Despite advances in treating estrogen receptor-positive (ER+) metastatic breast cancer, integration of newer targeted agents into combination therapies will necessitate the development of predictive biomarkers, according to a plenary talk presented at the 2016 San Antonio Breast Cancer Symposium.

“Endocrine therapy has a key role in the management of hormone receptor [HR]-positive metastatic breast cancer, and aromatase inhibitors [AIs] have been the standard of care for 15 years, but we know that success is limited by the development of endocrine resistance,” said Stephen RD Johnston, MD, FRCP, professor of breast cancer medicine at the Royal Marsden Hospital and Institute for Cancer Research in London, England.

Management of postmenopausal ER+ MBC entails determining the sites and extent of tumors, symptoms, ER and HER2 status, performance status, and using disease-free and treatment-free intervals, Dr Johnston noted. For patients with non-life-threatening hormone-responsive disease, first-line hormonal therapy is standard, while first-line chemotherapy is used for hormone-unresponsive or life-threatening disease.

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“If patients respond well to first-line treatment, they will respond well to subsequent lines, but survival falls dramatically to 3 to 4 months in the second-line setting,” Dr Johnston said. “So clearly, there is room for improvement.”

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“Resistance to endocrine therapy is the major clinical challenge,” he explained. We clearly need biomarkers. Biomarkers for response to CDK 4/6 inhibitors are needed but none have been identified to date, other than ER.”

Ten tumor signaling pathways are involved in these cancers—and perhaps more. All of those pathways ultimately involve just 3: ER, cell cycle, and PI3K/Akt/mTOR. “These are the 3 pillars,” he said.


  1. Johnston RD. Plenary Lecture: PL1 Management of Metastatic ER+ Breast Cancer. Paper presented at: 39th San Antonio Breast Cancer Symposium; December 2016; San Antonio, TX.