Breast Cancer Risk Factors and Hormone Receptors

Institution: Kaiser Foundation Research Institute
Investigator(s): Ann Geiger, M.P.H., Ph.D. -
Award Cycle: 1996 (Cycle II) Grant #: 2KB-0048 Award: $271,408
Award Type: New Investigator Awards
Research Priorities
Etiology and Prevention>Etiology: the role of environment and lifestyle

Initial Award Abstract (1996)
This epidemiologic study was designed to improve our understanding of how breast cancer develops in a way which may help us prevent breast cancer. The study specifically aims to determine whether established risk factors for breast cancer are related to the presence of estrogen and progesterone receptors in breast tumors.

Hormonal changes are a common explanation of how various factors increase risk for breast cancer. For example, beginning menstruation at a younger age or menopause at an older age are both risk factors for breast cancer. Both factors cause women to experience an increased number of menstrual cycles over their lifetime. The estrogen and progesterone present in these cycles stimulate the growth of breast tissue through estrogen and progesterone receptors present on breast cells. Greater amounts of estrogen and progesterone promote more growth than usual. This growth may increase the risk of breast cancer by increasing the chances of a genetic error (as cells reproduce themselves) or allowing genetic errors to be expressed more frequently.

The idea (hypothesis) to be tested in this study is that tumors with both estrogen and progesterone receptors will be more common in women with hormonally-related risk factors such as early age of first menstruation, late age at menopause, and late age at first birth. The accompanying hypothesis is that tumors without estrogen and progesterone receptors will be more common in women with risk factors which are not related to hormones. Such risk factors include having a mother or sister diagnosed with breast cancer. Finally, tumors with one receptor but not the other may occur in women with or without hormonally-related risk factors.

Female members of the Kaiser Permanente Southern California Medical Care Plan diagnosed with breast cancer from November 1996 to November 1998 will be included in this study. These patients will be asked to complete a short questionnaire about established breast cancer risk factors. Information about the presence of estrogen and progesterone receptors in these patients' tumors will be collected from pathologists' reports. Then the presence of breast cancer risk factors will be examined in four groups of patients with similar receptor status: both receptors positive; both receptors negative; estrogen positive with progesterone negative; and estrogen negative with progesterone positive.

This study was designed in response to two related BCRP priority issues: etiology and prevention. Improving our understanding of how breast cancer develops may suggest ways in which breast cancer can be prevented, thus having a dramatic impact on the health and well-being of the women in California and elsewhere.

Final Report (1999)
The aim of this study was to understand the possible relationships between commonly understood breast cancer risk factors and the presence of structures (receptors) in breast tumors that bind to the hormones estrogen and progesterone. These hormones then enter the tumor and influence the tumor's growth. To look at these relationships, over the last three years we conducted a prospective study of invasive breast cancer cases at a large health maintenance organization (HMO).

We reviewed 4,191 pathology reports to identify 3,124 eligible breast cancer cases diagnosed between September, 1996 and October, 1998. After physicians excluded women with severe physical or mental health problems, we mailed questionnaires to 2,985 women. Of the 2,441 women who returned the questionnaire, 2,236 had test results for estrogen or progesterone receptors or both. We also contacted 941 women without breast cancer and received 603 completed questionnaires.

We have been conducting analyses for the past nine months. Because most of the women who returned the questionnaire and had test results were postmenopausal, we are focusing on this group. The first analysis showed that when we compared women with breast cancer to women without breast cancer, our results were remarkably similar to the results obtained in other studies in that estrogen receptors are less common in blacks and Hispanics and more common in women with mothers, but not sisters, with breast cancer. This conclusion gives us confidence that our other results are reliable. Our study is too small to make other firm conclusions or to look clearly at progesterone receptors.

Another preliminary analysis suggests that women who have used hormone replacement therapy are diagnosed with earlier cancers.

Our next steps are to finalize the main and preliminary analyses and submit them to scientific journals for publication. We are also considering the possibility of using cancer registry data to look at survival by receptor and risk factor status. The ultimate goal of this project was to help us learn more about how breast cancer develops. We hope that the knowledge generated from this study will lead to better prevention and treatment of breast cancer.