Emilie Gadéa

Weight change during chemotherapy changes the prognosis in non metastatic breast cancer for the worse

BackgroundWeight change during chemotherapy is reported to be associated with a worse prognosis in breast cancer patients, both with weight gain and weight loss. However, most studies were conducted prior to the common use of anthracycline-base chemotherapy and on North American populations with a mean BMI classified as overweight. Our study was aimed to evaluate the prognostic value of weight change during anthracycline-based chemotherapy on non metastatic breast cancer (European population) with a long term follow-up.MethodsPatients included 111 women diagnosed with early stage breast cancer and locally advanced breast cancer who have been treated by anthracycline-based chemotherapy regimen between 1976 and 1989. The relative percent weight variation (WV) between baseline and postchemotherapy treatment was calculated and categorized into either weight change (WV > 5%) or stable (WV < 5%). The median follow-up was 20.4 years [19.4 - 27.6]. Cox proportional hazard models were used to evaluate any potential association of weight change and known prognostic factors with the time to recurrence and overall survival.ResultsBaseline BMI was 24.4 kg/m2 [17.1 - 40.5]. During chemotherapy treatment, 31% of patients presented a notable weight variation which was greater than 5% of their initial weight.In multivariate analyses, weight change (> 5%) was positively associated with an increased risk of both recurrence (RR 2.28; 95% CI: 1.29-4.03) and death (RR 2.11; 95% CI: 1.21-3.66).ConclusionsOur results suggest that weight change during breast-cancer chemotherapy treatment may be related to poorer prognosis with higher reccurence and higher mortality in comparison to women who maintained their weight.

The New Combination Docetaxel, Prednisone and Curcumin in Patients with Castration-Resistant Prostate Cancer: A Pilot Phase II Study

Objectives: Favorable phase I results justified this pilot phase II study to assess the efficacy of docetaxel/curcumin in patients with chemotherapy-naive metastatic castration-resistant prostate cancer (CRPC). Methods: Thirty patients with progressing CRPC and a rising prostate-specific antigen (PSA) received docetaxel/prednisone in standard conditions for 6 cycles in combination with per os curcumin, 6,000 mg/day (day -4 to day +2 of docetaxel). The co-primary endpoint was the overall response rate determined by PSA and target assessments. An ancillary study assessed the seric values of chromogranin A (CgA) and neuron-specific enolase (NSE). Results: Twenty-six patients received the scheduled treatment, 2 progressed and 2 died before the end of treatment. A PSA response was observed in 59% of patients (14% of PSA normalization) and achieved within the first three cycles for 88% of responders. Partial response was reached for 40% of evaluable patients. The regimen was well tolerated, and no adverse event was attributed to curcumin. Twenty patients were 100% curcumin compliant. The PSA level and objective response rate were not correlated with the serum values of CgA and NSE. Conclusion: This study produced additional data on curcumin as a treatment for cancer, with a high response rate, good tolerability and patient acceptability, justifying the interest to conduct a randomized trial.

Importance of metabolic changes induced by chemotherapy on prognosis of early‐stage breast cancer patients: a review of potential mechanisms

Weight variation has been reported as a side effect of chemotherapy treatment in early breast cancer patients and has been identified as a factor of poor prognosis. Causes of weight variation during chemotherapy and mechanisms involved in the poor prognosis have been little studied. Here is reviewed the current knowledge about the main causes and mechanisms involved in body weight change. Special emphasis is placed on factors associated with weight variation which could potentially be involved in the risk of relapse in breast cancer survivors. In recent decades, some studies have investigated the causes of weight variation by studying energy balance of breast cancer patients during chemotherapy. Weight gain or loss may be the consequence of energy imbalance through different factors linked with chemotherapy, such as poor treatment tolerance, decreased muscle mass and function, or hormonal alterations. This results in body composition modifications in favour of fat gain and/or lean body mass loss. Increased adipose tissue, especially in the abdominal region, could induce metabolic disturbances such as insulin resistance, through various pathways involving adipokines. These molecules have growth properties and could therefore play a role in cancer relapse. Understanding such mechanisms is key to developing preventive strategies for improving the prognosis of early‐stage breast cancer patients.

