Breast Cancer and Pregnancy: Current Concepts in Diagnosis and Treatment

This review evaluates the available data to help guide patients and caregivers when developing treatment plans for women diagnosed with breast cancer during pregnancy

Current management of treatment-induced bone loss in women with breast cancer treated in the United Kingdom

New therapeutic options in breast cancer have improved survival but consequently increase the relevance of late complications. Ovarian suppression/ablation and aromatase inhibitors (AI) in the adjuvant setting have improved outcome, but have clinically important adverse effects on bone health. However, investigation and management of cancer treatment-induced bone loss (CTIBL) is poorly defined with no national guidance. In 2004, a questionnaire was sent to over 500 breast surgeons and oncologists who treat breast cancer within the United Kingdom. The questionnaire evaluated access to bone densitometry and specialist expertise as well as attitudes to investigation of CTIBL and anticipated changes in the use of AI for postmenopausal early breast cancer. A total of 354 completed questionnaires were received, 47 from clinicians not currently treating breast cancer. Of the 307 evaluable questionnaires, 164 (53%) were from breast surgeons, 112 (36%) from clinical oncologists and 31 (10%) from medical oncologists. Although most respondents recognised that CTIBL was the responsibility of the treating breast team, investigations for CTIBL are limited even though most had adequate access to bone densitometry; 98 (32%) had not requested a DXA scan in the last 6 months and 224 (73%) had requested fewer than five scans. In all, 235 (76%) were not routinely investigating patients on AI for bone loss. A total of 277 (90%) felt that their practice would benefit from national guidelines to manage these patients, and the majority (59%) had little or no confidence in interpreting DXA results and advising on treatment. This questionnaire has highlighted clear deficiencies in management of CTIBL in early breast cancer. The development of national guidelines for the management of these patients and educational initiatives for breast teams are urgently required

Off-trial evaluation of bisphosphonates in patients with metastatic breast cancer

BACKGROUND: Bisphosphonate therapy has been readily accepted as standard of care for individuals with bone metastases from breast cancer. In this study we determined whether the proportion of patients experiencing a skeletal related event (SRE) in a clinical practice population was similar to that observed in phase III randomized controlled studies. METHODS: A retrospective chart review was conducted of 110 patients receiving intravenous bisphosphonates for advanced breast cancer. The proportion of patients experiencing at least one SRE after 12 months of therapy was determined. SRE included vertebral or non-vertebral fracture, cord compression, surgery and/or radiotherapy to bone. RESULTS: The proportion of patients who had an SRE was 30% (28 individuals) and the median time to first event was greater than 350 days. Non-vertebral events and radiotherapy were the most frequent type of SRE, while cord compression and hypercalcaemia were rare (1%). Most patients in the study had bone-only disease (58.2%) and most had multiple bone lesions. In the first 12 months the mean duration of exposure to intravenous bisphosphonates was 261 days and most patients remained on treatment until just before death (median 27 days). CONCLUSION: This study suggests that the rate of clinically relevant SREs is substantially lower than the event rate observed in phase III clinical trials. We attribute this lower rate to observational bias. In the clinical trial setting it is possible that over-detection of skeletal events occurs due to the utilisation of regular skeletal survey or radionucleotide bone scan, whereas these procedures are not routine in clinical practice. Phase IV observational studies need to be conducted to determine the true benefits of bisphosphonate therapy in order to implement rationale use of bisphosphonates

Pain outcomes in patients with bone metastases from advanced cancer: assessment and management with bone-targeting agents

Bone metastases in advanced cancer frequently cause painful complications that impair patient physical activity and negatively affect quality of life. Pain is often underreported and poorly managed in these patients. The most commonly used pain assessment instruments are visual analogue scales, a single-item measure, and the Brief Pain Inventory Questionnaire-Short Form. The World Health Organization analgesic ladder and the Analgesic Quantification Algorithm are used to evaluate analgesic use. Bone-targeting agents, such as denosumab or bisphosphonates, prevent skeletal complications (i.e., radiation to bone, pathologic fractures, surgery to bone, and spinal cord compression) and can also improve pain outcomes in patients with metastatic bone disease. We have reviewed pain outcomes and analgesic use and reported pain data from an integrated analysis of randomized controlled studies of denosumab versus the bisphosphonate zoledronic acid (ZA) in patients with bone metastases from advanced solid tumors. Intravenous bisphosphonates improved pain outcomes in patients with bone metastases from solid tumors. Compared with ZA, denosumab further prevented pain worsening and delayed the need for treatment with strong opioids. In patients with no or mild pain at baseline, denosumab reduced the risk of increasing pain severity and delayed pain worsening along with the time to increased pain interference compared with ZA, suggesting that use of denosumab (with appropriate calcium and vitamin D supplementation) before patients develop bone pain may improve outcomes. These data also support the use of validated pain assessments to optimize treatment and reduce the burden of pain associated with metastatic bone disease

The role of bisphosphonates in breast cancer: The present and future role of bisphosphonates in the management of patients with breast cancer

