Vertebral Fractures After Denosumab Discontinuation in Breast Cancer Survivors: A Single Institution Experience.

Denosumab is approved to prevent fragility fractures in patients with osteoporosis at high risk for fracture and to prevent bone loss in patients with breast and prostate cancer who receive endocrine therapy. The antiresorptive effect of denosumab rapidly dissipates when it is delayed or discontinued, but the risk for, and incidence of, multiple clinical vertebral fractures in patients with breast cancer after stopping denosumab is currently unclear. : We sought to identify the incidence of clinical vertebral fractures in patients with breast cancer who received at least 2 doses of denosumab (60 mg) and then discontinued the medication.

Does preoperative MRI accurately stratify early-stage HER2 + breast cancer patients to upfront surgery vs neoadjuvant chemotherapy?

Purpose: HER2 +- amplified breast cancer patients derive benefit from treatment with anti-HER2-targeted therapy. Though adjuvant treatment is based on final pathology, decisions regarding neoadjuvant chemotherapy are made in the preoperative setting with imaging playing a key role in staging. We examined the accuracy of pre-operative imaging in determining pathological tumor size  (pT) in patients undergoing upfront surgery.

A Phase I Study of Alpelisib in Combination with Trastuzumab and LJM716 in Patients with -Mutated HER2-Positive Metastatic Breast Cancer.

Purpose: Activating mutations in promote resistance to HER2-targeted therapy in breast cancer; however, inhibition of PI3K alone leads to escape via feedback upregulation of HER3. Combined inhibition of HER2, HER3, and PI3K overcomes this mechanism preclinically.

Patients And Methods: This phase I study investigated the MTD of alpelisib given in combination with trastuzumab and LJM716 (a HER3-targeted antibody) in patients with -mutant HER2-positive (HER2) metastatic breast cancer (MBC) using the continual reassessment method.

Phase II Study of Paclitaxel and Dasatinib in Metastatic Breast Cancer.

Background: Overexpression and activation of tyrosine kinase Src has been linked to breast carcinogenesis and bone metastases. We showed the feasibility of combining the SRC inhibitor dasatinib with weekly paclitaxel in patients with metastatic breast cancer (MBC) and herein report the subsequent phase II trial.

Patients And Methods: Patients had received ≤ 2 chemotherapy regimens for measurable, HER2-negative MBC.

Assessing fracture risk in early stage breast cancer patients treated with aromatase-inhibitors: An enhanced screening approach incorporating trabecular bone score.

Introduction: Aromatase-inhibitors (AIs) are commonly used for treatment of patients with hormone-receptor positive breast carcinoma, and are known to induce bone density loss and increase the risk of fractures. The current standard-of-care screening tool for fracture risk is bone mineral density (BMD) by dual-energy X-ray absorptiometry (DXA). The fracture risk assessment tool (FRAX®) may be used in conjunction with BMD to identify additional osteopenic patients at risk of fracture who may benefit from a bone-modifying agent (BMA).

A Pilot Study of Dose-Dense Paclitaxel With Trastuzumab and Lapatinib for Node-negative HER2-Overexpressed Breast Cancer.

Background: Dual anti-HER2 therapy is effective for HER2-amplified breast cancer. Weekly paclitaxel, trastuzumab, and full-dose lapatinib (PTL) is not feasible because of grade 3 diarrhea. We conducted a phase II feasibility study of dose-dense (DD; every other week) PTL (ClinicalTrials.

NCCN Task Force Report: Bone Health In Cancer Care.

Bone health and maintenance of bone integrity are important components of comprehensive cancer care. Many patients with cancer are at risk for therapy-induced bone loss, with resultant osteoporotic fractures, or skeletal metastases, which may result in pathologic fractures, hypercalcemia, bone pain, and decline in motility and performance status. Effective screening and timely interventions are essential for reducing bone-related morbidity.

Increased levels of urinary PGE-M, a biomarker of inflammation, occur in association with obesity, aging, and lung metastases in patients with breast cancer.

Elevated levels of COX-derived prostaglandin E2 (PGE2) occur in inflamed tissues. To evaluate the potential links between inflammation and breast cancer, levels of urinary prostaglandin E metabolite (PGE-M), a stable end metabolite of PGE2, were quantified. We enrolled 400 patients with breast cancer: controls with early breast cancer (n = 200), lung metastases (n = 100), and metastases to other sites (n = 100).

Limited overall survival in patients with brain metastases from triple negative breast cancer.

Patients with breast cancer, which lacks ER, PR, and HER2; "triple negative" (TNBC), are at increased risk of brain metastases (BMs). However, the impact of modern therapy on the risk of BMs and outcomes remains largely unknown. In this retrospective, single-institution study we assessed the incidence of BMs, the therapeutic options, and overall survival, in a recent cohort of patients with TNBC.

Ixabepilone-associated peripheral neuropathy: data from across the phase II and III clinical trials.

