Willingness of Women at Increased Risk of Breast Cancer to Participate in Prevention Trials.

Purpose: The factors affecting women's willingness to participate (WTP) in breast cancer (BC) prevention trials are poorly understood. This study aimed to identify the characteristics of interventions associated with a higher WTP among high BC risk women.

Methods: Women who self-identified as being at an increased risk of BC were recruited to a cross-sectional study of WTP in BC prevention trials.

Utility of Stereotactic Body Radiation Therapy in Establishing Local Control for Patients With Invasive Breast Cancer Not Undergoing Definitive Surgery.

Purpose: Surgery is the backbone of breast cancer (BC) treatment. For patients who cannot undergo surgery, improving local control (LC) of the primary tumor is paramount. To that end, this study explored the role of stereotactic body radiation therapy (SBRT).

Safety and Efficacy of Tucatinib, Letrozole, and Palbociclib in Patients with Previously Treated HR+/HER2+ Breast Cancer.

Purpose: To overcome resistance to antihormonal and HER2-targeted agents mediated by cyclin D1-CDK4/6 complex, we proposed an oral combination of the HER2 inhibitor tucatinib, aromatase inhibitor letrozole, and CDK4/6 inhibitor palbociclib (TLP combination) for treatment of HR+/HER2+ metastatic breast cancer (MBC).

Patients And Methods: Phase Ib/II TLP trial (NCT03054363) enrolled patients with HR+/HER2+ MBC treated with ≥2 HER2-targeted agents. The phase Ib primary endpoint was safety of the regimen evaluated by NCI CTCAE version 4.

Case report: Metastatic metaplastic breast cancer with choriocarinomatous features: Targeting the choriocarcinoma component for cure.

Breast cancer with choriocarcinomatous features (BCCF) is a rare and aggressive breast cancer. BCCF carries a poor prognosis and there is unfortunately scant literature to guide treatment beyond surgical resection with most patients receiving standard regimens for breast cancer. In our case, we present a 42-year-old female with an initial hCG of 2,324 and two suspicious lesions of the right breast.

Two fully automated data-driven 3D whole-breast segmentation strategies in MRI for MR-based breast density using image registration and U-Net with a focus on reproducibility.

Presence of higher breast density (BD) and persistence over time are risk factors for breast cancer. A quantitatively accurate and highly reproducible BD measure that relies on precise and reproducible whole-breast segmentation is desirable. In this study, we aimed to develop a highly reproducible and accurate whole-breast segmentation algorithm for the generation of reproducible BD measures.

Blood plasma derived extracellular vesicles (BEVs): particle purification liquid chromatography (PPLC) and proteomic analysis reveals BEVs as a potential minimally invasive tool for predicting response to breast cancer treatment.

Purpose: Circulating blood plasma derived extracellular vesicles (BEVs) containing proteins hold promise for their use as minimally invasive biomarkers for predicting response to cancer therapy. The main goal of this study was to establish the efficiency and utility of the particle purification liquid chromatography (PPLC) BEV isolation method and evaluate the role of BEVs in predicting breast cancer (BC) patient response to neoadjuvant chemotherapy (NAC).

Methods: PPLC isolation was used to separate BEVs from non-EV contaminants and characterize BEVs from 17 BC patients scheduled to receive NAC.

Risk factors associated with skeletal-related events following discontinuation of denosumab treatment among patients with bone metastases from solid tumors: A real-world machine learning approach.

Background: Clinical practice guidelines recommend the use of bone-targeting agents for preventing skeletal-related events (SREs) among patients with bone metastases from solid tumors. The anti-RANKL monoclonal antibody denosumab is approved for the prevention of SREs in patients with bone metastases from solid tumors. However, real-world data are lacking on the impact of individual risk factors for SREs, specifically in the context of denosumab discontinuation.

Experience with denosumab (XGEVA®) for prevention of skeletal-related events in the 10 years after approval.

Skeletal-related events (SREs) are complications of bone metastases and carry a significant patient and economic burden. Denosumab is a receptor activator of nuclear factor-κB ligand (RANKL) inhibitor approved for SRE prevention in patients with multiple myeloma and patients with bone metastases from solid tumors. In phase 3 trials, denosumab showed superiority to the bisphosphonate zoledronate in reducing the risk of first on-study SRE by 17% (median time to first on-study SRE delayed by 8.

