Publications by authors named "Vito Amoroso"

46 Publications

Everolimus plus aromatase inhibitors as maintenance therapy after first-line chemotherapy: Final results of the phase III randomised MAIN-A (MAINtenance Afinitor) trial.

Eur J Cancer 2021 09 2;154:21-29. Epub 2021 Jul 2.

Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy; Medical Oncology 2, Istituto Oncologico Veneto IOV - IRCCS, Padova, Italy.

Background: Despite endocrine therapy being the mainstay of treatment for hormone receptor positive (HR+)/HER2- metastatic breast cancer, patients at risk of visceral crisis or doubt for endocrine sensitivity are still offered first-line chemotherapy. Maintenance hormonal therapy is generally offered at the discontinuation of chemotherapy. The MAINtenance Afinitor study is a randomised, phase III trial comparing maintenance everolimus combined with aromatase inhibitors (AIs) versus AI monotherapy in patients with disease control after first-line chemotherapy.

Methods: Patients with stable disease, partial response or complete response after first-line chemotherapy were randomised to everolimus plus AIs (exemestane or letrozole or anastrozole) or to AIs alone. Primary aim was progression-free survival (PFS). Secondary aims included response rate, safety and overall survival (OS).

Results: In total, 110 patients were randomised to everolimus + AIs (n = 52) or to AIs (n = 58). Median PFS was 11.0 months (95% confidence interval [CI] 8.1-13.8) in the everolimus + AI arm and 7.2 months (95% CI 4.7-10.9) in the AI monotherapy arm (hazard ratio [HR] 0.71, 95% CI 0.47-1.06). Objective response rate was 22.4% in everolimus + AI arm and 19.2% in AI monotherapy arm. A higher proportion of disease progression as best response was reported in the AI monotherapy arm (28.8% versus 14.3%). Median OS was 35.7 months (95% CI 26.0-47.8) in the combination arm versus 33.5 (95% CI 26.4-42.7) in the AI alone arm (HR 1.0, 95% CI 0.61-1.62).

Conclusions: EVE + AIs did not significantly impact on the outcome of metastatic breast cancer patients deemed suitable for first-line chemotherapy. Also taking into account treatment tolerability, maintenance endocrine therapy remains the standard.

Trial Registration: EudraCT: 2013-004153-24.
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http://dx.doi.org/10.1016/j.ejca.2021.05.008DOI Listing
September 2021

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

Sci Rep 2021 06 21;11(1):12975. Epub 2021 Jun 21.

Medical Oncology Department, ASST-Spedali Civili of Brescia, Piazzale Spedali Civili 1, 20123, Brescia, Italy.

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.
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http://dx.doi.org/10.1038/s41598-021-92138-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8217237PMC
June 2021

Outcome of patients with intrathyroidal thymic carcinoma: a pooled analysis.

Endocr Relat Cancer 2021 Jul 5;28(8):593-604. Epub 2021 Jul 5.

Medical Oncology, Department of Medical and Surgical Specialties, Radiological Sciences and Public Health University of Brescia, ASST-Spedali Civili, Brescia, Italy.

Intrathyroidal thymic carcinoma (ITC) is a rare thyroid tumor that resembles thymic carcinoma, for which there are no recommendations on diagnostic and therapeutic approaches. We performed a pooled analysis of published ITC cases to describe the natural history of this disease and identify prognostic factors. We performed a systematic review of histopathological-confirmed ITC cases published in the literature in English. The following keywords were used: 'intrathyroidal thymic carcinoma', 'carcinoma showing thymus-like differentiation', 'CASTLE tumor', 'thyroid carcinoma showing thymus like differentiation'. Fifty eligible publications were identified, providing data from 132 patients, plus a case diagnosed at our institution. Median disease-free survival (DFS) of this patient series was 144 months (range 91-197), while median overall survival (OS) was not reached. Upfront surgery was performed in 97% of patients and 24% of them experienced disease recurrence after a median of 19 months (range 13-25). Complaining of major symptoms, as a sign of more advanced local stage, was the only prognostic factor significantly associated with a higher risk of death at multivariate analysis (HR 4.903, 95% CI: 1.092-22.008, P = 0.038). Postoperative radiation therapy was not associated with prognosis, while not enough data were available to assess the efficacy of chemotherapy. ITC is a rather indolent disease and ITC patients have a relatively good prognosis. Surgery is the mainstay of therapy. Survival outcome of patients depends on tumor burden and complete surgical resection. Postoperative radiation effect seems to be negligible. Data on the efficacy of chemotherapy in advanced patients are lacking.
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http://dx.doi.org/10.1530/ERC-21-0123DOI Listing
July 2021

Outcome of Patients With Metastatic Lung Neuroendocrine Tumors Submitted to First Line Monotherapy With Somatostatin Analogs.

Front Endocrinol (Lausanne) 2021 27;12:669484. Epub 2021 Apr 27.

Medical Oncology, Department of Medical and Surgical Specialties, Radiological Sciences and Public Health University of Brescia, ASST-Spedali Civili, Brescia, Italy.

Objective: Antiproliferative activity of somatostatin analogs (SSAs) has been demonstrated in digestive neuroendocrine tumors (NETs), but few data have been published in patients with pulmonary NETs. We therefore conducted a retrospective study to provide additional data on the outcome of patients with metastatic lung NETs submitted to front line SSAs.

Research Design And Methods: Patients with metastatic lung NET treated with first line SSA-monotherapy (octreotide or lanreotide) in two different reference Institutions were reviewed. Outcome measures were progression-free survival (PFS) overall survival (OS), overall response rate and safety. We also explored prognostic factors associated with PFS.

Methods: The outcome of consecutive patients (pts) with metastatic lung NETs, who underwent first-line treatment with SSAs, recruited from 2014 on 2019 in two Italian reference Institutions, was retrospectively evaluated.

Results: Thirty-one patients entered the study: 14 (45.2%) with typical and 17 (54.8%) atypical carcinoid. Six patients (19.4%) had a carcinoid syndrome. 60.0% of patients had Ki-67 ≤ 10%. Two (6.5%) patients obtained a partial response, 24 (77.4%) disease stabilization while 5 (16.1%) had progressive disease. Median progression free survival (PFS) was 28.6 months, median overall survival (OS) was not attained. Ki-67 ≤ 10%, typical carcinoid histotype and non-functioning disease, were associated with a non-significant PFS prolongation. PFS in patients with atypical carcinoids and in those with Ki-67 >10% was greater than 19 months.

Conclusions: The long PFS and OS obtained in this case series suggest that SSAs could be effective as first line approach in the management of patients with progressive, metastatic pulmonary NET.
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http://dx.doi.org/10.3389/fendo.2021.669484DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8111295PMC
December 2021

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.

JBMR Plus 2021 Feb 21;5(2):e10440. Epub 2020 Dec 21.

Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, Medical Oncology University of Brescia, Aziende Socio Sanitarie Territoriali (ASST) Spedali Civili Brescia Italy.

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 ( = .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. published by Wiley Periodicals LLC. on behalf of American Society for Bone and Mineral Research.
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http://dx.doi.org/10.1002/jbm4.10440DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7872339PMC
February 2021

The Spread of SARS-CoV-2 Infection Among the Medical Oncology Staff of ASST Spedali Civili of Brescia: Efficacy of Preventive Measures.

Front Oncol 2020 18;10:1574. Epub 2020 Aug 18.

Medical Oncology Unit, Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University of Brescia at ASST Spedali Civili, Brescia, Italy.

Patients with cancer are at a higher risk of developing serious disease-related complications in case of contracting SARS-CoV-2. Oncology units should implement all possible preventive measures to reduce the risk of viral transmission by healthcare professionals (HCPs) to patients. We conducted a surveillance for SARS-CoV-2 infection among the staff members of the Medical Oncology Unit of ASST Spedali Civili in Brescia, one of the Italian areas most affected by the SARS-CoV-2 pandemic. The aim of this study was to demonstrate whether the recommended preventive measures, promptly implemented by the unit, have been effective in reducing the spread of the virus among the HCPs. Between February 24 and May 19, 2020, SARS-CoV-2 infection was detected in 10 out of 76 healthy HCPs (13%). Six of them developed a symptomatic disease, leading to home quarantine, and four remained asymptomatic. The infection was revealed when a serology test was performed on all staff members of the unit. In seven HCPs, in which it was possible to trace the person-to-person infection, the contagion occurred as a result of unprotected contacts or partially protected with surgical masks. In particular, four asymptomatic HCPs did not stop working, but a widespread outbreak in the unit was avoided. Adherence to the recommended preventive strategies, in particular, wearing of surgical masks by both the HCPs and the patients, is effective in reducing and preventing the viral spread.
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http://dx.doi.org/10.3389/fonc.2020.01574DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7462005PMC
August 2020

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.

Int J Nurs Pract 2021 Jun 22;27(3):e12888. Epub 2020 Sep 22.

Medical Oncology, Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University of Brescia at ASST Spedali Civili, Brescia, Italy.

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.
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http://dx.doi.org/10.1111/ijn.12888DOI Listing
June 2021

Should everolimus be stopped after radiological progression in metastatic insulinoma? A "cons" point of view.

Endocrine 2020 09 2;69(3):481-484. Epub 2020 Jun 2.

Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, Medical Oncology, University of Brescia at ASST Spedali Civili, Brescia, Italy.

Insulinoma is a rare pancreatic neuroendocrine tumor (pNET) potentially associated with severe hypoglycaemic crisis. The great majority of these tumors are benign. In patients with metastatic malignant insulinoma, systemic therapies aim to control both the syndrome and tumor growth. Everolimus is a drug approved for the management of advanced pNETs that can achieve both these goals. According to international guidelines and regulatory authorities, everolimus in patients with pNET should be continued until the demonstration of disease progression with standard radiologic imaging techniques. The drug is neither recommended nor authorized beyond progression. This could not be the case of advanced insulinoma patients since the antineoplastic and the glycaemic effects of everolimus seem to follow independent mechanisms. The authors present here their point of view in favor of continuing everolimus beyond progression in symptomatic insulinoma patients on the basis of a robust rationale and describing a case.
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http://dx.doi.org/10.1007/s12020-020-02368-4DOI Listing
September 2020

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

J Geriatr Oncol 2020 07 13;11(6):976-981. Epub 2020 Apr 13.

Oncology Department, Treviglio-Caravaggio Hospital, Treviglio, Italy.

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.
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http://dx.doi.org/10.1016/j.jgo.2020.03.021DOI Listing
July 2020

Association of Fat Body Mass With Vertebral Fractures in Postmenopausal Women With Early Breast Cancer Undergoing Adjuvant Aromatase Inhibitor Therapy.

JAMA Netw Open 2019 09 4;2(9):e1911080. Epub 2019 Sep 4.

Medical Oncology Unit, Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, Spedali Civili Hospital, Brescia, Italy.

Importance: Aromatase inhibitors induce a profound depletion in serum estrogen levels. Postmenopausal obese women receiving aromatase inhibitor therapy may be at increased risk of bone fractures owing to the detrimental association of adiposity with bone quality and the loss of the protective effect of estrogens on bone mineral density.

Objective: To determine whether fat body mass (FBM), as measured by dual-energy x-ray absorptiometry, is associated with vertebral fracture prevalence in postmenopausal women undergoing adjuvant aromatase inhibitor therapy for breast cancer.

Design, Setting, And Participants: In this single-center, cross-sectional study, 556 postmenopausal women with early-stage breast cancer were consecutively enrolled from October 15, 2013, to June 30, 2018, and stratified according to whether they were aromatase inhibitor-naive or aromatase inhibitor-treated for at least 2 years. The database was locked on December 31, 2018, and data analysis was completed on February 28, 2019. Eligible patients in both groups had normal renal function, no metabolic diseases, and no previous or current treatment with antiosteoporotic drugs or glucocorticoids. Previous chemotherapy, but not tamoxifen, was permitted. Data were gathered once, at baseline.

Main Outcomes And Measures: Vertebral fracture prevalence associated with FBM in aromatase inhibitor-naive and aromatase inhibitor-treated patients.

Results: Of the 556 women enrolled, the mean age was 63.0 years (95% CI, 62.2-63.8 years). The 195 aromatase inhibitor-treated patients were older than the 361 aromatase inhibitor-naive patients (mean age, 66.1 vs 61.3 years; P < .001), had a higher body mass index (mean, 26.4 vs 25.3; P = .009), were less likely to engage in physical activity (65.3% vs 73.7%; P = .03), and were less likely to consume alcoholic beverages (68.4% vs 80.9%; P = .001). Among the aromatase inhibitor-naive patients, the vertebral fracture prevalence was higher in the subgroup with FBM below the median value than in those with high FBM, but the difference was not statistically significant (19.2% vs 13.3%; P = .13). Conversely, the proportion of vertebral fractures in the aromatase inhibitor-treated group was 20.0% in patients with low FBM vs 33.3% in patients with high FBM (P = .04). An opposite trend in the association of FBM with vertebral fracture prevalence according to aromatase inhibitor group was shown by multivariable analysis in the propensity score-matched sample: odds ratio, 0.38 (95% CI, 0.12-1.19) and 1.94 (95% CI, 0.67-5.64) in the aromatase inhibitor-naive and aromatase inhibitor-treated groups, respectively (odds ratio for the interaction, 5.77 [95% CI, 1.08-30.81]; P for interaction term = .03).

Conclusions And Relevance: Fat body mass may be associated with fragility-related fractures in patients with breast cancer who undergo aromatase inhibitor therapy. If these data are confirmed, obesity could be included in the algorithm for assessing fracture risk and selecting patients to receive bone resorption inhibitors.
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http://dx.doi.org/10.1001/jamanetworkopen.2019.11080DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6777242PMC
September 2019

Excess of second tumors in denosumab-treated patients: a metabolic hypothesis.

Future Oncol 2019 Jul 25;15(20):2319-2321. Epub 2019 Jun 25.

Department of Medical & Surgical Specialties, Radiological Sciences, & Public Health, Medical Oncology, University of Brescia at ASST Spedali Civili, Brescia, Italy.

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http://dx.doi.org/10.2217/fon-2019-0170DOI Listing
July 2019

Long-Term Outcomes of Immunohistochemically Defined Subtypes of Breast Cancer Less Than or Equal to 2 cm After Breast-Conserving Surgery.

J Surg Res 2019 04 27;236:288-299. Epub 2018 Dec 27.

Department of General Surgery II, University Hospital ASST Spedali Civili, Brescia, Italy.

Background: Molecular subtype predicts the prognosis of early-stage breast cancer patients. We assessed the long-term outcomes of breast cancer ≤2 cm treated with breast-conserving surgery (BCS) and stratified according to an immunohistochemically (IHC)-based subtype definition.

Methods: This retrospective study was conducted from a prospectively collected database. Included patients had pT1, any N, M0 breast cancer after BCS (without anti-HER2 therapy) and available information on estrogen receptor (ER), progesterone receptor (PR), HER2 status, Ki-67 index. Five IHC-defined subtypes were identified: luminal A-like (ER and/or PR-positive/HER2-negative/Ki-67 < 20%), luminal B-like/HER2-negative (ER and/or PR-positive/HER2-negative/Ki-67 ≥ 20%), luminal B-like/HER2-positive (ER and/or PR-positive/HER2-positive/any Ki-67 value), HER2-positive/nonluminal (ER and PR-negative/HER2-positive), and triple-negative (ER and PR-negative/HER2-negative).

Results: We analyzed 184 (65%) luminal A-like, 57 (20%) luminal B-like/HER2-negative, 17 (6%) luminal B-like/HER2-positive, 6 (2%) HER2-positive/nonluminal, and 18 (7%) triple-negative patients. Median follow-up was 112 (interquartile range 94-125) mo. The cumulative 5- and 10-y local recurrence (LR) rates were 1.5% and 4%, respectively. The cumulative 5- and 10-y distant recurrence (DR) rates were 3% and 8%, respectively. The Cox regression revealed that HER2-positive/nonluminal subtypes had the highest risk of LR (P = 0.0025). The luminal B-like/HER2-positive subtypes had the highest risk of DR (P = 0.0019). HER2 positivity carried a higher risk of DR in women with luminal breast cancer who completed 5 y of adjuvant hormonal therapy (P = 0.02).

