Breast Cancer Index in Premenopausal Women With Early-Stage Hormone Receptor-Positive Breast Cancer.

Importance: Adjuvant ovarian function suppression (OFS) with oral endocrine therapy improves outcomes for premenopausal patients with hormone receptor-positive (HR+) breast cancer but adds adverse effects. A genomic biomarker for selecting patients most likely to benefit from OFS-based treatment is lacking.

Objective: To assess the predictive and prognostic performance of the Breast Cancer Index (BCI) for OFS benefit in premenopausal women with HR+ breast cancer.

Radium-223 in women with hormone receptor-positive bone-metastatic breast cancer receiving endocrine therapy: pooled analysis of two international, phase 2, randomized, double-blind, placebo-controlled trials.

Background: Most women with advanced breast cancer have skeletal metastases. Radium-223 is an alpha-emitting radionuclide that selectively targets areas of bone metastases.

Methods: Two double-blind, placebo-controlled studies of radium-223 were conducted in women with hormone receptor-positive (HR+), bone-predominant metastatic breast cancer.

Chain Reaction of Fenton Autoxidation of Tartaric Acid: Critical Behavior at Low pH.

Autoxidation of tartaric acid in air-saturated aqueous solutions in the presence of Fe(II) at low pH, 2.5, shows autocatalytic behavior with distinct initiation, propagation, and termination phases. With increasing pH, the initiation phase speeds up, while the propagation phase shortens and reduces to none.

Adjuvant Endocrine Therapy in Premenopausal Breast Cancer: 12-Year Results From SOFT.

JCO The Suppression of Ovarian Function Trial (SOFT; ClinicalTrials.gov identifier: NCT00066690) randomly assigned premenopausal women with hormone receptor-positive breast cancer to 5 years of adjuvant tamoxifen, tamoxifen plus ovarian function suppression (OFS), or exemestane plus OFS. The primary analysis compared disease-free survival (DFS) between tamoxifen plus OFS versus tamoxifen alone; exemestane plus OFS versus tamoxifen was a secondary objective.

POSNOC-POsitive Sentinel NOde: adjuvant therapy alone versus adjuvant therapy plus Clearance or axillary radiotherapy: a randomised controlled trial of axillary treatment in women with early-stage breast cancer who have metastases in one or two sentinel nodes.

Introduction: ACOSOG-Z0011(Z11) trial showed that axillary node clearance (ANC) may be omitted in women with ≤2 positive nodes undergoing breast conserving surgery (BCS) and whole breast radiotherapy (RT). A confirmatory study is needed to clarify the role of axillary treatment in women with ≤2 macrometastases undergoing BCS and groups that were not included in Z11 for example, mastectomy and those with microscopic extranodal invasion. The primary objective of POsitive Sentinel NOde: adjuvant therapy alone versus adjuvant therapy plus Clearance or axillary radiotherapy (POSNOC) is to evaluate whether for women with breast cancer and 1 or 2 macrometastases, adjuvant therapy alone is non-inferior to adjuvant therapy plus axillary treatment, in terms of 5-year axillary recurrence.

Prognosis of Patients With Early Breast Cancer Receiving 5 Years vs 2 Years of Adjuvant Bisphosphonate Treatment: A Phase 3 Randomized Clinical Trial.

Importance: Bisphosphonate treatment in patients with early breast cancer has become part of care, but the optimal treatment duration is still unclear.

Objective: To compare 2 vs 5 years of zoledronate treatment following adjuvant chemotherapy in patients with early breast cancer.

Design, Setting, And Participants: The SUCCESS A phase 3 multicenter randomized open-label clinical trial with a 2 × 2 factorial design enrolled 3754 patients from September 21, 2005, to March 12, 2007 (last patient out, May 7, 2014).

M-EA (methotrexate, etoposide, dactinomycin) and EMA-CO (methotrexate, etoposide, dactinomycin / cyclophosphamide, vincristine) regimens as first-line treatment of high-risk gestational trophoblastic neoplasia.

