title: Phase II trial of neoadjuvant letrozole and lapatinib in Asian postmenopausal women with estrogen receptor (ER) and human epidermal growth factor receptor 2 (HER2)-positive breast cancer [Neo-ALL-IN]: Highlighting the TILs, ER expressional change after neoadjuvant treatment, and FES-PET as potential significant biomarkers.
abstract: OBJECTIVE
  Neo-ALL-IN (NCT 01275859) is a single-center, phase II study aimed to evaluate the efficacy and safety profiles of neoadjuvant letrozole plus lapatinib, as well as potential biomarkers, in postmenopausal women with ER- and HER2-positive (ER+HER2+) breast cancer.
  
  
  METHODS
  Postmenopausal ER+HER2+ breast cancer of stages II-III was eligible. Daily 2.5 mg letrozole plus 1500 mg lapatinib were administered for 18-21 weeks before surgery. Clinical responses were assessed by palpation with caliper, breast ultrasonography, mammogram, and/or MRI. Biologic samples were collected for biomarker analyses at three time points (baseline, day 14, and before surgery). Baseline fluorine-18 fluorodeoxyglucose and fluorine-18 fluoroestradiol PET-CT scans were performed.
  
  
  RESULTS
  Among 24 patients enrolled, 17 (70.8 %) completed planned neoadjuvant treatment, whereas 7 prematurely terminated the treatment and proceeded to surgery because of toxicity or progression; 2 patients showed definite progression, and 2 showed clinical regrowth by palpation regardless of minimal response. All patients eventually underwent breast cancer surgery. Toxicities were generally mild mostly within grades 1-2 except prolonged or recurrent grade 3 liver toxicities in 3 patients (13.6 %) regardless of sequential dose reduction, which finally led to discontinuation of treatment. The overall clinical response rates were 62.5 % (n = 15) including 1 CR in breast. However, no pathologic CR (ypT0-is N0) was achieved. SUVmax lower than 5.5 in baseline FES PET-CT (p = 0.007), baseline TILs over 20 % (p = 0.026), and decreased IHC ER Allred score after neoadjuvant treatment (p = 0.021) were significantly associated with adverse clinical response.
  
  
  CONCLUSIONS
  When this chemo-free, combination neoadjuvant therapy with letrozole and lapatinib is given for Asian postmenopausal ER+HER2+ breast cancer, TILs, change of ER expression following neoadjuvant treatment, and SUVmax in baseline FES-PET are to be considered potential biomarkers in these patients.
authors.affiliation: Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Korea.
authors.forename: Ji Hyun
authors.initials: JH
authors.lastname: Park
authors.affiliation: Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Korea.
authors.forename: Myung Joo
authors.initials: MJ
authors.lastname: Kang
authors.affiliation: Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Korea.
authors.forename: Jin-Hee
authors.initials: JH
authors.lastname: Ahn
authors.affiliation: Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Korea.
authors.forename: Jeong Eun
authors.initials: JE
authors.lastname: Kim
authors.affiliation: Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Korea.
authors.forename: Kyung Hae
authors.initials: KH
authors.lastname: Jung
authors.affiliation: Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Gyungyub
authors.initials: G
authors.lastname: Gong
authors.affiliation: Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Hee Jin
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Byung-Ho
authors.initials: BH
authors.lastname: Son
authors.affiliation: Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Sei-Hyun
authors.initials: SH
authors.lastname: Ahn
authors.affiliation: Department of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Hak-Hee
authors.initials: HH
authors.lastname: Kim
authors.affiliation: Department of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Hee Jung
authors.initials: HJ
authors.lastname: Shin
authors.affiliation: Department of Nuclear Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Dae-Hyuk
authors.initials: DH
authors.lastname: Moon
authors.affiliation: Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Korea. sbkim3@amc.seoul.kr.
authors.forename: Sung-Bae
authors.initials: SB
authors.lastname: Kim
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D044466:Asian People; D014408:Biomarkers, Tumor / Q000097:blood; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000601:surgery; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D000077341:Lapatinib; D000077289:Letrozole; D018655:Lymphocyte Count; D016246:Lymphocytes, Tumor-Infiltrating; D008408:Mastectomy; D008875:Middle Aged; D020360:Neoadjuvant Therapy / Q000009:adverse effects / Q000379:methods*; D009570:Nitriles / Q000008:administration & dosage; D049268:Positron-Emission Tomography; D017698:Postmenopause; D011799:Quinazolines / Q000008:administration & dosage; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics*; D011960:Receptors, Estrogen / Q000096:biosynthesis / Q000235:genetics*; D014230:Triazoles / Q000008:administration & dosage
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D000077341:Lapatinib; D000077289:Letrozole; D009570:Nitriles; D011799:Quinazolines; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D014230:Triazoles; C508053:ERBB2 protein, human
keywords: Breast cancer; FES-PET; Lapatinib; Letrozole; Neoadjuvant; Postmenopausal; TILs