Trastuzumab targets the extracellular domain of the HER2 protein. Adding trastuzumab to chemotherapy for patients with early-stage, HER2-positive breast cancer reduces the risk of recurrence and ...death, but is associated with cardiac toxicity. We investigated the long-term benefits and risks of adjuvant trastuzumab on breast cancer recurrence and cause-specific mortality.
We did a collaborative meta-analysis of individual patient data from randomised trials assessing chemotherapy plus trastuzumab versus the same chemotherapy alone. Randomised trials that enrolled women with node-negative or node-positive, operable breast cancer were included. We collected individual patient-level data on baseline characteristics, dates and sites of first distant breast cancer recurrence and any previous local recurrence or second primary cancer, and the date and underlying cause of death. Primary outcomes were breast cancer recurrence, breast cancer mortality, death without recurrence, and all-cause mortality. Standard intention-to-treat log-rank analyses, stratified by age, nodal status, oestrogen receptor (ER) status, and trial yielded first-event rate ratios (RRs).
Seven randomised trials met the inclusion criteria, and included 13 864 patients enrolled between February, 2000, and December, 2005. Mean scheduled treatment duration was 14·4 months and median follow-up was 10·7 years (IQR 9·5 to 11·9). The risks of breast cancer recurrence (RR 0·66, 95% CI 0·62 to 0·71; p<0·0001) and death from breast cancer (0·67, 0·61 to 0·73; p<0·0001) were lower with trastuzumab plus chemotherapy than with chemotherapy alone. Absolute 10-year recurrence risk was reduced by 9·0% (95% CI 7·4 to 10·7; p<0·0001) and 10-year breast cancer mortality was reduced by 6·4% (4·9 to 7·8; p<0·0001), with a 6·5% reduction (5·0 to 8·0; p<0·0001) in all-cause mortality, and no increase in death without recurrence (0·4%, –0·3 to 1·1; p=0·35). The proportional reduction in recurrence was largest in years 0–1 after randomisation (0·53, 99% CI 0·46 to 0·61), with benefits persisting through years 2–4 (0·73, 0·62 to 0·85) and 5–9 (0·80, 0·64 to 1·01), and little follow-up beyond year 10. Proportional recurrence reductions were similar irrespective of recorded patient and tumour characteristics, including ER status. The more high risk the tumour, the larger the absolute reductions in 5-year recurrence (eg, 5·7% 95% CI 3·1 to 8·3, 6·8% 4·7 to 9·0, and 10·7% 7·7 to 13·6 in N0, N1–3, and N4+ disease).
Adding trastuzumab to chemotherapy for early-stage, HER2-positive breast cancer reduces recurrence of, and mortality from, breast cancer by a third, with worthwhile proportional reductions irrespective of recorded patient and tumour characteristics.
Cancer Research UK, UK Medical Research Council.
Summary
Background
De novo non‐alcoholic fatty liver disease (NAFLD) in liver‐transplanted patients for cirrhosis not due to non‐alcoholic steatohepatitis (NASH) is becoming a growing phenomenon.
...Aims
We performed a systematic review and evaluated the prevalence of this event and possible associated factors.
Methods
A literature search in medical databases (PubMed, MEDLINE/OVIDSP, Science Direct and EMBASE) was performed in March 2017. Relevant publications were identified in most important databases. We estimated the pooled prevalence of NAFLD and NASH in patients with liver transplant. The data have been expressed as proportions/percentages, and 95% confidence intervals (CI) were calculated, using the inverse variance method. Odd ratios (OR) and 95% confidence intervals (95% CI) were estimated.
Results
Twelve studies were selected, enrolling 2166 subjects overall undergoing post‐liver transplant biopsy. The pooled weighted prevalence of de novo NAFLD was 26% (95% CI 20%‐31%). The pooled weighted prevalence of NASH was 2% (95% CI 0%‐3%). The highest prevalences of de novo NAFLD were found for patients transplanted for alcoholic cirrhosis (37%) and cryptogenic cirrhosis (35%) and for patients taking tacrolimus (26%). Tacrolimus showed a risk of NAFLD similar to ciclosporin (OR = 1.02, 95% CI 0.3‐3.51).
