Factors influencing 5-year persistence to adjuvant endocrine therapy in young women with breast cancer.

PURPOSE: Although younger age has been negatively associated with persistence to adjuvant endocrine therapy (ET), factors contributing to non-persistence remain poorly understood. We assessed factors associated with non-persistence to ET and described the 5-year trajectories of quality of life (QoL) and symptoms in young women (≤40 years) with hormone receptor-positive breast cancer (BC). METHODS: We retrieved data on clinical characteristics and non-persistence from the medical annual records in the European cohort of the "Helping Ourselves, Helping Others: The Young Women's BC Study" (IBCSG 43-09 HOHO). Women completed surveys at baseline, biannually for three years, and annually for another seven years. Data collection included sociodemographic information, QoL aspects assessed by the Cancer Rehabilitation Evaluation System-Short Form and symptoms assessed by the Breast Cancer Prevention Trial symptom scales. Cox regression models were applied to identify factors associated with non-persistence. RESULTS: The cumulative risk of interrupting ET within 5 years was 27.7 % (95 % CI, 21.5-35.2). The QoL subscale scores remained stable over 5 years, with slight improvements in the physical subscale. Hot flashes decreased (p < 0.001), while vaginal problems intensified (p < 0.001) over time. Being married without children and having difficulties interacting and communicating with the medical team were significantly associated with non-persistence. CONCLUSIONS: Discussing the desire to conceive with partnered childless women and establishing a good relationship with the medical team may be important in addressing the non-persistence in young BC survivors. As recent data suggests the safety of pausing ET to conceive, this approach may be a reasonable future option to limit non-persistence.

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.

Real-world use of multigene signatures in early breast cancer: differences to clinical trials.

PURPOSE: In Italy, Lombardy was the first region to reimburse multigene assays (MGAs) for patients otherwise candidates for chemotherapy. This is a real-world experience of MGAs usage in six referral cancer centers in Lombardy. METHODS: Among MGAs, Oncotype DX (RS) was used in 97% of cases. Consecutive patients tested with Oncotype DX from July 2020 to July 2022 were selected. The distribution of clinicopathologic features by RS groups (low RS: 0-25, high RS: 26-100) was assessed using chi-square and compared with those of the TAILORx and RxPONDER trials. RESULTS: Out of 1,098 patients identified, 73% had low RS. Grade and Ki67 were associated with RS (p < 0.001). In patients with both G3 and Ki67 > 30%, 39% had low RS, while in patients with both G1 and Ki67 < 20%, 7% had high RS. The proportion of low RS in node-positive patients was similar to that in RxPONDER (82% vs 83%), while node-negative patients with low RS were significantly less than in TAILORx (66% vs 86%, p < 0.001). The distribution of Grade was different from registration trials, with more G3 and fewer G1 (38% and 3%) than in TAILORx (18% and 27%) and RxPONDER (10% and 24%) (p < 0.001). Patients ≤ 50 years were overrepresented in this series (41%) than in TAILORx and RxPONDER (31% and 24%, respectively) (p < 0.001) and, among them, 42% were node positive. CONCLUSIONS: In this real-world series, Oncotype DX was the test almost exclusively used. Despite reimbursement being linked to pre-test chemotherapy recommendation, almost 3/4 patients resulted in the low-RS group. The significant proportion of node-positive patients ≤ 50 years tested indicates that oncologists considered Oncotype DX informative also in this population.

Breaking barriers in triple negative breast cancer (TNBC) - Unleashing the power of antibody-drug conjugates (ADCs).

Antibody-drug conjugates (ADCs) represent a novel class of molecules composed of a recombinant monoclonal antibody targeted to a specific cell surface antigen, conjugated to a cytotoxic agent through a cleavable or non-cleavable synthetic linker. The rationale behind the development of ADCs is to overcome the limitations of conventional chemotherapy, such as the narrow therapeutic window and the emergence of resistance mechanisms. ADCs had already revolutionized the treatment algorithm of HER2-positive breast cancer. Currently, emergent non-HER2 targeted ADCs are gaining momentum, with special focus on triple-negative disease therapeutic landscape. Sacituzumab govitecan (SG) is an ADC consisting of a humanized monoclonal antibody hRS7 targeting trophoblast cell surface antigen 2 (Trop2), linked to the topoisomerase I inhibitor SN-38 by a hydrolysable linker. It currently stands as the only non-HER2 targeted ADC that already received approval for the treatment of unresectable locally advanced or metastatic triple negative breast cancer (TNBC) in patients who had received two or more prior systemic therapies, with at least one for advanced disease. The purpose of these review is to analyze the available evidence regarding ADCs in TNBC, alongside with providing an overview on the ongoing and future research horizons in this field.