Conclusions: The IHC-defined subtype impacts on the prognosis of breast cancer ≤2 cm after BCS, determining significant differences in LR and DR rates. In the pre-"anti-HER2 therapy" era, patients with HER2-positive/nonluminal or luminal B-like/HER2-positive subtype had worse long-term outcomes than those with luminal A-like subtype.
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http://dx.doi.org/10.1016/j.jss.2018.11.028DOI Listing
April 2019

Comparative efficacy of palbociclib, ribociclib and abemaciclib for ER+ metastatic breast cancer: an adjusted indirect analysis of randomized controlled trials.

Breast Cancer Res Treat 2019 Apr 18;174(3):597-604. Epub 2019 Jan 18.

Medical Oncology Unit, ASST Bergamo Ovest, Piazzale Ospedale 1, 24047, Treviglio, BG, Italy.

Background: Several trials have demonstrated the benefit of anti-CDK4/6 inhibitors plus endocrine therapy in estrogen receptor-positive (ER+) advanced breast cancer (BC), in first or subsequent lines of therapy. However, due to the lack of direct/indirect comparisons, there are no data demonstrating the superiority of one drug over the other. We compared the effectiveness of palbociclib, ribociclib, and abemaciclib in advanced ER + BC via an indirect adjusted analysis.

Methods: We performed electronic searches in the PubMed, EMBASE, and Cochrane databases for prospective phase 3 randomized trials evaluating anti-CDK4/6 inhibitors plus endocrine agents. We compared the results with an adjusted indirect analysis of randomized-controlled trials. Outcomes of interest were progression-free survival (PFS), overall response rate (ORR) and G3-4 toxicities occurring in ≥ 5% of patients.

Results: Six trials and six treatment arms including a total of 3743 participants, were included. For PFS and ORR analysis, the three agents were similar in both first- and second-line studies. All G3-4 toxicities were similar, with reduced risk of diarrhea for palbociclib versus abemaciclib (relative risk [RR] 0.13, 95% CI 0.02-0.92; P = 0.04) and of QTc prolongation for palbociclib versus ribociclib (RR 0.02, 95% CI 0-0.83; P = 0.03). Despite different inclusion criteria and length of follow-up, similar features were noticed among second-line studies with the exception of increased risk of anemia G3-4 and diarrhea G3-4 for abemaciclib.

Conclusions: Based on PFS and ORR results of this indirect meta-analysis, palbociclib, ribociclib, and abemaciclib are equally effective in either first- or second-line therapy for advanced ER + BC. They, however, ported different toxicity profiles.
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http://dx.doi.org/10.1007/s10549-019-05133-yDOI Listing
April 2019

Outcome of EGFR-mutated adenocarcinoma NSCLC patients with changed phenotype to squamous cell carcinoma after tyrosine kinase inhibitors: A pooled analysis with an additional case.

Lung Cancer 2019 01 13;127:12-18. Epub 2018 Nov 13.

Department of Medical & Surgical Specialties, Radiological Sciences & Public Health, Medical Oncology Unit, University of Brescia at ASST Spedali Civili, Brescia, 25123, Italy. Electronic address:

The onset of a new histology is a resistant mechanism to tyrosine kinase inhibitors (TKI) in lung adenocarcinoma (ADK), but this phenomenon has not yet been fully clarified. We present a pooled analysis of the outcomes of EGFR-mutated ADK patients with changed phenotype to squamous cell carcinoma (SqCC) following TKI, along with the description of an additional case. A 67-year-old woman with EGFR-mutated NSCLC received gefitinib and subsequently osimertinib, due to the presence of T790 M at progression. The re-biopsy after third-generation TKI revealed SqCC histology along with the basal EGFR mutation, while T790 M disappeared. The patient rapidly progressed and died despite two chemotherapy cycles. Since this first description of SqCC transformation appearing after treatment with the third-generation TKI osimertinib, other 16 patients, with EGFR-mutated ADK developing a transformation to SqCC histology after treatment with TKIs, were up to now published. From our pooled analysis emerged that most patients were female (82%), 41% were former smokers and no current smokers were identified. Median time to SqCC onset was 11.5 months. In all cases, basal EGFR mutation was maintained, and 11 patients (65%) developed an acquired mutation on exon 20. Interestingly also 790 M mutation appeared in 8 patients (47%). The median survival after SqCC diagnosis was 3.5 months regardless the treatments received. Therefore, EGFR-mutated lung ADK destined to develop a squamous phenotype were often smokers and maintained the baseline genomic alterations. The prognosis after SqCC diagnosis was extremely poor and current treatments largely inefficacious.
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http://dx.doi.org/10.1016/j.lungcan.2018.11.016DOI Listing
January 2019

A New Genetic Risk Score to Predict the Outcome of Locally Advanced or Metastatic Breast Cancer Patients Treated With First-Line Exemestane: Results From a Prospective Study.

Clin Breast Cancer 2019 04 24;19(2):137-145.e4. Epub 2018 Nov 24.

Oncology Unit, Macerata Hospital, Macerata, Italy.

Introduction: Approximately 50% of locally advanced or metastatic breast cancer (MBC) patients treated with first-line exemestane do not show objective response and currently there are no reliable biomarkers to predict the outcome of patients using this therapy. The constitutive genetic background might be responsible for differences in the outcome of exemestane-treated patients. We designed a prospective study to investigate the role of germ line polymorphisms as biomarkers of survival.

Patients And Methods: Three hundred two locally advanced or MBC patients treated with first-line exemestane were genotyped for 74 germ line polymorphisms in 39 candidate genes involved in drug activity, hormone balance, DNA replication and repair, and cell signaling pathways. Associations with progression-free survival (PFS) and overall survival (OS) were tested with multivariate Cox regression. Bootstrap resampling was used as an internal assessment of results reproducibility.