Conclusions
Patients undergoing liver transplant are more prone to experience diabetes, hypertension or dyslipidaemia, and NAFLD may be an important element in this context. In this study, we show how the prevalence of NASH tends to remain significant and similar to the general population. Moreover, this study suggests a possible association with specific transplant indications. Further studies are required to confirm these findings.
Summary
Background
International guidelines rate class III (morbid) obesity (body mass index BMI≥40 kg/m2) as a relative contraindication for liver transplantation (LT) requiring further research. ...Moreover, data on the mortality risk in candidates with a BMI: 30‐34.9 and 35‐39.9 kg/m2 (class I and class II obesity, respectively) are weak.
Aim
To compare post‐operative complications and mortality risks in all obese candidates vs candidates with a BMI: 18.5‐29.9 (normal/overweight) assumed as controls.
Methods
We searched the Cochrane library, PubMed, Scopus, Web‐of‐Science and article reference lists, restricted to the English language, and selected cohort studies analysing the following outcomes: all‐causes mortality (at 30 days, 1‐2‐3‐5 years), post‐operative and cardiopulmonary complications, hospital and intensive care unit (ICU) length of stay. Two reviewers independently extracted the studies data and a third one resolved discrepancies.
Results
Twenty‐four studies comprising 132 162 patients met the inclusion criteria. As compared to controls, mortality risk was increased at all time‐periods (except at 3 years) for a BMI≥40, at 30 days for a BMI: 30‐34.9 and in none of the considered time‐periods for a BMI: 35‐39.9. Post‐operative complications were significantly higher for a BMI>30 and 30‐34.9. Due to the shortage/absence of data, we evaluated cardiopulmonary complications, hospital and ICU length of stay only in the BMI≥30 category. In these patients, only cardiopulmonary complications were increased as compared to controls.
Conclusions
Morbid obesity has an impact on patients’ survival after LT. However, since even a BMI>30 increases post‐transplant complications, new strategies should be included in the LT programme to favour weight loss in all obese candidates.
Linked ContentThis article is linked to Townsend and Newsome et al and Barone, Barone et al and Liu et al papers. To view these articles visit https://doi.org/10.1111/apt.14179, https://doi.org/10.1111/apt.14195, https://doi.org/10.1111/apt.14446 and https://doi.org/10.1111/apt.14425.
The 15th St. Gallen International Breast Cancer Conference 2017 in Vienna, Austria reviewed substantial new evidence on loco-regional and systemic therapies for early breast cancer. Treatments were ...assessed in light of their intensity, duration and side-effects, seeking where appropriate to escalate or de-escalate therapies based on likely benefits as predicted by tumor stage and tumor biology. The Panel favored several interventions that may reduce surgical morbidity, including acceptance of 2 mm margins for DCIS, the resection of residual cancer (but not baseline extent of cancer) in women undergoing neoadjuvant therapy, acceptance of sentinel node biopsy following neoadjuvant treatment of many patients, and the preference for neoadjuvant therapy in HER2 positive and triple-negative, stage II and III breast cancer. The Panel favored escalating radiation therapy with regional nodal irradiation in high-risk patients, while encouraging omission of boost in low-risk patients. The Panel endorsed gene expression signatures that permit avoidance of chemotherapy in many patients with ER positive breast cancer. For women with higher risk tumors, the Panel escalated recommendations for adjuvant endocrine treatment to include ovarian suppression in premenopausal women, and extended therapy for postmenopausal women. However, low-risk patients can avoid these treatments. Finally, the Panel recommended bisphosphonate use in postmenopausal women to prevent breast cancer recurrence. The Panel recognized that recommendations are not intended for all patients, but rather to address the clinical needs of the majority of common presentations. Individualization of adjuvant therapy means adjusting to the tumor characteristics, patient comorbidities and preferences, and managing constraints of treatment cost and access that may affect care in both the developed and developing world.
