Title:Treatment of Estrogen Receptor-Positive Breast Cancer
VOLUME: 20 ISSUE: 5
Author(s):F. Lumachi, A. Brunello, M. Maruzzo, U. Basso and S. M.M. Basso
Affiliation:Department of Surgical, Oncological & Gastroenterological Sciences (DiSCOG), University of Padua, School of Medicine, Via Giustiniani 2, 35128 Padova, Italy.
Keywords:Breast cancer, estrogen receptor, ovary suppression, SERM, SERD, tamoxifen, aromatase inhibitors, post-surgical survival, modulators (SERMs), aromatase inhibitors (AIs).
Abstract:Estrogen receptor (ER) expression is the main indicator of potential responses to endocrine therapy (ET), and approximately
70% of human breast cancers (BCs) are hormone-dependent and ER-positive. The introduction of adjuvant systemic therapy led to a
significant improvement in post-surgical survival and a reduction in disease relapse, especially in women with early BC and those with
ER+ tumors, who may receive ET alone or in combination with cytotoxic therapy. Adjuvant ET currently consists of (i) ovarian
suppression, (ii) selective estrogen receptor modulators (SERMs) and down-regulators, and (iii) aromatase inhibitors (AIs). In patients
with ER+ tumors pharmacologic ovary suppression with gonadotropin-releasing hormone agonists in combination with standard adjuvant
therapy is generally more effective than adjuvant chemotherapy alone. Tamoxifen is the best established SERM, has favorable effects on
BC control and bone metabolism, but also has adverse effects due to its estrogenic activity in other tissues. For these reasons, other
SERMs have been developed. Fulvestrant is an ER down-regulator with several potential advantages over SERMs, including a 100-fold
increase in its affinity for ER compared with tamoxifen and no estrogen-like activity in the uterus. The inhibition of the aromatase system
with third-generation AIs is associated with improved survival in patients with advanced BC compared with SERMs. In postmenopausal
patients with ER+ BC adjuvant treatment with AIs should be performed, either as sequential treatment after tamoxifen or as upfront
therapy. Studies evaluating the role of AIs as first-line therapy are ongoing and the results are encouraging.
