Abemaciclib for treating patients with HR+/HER2- metastatic breast cancer: a real-world study in France, Italy and Spain.

Aim: This real-world study aimed to describe patient and clinical characteristics, treatment patterns and outcomes for patients with HR+/HER2- metastatic breast cancer receiving abemaciclib in France, Italy and Spain. Materials & methods: A multicenter chart review was conducted for adult females with HR+/HER2- advanced/metastatic breast cancer who received abemaciclib in routine care. Real-world progression-free survival (rwPFS) was estimated via Kaplan-Meier curves. Results: This study included 151, 173 and 175 patients from France, Italy and Spain, respectively. Abemaciclib was mostly prescribed as first-line therapy concomitantly with hormone therapy. Median rwPFS was >20 months and the 1-year rwPFS rate was >70%. Conclusion: Effectiveness was similar across the three countries and aligns with pivotal studies.

Abemaciclib use in the clinic in France, Italy & SpainThis study describes patients, the treatments they have received and the results of those treatments for patients with the most common type of advanced breast cancer. These patients were taking abemaciclib plus hormonal therapy in routine breast cancer care in France, Italy and Spain. The information used to conduct this study was taken from patients' medical charts. In this real-world study, abemaciclib was mostly used as the initial treatment for advanced breast cancer. Abemaciclib effectiveness was similar across the three countries confirming findings from previous studies. Our study supports the use of abemaciclib for patients with HR+/HER2- advanced breast cancer.

Bone-active drugs in premenopausal women with breast cancer under hormone-deprivation therapies.

BACKGROUND: Bone health management in premenopausal women with breast cancer (BC) under hormone-deprivation therapies (HDTs) is often challenging, and the effectiveness of bone-active drugs is still unknown. METHODS: This retrospective multicenter study included 306 premenopausal women with early BC undergoing HDTs. Bone mineral density (BMD) and morphometric vertebral fractures (VFs) were assessed 12 months after HDT initiation and then after at least 24 months. RESULTS: After initial assessment, bone-active drugs were prescribed in 77.5% of women (151 denosumab 60 mg/6 months, 86 bisphosphonates). After 47.0 ± 20.1 months, new VFs were found in 16 women (5.2%). Vertebral fracture risk was significantly associated with obesity (odds ratio [OR] 3.87, P = .028), family history of hip fractures or VFs (OR 3.21, P = .040], chemotherapy-induced menopause (OR 6.48, P < .001), preexisting VFs (OR 25.36, P < .001), baseline T-score less than or equal to -2.5 standard deviation (SD) at any skeletal site (OR 4.14, P = .036), and changes at lumbar and total hip BMD (OR 0.94, P = .038 and OR 0.88, P < .001, respectively). New VFs occurred more frequently in women untreated compared to those treated with bone-active drugs (14/69, 20.8% vs 2/237, 0.8%; P < .001) and the anti-fracture effectiveness remained significant after correction for BMI (OR 0.03; P < .001), family history of fractures (OR 0.03; P < .001), chemotherapy-induced menopause (OR 0.04; P < .001), and preexisting VFs (OR 0.01; P < .001). CONCLUSIONS: Premenopausal women under HDTs are at high risk of VFs in relationship with high BMI, densitometric diagnosis of osteoporosis, preexisting VFs, and family history of osteoporotic fractures. Vertebral fractures in this setting might be effectively prevented by bisphosphonates or denosumab.

Gastrointestinal Toxicity of Antibody Drug Conjugates (ADCs) in Metastatic Breast Cancer: A Pooled Analysis.

