Impact of Breast Cancer and its Therapy on Bone Density

Institution: University of California, Los Angeles
Investigator(s): Carolyn Crandall, M.D. -
Award Cycle: 2002 (Cycle VIII) Grant #: 8KB-0035 Award: $300,000
Award Type: New Investigator Awards
Research Priorities
Community Impact of Breast Cancer>Health Policy and Health Services: better serving women's needs

Initial Award Abstract (2002)
Survival of women with breast cancer continues to improve. Thus, breast cancer survivors (BCS) must have more knowledge about how breast cancer and its treatment affect their long-term health. Menopause is a universal female event; consequences may include osteoporosis. Yet there is disturbing lack of information about how BCS experience menopause, whether BCS develop osteoporosis, and what can be done about it. This application seeks to: 1) allow a highly-qualified clinician to become a researcher in the field of menopause and osteoporosis in BCS; and 2) in the context of this training, to undertake specific research focused on osteoporosis in BCS. The candidate will acquire the skills to continue work in the intersection between breast cancer, menopause, and long-term health.

The central hypotheses of the research are: In order to facilitate the PI's career transition the candidate will: obtain a Masters in Clinical Epidemiology; undertake a strong breast cancer mentoring program with Dr. Patricia Ganz, to obtain in-depth understanding of the how breast cancer and its therapy affects the health and well-being of women; and undertake mentorship in research methods and osteoporosis with Dr. Gail Greendale.

To address the 3 questions outlined above, the candidate will be mentored in the conduct of three data analyses that focus on bone density in breast cancer survivors. She will use already-collected data from the Cancer and Menopause study, an ongoing study of breast cancer survivors led by Drs. Ganz and Greendale.

The good news is that women are living longer after breast cancer treatment. The bad news is that many of their questions about long term health, particularly related to menopause, remain unanswered. This project is innovative in that it will train a clinical researcher who will focus her research career on this under-studied area of survivorship. The innovative multidisciplinary approach to the training and the research outlined here, as well as the unique breast cancer survivor data base available to the candidate, are also critical elements of the project.

Final Report (2006)
The purpose of this application was to: 1) allow a highly-qualified clinician to become a researcher in the field of menopause and osteoporosis in BCS; and 2) in the context of this training, to undertake specific research focused on osteoporosis in BCS.

Aims for Career Development Component
1) To obtain formal training in clinical epidemiology and statistics, which will supply the necessary tools for research in survivorship issues:
Dr. Crandall has completed this training. She successfully completed course requirements for the Masters of Science in Clinical Research degree, conferred in June 2004.

2) To study, breast cancer’s natural history and treatment:
Dr. Crandall had regular meetings with Dr. Patricia Ganz, an expert in breast cancer survivorship issues. She focused on what is known about menopause symptoms in breast cancer survivors, as well as the impact of breast cancer therapy on ovarian function. Throughout the course of this award, by doing weekly searches in the PubMed database, Dr. Crandall was able to stay current on all pertinent abstracts regarding how menopause affects breast cancer survivors. She reviews the new journal literature weekly for studies involving osteoporosis in BCS.

3) To learn, the methods of designing, conducting, and analyzing clinical research:
Dr. Crandall met with Dr. Gail Greendale weekly and biweekly to learn how to analyze and report data. She learned in the “real-life” context of actual data analysis based on women in the CAMS database. Also, she obtained experience in analysis and paper-writing by working with Dr. Greendale in the PEPI mammographic density study and in the Study of Women’s Health Across the Nation (SWAN). She has led or participated in several analyses from CAMS, PEPI, and SWAN. She has submitted manuscripts to peer reviewed journals and abstracts to national meetings (Please see Form 6 Publications).

4) Beginning in the second half of the 3-year program, to prepare and submit additional grants to allow continued work in BCS survivorship issues:
Dr. Crandall received a K12 award (National Institute of Health research grant #5K12AG01004 from National Institute on Aging) in 9/1/2004. In addition, she applied for 2 other awards in 2006: a CBCRP award and a DOD BCRP award. All of these proposals are in keeping with the overarching goal of continuing research on breast cancer-menopause interrelations.

Aims for Primary Research Component Summary of central hypotheses of the proposed research, and subsequent findings:
Higher estrogen levels may put a woman at higher risk of breast cancer, but at the same time might help her build better bone mass. Women with breast cancer may start out with better bone health (higher bone density) than women without breast cancer. Dr. Crandall found support for this hypothesis. Whether or not they received adjuvant therapy, BCS did indeed appear to have the same, or even better BMD, compared to the reference comparison group of women. Perhaps the blood hormonal levels present in BCS allows BCS to develop a higher BMD than women without breast cancer.

Women with breast cancer will lose bone at different speeds after menopause compared to women without breast cancer. Dr. Crandall has tentative proof that BCS without a breast cancer therapy-associated menopause transition do not lose bone density any faster than the referent group. In contrast, breast cancer-therapy associated menopause did appear to increase the a risk for faster rate of BMD loss.

Dr. Crandall has completed, presented in abstract form, and published, many of her findings from analyzing the CAMS database. She has continued to pursue and publish findings related to the breast cancer-menopause-BMD interrelationship.

Bone mineral density and adjuvant therapy in breast cancer survivors.
Periodical:Breast Cancer Research and Treatment
Index Medicus: Breast Cancer Res Treat
Authors: Crandall C, Petersen L, Ganz PA, Greendale GA.
Yr: 2005 Vol: 88 Nbr: 3 Abs: Pg:257-261