- Women with early-stage breast cancer:
- Typically undergo surgery up front
- While women with more advanced disease:
- Larger tumors
- Locally advanced tumors
- High grade tumors
- Lymph node positive
- Triple-negative breast cancer
- HER2-positive breast cancer:
- May benefit from neoadjuvant therapy
- The Immediate Preoperative Anastrozole, Tamoxifen, or Combined with Tamoxifen (IMPACT) trial:
- Randomized 330 postmenopausal women with:
- ER-positive breast cancer
- Invasive breast cancer
- Non-metastatic breast cancer
- Operable breast cancer
- Locally advanced potentially operable breast cancer:
- To neoadjuvant:
- Tamoxifen, anastrozole, or a combination of tamoxifen and anastrozole:
- For three months
- Tamoxifen, anastrozole, or a combination of tamoxifen and anastrozole:
- To neoadjuvant:
- Among patients enrolled:
- The median age was 73
- The median tumor size was 4 cm
- No chemotherapy was given
- Overall response rates:
- Were similar among the three arms:
- At a median of 13 weeks
- Were similar among the three arms:
- In patients who were assessed as requiring mastectomy at baseline (n = 124):
- 44% received breast-conserving surgery after anastrozole and
- 31% after tamoxifen
- p = .23
- Randomized 330 postmenopausal women with:
- Importantly:
- pCR is rare:
- With neoadjuvant endocrine therapy
- pCR is rare:
- There have not been any Phase III randomized trials:
- Comparing neoadjuvant chemotherapy to neoadjuvant endocrine therapy
- A number of clinical trials have reported:
- Conversion rates of mastectomy to breast-conserving surgery:
- Ranging from 30% to 88%
- Conversion rates of mastectomy to breast-conserving surgery:
- In the ACOSOG Z1031 trial:
- Ki67 reduction:
- Was associated with response to:
- Neoadjuvant aromatase inhibitor therapy
- Was associated with response to:
- Tumor Ki67 levels determined after initiation:
- Of neoadjuvant endocrine treatment:
- Are more prognostic than baseline analysis
- Of neoadjuvant endocrine treatment:
- Ki67 reduction:
- Ellis et al described a:
- Preoperative endocrine prognostic index (PEPI) score:
- In which Ki67 data have been integrated into a post-treatment model that also includes:
- Pathologic stage and ER levels
- Patients with pathologically node-negative, T1 or T2 disease with a:
- Fully suppressed Ki67 level (2.7% or 1% on a natural log scale) and persistent ER expression:
- After completion of neoadjuvant endocrine therapy (PEPI of 0):
- Were found to have such a low risk of relapse that:
- Adjuvant chemotherapy after neoadjuvant endocrine therapy:
- May not be necessary
- Adjuvant chemotherapy after neoadjuvant endocrine therapy:
- Were found to have such a low risk of relapse that:
- After completion of neoadjuvant endocrine therapy (PEPI of 0):
- Fully suppressed Ki67 level (2.7% or 1% on a natural log scale) and persistent ER expression:
- Patients with pathologically node-negative, T1 or T2 disease with a:
- Pathologic stage and ER levels
- In which Ki67 data have been integrated into a post-treatment model that also includes:
- Preoperative endocrine prognostic index (PEPI) score:
- In the letrozole vs tamoxifen P024 trial:
- The relationship between ER expression by Allred score and log odds of response fit a linear model that was significant by logistic regression
- A recent systematic review and meta-analysis of 20 prospective, randomized, neoadjuvant clinical trials:
- That reported response rates concluded:
- Neoadjuvant endocrine therapy with aromatase inhibitors resulted in a similar clinical and radiological response rate and breast conservation surgery rate but:
- With lower toxicity than combination chemotherapy
- Neoadjuvant endocrine therapy with aromatase inhibitors resulted in a similar clinical and radiological response rate and breast conservation surgery rate but:
- Patients treated with aromatase inhibitors:
- Had a higher clinical tumor response rates than those treated with tamoxifen
- Overall, the pathologic complete response was:
- Less than 10% in the review
- That reported response rates concluded:
- References:
- Smith IE, Dowsett M, Ebbs SR, 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.
- Allred DC, Harvey JM, Berardo M, Clark GM. Prognostic and predictive factors in breast cancer by immunohistochemical analysis. Mod Pathol. 1998;11(2):155-168.
- Ellis MJ, Suman VJ, Hoog J, 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 PAM50-based intrinsic subtype – ACOSOG Z1031. J Clin Oncol. 2011;29(17):2342-2349.
- Olson JA Jr, Budd GT, Carey LA, et al. Improved surgical outcomes for breast cancer patients receiving neoadjuvant aromatase inhibitor therapy: Results from a multicenter phase II trial. J Am Coll Surg. 2009;208(5):906-914.
- Dowsett M, Smith IE, Ebbs SR, et al. Short-term changes in Ki-67 during neoadjuvant treatment of primary breast cancer with anastrozole or tamoxifen alone or combined correlate with recurrence free survival. Clin Cancer Res. 2005;11(2 Pt 2):951s-958s.
- Eiermann W, Paepke S, Appfelstaedt J, et al. Preoperative treatment of postmenopausal breast cancer patients with letrozole: A randomized doubleblind multicenter study. Ann Oncol. 2001;12(11):1527-1532.
#Arrangoiz #Surgeon #BreastSurgeon #CancerSurgeon #SurgicalOncologist #Cancer #BreastCancer #Teacher
Rodrigo Arrangoiz MS, MD, FACS, FSSO 