Trastuzumab emtansine (T-DM1), sacituzumab govitecan (SG), and trastuzumab deruxtecan (T-DXd) are three ADCs approved for the treatment of metastatic breast cancer (MBC). Since gastrointestinal toxicities have been commonly observed with these drugs in clinical trials, a pooled analysis evaluating gastrointestinal adverse events (AEs) in patients with MBC treated with ADCs in clinical trials was performed. PubMed, Embase, and the Cochrane Library were searched from inception until May 2023 for phase II and III clinical trials reporting frequency and severity of gastrointestinal AEs during treatment with ADCs. Data were retrieved for nausea, vomiting, diarrhea, constipation, and abdominal pain: overall and grade 3-4 toxicity rates according to NCI-CTCAE were collected and expressed as proportions. A pre-specified subgroup analysis according to the agent was also carried out. Fourteen studies, comprising 5608 patients, were included in the analysis. Gastrointestinal AEs were frequently registered with SG and T-DXd. A significantly higher frequency of nausea (65.6% with SG, 75% with T-DXd), vomiting (43.7% with SG, 45% with T-DXd), and diarrhea (59.7% with SG, 29% with T-DXd) was noticed with these ADCs compared to TDM-1. Furthermore, diarrhea was more frequently associated with SG (grade 3 in 7.5% of patients), while constipation and abdominal pain were less common. Gastrointestinal AEs, notably nausea and diarrhea, were frequently reported by MBC patients treated with SG and T-DXd in clinical trials. Since these ADCs are administered continuously until disease progression or occurrence of unbearable AEs, gastrointestinal toxicity may have a negative impact on patient quality of life. Therefore, appropriate management of gastrointestinal AEs is mandatory to ensure treatment efficacy and adherence.

Fat Body Mass and Vertebral Fracture Progression in Women With Breast Cancer.

Importance: Women with early breast cancer (EBC) exposed to aromatase inhibitors (AIs) may experience fragility fractures despite treatment with bone-active drugs. Risk factors for fractures in patients receiving AIs and denosumab have not been explored to date. Objectives: To evaluate whether an association exists between dual x-ray absorptiometry (DXA)-measured fat body mass (FBM) and vertebral fracture (VF) progression in postmenopausal women with EBC undergoing adjuvant therapy with AIs in combination with denosumab and to examine whether VF was associated with common risk factors for bone fracture and parameters of body composition other than FBM. Design, Setting, and Participants: For this prospective, single-center, cohort study, 237 patients with EBC who were undergoing adjuvant treatment with AIs and denosumab (60 mg every 6 months) were enrolled at the Breast Unit of the ASST Spedali Civili of Brescia from September 2014 to June 2018. Data analysis was conducted in June 2022. Exposure: Body composition parameters, bone mineral density, and morphometric VFs were assessed by DXA at study entry and after 18 months of therapy. Main Outcomes and Measures: VF progression, defined as either new or worsening of preexisting VFs, between the 2 time points. Results: Of the 237 patients enrolled (median [range] age, 61 [28-84] years), 17 (4.4%) reported VF progression. Univariable analysis found an association between VF progression and a history of clinical fractures (odds ratio [OR], 3.22; 95% CI, 1.19-8.74; P = .02), Fracture Risk Assessment Tool (FRAX) score for major fractures (OR, 4.42; 95% CI, 1.23-13.79; P = .04), percentage of FBM (OR, 6.04; 95% CI, 1.69-21.63; P = .006), and android fat (OR, 9.58; 95% CI, 1.17-78.21; P = .04) and an inverse association with appendicular lean mass index-FBM ratio (OR, 0.25, 95% CI, 0.08-0.82; P = .02). Multivariable analysis revealed percentage of FBM (OR, 5.41; 95% CI, 1.49-19.59; P = .01) and FRAX score (OR, 3.95; 95% CI, 1.09-14.39; P = .04) as independent variables associated with VF progression. Conclusions and Relevance: The findings of this study suggest that baseline FBM is an independent factor for VF progression in patients with EBC treated with adjuvant AIs and denosumab. This observation is new and indicates that diet and exercise may synergize with denosumab in the management of bone health in this patient setting.

