Preoperative Endocrine Therapy for Older Women with Breast Cancer: Renewed Interest in an Old Idea

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Abstract
Tamoxifen as sole therapy (primary tamoxifen therapy) was investigated in the 1970s and 1980s as an alternative to surgery for older patients with breast cancer. While the majority of primary breast tumors responded to tamoxifen, long-term local disease control was poor. The use of primary tamoxifen therapy is therefore restricted to frail, elderly, and infirm patients who cannot tolerate surgery. In contrast, short-term preoperative endocrine therapy to downstage estrogen receptor-positive (ER+) tumors is under increasing scrutiny as a nontoxic neoadjuvant approach for older women. The literature on primary tamoxifen therapy and preoperative endocrine therapy was reviewed to construct an opinion piece on the feasibility and safety of preoperative endocrine therapy. A review of nine phase II trials and a meta-analysis of two randomized trials suggest that the initial response rates to preoperative endocrine therapy will exceed 50% to 60% for patients with ER+ disease. A short delay in surgery to administer 3 to 4 months of preoperative endocrine therapy is unlikely to compromise long-term outcomes. Preoperative endocrine therapy is a logical approach for older patients with ER+ disease as a well-tolerated means to increase the rate of breast-conserving surgery. Several clinical trials comparing tamoxifen with selective aromatase inhibitors in the preoperative setting have been conducted, and the results are expected soon. These studies will determine if a large multicenter national trial of preoperative endocrine therapy should be conducted.