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.

Multigene signatures for early breast cancer in clinical practice: A report of the Lombardy genomic assays for breast cancer working group.

The increasing understanding of breast cancer biology has provided the basis for the development of multigene signatures aimed to improve the capability of clinicians to assess patients' prognostication and risk stratification. Incorporating these tools in clinical practice has profoundly impacted on the decision-making process for the adjuvant therapy of patients with ER+/HER2- early breast cancer and the results from prospective adjuvant trials have strengthened the clinical utility of multigene signatures in this setting. In July 2019, Lombardy was the first Region in Italy to reimburse genomic testing for patients with ER+/HER2- early breast cancer. Three years later, a group of investigators from six referral Cancer Centers in Lombardy convened to debate the use of multigene signatures in clinical practice and share their own experience with the tests after reimbursement. Here, we reviewed relevant data on the role of multigene signatures in tailoring adjuvant chemotherapy for patients with ER+/HER2- early breast cancer and discussed about the optimal use of these assays in current clinical practice. As the treatment landscape of early breast cancer evolves and novel questions about the possible additional applications of multigene assays arise, we also provide our viewpoint on the potential implementation of the assays in the evolving scenario ER+/HER2- early breast cancer treatment.

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.

Employment trajectories of young women with breast cancer: an ongoing prospective cohort study in Italy and Switzerland.

PURPOSE: Despite extensive research on cancer and work-related outcomes, evidence from longitudinal cohort studies is limited, especially in young women with breast cancer (BC). We aimed to investigate employment trajectories in young BC survivors and to identify potential factors associated with changes in work activity. METHODS: The HOHO European prospective multicenter cohort study enrolled 300 young women (≤ 40 years) with newly diagnosed BC. Women completed surveys at baseline and every 6 months for 3 years, then yearly for up to 10 years to assess, among other variables, employment status, sociodemographic, medical, and treatment data. Symptoms were assessed by the Breast Cancer Prevention Trial symptom scales and single items from the Cancer Rehabilitation Evaluation System. Univariable and multivariable multinomial logistic regression analyses identified factors associated with changes in employment status. RESULTS: Among the 245 women included in this analysis, 85% were employed at the last individual post-baseline assessment (1 to 10 years). At 5 years, women had a 29.4% probability (95% CI: 23.6-35.5) of experiencing any reduction and a 14.9% probability (95% CI: 10.6-19.9) of experiencing any increase in work activities. Being enrolled in Switzerland (vs. Italy) and reporting more trouble in performing daily activities were significantly associated with work reduction. CONCLUSION: Our results suggest that most young BC survivors remain employed in the long-term. IMPLICATIONS FOR CANCER SURVIVORS: Regular evaluation of symptoms which may interfere with daily life and identification of financial discomfort is critical in providing timely and individually tailored interventions and in limiting unwanted reductions in work activities.

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.

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.

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.

Changes in eating habits and food preferences in breast cancer patients undergoing adjuvant chemotherapy.

Change in eating habits in early breast cancer (EBC) patients during chemotherapy has been poorly studied in the literature. The primary aim of this study was to prospectively evaluate food preferences and weight change in EBC patients before and after adjuvant chemotherapy. From April 2014 to June 2018, 205 EBC patients underwent a dietary assessment according to the following timeline: baseline evaluation (one week before starting chemotherapy, T0); first follow-up (approximately 2-3 months after starting chemotherapy, T1); final follow-up (one week after chemotherapy end, T2). A statistically significant reduction of the following foods was reported after the start of chemotherapy: pasta or rice, bread, breadsticks/crackers, red meat, fat and lean salami, fresh and aged cheese, milk, yogurt, added sugar, soft drinks, alcoholic beverages (wine, beer, and schnapps), and condiments (oil and butter). Conversely, fruit consumption consistently increased. As a result of these changes, a Healthy Eating Index (HEI) specifically developed for this study and suggestive of a balanced diet, significantly increased. Body weight did not increase, despite reduction in physical activity. This prospective study shows that EBC patients tend to adopt "healthier dietary patterns" during adjuvant chemotherapy, leading to a non-change in weight, despite reduction in physical activity.

The Interaction of Lean Body Mass With Fat Body Mass Is Associated With Vertebral Fracture Prevalence in Women With Early Breast Cancer Undergoing Aromatase Inhibitor Therapy.

