Influence of Neoadjuvant Breast Cancer Therapy on Functional Performance

Aromatase inhibitors (AIs) are widely used as an adjuvant treatment in postmenopausal women with estrogen receptor-positive breast cancer. AIs arrest the final step in the synthesis of estrogen by blocking the activity of the enzyme aromatase. One of the most common side effects of AI treatment is joint pain, particularly in the hand and fingers. PURPOSE: To examine the effectiveness of an 8-week home-based exercise program in reducing joint pain and improving quality of life (QOL) and functional performance in breast cancer patients treated with AIs. METHODS: Participants underwent baseline measures of height, body mass, waist and hip circumference, and body composition. Functional performance was evaluated using grip strength, arm curl to exhaustion, and sit-to-stand. A 3-minute step test determined subject's cardiovascular endurance. Subjective measures of joint pain and QOL were conducted using self-administered surveys. Participants were instructed how to execute lower and upper body resistance exercises using Thera-BandR exercise bands and different hand exercises using an elastic band. A video was provided to each participant illustrating these exercises, as well as warm up, flexibility, and cool down. Participants were instructed how to monitor heart rate in order to pace aerobic activity. This was an 8 week, individualized, home-based program in which participants recorded daily activity on exercise logs and received interactive weekly phone calls to provide support. RESULTS: No significant pre-post changes were observed in the anthropometric measures (BMI, WHR, body composition). Grip strength, bicep curls to exhaustion and sit-to-stand improved significantly (8%, 45%, and 19%, respectively). HR recovery after the step test trended toward significance (5% reduction). Subjectively, participants reported an improvement in QOL, but no change in joint pain. CONCLUSIONS: An 8-week, home-based exercise program significantly improved functional performance and QOL in breast cancer patients suffering joint pain secondary to treatment with aromatase inhibitors. Supported by Susan G Komen for the Cure, WNY Affiliate.

Carriers of germline pathogenic variants of theBRCA1gene (gBRCA1) tend to have a higher incidence of haematological toxicity upon exposure to chemotherapy. We hypothesised that the occurrence of agranulocytosis during the first cycle of (neo-)adjuvant chemotherapy (C1) in breast cancer (BC) patients could predictgBRCA1pathogenic variants. The study population included non-metastatic BC patients selected for genetic counselling at Hôpitaux Universitaires de Genève (Jan. 1998 to Dec. 2017) with available mid-cycle blood counts performed during C1. The BOADICEA and Manchester scoring system risk-prediction models were applied. The primary outcome was the predicted likelihood of harbouringgBRCA1pathogenic variants among patients presenting agranulocytosis during C1. Three hundred seven BC patients were included: 32 (10.4%)gBRCA1, 27 (8.8%)gBRCA2, and 248 (81.1%) non-heterozygotes. Mean age at diagnosis was 40 years. Compared with non-heterozygotes,gBRCA1heterozygotes more frequently had grade 3 BC (78.1%; p = 0.014), triple-negative subtype (68.8%; p <0.001), bilateral BC (25%; p = 0.004), and agranulocytosis following the first cycle of (neo-)adjuvant chemotherapy (45.8%; p = 0.002). Agranulocytosis and febrile neutropenia that developed following the first cycle of chemotherapy were independently predictive forgBRCA1pathogenic variants (odds ratio: 6.1; p = 0.002). The sensitivity, specificity, positive predictive value, and negative predictive value for agranulocytosis predictinggBRCA1were 45.8% (25.6-67.2%), 82.8% (77.5-87.3%), 22.9% (6.1-37.3%), and 93.4% (88.9-96.4%), respectively. Agranulocytosis substantially improved the positive predictive value of the risk-prediction models used forgBRCA1evaluation. Agranulocytosis following the first cycle of (neo-)adjuvant chemotherapy is an independent predictive factor for gBRCA1detection in non-metastatic BC patients.

