Fulvestrant and/or Anastrozole in Treating Postmenopausal Patients With Stage II-III Breast Cancer Undergoing Surgery

Overview

The study is being conducted to determine whether neoadjuvant endocrine therapy with fulvestrant or the combination of anastrozole and fulvestrant, is better than anastrozole when given before surgery to shrink the cancer and stop it from growing. Anastrozole inhibits tumor growth by reducing the levels of estrogen and has been approved by the Food and Drug Administration (FDA) of the United States for use after surgery for postmenopausal women with estrogen receptor positive breast cancer. It is also considered a standard of care to give anastrozole for a few months before surgery to shrink the tumor. Fulvestrant inhibits tumor cell growth by reducing the levels of estrogen receptor in the tumor cell. It is not approved by the FDA for use in women with early stage breast cancer before or after surgery, but is approved by the FDA for patients with advanced (Stage 4) estrogen receptor positive breast cancer that has spread to other parts of the body.

This clinical trial was designed to examine the pathologic outcomes of patients whose neoadjuvant treatment course is determined using an early marker of endocrine resistance (namely, Ki67 after 4 or 12 weeks of neoadjuvant therapy) as well as assessing clinical outcome of patients whose disease burden after completing neoadjuvant endocrine therapy is classified as Modified PEPI 0. The primary and secondary objectives for the study are described below. Primary Objectives: 1. To determine whether fulvestrant administered for 24 weeks as neoadjuvant endocrine treatment increases the proportion of endocrine sensitive tumors relative to patients treated with anastrozole. 2. To determine whether fulvestrant in combination with anastrozole, administered for 24 weeks as neoadjuvant endocrine treatment, increases the proportion of endocrine sensitive tumors relative to patients treated with anastrozole. 3. If both of the fulvestrant containing arms are found to have an endocrine sensitive disease rate at least 10% higher than that of the anastrozole arm, we will assess whether the endocrine sensitive disease rate is greater with the combination of anastrozole and fulvestrant than with fulvestrant alone. 4. To assess whether the 5 year RFS rate among women treated with anastrozole with a modified preoperative endocrine prognostic index (PEPI) score 0 following 24 weeks of neoadjuvant therapy is at most 90%. 5. For the fulvestrant containing regimens, a point and interval estimate of the 5 year RFS will be obtained. Secondary Objectives: 1. To examine the differences in surgical outcome, clinical and radiological response rates, and safety profile between the fulvestrant arm and the anastrozole arm. 2. To examine the differences in surgical outcome, clinical and radiological response rates, and safety profile between patients randomized to fulvestrant in combination with anastrozole and those randomized to anastrozole. 3. To examine the rate of pathologic complete response (pCR) of 12 weeks of neoadjuvant paclitaxel in patients with endocrine resistant disease following 4 weeks or 12 weeks of neoadjuvant endocrine therapy (with either fulvestrant or anastrozole or the combination of fulvestrant and anastrozole). 4. To examine the rate of pathologic complete response (pCR) among those patients with endocrine resistant disease, following 4 weeks or 12 weeks of neoadjuvant endocrine therapy (with either fulvestrant or anastrozole or the combination of fulvestrant and anastrozole), who choose not to receive neoadjuvant paclitaxel, but another standard neoadjuvant taxane and/or anthracycline containing regimen or CMF. 5. To summarize the frequency of severe (NCI CTCAE grade \> 3) adverse events encountered with administration of paclitaxel in the neoadjuvant setting. 6. To assess time to breast cancer recurrence for patients with endocrine resistant tumors defined by tumor marker of proliferation Ki-67 (Ki67) \> 10% at week 4, Ki67 \> 10% at week 12 and modified preoperative endocrine prognostic index (PEPI) score of non-zero on neoadjuvant endocrine therapy, with all three groups combined or separated. 7. To determine the impact of NF1 gene copy loss and stop/gain mutations on short and long-term neoadjuvant/adjuvant endocrine therapy outcomes. 8. To assess whether women with circulating tumor-derive deoxyribonucleic acid (ctDNA) present after 4 weeks of neoadjuvant endocrine therapy (NET) is less likely to achieve modified (m)PEPI 0 or pCR among those with week 4 Ki67 =\< 10% and continued on NET. 9. To examine whether the proportion of women with ctDNA present at week 4 differs between those with week 4 Ki67 \>10% on NET and those with week 4 Ki67 =\< 10%. 10. To assess whether residual cancer burden (RCB) class differs with respect to the presence of ctDNA after week 4 NET among those with a week 4 Ki67 levels \> 10% who switched to neo-adjuvant chemotherapy.