Alexandra King

Major developments in adjuvant treatment of early HER2-positive breast cancer

breast cancers. As P-HER2 might be a moreaccurate reflection of the functional activity of the HER2 protein, its expression might be linked to the resistance to taxane therapy seen in preclinical studies. In this study, archived tissue samples from 126 women with metastatic breast cancer were tested for the presence of P-HER2 using immunohistochemistry and a newly available anti-P-HER2 antibody. Each case was scored semi-quantitatively and findings were compared with tumor response to taxane monotherapy. Twelve cases were P-HER2-positive, of which five showed clinical progression ontherapy and seven showed clinical benefit. Of the 114 P-HER2-negative cases, 20 demonstrated progression and 94 had clinical benefit. The likelihood of progression on taxane therapy was 42% in P-HER2-positive tumors, compared with 18% in P-HER2negative tumors (P = 0.046). Data from the small number of P-HER2positive patients in this study imply that HER2 activation is associated with taxane resistance. These findings are being further examined in a larger cohort of taxane-treated breast cancer patients. Carol Lovegrove

Autoantibodies as novel biomarkers for the early detection of prostate cancer

three treatment options, in various clinical scenarios. Patients with metastatic colo rectal cancer usually present to oncologists and general surgeons, either of whom may lack the specialist knowledge required for the management of this disease. OncoSurge was created to assist in the decision-making process, determine resectability, and identify an individualized optimal treatment strategy for each patient. A panel of 16 oncologists, surgeons, and radiologists rated the appropriateness of each possible treatment option in terms of patient characteristics and indications—a total of 1,872 ratings. The rated treatment strategies were then assimilated into a computerized decision matrix—OncoSurge. The model was tested using real and theoretical cases by comparing the panel’s modal treatment choice with the OncoSurge appropriateness rating. Of the 48 theoretical cases, the treatment strategy was validated in 37; therefore, in 23% of clinical situations the optimal therapeutic regimen was unclear, representing areas of scientific un certainty upon which future clinical trials could be focused. The authors conclude that, by combining the best scientific evidence with expert opinion, OncoSurge can assist medical practitioners at the primary and secondary level of care to determine the most appropriate treatment strategy and identify candidates for resection among patients with metastatic colorectal cancer. Alexandra King

IMRT for head-and-neck cancer improves quality of life and reduces xerostomia

three treatment options, in various clinical scenarios. Patients with metastatic colo rectal cancer usually present to oncologists and general surgeons, either of whom may lack the specialist knowledge required for the management of this disease. OncoSurge was created to assist in the decision-making process, determine resectability, and identify an individualized optimal treatment strategy for each patient. A panel of 16 oncologists, surgeons, and radiologists rated the appropriateness of each possible treatment option in terms of patient characteristics and indications—a total of 1,872 ratings. The rated treatment strategies were then assimilated into a computerized decision matrix—OncoSurge. The model was tested using real and theoretical cases by comparing the panel’s modal treatment choice with the OncoSurge appropriateness rating. Of the 48 theoretical cases, the treatment strategy was validated in 37; therefore, in 23% of clinical situations the optimal therapeutic regimen was unclear, representing areas of scientific un certainty upon which future clinical trials could be focused. The authors conclude that, by combining the best scientific evidence with expert opinion, OncoSurge can assist medical practitioners at the primary and secondary level of care to determine the most appropriate treatment strategy and identify candidates for resection among patients with metastatic colorectal cancer. Alexandra King

Effective new combination therapy for older patients with myeloma

frequency and types of undetected breastcancer-predisposing mutations among patients with breast cancer from high-risk families who had negative conventional genetic test results for BRCA1 and BRCA2. In this study, PROBANDS from 300 families with at least four cases of breast or ovarian cancer but negative genetic test results for BRCA1 and BRCA2 were screened for inherited re arrangements and germline mutations in BRCA1, BRCA2, CHEK2, TP53, and PTEN. In total, 52 probands were found to have inherited mutations in BRCA1 (n = 31), BRCA2 (n = 4), CHEK2 (n = 14), or TP53 (n = 3); no inherited mutations were detected in PTEN. A wide spectrum of BRCA1 and BRCA2 mutations— deletions, duplications and rearrangements— were found, including 14 rearrangements that were previously unreported. The authors conclude that the conventional genetic screening process currently available in the US for women at high risk of breast and ovarian cancer does not identify all women who carry cancer-predisposing genetic mutations. Methods such as multiplex ligation-dependent probe amplification might be useful in identifying a wider range of genomic rearrangements in families testing negative for BRCA1 and BRCA2 by conventional methods. Research is ongoing to identify other genes that confer cancer susceptibility and that could be incorporated into genetic tests. Rebecca Ireland