High-risk gestational trophoblastic neoplasia (GTN) is highly chemosensitive with an excellent prognosis with treatment. Historically in the United Kingdom, the high-risk regimens used have been M-EA (methotrexate, etoposide, dactinomycin) (Sheffield) and EMA-CO (methotrexate, etoposide, dactinomycin / cyclophosphamide, vincristine) (Charing Cross, London) with prior published data suggesting no difference in survival between these. Our Sheffield treatment policy changed in 2014, switching from M-EA to EMA-CO, aiming to reduce time in hospital, and harmonise UK practice.

Bone metastases.

Bone is the most frequent site for metastasis for many cancers, notably for tumours originating in the breast and the prostate. Tumour cells can escape from the primary tumour site and colonize the bone microenvironment. Within the bone, these disseminated tumour cells, as well as those arising in the context of multiple myeloma, may assume a state of dormancy, remaining quiescent for years before resuming proliferation and causing overt metastasis, which causes bone destruction via activation of osteoclast-mediated osteolysis.

Guidance for the assessment and management of prostate cancer treatment-induced bone loss. A consensus position statement from an expert group.

Context And Objective: Incidence of prostate cancer (PC) is increasing, but androgen deprivation therapy (ADT) and other therapies are substantially improving survival. In this context, careful consideration of skeletal health is required to reduce the risk of treatment-related fragility fractures and their associated morbidity and mortality. This risk is currently not well-managed.

Kinetics of autoxidation of tartaric acid in presence of iron.

The kinetics of the autoxidation reaction of tartaric acid in an air-saturated solution in the presence of Fe(II) show autocatalytic behavior with distinct initiation, propagation, and termination phases. The initiation phase, which involves activation of dissolved oxygen, decreases with increasing pH, over the test range of pH of 2.5-4.

Testosterone replacement in young male cancer survivors: A 6-month double-blind randomised placebo-controlled trial.

Background: Young male cancer survivors have lower testosterone levels, higher fat mass, and worse quality of life (QoL) than age-matched healthy controls. Low testosterone in cancer survivors can be due to orchidectomy or effects of chemotherapy and radiotherapy. We have undertaken a double-blind, placebo-controlled, 6-month trial of testosterone replacement in young male cancer survivors with borderline low testosterone (7-12 nmol/l).

An exploratory randomized-controlled trial of the efficacy of the Src-kinase inhibitor saracatinib as a novel analgesic for cancer-induced bone pain.

Pain is a major symptom of bone metastases from advanced cancer and represents a clinical challenge to treat effectively. Basic neurobiology in preclinical animal models implicates enhanced sensory processing in the central nervous system, acting through -methyl-D-aspartate (NMDA) glutamate receptors, as an important mechanism underpinning persistent pain. The non-receptor tyrosine kinase Src is thought to act as a hub for regulating NMDA receptor activity and the orally available Src inhibitor saracatinib has shown promise as a potential analgesic in recent animal studies.

Comparison of risedronate versus placebo in preventing anastrozole-induced bone loss in women at high risk of developing breast cancer with osteopenia.

Anastrozole has been shown to prevent breast cancer in postmenopausal women at high risk of the disease, but has been associated with substantial accelerated loss of bone mineral density (BMD) and increased fractures. Here, we investigate the effect of risedronate on BMD after 5 years of follow-up in the IBIS-II prevention trial. 1410 women were enrolled in the bone sub-study and stratified into three strata according to the lowest baseline T-score at spine or femoral neck.

Endogenous Production of IL1B by Breast Cancer Cells Drives Metastasis and Colonization of the Bone Microenvironment.

Purpose: Breast cancer bone metastases are incurable, highlighting the need for new therapeutic targets. After colonizing bone, breast cancer cells remain dormant, until signals from the microenvironment stimulate outgrowth into overt metastases. Here we show that endogenous production of IL1B by tumor cells drives metastasis and growth in bone.

Identification and validation of DOCK4 as a potential biomarker for risk of bone metastasis development in patients with early breast cancer.

Skeletal metastasis occurs in around 75% of advanced breast cancers, with the disease incurable once cancer cells disseminate to bone, but there remains an unmet need for biomarkers to identify patients at high risk of bone recurrence. This study aimed to identify such a biomarker and to assess its utility in predicting response to adjuvant zoledronic acid (zoledronate). We used quantitative proteomics (stable isotope labelling by amino acids in cell culture-mass spectrometry; SILAC-MS) to compare protein expression in a bone-homing variant (BM1) of the human breast cancer cell line MDA-MB-231 with parental non-bone-homing cells to identify novel biomarkers for risk of subsequent bone metastasis in early breast cancer.

