Longitudinal Serum Protein Analysis of Women with a High Risk of Developing Breast Cancer Reveals Large Interpatient Versus Small Intrapatient Variations:First Results from the TESTBREAST Study

The prospective, multicenter TESTBREAST study was initiated with the aim of identifying a novel panel of blood-based protein biomarkers to enable early breast cancer detection for moderate-to-high-risk women. Serum samples were collected every (half) year up until diagnosis. Protein levels were longitudinally measured to determine intrapatient and interpatient variabilities. To this end, protein cluster patterns were evaluated to form a conceptual basis for further clinical analyses. Using a mass spectrometry-based bottom-up proteomics strategy, the protein abundance of 30 samples was analyzed: five sequential serum samples from six high-risk women; three who developed a breast malignancy (cases) and three who did not (controls). Serum samples were chromatographically fractionated and an in-depth serum proteome was acquired. Cluster analyses were applied to indicate differences between and within protein levels in serum samples of individuals. Statistical analyses were performed using ANOVA to select proteins with a high level of clustering. Cluster analyses on 30 serum samples revealed unique patterns of protein clustering for each patient, indicating a greater interpatient than intrapatient variability in protein levels of the longitudinally acquired samples. Moreover, the most distinctive proteins in the cluster analysis were identified. Strong clustering patterns within longitudinal intrapatient samples have demonstrated the importance of identifying small changes in protein levels for individuals over time. This underlines the significance of longitudinal serum measurements, that patients can serve as their own controls, and the relevance of the current study set-up for early detection. The TESTBREAST study will continue its pursuit toward establishing a protein panel for early breast cancer detection

Radiotherapy does not compensate for positive resection margins in rectal cancer patients: report of a multicenter randomized trial.

Contains fulltext : 123522.pdf (publisher's version ) (Closed access)PURPOSE: Circumferential resection margin (CRM) involvement is a prognostic factor for local recurrence in rectal cancer. In a randomized trial comparing preoperative radiotherapy (5 x 5 Gy), followed by total mesorectal excision (TME) with TME alone, we demonstrated the beneficial effect of short-term preoperative radiotherapy on local recurrences. Here we evaluate the effect of radiotherapy on local recurrence rates in patients with different CRM involvements. METHODS AND MATERIALS: Circumferential margins were defined as positive (2 mm). Postoperative radiotherapy was mandatory for surgery-only patients with a positive CRM, but was not always administered and enabled us to compare local recurrence rates for patients with or without postoperative radiotherapy. Furthermore, the effect of preoperative radiotherapy was assessed in the different margin groups. RESULTS: Of 120 patients in the surgery-only group with a positive CRM, 47% received postoperative radiotherapy. There was no difference in the local recurrence rate between the irradiated and nonirradiated patients (17.3% vs. 15.7%, p = 0.98). Preoperative radiotherapy was effective in patients with a narrow CRM (0% vs. 14.9%, p = 0.02) or wide CRM (0.9 vs. 5.8%, p < 0.0001), but not in patients with positive margins (9.3% vs. 16.4%, p = 0.08). CONCLUSION: Preoperative hypofractionated radiotherapy has a beneficial effect in patients with wide or narrow resection margins, but cannot compensate for microscopically irradical resections resulting in positive margins

CYP2D6 genotype in relation to hot flashes as tamoxifen side effect in a Dutch cohort of the tamoxifen exemestane adjuvant multinational (TEAM) trial

Experimentele farmacotherapi

Common polymorphisms in the estrogen receptor-1 may determine risk of hot flashes in early breast cancer patients using tamoxifen

Experimentele farmacotherapi

Thyroid function is associated with the response to neoadjuvant chemotherapy in breast cancer patients: Results from the NEOZOTAC trial on behalf of the Dutch Breast Cancer Research Group (BOOG 2010-01)

Surgical oncolog

Thyroid function alters during neoadjuvant chemotherapy in breast cancer patients: results from the NEOZOTAC trial (BOOG 2010-01)

Surgical oncolog

Microsatellite instability and sex differences in resectable gastric cancer - A pooled analysis of three European cohorts.

Biological sex differences in cancer are increasingly acknowledged. Here, we examined these differences in clinicopathological characteristics and survival in microsatellite instability (MSI)-high and microsatellite stable (MSS) gastric cancer (GC). We analysed MSI status by polymerase chain reaction (PCR) and/or mismatch repair (MMR) status by immunohistochemistry in a pooled analysis of individual patient data from one retrospective cohort from Cologne, and the randomised phase III clinical trials D1/D2 and CRITICS. All patients had resectable adenocarcinoma of the stomach and/or gastro-oesophageal junction. Patients were treated with either surgery only or perioperative chemo(radio)therapy. MSI and/or MMR analyses on 1307 tumours resulted in 1192 (91.2%) MSS and/or MMR proficient (MMRP) [median age, 65 years; 759 males (63.7%); 619 treated with surgery only (51.9%)], and 115 (8.8%) MSI-high [median age, 69 years; 67 males (58.3%); 76 treated with surgery only (66.1%)] GC cases. Males had shorter overall survival (OS) than female MSI-high GC (5-year OS 34.7% vs. 69.7%; hazard ratio (HR) 2.68, 95%CI 1.60 to 4.49; p &lt; 0.001). Females with MSI-high had longer OS than those with MSS/MMRP GC (HR 0.61, 95%CI 0.41 to 0.92; p = 0.02). Males with MSI-high did not have longer OS than those with MSS/MMRP GC (HR 1.26, 95%CI 0.94 to 1.69; p = 0.12). MSI-high GC males had a significantly worse prognosis compared to their female counterparts in three independent cohorts. In addition, the favourable prognostic value of MSI was only seen in females and not in males. These observations emphasise the need to consider sex differences in prognosis and treatment effects in oncology. The CRITICS trial is registered at ClinicalTrials.gov, number NCT00407186; EudraCT, number 2006-004130-32; and CKTO, 2006-02