Ki-67: level of evidence and methodological considerations for its role in the clinical management of breast cancer: analytical and critical review

Clinicians can use biomarkers to guide therapeutic decisions in estrogen receptor positive (ER+) breast cancer. One such biomarker is cellular proliferation as evaluated by Ki-67. This biomarker has been extensively studied and is easily assayed by histopathologists but it is not currently accepted as a standard. This review focuses on its prognostic and predictive value, and on methodological considerations for its measurement and the cut-points used for treatment decision. Data describing study design, patients’ characteristics, methods used and results were extracted from papers published between January 1990 and July 2010. In addition, the studies were assessed using the REMARK tool. Ki-67 is an independent prognostic factor for disease-free survival (HR 1.05–1.72) in multivariate analyses studies using samples from randomized clinical trials with secondary central analysis of the biomarker. The level of evidence (LOE) was judged to be I-B with the recently revised definition of Simon. However, standardization of the techniques and scoring methods are needed for the integration of this biomarker in everyday practice. Ki-67 was not found to be predictive for long-term follow-up after chemotherapy. Nevertheless, high KI-67 was found to be associated with immediate pathological complete response in the neoadjuvant setting, with an LOE of II-B. The REMARK score improved over time (with a range of 6–13/20 vs. 10–18/20, before and after 2005, respectively). KI-67 could be considered as a prognostic biomarker for therapeutic decision. It is assessed with a simple assay that could be standardized. However, international guidelines are needed for routine clinical use

First-line therapy with gemcitabine and paclitaxel in locally, recurrent or metastatic breast cancer: A phase II study

BACKGROUND: This phase II study evaluated the efficacy and safety of gemcitabine (G) plus paclitaxel (T) as first-line therapy in recurrent or metastatic breast cancer. METHODS: Patients with locally, recurrent or metastatic breast cancer and no prior chemotherapy for metastatic disease received G 1200 mg/m(2 )on days 1 and 8, and T 175 mg/m(2 )on day 1 (before G) every 21 days for a maximum of 10 cycles. RESULTS: Forty patients, 39 metastatic breast cancer and 1 locally-advanced disease, were enrolled. Their median age was 61.5 years, and 85% had a World Health Organization performance status (PS) of 0 or 1. Poor prognostic factors at baseline included visceral involvement (87.5%) and ≥2 metastatic sites (70%). Also, 27 (67.5%) patients had prior adjuvant chemotherapy, 25 of which had prior anthracyclines. A total of 220 cycles (median 6; range, 1–10) were administered. Of the 40 enrolled patients, 2 had complete response and 12 partial response, for an overall response rate of 35.0% for intent-to-treat population. Among 35 patients evaluable for efficacy the response rate was 40%. Additional 14 patients had stable disease, and 7 had progressive disease. The median duration of response was 12 months; median time to progression, 7.2 months; median survival, 25.7 months. Common grade 3/4 toxicities were neutropenia in 17 (42.5%) patients each, grade 3 leukopenia in 19 (47.5%), and grade 3 alopecia in 30 (75.0%) patients; 1 (2.5%) patient had grade 4 thrombocytopenia. CONCLUSION: GT exhibited encouraging activity and tolerable toxicity as first-line therapy in metastatic breast cancer. Phase III trials for further evaluation are ongoing

Comparative study of neoadjuvant chemotherapy with and without Zometa for management of locally advanced breast cancer with serum VEGF as primary endpoint: The NEOZOL study

Introduction Neoadjuvant chemotherapy has become the treatment of choice for locally advanced breast cancer. Zoledronic acid (ZA) is a bisphosphonate initially used in the treatment of bone metastases because of its antibone resorption effect. Antitumor effects of ZA, including the inhibition of cell adhesion to mineralized bone or the antiangiogenic effect, have been demonstrated. However, the clinical significance of these effects remains to be determined. Materials and Methods We undertook a multicenter open-label randomized trial to analyze the value of adding ZA to neoadjuvant chemotherapy for TNM clinical stage T2/T3 breast cancer. The primary endpoint was the evolution of serum VEGF. Results The data from 24 patients were included in the ZA group and 26 in the control group. The evolution of serum VEGF was slightly in favor of ZA at 5.5 months (−0.7% vs. +7.5%), without reaching statistical significance (P = .52). The secondary endpoints were the breast conservation rate (higher with ZA; 83.3% vs. 65.4%; P = NS), pathologic complete response (no effect), and circulating tumor cells (odds ratio, 0.68 in favor of ZA; 95% confidence interval, 0.02-24.36). No cases of jaw necrosis or severe renal failure were observed in either group. Conclusion ZA is an antitumor drug of interest because of its multiple effects on tumor biology. Larger trials with longer follow-up that include additional endpoints such as relapse and survival rates would be of interest

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P < 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

Effets de l activité physique adaptée sur la fonction aérobie et la fatigue chez des patientes atteintes d un cancer du sein en situation adjuvante et néo-adjuvante

Objectifs. Le but de cette étude est d'évaluer la fonction cardio-pulmonaire mesurée par la VO2pic dans le cancer du sein avant un traitement (CT-RT) et après la réalisation d'un programme d'activité physique adaptée (APA). Méthodes. Le bras A (entraînement en endurance et résistance) et le bras B (groupe contrôle). Cette étude inclus 3 temps d'évaluation. (T0 : avant CT-RT) ; T1 (semaine 27) and T2 : évaluation finale à 54 semaines). Les examens réalisés sont une épreuve d'effort cardio-pulmonaire évaluant la VO2pic, un test de marche de 6 min 5TM6), des tests de la force musculaire, des explorations fonctionnelles respiratoires, l'évaluation de l'activité physique à l'aide du questionnaire IPAQ, de la fatigue (MFI 20), qualité de vie (EORTC QLQ-C30), de l'anxiété et de la dépression (HADS) et pour finir une évaluation de la composition corporelle. Résultats. Entre juin 2012 et juin 2013 44 patientes ont été incluses dans l'étude. A T0, la moyenne d'âge était de 52,3 +- 11,7 ans pour le bras A et de 48,8 +-8 pour le bras B. Avant traitement la VO2pic était de 22,5 +- 4,4 ml.kg-1.min-1pour le bras A et de 23,4 +- 5,1 ml.min-1kg-1 pour le bras B. Après traitement, en analyse par intention de traiter, la différence entre nos 2 groupes était de 2,3 ml.min-1kg-1, alors qu'en analyse per-protocole cette différence est de 3,49 ml.min-1kg-1 et est significative. La distance de marche s'améliore de 21,75 +- 7,15 m pour le bras A (P=.016) et diminue de 9,54 +- 6,82 m pour le bras B (P=.0,43). Conclusions. Notre étude a réussi à prouver qu'un entraînement individualisé et à domicile est faisable et sûr pour des patientes atteintes d'un cancer du sein en situation adjuvante ou néoadjuvante.LIMOGES-BU Médecine pharmacie (870852108) / SudocSudocFranceF

Etude rétrospective sur la prise en charge de 37 cas de cancers du sein métastatique traités par l'association bevacizumab paclitaxel au CHU de Limoges

LIMOGES-BU Médecine pharmacie (870852108) / SudocSudocFranceF

Le rôle du pharmacien d'officine dans la prise en charge du patient atteint de cancer

LIMOGES-BU Médecine pharmacie (870852108) / SudocLYON1-BU Santé (693882101) / SudocSudocFranceF

MENOPAUSE CHIMIO-INDUITE ET CANCER DU SEIN

LIMOGES-BU Médecine pharmacie (870852108) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF