18 research outputs found
Clinical Prognosticators in Patients Treated with CDK 4/6 Inhibitors for Hormone Receptors Positive Advanced Breast Cancer
No full textBackground: CDK4/6 inhibitors are the new standard of care in hormonal receptors positive (HR+) advanced
breast cancer (ABC). Phase III trials demonstrated an improvement in survival outcomes in patients with combined
endocrine approach compared to endocrine therapy (ET) alone. The aim of this retrospective study was to assess
prognostic factors for clinical response to CDK4/6 inhibitors.
Methods: All patients receiving CDK4/6 inhibitors from September 2016 to July 2019 were registered in a database.
Data on tumor and patient’s characteristics as well as concomitant medications were collected. Survival data were
analyzed by Kaplan Meier curves and log rank test. Treatment toxicities were graded according to CTCAE v5. A
drug-drug interactions analysis among CDK 4/6 inhibitors and co-administered medications was performed too.
Results: 121 patients were included in the study: 49% of patients treated in 1st -line, 25% in 2nd -line and 26%
in 3rd –or further lines. 1st-line objective response rate (ORR) and clinical benefit rate (CBR) was 56% and 68%,
compared to 40% and 50% in 2nd-line and 31% and 47% in heavily pre-treated patients, respectively. Median PFS
according to line setting was: not reached in 1st-line, 17 months (95% CI 13-21) in 2nd-line and 7 months (95% CI
4-12) in 3rd or further lines. Negative prognostic factors in term of PFS were: previous chemotherapy for metastatic
disease (p=0.0001), visceral metastatic sites (p=0.002) and endocrine sensitivity (p=0.001). No association among
concomitant drugs administered and survival outcome was found. 94% of patients experienced neutropenia (G3-G4
60%) with 3% of febrile neutropenia. 71% of patients treated with Abemaciclib had diarrhea. Management of AE
included 63% of treatment delay, 44% of 1st dose reduction and 15% of 2nd dose reduction, all due to neutropenia.
No treatment discontinuation due to any toxicity was observed.
Conclusion: Data on efficacy and safety profile of CDK 4/6 inhibitors administered outside the context of a clinical
trial are consistent with those reported in Phase III trials. Previous chemotherapy for metastatic disease, visceral
metastatic site as well as previous endocrine sensitivity negatively affect CDK 4/6 inhibitors efficacy. Concomitant
medications did not affect survival outcome or safety profile
Modulation of Mutational Landscape in HER2-Positive Breast Cancer after Neoadjuvant Chemotherapy
No full textImpact of body composition parameters on tumor response to neoadjuvant chemotherapy in operable breast cancer patients.
No full textFat tissue promotes cancer progression by increasing cell proliferation, cell survival and metastatic processes. Adipose tissue determines a dysregulation of several metabolic pathways by a continuous crosstalk between fat tissue and cancer cells. Moreover, influence of adipose tissue on cancer development depend on the type of fat too
BMI cannot account for differences in fat distribution and cannot distinguish between adipose tissue and muscles
Computed tomography (CT) imaging can be a useful tool for a directly measure of body fat distribution distinguishing among visceral, subcutaneous, internal fat tissue (mostly in the liver) and skeletal muscles mass.
Patients treated with neoadjuvant chemotherapy for early BC at the Modena Cancer Center from 2005 to 2017 we collected.
According to BMI score, patients were categorized in two main classes: normal weight (BMI < 25) and overweight (BMI ≥ 25) (Table 1)
Using Advance workstation (General Electric), software ADW server 3.2 or 4.7. we calculated body composition parameters (BCPs) from pre-treated CT scan images. BCPs considered are: subcutaneous fat area (SFA, cm2), visceral fat area (VFA, cm2), lumbar muscle cross-sectional area (LMCA, m2) and liver steatosis (L/S ratio)
BMI score and BCPs value were correlated with pathological complete response (pCR) and survival outcomes. All analyses were performed using STATA 14 (StataCorp. 2015. Stata Statistical Software: Release 14. College Station, TX: StataCorp LP).
pre-treatment CT scan imagine available for BCPs analysis
55% of the women had BMI < 25 versus 45% with BMI >25
Overweight was significantly associated with postmenopausal status, older age and hormonal receptor positive BC (Table 1)
Menopausal status was associated with higher VFA, presence of fatty liver disease and obesity disease compared to pre-menopausal one (Table 2).
