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 This is an original JCO publication from 2013. Please visit the JCO website to access the full article.


Use of Pharmacologic Interventions for Breast Cancer Risk Reduction: American Society of Clinical Oncology Clinical Practice Guideline


 

 Authors

Kala Visvanathan, Patricia Hurley, Elissa Bantug, Powel Brown, Nananda F. Col, Jack Cuzick, Nancy E. Davidson, Andrea DeCensi, Carol Fabian, Leslie Ford, Judy Garber, Maria Katapodi, Barnett Kramer, Monica Morrow, Barbara Parker, Carolyn Runowicz, Victor G. Vogel III, James L. Wade and Scott M. Lippman

THE BOTTOM LINE

 

 

Intervention

  • Pharmacologic interventions for breast cancer risk reduction, including selective estrogen receptor modulators and aromatase inhibitors

 

Target Audience

  • Medical Oncologists, Surgical Oncologists, Gynecologists, Primary Care Physicians, General Practitioners

 

Key Recommendations

  • Tamoxifen (20 mg/d orally for 5 years) should be discussed as an option to reduce the risk of invasive breast cancer, specifically estrogen (ER)-positive breast cancer, in premenopausal or postmenopausal women ≥ 35 years of age at increased risk of breast cancer, or with lobular carcinoma in situ (LCIS). Tamoxifen is not recommended for use in women with a history of deep vein thrombosis, pulmonary embolus, stroke, transient ischemic attack, during prolonged immobilization, in women who are pregnant or who may become pregnant, or nursing mothers. Tamoxifen is not recommended in combination with hormone therapy.
  • Raloxifene (60 mg/d orally for 5 years) should be discussed as an option to reduce the risk of invasive breast cancer, specifically ER-positive breast cancer, in postmenopausal women ≥ 35 years of age at increased risk of breast cancer, or with LCIS. It should not be used for breast cancer risk reduction in premenopausal women. Raloxifene is not recommended for use in women with a history of deep vein thrombosis, pulmonary embolus, stroke, transient ischemic attack, or during prolonged immobilization.
  • Exemestane (25 mg/d orally for 5 years) should be discussed as an alternative to tamoxifen or raloxifene to reduce the risk of invasive breast cancer, specifically ER-positive breast cancer, in postmenopausal women ≥ 35 years of age at increased risk of breast cancer, or with LCIS or atypical hyperplasia. Exemestane should not be used for breast cancer risk reduction in premenopausal women.
  • For tamoxifen and raloxifene, the most favorable risk-benefit profile is seen in women at greatest risk of developing breast cancer.
  • Discussions with patients and health care providers should include both the risks and benefits of each agent under consideration.
  • NOTE1: Refer to Table 1 for the complete recommendations.
  • NOTE2: Increased risk is defined as a 5 year projected absolute risk of breast cancer ≥1.66% on the NCI Breast Cancer Risk Assessment Tool or an equivalent measure.
  • NOTE3: Trials were not designed to assess mortality and the impact of the agent on overall survival or breast cancer-specific survival has not been demonstrated in 10 years of follow-up.

 

Methods

  • A systematic review of randomized controlled trials and meta-analyses published from June 2007 through June 2012 was completed using MEDLINE and the Cochrane Collaboration Library. An Update Committee was convened and reviewed the evidence to determine whether the 2009 ASCO clinical practice guideline recommendations needed to be updated.

 

Additional Information

 

 

 

 

SUMMARY OF RECOMMENDATIONS

Agent

OLD Recommendations (2009)*

NEW Recommendations

Strength of Recommendation and Strength of Evidence§

 

Tamoxifend

 

  • May be offered to reduce the risk of ER-positive invasive BC for premenopausal women with a 5-year projected BC risk ≥ 1.66% (according to the NCI Breast Cancer Risk Assessment Tool) or with LCIS. Risk reduction benefit continues for at least 10 years. Impact on BC mortality is unknown.
  • May be offered to reduce the risk of ER-positive invasive BC for postmenopausal women with a 5-year projected BC risk ≥ 1.66% (according to the NCI Breast Cancer Risk Assessment Tool), or with LCIS. Risk reduction benefit continues for at least 10 years. Impact on BC mortality is unknown.
  • Is not recommended for women with a prior history of deep vein thrombosis, pulmonary embolus, stroke, or transient ischemic attack.
  • Combined use of tamoxifen for BC prevention and hormone therapy is currently not recommended.
  • Follow-up should include a baseline gynecologic examination before initiation of treatment and annually thereafter, with a timely work-up of abnormal vaginal bleeding.
  • Risks and benefits should be given careful consideration during the decision-making process.
  • DOSAGE: 20 mg/d for 5 years.
 
