Predictive and prognostic effect of computed tomography-derived body composition analysis during neoadjuvant chemotherapy for operable and locally advanced breast cancer.

OBJECTIVES: Excess adiposity is associated with several factors involved in carcinogenesis and breast cancer progression. Evidence supporting the role of body composition in breast cancer treatment is promising, but still scanty and mainly focused on adjuvant treatment. The aim of this study was to evaluate the changes in body composition during neoadjuvant chemotherapy and its association with pathologic complete response and survival outcome in patients treated for operable/locally advanced breast cancer. METHODS: A retrospective review of patients with breast cancer treated with neoadjuvant chemotherapy was performed in the Oncology Section of the Department of Medicine, University of Verona between 2014 and 2019. Body composition was evaluated from clinically acquired computed tomography scans at diagnosis and after neoadjuvant chemotherapy. Descriptive statistic was adopted. The associations of body composition measures with pathologic complete response and disease-free survival were analyzed. Kaplan-Meier curves were compared with log-rank analysis. RESULTS: Data from 93 patients were collected. After neoadjuvant chemotherapy, the adipose compound changed significantly across all body mass index categories. Body composition parameters had no significant effect on pathologic complete response. Survival analysis showed that a high gain of visceral adipose tissue during neoadjuvant chemotherapy was associated with shorter disease-free survival (hazard ratio, 10.2; P = 0.026). In particular, disease-free survival was significantly worse in patients who gained ≥10% of visceral adipose tissue compared with patients who gained <10% of visceral adipose tissue (5-y disease-free survival 71.4 versus 96.3, P = 0.009, respectively). CONCLUSIONS: Our results indicated that neoadjuvant chemotherapy significantly affects body composition, which seems to have an effect on survival outcome of breast cancer, highlighting the relevance of the body composition assessment when estimating treatment outcomes.

Optimizing CDK4/6 inhibitors in advanced HR+/HER2- breast cancer: A personalized approach.

Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) combined with endocrine therapy (ET) are now a backbone of treatment for hormone receptor-positive/human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer. CDK4/6i plus ET is more effective than ET alone in this setting; however, the risk of grade 3-4 adverse events also increases. Approved agents in this class have similar efficacies, but important differences due to their structural and pharmacological properties. We review biomarkers and discuss determinants to inform a rational approach to therapy choice when selecting the most appropriate ET and CDK4/6i partners. We also identify subgroups that may benefit from specific ET-CDK4/6i combinations and discuss strategies to overcome resistance. This personalized approach aims to minimize treatment-related toxicities that may affect patient QoL and compliance, and ultimately therapy efficacy.

Evidence-based tailored nutrition educational intervention improves adherence to dietary guidelines, anthropometric measures and serum metabolic biomarkers in early-stage breast cancer patients: A prospective interventional study.

PURPOSE: The impact of the adherence to dietary guidelines of early-stage breast cancer (EBC) patients on body composition changes during treatment is not entirely defined. This study aimed to evaluate the role of an evidence-based nutrition educational intervention, according to adherence to dietary guidelines, in EBC patients. METHODS: This prospective study included EBC patients, candidates for neoadjuvant/adjuvant therapy. Patients received an evidence-based tailored nutrition educational intervention. The adherence to dietary guidelines, anthropometric and dietary assessments, and blood glucose and lipid profile tests were evaluated at baseline and after a 12-months nutritional intervention. RESULTS: Two hundred and forty-three patients were enrolled. At baseline, 38.3% and 23.9% of patients were overweight and obese, weight gain ≥5% (compared to 6-months before enrollment) and central obesity were observed in 47.3% and 52.7% of patients, respectively. Adherence to dietary guidelines was low (median Med-Diet score: 6 [IQR 4-8]). After the nutritional intervention (median follow-up: 22 months [range 12-45]), adherence to dietary guidelines significantly increased (median Med-Diet score: 12 [IQR 8-13]), p < 0.0001). High adherence to dietary guidelines (defines as Med-Diet score ≥10) significantly correlated with: 1) overall weight loss ≥5% (21.8% vs. 2.5%, p = 0.003); 2) median BMI drop (from 25.6 kg/m2 to 24.4 kg/m2, p = 0.003); 3) lower prevalence of central obesity (38.2% vs. 7.2%, p = 0.01); 4) improvement in blood glucose levels and lipid profile. CONCLUSION: This study suggests that an evidence-based tailored nutrition educational intervention during treatment for EBC significantly increases overall adherence to dietary guidelines, and it improves both anthropometric measures and serum metabolic biomarkers in patients with high adherence.

EFFECT: a randomized phase II study of efficacy and impact on function of two doses of nab-paclitaxel as first-line treatment in older women with advanced breast cancer.