Purpose: Dose-limiting neuropathy is a major adverse event associated with most of the microtubule-stabilizing agent-based chemotherapy regimens. Ixabepilone, a semisynthetic analogue of the natural epothilone B, has activity against a wide range of tumor types. Peripheral neuropathy (PN), associated with ixabepilone treatment, is usually mild to moderate, predominantly sensory and cumulative.

Serum N-telopeptide and bone-specific alkaline phosphatase levels in patients with osteonecrosis of the jaw receiving bisphosphonates for bone metastases.

Purpose: Oversuppression of bone turnover can be a critical factor in the pathogenesis of osteonecrosis of the jaw (ONJ). We investigated N-telopeptide of type I collagen (NTX) and bone-specific alkaline phosphatase (BAP) as potential predictors of ONJ onset.

Patients And Methods: Patients with ONJ and available stored serum were identified retrospectively from the institutional databases.

Approved agents for metastatic breast cancer.

The US Food and Drug Administration has approved three agents for treatment of patients with metastatic breast cancer refractory to anthracyclines and taxanes: capecitabine, ixabepilone, and eribulin mesylate. There is no fixed algorithm of therapeutic choices. Median survival remains measured in months, not years.

Dose dense cyclophosphamide, methotrexate, fluorouracil is feasible at 14-day intervals: a pilot study of every-14-day dosing as adjuvant therapy for breast cancer.

Purpose: Cyclophosphamide/methotrexate/fluorouracil (CMF) is a proven adjuvant option for patients with early-stage breast cancer. Randomized trials with other regimens demonstrate that dose-dense (DD) scheduling can offer greater efficacy. We investigated the feasibility of administering CMF using a DD schedule.

Algorithms for the treatment of patients with metastatic breast cancer and prior exposure to taxanes and anthracyclines.

At present, metastatic breast cancer (MBC) remains an incurable disease, with the goals of care aimed at maximizing the patient's duration and quality of life. Treatment options for a patient with MBC have become more efficacious and numerous. In addition to endocrine and chemotherapy agents, a number of targeted agents, including trastuzumab and bevacizumab, are available.

Optimizing the use of anthracyclines in older patients with breast cancer.

Recently, a greater understanding of tumor biology, including the use of genetic signatures, has led to a more precise classification of breast cancer. This has translated into a more granular assessment of risk-benefit calculations for the selection of patients for adjuvant therapies. For unselected patients, anthracyclines offer a survival benefit over non-anthracycline-based regimens, but are associated with long-term risks including congestive heart failure.

Locoregional outcomes of inflammatory breast cancer patients treated with standard fractionation radiation and daily skin bolus in the taxane era.

Purpose: To assess locoregional outcomes of inflammatory breast cancer (IBC) patients who received standard fractionation radiation with daily skin bolus and taxanes as part of combined-modality therapy (CMT).

Methods And Materials: We retrospectively reviewed the charts of 107 patients diagnosed with IBC between January 1995 and March 2006 who presented to our department for adjuvant radiation therapy (RT).

Results: All patients received chemotherapy (95% anthracycline and 95% taxane), modified radical mastectomy, and RT to the chest wall and regional lymphatics using standard fractionation to 50 Gy and daily skin bolus.

NCCN Task Force Report: Bone Health in Cancer Care.

Bone health and maintenance of bone integrity are important components of comprehensive cancer care in both early and late stages of disease. Risk factors for osteoporosis are increased in patients with cancer, including women with chemotherapy-induced ovarian failure, those treated with aromatase inhibitors for breast cancer, men receiving androgen-deprivation therapy for prostate cancer, and patients undergoing glucocorticoid therapy. The skeleton is a common site of metastatic cancer recurrence, and skeletal-related events are the cause of significant morbidity.

Ixabepilone and other epothilones: microtubule-targeting agents for metastatic breast cancer.

Taxanes, derived from the bark of the Pacific yew tree, were the last major group of cytotoxic agents to be developed. Their proven efficacy in a variety of malignancies has constituted a real breakthrough in the treatment of cancer. Wider clinical use of taxanes has several important limitations, including acquired and intrinsic tumor resistance, hypersensitivity reactions, and cumulative neurotoxicity and hematopoietic toxicity.

Novel anti-tubulin cytotoxic agents for breast cancer.

Regardless of stage of disease, cytotoxic chemotherapy remains an important part of the treatment paradigm for breast cancer. Anthracyclines and taxanes are the most active agents; however, limitations with their use exist. These include a maximum lifetime dose and tumor resistance with anthracycline, hypersensitivity reactions and cumulative toxicity with taxanes.

Microtubule active agents: beyond the taxane frontier.

Microtubules are essential to cell transport, signaling, and mitosis. An increasing range of anticancer drugs interferes with the normal formation and function of microtubules. Vinca alkaloids act as microtubule destabilizers and the taxanes act as microtubule stabilizers.