Sulindac Improves Stiffness and Quality of Life in Women Taking Aromatase Inhibitors for Breast Cancer.

Purpose: To examine benefit of sulindac for relief of musculoskeletal symptoms (MSS) in patients stable on aromatase inhibitors (AIs).

Methods: Sulindac was evaluated at 150 mg twice daily for effects on MSS at 3, 6, 9, and 12 months in 50 postmenopausal women stable on AI therapy for a median of 12.5 months for hormone receptor-positive breast cancer.

A Phase II Study Evaluating the Safety and Efficacy of Sunitinib Malate in Combination With Weekly Paclitaxel Followed by Doxorubicin and Daily Oral Cyclophosphamide Plus G-CSF as Neoadjuvant Chemotherapy for Locally Advanced or Inflammatory Breast Cancer.

Introduction: Neoadjuvant chemotherapy is standard treatment for locally advanced breast cancer (LABC) or inflammatory breast cancer (IBC). We hypothesized that adding sunitinib, a tyrosine kinase inhibitor with antitumor and antiangiogenic activity, to an anthracycline and taxane regimen would improve pathologic complete response (pCR) rates to a prespecified endpoint of 45% in patients with HER2-negative LABC or IBC.

Methods: We conducted a multicenter, phase II trial of neoadjuvant sunitinib with paclitaxel (S+T) followed by doxorubicin and cyclophosphamide plus G-CSF for patients with HER2-negative LABC or IBC.

Sulindac, a Nonselective NSAID, Reduces Breast Density in Postmenopausal Women with Breast Cancer Treated with Aromatase Inhibitors.

Purpose: To evaluate the effect of sulindac, a nonselective anti-inflammatory drug (NSAID), for activity to reduce breast density (BD), a risk factor for breast cancer.

Experimental Design: An open-label phase II study was conducted to test the effect of 12 months' daily sulindac at 150 mg twice daily on change in percent BD in postmenopausal hormone receptor-positive breast cancer patients on aromatase inhibitor (AI) therapy. Change in percent BD in the contralateral, unaffected breast was measured by noncontrast magnetic resonance imaging (MRI) and reported as change in MRI percent BD (MRPD).

Changes in serum estradiol levels with Estring in postmenopausal women with breast cancer treated with aromatase inhibitors.

Background: Anti-estrogen therapy is an effective intervention for preventing reoccurrence of hormone receptor-positive breast cancer in women. However, the side effects of anti-estrogen therapy, including urogenital symptoms, have been reported to cause significant morbidity. There is controversial data, mainly due to small sample sizes, reporting on the safety and efficacy of using vaginal estrogen to treat urogenital symptoms in patients on aromatase inhibitor therapy.

Phase III Randomized Trial of Bisphosphonates as Adjuvant Therapy in Breast Cancer: S0307.

Background: Adjuvant bisphosphonates, when given in a low-estrogen environment, can decrease breast cancer recurrence and death. Treatment guidelines include recommendations for adjuvant bisphosphonates in postmenopausal patients. SWOG/Alliance/Canadian Cancer Trials Group/ECOG-ACRIN/NRG Oncology study S0307 compared the efficacy of three bisphosphonates in early-stage breast cancer.

A Phase II Study of Irinotecan and Etoposide as Treatment for Refractory Metastatic Breast Cancer.

Lessons Learned: The combination of irinotecan and etoposide showed modest efficacy in terms of response rate in the refractory setting for patients with metastatic breast cancer.The studied dose and schedule of irinotecan and etoposide is very toxic, with >70% grade 3 or 4 treatment-related adverse events.

Background: As single agents, both irinotecan and etoposide have documented activity against breast cancer among patients who have received multiple lines of prior chemotherapy.

Cost-effectiveness of denosumab for the prevention of skeletal-related events in patients with solid tumors and bone metastases in the United States.