BACKGROUND: Limited data are available regarding the use of nab-paclitaxel in older patients with breast cancer. A weekly schedule is recommended, but there is a paucity of evidence regarding the optimal dose. We evaluated the efficacy of two different doses of weekly nab-paclitaxel, with a specific focus on their corresponding impact on patient function, in order to address the lack of data specifically relating to the older population. METHODS: EFFECT is an open-label, phase II trial wherein 160 women with advanced breast cancer aged ≥ 65 years were enrolled from 15 institutions within Italy. Patients were randomly assigned 1:1 to receive nab-paclitaxel 100 mg/m2 (arm A) or 125 mg/m2 (arm B) on days 1, 8, and 15 on a 28-day cycle, as first-line treatment for advanced disease. The primary endpoint was event-free survival (EFS), wherein an event was defined as disease progression (PD), functional decline (FD), or death. In each arm, the null hypothesis that the median EFS would be ≤ 7 months was tested against a one-sided alternative according to the Brookmeyer Crowley test. Secondary endpoints included objective response rate (ORR), clinical benefit rate (CBR), progression-free survival (PFS), overall survival (OS), and safety. RESULTS: After a median follow-up of 32.6 months, 140 events were observed in 158 evaluable patients. Median EFS was 8.2 months (90% CI, 5.9-8.9; p = 0.188) in arm A vs 8.3 months (90% CI, 6.2-9.7, p = 0.078) in arm B. Progression-free survival, overall survival, and response rates were similar in both groups. A higher percentage of dose reductions and discontinuations due to adverse events (AEs) was noted in arm B. The most frequently reported non-haematological AEs were fatigue (grade [G] 2-3 toxicity occurrence in arm A vs B, 43% and 51%, respectively) and peripheral neuropathy (G2-3 arm A vs B, 19% and 38%, respectively). CONCLUSION: Pre-specified outcomes were similar in both treatment arms. However, 100 mg/m2 was significantly better tolerated with fewer neurotoxicity-related events, representing a more feasible dose to be recommended for older patients with advanced disease. TRIAL REGISTRATION: EudraCT, 2012-002707-18 . Registered on June 4, 2012. NIH ClinicalTrials.gov, NCT02783222 . Retrospectively registered on May 26, 2016.

Organisational challenges, volumes of oncological activity and patients' perception during the severe acute respiratory syndrome coronavirus 2 epidemic.

BACKGROUND: On February 23rd, the 1st case of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was diagnosed at the University Hospital Trust of Verona, Italy. On March 13th, the Oncology Section was converted into a 22-inpatient bed coronavirus disease (COVID) Unit, and we reshaped our organisation to face the SARS-CoV-2 epidemic, while maintaining oncological activities. METHODS: We tracked down (i) volumes of oncological activities (January 1st - March 31st, 2020 versus the same period of 2019), (ii) patients' and caregivers' perception and (iii) SARS-CoV-2 infection rate in oncology health professionals and SARS-CoV-2 infection-related hospital admissions of "active"' oncological patients. RESULTS: As compared with the same trimester in 2019, the overall reduction in total numbers of inpatient admissions, chemotherapy administrations and specialist visits in January-March 2020 was 8%, 6% and 3%, respectively; based on the weekly average of daily accesses, reduction in some of the oncological activities became statistically significant from week 11. The overall acceptance of adopted measures, as measured by targeted questionnaires administered to a sample of 241 outpatients, was high (>70%). Overall, 8 of 85 oncology health professionals tested positive for SARS-CoV-2 infection (all but one employed in the COVID Unit, no hospital admissions and no treatment required); among 471 patients admitted for SARS-CoV-2 infection, 7 had an "active"' oncological disease (2 died of infection-related complications). CONCLUSIONS: A slight, but statistically significant reduction in oncology activity was registered during the SARS-CoV-2 epidemic peak in Verona, Italy. Organisational and protective measures adopted appear to have contributed to keep infections in both oncological patients and health professionals to a minimum.

Sharing real-world experiences to optimize the management of olaparib toxicities: a practical guidance from an Italian expert panel.

Olaparib is the first poly(ADP-ribose) polymerase inhibitor approved as maintenance therapy of recurrent ovarian cancer (OC) patients with a BRCA mutation. To achieve the maximum clinical benefit, adherence to olaparib must be persistent. However, in clinical practice, this is challenged by the frequent suboptimal management of toxicities. In view of the expanding use of olaparib also in Italy, physicians must learn how to adequately and promptly manage drug toxicities not to unnecessarily interrupt or reduce the dose. The experts agreed that nausea,vomiting, anemia, and fatigue are the most frequent events experienced by OC patients on olaparib, and that these toxicities usually develop early during treatment, are mainly of grade 1-2 and transient and can be managed with simple non-pharmacological interventions. By sharing their real-world experiences, the panel prepared, for each toxicity, an algorithm organized by grade and besides the procedures indicated in the local label, included supportive care interventions based also on nutritional and lifestyle modifications and psycho-oncology consultation. Moreover, in view of the tablet entry into the Italian market, the full and reduced dosages of capsules and tablets were compared. This practical guidance is intended to be a tool to support especially less-experienced physicians in the management of these complex patients, with the aim to help preventing the worsening of patients' conditions and the unnecessary interruption/reduction of olaparib dosage, which may jeopardize treatment efficacy.

