Fulvestrant in management of hormone receptor-positive metastatic breast cancer.

Fulvestrant is a steroidal selective estrogen receptor degrader that was approved by the US FDA in 2002 for treatment of ER-positive metastatic breast cancer (ER + MBC) post-progression on aromatase inhibitors. In 2017, the label was updated to include endocrine therapy naive ER + MBC. While initially fulvestrant was thought to be equivalent to aromatase inhibitors with monthly dose of 250 mg intramuscular injection, several postmarketing trials challenged this understanding. Subsequently, the recommended dose changed to 500 mg monthly plus loading dose, and this was proven to be superior to anastrozole in efficacy. Most recently the results of FALCON trial have further challenged the way fulvestrant is viewed and used. This report provides a historical perspective on this compound, its evolving role in management of ER + MBC and what the future may hold for this drug.

Body mass index, diabetes, and triple-negative breast cancer prognosis.

Higher body mass index (BMI) and diabetes are associated with worse breast cancer prognosis. However, few studies have focused on triple-negative breast cancer (TNBC). The goal of this study is to examine this association in a cohort of patients with TNBC. We retrospectively reviewed 501 consecutive patients with TNBC seen at the Washington University Breast Oncology Clinic. Cox proportional hazard models were used to determine the relationship between BMI and diabetes at diagnosis with overall survival (OS) and disease free survival (DFS). Four hundred and forty-eight patients had BMI recorded and 71 patients had diabetes. The median age at diagnosis was 53 (23-98) years and follow-up was 40.1 months (IQR 25.2-62.9). Baseline BMI and diabetes were not associated with OS or DFS. OS hazard ratios (HRs) for patients who were overweight (BMI 25.0-29.99), with class I obesity (BMI 30-34.99), or BMI ≥35 were 1.22 (CI 0.78-1.91), 0.92 (CI 0.59-1.43), and 1.16 (CI 0.70-1.90), respectively. The HRs for DFS in patients who were overweight, with class I obesity, or BMI ≥35 were 1.01 (CI 0.65-1.56), 0.94 (CI 0.60-1.47), and 0.99 (CI 0.63-1.57), respectively. Similarly, the HRs for diabetics were 1.27 (CI 0.82-1.96) for OS and 0.98 (CI 0.64-1.51) for DFS. Obesity and diabetes did not significantly affect survival for patients with TNBC in this study.

Use of neoadjuvant data to design adjuvant endocrine therapy trials for breast cancer.

Mature outcomes from adjuvant endocrine therapy trials in estrogen receptor-positive breast cancer have enabled comparisons with neoadjuvant clinical trials that have parallel randomizations of treatment in terms of the response of disseminated disease versus the local response within the breast. Imprecise end points, such as 'clinical response', have produced inconsistent results regarding the relationship between neoadjuvant and adjuvant endocrine therapy outcomes. However, the proliferation marker Ki-67, measured during neoadjuvant treatment, has predicted accurately and consistently the results of much larger studies in the adjuvant setting. In this Review, we summarize these trials and discuss the implications for the design of future adjuvant endocrine therapy trials. We conclude that there is sufficient evidence supporting the view that the degree of Ki-67 suppression is a reliable short-term surrogate for the adjuvant potential of endocrine drugs, at least in postmenopausal women. We propose that adjuvant endocrine therapy trials should only be conducted once adequately-powered neoadjuvant studies have indicated superior Ki-67 suppression in patients receiving experimental endocrine treatment versus the standard treatment.