Successful Targeted Therapies for Breast Cancer: the Worcester Foundation and Future Opportunities in Women's Health.

Abstract

The signing of the National Cancer Act in 1971 was designed to take laboratory discoveries rapidly from the bench to the bedside. A "war on cancer" had been declared. Combination cytotoxic chemotherapy was predicted to cure all cancers, based on the stunning success in treating childhood leukemia. Breast cancer treatments were primitive; radical mastectomy and radiation were standard of care for disease that had not spread. Ablative endocrine surgery (oophorectomy, hypophysectomy, and adrenalectomy) was a palliative last option for metastatic breast cancer. However, only 30% responded, surviving for only 1 or 2 years: every patient soon died. The discovery of the estrogen receptor (ER) and translation to breast cancer treatment triggered a revolution in women's health. Two important but interconnected events occurred in 1972 at the Worcester Foundation for Experimental Biology (WFEB) that would exploit the breast tumor ER as the first target to save lives and prevent breast cancer development. Two new groups of medicines-selective ER modulators (SERMs) and aromatase inhibitors (AIs)-would continue the momentum of research at the WFEB to improve women's health. Here, we recount the important progress made in women's health based on knowledge of the endocrinology of breast cancer. We propose future opportunities in SERM therapeutics to "refresh" the current standards of care for breast cancer treatment. The opportunity is based on emerging knowledge about acquired resistance to long-term adjuvant AI therapy used to treat breast cancer.

• Authors: Balkees Abderrahman, V Craig Jordan
• Journal: Endocrinology (Endocrinology) Vol. 159 Issue 8 Pg. 2980-2990 (08 01 2018) ISSN: 1945-7170 [Electronic] United States
• PMID: 29931061 (Publication Type: Historical Article, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Antineoplastic Agents, Hormonal
• Aromatase Inhibitors
• Receptors, Estrogen
• Selective Estrogen Receptor Modulators

Topics

• Antineoplastic Agents, Hormonal (therapeutic use)
• Aromatase Inhibitors (therapeutic use)
• Breast Neoplasms (drug therapy, metabolism)
• Chemotherapy, Adjuvant
• Drug Resistance, Neoplasm
• Female
• Foundations
• History, 20th Century
• History, 21st Century
• Humans
• Mastectomy
• Molecular Targeted Therapy (history, trends)
• Receptors, Estrogen (metabolism)
• Selective Estrogen Receptor Modulators (therapeutic use)
• Women's Health (history)