Hand grip strength is supported as a valid physical capacity measure in older adults. Normative values for community-dwelling older adult hand grip strength were recently updated. With the majority of community-dwelling older adults identified as sedentary, it is likely that current norms represent a group that is relatively inactive. A sub-population of senior athletes who actively engage in exercise and competitive sport have consistently demonstrated superior performance on measures of physical capacity when compared to the general population. Normative values for hand grip strength have not been established for this unique group of aging athletes. To establish hand grip strength norms for senior athletes and to compare these outcomes to available normative data in community-dwelling older adults. Cross-Sectional Study. Measures of hand grip strength were taken on 2,333 senior athletes registered to compete in the National Senior Games between 2011 and 2017. Findings were divided into age and gender categories consistent with community-dwelling norms. Student t tests were used to compare senior athlete means to community-dwelling norms. Cohen's d was calculated to estimate the effect size of each comparison. Normative values for senior athlete hand grip strength are reported in kilograms by age, gender and hand dominance. For each age and gender category tested, senior athletes demonstrate dominant hand grip strength that ranges from 8.6-11.1 kg higher for males and 5.5 to 8.9 kg higher for females (p values<.0001) than published community-dwelling norms. Non-dominant grip strengths were also significantly higher (p values<.0001). Effect sizes were medium to large (Cohen's ds = 0.44-1.5). Senior athletes demonstrate hand grip strength that is significantly higher than their community-dwelling peers and more similar to a younger community-dwelling population. The population--specific norms presented here will assist health care providers in more accurately assessing this high-functioning subset of aging adults. 2b.

ObjectiveTo establish reference values for hand grip strength (HGS) in a healthy Korean population and to identify the dependent anthropometric variables that affect HGS.MethodsBased on the sixth Korea National Health and Nutrition Examination Survey from 2014 to 2015, we analyzed the HGS data of 7,969 South Koreans. Individuals with specific chronic diseases and who reported poor subjective health status were excluded to ensure a healthy population sample. Means with standard deviations (SDs) and 95% confidence intervals were calculated for each 5-year interval starting from 10 years of age. To determine the relationship between HGS and anthropometric variables, we performed correlation analyses between HGS and height, weight, and body mass index (BMI). Additionally, based on these findings, the cut-off value for low HGS was presented by deriving -2SD values of healthy young adults as recommended by the European Working Group on Sarcopenia in Older People.ResultsThe mean age and BMI of men and women were 38.3 and 38.2 years and 23.8 and 22.4 kg/m2, respectively. Mean HGS of the dominant hand in men and women was 39.5 and 24.2 kg, respectively. The peak in HGS was at 35–39 years of age, after which HGS decreased in both sexes. HGS was significantly correlated with height, weight, and BMI. The cut-off values for weak HGS were < 28.9 and < 16.8 kg in men and women, respectively.ConclusionThese results provide useful reference values to assess HGS in patients who undergo hand surgery or who have various diseases that affect HGS. Moreover, a cut-off value for low HGS may help in defining sarcopenia among the Korean population.

FDG-PET may be a powerful examination to evaluate the effectiveness of neoadjuvant chemotherapy: it appears to be possible to predict the preoperative histological response after the first cycle of chemotherapy. The aim of this prospective study was to investigate the prognostic value of the early decrease of tumoral glucidic metabolism, evaluated with FDG-PET, after the first cycle of neoadjuvant chemotherapy in breast cancer. Material and methods: FDG-PET was performed before and after the first cycle of neoadjuvant chemotherapy in 92 patients with large or locally advanced, non inflammatory, breast cancer. The change of 18F-FDG tumoral uptake was calculated from the maximum Standard Uptake Value corrected for body surface and glycemia (ΔSUVmax). Disease free survival (DFS) was assessed, and the prognostic value of ΔSUVmax was first studied among all patients. Using immunohistochemistry as a surrogate for expression profiling, patients were then classified according to tumoral phenotypes as follow: triple negative (defined by the lack of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) expression), luminal (ER positive or PR positive, HER2 negative) and HER2 positive. Results: The median follow-up was 46.3 months (range: 37–52 months). Twenty one patients had recurrent disease, 9 of whom died. Using univariate Cox regression analysis with all patients, DFS showed significant correlation with initial tumor size measured with ultrasound scan (p=0.03), and ΔSUVmax after the first cycle of neoadjuvant chemotherapy (cut-off = -45%, p=0.01). Using multivariate cox regression analysis, only ΔSUVmax remained an independent prognostic factor of DFS at four years (p=0.028). According to tumoral phenotypes, ΔSUVmax was a prognostic factor of DFS for the 50 patients with a luminal cancer : the risk of relapse was 8.7 times higher in women whose SUVmax decreased less than 24% after the first course of chemotherapy (p=0,04). No significant correlation between ΔSUVmax and DFS was shown in the 22 triple negative phenotypes. For the 31 patients overexpressing HER2, a tumoral SUVmax lower than 1,8 after one cycle of chemotherapy tended to be a favorable prognostic factor with a lower risk of relapse (p = 0,058) but ΔSUVmax had no significant prognostic value (p=0.08). Conclusion: Using immunohistochemistry, the change of tumoral FDG uptake after the first cycle of neoadjuvant chemotherapy in operable breast cancer patients appears to be an early surrogate marker of disease free survival for luminal tumors in this study. For HER2 positive tumors, FDG-PET seems to provide prognostic information but, as for the triple negative tumors, it was not statistically significant. FDG-PET might be useful to guide the early therapeutic choice for breast cancer treated with neoadjuvant chemotherapy. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P5-01-05.

