Biography

Dr. Lacey received a M.P.H. in Epidemiology in 1995 and a Ph.D. in Epidemiologic Science from the University of Michigan School of Public Health in 1998.  He joined the Hormonal Studies Section of the Environmental Epidemiology Branch as a CRTA Fellow in 1998 and became an Investigator in 2001.  His work at DCEG explores hormonal carcinogenesis of the breast, endometrium, ovary, with particular emphasis on the role of exogenous hormones.  Dr. Lacey received the inaugural DCEG Fellowship Achievement Award, an NIH Fellows Award for Research Excellence, and the NIH Award of Merit.

Research Interests

Reproductive hormones play an undisputed but incompletely understood role in cancers of the endometrium, ovary, and breast.  As methodologies to understand their mechanisms evolve and improve, our multidisciplinary epidemiologic studies attempt to better understand the role of hormones in female reproductive cancers.  I primarily focus on two aspects of this broad issue: menopausal hormone therapy’s cancer risks and the natural history of endometrial carcinoma. 

Endometrial Cancer Natural History

Just as hormone therapy represents a useful model of the influence of exogenous hormones on carcinogenesis, endometrial carcinoma offers an excellent setting in which to understand hormonal carcinogenesis.  This tumor’s clear hormonal component provides unique opportunities to better understand the action of hormonal risk factors.  And, because it is also often preceded by a diagnosis of the candidate precursor lesion, endometrial hyperplasia, endometrial cancer natural history is a promising area for uncovering clues about when and how hormonal carcinogenesis occurs.  I am Principal Investigator of a multidisciplinary study to clarify the subsequent risk of endometrial cancer risk in women diagnosed with endometrial hyperplasia.  A better understanding of these risks would improve clinical management of women with abnormal uterine bleeding, increase the efficiency of early detection of endometrial cancer, and highlight time periods in which prevention efforts might be most effective.  But, as in most epithelial cancers, the first steps toward carcinogenesis likely occur long before signs and symptoms appear.  Our team is also hunting for silent molecular lesions, defined as molecular alterations that are detectable in histologically normal tissues but that have no clinical or pathologic manifestations, in endometrial tissues.  These silent lesions represent candidates for early detection, risk stratification, and molecular-based prevention.

Cancer Risks Associated with Menopausal Hormone Therapy

Menopausal hormone therapy is both an important public health issue and an excellent example of a modifiable risk factor that can reveal clues about hormonal carcinogenesis in the endometrium, ovary, and breast.  DCEG has held a long-standing interest in understanding cancer risks associated with menopausal hormone therapy use, and I have worked to continue that tradition.  The increased risks of breast cancer among estrogen plus progestin users, and of endometrial cancer among unopposed estrogen users are well established, but ovarian cancer risks among hormone therapy users are less clear.  Using large cohort studies, such as the Breast Cancer Detection Demonstration Project (BCDDP) Follow-Up Study and the NIH-AARP Diet and Health Study, I have helped to describe the potential increased ovarian cancer risks associated with menopausal hormone therapy use.  Patterns of hormone therapy use in the U.S. have changed dramatically since the 1960s, and new evidence of hormone therapy’s risks and benefits continue to shape the way in which women view and use hormone therapy.  I therefore continue to lead investigations to address the currently unresolved questions about gynecologic cancer risk among hormone therapy users.

Other Hormonal Risk Factors

Many of these issues are also relevant to breast cancer, ovarian cancer, and other hormone-related cancers.  I therefore maintain a portfolio of related analyses of hormonal risk factors in DCEG cohort studies; investigations of new, potential hormonal risk factors, such as bone mineral density; and consideration of the important role that familial factors play in these cancers.  These efforts include intramural and extramural collaborations, and I welcome opportunities for additional collaborative partnerships, both at and beyond NIH, on these or related issues.

Keywords

endometrial cancer, ovarian cancer, breast cancer, menopausal hormone therapy, bone mineral density, endometrial hyperplasia, estrogens, progestins.