Hibernoma: A Clinical Model for Exploring the Role of Brown Adipose Tissue in the Regulation of Body Weight?

CONTEXT Hibernoma is a rare benign tumor histologically similar to brown adipose tissue. Some studies reported weight loss in patients with this tumor; however, the mechanisms have never been investigated. OBJECTIVE The purpose of this study is to explore the impact of hibernoma resection on the whole-body metabolism. PATIENT AND METHODS A 68-year-old woman was examined after a weight loss of 10 kg in 6 months. Body composition, food intake, physical activity, blood levels of thyroid hormones, and lipid profile were assessed before surgery and during 1 year after surgery. The patients resting energy expenditure (REE) over time was compared to a control group of 18 matched healthy volunteers. RESULTS Within 1 year after hibernoma resection, the patient gained 15 kg of body weight. This was associated with fat mass gain (+41%), mainly in the abdominal region (+48%). The patient also developed hepatic nonalcoholic steatosis, mild hypertriglyceridemia, and reduced levels of high-density lipoproteins. REE increased during the dynamic phase of weight gain, compared to the presurgery measurement, and returned to baseline after 1 year. Food intake was increased by 37.5% 6 weeks after resection of the hibernoma and returned to baseline values within 6 months. CONCLUSIONS In our study conditions, hibernoma did not alter REE, but weight gain did. Specific physical activities and dietetic follow-ups are suggested for those patients to prevent excess fat mass gain and metabolic disorders after hibernoma resection. More studies should focus on hibernoma mechanisms inducing weight loss.

Valeur péjorative des variations de poids en cours de chimiothérapie dans le cancer du sein non métastatique : causes, mécanismes impliqués et stratégies préventives

Numerous studies have demonstrated that a significant change in weight during chemotherapy treatment was a factor of poor prognosis in early breast cancer women. However, the causes and mechanisms involved in this phenomenon are not fully known. This review summarizes current knowledge about the causes of energy imbalance during chemotherapy treatment and the mechanisms that have been proposed as responsible for the increased risk of relapse and death in this population. Current preventive strategies focus on physical activity programs but also on the use of metformin during and after chemotherapy.

Long-term Significance (15 years) of Pathological Complete Response after Dose-dense Neoadjuvant Chemotherapy in Breast Cancer

To the Editor: Chollet et al. have demonstrated that in using the dose-dense neoadjuvant regimen TNCF (THP-doxorubicin, vinorelbine, cyclophamide, and fluorouracile), pCR (pathological complete response) rate could up to 30% (1). PCR definition varied in the literature, and this variation makes the comparison between literatures very difficult. In general, pCR rate varies between 9% and 26% (2). This figure has never been widely surpassed with general treatments. Only nowadays, they are surpassed in some defined subsets (Her2, Triple Negative [TN] tumors) (3). Due to this high pCR rate, we think that it would be interesting to study the late survival outcome with a follow-up of 15 years and to discuss the validation of pCR as a surrogate end point for patient’s survival. Sixty-one breast cancer patients (Centre Jean Perrin, France) have been analyzed. Patient and tumor characteristics were shown in Table 1. The survival rate at 5 years is usually reported in the literature with neoadjuvant treatments. However, it is known with breast cancer that 5 years results are not sufficient to establish long-term survival due to late relapses, mainly in hormonal dependant tumors. In our current study, the first interest point was a long follow-up time for patient’s survival. The median was 14 years. Disease-Free Survival (DFS) and Overall survival (OS) rates at 10 years were 54% and 71%; at 15 years, were 46% and 69%, respectively. The main interest is the fact that pCR at surgery was still found to be an individual prognostic factor with long-term implication. Univariate and multivariate (COX model (4)) analysis (Table 2) shows that pCR in breast and the number of nodes involved can significantly predict DFS with a follow-up of 15 years. Moreover, these two factors were significantly related. We observed that patients who achieved pCR in breast have the best survival, and if pCR was failed, the number of involved nodes could predict DFS and OS (Fig. 1a, 1b). Rastogi et al. demonstrated that pCR in breast improved DFS and OS (5). On the contrary, some authors reported that pCR in nodes was a stronger prognostic predictor than pCR in breast (6,7). In addition, several investigators demonstrated that pCR both in breast and nodes can predict patient’s survival (8–10). According to these results, there are discrepancies about the role of pCR in nodes.