Results: Cytochrome P450 19A1-rs10046TC/CC, solute carrier organic anion transporter 1B1-rs4149056TT, adenosine triphosphate binding cassette subfamily G member 2-rs2046134GG, fibroblast growth factor receptor-4-rs351855TT, and X-ray repair cross complementing 3-rs861539TT were significantly associated with PFS and then combined into a risk score (0-1, 2, 3, or 4-6 risk points). Patients with the highest risk score (4-6 risk points) compared with ones with the lowest score (0-1 risk points) had a median PFS of 10 months versus 26.3 months (adjusted hazard ratio [AdjHR], 3.12 [95% confidence interval (CI), 2.18-4.48]; P < .001) and a median OS of 38.9 months versus 63.0 months (AdjHR, 2.41 [95% CI, 1.22-4.79], P = .012), respectively.

Conclusion: In this study we defined a score including 5 polymorphisms to stratify patients for PFS and OS. This score, if validated, might be translated to personalize locally advanced or MBC patient treatment and management.
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http://dx.doi.org/10.1016/j.clbc.2018.11.009DOI Listing
April 2019

Systemic therapies in patients with advanced well-differentiated pancreatic neuroendocrine tumors (PanNETs): When cytoreduction is the aim. A critical review with meta-analysis.

Cancer Treat Rev 2018 Dec 13;71:39-46. Epub 2018 Oct 13.

Division of Gastrointestinal Medical Oncology and Neuroendocrine Tumors, IEO, European Institute of Oncology IRCCS, Milan, Italy. Electronic address:

Introduction: Cytoreduction is sometimes an important aim of systemic anti-tumor therapies in well-differentiated pancreatic neuroendocrine tumors (PanNETs). As there is not a gold standard treatment for these tumors in this field, we conducted a literature review in order to identify objective criteria for treatment choice.

Materials And Methods: We critically reviewed and performed a meta-analysis of all published clinical studies of systemic therapies in patients with well-differentiated unresectable PanNETs, selecting only those articles which reported tumor shrinkage (TS) with a waterfall plot (WP). Tumor downsizing of ≥10% was considered as objective response.

Results: We selected 17 out of 2758 studies, comprising 1118 patients with tumor response reported as WP. Proliferation index, tumor burden and anti-tumor therapies were heterogeneous. Chemotherapy alone (mainly, capecitabine/temozolomide) or in combination showed the best results, with ≥10% TS ranging from 65% to 93%. Peptide receptor radionuclide therapy combined with chemotherapy (Chemo-PRRT) and sunitinib appeared promising by inducing objective response in a significant proportion of patients (93% and 60%, respectively). Time to tumor response was reported in only two trials. No clear clinical and/or biological predictive factors emerged.

Conclusion: Based on response criteria used in our retrospective analysis, systemic chemotherapy alone or in combination appeared to have the main cytoreductive impact. However no conclusions regarding either a specific regimen or combination can be drawn. Furthermore, tumor population selection and/or choice of regimen may have a significant influence. Further analysis should be also conducted to identify potential predictive biomarkers of responses, in order to design future prospective interventional clinical trials enrolling more homogenous populations of advanced well-differentiated PanNETs.
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http://dx.doi.org/10.1016/j.ctrv.2018.10.008DOI Listing
December 2018

Eribulin in Heavily Pretreated Metastatic Breast Cancer Patients in the Real World: A Retrospective Study.

Oncology 2018 23;94 Suppl 1:10-15. Epub 2018 Jul 23.

Oncology Department, Spedali Civili Hospital, Brescia, Italy.

Objectives: The aim of this study was to investigate efficacy and safety of eribulin in heavily pretreated patients with advanced breast cancer (BC) in a real-life setting.

Methods: This retrospective monocentric study included patients with HER-2-negative metastatic BC, pretreated with anthracyclines and taxanes, who were referred to the Oncology Department of Spedali Civili of Brescia from May 2012 to April 2017. Patients received the same dose of eribulin as that used in the EMBRACE trial: 1.4 mg/m2 on days 1 and 8 every 21 days.

Results: In a total of 53 patients, 32% obtained a partial response, 11% a stable disease, and 43% a clinical benefit (CB). After a median follow-up of 36 months, median progression-free survival (PFS) was 4.7 months and median overall survival (OS) 13.53 months. Median PFS was significantly longer in patients who reported a CB compared to those with no CB, while survival outcomes (PFS and OS) were better in patients who received > 6 cycles of eribulin. Eribulin showed a good tolerability profile with acceptable toxicities, similar to those reported in EMBRACE.

Conclusions: Our experience in a real-world setting confirms the activity, efficacy, and good tolerability profile of eribulin in heavily pretreated BC patients.
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http://dx.doi.org/10.1159/000489063DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6193751PMC
July 2018

Osimertinib in EGFR Mutation–Positive Advanced NSCLC.

N Engl J Med 2018 03;378(13):1261-2

University of Brescia, Brescia, Italy

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http://dx.doi.org/10.1056/NEJMc1801669DOI Listing
March 2018

IFN-α in advanced well-differentiated neuroendocrine tumors: the neglected drug?

Future Oncol 2018 04 12;14(10):897-899. Epub 2018 Mar 12.

Department of Medical & Surgical Specialties, Radiological Sciences & Public Health, Medical Oncology Unit, University of Brescia at ASST Spedali Civili, Brescia 25123, Italy.

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http://dx.doi.org/10.2217/fon-2017-0667DOI Listing
April 2018

Testosterone Levels and Prostate Cancer Prognosis: Systematic Review and Meta-analysis.

Clin Genitourin Cancer 2018 06 2;16(3):165-175.e2. Epub 2018 Feb 2.

