bims-cyhorp Biomed News
on Cyclin-dependent kinases in hormone receptor positive breast cancer
Issue of 2023–01–22
two papers selected by
Piotr Okupski,



  1. Ann Transl Med. 2022 Dec;10(24): 1413
       Background: Postpartum breast cancer (PPBC) as an independent entity different from PABC. PPBC is defined as breast cancer (BC) diagnosed within 5 years after delivery in many relevant literatures and is associated with a poor prognosis and a decrease in overall survival. PPBC patients commonly present with inflammatory breast cancer (IBC) phenotype, multifocal lesions, and lymph node metastasis. Hormone receptor-positive (HR+) PPBC is an under-investigated subtype. In PPBC, the risk of death of HR+ subtype significantly increased two-fold, while that was only modestly increased for triple-negative breast cancer (TNBC) subtype, and was not significant in human epidermal growth factor receptor 2-positive (HER2+) subtype. HR+ PPBC is a subtype associating with enhanced signatures of cell cycle control, T-cell activation and exhaustion, decreased HR signaling, and altered P53 signaling. The recommended treatment for HR+ PPBC patients is still lacking. Cyclin-dependent kinase (CDK) 4/6 inhibitors are used as a novel treatment standard not only in pretreated patients but also in the first-line setting of HR+ metastatic breast cancer (MBC). However, there is no clinical case report on the application and efficacy of CDK4/6 inhibitors in HR+ PPBC patients.
    Case Description: This article describes the clinical cases of two patients with advanced HR+ PPBC who were rapidly relieved after receiving leuprorelin combined with letrozole combined with dalpiciclib. We reviewed the related literature of PPBC, and found that HR+ PPBC has not been clinically classified as a BC subtype, and only some basic studies suggested that HR+ PPBC may be sensitive to CDK4/6 inhibitors. The purpose of this study is to provide the basis for the related research on the therapeutic effect of CDK4/6 inhibitors in HR+ PPBC through the report of clinical cases.
    Conclusions: This article reports for the first time the good therapeutic effects of CDK4/6 inhibitors on HR+ PPBC patients. Based on our findings, we suggest that dalpiciclib combined with endocrine therapy can be considered as the first-line treatment for patients with advanced HR+ PPBC. Our case report provides new clinical evidence for the related research on the role of CDK4/6 inhibitors in HR+ PPBC therapy.
    Keywords:  case report; cyclin-dependent kinase (CDK) 4/6 inhibitors; hormone receptor-positive (HR+) breast cancer; mammary stem cell (MaSC); postpartum breast cancer (PPBC)
    DOI:  https://doi.org/10.21037/atm-22-5201
  2. Breast. 2023 Jan 12. pii: S0960-9776(23)00005-X. [Epub ahead of print]
       INTRODUCTION: Targeting low levels of human receptor epidermal growth factor 2 (HER2) expression has reshaped the treatment paradigm for half of the patients with advanced breast cancer. HER2-low is currently defined as a HER2 immunohistochemical expression of 1+ or 2+ without amplification by in-situ hybridization. Until recently, HER2-targeted agents were ineffective in treating patients with HER2-low disease.
    AREAS COVERED: In this narrative review, we summarize the current management of HER2-low breast cancer. We highlight the findings of the DESTINY-Breast 04 phase 3 trial, which confirmed the efficacy of trastuzumab-deruxtecan (T-DXd) for the treatment of patients with advanced, pretreated HER2-low breast cancer. We also discuss how to implement this new treatment option in treatment algorithms of hormone receptor (HR)-positive and triple-negative tumors, as well as how to optimally manage selected toxicities of T-DXd.
    EXPERT OPINION: T-DXd is currently the standard of care for patients with advanced, pretreated, HER2-low breast cancer. Based on the design of the DESTINY-Breast04 trial, the current optimal place in treatment algorithms is after the first line of chemotherapy, both in HR-positive and triple-negative breast cancer. Up to 10-15% of the patients receiving T-DXd are expected to develop interstitial lung disease, which in 1-2% of the cases can be fatal. Adequate monitoring and prompt management are required to minimize the impact of ILD and to safely implement T-DXd in clinical practice.
    Keywords:  Breast cancer; HER2; HER2-Low; Trastuzumab-deruxtecan
    DOI:  https://doi.org/10.1016/j.breast.2023.01.005