Novel Hormone Strategies Gain Ground in Breast Cancer

Anita T. Shaffer @Shaffer1
Published: Thursday, Nov 16, 2017
Hope Rugo, MD
Hope Rugo, MD
Although hormone-targeting therapies have been a long-established strategy for the treatment of estrogen receptor (ER)-positive breast cancer, more than 20% of patients with early-stage disease relapse and those who progress to a metastatic stage eventually die from their illness.1

Resistance to endocrine therapy in patients with ER-positive breast cancer is defined in 2 ways 2 :
  • Primary resistance: recurrence within adjuvant therapy or disease progression less than 6 months after treatment
  • Acquired resistance: recurrence at least 12 months after completion of adjuvant therapy or progression 6 months or more after the initiation of endocrine therapy in the metastatic setting
Several key mechanisms of endocrine resistance have been identified, including the PI3K/AKT/ mTOR growth factor signaling network, cyclindependent kinase (CDK) signaling, and histone deacetylase (HDAC) activity. Strategies aimed at these processes have been among the most active attempts to boost the efficacy of endocrine therapies (Figure).1,2


Figure. Targeting Endocrine Therapy Resistance

Figure. Targeting Endocrine Therapy Resistance
Ingrid A. Mayer, MD, MSCI, co-leader and clinical director of the Breast Cancer Research Program at Vanderbilt-Ingram Cancer Center, distinguished between mechanisms of primary and acquired resistance during a presentation at the 2017 American Society of Clinical Oncology (ASCO) Annual Meeting in June.2

“We have very effective therapies for ER-positive metastatic breast cancer, there’s no question about that,” Mayer said. “But we don’t know yet if these therapies are needed at all times. A lot of the ongoing trials are trying to answer whether we are going to sequence or combine all these approved or to-beapproved targeted [therapies] in everybody and what is going to be the cost of that not just financially but obviously from a side effect and tolerance point of view. My answer to that is, we don’t know yet.”

CDK4/6 Inhibitors

The development of CDK4/6 inhibitors has been an area of rapid growth in the breast cancer field in the past several years and 3 agents are now approved that employ this approach: palbociclib (Ibrance), ribociclib (Kisqali), and abemaciclib (Verzenio).

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TitleExpiration DateCME Credits
Advances In™ Tumor Testing: Interpreting Genomic Profiles to Optimize Breast Cancer TreatmentJun 29, 20191.5
Oncology Briefings™: Current Perspectives on Preventing and Managing Tumor Lysis SyndromeJun 30, 20191.0
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