Prostate cancer is the most common male cancer and one of the top causes of male cancer-related death. Most patients with prostate cancer respond to initial androgen deprivation therapy before progressing to castration-resistant prostate cancer (CRPC) and eventually developing bone metastases. Growth of prostate cancer metastases in the bone microenvironment produces numerous factors that disrupt the dynamic equilibrium of osteogenesis and osteolysis existing in healthy bone, leading to progressive morbidity, poor quality of life, and increased treatment costs.

Relevant studies of CRPC and targeted therapies were identified from literature and clinical trial databases, websites, and conference abstracts.

Available data on agents potentially targeting bone metastatic CRPC or the bone microenvironment in patients with CRPC are discussed, including inhibitors of tumor growth/survival and bone turnover (SRC family kinase inhibitors, endothelin-1 inhibitors, MET inhibitors, and thalidomide and its derivatives), inhibitors of bone turnover (bisphosphonates and receptor activator of nuclear factor-kB ligand inhibitors), antiangiogenic agents (vascular endothelial growth factor receptor and platelet-derived growth factor blockers), prostate cancer vaccines, and bone-directed radiopharmaceuticals.

With increasing data availability demonstrating tumor–bone microenvironment interactions and routine incorporation of bone-related end points into CRPC trials, bone microenvironment-targeted agents are likely to become an increasingly important component of CRPC treatment.

Bevacizumab is a monoclonal antibody against vascular endothelial growth factor. Severe pulmonary haemorrhage (PH) is a rare but serious potential adverse event associated with bevacizumab therapy for advanced non-squamous non-small-cell lung cancer (NSCLC).

A panel of expert oncologists, pulmonologists and radiologists reviewed the available data to identify predictive factors for PH in order to help guide physicians using bevacizumab in patients with NSCLC.

Patients with NSCLC are at an increased risk of PH owing to the underlying disease process. Patients with squamous histology and/or a history of grade ≥2 haemoptysis (≥2.5 ml per event) should not receive bevacizumab. No clinical or radiological features (including cavitation and central tumour location) reliably predict severe PH in bevacizumab-treated patients. Major blood vessel infiltration and bronchial vessel infiltration, encasement and abutting may predict PH; however, standardised radiological criteria for defining infiltration have not been established. Eligibility for bevacizumab is not affected by patient age, performance status or anticoagulation or antiplatelet therapy.

An individualised risk–benefit assessment should be undertaken in all patients with NSCLC in whom bevacizumab is being considered. Further research is required to elucidate the mechanisms underlying PH and the clinical risk factors.

The Gruppo Oncologico Italia Meridionale 9902 trial compared four cycles of high-dose epirubicin plus cyclophosphamide (EC) with four cycles of docetaxel (Taxotere, D) followed by four cycles of EC as adjuvant treatment of node-positive breast cancer.

Patients were randomly assigned to EC (E 120 mg/m², C 600 mg/m², arm A) for four cycles or four cycles of D (100 mg/m²) followed by four cycles of EC (arm B), both regimens every 21 days. Hormone receptor-positive patients were given hormonal therapy for 5 years. Primary end point was 5-year disease-free survival (DFS). Secondary objectives were overall survival (OS) and safety.

There were 750 patients enrolled. With a median follow-up of 64 months, 5-year DFS was 73.4% in both arms, and 5-year OS was 89.5% versus 90.7% in arm A and B [hazard ratio was 0.99 (95% confidence interval for DFS 0.75–1.31; P = 0.95)], respectively. Grade 3–4 toxicity was more common in arm B.

This study did not show advantages from the addition of docetaxel to high-dose EC as adjuvant chemotherapy in node-positive breast cancer. The small sample size and low number of DFS events may have limited the ability to observe statistically significant difference between the two arms.

Bevacizumab is a monoclonal antibody against vascular endothelial growth factor with the ability to increase progression-free survival in metastatic breast cancer (MBC). A systematic review and meta-analysis was conducted to determine the risk of the most clinically relevant adverse outcomes associated with the use of bevacizumab in the treatment of breast cancer.

We included phase III clinical trials that used bevacizumab alone or in combination with chemotherapy as for MBC or locally recurrent. Statistical analyses were conducted to calculate summary odds ratio (OR) of the eight most relevant adverse outcomes related with bevacizumab.