Aromatase inhibitors (AIs) induce depletion of estrogen levels, causing bone loss and increased fracture risk in women with breast cancer. High-fat body mass (FBM) emerged as an independent factor associated with the prevalence of morphometric vertebral fractures (VFs) in patients undergoing AIs. We explored the role of lean body mass (LBM) and the interaction of LBM with FBM in predicting the occurrence of VFs in postmenopausal women who were either AI-naïve or AI-treated. A total of 684 consecutive breast cancer patients were enrolled in this cross-sectional study. Each woman underwent a dual-energy X-ray absorptiometry (DXA) scan, measuring bone mineral density (BMD), LBM, and FBM; VFs were assessed using a quantitative morphometric analysis of DXA images. After propensity score matching, the study population was restricted to 480 women, 240 AI-naïve and 240 AI-treated. We used multivariable logistic regression models to explore the associations between baseline characteristics, VF prevalence and the interaction between LBM, FBM and AI therapy. No interaction between LBM and AI therapy on VF prevalence was shown. Conversely, we reported a significant interaction between LBM, FBM and AI therapy (p = .0311). Among AI-treated women having LBM below and FBM above or equal the median value, VF prevalence was numerically higher (15/31; 48.4%) than in other subgroups (VF prevalence: 35.7% in high-LBM and low-FBM group, 23.2% in high-LBM and high-FBM group, and 19.8% in low-LBM and low-FBM group). Among AI-naïve women, the greatest VF proportion was observed in the subgroup with LBM and FBM below median value (25/92; 27.2%). This study suggests a synergism between LBM and FBM in predicting the morphometric VF in women with early breast cancer undergoing AIs. This observation is new and deserves further investigation. The assessment of body composition by DXA might be useful when estimating fracture risk in this population. © 2020 American Society for Bone and Mineral Research © 2020 The Authors. JBMR Plus published by Wiley Periodicals LLC. on behalf of American Society for Bone and Mineral Research.

Genomic Aberrations and Late Recurrence in Postmenopausal Women with Hormone Receptor-positive Early Breast Cancer: Results from the SOLE Trial.

PURPOSE: Women with hormone receptor-positive early breast cancers have a persistent risk of relapse and biomarkers for late recurrence are needed. We sought to identify tumor genomic aberrations associated with increased late-recurrence risk. EXPERIMENTAL DESIGN: In a secondary analysis of Study of Letrozole Extension trial, a case-cohort-like sampling selected 598 primary breast cancers for targeted next-generation sequencing analysis of gene mutations and copy-number gains (CNGs). Correlations of genomic aberrations with clinicopathologic factors and breast and distant recurrence-free intervals (BCFIs and DRFIs) were analyzed using weighted Cox models. RESULTS: Analysis of mutations and CNGs was successfully performed for 403 and 350 samples, including 148 and 134 patients with breast cancer recurrences (median follow-up time, 5.2 years), respectively. The most frequent alterations were PIK3CA mutations (42%) and CNGs of CCND1 (15%), ERBB2 (10%), FGFR1 (8%), and MYC (8%). PIK3CA mutations and MYC CNGs were associated with lower (P = 0.03) and higher (P = 0.004) tumor grade, respectively; a higher Ki-67 was seen in tumor with CCND1, ERBB2, and MYC CNGs (P = 0.01, P < 0.001, and P = 0.03, respectively). FGFR1 CNG was associated with an increased risk of late events in univariate analyses [17/29 patients; BCFI: HR, 3.2; 95% confidence interval (CI), 1.48-6.92; P = 0.003 and DRFI: HR, 3.5; 95% CI, 1.61-7.75; P = 0.002) and in multivariable models adjusted for clinicopathologic factors. CONCLUSIONS: Postmenopausal women with hormone receptor-positive early breast cancer harboring FGFR1 CNG had an increased risk of late recurrence despite extended therapy. FGFR1 CNG may represent a useful prognostic biomarker for late recurrence and a therapeutic target.

Efficacy of the DigniCap System in preventing chemotherapy-induced alopecia in breast cancer patients is not related to patient characteristics or side effects of the device.

BACKGROUND: The DigniCap System is an effective scalp cooling device for the prevention of chemotherapy-induced alopecia in early breast cancer patients. AIM: This prospective study was designed to confirm the efficacy and tolerability of the device, to explore potential factors associated with its efficacy and to collect data on patient perceptions and satisfaction. METHODS: Between January 2016 and June 2018, 163 early breast cancer patients eligible for adjuvant chemotherapy were enrolled. Hair loss was assessed using the Dean scale, where a score of 0-2 (hair loss ≤50%) was defined as successful. RESULTS: Hair preservation was successful in 57% of patients in the overall series. The proportion was even higher (81%) in the patient subgroup treated with a paclitaxel and trastuzumab regimen. Side effects (feeling cold, headache, head heaviness, scalp and cervical pain) were mild to moderate and did not correlate with the rate of hair loss. Lifestyle, anthropometric factors and hair characteristics failed to be associated with device efficacy. CONCLUSIONS: The DigniCap System was well tolerated and found to be effective in preventing alopecia in early breast cancer patients. Our study failed to identify factors other than type of chemotherapy regimen associated with hair preservation.

