Changes in body composition in early breast cancer patients treated with aromatase inhibitors.

PURPOSE: The aim of the study was to analyze the modification of total and regional body composition in early breast cancer patients treated with aromatase inhibitors (AIs). METHODS: This is a prospective, single-center, observational, longitudinal study. Four-hundred and twenty-eight patients treated with adjuvant aromatase inhibitors were enrolled at the Medical Oncology and Breast Unit of Spedali Civili Hospital in Brescia from September 2014 to June 2022. Several body composition parameters including total and regional fat and lean body mass were investigated with dual-energy X-ray absorptiometry (DXA) scan at baseline and after 18 months of treatment with aromatase inhibitors. RESULTS: A significant increase in fat body mass (mean + 7.2%, 95% confidence interval [CI]: 5.5;8.9%) and a reduction in lean body mass (mean -3.1%, 95% CI -3.9; -2.4) were documented in this population. The changes in fat and lean body mass varied considerably according to different body districts ranging between + 3.2% to + 10.9% and from-1.3% to -3.9%, respectively. CONCLUSION: Aromatase inhibitor adjuvant therapy in early breast cancer is associated with changes in body composition, with a wide variability among different body districts, leading to a risk of sarcopenic obesity. Supervised physical exercise that focuses on single body parts that may display detrimental variations may be beneficial for AIs treated patients.

Denosumab improves trabecular bone score in relationship with decrease in fracture risk of women exposed to aromatase inhibitors.

PURPOSE: Trabecular bone score (TBS) is a gray-level textural metric that has shown to correlate with risk of fractures in several forms of osteoporosis. The value of TBS in predicting fractures and the effects of bone-active drugs on TBS in aromatase inhibitors (AIs)-induced osteoporosis are still largely unknown. The primary objective of this retrospective study was to assess the effects of denosumab and bisphosphonates (BPs) on TBS and vertebral fractures (VFs) in women exposed to AIs. METHODS: 241 consecutive women (median age 58 years) with early breast cancer undergoing treatment with AIs were evaluated for TBS, bone mineral density (BMD) and morphometric VFs at baseline and after 18-24 months of follow-up. During the study period, 139 women (57.7%) received denosumab 60 mg every 6 months, 53 (22.0%) BPs, whereas 49 women (20.3%) were not treated with bone-active drugs. RESULTS: Denosumab significantly increased TBS values (from 1.270 to 1.323; P < 0.001) accompanied by a significant decrease in risk of VFs (odds ratio 0.282; P = 0.021). During treatment with BPs, TBS did not significantly change (P = 0.849) and incidence of VFs was not significantly different from women untreated with bone-active drugs (P = 0.427). In the whole population, women with incident VFs showed higher decrease in TBS vs. non-fractured women (P = 0.003), without significant differences in changes of BMD at any skeletal site. CONCLUSIONS: TBS variation predicts fracture risk in AIs treated women. Denosumab is effective to induce early increase of TBS and reduction in risk of VFs.

Working tables on Hormone Receptor positive (HR+), Human Epidermal growth factor Receptor 2 negative (HER2-) early stage breast cancer: Defining high risk of recurrence.

Hormone-receptor positive (HR+), Human-Epidermal-growth Factor negative (HER2-) breast cancer, including the Luminal A and the Luminal B subtypes, is the most common in women diagnosed with early-stage BC. Despite the advances in screening, surgery and therapies, recurrence still occurs. Therefore, it is important to identify early those factors that significantly impact the recurrence risk. Based on current evidence and their professional expertise, a Panel of oncologists discussed the definition of high risk of recurrence in early breast cancer. Histological grade, nodal involvement, genomic score, histological grade, tumor size, and Ki-67 proliferation index were rated as the most important factors to define the high risk in patients with early breast cancer. All these factors should be considered comprehensively to tailor the choice of treatment to the peculiar characteristics of each patient.

Immune-related adverse events as potential surrogates of immune checkpoint inhibitors' efficacy: a systematic review and meta-analysis of randomized studies.

