by M. Patricia Madigan
The Hormonal and Reproductive Epidemiology Branch (HREB) hosted Dr. Malcolm Pike as a Distinguished Lecturer in October 2011. Dr. Pike is widely known for his research on the etiology and chemoprevention of breast, endometrial, and ovarian cancers and has conducted landmark research to clarify our understanding of how pregnancy and oral contraceptives affect these cancers. He is a member of the Epidemiology Service at Memorial Sloan-Kettering Cancer Center in New York, New York, and the Department of Preventive Medicine at the University of Southern California Norris Cancer Center in Los Angeles. He currently is assessing the characteristics of breast tissue in normal nulliparous and parous volunteers to help clarify the biological basis for the effects of various reproductive factors on risk of breast cancer. Dr. Pike's major interest is in designing an oral contraceptive that could reduce the risk of breast cancer without losing the protection offered by these drugs against endometrial and ovarian cancers. To this end, he is studying the effects on the breast tissue of different hormonal contraceptives in volunteers.
During his visit, Dr. Pike gave a seminar titled "Hormonal chemoprevention of breast, endometrial, and ovarian cancer in young women." Beginning around the time of menopause, the incidence of breast, endometrial, and ovarian cancers show a marked slowing in the degree to which their incidence rates increase with age. Dr. Pike proposed that this slowing is the result of the reduction in the cell division of the relevant tissue and that cell division is an important mechanism of carcinogenesis in women. The varying effects of oral contraceptives on different cancers—reductions in ovarian and endometrial cancers but no reduction in breast cancer—could be explained on this basis. The goal is to use our understanding of the effects of hormones on the breast to help design a hormonal contraceptive that will reduce breast cell division and hence reduce breast cancer risk. Dr. Pike pointed out that the anti-estrogens tamoxifen and raloxifene are very effective in preventing breast cancer in postmenopausal women and that they could become widely used if their significant side effects could be ameliorated.
During his presentation, Dr. Pike discussed the protective effects of oral contraceptives on the risk of ovarian and endometrial cancers and addressed optimal usage regimens. He also discussed an approach to preventing breast cancer that involves giving women a gonadotropin-releasing hormone (GnRH) analog contraceptive with low-dose estrogen. Carriers of the BRCA1 mutation who are treated with a GnRH agonist have reduced mammographic densities, which would improve the utility of mammographic surveillance and would help to reduce their breast cancer risk. However, it is likely that such a regimen would not provide any protection against ovarian or endometrial cancer. A progestin is needed to reduce the risk of endometrial and probably ovarian cancer, but the systemic level must be kept very low in order to not affect the breast. A GnRH analog with ultra-low doses of estrogen and progestin may, however, lead to a loss of protection against endometrial and ovarian cancer.
Dr. Pike also participated in a series of roundtable discussions moderated by HREB investigators. Gretchen L. Gierach, Ph.D., led a session titled "Breast tissue age, tissue composition, and breast cancer risk"; Mark E. Sherman, M.D., facilitated a discussion on "Developing novel designs for chemoprevention studies of breast cancer"; and Nicolas Wentzensen, M.D., Ph.D., moderated a session titled "Etiologic heterogeneity of endometrial and ovarian cancers."