A single-center retrospective safety analysis of cyclin-dependent kinase 4/6 inhibitors concurrent with radiation therapy in metastatic breast cancer patients.

Cyclin dependent kinases 4/6 (CDK4/6) inhibitors gained an essential role in the treatment of metastatic breast cancer. Nevertheless, data regarding their use in combination with radiotherapy are still scarce. We performed a retrospective preliminary analysis of breast cancer patients treated at our Center with palliative radiation therapy and concurrent CDK4/6 inhibitors. Toxicities were measured according to CTCAE 4.0, local response according to RECIST 1.1 or PERCIST 1.0 and pain control using verbal numeric scale. 18 patients (32 treated sites) were identified; 50% received palbociclib, 33.3% ribociclib and 16.7% abemacliclib. Acute non-hematologic toxicity was fair, with the only exception of a patient who developed G3 ileitis. During 3 months following RT, 61.1% of patients developed G 3-4 neutropenia; nevertheless no patient required permanent suspension of treatment. Pain control was complete in 88.2% of patients three months after radiotherapy; 94.4% of patients achieved and maintained local control of disease. Radiotherapy concomitant to CDK4/6 inhibitors is feasible and characterized by a fair toxicity profile, with isolated episodes of high-grade reversible intestinal toxicity. Rate of G 3-4 neutropenia was comparable with that measured for CDK4/6 inhibitors alone. Promising results were reported in terms of pain relief and local control of disease.

Prospective observational study on the impact of the 21-gene assay on treatment decisions and resources optimization in breast cancer patients in Lombardy: The BONDX study.

PURPOSE: Adjuvant treatment decisions in early breast cancer (eBC) have traditionally been driven by risk stratification based on clinical and pathological risk factors. The 21-gene Oncotype DX® assay has been validated as a predictive test for benefit from adjuvant chemotherapy (CT), hence assessing its impact in clinical decisions is of high interest. The objective of this study was to estimate the rate of adjuvant treatment decision modification impacted by the Recurrence Score® result, and the consequent budget impact. METHODS: The study was a multicentre, prospective, real-life experience in Lombardy (Italy) including consecutive patients with T1-T3, N0-N1a, and ER+/HER2-eBC with clinical-pathologic "intermediate risk" of relapse. The change in treatment recommendations was assessed before and after availability of Recurrence Score result. A budget model evaluated the implications of 21-gene testing in the study population. RESULTS: The overall proportion of CT recommendations was reduced from 24.6% to 15.2% after 21-gene testing, with a major impact in patients initially considered for CT plus hormone therapy (CHT). In these patients, the total budget was reduced, leading to a net saving of -€81,017. The greater the physician propensity to prescribe CHT, the higher the potential savings for the health system from sparing CT in most tested patients. CONCLUSIONS: Our real-life experience suggests that all intermediate-risk ER+/HER2-eBC patients who are initially deemed candidates for CHT should be tested with the 21-gene test. The potential to spare CT in at least half of them offers relevant advantages for patients and national health services.

Efficacy of Eribulin mesylate in older patients with breast cancer: A pooled analysis of clinical trial and real-world data.

PURPOSE: Eribulin mesylate (EM) is a non-taxane microtubule inhibitor approved for use in patients with metastatic breast cancer. With this pooled analysis of retrospective studies, we evaluated the efficacy and toxicity profile of EM in older patients with breast cancer in the real-world setting. METHODS: We performed a systematic database search for studies published up to March 2019 and reporting outcome and adverse events with EM in older patients (≥70 years). Overall survival (OS), progression-free survival (PFS), and overall response rate (ORR) were described and aggregated in a pooled analysis. Main toxicity rates (G1-2 and G3-4) were also described. RESULTS: The analysis included five studies for a total of 301 patients. The median age was 71 to 74 years. Pooled ORR, median PFS and OS were 23.2%, 4.8 and 13.1 months, respectively. The disease control rate was 47%. Grade 3-4 neutropenia was 0 to 49%, G3-4 anemia and thrombocytopenia were rare. The most frequent G3-4 adverse events among non-hematological toxicities were fatigue (5-16.5%) and neurotoxicity (0-10.1%). Dose reduction rate was reported in three studies and carried out in 40% of patients (18.6-84%). CONCLUSIONS: This pooled analysis shows that the median OS in older patients with breast cancer is 13 months, with an ORR of 23%. Control of disease was achieved in about 50% of patients. Dose reduction was relatively frequent and severe toxicities were rare. EM treatment of older patients with breast cancer is feasible and reflects the outcomes for the general population.