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The tumor‐stroma ratio (TSR) has proven to be a strong prognostic factor in breast cancer, demonstrating better survival for patients with stroma‐low tumors. Since the role of the TSR as a predictive marker for neoadjuvant chemotherapy outcome is yet unknown, this association was evaluated for HER2‐negative breast cancer in the prospective DIRECT and NEOZOTAC trials. The TSR was assessed on 375 hematoxylin and eosin‐stained sections of pre‐treatment biopsies. Associations between the TSR and chemotherapy response according to the Miller‐Payne (MP) grading system, and between the TSR and pathological response were examined using Pearson's chi‐square, Cochran‐Armitage test for trend and regression analyses. A stroma‐low tumor prior to neoadjuvant chemotherapy was significantly associated with a higher MP score (P = .005). This relationship remained significant in the estrogen receptor (ER)‐negative subgroup (P = .047). The univariable odds ratio (OR) of a stroma‐low tumor on pathological complete response (pCR) was 2.46 (95% CI 1.34‐4.51, P = .004), which attenuated to 1.90 (95% CI 0.85‐4.25, P = .119) after adjustment for relevant prognostic factors. Subgroup analyses revealed an OR of 5.91 in univariable analyses for ER‐negativity (95% CI 1.19‐29.48, P = .030) and 1.48 for ER‐positivity (95% CI 0.73‐3.01, P = .281). In conclusion, a low amount of stroma on pre‐treatment biopsies is associated with a higher MP score and pCR rate. Therefore, the TSR is a promising biomarker in predicting neoadjuvant treatment outcome. Incorporating this parameter in routine pathological diagnostics could be worthwhile to prevent overtreatment and undertreatment.

Purpose In the phase II DIRECT study a fasting mimicking diet (FMD) improved the clinical response to neoadjuvant chemotherapy as compared to a regular diet. Quality of Life (QoL) and illness perceptions regarding the possible side effects of chemotherapy and the FMD were secondary outcomes of the trial. Methods 131 patients with HER2-negative stage II/III breast cancer were recruited, of whom 129 were randomly assigned (1:1) to receive either a fasting mimicking diet (FMD) or their regular diet for 3 days prior to and the day of neoadjuvant chemotherapy. The European Organisation for Research and Treatment of Cancer (EORTC) questionnaires EORTC-QLQ-C30 and EORTC-QLQ-BR23; the Brief Illness Perception Questionnaire (BIPQ) and the Distress Thermometer were used to assess these outcomes at baseline, halfway chemotherapy, before the last cycle of chemotherapy and 6 months after surgery. Results Overall QoL and distress scores declined during treatment in both arms and returned to baseline values 6 months after surgery. However, patients’ perceptions differed slightly over time. In particular, patients receiving the FMD were less concerned and had better understanding of the possible adverse effects of their treatment in comparison with patients on a regular diet. Per-protocol analyses yielded better emotional, physical, role, cognitive and social functioning scores as well as lower fatigue, nausea and insomnia symptom scores for patients adherent to the FMD in comparison with non-adherent patients and patients on their regular diet. Conclusions FMD as an adjunct to neoadjuvant chemotherapy appears to improve certain QoL and illness perception domains in patients with HER2-negative breast cancer. Trialregister ClinicalTrials.gov Identifier: NCT02126449.

Contains fulltext : 165680.pdf (Publisher’s version ) (Open Access) BACKGROUND: The insulin-like growth factor 1 (IGF-1) pathway is involved in cell growth and proliferation and is associated with tumorigenesis and therapy resistance. This study aims to elucidate whether variation in the IGF-1 pathway is predictive for pathologic response in early HER2 negative breast cancer (BC) patients, taking part in the phase III NEOZOTAC trial, randomizing between 6 cycles of neoadjuvant TAC chemotherapy with or without zoledronic acid. METHODS: Formalin-fixed paraffin-embedded tissue samples of pre-chemotherapy biopsies and operation specimens were collected for analysis of IGF-1 receptor (IGF-1R) expression (n = 216) and for analysis of 8 candidate single nucleotide polymorphisms (SNPs) in genes of the IGF-1 pathway (n = 184) using OpenArray(R) RealTime PCR. Associations with patient and tumor characteristics and chemotherapy response according to Miller and Payne pathologic response were performed using chi-square and regression analysis. RESULTS: During chemotherapy, a significant number of tumors (47.2 %) showed a decrease in IGF-1R expression, while in a small number of tumors an upregulation was seen (15.1 %). IGF-1R expression before treatment was not associated with pathological response, however, absence of IGF-1R expression after treatment was associated with a better response in multivariate analysis (P = 0.006) and patients with a decrease in expression during treatment showed a better response to chemotherapy as well (P = 0.020). Moreover, the variant T allele of 3129G > T in IGF1R (rs2016347) was associated with a better pathological response in multivariate analysis (P = 0.032). CONCLUSIONS: Absent or diminished expression of IGF-1R after neoadjuvant chemotherapy was associated with a better pathological response. Additionally, we found a SNP (rs2016347) in IGF1R as a potential predictive marker for chemotherapy efficacy in BC patients treated with TAC. TRIAL REGISTRATION: ClinicalTrials.gov NCT01099436 . Registered April 6, 2010.

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In a 17-year-old woman with anorexia nervosa, scurvy was diagnosed as the cause of fatigue, abdominal pain, vaginal bleeding and several distinctive skin lesions.

To improve primary diabetes care in the Netherlands, in 2007 a ‘care group’ system is initiated. We first studied the association between adherence to a structured diabetes protocol and patient outcomes. We then investigated what practices actually require when seeking to adjust care to patient needs. With that aim in mind, we explored the effect of dispensing with protocol and the key conditions for successful implementation of self-management interventions. Finally, we measured patient outcomes with regard to treatment satisfaction, quality of life and monitoring.A structured care protocol has added value for people with diabetes; the proportion of people having recommended monitoring increases sharply. Practices likely undergo an intensive learning process when they join a care group and appear to reach the same as experienced practice within a year. When comparing the HbA1 levels of people with recommended and incomplete monitoring, we found that the HbA1c levels in people with recommended monitoring are significantly circa 2 mmol/mol lower compared to incomplete monitoring. In other words, recommended monitoring is far more than merely an administrative procedure; it actually reflects better real-world HbA1c levels. Differences in HbA1c level between people with recommended versus incomplete monitoring were greater in vulnerable populations, to the extent of approximately 3 mmol/mol, whereas a circa 1 mmol/mol difference was found in the intermediate category. In other words, within a care group setting people in the deprived category derive the most benefit from recommended monitoring.Protocol-free care provided room for reflection concerning ‘tailored care’; varying self-management interventions were chosen Our study revealed three key conditions for successful implementation of self-management interventions. Considering that patient satisfaction and monitoring decreased, this thesis ends with a roadmap consisting of several recommendations to improve and tailor diabetes care in general practice.