Background:The enzymatic and non-enzymatic antioxidant defense systems of the cell prevent oxidant mediated damage to different biomolecules by neutralizing free radicals generated during anticancer drug metabolism.Reduced glutathione (GSH) and glutathione dependent enzymes such as glutathione peroxidase (GP x ) and glutathione-s-transferase (GST) are the key determinants of cellular response to oxidative stress.The objective of this study was to evaluate changes in serum levels of these antioxidants after first cycle of adjuvant chemotherapy in breast cancer patients.Material and Methods: Histopathologically proven 60 breast cancer patients were included in the present study.The blood samples were taken after surgery before chemotherapy and after 3 weeks of administration of first cycle of chemotherapy.30 healthy female controls were selected for comparison.Serum GSH and GST were estimated by spectrophotometric methods and serum GP x was estimated by ELISA. Results:The serum levels of GSH, GST and GP x were significantly decreased (P<0.0001) after first cycle of adjuvant chemotherapy in breast cancer patients as compare to levels before chemotherapy.A significant positive correlation was found between serum levels of GSH and GST as well as GSH and GP x after first chemotherapy cycle. Conclusion:Our data suggests that administration of chemotherapeutic drugs causes depletion of reduced glutathione and glutathione-dependent enzymatic antioxidants such as GST and GP x , which may be due to higher oxidative stress after chemotherapy.

We investigated the accuracy of Automated Breast Volume Scanner (ABVS) compared to handheld ultrasound (HHUS) for monitoring tumor response to neoadjuvant treatment (NAT) in breast cancer (BC). All the patients submitted to biopsy in our Institution, from January 2017 to May 2017, proven invasive BC and eligible for NAT, were enrolled in this prospective study. The participants underwent ABVS, HHUS, dynamic contrast-enhanced Magnetic Resonance Imaging (DCE-MRI) and mammography at the beginning of NAT and ABVS, HHUS and DCE-MRI at the halfway point of therapy and before the surgery. DCE-MRI was considered the standard of reference. Two breast radiologists (R1, R2), with fifteen and five years of experience in breast imaging, independently assigned a visibility score (ordinal 5-point scale) to ABVS, HHUS, and DCE-MRI. Diagnostic performance of ABVS and HHUS as measured by sensitivity, specificity, positive and negative predictive values (PPV and NPV) was calculated. Correlations between ABVS and MRI, and between HHUS and MRI were analyzed using Pearson's correlation test. A total of 21 patients were enrolled. 189 examinations were performed. The comparison between ABVS and DCE-MRI was similar for the both readers: ABVS had a sensitivity of 63,16%, specificity of 83,58%, PPV of 76,60%, NPV of 72,73%, accuracy of 74,19% (R1) and a sensitivity of 54.54%, specificity of 85.51%, PPV of 75%, NPV of 70,24%, accuracy of 71.77% (R2). The comparison between HHUS and DCE-MRI showed that HHUS had a sensitivity of 63,16 %, specificity of 83,58%, PPV of 76,60%, NPV of 72,73%, accuracy of 74,19% (R1) and a sensitivity of 36.84%, specificity of 85.07%, PPV of 67.74%, NPV of 61.29%, accuracy of 62.90% (R2). The calculated Pearson's correlation coefficient r values were 7.8 for HHUS vs. DCE-MRI and 28.5 for ABVS vs. DCE-MRI (R1) and 7.8 for HHUS vs. DCE-MRI and 22.4 for ABVS vs. DCE-MRI (R2). Statistical significance of ABVS and HHUS was p < 0.0001 and 0.005 < p < 0.01, respectively (R1, R2). DCE-MRI is recommended for the tumor response assessment. ABVS, a product of the biotechnology development, providing reproducible images, in addition to DCE-MRI, can be a potentially useful tool for the monitoring of response to NAT.