CD73 is an ecto-enzyme that promotes tumor immune escape through the production of immunosuppressive extracellular adenosine in the tumor microenvironment. Several CD73 inhibitors and adenosine ...receptor antagonists are being evaluated in phase I clinical trials.
Full-face sections from formalin-fixed paraffin-embedded primary breast tumors from 122 samples of triple-negative breast cancer (TNBC) from the BIG 02-98 adjuvant phase III clinical trial were included in our analysis. Using multiplex immunofluorescence and image analysis, we assessed CD73 protein expression on tumor cells, tumor-infiltrating leukocytes and stromal cells. We investigated the associations between CD73 protein expression with disease-free survival (DFS), overall survival (OS) and the extent of tumor immune infiltration.
Our results demonstrated that high levels of CD73 expression on epithelial tumor cells were significantly associated with reduced DFS, OS and negatively correlated with tumor immune infiltration (Spearman’s R=−0.50, P<0.0001). Patients with high levels of CD73 and low levels of tumor-infiltrating leukocytes had the worse clinical outcome.
Taken together, our study provides further support that CD73 expression is associated with a poor prognosis and reduced anti-tumor immunity in human TNBC and that targeting CD73 could be a promising strategy to reprogram the tumor microenvironment in this BC subtype.
The 2012 IMPAKT task force investigated the medical usefulness of current methods for the classification of breast cancer into the ‘intrinsic’ molecular subtypes (luminal A, luminal B, basal-like and ...HER2). A panel of breast cancer and/or gene expression profiling experts evaluated the analytical validity, clinical validity and clinical utility of two approaches for molecular subtyping of breast cancer: the prediction analysis of microarray (PAM)50 assay and an immuno-histochemical (IHC) surrogate panel including oestrogen receptor (ER), HER2 and Ki67. The panel found the currently available evidence on the analytical validity and clinical utility of Ki67 based on a 14% cut-off and PAM50 to be inadequate. The majority of the working group members found the available evidence on the analytical validity, clinical validity and clinical utility of ER/HER2 to be convincing. The panel concluded that breast cancer classification into molecular subtypes based on the IHC assessment of ER, HER2 and Ki67 with a 14% cut-off and on the PAM50 test does not provide sufficiently robust information to modify systemic treatment decisions, and recommended the use IHC for ER and HER2 for the identification of clinically relevant subtypes of breast cancers. Methods for breast cancer classification into molecular subtypes should, however, be incorporated into clinical trial design.
There are conflicting data on the effect of a gluten-free diet (GFD) on the nutritional status of celiac patients. In the present study, we evaluated, in adult celiac patients, the influence of a ...long-term, strictly GFD on their nutritional status and compared it with matched healthy volunteers.
Our study included 39 celiac patients and 39 healthy volunteers. The body mass index (BMI) of patients and controls was evaluated at enrollment, while the patients' BMI before the GFD was retrieved from clinical records. In addition, at enrollment, in both groups, we compared BMI, fat mass (FM), bone mineral density (BMD), as well as their dietary intake, recorded on a 7-day diary.
At the time of diagnosis, the majority of celiac patients (82.0%) had a normal BMI or were overweight, while 10.3% were malnourished. After the GFD, patients with a normal BMI showed a significant weight increase (P=0.002), but none of them switched in the overweight or obese category. Two (50%) of the four malnourished patients achieved a normal BMI. Controls and patients on a GFD had a similar BMI, FM, BMD and total calorie intake, but the amount of lipids and fiber intake was significantly different in the two groups (P=0.003 and P<0.0001, respectively).
Our study demonstrates that a GFD is able to improve the nutritional status of celiac patients without inducing overweight or obesity. Our findings are related to a celiac population adopting a GFD based on a Mediterranean-type diet.
PDF
