In 2013, there will be an estimated 232,340 new cases of breast cancer in the United States, and 39,620 women will die from the disease. The chance that breast cancer will be responsible for a woman’s death is about 1 in 36 (~ 3%).1
Some women, such as those with lobular carcinoma in situ (LCIS), are more at risk than others of being diagnosed with breast cancer during later stages of their life.2 Despite its name, LCIS is not considered a cancer, but rather an abnormal growth of cells inside the small lobes of the breast, that has not spread to the surrounding tissues.3
Compared with other women, however, those with LCIS are 7 to 12 times more likely to develop invasive cancer in either breast.4 Even though LCIS is a risk factor for breast cancer, it is not a precursor to breast cancer. LCIS can develop into invasive lobular cancer or invasive ductal cancer in the future.5
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Those who have a 5-year predicted risk of breast cancer of 1.66% or higher on the Breast Cancer Risk Assessment Tool (based on the Gail Model) from the National Cancer Institute (NCI) are also considered high risk.2 The Breast Cancer Risk Assessment tool evaluates a woman’s risk of developing invasive breast cancer during a 5-year period and up to the age of 90 (lifetime risk) based on the woman’s age and the risk factor information available.
The tool also shows the average risk for developing breast cancer for a woman of the same age for comparison. The risk estimates calculated by the tool are based on absolute breast cancer risk, which is the chance or probability of developing invasive breast cancer within a defined age interval. Although a women’s risk may be accurately estimated, the predictions do not state a definitive time when a woman will develop breast cancer.6
In an era of growing options for breast cancer prevention and risk reduction the Breast Cancer Risk Assessment Tool is being used more often during routine healthcare visits. The tool can supplement the healthcare team’s clinical knowledge regarding each patient’s breast cancer risk, and help guide a patient in making decisions about preventive options.
As a basis for encouraging a proactive approach to breast cancer assessment and management, the American Society of Clinical Oncology (ASCO) has developed recommendations for the use of tamoxifen, raloxifene, and exemestane to help lower the risk of breast cancer in women at high risk (Table 1). The recommended use of these drugs should be discussed as options for lowering the risk of developing invasive breast cancer in appropriate candidates.
Table 1. ASCO Recommendations for Preventive Pharmacotherapy in Women at High Breast Cancer Risk
| Drug |
Recommended Use | Not Recommended |
| Tamoxifen Dose: 20 mg per day orally for 5 years |
• Patients with ER (+) BC
• Premenopausal women age ≥ 35 years with a 5-year projected absolute BC risk ≥ 1.66% • Women with LCIS
Risk reduction benefit continues for at least 10 years |
• Women with a history of deep vein thrombosis, pulmonary embolus, stroke, or transient ischemic attack or during prolonged immobilization
• Women who are pregnant or may become pregnant; or nursing mothers
• Not for use in combination with hormone therapy |
| Raloxifene Dose: 60 mg per day orally for 5 years |
• Patients with ER (+) BC
• Postmenopausal women age ≥ 35 years with a 5-year projected absolute BC risk ≥ 1.66%
• Women with LCIS May be used longer than 5 years in women with osteoporosis, in whom BC risk reduction is a secondary benefit |
• Women with a history of deep vein thrombosis, pulmonary embolus, stroke, or transient ischemic attack or during prolonged immobilization
• Women who are pregnant or may become pregnant; or nursing mothers
• Not for use in premenopausal women
• Not for use in combination with hormone therapy |
| Exemestane* Dose: 25 mg per day orally for 5 years |
• Patients with ER positive BC
• Postmenopausal women age ≥ 35 years with a 5-year projected absolute BC risk ≥ 1.66%
• Women with LCIS • Women with atypical hyperplasia |
• Women who are pregnant or may become pregnant; or nursing mothers
• Not for use in combination with hormone therapy
• Not for use in premenopausal women |
| *Exemestane is currently being investigated and is not currently FDA-approved for breast cancer risk reduction. Abbreviations: ER, Estrogen receptor; BC, breast cancer, LCIS, lobular carcinoma in situ. |
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ASCO recommendations are based on past clinical studies.
- The Bowel Project P-1 Study found tamoxifen reduced the risk of invasive breast cancer by 49% (P<0.00001) over the course of 69 months.7
- The MORE trial showed that raloxifene decreased the risk of estrogen receptor (ER)–positive breast cancer by 90%.8
- The CORE trial revealed those treated with raloxifene had a reduction of 59% and 66% for the 4-year incidence of invasive breast cancer and ER-positive invasive breast cancer, respectively.9
Exemestane is currently not approved by the US Food and Drug Administration for prevention of breast cancer in high-risk female populations. However, previous studies show that exemestane has a 65% relative reduction in the annual incidence of invasive breast cancer, when compared with those patients that had not undergone treatment with the drug.10 Apart from the clinically proven data, potential side effects of the drugs are also important to consider when deciding which treatment option to select (Table 2).
