Early prediction of endocrine responsiveness in ER+/HER2-negative metastatic breast cancer (MBC): Pilot study with 18F-Fluoroestradiol (18F-FES) CT/PET.

BACKGROUND: 18F-FES PET/CT is considered an accurate diagnostic tool to determine whole-body endocrine responsiveness. In the ET-FES trial, we evaluated 18F-FES PET/CT as a predictive tool in ER+/HER2- metastatic breast cancer (MBC). METHODS: Eligible patients underwent a 18F-FES PET/CT at baseline. Patients with SUV≥2 received single agent ET until PD; patients with SUV<2 were randomized to single agent ET (Arm A) or chemotherapy (CT) (Arm B). Primary objective was to compare the activity of first line ET versus CT in patients with 18F-FES SUV <2. RESULTS: Overall, 147 patients were enrolled; 117 presented with 18F-FES SUV≥2 and received ET; 30 pts with SUV<2 were randomized to ET or CT. After a median follow up of 62.4 months, 104 patients (73.2%) had disease progression and 53 died (37.3%). Median PFS was 12.4 months (95%CI 3.1-59.6) in patients with SUV <2 randomised to Arm A versus 23.0 months (95%CI 7.7-30.0) in Arm B, (HR = 0.71, 95%CI 0.3 - 1.7); median PFS was 18.0 months (95%CI 11.2-23.1) in patients with SUV≥2 treated with ET. Median OS was 28.2 months (95%CI 14.2-NE) in patients with SUV <2 randomized to ET (Arm A) versus 52.8 months (95%CI 16.2-NE) in Arm B (CT). Median OS was not reached in patients with SUV≥2. 60-month OS rate was 41.6% (95%CI 10.4-71.1%) in Arm A, 42.0% (95%CI 14.0-68.2%) in Arm B and 59.6% (95%CI 48.6-69.0%) in patients with SUV≥2. In patients with SUV≥2, 60-months OS rate was 72.6% if treated with aromatase inhibitors versus 40.6% in case of fulvestrant or tamoxifen (p<0.005). CONCLUSIONS: The ET-FES trial demonstrated that ER+/HER2- MBC patients are a heterogeneous population, with different levels of endocrine responsiveness based on 18F-FES CT/PET SUV.

Metformin plus chemotherapy versus chemotherapy alone in the first-line treatment of HER2-negative metastatic breast cancer. The MYME randomized, phase 2 clinical trial.

PURPOSE: To investigate the efficacy of metformin (M) plus chemotherapy versus chemotherapy alone in metastatic breast cancer (MBC). METHODS: Non-diabetic women with HER2-negative MBC were randomized to receive non-pegylated liposomal doxorubicin (NPLD) 60 mg/m2 + cyclophosphamide (C) 600 mg/m2 × 8 cycles Q21 days plus M 2000 mg/day (arm A) versus NPLD/C (arm B). The primary endpoint was progression-free survival (PFS). RESULTS: One-hundred-twenty-two patients were evaluable for PFS. At a median follow-up of 39.6 months (interquartile range [IQR] 24.6-50.7 months), 112 PFS events and 71 deaths have been registered. Median PFS was 9.4 months (95% CI 7.8-10.4) in arm A and 9.9 (95% CI 7.4-11.5) in arm B (P = 0.651). In patients with HOMA index < 2.5, median PFS was 10.4 months (95% CI 9.6-11.7) versus 8.5 (95% CI 5.8-9.7) in those with HOMA index ≥ 2.5 (P = 0.034). Grade 3/4 neutropenia was the most common toxicity, occurring in 54.4% of arm A patients and 72.3% of the arm B group (P = 0.019). M induced diarrhea (G2) was observed in 8.8% of patients in Arm A. The effect of M was similar in patients with HOMA index < 2.5 and ≥ 2.5, for PFS and OS. CONCLUSIONS: The MYME trial failed to provide evidence in support of an anticancer activity of M in combination with first line CT in MBC. A significantly shorter PFS was observed in insulin-resistant patients (HOMA ≥ 2.5). Noteworthy, M had a significant effect on CT induced severe neutropenia. Further development of M in combination with CT in the setting of MBC is not warranted.