BackgroundNormative values for hand grip and pinch strength among children in Saudi Arabia has not been well established. Therefore, the main aim of this study is to establish normative values for hand grip and pinch strength in children aged 6 to 18 years in Saudi Arabia.MethodsA cross-sectional study was conducted from different 5 regions in Saudi Arabia. Participants between the age of 6 years and 18 years old were recruited through different primary and secondary schools in Saudi Arabia. Data for age, gender, Body Mass Index, and preferred hand were collected. Hand grip strength was measured using digital hand dynamometer and the tip pinch, palmar pinch, and key pinch strength were measured using the hydraulic pinch gauge.ResultsA total of 616 participants included in this study (318 boys and 298 girls). Participants were stratified into 5 chronological age groups of 6–7 years, 8–9, 10–11, 12–13, 14–15, 16–17, and 18 years. The results showed an overall trend of increasing hand grip strength and pinch strength with age regardless of hand preference. Boys had significantly higher grip strength than girls in all age groups (P < 0.05).ConclusionThis study established normative values for hand grip and pinch strength in the healthy Saudi pediatric and adolescent population, using boys and girls aged 6 to 18. The outcomes of this study also demonstrated that gender, age, and hand preference can all have an impact on how strong a handgrip develops.

IntroductionThe combination of doxorubicin and paclitaxel (AP) is widely used in our country for the neoadjuvant treatment of breast cancer as well as metastatic breast cancer. The AP regimen has shown promise as a neoadjuvant therapy for breast cancer that improves pathological complete response (pCR), increases the rate of conservative surgery, and improves the survival of patients. However, up to now, no research has evaluated the response of this regimen for the neoadjuvant treatment of advanced breast cancer, especially with a 10-year period of follow-up.MethodsThis retrospective analysis reviewed 126 patients with inoperable stage III breast cancer who received neoadjuvant chemotherapy with doxorubicin 50 mg/m2 plus paclitaxel 175 mg/m2 every 3 weeks for a maximum of six courses followed by surgery. pCR was evaluated. Survival was analyzed for all breast cancer patients using Kaplan–Meier and log-rank models.ResultsOf 126 women treated with neoadjuvant chemotherapy (NAC), the overall pCR rate was 25.4% and was significantly higher in patients with tumor stage cT1–T2, hormone receptor-negative (HR-negative), and human epidermal growth factor receptor 2 (HER2)-positive disease. Patients achieving pCR had significantly longer disease-free survival (DFS) and overall survival (OS). Ten-year DFS rates were 43.8% vs. 25.0% (p = 0.030) and 10-year OS rates were 59.4% vs. 28.9% (p = 0.003) for patients with pCR and non-pCR, respectively. The cumulative 10-year DFS was 19.6% for patients with HR-negative disease and 37.3% for those with HR-positive disease. Achieving pCR was associated with improved 10-year OS and DFS. Several clinicopathological features were closely associated with pCR in the inoperable stage III breast cancer patients who were treated by neoadjuvant chemotherapy.ConclusionAchieving pCR was associated with improved 10-year OS and DFS. Patients with advanced breast cancer with HR-negative and HER2-positive status who benefited from the AP neoadjuvant therapy regimen were significantly more likely to achieve pCR.