Peripheral blood lymphocytes predict clinical outcomes in hormone receptor-positive HER2-negative advanced breast cancer patients treated with CDK4/6 inhibitors.

Background: Cyclin-Dependent Kinase 4/6 inhibitors (CDK4/6i) combined with Endocrine Therapy (ET) are the standard treatment for patients with Hormone Receptor-positive/HER2-negative advanced breast cancer (HR+/HER2- aBC). Objectives: While CDK4/6i are known to reduce several peripheral blood cells, such as neutrophils, lymphocytes and platelets, the impact of these modulations on clinical outcomes is unknown. Design: A multicenter, retrospective-prospective Italian study. Methods: We investigated the association between baseline peripheral blood cells, or their early modifications (i.e. 2 weeks after treatment initiation), and the progression-free survival (PFS) of HR+/HER2- aBC patients treated with ETs plus CDK4/6i. Random Forest models were used to select covariates associated with patient PFS among a large list of patient- and tumor-related variables. Results: We evaluated 638 HR+/HER2- aBC patients treated with ET plus CDK4/6i at six Italian Institutions between January 2017 and May 2021. High baseline lymphocyte counts were independently associated with longer PFS [median PFS (mPFS) 20.1 versus 13.2 months in high versus low lymphocyte patients, respectively; adjusted Hazard Ratio (aHR): 0.78; 95% confidence interval (CI): 0.66-0.92; p = 0.0144]. Moreover, patients experiencing a lower early reduction of lymphocyte counts had significantly longer PFS when compared to patients undergoing higher lymphocyte decrease (mPFS 18.1 versus 14.5 months; aHR: 0.82; 95% CI: 0.73-0.93; p = 0.0037). Patients with high baseline lymphocytes and undergoing a lower reduction, or even an increase, of lymphocyte counts during CDK4/6i therapy experienced the longest PFS, while patients with lower baseline lymphocytes and undergoing a higher decrease of lymphocytes had the lowest PFS (mPFS 21.4 versus 11 months, respectively). Conclusion: Baseline and on-treatment modifications of peripheral blood lymphocytes have independent prognostic value in HR+/HER2- aBC patients. This study supports the implementation of clinical strategies to boost antitumor immunity in patients with HR+/HER2- aBC treated with ETs plus CDK4/6i.

Real-world ANASTASE study of atezolizumab+nab-paclitaxel as first-line treatment of PD-L1-positive metastatic triple-negative breast cancer.

The combination of atezolizumab and nab-paclitaxel is recommended in the EU as first-line treatment for PD-L1-positive metastatic triple-negative breast cancer (mTNBC), based on the results of phase III IMpassion130 trial. However, 'real-world' data on this combination are limited. The ANASTASE study (NCT05609903) collected data on atezolizumab plus nab-paclitaxel in PD-L1-positive mTNBC patients enrolled in the Italian Compassionate Use Program. A retrospective analysis was conducted in 29 Italian oncology centers among patients who completed at least one cycle of treatment. Data from 52 patients were gathered. Among them, 21.1% presented de novo stage IV; 78.8% previously received (neo)adjuvant treatment; 55.8% patients had only one site of metastasis; median number of treatment cycles was five (IQR: 3-8); objective response rate was 42.3% (95% CI: 28.9-55.7%). The median time-to-treatment discontinuation was 5 months (95% CI: 2.8-7.1); clinical benefit at 12 months was 45.8%. The median duration of response was 12.7 months (95% CI: 4.1-21.4). At a median follow-up of 20 months, the median progression-free survival was 6.3 months (95% CI: 3.9-8.7) and the median time to next treatment or death was 8.1 months (95% CI: 5.5-10.7). At 12 months and 24 months, the overall survival rates were 66.3% and 49.1%, respectively. The most common immune-related adverse events included rash (23.1%), hepatitis (11.5%), thyroiditis (11.5%) and pneumonia (9.6%). Within the ANASTASE study, patients with PD-L1-positive mTNBC treated with first-line atezolizumab plus nab-paclitaxel achieved PFS and ORR similar to those reported in the IMpassion130 study, with no unexpected adverse events.

