Risk of early-onset breast cancer among women exposed to thoracic computed tomography in pregnancy or early postpartum.

Essentials Tests for pulmonary embolism expose women to low-dose radiation. 5859 pregnancies had a thoracic computed tomography (T-CT) vs. 1.3 million who did not. The adjusted hazard ratio for breast cancer was 1.17 (95% confidence interval 0.80-1.70). The long-term risk of breast cancer among women who had a T-CT remains unknown. SUMMARY: Background The risk of breast cancer may be higher with direct exposure to ionizing radiation from thoracic computed tomography (CT) during pregnancy or the postpartum. We evaluated the short-term risk of maternal breast cancer after exposure to thoracic CT during these periods. Methods We completed a retrospective population-based cohort study of all deliveries between 1995 and 2014 using universal healthcare databases in the province of Ontario, Canada. The main exposure was thoracic CT in pregnancy or ≤ 42 days postpartum. The passive exposure was ventilation-perfusion scintigraphy (VQ) scan in pregnancy or ≤ 42 days postpartum. Each was compared to pregnancies unexposed to thoracic CT or VQ scan. The primary study outcome was newly diagnosed breast cancer starting 366 days post-index delivery date. Results A total of 5859 pregnancies were exposed to thoracic CT, 4075 to VQ scan and 1 292 059 to neither. Starting from 1 year after the index delivery, the median duration of follow-up was 5.9, 7.3 and 11.1 years, respectively. A total of 10 129 women were diagnosed with breast cancer, of whom 9039 (89.2%) were aged ≤ 50 years. There were 27 new cases of breast cancer (7.1 per 10 000 person-years) following thoracic CT vs. 10 080 (7.0 per 10 000 person-years) among the unexposed, an adjusted hazard ratio (HR) of 1.17 (95% confidence interval [CI], 0.80-1.70). Following VQ scan exposure, the incidence rate of breast cancer was 7.0 per 10 000 person-years, an adjusted HR of 1.23 (95% CI 0.81-1.87), compared with the unexposed cohort. Conclusion Exposure to thoracic CT during pregnancy or the postpartum was not associated with an increased short-term risk of maternal breast cancer. The long-term risk should be studied.

Dual blockade of HER2 - twice as good or twice as toxic?

With about 20% of breast cancers overexpressing HER2, the implementation of trastuzumab and, more recently, lapatinib has revolutionised the care of these patients. Despite these successes, de novo and acquired resistance to these agents represent significant barriers that need to be overcome if further progress is to be achieved. Given that resistance can involve interplay between different members of the HER family multi-targeted inhibition of HER receptors represents an interesting therapeutic strategy. To date, clinical trials have shown that a number of targeted drugs can be combined with trastuzumab and lead to improved overall response rates and potentially also survival. However, such progress leads to an increased burden of toxicity. This review will discuss the mechanisms behind HER2 resistance, the preclinical basis for combining different agents with trastuzumab and the available results from clinical studies evaluating these combinations.

Histomorphometric and microarchitectural analyses using the 2 mm bone marrow trephine in metastatic breast cancer patients-preliminary results.

BACKGROUND: Bone-targeted agents are widely used for the treatment of osteoporosis, the prevention of cancer-therapy induced bone loss, and for reducing the risk of skeletal related events in patients with metastatic disease. Despite widespread use, relatively little is known about the in vivo effect of these agents on bone homeostasis, bone quality, and bone architecture in humans. Traditionally bone quality has been assessed using a transiliac bone biopsy with a 7 mm "Bordier" core needle. We examined the possibility of using a 2 mm "Jamshidi" core needle as a more practical and less invasive method to assess bone turnover and potentially other tumor effects. METHODS: A pilot study on the feasibility of assessing bone quality and microarchitecture and tumor invasion using a 2 mm bone marrow trephine was conducted. Patients underwent a posterior trans-iliac trephine biopsy and bone marrow aspirate. Samples were analyzed for bone microarchitecture, bone density, and histomorphometry. The study plan was to accrue three patients with advanced breast cancer to assess the feasibility of the study before enrolling more patients. RESULTS: The procedure was well tolerated. The sample quality was excellent to analyze bone trabecular microarchitecture using both microCT and histomorphometry. Intense osteoclastic activity was observed in a patient with extensive tumor burden in bone despite intravenous bisphosphonate therapy. DISCUSSION: Given the success of this study for assessing bone microarchitecture, bone density, and histomorphometry assessment using a 2 mm needle the study will be expanded beyond these initial three patients for longitudinal assessment of bone-targeted therapy.

Radiological changes following second-line zoledronic acid treatment in breast cancer patients with bone metastases.

Initiation of bisphosphonate therapy in bisphosphonate-naïve patients is known to be associated with radiological changes such as increased bone density in both osteolytic and osteoblastic metastases. It is not known, however, whether switching from a second-generation bisphosphonate to a more potent agent is associated with similar changes. This study aimed to prospectively explore radiological changes, as assessed by thoracolumbar CT scanning, in patients switching from an early generation bisphosphonate (i.e., oral clodronate or intravenous pamidronate) to intravenous zoledronic acid. Patients with progressive bone metastases despite use of an earlier generation bisphosphonate were switched to zoledronic acid as part of a study to evaluate the palliative benefit of this intervention. Quantitative computed tomography (QCT) scanning of the thoracolumbar spine was carried out at baseline, and repeated 4 months after commencing zoledronic acid. The effect of this change of therapy was explored in terms of bone density, as well as volume of osteolytic and osteoblastic disease. Fifteen patients were assessed. Switching of bisphosphonate therapy was associated with a significant increase in bone density, and an increase in osteoblastic volume. There was an insignificant trend towards reduced osteolytic volume. In conclusion, switching from early generation bisphosphonates to a more potent agent is associated with radiological changes similar to those seen when commencing a bisphosphonate in treatment-naïve patients. This is consistent with the observed palliative benefit. The use of QCT may be of benefit in the monitoring of bone metastases.