancer Center, Houston; Debra A. Patt, Texas Oncology, Austin, TX; Sarah Temin, American Society of Clinical Oncology, Alexandria, VA; Jeffrey J. Kirshner, Hematology/Oncology Associates of Central New York, East Syracuse; Sarat Chandarlapaty and Shanu Modi, Memorial Sloan Kettering Cancer Center; Francisco J. Esteva, New York University Cancer Institute, New York, NY; Jennie R. Crews, PeaceHealth St Joseph Cancer Center, Bellingham, WA; Nancy E. Davidson, University of Pittsburgh Cancer Institute and University of Pittsburgh Medical Center Cancer Center, Pittsburgh, PA; Ian Krop, Nancy U. Lin, and Eric P. Winer, Dana-Farber Cancer Institute, Boston, MA; Jennifer Levinson, Ponte Vedra Beach; Edith A. Perez, Mayo Clinic, Jacksonville; Naren Ramakrishna, University of Florida Health Cancer Center at Orlando Health, Orlando, FL; and Jane Perlmutter, Ann Arbor, MI.
authors.forename: Nancy U
authors.initials: NU
authors.lastname: Lin
authors.affiliation: Sharon H. Giordano and Ana M. Gonzalez-Angulo, University of Texas MD Anderson Cancer Center, Houston; Debra A. Patt, Texas Oncology, Austin, TX; Sarah Temin, American Society of Clinical Oncology, Alexandria, VA; Jeffrey J. Kirshner, Hematology/Oncology Associates of Central New York, East Syracuse; Sarat Chandarlapaty and Shanu Modi, Memorial Sloan Kettering Cancer Center; Francisco J. Esteva, New York University Cancer Institute, New York, NY; Jennie R. Crews, PeaceHealth St Joseph Cancer Center, Bellingham, WA; Nancy E. Davidson, University of Pittsburgh Cancer Institute and University of Pittsburgh Medical Center Cancer Center, Pittsburgh, PA; Ian Krop, Nancy U. Lin, and Eric P. Winer, Dana-Farber Cancer Institute, Boston, MA; Jennifer Levinson, Ponte Vedra Beach; Edith A. Perez, Mayo Clinic, Jacksonville; Naren Ramakrishna, University of Florida Health Cancer Center at Orlando Health, Orlando, FL; and Jane Perlmutter, Ann Arbor, MI.
authors.forename: Shanu
authors.initials: S
authors.lastname: Modi
authors.affiliation: Sharon H. Giordano and Ana M. Gonzalez-Angulo, University of Texas MD Anderson Cancer Center, Houston; Debra A. Patt, Texas Oncology, Austin, TX; Sarah Temin, American Society of Clinical Oncology, Alexandria, VA; Jeffrey J. Kirshner, Hematology/Oncology Associates of Central New York, East Syracuse; Sarat Chandarlapaty and Shanu Modi, Memorial Sloan Kettering Cancer Center; Francisco J. Esteva, New York University Cancer Institute, New York, NY; Jennie R. Crews, PeaceHealth St Joseph Cancer Center, Bellingham, WA; Nancy E. Davidson, University of Pittsburgh Cancer Institute and University of Pittsburgh Medical Center Cancer Center, Pittsburgh, PA; Ian Krop, Nancy U. Lin, and Eric P. Winer, Dana-Farber Cancer Institute, Boston, MA; Jennifer Levinson, Ponte Vedra Beach; Edith A. Perez, Mayo Clinic, Jacksonville; Naren Ramakrishna, University of Florida Health Cancer Center at Orlando Health, Orlando, FL; and Jane Perlmutter, Ann Arbor, MI.
authors.forename: Debra A
authors.initials: DA
authors.lastname: Patt
authors.affiliation: Sharon H. Giordano and Ana M. Gonzalez-Angulo, University of Texas MD Anderson Cancer Center, Houston; Debra A. Patt, Texas Oncology, Austin, TX; Sarah Temin, American Society of Clinical Oncology, Alexandria, VA; Jeffrey J. Kirshner, Hematology/Oncology Associates of Central New York, East Syracuse; Sarat Chandarlapaty and Shanu Modi, Memorial Sloan Kettering Cancer Center; Francisco J. Esteva, New York University Cancer Institute, New York, NY; Jennie R. Crews, PeaceHealth St Joseph Cancer Center, Bellingham, WA; Nancy E. Davidson, University of Pittsburgh Cancer Institute and University of Pittsburgh Medical Center Cancer Center, Pittsburgh, PA; Ian Krop, Nancy U. Lin, and Eric P. Winer, Dana-Farber Cancer Institute, Boston, MA; Jennifer Levinson, Ponte Vedra Beach; Edith A. Perez, Mayo Clinic, Jacksonville; Naren Ramakrishna, University of Florida Health Cancer Center at Orlando Health, Orlando, FL; and Jane Perlmutter, Ann Arbor, MI.