Prognostic impact of proliferation for resected early stage 'pure' invasive lobular breast cancer: Cut-off analysis of Ki67 according to histology and clinical validation.

INTRODUCTION: The intent of this analysis was to investigate and validate the prognostic potential of Ki67 in a multi-center series of patients affected by early stage 'pure' invasive lobular carcinoma (ILC). METHODS: Clinical-pathological data of patients affected by ILC were correlated with overall survival and disease-free survival (OS/DFS); data from a parallel invasive ductal carcinoma (IDC) patients' cohort were gathered as well. The maximally selected Log-Rank statistics analysis was applied to Ki67 continuous variable to estimate the appropriate cut-off. The Subpopulation Treatment Effect Pattern Plot (STEPP) analysis was performed as well. RESULTS: Data from overall 1097 (457/222 ILC: training/validation set; 418 IDC) patients were gathered. The identified optimal Ki67 cut-offs were 4% and 14% for DFS in ILC and IDC cohort, respectively. In ILC patients, the Ki67 cut-off was an independent OS predictor. Ten-years OS and DFS were 89.9% and 77.2% (p = 0.007) and 79.4% and 69.2% (p = 0.03) for patients with Ki67 ≤ 4% and >4%, respectively. In IDC patients, 10-years OS was 93.8% and 71.7%, p = 0.02, DFS was 84.0% and 52.6%, p = 0.0003, for patients with Ki67 ≤ 14% and >14%, respectively. In the validation set, the optimal Ki67 OS cut-off was 5%. The STEPP analysis showed that in the presence of low Ki67 values, IDC patients have a better DFS than ILC patients, while with the increase of values the prognosis tends to overlap. CONCLUSIONS: Despite the retrospective design of the study, the prognostic relevance of Ki67 (as well as its optimal cut-off) seems to significantly differ according to breast cancer histology.

Clinical results of randomized trials and 'real-world' data exploring the impact of Bevacizumab for breast cancer: opportunities for clinical practice and perspectives for research.

INTRODUCTION: Angiogenesis plays a fundamental role in breast cancer (BC) growth, progression and metastatic spread. After the promising introduction of bevacizumab for the treatment of advanced BC, the initial enthusiasm decreased when the FDA withdrew its approval in 2011. Nevertheless, several clinical studies exploring the role of bevacizumab have been subsequently published. Areas covered: The aim of this study is to review the available clinical trials exploring the potential effectiveness of bevacizumab in BC, regardless of the disease setting. Expert opinion: Even if the evidence suggests that bevacizumab must be ruled out from the HER2-positive and adjuvant setting, bevacizumab's benefit remains uncertain in the neoadjuvant setting and in the advanced treatment of HER2-negative patients. In the first setting, the addition of bevacizumab to chemotherapy increased the pathological complete response (pCR) rate in most clinical trials. However, the current absence of evidence that pCR is a trial-level surrogate for survival requires waiting for long-term results. In the advanced setting, all trials showed a benefit in progression-free survival, but not in overall survival, highlighting an increase of adverse events. The lack of predictors of response represents the main unmet need in which future clinical research will undoubtedly invest.

Bone metastases from primary cardiac sarcoma: case report.

Tumor spread from primary cardiac sarcoma to the bone is very rare and has a poor prognosis. Only six cases have been reported in the literature. We present a 32-year-old female patient with bone metastases from primary cardiac sarcoma.

Leptin/HER2 crosstalk in breast cancer: in vitro study and preliminary in vivo analysis.

BACKGROUND: Obesity in postmenopausal women is associated with increased breast cancer risk, development of more aggressive tumors and resistance to certain anti-breast cancer treatments. Some of these effects might be mediated by obesity hormone leptin, acting independently or modulating other signaling pathways. Here we focused on the link between leptin and HER2. We tested if HER2 and the leptin receptor (ObR) can be coexpressed in breast cancer cell models, whether these two receptors can physically interact, and whether leptin can transactivate HER2. Next, we studied if leptin/ObR can coexist with HER2 in breast cancer tissues, and if presence of these two systems correlates with specific clinicopathological features. METHODS: Expression of ObR, HER2, phospho-HER2 was assessed by immunoblotting. Physical interactions between ObR and HER2 were probed by immunoprecipitation and fluorescent immunostaining. Expression of leptin and ObR in breast cancer tissues was detected by immunohistochemistry (IHC). Associations among markers studied by IHC were evaluated using Fisher's exact test for count data. RESULTS: HER2 and ObR were coexpressed in all studied breast cancer cell lines. In MCF-7 cells, HER2 physically interacted with ObR and leptin treatment increased HER2 phosphorylation on Tyr 1248. In 59 breast cancers, the presence of leptin was correlated with ObR (the overall association was about 93%). This result was confirmed both in HER2-positive and in HER2-negative subgroups. The expression of leptin or ObR was numerically more frequent in larger (> 10 mm) tumors. CONCLUSION: Coexpression of HER2 and the leptin/ObR system might contribute to enhanced HER2 activity and reduced sensitivity to anti-HER2 treatments.