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Chemoprevention of Breast Cancer in High Risk Patients Guideline Summary


(O): May 31, 2011 (R):

Date Signed: May 23, 2012
Tumor Group: Breast Disease Site Group
Issuing Authority: Dr. Kara Laing, Clinical Chief,
Cancer Care Program
Adapted From: Alberta Health Services "risk reduction and surveillance strategies for individuals at high genetic risk for breast and ovarian cancer" guideline, April 2011 (11).

View the complete guideline: Chemoprevention of Breast Cancer in High Risk Patients

Target Population:

Patients who meet the high risk criteria for the development of breast cancer.


All premenopausal patients ≥ 35 years of age and postmenopausal patients who are deemed high risk for the development of breast cancer, and with no contraindications, should be offered tamoxifen 20mg/daily taken orally, for five consecutive years. Raloxifene 60mg/daily taken orally, for five consecutive years is an option for postmenopausal patients only. Exemestane 25mg/daily taken orally, for five consecutive years is also an option for postmenopausal patients only.

Supporting Evidence:

The current standard of treatment offered to high risk patients would be tamoxifen 20mg/daily taken orally, for five consecutive years, as per the National Surgical Breast and Bowel Project (NSABP) P-1 clinical trial (1,2). The conclusion reached from this trial suggests that tamoxifen reduces the risk of invasive breast cancer by 49% compared to placebo. The Early Breast Cancer Trialists’ meta-analysis (3) confirmed that the risk of contralateral primary breast cancer is substantially reduced by 5 years of tamoxifen therapy in women with first breast cancers that are estrogen receptor-positive or have an unknown estrogen receptor status.

An alternative to tamoxifen for postmenopausal women is raloxifene 60mg/daily, taken orally, for five consecutive years, as per the STAR trial (Study of Tamoxifen and Raloxifene) (4). This trial concluded that raloxifene is as effective as tamoxifen in reducing the risk of invasive breast cancer. Also, findings suggest that though the risk of thromboembolic events and cataracts exist with both SERMs, the risk appears to be less for raloxifene. However, raloxifene did not reduce the risk of developing ductal carcinoma insitu (DCIS) in the STAR trial.

Another alternative for postmenopausal patients is exemestane 25mg/daily, taken orally, for five consecutive years as per the recently published NCIC CTG MAP.3 clinical trial (5). In this large chemoprevention trial, 4560 women were randomly assigned to exemestane or placebo.

At a median follow-up of 35 months, there was a 65% relative reduction in the annual incidence of invasive breast cancer in the exemestane arm compared to the placebo arm. No significant differences were noted between the two arms in terms of skeletal fractures, cardiovascular events, other cancers, or treatment-related deaths.

Qualifying Statements:

  • A risk assessment should be carried out using a tool such as the Gail model (6), which takes into account the patient’s own personal medical history, reproductive history, and history of breast cancer among first degree relatives, to determine the individual’s own personal risk. A person determined to have a ≥ 1.66% five year risk of breast cancer is considered high risk according to the Gail model
  • The patient may be a genetic carrier of known mutations, such as BRCA1 and BRCA2 (7,8), as well as E-Cadherin gene mutations (9,10) and have already undergone genetic testing or are from families, with well-documented, pedigrees of known genetic carriers. There are also other patients who meet the criteria for high risk status, but may not have had genetic testing, or may not carry these particular mutations
  • The consultation with the medical oncologist will also include a thorough discussion with the patient of the known side effects of tamoxifen, raloxifene, or exemestane to allow the patient to make a fully informed treatment decision


These guidelines are a statement of consensus of the Breast Disease Site Group regarding their views of currently accepted approaches to diagnosis and treatment. Any clinician seeking to apply or consult the guidelines is expected to use independent medical judgment in the context of individual clinical circumstances to determine any patient’s care or treatment.

Contact Information:
For more information on this guideline, please contact:

Dr. Kara Laing MD FRCPC
Dr. H. Bliss Murphy Cancer Center
St. John’s, NL
Telephone (709) 777-8095

For the complete guideline (PDF) on this topic or for access to any of our guidelines, please visit our Cancer Care Program website.

Literature Support:
  1. Fisher B, Constantino JP, et al. Tamoxifen for the prevention of breast cancer: report of the National Surgical Adjuvant Breast and Bowel Project P-1 Study. J Natl Cancer Inst. 1998;90(18):1371-1388.
  2. Cuzick J, Powles T, et al. Overview of the main outcomes in breast cancer prevention trials. Lancet. 2003;361:296-300.
  3. Early Breast Cancer Trialists’ Collaborative Group (EBCTCG). Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet. 2005;365(9472):1687-1717.
  4. Vogel VG, Constantino JP, et al. 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. JAMA. 2006;295(23):2727-2741.
  5. Goss PE, Ingle JN, et al. Exemestane for breast-cancer prevention in postmenopausal women. New Eng J Med. 2011;364(25):2381-2391.
  6. Gail MH, Constantino JP, et al. Weighing the risks and benefits of tamoxifen treatment for preventing breast cancer. J Natl Cancer Inst. 1999;91(21):1829-1846.
  7. Brekelmans CTM, Seynaeve C, et al. Effectiveness of breast cancer surveillance in BRCA1/2 gene mutation carriers and women with high familial risk. J Clin Oncol. 2001;19(4):924-930.
  8. Peshkin BN, DeMarco TA, et al. BRCA1/2 testing: complex themes in result interpertation. J Clin Oncol. 2001;19(9):2555-2565.
  9. Pharoah PDP, Guilford P, et al. Incidence of gastric cancer and breast cancer in CDH1 (E-Cadherin) mutation carriers from hereditary diffuse gastric cancer families. Gastroenterology. 2001;121:1348-1353.
  10. Oliveira C, Bordin MC, et al. Screening E-Cadherin in gastric cancer families reveals germline mutations only in hereditary diffuse gastric cancer kindred. Human Mutation. 2002;19:510-517.
  11. Alberta Health Services. Clinical Practice Guideline BR-011: Risk reduction and surveillance strategies for individuals at high genetic risk for breast and ovarian cancer. April 2011.



Updated Apr 7, 2014