Prospective Study on Body Composition, Energy Balance and Biological Factors Changes in Post-menopausal Women with Breast Cancer Receiving Adjuvant Chemotherapy Including Taxanes

Abstract In breast cancer patients, weight and fat mass changes observed after chemotherapy have been related to poor prognosis but some recent works using modern chemotherapy failed to find this correlation with weight gain. In this study, the extent of changes in weight and body composition (DEXA, impedance) was characterized until six months after current chemotherapy, in 50 post-menopausal women with breast cancer. The evolution of factors contributing to the energy balance and some biological factors were also described. During chemotherapy, 20% of women lost weight due to both fat (−13.1% ± 10.3) and lean soft tissue mass loss (−3.6% ± 4.6). Twenty percent of women gained weight. No significant fat mass gain was observed in these women but significant water gain was highlighted. Six months later, women who gained weight presented a gain in fat mass (15.4% ± 19.0), especially in the abdominal region. Age and initial BMI were negatively correlated with fat mass in multivariate analyzes (r = 0.486, P = 0.0030). No significant variation of the glucose homeostasis, triglycerides, and HDL-Cholesterol was found six months after chemotherapy. These results do not suggest major adverse metabolic disturbances six months after modern chemotherapy and only a mild fat mass gain was observed in women who gained weight.

Weight Evolution During Endocrine Therapy for Breast Cancer in Postmenopausal Patients: Effect of Initial Fat Mass Percentage and Previous Adjuvant Treatments

Background Weight changes during adjuvant treatment for early‐stage breast cancer has been associated with a poor prognosis. The long‐term evolution of body composition during adjuvant treatment for breast cancer, in particular, endocrine therapy, is not well known, and new data on this topic are required. The present study assessed the evolution of weight and body composition among 33 postmenopausal breast cancer patients receiving endocrine therapy after standard adjuvant chemotherapy that included taxanes. Patients and Methods Dual‐energy x‐ray absorptiometry was used to measure the fat and lean body mass. Body water was assessed using multifrequency bioelectrical impedance analysis. The Hospital Anxiety and Depression questionnaire and the short version of the International Physical Activity Questionnaire were also administered. Results During endocrine therapy, 5 of the 33 patients (15.2%) lost weight and 12 (36.4%) gained weight. The overall average gain was 2.0 ± 5.5 kg (P = .04). During this period, the fat mass, lean body mass, and body water increased. The factors linked to fat mass gain included an excess fat mass (≥ 36%) before treatment and weight loss during chemotherapy. In the overall period of adjuvant cancer treatment, 30% of the population gained > 5% of their initial weight. The average gain was the same as that during the endocrine therapy period (2.0 ± 5.4 kg; P = .031) and was characterized by an increase in total lean body mass, mainly localized in the trunk region. Conclusion Endocrine therapy appears as a pivotal period in weight and body composition management. Overfat and obese patients and those who lose weight during chemotherapy were more subject to weight and fat mass gain during endocrine therapy. Micro‐Abstract Weight variations during treatment have been associated with a poor prognosis for early‐stage breast cancer patients. The study of body composition during adjuvant treatment is key to understanding this interaction. With a median follow‐up of 3 years after chemotherapy, our results showed a small weight gain but highlighted that the initial fatness in postmenopausal breast cancer patients promotes a longitudinal 3‐year weight gain.