authors.forename: Edith A
authors.initials: EA
authors.lastname: Perez
authors.affiliation: Sharon H. Giordano and Ana M. Gonzalez-Angulo, University of Texas MD Anderson Cancer Center, Houston; Debra A. Patt, Texas Oncology, Austin, TX; Sarah Temin, American Society of Clinical Oncology, Alexandria, VA; Jeffrey J. Kirshner, Hematology/Oncology Associates of Central New York, East Syracuse; Sarat Chandarlapaty and Shanu Modi, Memorial Sloan Kettering Cancer Center; Francisco J. Esteva, New York University Cancer Institute, New York, NY; Jennie R. Crews, PeaceHealth St Joseph Cancer Center, Bellingham, WA; Nancy E. Davidson, University of Pittsburgh Cancer Institute and University of Pittsburgh Medical Center Cancer Center, Pittsburgh, PA; Ian Krop, Nancy U. Lin, and Eric P. Winer, Dana-Farber Cancer Institute, Boston, MA; Jennifer Levinson, Ponte Vedra Beach; Edith A. Perez, Mayo Clinic, Jacksonville; Naren Ramakrishna, University of Florida Health Cancer Center at Orlando Health, Orlando, FL; and Jane Perlmutter, Ann Arbor, MI.
authors.forename: Jane
authors.initials: J
authors.lastname: Perlmutter
authors.affiliation: Sharon H. Giordano and Ana M. Gonzalez-Angulo, University of Texas MD Anderson Cancer Center, Houston; Debra A. Patt, Texas Oncology, Austin, TX; Sarah Temin, American Society of Clinical Oncology, Alexandria, VA; Jeffrey J. Kirshner, Hematology/Oncology Associates of Central New York, East Syracuse; Sarat Chandarlapaty and Shanu Modi, Memorial Sloan Kettering Cancer Center; Francisco J. Esteva, New York University Cancer Institute, New York, NY; Jennie R. Crews, PeaceHealth St Joseph Cancer Center, Bellingham, WA; Nancy E. Davidson, University of Pittsburgh Cancer Institute and University of Pittsburgh Medical Center Cancer Center, Pittsburgh, PA; Ian Krop, Nancy U. Lin, and Eric P. Winer, Dana-Farber Cancer Institute, Boston, MA; Jennifer Levinson, Ponte Vedra Beach; Edith A. Perez, Mayo Clinic, Jacksonville; Naren Ramakrishna, University of Florida Health Cancer Center at Orlando Health, Orlando, FL; and Jane Perlmutter, Ann Arbor, MI.
authors.forename: Naren
authors.initials: N
authors.lastname: Ramakrishna
authors.affiliation: Sharon H. Giordano and Ana M. Gonzalez-Angulo, University of Texas MD Anderson Cancer Center, Houston; Debra A. Patt, Texas Oncology, Austin, TX; Sarah Temin, American Society of Clinical Oncology, Alexandria, VA; Jeffrey J. Kirshner, Hematology/Oncology Associates of Central New York, East Syracuse; Sarat Chandarlapaty and Shanu Modi, Memorial Sloan Kettering Cancer Center; Francisco J. Esteva, New York University Cancer Institute, New York, NY; Jennie R. Crews, PeaceHealth St Joseph Cancer Center, Bellingham, WA; Nancy E. Davidson, University of Pittsburgh Cancer Institute and University of Pittsburgh Medical Center Cancer Center, Pittsburgh, PA; Ian Krop, Nancy U. Lin, and Eric P. Winer, Dana-Farber Cancer Institute, Boston, MA; Jennifer Levinson, Ponte Vedra Beach; Edith A. Perez, Mayo Clinic, Jacksonville; Naren Ramakrishna, University of Florida Health Cancer Center at Orlando Health, Orlando, FL; and Jane Perlmutter, Ann Arbor, MI.
authors.forename: Eric P
authors.initials: EP
authors.lastname: Winer
mesh_terms: D000080044:Ado-Trastuzumab Emtansine; D000077384:Anastrozole; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D002986:Clinical Trials as Topic / Q000592:standards; D015897:Comorbidity; D000077143:Docetaxel; D004334:Drug Administration Schedule; D019317:Evidence-Based Medicine; D005260:Female; D054624:Health Status Disparities; D054625:Healthcare Disparities; D006801:Humans; D000077341:Lapatinib; D000077289:Letrozole; D008453:Maytansine / Q000008:administration & dosage / Q000031:analogs & derivatives; D058990:Molecular Targeted Therapy / Q000379:methods*; D009570:Nitriles / Q000008:administration & dosage; D011799:Quinazolines / Q000008:administration & dosage; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis*; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis; D012955:Societies, Medical; D043823:Taxoids / Q000008:administration & dosage; D000068878:Trastuzumab; D016896:Treatment Outcome; D014230:Triazoles / Q000008:administration & dosage; D014481:United States
chemical_list: D000080044:Ado-Trastuzumab Emtansine; D000077384:Anastrozole; D061067:Antibodies, Monoclonal, Humanized; D018931:Antineoplastic Agents, Hormonal; D014408:Biomarkers, Tumor; D000077143:Docetaxel; D000077341:Lapatinib; D000077289:Letrozole; D008453:Maytansine; D009570:Nitriles; D011799:Quinazolines; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D043823:Taxoids; D000068878:Trastuzumab; D014230:Triazoles; C508053:ERBB2 protein, human; C485206:pertuzumab