R.A.E.M. Tollenaar

Improved overall survival after contralateral risk-reducing mastectomy in BRCA1/2 mutation carriers with a history of unilateral breast cancer: a prospective analysis

Data on survival of BRCA1/2‐associated primary breast cancer (PBC) patients who opt for subsequent contralateral risk‐reducing mastectomy (CRRM) are scarce and inconsistent. We examined the efficacy of CRRM on overall survival in mutation carriers with a history of PBC. From a Dutch multicentre cohort, we selected 583 BRCA‐associated PBC patients, being diagnosed between 1980 and 2011. Over time, 242 patients (42%) underwent CRRM and 341 patients (58%) remained under surveillance. Survival analyses were performed using Cox models, with CRRM as a time‐dependent covariate. The median follow‐up after PBC diagnosis was 11.4 years. In the CRRM group, four patients developed contralateral breast cancer (2%), against 64 patients (19%) in the surveillance group (pu2009<u20090.001). The mortality was lower in the CRRM group than in the surveillance group (9.6 and 21.6 per 1000 person‐years of observation, respectively; adjusted hazard ratio 0.49, 95% confidence interval 0.29–0.82). Survival benefit was especially seen in young PBC patients (<40 years), in patients having a PBC with differentiation grade 1/2 and/or no triple‐negative phenotype, and in patients not treated with adjuvant chemotherapy. We conclude that CRRM is associated with improved overall survival in BRCA1/2 mutation carriers with a history of PBC. Further research is warranted to develop a model based on age at diagnosis and tumour and treatment characteristics that can predict survival benefit for specific subgroups of patients, aiming at further personalized counselling and improved decision making.

Case–controlled identification of colorectal cancer based on proteomic profiles and the potential for screening

Colorectal cancer (CRC) screening programmes detect early cancers but unfortunately have limited sensitivity and specificity. Mass spectrometry‐based determination of serum peptide and protein profiles provides a new approach for improved screening.

Stroma-High Lymph Node Involvement Predicts Poor Survival More Accurately for Patients with Stage III Colon Cancer

Objective: The tumor microenvironment has ample impact on the behavior of the malignant process in colon cancer (CC). Patients with a high percentage of stroma within the primary tumor, determined by the tumor-stroma ratio (TSR), have a poor prognosis. In metastatic lymph nodes from patients with stage III CC, the TSR is heterogeneous, but the impact on patients’ prognosis is unknown. Methods: Haematoxylin and eosin stained tissue slides of primary tumor (PT) and associated lymph nodes (LNs) metastases from 102 patients with stage III CC were analyzed for the TSR. Stroma-high (>50% stroma) and stromalow (≤ 50% stroma) groups were evaluated with respect to disease free survival (DFS). Results: Of 102 analyzed primary tumors, 47 (46.1%) scored as stroma-high and 55 (53.9%) as stroma-low. In total, 33 patients had at least one stroma-high LN and 69 patients had one or more stroma-low LNs. Interestingly, 28 patients (27.5%) had both stroma-high and stroma-low LNs, but in another 44 cases the TSR between PT and LNs differed: 29 patients had a stroma-high PT with stroma-low LNs, while 15 patients displayed the opposite. As a result of the combination of the TSR analysis of the PT and the involved metastatic LNs, 62 patients (60.8%) were classified as stroma-high and 40 (39.2%) as stroma-low, restaging 14.7% of the patients to stroma-high with a significantly worse 5-year DFS compared to stroma-low patients (59% vs. 82%, HR=2.83 (95%CI 1.34–5.97), P=0.006). In multivariate analysis, the TSR retained its independent prognostic impact (HR=2.85 (95%CI 1.33-6.10), P=0.007). Conclusion: The presence of abundant stroma in metastatic LNs from patients with stage III CC adds to the prognostic information learned from the primary tumor independently, and supports selective patient treatment.

The value of additional bevacizumab in patients with high-risk stroma-high colon cancer. A study within the QUASAR2 trial, an open-label randomized phase 3 trial

Patients with a high stroma percentage within the primary tumor have a poor prognosis. In this study, we investigate whether anti‐angiogenic therapy might improve survival of patients with a stroma‐high profile with potentially increased angiogenesis.