Cancer Chemotherapy and Pharmacology

, Volume 78, Issue 4, pp 685–695 | Cite as

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

  • Ji Hyun Park
  • Myung Joo Kang
  • Jin-Hee Ahn
  • Jeong Eun Kim
  • Kyung Hae Jung
  • Gyungyub Gong
  • Hee Jin Lee
  • Byung-Ho Son
  • Sei-Hyun Ahn
  • Hak-Hee Kim
  • Hee Jung Shin
  • Dae-Hyuk Moon
  • Sung-Bae KimEmail author
Original Article



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.


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.


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.


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.


Neoadjuvant Lapatinib Letrozole Postmenopausal FES-PET TILs Breast cancer 



The study (2007-0729) was partly granted from Novartis and GSK.

Compliance with ethical standards

Conflict of interest


Supplementary material

280_2016_3107_MOESM1_ESM.docx (56 kb)
Supplementary material 1 (DOCX 55 kb)


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Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Ji Hyun Park
    • 1
  • Myung Joo Kang
    • 1
  • Jin-Hee Ahn
    • 1
  • Jeong Eun Kim
    • 1
  • Kyung Hae Jung
    • 1
  • Gyungyub Gong
    • 2
  • Hee Jin Lee
    • 2
  • Byung-Ho Son
    • 3
  • Sei-Hyun Ahn
    • 3
  • Hak-Hee Kim
    • 4
  • Hee Jung Shin
    • 4
  • Dae-Hyuk Moon
    • 5
  • Sung-Bae Kim
    • 1
    Email author
  1. 1.Department of Oncology, Asan Medical CenterUniversity of Ulsan College of MedicineSeoulKorea
  2. 2.Department of Pathology, Asan Medical CenterUniversity of Ulsan College of MedicineSeoulKorea
  3. 3.Department of Surgery, Asan Medical CenterUniversity of Ulsan College of MedicineSeoulKorea
  4. 4.Department of Radiology, Asan Medical CenterUniversity of Ulsan College of MedicineSeoulKorea
  5. 5.Department of Nuclear Medicine, Asan Medical CenterUniversity of Ulsan College of MedicineSeoulKorea

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