Adjuvant endocrine therapy in premenopausal patients with hormone receptor-positive early breast cancer: evidence evaluation and GRADE recommendations by the Italian Association of Medical Oncology (AIOM)

Premenopausal women with hormone receptor-positive early breast cancer are candidates for adjuvant endocrine therapy, as recommended by the major international guidelines. To date, adjuvant endocrine options for premenopausal women include tamoxifen with or without ovarian function suppression (OFS) or an aromatase inhibitor with OFS. Multiple strategies for endocrine treatment of premenopausal women with hormone-responsive breast cancer have been assessed, and the results of randomised clinical trials have been reported over the last years. Despite this evidence, the optimal algorithm for endocrine therapy for premenopausal women with hormone receptor-positive early stage invasive breast cancer shows open questions regarding the role of OFS in addition to tamoxifen and the optimal use of hormonal agents. The panel of the Italian Association of Medical Oncology (AIOM) Clinical Practice Guidelines on Breast Cancer applied the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) methodology on three critical questions on the choice of the adjuvant hormonal therapy in premenopausal breast cancer patients to summarise available evidence and to create recommendations to help physicians in their clinical practice.

Guidance for the prevention of bone loss and fractures in postmenopausal women treated with aromatase inhibitors for breast cancer: an ESCEO position paper.

UNLABELLED: Aromatase inhibitors (AIs) are widely used in women with breast cancer, but they are known to increase bone loss and risk of fractures. Based on available evidence and recommendations, an ESCEO working group proposes specific guidance for the prevention of AIs-induced bone loss and fragility fractures. INTRODUCTION: Aromatase inhibitors (AIs) are now the standard treatment for hormone receptor-positive breast cancer. However, deleterious effects of AIs on bone health have been reported. An ESCEO working group proposes guidance for the prevention of bone loss and fragility fractures in post-menopausal women with breast cancer receiving AIs. METHODS: A panel of experts addressed the issue of skeletal effects of AIs and effectiveness of antifracture therapies for the prevention of AI-induced bone loss and fractures. Recommendations by national and international organizations, and experts' opinions on this topic were evaluated. RESULTS: All aromatase inhibitors are associated with negative effects on the skeleton, resulting in bone loss and increased risk of fragility fractures. Current guidelines suggest approaches that differ both in terms of drugs proposed for fracture prevention and duration of treatment. CONCLUSION: The ESCEO working group recommends that all AI-treated women should be evaluated for fracture risk. Besides general recommendations, zoledronic acid 4 mg i.v. every 6 months, denosumab s.c., or possibly oral bisphosphonates should be administered for the entire period of AI treatment to all osteoporotic women (T-score hip/spine <-2.5 or ≥ 1 prevalent fragility fracture), to women aged ≥ 75 irrespective of BMD, and to patients with T-score <-1.5 + ≥ 1 clinical risk factor or T-score <-1.0 + ≥ 2 clinical risk factors. Alternatively, therapy could be considered in patients with a FRAX-determined 10-year hip fracture probability ≥ 3%.

Role of traditional and new biomarkers in breast carcinogenesis.

In recent decades, several biomarkers have been investigated as predictors of breast cancer risk, development, prognosis and treatment efficacy.The detection of biomarkers strongly associated with breast carcinogenesis has an enormous potential, especially for selecting subjects at high risk of developing breast cancer who could benefit from chemopreventive treatments.Although the number of potential biomarkers continues to increase, a unique biomarker for breast cancer risk prediction has not been identified and it is probable that a panel of biomarkers will prove optimal. Further studies are needed to validate breast cancer biomarkers evaluation for individual risk assessment.This review summarizes the main biomarkers, which are important at different stages of breast carcinogenesis with updates from the recent literature.