Several strategies are available for primary prevention among women with an increased risk of developing breast cancer. For women with confirmed BRCA1 or BRCA2 mutations, referral to the high risk screening program at the BCCA and counselling about prophylactic surgery is advisable. For women with a strong family history and no prior BRCA testing, referral to the Hereditary Cancer Program at the BCCA may be appropriate [add link to appropriate section on CMM].

Three drugs have been shown to effectively reduce the risk of developing estrogen receptor positive pre invasive (ductal carcinoma in situ, DCIS) and invasive breast cancer among women with elevated risk, as determined by the sum of their risk factors using a validated risk prediction tool (the Gail model). To date there are no drug prevention strategies that have been shown to reduce the incidence of estrogen receptor negative breast cancer.

Tamoxifen reduces the risk of developing primary breast cancer by 50%. In the largest study, among 13,388 women randomized to tamoxifen or placebo, DCIS and invasive breast cancer occurred in the 244 placebo group and 124 in the tamoxifen group over a 5.5 year period.(1) Taking tamoxifen for five years in this population resulted in a doubling in the incidence of endometrial cancer, from 0.09% increased to 0.23%, a small increase in the incidence of stroke, from 0.36% to 0.58%, and of deep venous thrombosis (.08 vs 0.13% per year). Other primary prevention studies have shown similar effects. (2,3) The protective effect of 5 years of tamoxifen persists after its discontinuation, to at least ten years from treatment start. There was no increase in cardiac events and there was a modest reduction in hip, wrist, and vertebral fractures in the tamoxifen group.

Raloxifene (Evista®) has also demonstrated reduction in both DCIS and invasive breast cancer by the same degree as tamoxifen in a large clinical trial comparing the two drugs.(4) The advantage of raloxifene over tamoxifen is a greatly reduced incidence of postmenopausal vaginal bleeding, the need for endometrial investigations, and of endometrial cancer (incidence 0.2% for tamoxifen versus 0.12% for raloxifene). Long term follow up again shows an effect that lasts beyond five years of exposure (5).

Exemestane, an irreversible steroidal aromatase inhibitor, has recently been shown to reduce the risk of ER+ breast cancer in postmenopausal women by 65% compared to placebo in a large prevention trial (6). The placebo group had a 0.55% annual incidence rate of breast cancer compared with 0.19% in the exemestane group. There was no increased incidence of cardiovascular events, second cancers, fractures, or self reported development of osteoporosis. More women on exemestane reported joint and musculoskeletal pain while on medication (30% versus 17%). Long term follow up is clearly warranted for more safety data and to determine the duration of the protective effect that five years of therapy provides. Ongoing trials are exploring the effectiveness of other aromatase inhibitors in this setting.

The effectiveness of secondary prevention on breast cancer mortality through screening mammography has been clearly demonstrated in randomized controlled trials, even though 10% of breast cancers will not show up on a mammogram. Asymptomatic women between the ages of 40-79 should be encouraged to have regular screening mammography at the Screening Mammography Program of BC (SMPBC) centres or mobile vans, at intervals as set out in the SMPBC See section 3.3 Screening Mammography.. Appointments can be booked through 660-3639 for the Lower Mainland and at 1-800-663-9203 for the rest of the province.

Women younger than age 40 at very high risk (2 or more first degree relatives with the disease) are eligible to attend the SMPBC on a physician referral basis. Such women may also be interested in and eligible for a referral for genetic counselling and testing. Women over the age of 79, who are in good general health (life expectancy of 10 or more years) may benefit from screening and can be referred to the SMPBC.

Annual physical examination of healthy women should include a clinical breast examination. The physical examination serves as a screening procedure, and provides an opportunity for the health professional to teach breast self-examination. It should be noted however that the value of breast self-examination alone in reducing mortality from breast cancer has not been convincingly demonstrated.

References:

1. Tamoxifen for Prevention of Breast Cancer: Report of the National Surgical Adjuvant Breast and Bowel Project P-1 Study. Fisher B, Costantino JP, Wickerham DL, et al. Journal of the National Cancer Institute, 90 (18), 1998
Long-Term Results of Tamoxifen Prophylaxis for Breast Cancer—96-Month Follow-up of the Randomized IBIS-I Trial. Cuzick J, Forbes JF, Sestak I, et al. J Natl Cancer Inst 99: 272 – 82, 2007
2. Twenty-Year Follow-up of the Royal Marsden Randomized, Double-Blinded Tamoxifen Breast Cancer Prevention Trial. Powles TJ , Ashley S, Tidy A Smith IE , Dowsett M. J Natl Cancer Inst 99: 283 – 90, 2007
3. Effects of Tamoxifen vs Raloxifene on the Risk of Developing Invasive Breast Cancer and Other Disease Outcomes. The NSABP Study of Tamoxifen and Raloxifene (STAR) P-2 Trial.. Vogel VG, Costantino JP, Wickerham DL, et al. JAMA, June295: 2727, 2006
4. Update of the National Surgical Adjuvant Breast and Bowel Project Study of Tamoxifen and Raloxifene (STAR) P-2 Trial:Preventing Breast Cancer. Vogel VG, Costantino JP, Wickerham DL, et al. Cancer Prev Res; 3(6); 696–706, 2010.
5. Exemestane for Breast-Cancer Prevention in Postmenopausal Women Paul E. Goss, M.D., Ph.D., James N. Ingle, M.D.,  José E Alés-Martínez, This article (10.1056/NEJMoa1103507) was published on June 4, 2011, at NEJM.org. N Engl J Med 2011.
6. Benefit of screening mammography in women aged 40-49: a new meta-analysis of randomized controlled trials. Hendrick RE, Smith RA, Rutledge JH 3rd, Smart CR. J Natl Cancer Inst Monograph.22:87-92,1997.
7. Efficacy of screening mammography among women aged 40 to 49 years and 50 to 69 years: comparison of relative and absolute benefit. Kerlikowske K. J Natl Cancer Inst Monogr. 22:79-86, 1997.