Neoadjuvant Endocrine Therapy in Breast Cancer

  • In the preoperative setting:
    • Chemotherapy is typically recommended to:
      • Improve breast cancer operability or downstage the axilla among medically fit patients
    • However, neoadjuvant endocrine therapy (NET):
      • Is a good option for post-menopausal women with ER+ breast cancers:
        • When aiming for improved candidacy for breast conservation or 
        • In patients in whom chemotherapy will not be safely tolerated
  • Studies evaluating NET:
    • Have demonstrated similar rates of:
      • Clinical and radiographic response and breast conservation therapy (BCT):
        • To those reported from studies using neoadjuvant chemotherapy:
          • When neoadjuvant chemotherapy (4 cycles of doxorubicin and paclitaxel) was compared directly to NET (12 weeks of aromatase inhibitors; exemestane or anastrozole):
            • NET was associated with:
              • Comparable clinical response
              • Higher rates of breast conservation:
                • 33% vs. 24%
              • No difference in local recurrence at approximately 3 years
  • Meta-analysis and clinical trial data:
    • Support use of aromatase inhibitors (letrozole or anastrozole) over tamoxifen, including:
      • Higher clinical and radiographic response rates:
        • 55% vs. 36%
      • Improved rates of BCT:
        • 45% versus 35%
  • The ACOSOG Z1031 trial:
    • Demonstrated comparable effectiveness of exemestane, letrozole and anastrozole:
      • For 16 to 18 weeks before surgery
  • NET requires a longer duration of treatment than preoperative chemotherapy and depends on the patient’s individual eligibility for breast conservation
  • NET is typically recommended for 3 to 6 months prior to surgery:
    • However, extended treatment for up to 12 months:
      • Has been safe and is associated with a greater response to treatment
  • Although tumor progression is rare on NET:
    • Continued surveillance is important for women with an intact primary breast tumor taking endocrine therapy:
      • Cancer growth would be an indication for surgery
  • The majority of clinical trials for NET have focused on postmenopausal women:
    • In that younger patients often have higher-risk tumor biology and are likely candidates for chemotherapy:
      • Thus, data on the use of NET in premenopausal patients are limited to phase II trials and include:
        • Ovarian suppression plus aromatase-inhibitors (i.e., exemestane + goserelin)

References

1. Semiglazov VF, Semiglazov VV, Dashyan GA, Ziltsova EK, Ivanov VG, Bozhok AA, et al. Phase 2 randomized trial of primary endocrine therapy versus chemotherapy in postmenopausal patients with estrogen receptor-positive breast cancer. Cancer. 2007;110(2):244-254.

2. Ellis MJ, Ma C. Letrozole in the neoadjuvant setting: the P024 trial. Breast Cancer Res Treat. 2007;105(suppl 1):133-143.

3. Eiermann W, Paepke S, Appfelstaedt J, Llombart-Cussac A, Eremin J, Vinholes J, et al. Preoperative treatment of postmenopausal breast cancer patients with letrozole: a randomized double-blind multicenter trial. Ann Oncol. 2001;12(11):1527-1532.

4. Smith IE, Dowsett M, Ebbs SR, Dixon JM, Skene A, Blohmer JU, et al. Neoadjuvant treatment of postmenopausal breast cancer with anastrozole, tamoxifen, or both in combination: The Immediate Preoperative Anastrozole, Tamoxifen, or Combined with Tamoxifen (IMPACT) multicenter double-blind randomized trial. J Clin Oncol. 2005;23(22):5108-5116.

5. Cataliotti L, Buzdar AU, Noguchi S, Bines J, Takatsuka Y, Petrakova K, et al. Comparison of Anastrozole versus tamoxifen as preoperative therapy in postmenopausal women with hormone receptor-positive breast cancer: the pre-operative “arimidex” compared to tamoxifen (PROACT) trial. Cancer. 2006;106(10):2095-2103.

6. Ellis MJ, Suman VJ, Hoog J, Lin L, Snider J, Prat A, et al. Randomized phase II neoadjuvant comparison between letrozole, anastrozole, and exemestane for postmenopausal women with estrogen receptor-rich stage 2 to 3 breast cancer: clinical and biomarker outcomes and predictive value of the baseline PAM5-based intrinsic subtype—ACOSOG Z1031. J Clin Oncol. 2011;29(17):2342-2349.

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