Neoadjuvant Endocrine Therapy For Breast Cancer Research Articles

Neoadjuvant Endocrine Therapy for Operable Breast Cancer: A Retrospective Analysis of Real-World Use.

A retrospective study of the real-world use of neoadjuvant endocrine therapy (NET) is important for standardizing the role of NET in breast cancer care. In a consecutive series of women with operable breast cancer who received NET for ≥28 days, associations of NET objectives, NET outcomes, adjuvant chemotherapy use after NET, and survival with clinicopathological factors were examined. NET objectives were reduction in surgical extent in 49 patients, avoidance of surgery in 31, and treatment until scheduled surgery in 8. The mean duration of NET was 349.5 (range, 34-1,923), 869.8 (range, 36-4,859), and 55.8 (range, 39-113) days, respectively, in these cohorts (success rate: 79.6%, 64.5%, and 100%, respectively), and the differences were significant. Among patients in the former two cohorts, progression-free survival was significantly better in patients with stage 0 or I disease, ductal carcinoma in situ or invasive ductal carcinoma, ≥71% estrogen receptor (ER) positivity, and the surgical extent reduction cohort than the other counterparts. Postoperative chemotherapy use was significantly associated with lymph node metastasis, a high Ki67 labeling index, lymphovascular invasion, and a high preoperative endocrine prognostic index at the time of surgery after NET. Better recurrence-free survival after surgery was significantly associated with high ER expression after NET or high progesterone receptor expression before or after NET. NET can help reduce surgical extent or avoid surgery in women with early breast cancer, ductal carcinoma, or high ER expression. NET may also aid in decisions related to postoperative systemic therapy to improve survival.

Multidisciplinary Approach to Neoadjuvant Endocrine Therapy in Breast Cancer: A Comprehensive Review.

Breast cancer is the most common type of cancer and the leading cause of cancer-related death among women worldwide. Hormone receptor-positive (HR+) tumors represent the most common form of this disease, with more than 70% of breast cancers expressing these receptors. Response and benefit to neoadjuvant chemotherapy (NCT) varies according to HR expression, with lower responses in luminal tumors as compared with hormone receptor-negative (HR-) and human epidermal growth factor receptor 2-positive (HER2+) tumors. Neoadjuvant endocrine therapy (NET) is an option for selected patients with HR+ locally advanced breast cancer. Neoadjuvant endocrine therapy has a favorable toxicity profile, and is associated with benefits such as having low cost and being more easily available even for cancer care professionals outside major urban areas or tertiary centers. These factors are particularly relevant, as 70% of breast cancer deaths occur in women from low-income and middle-income countries. Additionally, NET is being increasingly explored, not simply to allow for less extensive surgery, but also as a scientific tool, with the use of biomarkers to predict outcomes in adjuvant trials and for the individual patient. This review details the current and most relevant evidence about NET for breast cancer as well as the future directions of this field.

Abstract PD07-02: Anticancer activity of letrozole plus zoledronic acid as neoadjuvant therapy for postmenopausal patients with breast cancer: FEMZONE trial results

Abstract Background: Clinical evidence for the anticancer activity of adjuvant zoledronic acid (ZOL) in patients with early stage breast cancer (BC) has been reported in several randomized clinical trials including ZO-FAST, AZURE (>5 yr postmenopausal subset), and ABCSG-12. In addition, combining ZOL with standard neoadjuvant therapy improved pathologic complete response (pCR) and reduced the need for mastectomy in the AZURE trial. The open-label, multicenter, phase 2, FEMZONE trial examined the effect of neoadjuvant letrozole (LET) ± ZOL on tumor response in postmenopausal patients with hormone receptor-positive (HR+) primary BC. Here, we report the efficacy and safety after 6 mo of treatment. Methods: Postmenopausal women with HR+ BC and ECOG performance status of 0–2 were randomized to LET (2.5 mg/d) ± ZOL (4 mg q4w). The primary efficacy endpoint was objective response rate (ORR; complete + partial response per RECIST criteria) at 6 mo by central review. Secondary endpoints included ORR in the per-protocol and safety populations, best response, breast-conserving surgery, pCR, change in tumor size, overall survival, and safety. Between-group differences in ORR were evaluated using Fisher's exact test. Results: Among enrolled patients (N = 168; mean age 70.9 yr; mean treatment duration 6.5 mo), patients receiving LET + ZOL experienced numerically better ORR at 6 mo versus LET alone (69.2% vs 54.5%, respectively), with a between-group difference of 14.7% (P = .106). Although the primary endpoint did not reach statistical significance because of insufficient patient recruitment, the prespecified between-group difference of ≥10% was met. A similar trend in ORR at 6 mo favoring ZOL was also seen by local assessment (Δ11%, P = .192). At 4 mo, higher ORR was observed for LET + ZOL versus LET alone both for the local (33.3% vs 24%, respectively) and central assessments (41.5% vs 30.3%, respectively). Numerically more patients receiving LET + ZOL experienced a partial response at 6 mo versus LET alone (66.2% vs 54.5%, respectively). At 6 mo, the mean tumor size had decreased from 3.34 ± 1.98 cm to 2.1 ± 1.76 cm in the overall patient population, and the decrease was slightly larger with LET + ZOL compared with LET alone (–1.37 ± 0.96 cm vs −1.12 ± 0.92 cm, respectively). Overall, there was no difference in the number of patients requiring mastectomy between LET + ZOL and LET alone (15.6% vs 15.2%, respectively). Incidence of adverse events (AEs) was slightly higher among patients receiving LET + ZOL versus LET alone (92.1% vs 81%, respectively), and the types of AEs were consistent with the known safety profiles of these agents. No deaths or osteonecrosis of the jaw was reported during the course of the study. Conclusions: This study provides additional confirmation of the efficacy of LET as neoadjuvant therapy for early HR+ BC, and supports previous reports of ZOL's anticancer activity in this setting (as evidenced by the trend toward improved ORR with ZOL + LET versus LET alone). These data, together with other published ZOL studies, suggest that adding ZOL to neoadjuvant therapy may be considered for postmenopausal patients scheduled to receive neoadjuvant endocrine therapy for BC. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr PD07-02.