The initial hormone receptor/HER2 subtype is the main determinator of subtype discordance in advanced breast cancer: a study of the SONABRE registry.

PURPOSE: The hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) are the main parameters in guiding systemic treatment choices in breast cancer, but can change during the disease course. This study aims to evaluate the biopsy rate and receptor subtype discordance rate in patients diagnosed with advanced breast cancer (ABC). METHODS: Patients diagnosed with ABC in seven hospitals in 2007-2018 were selected from the SOutheast Netherlands Advanced BREast cancer (SONABRE) registry. Multivariable logistic regression analyses were performed to identify factors influencing biopsy and discordance rates. RESULTS: Overall, 60% of 2854 patients had a biopsy of a metastatic site at diagnosis. One of the factors associated with a reduced biopsy rate was the HR + /HER2 + primary tumor subtype (versus HR + /HER2- subtype: OR = 0.68; 95% CI: 0.51-0.90). Among the 748 patients with a biopsy of the primary tumor and a metastatic site, the overall receptor discordance rate was 18%. This was the highest for the HR + /HER2 + primary tumor subtype, with 55%. In 624 patients with metachronous metastases, the HR + /HER2 + subtype remained the only predictor significantly related to a higher discordance rate, irrespective of prior (neo-)adjuvant therapies (OR = 7.49; 95% CI: 3.69-15.20). CONCLUSION: The HR + /HER2 + subtype has the highest discordance rate, but the lowest biopsy rate of all four receptor subtypes. Prior systemic therapy was not independently related to subtype discordance. This study highlights the importance of obtaining a biopsy of metastatic disease, especially in the HR + /HER2 + subtype to determine the most optimal treatment strategy.

Normal protein intake is required for body weight loss and weight maintenance, and elevated protein intake for additional preservation of resting energy expenditure and fat free mass.

Energy-restricted high-protein diets (HPDs) have shown favorable results for body weight (BW) management, yet studies differ in their outcomes depending on the dietary protein content. Our objective was to determine the effects of dietary protein content on BW loss-related variables during a 6-mo energy restriction with the use of diets containing protein at the level of requirement [normal-protein diet (NPD), 0.8 g · kg BW(-1) (.) d(-1)] and above (HPD, 1.2 g · kg BW(-1) (.) d(-1)). In overweight and obese participants (24 men and 48 women), BW, body composition, and metabolic responses were assessed before and after subsequent energy intakes of 100, 33, and 67% of the original individual daily energy requirements. Protein intake was consistent in the NPD (0.8 ± 0.3 g · kg BW(-1) (.) d(-1)) and HPD (1.2 ± 0.3 g · kg BW(-1) (.) d(-1)) groups throughout the study (P < 0.001). BMI and body fat mass similarly decreased in the NPD and HPD groups (P < 0.01). Fat free mass (FFM), resting energy expenditure (REE) compared with predicted REE, and diastolic blood pressure (DBP) changed favorably with the HPD compared with the NPD group after BW loss (P < 0.05). A NPD of 0.8 g · kg BW(-1) (.) d(-1) is sufficient for BW management, whereas a HPD of 1.2 g · kg BW(-1) (.) d(-1) is necessary for preservation of REE and a stronger initial sparing effect of FFM and lowering of DBP.

Embracing change: practical and theoretical considerations for successful implementation of technology assisting upper limb training in stroke.