Table 2: Percentage of Women Experiencing Common Side Effects with Tamoxifen, Raloxifene, and Exemestane
| Tamoxifen11 (n= 1,422) |
Raloxifene12 (n= 581) |
Exemestane10 (n= 2,240) |
|
| Hot Flashes | 64 | 24.6 | 40 |
| Fluid Retention | 32 | 3.3 | N/A |
| Sweating | N/A | 3.1 | 22 |
| Fatigue | N/A | 14.6 | 23 |
| Nausea | 26 | 8.8 | 7 |
| Irregular Menses | 25 | N/A | N/A |
| Vaginal Discharge | 30 | 4.3 | N/A |
| Musculoskeletal arthritis | N/A | 7.5 | 11 |
| Joint Pain | N/A | N/A | 30 |
Although preventive options are available for women at high risk of developing breast cancer, the benefits and risks should be considered before starting any of these drugs. The benefits of choosing a tamoxifen, raloxifene, or exemestane treatment regimen may decrease a patient’s risk of procuring invasive breast cancer, but side effects may potentially occur, which may affect a patient’s quality of life. Ultimately, it is up to the patient to decide whether or not to take preventive measures; however these guidelines can help healthcare professionals provide relevant data and information, thereby allowing the patient to make the appropriate choice for their particular situation.
References
1. Cancer Facts and Figures 2013. American Cancer Society. Atlanta, Ga. http://www.cancer.org/cancer/breastcancer/detailedguide/breast-cancer-key-statistics. Accessed July 19, 2013.
2. Visvanathan K, Hurley P, Bantug E, et al. Use of Pharmacologic Interventions for Breast Cancer Risk Reduction: American Society of Clinical Oncology Clinical Practice Guideline. Journal of Clinical Oncology. July 2013, 49. 3122.
3. Lobular Carcinoma in Situ (LCIS), Susan G. Komen Breast Cancer Foundation. http://ww5.komen.org/BreastCancer/CarcinomainSitu.html. Accessed July 22, 2013.
4. Kilbride KE and Newman LA. Chapter 25: Lobular Carcinoma In Situ: Clinical Management, in Harris JR, Lippman ME, Morrow M, Osborne CK. Diseases of the Breast, 4th edition, Lippincott Williams & Wilkins, 2010.
5. Bagaria SP, Shamonki J, Kinnaird M, Ray PS, Giuliano AE. The florid subtype of lobular carcinoma in situ: marker or precursor for invasive lobular carcinoma? Ann Surg Oncol. 18(7):1845-51, 2011.
6. Breast Cancer Risk Assessment Tool. National Cancer Institute. Bethesda, MD http://www.cancer.gov/bcrisktool/about-tool.aspx#gail. Accessed July 22, 2013.
7. Fisher B., Joseph P., Costantino D., et al Tamoxifen for Prevention of Breast Cancer: Report of the National Surgical Adjuvant Breast and Bowel Project P-1 Study. Journal of the National Cancer Institute. Vol. 90, No. 18, September 16, 1998. 1371-1388
8. Cummings S., Eckert S., Krueger K., et al The Effect of Raloxifene on Risk of Breast Cancer in Postmenopausal Women: Results from the MORE Randomized Trial. JAMA. 1999, 281, 2189-2197.
9. Martino S., Cauley J., Barrett-Connor E., at al. Continuing Outcomes Relevant to Evista: Breast Cancer Incidence in Postmenopausal Osteoporotic Women in a Randomized Trail of Raloxifene. Journal of the National Cancer Institute. December, 2004. Vol. 96, No. 23, 1751- 1761.
10. Goss P.M.D. Ph.D., Ingle J. M.D., Ales-Martinez J. M.D. Ph.D., et al. Exemestane for Breast Cancer Prevention in Postmenopausal Women. The New England Journal of Medicine. June, 2011. Vol. 364, No. 25, 2381-2391.
11. Nolvadex Monograph. http://www.accessdata.fda.gov/drugsatfda_docs/label/2005/17970s053lbl.pdf Accessed July 24, 2013.
12. Evista Package Insert. http://pi.lilly.com/us/evista-pi.pdf Accessed July 24, 2013.