Selected Publications

• Lacey JV Jr, Mutter GL, Nucci MR, Ronnett BM, Ioffe OB, Rush BB, Glass AG, Richesson DA, Chatterjee N, Langholz B, Sherman ME. Risk of subsequent endometrial carcinoma associated with endometrial intraepithelial neoplasia classification of endometrial biopsies. Cancer. 2008 Aug 21. Epub ahead of print.
• Lacey JV Jr, Mutter GL, Ronnett BM, Ioffe OB, Duggan MA, Rush BB, Glass AG, Richesson DA, Chatterjee N, Langholz B, Sherman ME. PTEN expression in endometrial biopsies as a marker of progression to endometrial carcinoma. Cancer Res. 2008 Jul 15;68(14):6014-20.
• Sherman ME, Ronnett BM, Ioffe OB, Richesson DA, Rush BB, Glass AG, Chatterjee N, Duggan MA, Lacey JV Jr. Reproducibility of biopsy diagnoses of endometrial hyperplasia: evidence supporting a simplified classification. Int J Gynecol Pathol. 2008 Jul;27(3):318-25.
• Lacey JV Jr, Ioffe OB, Ronnett BM, Rush BB, Richesson DA, Chatterjee N, Langholz B, Glass AG, Sherman ME. Endometrial carcinoma risk among women diagnosed with endometrial hyperplasia: the 34-year experience in a large health plan. Br J Cancer. 2008 Jan 15;98(1):45-53.
• Lacey JV Jr. Ovarian cancer and menopausal hormone therapy: more data and new questions. Cancer Epidemiol Biomarkers Prev. 2007 Dec;16(12):2524-5. Review.
• Glass AG, Lacey JV Jr, Carreon JD, Hoover RN. Breast cancer incidence, 1980-2006: combined roles of menopausal hormone therapy, screening mammography, and estrogen receptor status. J Natl Cancer Inst. 2007 Aug 1;99(15):1152-61.
• Lacey JV Jr, Greene MH, Buys SS, Reding D, Riley TL, Berg CD, Fagerstrom RM, Hartge P. Ovarian cancer screening in women with a family history of breast or ovarian cancer. Obstet Gynecol. 2006 Nov;108(5):1176-84.
• Lacey JV Jr, Brinton LA, Leitzmann MF, Mouw T, Hollenbeck A, Schatzkin A, Hartge P. Menopausal hormone therapy and ovarian cancer risk in the National Institutes of Health-AARP Diet and Health Study Cohort. J Natl Cancer Inst. 2006 Oct 4;98(19):1397-405.
• Brinton LA, Lacey JV Jr, Trimble EL. Hormones and endometrial cancer--new data from the Million Women Study. Lancet 2005;365:1517-8.
• Lacey JV Jr, Brinton LA, Lubin JH, Sherman ME, Schatzkin A, Schairer C. Endometrial carcinoma risks among menopausal estrogen plus progestin and unopposed estrogen users in a cohort of postmenopausal women. Cancer Epidemiol Biomarkers Prev 2005;14:1724-31.
• Lacey JV Jr, Mink PJ, Lubin JH, Sherman ME, Troisi R, Hartge P, Schatzkin A, Schairer C. Menopausal hormone replacement therapy and risk of ovarian cancer. JAMA 2002;288:334-41.

Collaborators

DCEG Collaborators

• Louise A. Brinton, Ph.D.; Nilanjan Chatterjee, Ph.D.; Montserrat Garcia-Closas, M.D., Dr.P.H.; Mark H. Greene, M.D.; Patricia Hartge, Sc.D.; Allan Hildesheim, Ph.D.; Ann W. Hsing, Ph.D.; Michael F. Leitzmann, M.D., Dr.P.H.; Jay Lubin, Ph.D.; Catherine Schairer, Ph.D.; Arthur Schatzkin, M.D., Dr.P.H.; Mark E. Sherman, M.D.; Sophia S. Wang, Ph.D.

Other ScientificCollaborators

• Douglas C. Bauer, M.D., University of California at San Francisco, San Francisco, CA
• Diana S.M. Buist, Ph.D., Group Health Cooperative, Seattle, WA
• Jane Cauley, Ph.D., University of Pittsburgh, Pittsburgh, PA
• Andrew G. Glass, M.D., Kaiser Permanente Center for Health Research, Portland, OR
• Richard S. Guido, M.D., University of Pittsburgh, PA 
• Olga Ioffe, M.D., University of Maryland, Baltimore, MD
• George L. Mutter, M.D., Brigham and Women’s Hospital, Boston, MA
• Brigitte Ronnett, M.D., Johns Hopkins University, Baltimore, MD