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Populations as Targets for Breast Cancer Prevention Trials’ VICTORG.




University of Texas M. D. Anderson Cancer Center, Department of Medical Oncology, 1515 Holcombe Boulevard, Box 501, Houston, Texas 77030 Breast cancer risk factors include age; a family history of the disease in first-degree relatives (particularly if premenopausal with bilateral disease); proliferative benign breast disease with or without atypia; mammographic parenchymal pattern showing glandular, dense, dysplastic, or Wolfe I2 changes; and obesity. Women in these risk groups have annual breast cancer incidence rates 2 to 10 times higher than baseline. Using data from the National Cancer Institute SEER Program, the U.S. 1987 census estimates, and published prevalence and incidence estimates for breast cancer risk factors, estimates were made for the number of women in the white female population who are at increased risk for breast cancer and who might serve as suitable subjects for an antiestrogen chemoprevention intervention trial. More than 30 million white women are older than 50 years. Two million women older than 50 years have at least one first-degree relative with breast cancer. Six million women over age 50 have undergone breast biopsy for benign disease; one-fourth of these women have proliferative changes, and 11% also have a family history of breast cancer. More than 8 million women older than 50 years are obese, and at least a million older women have high-risk mammographic parenchymal patterns. Thus, there are at least 12 million women at increased risk for breast cancer in the United States, and each year 200,000 additional women enter the high-risk pool. These data indicate that sufficient numbers of women at increased risk for breast cancer are present in the population to justify a chemoprevention trial. The optimal recruitment strategy is yet to be identified. 0 1991 Academic

Press, Inc.


The epidemiology of breast cancer has been thoroughly studied, and the major breast cancer risk factors are well recognized (l-3). Established breast cancer risk factors are associated with relative risks of breast cancer ranging from slightly greater than 1 to 10 or more. A relative risk can be thought of as the multiplier of the incidence of a disease. Hence, subjects with increased relative risk of a disease have, as a group, an increased incidence of the disease. When designing clinical trials that require recruitment and follow-up of a large number of subjects over many years, the number of “events” is an important consideration in sample size estimations. For breast cancer prevention trials, the event of interest is a histologically confirmed diagnosis of breast cancer. Groups of subjects with substantially increased relative risks of breast cancer will have, correspondingly, a greater annual number of breast cancer diagnoses. This increased number of cases reduces the number of subjects required to demonstrate treatment-related differ’ Presented at the Workshop on Antiestrogen Prevention of Breast Cancer, October 2-3, 1989, Madison, WI. Proceedings cosponsored by the National Cancer Institute (Grant 1 R13 CA49561-01) and the American Cancer Society (Grant RD 291). 86 0091-7435/91 $3.00 Copyright 0 1991 by Academic Press, Inc. AlI rights of reprcduction in any form reserved.








ences in cancer incidences with acceptable statistical power. Furthermore, subjects at increased risk for development of a disease may be better motivated to enter a clinical prevention trial and to remain to its completion. These, then, are the reasons for focusing on women with risk factors for breast cancer when designing a chemoprevention trial. There are, however, potential difficulties in identifying and contacting high-risk subjects in order to offer them participation in the trial. Ultimately, it may be more efficient to enroll more subjects at lower risk of developing a disease than to screen many more potential subjects in order to identify and enroll only those at highest risk. This study reviews the numbers of white women in the United States who have readily identifiable factors that place them at increased risk for breast cancer. The calculations which follow are restricted to white women because of the paucity of data available for breast cancer risk factors among blacks, especially with reference to family history and benign breast disease. BREAST



Established breast cancer risk factors are shown in Table 1. While more than a dozen risk factors have been identified, the majority are associated with lifetime relative risks of ~1.5. In addition, some risk factors remain controversial (e.g. oral contraceptive use) with some reported studies showing reduction in breast cancer risk in the presence of the risk factor, and other contradictory studies showing protection against breast cancer risk in the presence of the same risk factor. At least four factors have been shown to provide protection against breast TABLE







Relative risk


Family history Proliferative BBD Obesity

7.8% 2.3% 2040%

4 1.5-16 2-11 2-4


Protective factors

Relative risk

Surgical menopause 0.25-0s First birth

High-risk populations as targets for breast cancer prevention trials.

Breast cancer risk factors include age; a family history of the disease in first-degree relatives (particularly if premenopausal with bilateral diseas...
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