BACKGROUND: Rehabilitation technology for upper limb training of stroke patients may play an important role as therapy tool in future, in order to meet the increasing therapy demand. Currently, implementation of this technology in the clinic remains low. This study aimed at identifying criteria and conditions that people, involved in development of such technology, should take into account to achieve a (more) successful implementation of the technology in the clinic. METHODS: A literature search was performed in PubMed and IEEE databases, and semi-structured interviews with therapists in stroke rehabilitation were held, to identify criteria and conditions technology should meet to facilitate (implementation of) technology-assisted arm-hand skills training in rehabilitation therapy of stroke patients. In addition, an implementation strategy frequently applied in general health care was used to compose a stepwise guidance to facilitate successful implementation of this technology in therapy of stroke patients. Implementation-related criteria mentioned by therapists during the interviews were integrated in this guidance. RESULTS: Results indicate that, related to therapy content, technology should facilitate repetition of task-related movements, tailored to the patient and patient's goals, in a meaningful context. Variability and increasing levels of difficulty in exercises should be on offer. Regarding hardware and software design of technology, the system should facilitate quick familiarisation and be easily adjustable to individual patients during therapy by therapists (and assistants). The system should facilitate adaptation to individual patients' needs and their progression over time, should be adjustable as to various task-related variables, should be able to provide instructions and feedback, and should be able to document patient's progression. The implementation process of technology in the clinic is provided as a stepwise guidance that consists of five phases therapists have to go through. The guidance includes criteria and conditions that motivate therapists, and make it possible for them, to actually use technology in their daily clinical practice. CONCLUSIONS: The reported requirements are important as guidance for people involved in the development of rehabilitation technology for arm-hand therapy of stroke patients. The stepwise guide provides a tool for facilitating successful implementation of technology in clinical practice, thus meeting future therapy demand.

Effects of a supra-sustained gelatin-milk protein diet compared with (supra-)sustained milk protein diets on body-weight loss.

Diets higher in protein content result in increased satiety and energy expenditure. In the short term, gelatin showed stronger hunger suppression and less subsequent energy intake compared with other proteins. The present study investigated whether a supra-sustained gelatin-milk protein (GMP) diet promotes weight loss compared with a sustained milk protein (SMP) diet and a supra-sustained milk protein (SSMP) diet during an 8-week diet period. A total of seventy-two healthy subjects (31·2 (sd 4·8) kg/m2; 43 (sd 10) years) followed one of the three diets in a subject-specific amount: SMP, SSMP or GMP diet. During weeks 1-4, energy intake was 100 % of individual energy requirement: 10, 40 and 50 % of energy (En %) as protein, fat and carbohydrate, respectively (SMP diet), and 20, 30 and 50 En % as protein, fat and carbohydrate, respectively (SSMP diet or GMP diet). During weeks 5-8, energy intake was 33 % of individual energy requirement: 30, 35 and 35 En % as protein, fat and carbohydrate, respectively (SMP diet), and 60, 5 and 35 En % as protein, fat and carbohydrate, respectively (SSMP diet or GMP diet). Thus, absolute protein intake was kept constant throughout per subject. Significant decreases in BMI (P < 0·0001) were similar between the GMP ( - 1·7 (sd 0·5) kg/m2) and the SMP ( - 2·1 (sd 0·8) kg/m2) and SSMP ( - 1·6 (sd 0·5) kg/m2) diets. Decreases in fat-free mass (FFM), fat mass (FM) and FM %, and increases in FFM % were similar between the GMP and both control diets. Changes in RQ differed (P < 0·05) between the GMP ( - 0·01 (sd 0·06)) and SSMP ( - 0·04 (sd 0·04)) diets. Changes in HDL concentrations differed (P < 0·05) between the GMP ( - 0·21 (sd 0·18) mmol/l) and the SMP and SSMP diets ( - 0·08 (sd 0·18) mmol/l and - 0·09 (sd 0·26) mmol/l, respectively). In conclusion, a gelatin-milk protein diet does not induce more beneficial effects during an 8-week weight-loss period compared with a SMP or SSMP diet.

Efficacy of α-lactalbumin and milk protein on weight loss and body composition during energy restriction.

Our objective was to examine whether elevated α-lactalbumin (αlac) protein intake compared to elevated supra sustained milk protein (SSP) and sustained milk protein (SP) intake results into a difference in body weight and body composition over a 6-month energy-restriction intervention. Body weight, body composition, resting energy expenditure (REE), satiety and blood- and urine-parameters of 87 subjects (BMI 31 ± 5 kg/m(2) and fat percentage 40 ± 8%) were assessed before and after daily energy intakes of 100, 33, and 67% for 1, 1, and 2 months respectively (periods 1, 2, and 3), with protein intake from meal replacements and 2 months of 67% with ad libitum protein intake additional to the meal replacements (period 4). The diets resulted in 0.8 ± 0.3 g/kg body mass (BM) for SP and significant higher protein intake (24-h nitrogen) of 1.2 ± 0.3 and 1.0 ± 0.3 g/kgBM for SSP and αlac (P < 0.05). Body weight and fat percentage was decreased in all groups after 6 months (SP -7 ± 5 kg and -5 ± 3%; SSP -6 ± 3 kg and -5 ± 3%; αlac -6 ± 4 kg and -4 ± 4%, P < 0.001; there was no significant group by time difference). Furthermore, sparing of fat-free mass (FFM) and preservation of REE in function of FFM during weight loss was not significantly different between the αlac-group and the SSP- and SP-groups. In conclusion, the efficacy of αlac in reduction of body weight and fat mass (FM), and preservation of FFM does not differ from the efficacy of similar daily intakes of milk protein during 6 months of energy restriction.