Is weight gain preventable in women with early breast cancer undergoing chemotherapy? A real-world study on dietary pattern, physical activity, and body weight before and after chemotherapy.

PURPOSE: We aimed to investigate the role of a lifestyle intervention and clinical and therapeutic factors for preventing weight gain in early breast cancer (BC) patients from one week before to 12 months after chemotherapy. METHODS: Dietary assessments were conducted by a trained dietician using a food-frequency questionnaire at each clinical assessment. Total energy, macronutrients intakes, and physical activity were estimated and the Mediterranean Diet Score (MDS) for adherence to Mediterranean diet was calculated. At each follow-up visit, patients were provided with dietary advices according to Mediterranean and Italian guidelines by a registered dietician, after evaluation of their food records. The associations of clinical characteristics, dietary pattern, and physical activity with weight gain were evaluated by multiple logistic regression, with weight gain ≥5% from baseline value as a dichotomous dependent variable. RESULTS: 169 early BC patients who met all follow-up visits and provided complete data were included in the analysis. From baseline to last assessment, weight loss (≥5% decrease from baseline value), stable weight, and weight gain were observed in 23.1%, 58%, and 18.9% women, respectively. Overall, a 0.68 kg mean decrease in women's weight (-1.1% from baseline) was observed. The risk of gaining weight increased for having normal weight/underweight at baseline, receiving hormone therapy, MDS worsening, and physical activity decreasing from baseline to last assessment. CONCLUSION: Providing simple suggestions on Mediterranean diet principles was effective for preventing weight gain in normal weight women and favoring weight loss in overweight and obese women.

Role of Body Composition in the Prediction of Skeletal Fragility Induced by Hormone Deprivation Therapies in Cancer Patients.

PURPOSE OF REVIEW: This review paper is intended to show that changes in body composition are key in the pathogenesis of bone fragility amongst patients with breast and prostate cancer receiving hormone deprivation therapies (HDTs) and that the mechanism is based on the development of alterations in bone quality rather than in bone quantity. RECENT FINDINGS: Preclinical and clinical data suggest a tight connection amongst bone, adipose and muscular tissues by means of several soluble mediators, potentially leading to (1) bone resorption and bone quality deterioration in sarcopenic obese subjects, (2) bone mineral deposition in healthy trained subjects. Cancer patients treated with HDTs frequently fall into the first condition, named osteosarcopenic obesity. Current clinical guidelines for the prevention of treatment-induced osteoporosis focus on bone mineral density (BMD) as a main predictive factor for fracture risk; however, the pathophysiology underlying HDT-induced bone fragility differs from that of primary and postmenopausal osteoporosis, suggesting a prevalent role for bone quality alterations. Focusing on available data from clinical trials, in our review we suggest osteosarcopenic obesity as a common target for the prevention and treatment of HDTs-related metabolic and skeletal complications, beyond a BMD-centred approach.

Prognostic significance of HER2-low status in HR-positive/HER2-negative advanced breast cancer treated with CDK4/6 inhibitors.

Whether Human Epidermal growth factor Receptor 2 (HER2)-low status has prognostic significance in HR + /HER2- advanced Breast Cancer (aBC) patients treated with first-line Endocrine Therapy plus CDK 4/6 inhibitors remains unclear. In 428 patients evaluated, HER2-low status was independently associated with significantly worse PFS and OS when compared with HER2-0 status. Based on our findings, HER2-low status could become a new prognostic biomarker in this clinical setting.

Sacituzumab govitecan and radiotherapy in metastatic, triple-negative, and BRCA-mutant breast cancer patient with active brain metastases: A case report.