Prevalence and course of fatigue in breast cancer patients receiving adjuvant chemotherapy

Simple SummaryThis study examined whether the DNA methylation state of peripheral blood mononuclear cells (PBMCs) could predict cardiotoxicity caused by doxorubicin (DOX)-based chemotherapy in breast cancer patients. The results showed a significant difference in the pattern of DNA methylation of PBMCs associated with a risk of cardiotoxicity. These preliminary findings have the potential to further the goal of personalized medicine and tailor the treatment of breast cancer with DOX-based chemotherapy to reduce the toxicity to the heart.Chemotherapy with doxorubicin (DOX) may cause unpredictable cardiotoxicity. This study aimed to determine whether the methylation signature of peripheral blood mononuclear cells (PBMCs) prior to and after the first cycle of DOX-based chemotherapy could predict the risk of cardiotoxicity in breast cancer patients. Cardiotoxicity was defined as a decrease in left ventricular ejection fraction (LVEF) by >10%. DNA methylation of PBMCs from 9 patients with abnormal LVEF and 10 patients with normal LVEF were examined using Infinium HumanMethylation450 BeadChip. We have identified 14,883 differentially methylated CpGs at baseline and 18,718 CpGs after the first cycle of chemotherapy, which significantly correlated with LVEF status. Significant differentially methylated regions (DMRs) were found in the promoter and the gene body of SLFN12, IRF6 and RNF39 in patients with abnormal LVEF. The pathway analysis found enrichment for regulation of transcription, mRNA splicing, pathways in cancer and ErbB2/4 signaling. The preliminary results from this study showed that the DNA methylation profile of PBMCs may predict the risk of DOX-induced cardiotoxicity prior to chemotherapy. Further studies with larger cohorts of patients are needed to confirm these findings.

The aim of this study was to determine the structure of qualitative relationships between a test for assessing strength status and a battery of tests for assessing motor abilities in primary school children from rural areas. The research was conducted on a sample of 141 students from primary schools, from the first to the eighth grade, in Kušiljevo and Vraćevšnica (central Serbia). The tested sample included 27 girls and 33 boys (from the first to the fourth grade) and 42 girls and 39 boys (from the fifth to the eighth grade). The following variables were used for this research: age, maximum muscle strength of the dominant (FmaxD) and non-dominant hand grip (FmaxN), as well as the total sum (FmaxSUM), sit-and-reach test, standing long jump, sit-ups test, isometric chin-up, and 4x10m running test. Pearson correlation results showed that age correlates with the sit-and-reach (r=0.387, p=0.034), standing long jump (r=0.536, p=0.002), and 4×10 m running test (r=–0.561, p=0.001) in boys from the first to the fourth grade, and with the isometric chin-up test in girls (r=–0.402, p=0.042). Additionally, the absolute value of hand grip strength, regardless of whether it is the result of the dominant, non-dominant, or the sum of both hands, generally does not correlate with any test for assessing motor abilities in the tested sample, except for boys from the fifth to the eighth grade, where a statistically significant correlation was found with the standing long jump (FmaxD: r=0.479, p=0.002; FmaxN: r=0.454, p=0.004; FmaxSUM: r=0.471, p=0.002). When age was controlled through partial correlation analysis, significant relationships between hand grip strength and standing long jump remained only in boys from the fifth to the eighth grade (FmaxD: r=0.459, p=0.004; FmaxN: r=0.425, p=0.009; FmaxSUM: r=0.447, p=0.006). In addition, a significant negative correlation was found between FmaxN and sit-ups in boys from grades 1–4 (r=–0.401, p=0.031), and between FmaxD and 4×10 m running in boys from grades 5–8 (r=–0.331, p=0.046).Since the hand grip strength test is a standardized test for assessing overall body strength, it can be concluded that the standard battery of tests does not cover the entire range of physical, i.e., motor abilities. Based on the obtained results, it can be concluded that the hand grip strength test can be recommended as an addition to testing physical, i.e., motor abilities in primary schools, as a proven and simple screening test for assessing overall body strength.