Single-protein casein and gelatin diets affect energy expenditure similarly but substrate balance and appetite differently in adults.

Increasing the protein content of a diet results in increased satiety and energy expenditure (EE). It is not clear whether the magnitude of these effects differs between proteins differing in concentrations of indispensable amino acids (IAA). We hypothesized that a protein lacking IAA may stimulate appetite suppression and EE and may limit positive protein balance. Therefore, we compared appetite, EE, and substrate balances between gelatin (incomplete protein) and casein (complete protein) in single-protein diets with either 25 or 10% of energy (En%) from protein. During a 36-h stay in a respiration chamber, 23 healthy men (n = 11) and women (n = 12) (BMI, 22.2 +/- 2.3 kg/m(2); age, 25 +/- 7 y) consumed 4 isoenergetic diets: 25 En% (25/20/55 En% protein/fat/carbohydrate) and 10 En% (10/35/55 En% protein/fat/carbohydrate) casein or gelatin diet in a randomized crossover design. For 3 d before the study, participants consumed a diet at home with similar macronutrient distribution as the diet they would receive during the subsequent stay in the chamber. Hunger was suppressed 44% more (P < 0.05) and protein balance was more negative when consuming the 10 En% gelatin diet (-0.17 +/- 0.03 MJ/d) compared with the 10 En% casein diet (-0.07 +/- 0.03 MJ/d; P < 0.05); carbohydrate and fat balances did not differ between the treatments. EE did not differ when participants consumed the 25 En% or 10 En% diets. Participants were in higher protein balance (0.56 +/- 0.05 vs. 0.30 +/- 0.04 MJ/d; P < 0.0001), lower carbohydrate balance (0.86 +/- 0.14 vs. 1.37 +/- 0.17 MJ/d; P < 0.01), and similar negative fat balance when they consumed the 25 En% casein compared with the 25 En% gelatin diet. In conclusion, when we compared the effects of an incomplete protein (gelatin) and a complete protein (casein) at 2 concentrations over 36 h, gelatin resulted in a greater appetite suppression; casein caused a greater positive (smaller negative) protein balance, and effects on EE did not differ. In terms of weight loss for people with obesity, the greater hunger-suppressing effect of gelatin may play a role in reducing energy intake if this effect is maintained when consuming a gelatin diet in the long term. In addition, long-term use of casein may contribute to preservation of fat-free mass.

Dose-dependent satiating effect of whey relative to casein or soy.

Dietary protein plays a role in body weight regulation, partly because of its effects on appetite. The objective was to compare the effects of high or normal casein-, soy-, or whey-protein breakfasts on appetite, specific hormones, amino acid responses and subsequent energy intake. Twenty-five healthy subjects (mean+/-SEMBMI:23.9+/-0.3 kg/m2; age:22+/-1 years) received standardized breakfasts: custards with either casein-, soy, or whey-protein with either 10/55/35 (normal) or 25/55/20 (high)En% protein/carbohydrate/fat in a randomized, single-blind design. Appetite profile (Visual Analogue Scales) and amino acid concentrations were determined for 4 h whereas plasma glucose, insulin, active Glucagon-like Peptide 1 (GLP-1), and active ghrelin concentrations were determined for 3 h; the sensitive moment for lunch was determined. Subjects returned for a second set of experiments and received the same breakfasts, ad lib lunch was offered 180 min later; energy intake (EI) was assessed. At 10En%, whey decreased hunger more than casein or soy (p <0.05), coinciding with higher leucine, lysine, tryptophan, isoleucine, and threonine responses (p<0.05). At 25En% there were no differences in appetite ratings. Whey triggered the strongest responses in concentrations of active GLP-1 (p<0.05) and insulin (p<0.05) compared with casein and/or soy. There were no differences in EI. In conclusion, differences in appetite ratings between different proteins appeared at a normal concentration; at 10En% whey-protein decreased hunger more than casein- or soy-protein. At 25En% whey-protein triggered stronger responses in hormone concentrations than casein- or soy-protein. The results suggest that a difference in appetite ratings between types of protein appears when certain amino acids are above and below particular threshold values.