Background: Triple-negative breast cancer (TNBC) is an aggressive cancer subtype, owing to its high metastatic potential: Patients who develop brain metastases (BMs) have a poor prognosis due to the lack of effective systemic treatments. Surgery and radiation therapy are valid options, while pharmacotherapy still relies on systemic chemotherapy, which has limited efficacy. Among the new treatment strategies available, the antibody-drug conjugate (ADC) sacituzumab govitecan has shown an encouraging activity in metastatic TNBC, even in the presence of BMs. Case presentation: A 59-year-old woman was diagnosed with early TNBC and underwent surgery and subsequent adjuvant chemotherapy. A germline pathogenic variant in BReast CAncer gene 2 (BRCA2) was revealed after genetic testing. After 11 months from the completion of adjuvant treatment, she had pulmonary and hilar nodal relapse and began first-line chemotherapy with carboplatin and paclitaxel. However, after only 3 months from starting the treatment, she experienced relevant disease progression, due to the appearance of numerous and symptomatic BMs. Sacituzumab govitecan (10 mg/kg) was started as second-line treatment as part of the Expanded Access Program (EAP). She reported symptomatic relief after the first cycle and received whole-brain radiotherapy (WBRT) concomitantly to sacituzumab govitecan treatment. The subsequent CT scan showed an extracranial partial response and a near-to-complete intracranial response; no grade 3 adverse events were reported, even if sacituzumab govitecan was reduced to 7.5 mg/kg due to persistent G2 asthenia. After 10 months from starting sacituzumab govitecan, a systemic disease progression was documented, while intracranial response was maintained. Conclusions: This case report supports the potential efficacy and safety of sacituzumab govitecan in the treatment of early recurrent and BRCA-mutant TNBC. Despite the presence of active BMs, our patient had a progression-free survival (PFS) of 10 months in the second-line setting and sacituzumab govitecan was safe when administered together with radiation therapy. Further real-world data are warranted to confirm sacituzumab govitecan efficacy in this patient population.

Assessment of DXA derived bone quality indexes and bone geometry parameters in early breast cancer patients: A single center cross-sectional study.

Background: Bone mineral density (BMD) lacks sensitivity in individual fracture risk assessment in early breast cancer (EBC) patients treated with aromatase inhibitors (AIs). New dual-energy X-ray absorptiometry (DXA) based risk factors are needed. Methods: Trabecular bone score (TBS), bone strain index (BSI) and DXA parameters of bone geometry were evaluated in postmenopausal women diagnosed with EBC. The aim was to explore their association with morphometric vertebral fractures (VFs). Subjects were categorized in 3 groups in order to evaluate the impact of AIs and denosumab on bone geometry: AI-naive, AI-treated minus (AIDen-) or plus (AIDen+) denosumab. Results: A total of 610 EBC patients entered the study: 305 were AI-naive, 187 AIDen-, and 118 AIDen+. In the AI-naive group, the presence of VFs was associated with lower total hip BMD and T-score and higher femoral BSI. As regards as bone geometry parameters, AI-naive fractured patients reported a significant increase in femoral narrow neck (NN) endocortical width, femoral NN subperiosteal width, intertrochanteric buckling ratio (BR), intertrochanteric endocortical width, femoral shaft (FS) BR and endocortical width, as compared to non-fractured patients. Intertrochanteric BR and intertrochanteric cortical thickness significantly increased in the presence of VFs in AIDen- patients, not in AIDen+ ones. An increase in cross-sectional area and cross-sectional moment of inertia, both intertrochanteric and at FS, significantly correlated with VFs only in AIDen+. No association with VFs was found for either lumbar BSI or TBS in all groups. Conclusions: Bone geometry parameters are variably associated with VFs in EBC patients, either AI-naive or AI treated in combination with denosumab. These data suggest a tailored choice of fracture risk parameters in the 3 subgroups of EBC patients.

Sleep disturbances and restless legs syndrome in postmenopausal women with early breast cancer given adjuvant aromatase inhibitor therapy.

