High-dose synthetic estrogens were the first successful chemical therapy used in the treatment of metastatic breast cancer in postmenopausal women, and this approach became the standard of care in postmenopausal women with metastatic breast cancer between the 1950s and the end of the 1970s. The most recent analysis of the Women’s Health Initiative estrogen-alone trial in hysterectomized women revealed a persistently significant decrease in the incidence of breast cancer and breast cancer mortality. Although estrogens are known to induce the proliferation of breast cancer cells, we have shown that physiologic concentrations induce apoptosis in breast cancer cells with long-term estrogen deprivation. We have developed laboratory models that illustrate the new biology of estrogen-induced apoptosis or growth to explain the effects of estrogen therapy. The key to the success of estrogen therapy lies in a sufficient period of withdrawal of physiologic estrogens (5-10 y) and the subsequent regrowth of nascent breast tumor cells that survive under estrogen-deprived conditions. These nascent tumors are now vulnerable to estrogen-induced apoptosis.
From the Lombardi Comprehensive Cancer Center, Department of Oncology, Georgetown University Medical Center, Washington, DC.
Received November 27, 2012; revised and accepted January 16, 2013.
The content of this article was presented by Dr. V. Craig Jordan as the NAMS/Pfizer — Wulf H. Utian Endowed Lecture on October 6, 2012, in Orlando, FL at the Annual Meeting of The North American Menopause Society (NAMS).
An endowment to NAMS from Pfizer established this annual lectureship, with faculty selected by The North American Menopause Society Scientific Program Committee.
Funding/support: This work was supported by the Department of 1090 Defense Breast Program Center of Excellence (award W81XWH-06-1-0590 to V.C.J.), the Susan G. Komen for the Cure Foundation (award SAC100009), and the Lombardi Comprehensive Cancer 1095 Center Support Grant (core grant NIH P30 CA051008).
The views and opinions of the authors do not reflect those of the US Army or the Department of Defense.
Financial disclosure/conflicts of interest: None reported.
Address correspondence to: V. Craig Jordan, OBE, PhD, DSc, FMedSci, Georgetown University Medical Center, Suite E501, Research Building, 3970 Reservoir Road NW, Washington, DC 20057. E-mail: firstname.lastname@example.org