Clinical Review

The case for chemoprevention as a tool to avert breast cancer

Author and Disclosure Information

Women at high risk of invasive breast cancer can elect chemoprevention with tamoxifen or raloxifene. An aromatase inhibitor may one day be an option.



The author reports that he is a consultant to Eli Lilly, Pfizer, and Wyeth, and a speaker for Eli Lilly and Wyeth.

CASE 1: Premenopausal woman
at high risk of breast cancer

R. J. is a 43-year-old, nulliparous woman who reached menarche at age 11. She has undergone two breast biopsies, the most recent of which revealed ductal hyperplasia with marked atypia.

R. J.’s sister had breast cancer at 49 years of age; her mother had breast cancer at 66 years. Because of R. J.’s family history, she underwent testing for a BRCA mutation. The result was negative.

R. J. has come to your office today to find out if she can do anything to reduce her risk of breast cancer. What options can you offer?

The most common method of “prevention” of breast cancer involves early detection and assessment of abnormalities through frequent surveillance with mammography. Some women who have dense breasts, a history of breast biopsy, or other risk factors for breast cancer may benefit from intensive surveillance with both mammography and ultrasonography—and, in some cases, magnetic resonance imaging.

More aggressive options include:

  • the use of a chemopreventive agent such as tamoxifen or raloxifene
  • in rare cases—usually when a BRCA mutation is present—prophylactic mastectomy.

Before it is possible to determine the optimal approach for a particular woman, it is necessary to conduct an individualized assessment of her risk—that is, to estimate the probability that she will develop breast cancer over a defined period of time. Such an estimate is also useful for designing prevention trials in high-risk subsets of the population. (Prevention trials differ from therapeutic clinical trials in that asymptomatic healthy women are exposed to potentially toxic interventions for prolonged periods to reduce their risk of breast cancer.)

This article describes chemopreventive options for women at high risk, based on individualized risk assessment using the Gail model.

(Editor’s note: For additional discussion of the important role ObGyns play in the fight against breast cancer, see Editor in Chief Dr. Robert L. Barbieri’s Editorial.)

What constitutes high risk?

You can estimate the likelihood that a woman like your patient may develop breast cancer using various individual risk factors ( TABLE 1 ), but estimates for combinations of risk factors are preferable. The Gail model takes into account some nongenetic factors, such as parity and age at menarche, but also genetic factors, such as family history. The model calculates a woman’s individualized breast cancer probability and yields a numerical risk (a percentage) that she will develop invasive breast cancer over the next 5 years; it also yields an estimate of her risk of developing the malignancy over the remainder of her life.1,2

A Gail-model 5-year estimate of 1.66% or higher denotes a high risk of developing breast cancer. That benchmark was the one employed in the Breast Cancer Prevention Trial (BCPT), conducted as part of the National Surgical Adjuvant Breast and Bowel Project (NSABP).3


What are the risk factors for breast cancer?
And what degree of relative risk do they confer?

Relative risk
• Age 25–34 years at first live birth
• Early menarche
• Late menopause
• Benign proliferative disease
• Postmenopausal obesity
• Alcohol use
• Hormone replacement therapy
• Age >35 years at first live birth
• First-degree relative with breast cancer
• Nulliparity
• Radiation exposure
• Personal history of breast cancer
• Gene mutation (BRCA 1 or 2)
• Lobular carcinoma in situ
• Ductal carcinoma in situ
• Atypical hyperplasia
Adapted from Bilimoria and Morrow23

Weaknesses of the Gail model

The Gail model’s approach to estimating risk has some limitations. The model uses the number of prior breast biopsies in its assessment—but the relative risk associated with prior biopsy is smaller for women older than 50 years than it is for younger women.

Furthermore, data on which Gail bases its estimates were collected in the late 1970s and early 1980s. Since then, the increasing ease of breast histopathologic assessment—through fine-needle aspiration and outpatient core-needle biopsy—has confused the issue of just what constitutes a breast “biopsy.” (Most patients surveyed consider it to be any histologic sampling of the breast.)


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