Comprehensive geriatric assessment and decision-making in older men with incurable but manageable (chronic) cancer.

Purpose: In older cancer patients, treatment decision-making is often complex. A comprehensive geriatric assessment (CGA) is an established tool used in geriatric medicine to identify unmet need requiring intervention. This study aimed to assess whether using a CGA in older male cancer patients with incurable but manageable disease provides information that would alter a cancer clinician's intended management plan.

Modulating Bone Marrow Hematopoietic Lineage Potential to Prevent Bone Metastasis in Breast Cancer.

The presence of disseminated tumor cells in breast cancer patient bone marrow aspirates predicts decreased recurrence-free survival. Although it is appreciated that physiologic, pathologic, and therapeutic conditions impact hematopoiesis, it remains unclear whether targeting hematopoiesis presents opportunities for limiting bone metastasis. Using preclinical breast cancer models, we discovered that marrow from mice treated with the bisphosphonate zoledronic acid (ZA) are metastasis-suppressive.

Current perspectives on bone metastases in castrate-resistant prostate cancer.

Prostate cancer is the most frequent noncutaneous cancer occurring in men. On average, men with localized prostate cancer have a high 10-year survival rate, and many can be cured. However, men with metastatic castrate-resistant prostate cancer have incurable disease with poor survival despite intensive therapy.

Advances in the management of HER2-positive early breast cancer.

While trastuzumab is firmly established as the cornerstone of therapy for both early and advanced breast cancer expressing human epidermal growth factor receptor 2 (HER2), many patients either do not respond to trastuzumab treatment or progress following therapy. Improved understanding of breast cancer biology, particularly the complex signaling interactions managed by the HER family of receptors, have resulted in development of several novel HER2-directed therapies and combinations. This article will review the novel approaches to HER2 targeting that have been developed in recent years, with particular focus on results from these approaches in early breast cancer, and will discuss strategies to improve the tolerability of HER2-directed therapies, including prevention of cardiac toxicity and diarrhea.

Three-year Safety of Radium-223 Dichloride in Patients with Castration-resistant Prostate Cancer and Symptomatic Bone Metastases from Phase 3 Randomized Alpharadin in Symptomatic Prostate Cancer Trial.

Background: In Alpharadin in Symptomatic Prostate Cancer (ALSYMPCA) trial, radium-223 versus placebo prolonged overall survival with favorable safety in castration-resistant prostate cancer patients with symptomatic bone metastases. Long-term radium-223 monitoring underlies a comprehensive safety and risk/benefit assessment.

Objective: To report updated ALSYMPCA safety, including long-term safety up to 3 yr after the first injection.

Management of Aromatase Inhibitor-Associated Bone Loss (AIBL) in postmenopausal women with hormone sensitive breast cancer: Joint position statement of the IOF, CABS, ECTS, IEG, ESCEO IMS, and SIOG.

Background: Several guidelines have been reported for bone-directed treatment in women with early breast cancer (EBC) for averting fractures, particularly during aromatase inhibitor (AI) therapy. Recently, a number of studies on additional fracture related risk factors, new treatment options as well as real world studies demonstrating a much higher fracture rate than suggested by randomized clinical controlled trials (RCTs). Therefore, this updated algorithm was developed to better assess fracture risk and direct treatment as a position statement of several interdisciplinary cancer and bone societies involved in the management of AI-associated bone loss (AIBL).

Effect of radium-223 dichloride (Ra-223) on hospitalisation: An analysis from the phase 3 randomised Alpharadin in Symptomatic Prostate Cancer Patients (ALSYMPCA) trial.

Symptomatic skeletal events (SSEs) commonly occur in patients with bone metastases, often leading to hospitalisations and decreased quality-of-life. In the ALSYMPCA trial, radium-223 significantly improved overall survival (hazard ratio 0.70, 95% confidence interval [CI] 0.