Five clinical trials were included in the meta-analysis. Summary odds ratios obtained showed a statistically significant bevacizumab-associated increased risk in four of the adverse outcomes studied: proteinuria (OR = 27.68), hypertension (OR = 12.76), left ventricular dysfunction (LVD) (OR = 2.25), and hemorrhagic events (OR = 4.07). No statistically significant differences were found for gastrointestinal (GI) perforation, vascular events, fatal events, or febrile neutropenia.

Bevacizumab did increase the risk of LVD and hemorrhagic events. The addition of bevacizumab to chemotherapy in patients with metastatic breast cancer was not associated with a significant increase in grade ≥3 arterial or venous thromboembolic events, GI perforation, or fatal events.

Estrogen Receptor 1 (ESR1) aberrations may be associated with expression of estrogen receptor (ER) or progesterone receptor (PgR), human epidermal growth factor receptor-2 (HER2) or Ki-67 labeling index and prognosis.

ESR1 was assessed in 1129 (81%) of 1396 postmenopausal Danish women with early breast cancer randomly assigned to receive 5 years of letrozole, tamoxifen or a sequence of these agents in the Breast International Group 1-98 trial and who had ER ≥1% after central review.

By FISH, 13.6% of patients had an ESR1-to-Centromere-6 (CEN-6) ratio ≥2 (amplified), and 4.2% had ESR1-to-CEN-6 ratio <0.8 (deleted). Deletion of ESR1 was associated with significantly lower levels of ER (P < 0.0001) and PgR (P = 0.02) and more frequent HER2 amplification. ESR1 deletion or amplification was associated with higher-Ki-67 than ESR1-normal tumors. Overall, there was no evidence of heterogeneity of disease-free survival (DFS) or in treatment effect according to ESR1 status. However, significant differences in DFS were observed for subsets based on a combination of ESR1 and HER2 status (P = 0.02).

ESR1 aberrations were associated with HER2 status, Ki-67 labeling index and ER and PgR levels. When combined with HER2, ESR1 may be prognostic but should not be used for endocrine treatment selection in postmenopausal women with endocrine-responsive early breast cancer.

Circulating tumor cells (CTCs) are associated with inferior prognosis in metastatic breast cancer (MBC). We hypothesized that the relationship between CTCs and disease subtype would provide a better understanding of the clinical and biologic behavior of MBC.

We retrospectively analyzed 517 MBC patients treated at a single institution. Subtypes of primary tumors were analyzed by immunohistochemical (IHC) or fluorescent in situ hybridization analyses and CTCs were enumerated by CellSearch^® at starting a new therapy. Overall survival (OS) and progression-free survival durations for each IHC subtype were determined.

At a median follow-up of 24.6 months, 276 of 517 (53%) patients had died. The median OS for patients with <5 and ≥5 CTCs were 32.4 and 18.3 months, respectively (P < 0.001). Except in HER2+ patients, the prognostic value of CTCs was independent of disease subtype and disease site.

In this large retrospective study, CTCs were strongly predictive of survival in all MBC subtypes except HER2+ patients who had been treated with targeted therapy. Our results clearly demonstrate the value of enumerating CTCs in MBC and strongly suggest an interesting biological implication in the HER2+ subset of patients that need to be further explored.

The purpose of this study was to describe bone status in a large cohort of postmenopausal women with nonmetastatic breast cancer, at the initiation of aromatase inhibitor therapy.

A prospective, transversal and clinical study was conducted. Each woman had an extensive medical history, a biological evaluation, a bone mineral density (BMD) measurement and spinal X-rays.

Four hundred and ninety-seven women aged 63.8 ± 9.6 years were included in this study. Eighty-five percent of these women had a 25-OH vitamin D concentration <75 nmol/l. One hundred and fifty-six women (31.4%) had a T-score < –2 at one of the three site measurements. Ninety-five women (19.1%) had a history of nonvertebral fracture with a total of 120 fractures. Spine X-rays evaluation revealed that 20% of the women had at least one vertebral fracture. The presence of vertebral fracture was associated with nonvertebral fracture history [odds ratio (OR) 1.6, 95% confidence interval (CI) 1.1–2.4] and with spine BMD (OR 1.4, 95% CI 1.1–1.7). The prevalence of vertebral fracture reached 62.9% in women with age above 70 years and femoral T-score < –2.5.

Before starting aromatase inhibitor therapy for breast cancer, a large proportion of women had a vitamin D insufficiency and vertebral fractures.