BACKGROUND: Immune-related adverse events (irAEs) are frequently reported during immune checkpoint inhibitor (ICI) therapy and are associated with long-term outcomes. It is unknown if the irAE occurrence is a valid surrogate of ICIs' efficacy. METHODS: We identified articles reporting the results of randomized trials of experimental ICI therapy in solid tumors with a systematic search. The control arms could be placebo, cytotoxic/targeted therapy, or ICI therapy. We extracted the hazard ratios for overall survival (OS) with the number of OS events per arm and the number and percentages of overall and specific irAEs of grade 1-2 and grade 3-4 per arm. We estimated the treatment effect on the potential surrogate outcome with the odds ratio of the irAE rate between the experimental and the control arm. The statistical analysis consisted of weighted linear regression on a logarithmic scale between treatment effects on irAE rate and treatment effects on OS. RESULTS: Sixty-two randomized trials were included for a total of 79 contrasts and 42 247 patients. The analyses found no significant association between the treatment effects for overall grade 1-2 or grade 3-4 irAE rates or specific (skin, gastrointestinal, endocrine) irAE rates. In the non-small-cell lung cancer (NSCLC) trial subset, we observed a negative association between treatment effects on overall grade 1-2 irAEs and treatment effects on OS in studies with patients selected for programmed death-ligand 1 expression (R2 = 0.55; 95% confidence interval 0.20-0.95; R = -0.69). In the melanoma trial subset, a negative association was shown between treatment effects on gastrointestinal grade 3-4 irAEs and treatment effects on OS in trials without an ICI-based control arm (R2 = 0.77; 95% confidence interval 0.24-0.99; R = -0.89). CONCLUSIONS: We found low-strength correlations between the ICI therapy effects on overall or specific irAE rates and the treatment effects on OS in several cancer types.

Correlations between family history and cancer characteristics in 2256 breast cancer patients.

A comparison of 692 early invasive breast cancer with, and 1564 without, a family history of breast cancer showed that the former were younger at diagnosis (P=0.002), had smaller tumours (P=0.012), were more frequently oestrogen receptor positive (P=0.006) and diagnosed preclinically (P<0.001).

A phase II study of induction chemotherapy with gemcitabine (G) and cisplatin (P) in locally advanced non-small cell lung cancer: interim analysis.

BACKGROUND: Gemcitabine-cisplatin (GP) combination is one of the most active and well tolerated regimens in advanced non-small cell lung cancer (NSCLC). The aim of this study is to evaluate the activity and toxicity of the GP regimen as a 21-day schedule in patients (pts) with stage IIIAN2-IIIB NSCLC. PATIENTS AND METHODS: From October 1997 to July 2000, 47 pts entered the study: 43 were eligible (40 men and three women); median age was 61 years (range 45-73); ECOG PS 0-1; histology was squamous (20 pts), adenocarcinoma (12 pts), large cell (five pts), and undifferentiated (six pts); stage was IIIAN2 (14 pts, 32.56%), and IIIB (29 pts, 67.44%). Malignant pleural effusion or superior vena cava syndrome was criteria of exclusion. Induction treatment consisted of three cycles of GP (G 1250 mg/m(2) i.v. on days 1 and 8, and P 100 mg/m(2) on day 8 every 3 weeks). Responding and stable pts underwent surgery (S) and/or radiotherapy (RT). RESULTS: Following a minimum of two cycles, 39 pts were evaluable for response and 42 for toxicity. Two pts had complete responses (CR; 5.2%), 24 had partial response (PR; 61.5%), eight had stable disease (SD; 20.5%), and five had progressive disease (PRO; 12.8%). WHO grades 3 and 4 anaemia, neutropenia and thrombocytopenia were observed in two, four and two pts, respectively; non-haematological toxicity was moderate. After induction, stable and responding pts received either RT (18 pts) or S+RT (13 pts). Among the 16 resected pts, a radical complete resection was possible in 13 cases (81.3%), whereas tumour down-staging was observed in nine pts (56.2%). CONCLUSION: GP, as a 3-week neoadjuvant schedule, appears a safe and active regimen.

Comparative study of clinical, pathological and biological characteristics of symptomatic versus asymptomatic breast cancers.

BACKGROUND: It is well known that mammographic screening reduces breast cancer mortality. One possible explanation for this effect is that screening makes it possible to detect smaller breast cancers with fewer involved nodes, but another hypothesis is that some screening-detected tumors are in a pathologically and biologically different phase of evolution from those that are detected clinically. The aim of the present study was to compare the biological, pathological and clinical characteristics of symptomatic vs. asymptomatic breast cancers. PATIENTS AND METHODS: The study considers a series of 1916 consecutive patients who underwent surgery for stage I and II infiltrating breast cancer at Verona hospitals after having undergone ultrasound and mammography (at least one of which was positive). They were divided into two groups on the basis of why they decided to undergo the imaging examinations: group A refers to the 1247 patients with a palpable lump, and group B to the 616 who were asymptomatic. RESULTS: The patients in group A were older, and had larger tumors and a higher percentage of positive nodes than those in group B; they also had significantly higher grade tumors, higher Ki-67 levels, and a higher percentage of ER and PgR negative and c-erbB-2 positive tumors (all of the P-values were significant). A logistic regression analysis adjusted for tumor diameter and age showed a reduction in the significance of each of the considered variables, but all of them remained significantly associated with the modality of diagnosis except ER, PgR and c-erbB-2. CONCLUSIONS: Our results suggest that asymptomatic tumors are biologically different from their clinically presenting counterparts, thus confirming the hypothesis that progression towards greater malignancy may occur during the natural history of breast cancer.