Medical Oncology Unit, Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia at Spedali Civili Hospital, Brescia, Italy. Electronic address:

Androgen receptor is the major driver of and testosterone the natural growth factor of prostate cancer (PC). Studies exploring the relationship among circulating testosterone levels, PC aggressiveness, and patient prognosis showed contradictory results. We performed a comprehensive literature search for studies reporting the independent relationship between serum testosterone and prognosis of PC patients. Meta-analyses using random effects models were conducted to estimate pooled hazard ratios (HRs) and 95% confidence intervals (CIs). We identified 25 articles that evaluated the prognostic value of testosterone in early-stage PC (8 studies), in advanced PC either before (4 studies) or during androgen deprivation therapy (ADT) (5 studies), and in castration-resistant PC (8 studies). In early PC, serum testosterone level was not prognostic in terms of overall survival (HR = 1.03; 95% CI, 0.99-1.08; P = .19) and biochemical recurrence (HR = 0.99; 95% CI, 0.87-1.13; P = .93). In advanced PC, higher testosterone levels before ADT were associated with a reduced risk of death (HR = 0.58; 95% CI, 0.45-0.74; P < .0001). During ADT, lower levels were associated with a reduced risk of death (HR = 0.48; 95% CI, 0.28-0.81; P = .006) and progression (HR = 0.59; 95% CI, 0.46-0.77; P < .0001). In castration-resistant PC patients, higher testosterone levels predicted a reduced risk of progression (HR = 0.33; 95% CI, 0.11-0.97; P = .04) but not of death (HR = 0.86; 95% CI, 0.69-1.07; P = .18). The heterogeneity of the included studies is a major limitation of this meta-analysis. The relationship between circulating testosterone and PC prognosis varies in different clinical settings and according to ADT administration.
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http://dx.doi.org/10.1016/j.clgc.2018.01.005DOI Listing
June 2018

Outcome of patients with lung adenocarcinoma with transformation to small-cell lung cancer following tyrosine kinase inhibitors treatment: A systematic review and pooled analysis.

Cancer Treat Rev 2017 Sep 31;59:117-122. Epub 2017 Jul 31.

University of Brescia, Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, Medical Oncology and Department of Molecular and Translational Medicine Section of Pathology, at Spedali Civili Hospital, Brescia, Italy. Electronic address:

Background: Lung adenocarcinoma can transform to small-cell lung cancer (SCLC) when resistance to tyrosine kinase inhibitors (TKIs) develops. This phenomenon has repeatedly been described in several case reports and small patient series. The characteristics and treatment outcomes of this population, however, have not been comprehensively reported.

Methods: We performed a systematic review of the published literature to obtain explorative information on the clinical and pathological features and prognosis of the reported cases.

Results: Twenty-five eligible publications were identified, contributing to 39 patients. The median time from initial diagnosis of lung adenocarcinoma to the transformation to SCLC (ttSCLC) was 19months (range 1-61months). The median survival after SCLC diagnosis was 6months. Female gender was significantly associated with longer ttSCLC at the multivariable analysis. Smoking status seemed to be associated with worse prognosis after the diagnosis of SCLC.

Conclusion: In this series of published cases, the transformation to a SCLC phenotype after an initial diagnosis of lung adenocarcinoma following TKI therapy appeared to be a late phenomenon. The prognosis after SCLC diagnosis is poor and current treatment strategies derived from primary SCLC seem to be largely inefficacious. New therapies are needed in the management of transformed SCLC.
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http://dx.doi.org/10.1016/j.ctrv.2017.07.007DOI Listing
September 2017

The involvement of early stage breast cancer patients during oncology consultations in Italy: a multi-centred, randomized controlled trial of a question prompt sheet versus question listing.

BMJ Open 2017 08 11;7(8):e015079. Epub 2017 Aug 11.

Department of Health Behavior and Policy, School of Medicine, Virginia Commonwealth University, Richmond, USA.

Objectives: To investigate, prior to an oncology consultation, the use of a pre-prepared list of evidence based questions, Question Prompt Sheet (QPS), compared with a Question List (QL), a patient self-generated list of questions.

Design: Multi-centred, randomised controlled trial.

Setting: Secondary-care patients attending three outpatient oncology clinics in Northern Italy.

Participants: 308 women completed the study. Inclusion criteria were an age between 18 and 75 years, a recent diagnosis of early stage, non-metastatic breast cancer, adequate Italian language skills, no previous oncology visits and no evidence of cognitive impairment.

Intervention: Patients received the QPS or the QL prior to the consultation, completed it without suggestion or coaching session and delivered back before the visit.The consultations were audio-recorded and analysed for the number and content of questions. Multilevel linear models were used to compare the two groups.

Outcome Measures: The primary outcome was the comparison of questions asked between QPS and QL group. Secondary outcomes included satisfaction about questions asked, satisfaction with decision, and level of anxiety.

Results: Patients in the QPS and QL group asked 13 and 16 questions respectively. The difference was not significant (b=1.7, CI -0.3 to 3.6, p=0.10). A mean of 22 questions was selected in the QPS, while a mean of 2 questions was written in the QL. Patients in the QPS group were significantly less satisfied (t=3.60, p<0.01) with questions asked but wanted less additional information (t=2.20, p<0.05). Levels of patient decisional satisfaction were equivalent between groups. Similarly, anxiety levels were equal between groups prior to the consultation and decreased in similar way after the consultation.

Conclusions: Both interventions have similar impact on patients' participation in terms of question asking during the consultation. Future research is needed in order to explore which components of the interventions are really useful and efficacious.

