Chemoprevention in Women with High Risk for Breast Cancer

  • Tamoxifen and raloxifene:
    • Reduce the risk of invasive breast cancer in high-risk women when compared to placebo:
      • But are associated with increased vasomotor symptoms
    • In the NSABP P-2 / STAR trial:
      • When compared to raloxifene, tamoxifen use:
        • Resulted in higher rates of:
          • Uterine cancer:
            • 2 / 1000 vs. 1.5 / 1000
          • Deep vein thrombosis:
            • 2.29 / 1000 vs 1.69 / 1000
          • Pulmonary embolism:
            • 1.41 / 1000 vs. 0.96 / 1000
    • Use of concomitant hormone replacement therapy with tamoxifen or raloxifene:
      • Was not allowed in the STAR trial:
        • Is discouraged in the 2013 American Society of Clinical Oncology chemoprevention guidelines
  • Aromatase inhibitors:
    • Are not associated with a risk of thrombosis
    • In the MAP.3 prevention trial:
      • Exemestane significantly reduced the incidence of invasive breast cancer:
        • Was not associated with serious adverse effects
        • Resulted in only minimal changes in health-related quality of life
        • However, it is not FDA-approved for chemoprevention of breast cancer:
          • But can be used in an off-label manner
    • Decision tables weighing the risks and benefits of chemoprevention agents are available:
      • Can identify the most appropriate drug with the fewest side effects for each individual patient
    • Compliance with chemoprevention varies by the agent used:
      • In the MAP.3 trial
        • 85% of enrolled women were compliant with exemestane
      • Whereas in the NSABP P-1 trial:
        • 76% of women with compliant with tamoxifen
    • In clinical practice:
      • Overall compliance with chemoprevention is even lower:
        • With a study by Flanagan and colleagues:
          • Reporting a 61% rate of completion of planned chemoprevention in high-risk patients.
  • References:
    • Visvanathan K, Hurley P, Bantug E, Brown P, Col NF, Cuzick J, et al. Use of pharmacologic interventions for breast cancer risk reduction: American Society of Clinical Oncology clinical practice guideline. J Clin Oncol. 2013;31(23):2942-2962.
    • Freedman AN, Yu B, Gail MH, Costantino JP, Graubard BI, Vogel VG, et al. Benefit/risk assessment for breast cancer chemoprevention with raloxifene or tamoxifen for women age 50 years or older. J Clin Oncol.2011;29(17):2327-2333.
    • Goss PE, Ingle JN, Ales-Martinez JE, Cheung AM, Chlebowski RT, Wactawski-Wende J, et al. Exemestane for breast-cancer prevention in postmenopausal women. N Engl J Med. 2011;364(25):2381-2391.
    • Nelson HD, Fu R, Humphrey L, et al. Comparative Effectiveness of Medications To Reduce Risk of Primary Breast Cancer in Women[Internet]. Rockville (MD): Agency for Healthcare Research and Quality (US); 2009 Sep. (AHRQ Comparative Effectiveness Reviews, No. 17.)
    • Fisher B, Costantino JP, Wickerham DL, et al. Tamoxifen for 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.
    • Flanagan MR, Zabor EC, Stempel M, Mangino DA, Morrow M, Pilewskie ML. Chemoprevention Uptake for Breast Cancer Risk Reduction Varies by Risk Factor. Ann Surg Oncol. 2019;26(7):2127-2135.

#Arrangoiz #BreastSurgeon #CancerSurgeon #SurgicalOncologist #BreastCancer #CASO #CenterforAdvancedSurgicalOncology #PalmettoGeneralHospital

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