The determination of hand grip strength is an objective method of evaluation of upper members' integrity. It is also used as a general health indicator. Data about grip strength values in healthy children is useful in the research and diagnosis of diseases that interfere with grip force. The aim of this study was to determine average values of children hand grip strength by age and evaluate its relation with weight and height. Hand grip strength was measured with the dynamometer Jamar Hydraulic Hand in a convenience sample of 195 children of either gender, with ages between 11 and 14 years old. Statistical significant differences were observed in hand grip strength between genders, being higher in boys. Moderate correlations were found between grip strength and age (R = 0.679, p < 0.001), height (R = 0.691, p < 0.001), and weight (R = 0.620, p < 0.001). The present study presents values of hand grip strength obtained from a sample of Portuguese children of 11 to 14 years old, which are directly associated with height and weight.

Aromatase inhibitors (AIs) block estrogen synthesis and are commonly used as adjuvant treatments for breast cancer patients. A common side effect is joint pain. This was a pilot study to examine implementation of an exercise program in reducing joint pain and improving quality of life (QoL) and functional performance in breast cancer patients treated with AIs. Twenty-six participants completed an 8-week, home-based program that combined upper and lower body resistance exercises with self-selected aerobic exercises. We measured: (1) anthropometry (2) functional performance (grip strength, biceps curl to exhaustion, and sit-to-stand and cardiovascular endurance (3-min step test). Joint pain and QoL were assessed using self-administered surveys. Participants reported a significantly lower number of painful joints, an improvement in QoL and a reduction in depressive symptoms. Significant improvements in grip strength, biceps curl, and sit-to-stand (by 14%, 51% and 15% respectively) were also observed. However, we found no significant changes in cardiovascular endurance or in anthropometric measures. An 8-week, home-based exercise program may provide potential benefit to the breast cancer patients undergoing AI treatment by reducing joint pain, improving functional performance and QoL, and reducing depressive symptoms. Further studies are needed to confirm these results.

ObjectiveThe radiomics model based on single imaging modality has been demonstrated as a promising approach for predicting the response to neoadjuvant treatment (NAT) in breast cancer. However, whether integrating multiple imaging modalities improve the performance of the radiomics model is undetermined. This study aims to develop a multi-modal radiomics model based on four imaging modalities, including ultrasound (US), mammography (MM), computed tomography (CT), and magnetic resonance imaging (MRI), for predicting pathological complete response (pCR) in breast cancer after NAT.MethodsPatients who underwent surgery after NAT from January 2019 to July 2023 were retrospectively studied. Univariate and multivariate analyses were performed to identify independent clinical risk factors for pCR. The radiomic features were extracted from the volume of interest on the four imaging modalities. The least absolute shrinkage and selection operator was used for developing radiomic signatures. The multi-modal radiomics model was developed by combining four radiomic signatures. The combined model was developed by combining clinical risk factors and four radiomic signatures. A nomogram was developed to visualize the combined model. Model performance was internally validated by using the five-fold cross-validation.ResultsIn total, 89 patients were included, with the pCR rate of 31.5% (28/89). Multivariate analyses identified PR status (OR = 4.450, 95% confidence interval [CI], 1.228–18.063, P = 0.028), HER2 status (OR = 9.95, 95% CI, 1.525–201.894, P = 0.044) and clinical T stage (OR = 0.253, 95% CI, 0.076–0.753, P = 0.016) were independent clinical risk factors for pCR. The AUCs and brier scores of the radiomic signatures of US, MM, CT, and MRI were 0.702 (95% CI: 0.583–0.821), 0.762 (95% CI: 0.660–0.865), 0.814 (95% CI: 0.725–0.903), 0.787 (95% CI: 0.685–0.889) and 0.198, 0.177, 0.165, 0.170 respectively. The performance of the multi-modal radiomics model was superior to all radiomic signatures with an AUC of 0.904 (95% CI: 0.838–0.970) and with the brier score of 0.111. After adding independent clinical risk factors, the performance of the combined model further improved, achieving an AUC of 0.943 (95% CI: 0.893–0.992) and a brier score of 0.082. The nomogram showed potential clinical value.ConclusionThe multi-modal radiomics model based on US, MM, CT, and MRI could accurately predict pCR in breast cancer after NAT, which was superior to all radiomic signatures. Incorporating clinical risk factors may further improve the performance of the muti-modal radiomics model, which could provide valuable information for guiding treatment decisions.