A breakfast with alpha-lactalbumin, gelatin, or gelatin + TRP lowers energy intake at lunch compared with a breakfast with casein, soy, whey, or whey-GMP.

BACKGROUND & AIMS: Dietary protein plays a role in body weight regulation, partly due to its effects on satiety. The objective was to compare the effects of casein-, soy-, whey-, whey without glycomacropeptide (GMP)-, alpha-lactalbumin-, gelatin-, or gelatin with tryptophan (TRP)-protein breakfasts at two concentrations on subsequent satiety and energy intake (EI). METHODS: Twenty-four healthy subjects (mean+/-SEM BMI: 24.8+/-0.5 kg/m(2); age: 25+/-2 years) received a breakfast; a custard with casein, soy, whey, whey-GMP, alpha-lactalbumin, gelatin, or gelatin+TRP as protein source with either 10/55/35 (normal) or 25/55/20 (high) En% protein/carbohydrate/fat in a randomized, single-blind design. At the precedingly determined time point for lunch, 180 min, subjects were offered an ad lib lunch. Appetite profile (Visual Analogue Scales, VAS) and EI were determined. RESULTS: Both at the level of 10 and 25 En% from protein, EI at lunch was approximately 20% lower after an alpha-lactalbumin or gelatin (+TRP) breakfast (2.5+/-0.2 MJ) compared with after a casein, soy, or whey-GMP breakfast (3.2+/-0.3 MJ, p<0.05). Appetite ratings at 180 min differed 15-25 mm (approximately 40%, p<0.05) between types of protein. Differences in EI were a function of differences in appetite ratings (R(2)=0.4, p<0.001). CONCLUSIONS: Different proteins (alpha-lactalbumin, gelatin, gelatin+TRP) that are approximately 40% more satiating than other proteins (casein, soy, whey, whey-GMP) induce a related approximately 20% reduction of subsequent energy intake.

Effects of high and normal soyprotein breakfasts on satiety and subsequent energy intake, including amino acid and 'satiety' hormone responses.

BACKGROUND: The role of dietary protein in short term satiety is of interest with respect to body weight regulation. AIM: To compare the effects of a high versus a normal soyprotein breakfast on satiety and subsequent energy intake (EI), including 'satiety' hormones and plasma amino acid responses. METHODS: Twenty-five healthy subjects (mean +/- SEM, BMI: 23.9 +/- 0.3 kg/m(2); age: 22 +/- 1 years) received a subject-specific standardized breakfast: a custard with soy as single protein type with either 10/55/35 (normal-protein) or 25/55/20 (high-protein) En% protein/carbohydrate/fat in a randomized, single-blind design. Appetite profile (Visual Analogue Scale, VAS), plasma glucose, insulin, Glucagon-like Peptide 1, ghrelin, and amino acid concentrations were determined for 4 h, determining the sensitive time point to assess EI. Since at 180 min glucose and insulin concentrations still were significantly different, in a second set of experiments subjects received an ad lib lunch at 180 min after the breakfasts; EI was assessed. RESULTS: Overall the 25 En% soy-custard was rated as being more satiating than the 10 En% soy-custard (P < 0.01) and there was a difference at 20 min after breakfast (64 +/- 5 vs. 52 +/- 5 mmVAS, P < 0.05), related to higher postprandial taurine concentrations (P < 0.05). Insulin response was increased more after the 25 En% than after the 10 En% soy-custard (AUC: 7,520 +/- 929 vs. 4,936 +/- 468 mU/l h, P < 0.001). There was no difference in EI (25 En%: 3,212 +/- 280 kJ vs. 10 En%: 3,098 +/- 286 kJ, ns). CONCLUSION: A high soyprotein breakfast is more satiating than a normal soyprotein breakfast related to elevated taurine and insulin concentrations.