Bone complications (also known as skeletal-related events [SREs]) pose significant health and financial burdens on patients with bone metastases. Denosumab demonstrated superiority over zoledronic acid in delaying the time to first SRE. This study examined the lifetime cost-effectiveness of denosumab vs zoledronic acid from both US payer and societal perspectives.

Phase 1b Study of Trebananib Plus Paclitaxel and Trastuzumab in Patients With HER2-Positive Locally Recurrent or Metastatic Breast Cancer.

Introduction: Trebananib, a peptide-Fc fusion protein, blocks angiogenesis by inhibiting binding of angiopoietin-1/2 to the receptor tyrosine kinase Tie2. Trebananib plus trastuzumab and paclitaxel was evaluated in human epidermal growth factor receptor 2-positive breast cancer in an open-label phase 1b clinical study.

Patients And Methods: Women with human epidermal growth factor receptor 2-positive breast cancer received weekly paclitaxel (80 mg/m), trastuzumab (8 mg/m then 6 mg/kg every 3 weeks), and intravenous trebananib (10 mg/kg or 30 mg/kg weekly) beginning week 2.

Reproducible automated breast density measure with no ionizing radiation using fat-water decomposition MRI.

Background: Increased breast density is a significant independent risk factor for breast cancer, and recent studies show that this risk is modifiable. Hence, breast density measures sensitive to small changes are desired.

Purpose: Utilizing fat-water decomposition MRI, we propose an automated, reproducible breast density measurement, which is nonionizing and directly comparable to mammographic density (MD).

A randomized, placebo-controlled trial of diindolylmethane for breast cancer biomarker modulation in patients taking tamoxifen.

Purpose: Diindolylmethane (DIM), a bioactive metabolite of indole-3-carbinol found in cruciferous vegetables, has proposed cancer chemoprevention activity in the breast. There is limited evidence of clinically relevant activity of DIM or long-term safety data of its regular use. A randomized, double-blind, placebo-controlled trial was conducted to determine the activity and safety of combined use of BioResponse DIM® (BR-DIM) with tamoxifen.

Changes in Bone Turnover Marker Levels and Clinical Outcomes in Patients with Advanced Cancer and Bone Metastases Treated with Bone Antiresorptive Agents.

Purpose: Bone antiresorptive agents can significantly reduce bone turnover markers (BTM) in patients with advanced cancer. We evaluated association of changes in BTMs with overall survival (OS), disease progression (DP), and disease progression in bone (DPB) in patients with advanced cancer and bone metastases following denosumab or zoledronic acid treatment.

Experimental Design: This is an integrated analysis of patient-level data from three identically designed, blinded, phase III trials with patients randomized to subcutaneous denosumab or intravenous zoledronic acid.

Phase II study of metformin for reduction of obesity-associated breast cancer risk: a randomized controlled trial protocol.

Background: Two-thirds of U.S. adult women are overweight or obese.

Extending Aromatase-Inhibitor Adjuvant Therapy to 10 Years.

Background: Treatment with an aromatase inhibitor for 5 years as up-front monotherapy or after tamoxifen therapy is the treatment of choice for hormone-receptor-positive early breast cancer in postmenopausal women. Extending treatment with an aromatase inhibitor to 10 years may further reduce the risk of breast-cancer recurrence.

Methods: We conducted a double-blind, placebo-controlled trial to assess the effect of the extended use of letrozole for an additional 5 years.

Circulating Carbonic Anhydrase IX and Antiangiogenic Therapy in Breast Cancer.

Introduction: Carbonic anhydrase IX (CAIX) is a hypoxia regulated metalloenzyme integral to maintaining cellular pH. Increased CAIX expression is associated with poor prognosis in breast cancer. To explore CAIX as a biomarker for breast cancer therapies, we measured plasma CAIX levels in healthy control subjects and in breast cancer patients.

Pathophysiology of tumour-induced microangiopathic haemolytic anaemia.

Cancer-associated microangiopathic haemolytic anaemia (CA-MAHA) is a syndrome characterised by Coombs-negative haemolytic anaemia and thrombocytopenia. It is primarily seen in advanced solid tumours and is distinct from thrombotic thrombocytopenic purpura/haemolytic uraemic syndrome. Diagnosis is often delayed and patients have a high mortality.