INTRODUCTION: Whether adjuvant therapy with aromatase inhibitors (AIs) causes sleep disturbances or not in postmenopausal women with early breast cancer (EBC) is still a controversial issue. METHODS: Between March 2014 and November 2017, validated questionnaires for assessing insomnia, anxiety, depression, quality of life (QoL) and restless legs syndrome (RLS) were administered to 160 EBC patients at baseline and after 3, 6, 12, and 24 months of AI therapy. RESULTS: AI therapy significantly decreased the patients' QoL, but did not influence insomnia, anxiety or depression. However, it significantly increased the frequency and severity of RLS. Patients with RLS at baseline (19%) or who developed RLS during AI therapy (26.3%) reported statistically lower quality of sleep, higher anxiety and depression, and worse QoL compared to patients who never reported RLS (54.7%). CONCLUSION: Although AI therapy does not affect sleep quality, it may increase RLS frequency. The presence of RLS could identify a group of EBC patients who may benefit from psychological support.

Real-World Effectiveness of Denosumab and Bisphosphonates on Risk of Vertebral Fractures in Women with Breast Cancer Undergoing Treatment with Aromatase Inhibitors.

Bone-active drugs are recommended to protect the skeleton from detrimental actions of aromatase inhibitors (AIs). However, most of literature data are focused on bone mineral density (BMD), whereas data on fractures are scant. The aim of this prospective study was to investigate the real-life effectiveness of denosumab, oral bisphosphonates (BPs) and intravenous zoledronate on risk of vertebral fractures (VFs) induced by AIs. 567 consecutive women (median age 62 years, range 28-83) with early breast cancer undergoing treatment with AIs were evaluated for morphometric VFs and BMD at baseline and after 18-24 months of follow-up. After enrollment, 268 women (47.3%) started denosumab 60 mg subcutaneously every 6 months, 115 (20.3%) BPs (59 with oral BPs and, 56 with intravenous zoledronate 5 mg/12 months), whereas 184 women (32.5%) were not treated with bone-active drugs for several reasons. During follow-up, 54 women (9.5%) developed incident VFs in association with age of subjects (P < 0.001), baseline FRAX scores for major fractures (P < 0.001) and hip fractures (P = 0.003), pre-existing VFs (P < 0.001), change in BMD at lumbar spine (P = 0.015), femoral neck (P = 0.003) and total hip (P < 0.001). Risk of VFs was higher in subjects who were untreated as compared to those treated with bone-active drugs (32/184 vs. 22/383; P < 0.001). Specifically, fracture risk was significantly decreased by denosumab [odds ratio (OR) 0.22; P < 0.001] and zoledronate (OR 0.27; P = 0.035), but not by oral BPs (P = 0.317). These data suggest that in real-world clinical practice, denosumab and zoledronate can reduce AI-related risk of VFs after only 24 months of treatment.

Taste Alterations Do Not Affect Change in Food Habits and Body Weight in Breast Cancer Patients.

BACKGROUND/AIM: Chemotherapy-induced taste alterations (TAs) affect approximately 53-84% of breast cancer patients with significant consequences on flavor perception, possibly leading to food aversion and changes in daily dietary habits. The aim of this study was to investigate the relationship between TAs and changes in food habits and body weight among early breast cancer (EBC) patients undergoing adjuvant chemotherapy. PATIENTS AND METHODS: TAs were prospectively evaluated in 182 EBC patients from April 2014 to June 2018. TAs, dietary habits, and body weight were collected by a trained dietician. TAs were classified into different subtypes according to the following basic taste perception: metallic, sweet, bitter, salty, sour, and umami taste. RESULTS: During adjuvant chemotherapy, a significant reduction in the consumption of bread, breadsticks, red meat, fat salami, snacks, added sugar, milk, and alcoholic beverages was observed, regardless of TAs onset. No correlation between these dietary changes and different TAs subtypes was found. Body weight remained stable in most EBC patients (71.4%) and was not influenced by TAs onset and by different TAs subtypes. CONCLUSION: EBC patients change their dietary habits during adjuvant chemotherapy, mostly following the World Cancer Research Fund recommendations, irrespective of TAs onset and without affecting body weight.