Comparison of 2 diets with either 25% or 10% of energy as casein on energy expenditure, substrate balance, and appetite profile.

BACKGROUND: An increase in the protein content of a diet results in an increase in satiety and energy expenditure. It is not clear to what extent a specific type of protein has such effects. OBJECTIVE: The objective was to compare the effects of 2 diets with either 25% or 10% of energy from casein (25En% and 10En% casein diets), as the only protein source, on energy expenditure, substrate balance, and appetite profile. DESIGN: During a 36-h stay in a respiration chamber, 24 healthy subjects [12 men and 12 women, body mass index (in kg/m(2)) of 22.4 +/- 2.4, age 25 +/- 7 y] received isoenergetic diets according to subject-specific energy requirements: 25En% diet (25%, 20%, and 55% of energy as protein, fat, and carbohydrate, respectively) and 10En% diet (10%, 35%, and 55% of energy as protein, fat, and carbohydrate, respectively) in a randomized crossover design. Three days before the diets began, the subjects consumed a similar diet at home. Energy expenditure, substrate oxidation, and appetite scores were measured. RESULTS: The 25En% casein diet resulted in a 2.6% higher 24-h total energy expenditure (9.30 +/- 0.24 compared with 9.07 +/- 0.24 MJ/d; P < 0.01) and a higher sleeping metabolic rate (6.74 +/- 0.16 compared with 6.48 +/- 0.17 MJ/d; P < 0.001) than did the 10En% casein diet. With the 25En% casein diet, compared with the 10En% casein diet, the subjects were in positive protein balance (0.57 +/- 0.05 compared with -0.08 +/- 0.03 MJ/d; P < 0.0001) and negative fat balance (-0.83 +/- 0.14 compared with 0.11 +/- 0.17 MJ/d; P < 0.0001), whereas positive carbohydrate balances were not significantly different between diets. Satiety was 33% higher with the 25En% casein diet than with the 10En% casein diet (P < 0.05). CONCLUSION: A 25En% casein diet boosts energy expenditure, protein balance, satiety, and negative fat balance, which is beneficial to body weight management.

Effects of complete whey-protein breakfasts versus whey without GMP-breakfasts on energy intake and satiety.

AIM: To compare the effects of whey versus whey without glycomacropeptide (GMP) in a high and a normal amount of protein in a breakfast custard on satiety and energy intake (EI), taking concentrations of amino acids (AA), glucose, insulin, glucagon-like peptide 1 (GLP-1) and ghrelin into account. METHODS: Twenty-five healthy subjects (mean+/-S.E.M., BMI: 23.9+/-0.3 kg/m(2); age: 22+/-1 years) received a breakfast containing whey or whey without GMP as protein type with 10/55/35 or 25/55/20 En% protein/carbohydrate/fat in a randomized, single-blind design. Appetite profile (Visual Analogue Scale, VAS), glucose, insulin, GLP-1, ghrelin and AA concentrations were measured, and the adequate moment for ad libitum lunch was determined based on differences in ghrelin concentration. In a second set of experiments subjects received the same breakfasts; ad libitum lunch was offered at the pre-determined moment. RESULTS: After a breakfast with 25 En% protein increases in insulin and GLP-1 and decreases in ghrelin concentrations were larger; increases in satiety ratings were lower than after 10 En% (p<0.05); there was a treatment x time interaction effect on glucose and insulin concentrations (p<0.001). After a breakfast with whey without GMP insulin concentrations were increased more than after whey (p<0.05). EI at lunch was lower after whey than after whey without GMP (2877+/-165 kJ versus 3208+/-178 kJ, p<0.05), coinciding with more increased concentrations of serine, threonine, alanine, alpha-aminobutyric acid and isoleucine (p<0.05). CONCLUSION: GMP as a whey-fraction reduced energy intake coinciding with increased concentrations of certain amino acids, irrespective of the concentration of whey-protein. Although between different concentrations of whey-protein differences in hormone responses were observed, these were unrelated to satiety ratings or energy intake.

