ANETT: PhAse II trial of NEoadjuvant TAK-228 plus Tamoxifen in patients with hormone receptor-positive breast cancer

Emre Koca, Polly Ann Niravath, Joe Ensor, Tejal Amar Patel, Xiaoxian Li, Pej Hemati, Helen Wong, Wei Qian, Toniva Boone, Jing Zhao, Priya V. Ramshesh, Adam Louis Cohen, Asha Murthy, Sindhu Nair, Jorge German Darcourt, Anna Belcheva, Virginia G. Kaklamani, Jenny Chee Ning Chang

Research output: Contribution to journalArticlepeer-review

4 Scopus citations


Introduction: Neoadjuvant endocrine therapy is often utilized to downstage Estrogen Receptor-positive (ER+) breast cancer prior to surgery. However, this approach is sometimes met with endocrine resistance mechanisms within the tumor. This trial examines the safety and efficacy of tamoxifen in combination with an mTORC1/2 inhibitor, TAK-228, in the neoadjuvant treatment of ER+ breast cancer. Methods: In this single-arm, open-label trial, pre- and post-menopausal women were enrolled to receive neoadjuvant tamoxifen (20 mg daily) with TAK-228 (30 mg weekly) for 16 weeks prior to surgery. Patient had tissue sampling at baseline, week 6, and week 16. The primary endpoint was change in Ki-67 from baseline to 6 weeks. The toxicity, change in tumor size, pathologic complete response rate, PEPI score, and baseline Oncotype Dx score were also assessed. Results: Twenty-eight women were enrolled on the trial, and 25 completed the entire study course. The combination of tamoxifen and TAK-228 resulted in a significant reduction in Ki-67 from 18.3 to 15.2% (p = 0.0023). The drug was also found to be safe and tolerable. While nausea and hyperglycemia were common side effects, these were manageable. The tumor size also significantly decreased with the treatment, with a median decrease of 0.75 cm (p < 0.0001). There were no pathologic complete responses. Conclusion: Tamoxifen and TAK-228 was safe and well tolerated neoadjuvant treatment for ER+ breast cancer, preliminary evidence of activity with significant reduction in both Ki-67 and tumor size, warranting further evaluation in a larger study.

Original languageEnglish (US)
Pages (from-to)433-439
Number of pages7
JournalBreast Cancer Research and Treatment
Issue number2
StatePublished - Jul 2021


  • Breast cancer
  • Hormone receptor-positive
  • MTOR inhibitor
  • Neoadjuvant therapy
  • TAK-228
  • Receptors, Estrogen
  • Humans
  • Nitriles/therapeutic use
  • Tamoxifen/therapeutic use
  • Treatment Outcome
  • Receptor, ErbB-2/genetics
  • Antineoplastic Combined Chemotherapy Protocols/adverse effects
  • Benzoxazoles
  • Pyrimidines
  • Female
  • Neoadjuvant Therapy
  • Hormones/therapeutic use
  • Triazoles/therapeutic use
  • Breast Neoplasms/drug therapy

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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