Meta-analysis supports use of polysaccharide K in adjuvant therapy for colorectal cancer

these patients. Van Hogezand et al.’s study, therefore, aimed to identify which factors were most predictive of skeletal pathology in these patients. Overall, 146 patients with Crohn’s disease who attended outpatient clinics at the Leiden University Medical Center, The Netherlands, were studied over a 1-year period. Their mean duration of disease was 20 years. In total, 37 patients had disease localized to the ileum, 26 to the colon, and 83 to both the ileum and colon. In addition, 96 patients had previously undergone intestinal resection, most frequently of the ileum. Although nearly half of the patients were found to have reduced BMD, only 38 patients had osteoporosis of the lumbar spine, femoral neck, or both. The prevalence of fracture was also low. The most important risk factor for osteoporosis was ileum resection, followed by age. In contrast to previous studies, there was no association between current or past use of glucocorticoids and increased risk of either osteoporosis or fracture. No relationship was observed between duration of Crohn’s disease and BMD in this cohort. The authors strongly recommend BMD screening for all patients with Crohn’s disease who have undergone ileum resection; they suggest that this will allow the early initiation of bone-protective treatment in those patients identified to be most at risk of osteoporosis.

Combination targeted therapy for metastatic renal-cell carcinoma

patients with stage T1–T2 disease received radiation to the prostate only. Toxicities were assessed 6 weeks after completion of therapy, then every 3 months for the first year, and every 6 months thereafter. At 5 years, the overall bio chemical relapse-free survival rate (bRFS) was 85% according to the ASTRO failure definition; using an alternative definition of nadir PSA + 2 μg/l, the overall 5-year bRFS rate was 88%. The 5-year bRFS rates for patients with disease of low, medium, or high risk were comparable for both definitions. Rectal and urinary grade 2 and 3 late toxicities were 5% and 8%, respectively, when calculated from last follow-up. From these encouraging results, the authors conclude that this regimen is highly effective for the treatment of localized prostate cancer and is substantially more convenient for the patient than longer treatment schedules. Alexandra King

MRI is important for preradiotherapy evaluation of nasopharyngeal carcinoma

patients with stage T1–T2 disease received radiation to the prostate only. Toxicities were assessed 6 weeks after completion of therapy, then every 3 months for the first year, and every 6 months thereafter. At 5 years, the overall bio chemical relapse-free survival rate (bRFS) was 85% according to the ASTRO failure definition; using an alternative definition of nadir PSA + 2 μg/l, the overall 5-year bRFS rate was 88%. The 5-year bRFS rates for patients with disease of low, medium, or high risk were comparable for both definitions. Rectal and urinary grade 2 and 3 late toxicities were 5% and 8%, respectively, when calculated from last follow-up. From these encouraging results, the authors conclude that this regimen is highly effective for the treatment of localized prostate cancer and is substantially more convenient for the patient than longer treatment schedules. Alexandra King

OncoSurge: rating treatment for patients with metastatic colorectal cancer

disorder (a serum ferritin level >200 μg/l in women or >300 μg/l in men with a transferri n saturation >55% is indicative of disease). Third, in patients with an inherent risk of hereditar y hemochromatosis or those with raised serum ferritin levels or transferrin saturation, clinician s should discuss the risks and benefits of genetic testing with patients. Finally, further clinical research into hereditary hemo chromatosis should be undertaken. The systematic review and guidelines go some way to clarify the usefulness of variou s diagnostic measures. Further research is, howeve r, needed in order to gain a clearer understanding of the natural history of this disease, and to standardize diagnostic criteria. Rachel Jones

Autoimmunity is associated with improved survival during interferon therapy for melanoma

cancer in the different groups (although a low level of education was associated with increased risk of lung cancer regardless of smoking habits). Possible explanations for the differences seen include variation in the metabolism of nicotine or susceptibility to tobacco carcinogen effects between different racial/ethnic groups, and additional differences in smoking behavior between the groups. Further study into these areas is needed. Pippa Murdie

Occult gynecologic malignancies in BRCA1 and BRCA2 mutation carriers

been taking tamoxifen 20 mg daily for at least 3 months. Patients continued with tamoxifen 20 mg daily, and blood samples were taken after 4 weeks. Patients then received exemestane 25 mg daily for 8 weeks, in addition to tamoxifen; further blood samples were taken after this time. No serious adverse events were reported when tamoxifen and exemestane were administered at the same time. Exemestane had no significant effect on tamoxifen’s AREA UNDER THE CONCENTRATION–TIME CURVE (AUC), and was therefore considered to have had no significant effect on tamoxifen BIOAVAILABILITY. The elimination half-life for tamoxifen did not change significantly with concurrent exemestane. Concentrations of tamoxifen and its metabolites were not affected by 8 weeks of concurrent exemestane, and tamoxifen had no significant effect on exemestane pharmaco kinetics. As expected, exemestane significantly reduced plasma concentrations of estradiol and its metabolites over 8 weeks (P <1.0×10–6 for all). The authors conclude that the combination of exemestane and tamoxifen was well tolerated over 8 weeks, and that there was no significant pharmacokinetic interaction between the two drugs. Rebecca Ireland