Trial Registration: ClinicalTrials.gov NCT01510964.
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http://dx.doi.org/10.1136/bmjopen-2016-015079DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5724137PMC
August 2017

When Should Everolimus Be Administered in the Natural History of Pancreatic Neuroendocrine Tumors?

J Clin Oncol 2017 05 23;35(13):1487-1488. Epub 2017 Jan 23.

Vito Amoroso, University of Brescia at ASST Spedali Civili, Brescia, Italy; Nicola Fazio, European Institute of Oncology, Milan, Italy; Alessandra Mosca, Maggiore della Carità University Hospital, University of Eastern Piedmont, Novara, Italy; Elisa Roca, University of Brescia at ASST Spedali Civili, Brescia, Italy; Francesca Spada, European Institute of Oncology, Milan, Italy; and Chiara Foroni, Giorgio Maria Agazzi, and Alfredo Berruti, University of Brescia at ASST Spedali Civili, Brescia, Italy.

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http://dx.doi.org/10.1200/JCO.2016.71.0103DOI Listing
May 2017

Morphometric vertebral fractures in breast cancer patients treated with adjuvant aromatase inhibitor therapy: A cross-sectional study.

Bone 2017 04 16;97:147-152. Epub 2017 Jan 16.

Endocrinology, San Raffaele Vita-Salute University, Milan, Italy.

Background: The impact of long-term adjuvant therapy with aromatase inhibitors (AIs) on vertebral fracture (VF) risk is still unclear.

Objective: In this cross-sectional study, we explored the prevalence and determinants of VFs in breast cancer (BC) patients before and during AI therapy. Each woman underwent a dual-energy X-ray absorptiometry (DXA) to evaluate bone mineral density (BMD) and identify VFs by a quantitative morphometric approach. Blood samples were collected to measure serum hormone and calcium levels.

Results: We consecutively included 263 postmenopausal women with hormone receptor-positive early BC. One-hundred-sixty-nine women were AI-naïve, and 94 were AI-treated. AI-treated patients had lower BMD at total hip (p=0.01) and lumbar spine (p=0.03), higher serum vitamin D (p<0.001) and parathyroid hormone (p=0.006) values as compared to AI-naïve patients. The prevalence of VFs was 18.9% in AI-naïve patients, and 31.2% in those assessed during AI therapy (odds ratio 1.90, 95% CI 1.1-3.5, p=0.03). In AI-naïve patients, VFs were associated with older age (p=0.002) and lower BMD values at femoral neck (p=0.04) and total hip (p=0.007), whereas VFs occurred without association with any parameter analyzed in AI-treated patients. In AI-treated group, the prevalence of VFs was not significantly different between patients with osteoporosis and those with normal BMD (36.7% vs. 20.0%; p=0.31).

Conclusions: In women with early BC, AI therapy is associated with high prevalence of radiological VFs, which were shown to be independent of BMD values during the adjuvant treatment. These findings may be clinically relevant since they may lead to a change in management of AI-induced skeletal fragility. Specifically, the results of this study provide a rationale for performing a morphometric evaluation of VFs in all women undergoing treatment with AIs.
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http://dx.doi.org/10.1016/j.bone.2017.01.013DOI Listing
April 2017

Regression of advanced neuroendocrine tumors among patients receiving placebo.

Endocr Relat Cancer 2017 02 13;24(2):L13-L16. Epub 2016 Dec 13.

Department of Medical and Surgical SpecialtiesRadiological Sciences, and Public Health, Medical Oncology Unit, University of Brescia at ASST Spedali Civili, Brescia, Italy.

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http://dx.doi.org/10.1530/ERC-16-0475DOI Listing
February 2017

Serum Vitamin D and Prostate Cancer Prognosis: The Story Continues.

J Clin Oncol 2016 Oct;34(30):3709-3710

University of Brescia, Azienda Socio Sanitaria Territoriale degli Spedali Civili, Brescia, Italy.

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http://dx.doi.org/10.1200/JCO.2016.68.2617DOI Listing
October 2016

Current challenges in HER2-positive breast cancer.

Crit Rev Oncol Hematol 2016 Feb 31;98:211-21. Epub 2015 Oct 31.

Facoltà di Medicina e Psicologia "Sapienza" Università di Roma, Ospedale Sant'Andrea & IDI - I.R.C.C.S., Roma, Italy.

The introduction of trastuzumab into routine clinical practice has had a dramatic effect on the outlook for patients with HER2-positive breast cancer. Nevertheless, answers to some long unresolved questions about the optimal use of trastuzumab (such as its role in small tumors or low-risk disease, cardiac safety in the elderly, and treatment duration) have emerged only relatively recently. Moreover, with the availability of new highly effective HER2-directed therapies, including pertuzumab and trastuzumab-emtansine (T-DM1), the treatment algorithm for HER2-positive breast cancer continues to evolve. This review provides a summary of the latest evidence providing insight into the management of early and advanced HER2-positive breast cancer and delineates future perspectives of study and treatment for these patients.
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http://dx.doi.org/10.1016/j.critrevonc.2015.10.016DOI Listing
February 2016

Adjuvant bisphosphonates in patients with breast cancer: does the potency matter?

Future Oncol 2015 25;11(21):2853-6. Epub 2015 Sep 25.

Medical Oncology Unit, Department of Medical & Surgical Specialties, Radiological Sciences & Public Health, University of Brescia at Spedali Civili Hospital, Brescia, Italy.

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http://dx.doi.org/10.2217/fon.15.210DOI Listing
August 2016

International Expert Consensus on Primary Systemic Therapy in the Management of Early Breast Cancer: Highlights of the Fifth Symposium on Primary Systemic Therapy in the Management of Operable Breast Cancer, Cremona, Italy (2013).