Ovarian Strumal Carcinoid: Case Report, Systematic Literature Review and Pooled Analysis.

Background: Ovarian strumal carcinoid is a rare tumor in which thyroid (struma) and carcinoid components coexist. The disease is generally considered to be a borderline malignancy, however, cases with metastatic disease have been described. No data in the literature are available to guide diagnosis and therapy. Methods: We performed a pooled analysis and a systematic review of histopathological-confirmed strumal carcinoid cases published in the literature using the following keywords: "strumal carcinoid of the ovary", "strumal carcinoid case report". A case of strumal carcinoid tumor diagnosed and followed-up at the Medical Oncology Unit of Spedali Civili (Brescia, Italy) was also described and included. Results: Sixty-six eligible publications were identified, providing data from one hundred and seventeen patients, plus a case diagnosed at our institution. At presentation, among the eighty-eight patients with symptomatic disease, 37% of patients suffered from abdominal distention and 49% from pain due to a growing abdominal tumor mass, 37% from constipation (peptide YY was analyzed in only nine of them, resulting above the physiologic range). Surgery was the primary therapy in 99% of the patients. Three patients had metastatic disease at diagnosis and five patients underwent recurrence after radical surgery. Histology at disease recurrence concerned the thyroid component in two patients, the carcinoid component in two patients, both histologies in one patient. Median disease-free survival and overall survival in this series were not attained. Conclusion: Strumal carcinoid of the ovary generally presents a benign behavior and surgery is curative in most cases. However, a small group of patients with this disease can undergo disease recurrence due to both the thyroid and the neuroendocrine (carcinoid) components. A follow-up in radically operated patients is therefore needed, particularly in those with a voluminous disease at diagnosis.

Taste alterations during neo/adjuvant chemotherapy and subsequent follow-up in breast cancer patients: a prospective single-center clinical study.

PURPOSE: Dysgeusia and taste alterations (TAs) are side effects of cytotoxic chemotherapy and affect patients' quality of life; however, the prevalence, types, and duration of TAs and their potential relationship with other clinical disturbances are not well-described. Our primary aim was to prospectively evaluate the characteristics of TAs in early breast cancer (EBC) patients during (neo)adjuvant chemotherapy and up to 1 year after its completion. METHODS: From April 2014 to June 2018, 182 EBC patients entered the study and received (neo)adjuvant chemotherapy, mostly with taxane and anthracycline-containing regimens (65% of cases). A dietitian performed TAs assessment through the Common Terminology Criteria for Adverse Event v4.0 (CTCAE) and the Chemotherapy-induced Taste Alteration Scale (CiTAS) questionnaire during chemotherapy and follow-up according to defined time points: at baseline (T0, before starting chemotherapy); at the first follow-up visit, (T1, 2 months after starting chemotherapy); at the final follow-up visit (T2, 1 week after completing chemotherapy); after that, every 3 months up to 12 months. RESULTS: Dysgeusia was reported by 69.8% of patients at T1 and declined subsequently; salty flavor distortion was the most frequently reported TA (51.6% of cases). CiTAS was significantly different between T0 and T2 (p < 0.001). Dysgeusia occurred more frequently in patients reporting nausea, mucositis, diarrhea, and appetite modification. CONCLUSIONS: TAs are common but transient during chemotherapy and occurred frequently with other distressing gastrointestinal side effects. The assessment of these side effects is crucial in managing EBC patients during (neo)adjuvant chemotherapy.

Ribociclib in the Treatment of Hormone-Receptor Positive/HER2-Negative Advanced and Early Breast Cancer: Overview of Clinical Data and Patients Selection.

