Oral SERD Promising in ER-Positive Breast Cancer With ESR1 Mutations


“The investigational third-generation nonsteroidal oral selective estrogen receptor degrader (SERD) RAD1901 was associated with a 23% objective response rate among 40 heavily pretreated women with estrogen receptor (ER)-positive, HER2-negative breast cancer, according to authors of a phase I dose-escalation and safety cohort study (NCT02338349) presented (abstract 1014) at the 2017 American Society of Clinical Oncology (ASCO) Annual Meeting, held June 2–6 in Chicago.”

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Mutation Status May Guide Endocrine Therapy for Advanced Breast Cancer


“Plasma analysis of ESR1 mutations may aid in the identification of appropriate endocrine therapy for patients with advanced breast cancer who progress after treatment with aromatase inhibitors, according to study results published in Journal of Clinical Oncology.

“ ‘Although diverse mechanisms of resistance to endocrine therapy have been described, recent evidence identified mutations in the ER gene (ESR1),’ Nicholas C. Turner, MA, MRCP, PhD, consultant medical oncologist at The Royal Marsden NHS Foundation Trust and team leader at the Breakthrough Breast Cancer Research Centre at Institute for Cancer Research, London, and colleagues wrote. ‘ESR1 mutations occur rarely in primary breast cancer, but have a high prevalence in advanced breast cancers previously treated with aromatase inhibitors, implying evolution through selective treatment pressure.’ ”

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Genetic Variant May Shield Latinas From Breast Cancer

“A genetic variant that is particularly common in some Hispanic women with indigenous American ancestry appears to drastically lower the risk of breast cancer, a new study found.

“About one in five Latinas in the United States carry one copy of the variant, and roughly 1 percent carry two.

“The function of the gene is not entirely clear. But the authors of the study, which was led by a team at the University of California, San Francisco, and funded by the National Cancer Institute, said women who carry the variant have breast tissue that appears less dense on mammograms — a factor that is known to play a role in breast cancer risk. They suspect that the genetic variant may affect the production of estrogen receptors.

“ ‘This is a really important study,’ said Marc Hurlbert, executive director of the Avon Foundation Breast Cancer Crusade, who was not involved in the study. ‘If we can understand how this is protective, it might help us to develop better treatments for those who do get breast cancer.’

“The findings may also explain why Latinas have lower rates of breast cancer than other Americans. According to federal data, Hispanics have less than a 10 percent lifetime risk of breast cancer, compared with about 13 percent for non-Hispanic whites and 11 percent for blacks.”

Genetic Variant Protects Some Latina Women from Breast Cancer

“An international research collaboration led by UC San Francisco researchers has identified a genetic variant common in Latina women that protects against breast cancer.

“The variant, a difference in just one of the three billion ‘letters’ in the human genome known as a single-nucleotide polymorphism (SNP), originates from indigenous Americans and confers significant protection from breast cancer, particularly the more aggressive estrogen receptor–negative forms of the disease, which generally have a worse prognosis.

“ ‘The effect is quite significant,’ said Elad Ziv, MD, professor of medicine and senior author of the study. ‘If you have one copy of this variant, which is the case for approximately 20 percent of U.S. Latinas, you are about 40 percent less likely to have breast cancer. If you have two copies, which occurs in approximately 1 percent of the US Latina population, the reduction in risk is on the order of 80 percent.’

“Published in the October 20, 2014 issue of Nature Communications, the new study showed that women who carry the variant have breast tissue that appears less dense on mammograms. High ‘mammographic density’ is a known risk factor for breast cancer.”