  • Should be discussed as an option to reduce the risk of invasive BC, specifically estrogen (ER)-positive breast cancer, in premenopausal women who are ≥ 35 years of age with a 5-year projected absolute BC risk ≥ 1.66%,a or with LCIS .Risk reduction benefit continues for at least 10 years.b
  • Should be discussed as an option to reduce the risk of invasive BC, specifically estrogen (ER)-positive breast cancer, in postmenopausal women who are ≥ 35 years of age with a 5-year projected absolute BC risk ≥ 1.66%,a or with LCIS. Risk reduction benefit continues for at least 10 years.b
  • Is not recommended for use in women with a history of deep vein thrombosis, pulmonary embolus, stroke, transient ischemic attack, or during prolonged immobilization.
  • Is not recommended for women who are pregnant, women who may become pregnant, or nursing mothers.
  • Is not recommended in combination with hormone therapy.
  • Follow-up should include a timely work-up of abnormal vaginal bleeding. 
  • Discussions with patients and health care providers should include both the risks and benefits of tamoxifen in the preventive setting.c
  • DOSAGE: 20 mg/d orally for 5 years.

Strong, evidence-based recommendation.

Strength of evidence: Strong evidence - based on 5 RCTs with low risk of bias

 

Raloxifenee

 

  • May be offered to reduce the risk of ER-positive invasive BC in postmenopausal women with a 5-year projected BC risk ≥ 1.66% (according to the NCI Breast Cancer Risk Assessment Tool) or with LCIS. Impact on BC mortality is unknown.
  • May be used longer than 5 years in women with osteoporosis, in whom BC risk reduction is a secondary benefit.
  • Should not be used for BC risk reduction in premenopausal women.
  • Is not recommended for use in women with a prior history of deep vein thrombosis, pulmonary embolus, stroke, or transient ischemic attack.
  • Risks and benefits should be given careful consideration during the decision-making process.
  • DOSAGE: 60 mg/d for 5 years.
 
  • Should be discussed as an option to reduce the risk of invasive BC, specifically estrogen  (ER)-positive breast cancer, in postmenopausal women who are ≥ 35 years of age with a 5-year projected absolute BC risk ≥ 1.66%,a or with LCIS.b
  • May be used longer than 5 years in women with osteoporosis, in whom BC risk reduction is a secondary benefit.
  • Should not be used for BC risk reduction in premenopausal women.
  • Is not recommended for use in women with a history of deep vein thrombosis, pulmonary embolus, stroke, or transient ischemic attack, or during prolonged immobilization.
  • Discussions with patients and health care providers should include both the risks and benefits of raloxifene in the preventive setting.c
  • DOSAGE: 60 mg/d orally for 5 years.

Strong, evidence-based recommendation.

 

Strength of evidence: Strong evidence - based on 4 RCTs with low risk of bias

 

Exemestanef

  • Use [of aromatase inhibitors] is not recommended outside of the clinical trial setting to lower BC risk.
  •  Should be discussed as an alternative to tamoxifen and/or raloxifene to reduce the risk of invasive breast cancer, specifically estrogen  (ER)-positive breast cancer, in postmenopausal women who are ≥ 35 years of age with a 5-year projected absolute BC risk ≥ 1.66%, or with LCIS or atypical hyperplasia.ab
  • Should not be used for BC risk reduction in premenopausal women.
  • Discussions with patients and health care providers should include both the risks and benefits of exemestane in the preventive setting.c
  • DOSAGE: 25 mg/d orally for 5 years.

Moderate, evidence-based recommendation.


Strength of evidence: Moderate evidence - based on 1 RCT with low risk of bias

 

Abbreviations: BC, breast cancer; ER, estrogen receptor; LCIS, lobular carcinoma in situ; DCIS, ductal carcinoma in situ; SERM, selective estrogen receptor modulator; RCT, randomized controlled trial.

Substantive additions in the 2013 guideline appear as italicized text.

*Substantive deletions from the 2009 guideline appear as bolded text.

aAccording to the National Cancer Institute Breast Cancer Risk Assessment Tool or equivalent measures.

bTrials were not designed to assess mortality and the impact of the agent on overall survival or breast cancer-specific survival has not been demonstrated in 10 years of follow-up.

cRisks and benefits may vary in postmenopausal women by specific risk factors including age, race, breast cancer risk, and history of hysterectomy (Freedman et al, JCO, 2011). Refer to guideline text for a more detailed discussion on risks and benefits.

dFDA label: ref http://www.accessdata.fda.gov/drugsatfda_docs/label/2006/017970s054lbl.pdf

eFDA label ref http://www.accessdata.fda.gov/drugsatfda_docs/label/2007/020815s018lbl.pdf.

fExemestane is currently approved by the US FDA only for the adjuvant treatment of early breast cancer and the treatment of advanced breast cancer, not for breast cancer risk reduction.{ref: http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/020753s009s011s012lbl.pdf}

§Ratings based on ASCO’s Strength of Evidence and Recommendations Ratings. (Refer to Data Supplement DS11, DS12, DS13.)

NOTE 1: Editorial revisions to the 2009 recommendations that leave the substance unaltered have been made but are not indicated by font changes.

NOTE 2: Women with abnormal bleeding should be evaluated prior to starting tamoxifen or raloxifene.

NOTE 3: Fenretinide has been removed from the 2012 guideline update. The Update Committee concluded that the agent is no longer relevant for breast cancer chemoprevention.

NOTE 4: Postmenopausal women include women who underwent natural or artificial menopause.

 

 

 

 

 

 

 

 

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