Acute effects of breakfasts containing alpha-lactalbumin, or gelatin with or without added tryptophan, on hunger, 'satiety' hormones and amino acid profiles.

Proteins are the most satiating macronutrients. Tryptophan (TRP) may contribute to the satiating effect, as it serves as a precursor for the anorexigenic neurotransmitter serotonin. To address the role of TRP in the satiating properties of dietary protein, we compared three different breakfasts, containing either alpha-lactalbumin (high in TRP), gelatin (low in TRP) or gelatin with added TRP (gelatin+TRP, high in TRP), on appetite. Twenty-four subjects (22-29 kg/m2; aged 19-37 years) received a subject-specific breakfast at t = 0 with 10, 55 and 35 % energy from protein, carbohydrate and fat respectively in a randomised, single-blind design. Hunger, glucagon-like peptide (GLP)-1, ghrelin, amino acid concentrations and energy intake during a subsequent lunch were determined. Suppression of hunger was stronger 240 min after the breakfast with alpha-lactalbumin compared with gelatin and gelatin+TRP. Total plasma amino acid concentrations were lower with alpha-lactalbumin compared with gelatin with or without TRP (from t = 180-240 min). TRP concentrations were higher after alpha-lactalbumin than after gelatin with or without TRP from t = 0-100 min, whereas from t = 100-240 min, TRP concentrations were lower after gelatin than after alpha-lactalbumin and gelatin+TRP. The plasma ratio of TRP to other large neutral amino acids (LNAA) was, only at t = 100 min, lower after gelatin+TRP than after the other breakfasts. Plasma amino acid responses, TRP concentrations and TRP:LNAA ratios were not correlated with hunger. GLP-1 and ghrelin concentrations were similar for all diets. Energy intake during a subsequent lunch was similar for all diets. Summarised, an alpha-lactalbumin breakfast suppresses hunger more than a gelatin or gelatin+TRP breakfast. This cannot be explained by (possible) differences found in TRP concentrations and TRP:LNAA ratios in the breakfasts and in plasma, as well as in circulating total amino acids, GLP-1 and ghrelin.

Comparison of the effects of a high- and normal-casein breakfast on satiety, 'satiety' hormones, plasma amino acids and subsequent energy intake.

The present study compared the effects of a high- and normal-casein-protein breakfast on satiety, 'satiety' hormones, plasma amino acid responses and subsequent energy intake. Twenty-five healthy subjects (BMI 23.9 (SEM 0.3) kg/m2; age 22 (SEM 1) years) received a subject-specific standardised breakfast (20% of daily energy requirements): a custard with casein as the single protein source with either 10, 55 and 35 (normal-casein breakfast) or 25, 55 and 20 (high-casein breakfast) % of energy (En%) from protein, carbohydrate and fat respectively in a randomised, single-blind design. Appetite profile (visual analogue scale; VAS), plasma glucose, insulin, glucagon-like peptide 1, ghrelin and amino acid concentrations were determined for 4 h; here the sensitive moment in time for lunch was determined. Subjects came for a second set of experiments and received the same custards for breakfast, and an ad libitum lunch was offered at 180 min after breakfast; energy intake was assessed. There were increased scores of fullness and satiety after the 25 En% casein-custard compared with the 10 En% casein-custard, particularly at 180 min (26 (SEM 4) v. 11 (SEM 5) mm VAS; P<0.01) and 240 min (13 (SEM 5) v. -1 (SEM 5) mm VAS; P<0.01). This coincided with prolonged elevated plasma amino acid concentrations; total amino acids and branched-chain amino acids were higher after the 25 En% casein-custard compared with the 10 En% casein-custard at 180 and 240 min (P<0.001). There was no difference in energy intake (3080 (SEM 229) v. 3133 (SEM 226) kJ for 25 En% and 10 En% respectively; NS) from the ad libitum lunch. In conclusion, a breakfast with 25% of energy from casein is rated as being more satiating than a breakfast with 10% of energy from casein at 3 and 4 h after breakfast, coinciding with prolonged elevated concentrations of plasma amino acids, but does not reduce subsequent energy intake.