At least 25% of patients with breast cancer develop skeletal metastases, with bone the site of disease producing the greatest morbidity. It is apparent that the bisphosphonates present an important component of the treatment strategy. They are now the treatment of choice in tumour-induced hypercalcaemia, and they can reduce bone pain and skeletal complications such as pathological fractures. In addition, bisphosphonates are being increasingly evaluated in the prevention of bone metastases and to prevent and treat cancer therapy-induced osteoporosis. Ongoing research is aimed at trying to define the optimum route, dose, schedule and type of bisphosphonate

Bone resorption predicts for skeletal complications in metastatic bone disease

Relationships between the rate of bone resorption (measured by urinary N-telopeptide (Ntx) excretion) and a range of skeletal complications have been evaluated in patients with metastatic bone disease. A total of 121 patients had monthly measurements of Ntx during treatment with bisphosphonates. All skeletal-related events, plus hospital admissions for bone pain and death during the period of observation, were recorded. Data were available for 121 patients over the first 3-month period of monitoring (0–3 months) and 95 patients over the second 3-month period (4–6 months). N-telopeptide levels were correlated with the number of skeletal-related events and/or death (r=0.62, P<0.001 for 0–3 months and r=0.46, P<0.001 for 4–6 months, respectively). Patients with baseline Ntx values greater than or equal to100 nmol mmol−1 creatinine (representing clearly accelerated bone resorption) were 19.48 times (95% CI 7.55, 50.22) more likely to experience a skeletal-related event/death during the first 3 months than those with Ntx <100 (P<0.001). In a multivariate logistic regression model, Ntx was highly predictive for events/death. This study is the first to indicate a strong correlation between the rate of bone resorption and the frequency of skeletal complications in metastatic bone disease. N-telopeptide appears useful in the prediction of patients most likely to experience skeletal complications and thus benefit from bisphosphonate treatment

Metastatic breast carcinoma of the coracoid process: two case reports

<p>Abstract</p> <p>Background</p> <p>The coracoid process of the scapula is a rare site of involvement for metastatic disease or for primary tumors. We are unaware of any reports in the literature of pathologic coracoid process fractures and only one report of metastatic disease to the coracoid.</p> <p>Methods and Results</p> <p>In this case report, we present two cases with metastatic breast carcinoma of the coracoid process, one of which presented with a pathologic fracture of the coracoid.</p> <p>Conclusions</p> <p>An orthopaedic surgeon must be aware of the potential for metastatic disease to the coracoid as they may be the first medical provider to encounter evidence of malignant disease.</p

Tumor markers in breast cancer - European Group on Tumor Markers recommendations

Recommendations are presented for the routine clinical use of serum and tissue-based markers in the diagnosis and management of patients with breast cancer. Their low sensitivity and specificity preclude the use of serum markers such as the MUC-1 mucin glycoproteins ( CA 15.3, BR 27.29) and carcinoembryonic antigen in the diagnosis of early breast cancer. However, serial measurement of these markers can result in the early detection of recurrent disease as well as indicate the efficacy of therapy. Of the tissue-based markers, measurement of estrogen and progesterone receptors is mandatory in the selection of patients for treatment with hormone therapy, while HER-2 is essential in selecting patients with advanced breast cancer for treatment with Herceptin ( trastuzumab). Urokinase plasminogen activator and plasminogen activator inhibitor 1 are recently validated prognostic markers for lymph node-negative breast cancer patients and thus may be of value in selecting node-negative patients that do not require adjuvant chemotherapy. Copyright (C) 2005 S. Karger AG, Basel

Bone Degeneration and Recovery after Early and Late Bisphosphonate Treatment of Ovariectomized Wistar Rats Assessed by In Vivo Micro-Computed Tomography

Bisphosphonates are antiresorptive drugs commonly used to treat osteoporosis. It is not clear, however, what the influence of the time point of treatment is. Recently developed in vivo micro-computed tomographic (CT) scanners offer the possibility to study such effects on bone microstructure in rats. The aim of this study was to determine the influence of early and late zoledronic acid treatment on bone in ovariectomized rats, using in vivo micro-CT. Twenty-nine female Wistar rats were divided into the following groups: ovariectomy (OVX, n = 5), OVX and zoledronic acid (ZOL) at week 0 (n = 8), OVX and ZOL at week 8 (n = 7), and sham (n = 9). CT scans were made of the proximal tibia at weeks 0, 2, 4, 8, 12, and 16; and bone structural parameters were determined in the metaphysis. Two fluorescent labels were administered to calculate dynamic histomorphometric parameters. At week 16, all groups were significantly different from each other in bone volume fraction (BV/TV), connectivity density, and trabecular number (Tb.N), except for the early ZOL and control groups which were not significantly different for any structural parameter. After ZOL treatment at week 8, BV/TV, structure model index, Tb.N, and trabecular thickness significantly improved in the late ZOL group. The OVX and ZOL groups showed, respectively, higher and lower bone formation rates than the control group. Early ZOL treatment inhibited all bone microstructural changes seen after OVX. Late ZOL treatment significantly improved bone microstructure, although the structure did not recover to original levels. Early ZOL treatment resulted in a significantly better microstructure than late treatment. However, late treatment was still significantly better than no treatment