Rodrigo Arrangoiz MS, MD, FACS, FSSO

The Clinical Response to Neoadjuvant Endocrine Therapy Correlates with the Duration of Treatment

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 (four 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 three years
Meta-analysis and clinical trial data support use of aromatase inhibitors (letrozole or anastrozole) over tamoxifen:
- Higher clinical and radiographic response rates:
  - 55% vs. 36%
- Improved rates of BCT:
  - 45% versus 35%
The ACOSOG Z10316 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:
- Three to six 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, and 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
- 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.
- Ellis MJ, Ma C. Letrozole in the neoadjuvant setting: the P024 trial. Breast Cancer Res Treat. 2007;105(suppl 1):133-143.
- 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.
- 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.
- 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.
- 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.