Among pre- and postmenopausal women with hormone receptor-positive (HR+) breast cancer (BC), combinations of an aromatase inhibitor (AI) or fulvestrant with a CDK 4/6 inhibitor (palbociclib, ribociclib, or abemaciclib) have demonstrated improved progression-free survival (PFS) and overall survival (OS) compared to standard single-agent hormone therapy alone as first-line therapy for de novo metastatic disease or relapse during or after adjuvant therapy and no previous therapies in an advanced setting. We here reviewed clinical data about ribociclib in advanced and early BC. Also, we shed light on patient selection and special settings in which medical oncologists urgently await an advance in treatment. Ribociclib was FDA-approved in combination with letrozole based on a Phase III study in which 668 postmenopausal women with HR+, HER2-negative recurrent or metastatic BC were treated with first-line letrozole with or without ribociclib. For patients with metastatic disease at presentation or after a course of AIs, the results of the MONALEESA-3 trial suggest ribociclib's efficacy in combination with fulvestrant, and this combination is FDA-approved for initial- and subsequent-line endocrine therapy for postmenopausal women with metastatic hormone receptor-positive, HER2-negative BC. In adjuvant and neoadjuvant settings, the use of CDK 4/6 inhibitors may be useful to boost outcomes in high-risk patients with HR+ BC, but data contrast with those of a phase III study, which produced positive results. New combinations are being explored in upfront disease (neoadjuvant) or in association with other targeted agents in metastatic disease. Compared to other CDK 4/6 available, ribociclib has a higher incidence of liver function test abnormalities than the other agents and can cause QTc prolongation, and therefore may be prudently avoided in patients with cardiac morbidities or other risk factors for QTc prolongation (drugs, interactions). In these cases, different agents (palbociclib or abemaciclib) may be used. In conclusion, ribociclib with letrozole or with fulvestrant is effective for the entire spectrum of patients with HR+ BC in the advanced setting. Ribociclib has all the characteristics of an innovative drug able to change the clinical practice and most BC patients' prognoses.

Prediction of vertebral fractures in cancer patients undergoing hormone deprivation therapies: Reliability of who fracture risk assessment tool (frax) and bone mineral density in real-life clinical practice.

Background and Objective: Prediction of fractures in cancer survivors exposed to hormone-deprivation therapies (HDTs) is a challenge since bone loss is rapid and severe, and determinants of fractures in this setting are still largely unknown. In this study we investigated reliability of the WHO Fracture Risk Assessment Tool (FRAX) and bone mineral density (BMD) to identify subjects developing vertebral fractures during HDTs. Design: Five-hundred-twenty-seven consecutive subjects (429 females with breast cancer, 98 males with prostate cancer; median age 61 years), under HDTs for at least 6 months, were evaluated for vertebral fractures by a radiological and morphometric approach, in relationship with FRAX score, body mass index (BMI), BMD, age and duration of HDTs. Results: Vertebral fractures were found in 140 subjects (26.6%) and spine deformity index was significantly associated with duration of HDTs (rho 0.38; p < 0.001). Only in females, vertebral fractures were significantly associated with FRAX score for major fractures [OR 1.08; P < 0.001]. The best cut-off of FRAX score for major fractures, as calculated by receiving operating characteristic (ROC) analysis was 6.35%. In males, however, vertebral fractures were significantly and independently associated with BMI ≥ 25 Kg/m2 (OR 17.63; P < 0.001), BMD T-score below -1.0 SD at any skeletal site (OR 7.79; P < 0.001) and gonadotropin-releasing hormone agonists (GnRHa) plus abiraterone treatment (OR 11.51; P = 0.001). Conclusions: FRAX and BMD may be useful for predicting vertebral fractures in subjects undergoing HDTs, but the thresholds seem to be lower than those used in the general population. High BMI is a determinant of vertebral fractures in males under HDT.