J Natl Cancer Inst Monogr 2015 May;2015(51):90-6

Medical Oncology Unit (VA, ABe), University of Brescia, and Breast Unit (RP, LV, ELS) Spedali Civili Hospital, Brescia, Italy; U.O. Multidisciplinare di Patologia Mammaria, S.S. Terapia Molecolare e Farmacogenomica, AZ. Istituti Ospitalieri di Cremona, Cremona, Italy (DG, AR, MRC, LD, ABo); Departments of Radiation Oncology (TB) and Pathology (FS), University of Texas MD Anderson Cancer Center, Houston, TX; Department of Medical Oncology and Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA (MC); Division of Experimental Therapeutics, Breast Cancer Program, Istituto Europeo di Oncologia, Milan, Italy (GC); Biomarkers Unit, Department of Experimental Oncology and Molecular Medicine (MGD), and Medical Oncology Unit (SDC), Fondazione IRCCS - Istituto Nazionale Tumori, Milan, Italy (MGD); Academic Department of Biochemistry, Biochemical Endocrinology (MD), Department of Surgery, Breast Unit (PB), and The Breakthrough Breast Cancer Research Centre, The Institute of Cancer Research and Breast Unit (MD, GS), Royal Marsden Hospital, London, UK; Department of Pathology, Melbourne University, Parkville, Australia (SF); Molecular Oncology Laboratories, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK (ALH); Mount Vernon Cancer Centre, London, UK (AM); Section of Medical Oncology, Yale Cancer Center, Yale School of Medicine, New Haven, CT (CH); Memorial Sloan Kettering Cancer Center, New York, NY (CAH); Division of Medical Oncology, Department of Hemato-oncology, IRCCS Policlinico 'San Matteo' Foundation, Pavia, Italy (PP); Dipartimento Medicina di Laboratorio, SC Anatomia ed Istocitopatologia Diagnostica e di Screening, A.O.U. Città della Salute e della Scienza di Torino, Università di Torino, Turin, Italy (AS); N. N. Petrov Research Institute of Oncology, St. Petersburg, Russia (VS); German Breast Group & University of Frankfurt, Neu-Isenburg, Germany (GvM); The Russell H. Morgan Department of Radiology

Expert consensus-based recommendations regarding key issues in the use of primary (or neoadjuvant) systemic treatment (PST) in patients with early breast cancer are a valuable resource for practising oncologists. PST remains a valuable therapeutic approach for the assessment of biological antitumor activity and clinical efficacy of new treatments in clinical trials. Neoadjuvant trials provide endpoints, such as pathological complete response (pCR) to treatment, that potentially translate into meaningful improvements in overall survival and disease-free survival. Neoadjuvant trials need fewer patients and are less expensive than adjuvant trial, and the endpoint of pCR is achieved in months, rather than years. For these reasons, the neoadjuvant setting is ideal for testing emerging targeted therapies in early breast cancer. Although pCR is an early clinical endpoint, its role as a surrogate for long-term outcomes is the key issue. New and better predictors of treatment efficacy are needed to improve treatment and outcomes. After PST, accurate management of post-treatment residual disease is mandatory. The surgery of the sentinel lymph-node could be an acceptable option to spare the axillary dissection in case of clinical negativity (N0) of the axilla at the diagnosis and/or after PST. No data exists yet to support the modulation of the extent of locoregional radiation therapy on the basis of the response attained after PST although trials are underway.
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http://dx.doi.org/10.1093/jncimonographs/lgv023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5009414PMC
May 2015

Neoadjuvant Treatment Approach: The Rosetta Stone for Breast Cancer?

J Natl Cancer Inst Monogr 2015 May;2015(51):32-5

U.O. Multidisciplinare di Patologia Mammaria, U.S Terapia Molecolare e Farmacogenomica, A.O. Istituti Ospitalieri di Cremona, Cremona, Italy (DG, MA, CS, MMi, MRC, LZ, MF, FB, MMa, ABo); U.O. Oncologia Medica, Spedali Civili si Brescia, Brescia, Italy (VA, ES, ABe); Section of Pharmacology, Department of Molecular and Translational Medicine, University of Brescia Medical School, Brescia, Italy (FB, SS).

Breast cancer represents a heterogeneous group of diseases with varied biological features, behavior, and response to therapy; thus, management of breast cancer relies on the availability of robust predictive and prognostic factors to support therapy decision-making. Traditionally, neoadjuvant treatment for breast cancer was preserved for locally advanced, converting an inoperable to a surgical resectable cancer. Neoadjuvant trials, additionally, offer: 1) the opportunity to evaluate new treatment options in a faster way and with fewer patients than large adjuvant trials; 2) to identify and validate the prognostic and predictive value of a marker with its association with clinical outcome in relation to the administered treatment. In this setting, thanks to new, affordable technologies which help to detail the molecular profiles of tumors, new trial designs based on new target therapies, like window-of-opportunity, are also suggested, as they represent the chance to identify tumor sensitivity or to overcome tumor resistance to the treatment used, based on its interaction with tumor biology in early tumor stages. However, clinicians and researchers should pay particular attention: In this setting, the safety of patients is paramount, given the exposure of potentially curable patients to investigational agents with limited safety experience, the definition of the study population and the study design, such as adaptive strategies, should limit patient exposure to ineffective agents, and intensify safety monitoring in the course of the treatment. Here, issues related to outcome determination in breast cancer, including some critical points of view, are presented.
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http://dx.doi.org/10.1093/jncimonographs/lgv019DOI Listing
May 2015
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