The screening that was discussed in the previous section is actually considered a form of prevention. By definition, secondary prevention refers to any modality that leads to the earlier detection of a breast cancer, thereby resulting in a potential decrease in mortality from the disease. Both breast examinations and screening mammography fall into this category.

In addition to current efforts at secondary prevention, primary prevention of breast cancer (elimination of or significant delay in clinical appearance of disease) remains an important goal. Currently, the two methods of primary prevention that exist are prophylactic surgery and chemoprevention.

Prophylactic bilateral mastectomies may be considered in women with the diagnosis of lobular carcinoma in situ, in women with a significant family history of breast cancer and in women who are known carriers of a genetic mutation. Data regarding the actual numbers of patients who undergo this procedure are lacking, however, over 1000 women responded to a national inquiry concerning prophylactic mastectomy. Based on the tremendous response to a single advertisement in one publication, it is likely that prophylactic mastectomies are performed more commonly than is thought.

In order to validate this method as appropriate for primary prevention, it is important to know the rate of subsequent breast cancer development after such a procedure. In an analysis of these patients by Memorial Sloan-Kettering Cancer Center, the incidence of subsequent breast cancer was approximately 3%. Additional data from a single-institution study at the Mayo Clinic suggest that subsequent breast cancers may occur in 10% of patients. In that study, all of the cancers developed in women who had undergone subcutaneous mastectomies rather than total mastectomies. Thus, it appears that, if the goal of prophylactic surgery is to reduce the risk of subsequent cancer by the greatest amount, total mastectomies are more appropriate than subcutaneous mastectomies.

Despite the risk reduction associated with bilateral total mastectomy, for obvious reasons it will not be the preventive option of choice in most instances.

Chemoprevention should therefore be considered for all women with significant risk for future breast cancer development. Currently, the only FDA-approved medication for prevention of breast cancer is tamoxifen. Tamoxifen acts as an antiestrogen and has been used for many years for the treatment of both metastatic breast cancers and early-stage breast cancers. As patients with breast cancer taking tamoxifen had significantly reduced numbers of contralateral breast cancers, it was felt to be an ideal agent to use in trials of chemoprevention. The largest trial to determine tamoxifin’s role in chemoprevention was performed by the National Surgical Adjuvant Breast and Bowel Project (NSABP). In this randomized, double-blind trial, women with a projected risk of breast cancer of greater than 1.66% over a 5-year period received either tamoxifen or a placebo for a period of 5 years. When an independent reviewing agency verified a 50% reduction in both invasive and noninvasive breast cancer cases in the population taking tamoxifen, the trial results were unblinded earlier than expected. Shortly thereafter, its use for chemoprevention was approved.

Raloxifene, an agent considered to be a selective estrogen-receptor modulator, will soon be investigated in an attempt to define its role in breast cancer chemoprevention. In studies in which raloxifene was used for treatment of osteoporosis, a secondary finding was the reduction of breast cancer risk of 50-70% in the population taking the medication. While the results were promising, the women in those trials were at fairly low risk of breast cancer development. A randomized, double-blind trial to compare raloxifene with tamoxifen in a population of postmenopausal women at increased risk for breast cancer development is currently being organized. This medication may hold promise for chemoprevention in the future.

Conclusion
Screening for breast cancer is clearly indicated for all women at the appropriate age. Determining a woman’s unique risk factors will help to determine both the age at which that screening should begin and also the intensity of that screening. It will also help to identify those women who need to be counseled regarding options for prevention of breast cancer. By correctly identifying high-risk populations and then applying appropriate screening schedules and chemopreventive agents, the hope is that many cases of breast cancers will be averted completely and that those that still occur will be found at the earliest stages.

Alexandra S. Heerdt
Breast cancer detection demonstration project: five-year summary report. CA 2003