No association between BMI classes and pCR was detected. High VFA and liver steatosis were negative predictive factors for pCR (pCR rate: 35% normal VFA vs 20% high VFA, no steatosis 32% vs steatosis 13%; p<0.05) ( Figure 1)
Neither BMI classes nor BCPs significantly influenced overall survival and relapse free survival.
The evaluation of BCPs is the best way to assess the real body composition
Menopausal status is associated with higher VFA, presence of fatty liver disease and obesity disease
Visceral adiposity as well as liver steatosis were negative predictive factors for pCR in BC patients treated with neoadijuvant chemotherapy
Circulating and Intracellular miRNAs as Prognostic and Predictive Factors in HER2-Positive Early Breast Cancer Treated with Neoadjuvant Chemotherapy: A Review of the Literature
No full textMicroRNAs (miRNA) are small noncoding RNAs that can act as both oncogene and tumor suppressors. Deregulated miRNA expression has been detected in human cancers, including breast cancer (BC). Considering their important roles in tumorigenesis, miRNAs have been investigated as potential prognostic and diagnostic biomarkers. Neoadjuvant setting is an optimal model to investigate in vivo the mechanism of treatment resistance. In the management of human epidermal growth factor receptor-2 (HER2)-positive early BC, the anti-HER2-targeted therapies have drastically changed the survival outcomes. Despite this, growing drug resistance due to the pressure of therapy is relatively frequent. In the present review, we focused on the main miRNAs involved in HER2-positive BC tumorigenesis and discussed the recent evidence on their predictive and prognostic value
Endocrine-based targeted combination versus endocrine therapy alone as first-line treatment in elderly patients with hormone receptor-positive advanced breast cancer: Meta-analysis of phase II and III randomized clinical trials.
No full textBackground: Combined endocrine approaches have been widely investigated as 1st-line treatment in hormone receptors
positive metastatic breast cancer. In particular, multiple randomized trials showed that the addiction of CDK (cyclindependent
kinase) 4/6 inhibitors to endocrine therapy (ET) increase progression free survival (PFS). Elderly patients (aged ≥
65 years) are under represented in most of the clinical studies. Moreover, due to the multi-morbidity and the major toxicity
associated with the targeted agents, the combination strategy in that subgroup is widely discussed. The present metaanalysis
aimed to understand the role of the new endocrine approaches in women aged ≥65 years. Methods: This metaanalysis
included first line phase II/III randomized published trials comparing (ET) to the experimental strategy. Trials with no
data about hazard ratios (HR) for PFS in the subgroup of patients aged ≥ 65 years were excluded. The heterogeneity of the
data was evaluated by Chi-square Q test and I2 statistic. Results: 8 studies were included in the analysis. 4 trials
(Paloma1/TRIO-18, Paloma2, Monaleesa2, Monarch3) investigated the role of CDK 4/6 inhibitors, 2 trials (SWOG and
FACT) analysed the combination of Fulvestrant plus Aromatase Inhibitors, while other two trials explored the association of
ET with Bevacizumab (LEA) and Temsirolimus (HORIZON), respectively. Overall, the meta-analysis showed a PFS
advantage for the experimental arms [HR 0.77, p 0.016] with a significant high/moderate heterogeneity [I2 65.46%, p 0.005].
The 4 studies adding CDK4/6 inhibitors to ET showed a significant improvement in PFS compared to ET alone. No
significant advantages for the addition of anti-angiogenic agents or Fulvestrant to ET have been found in elderly population
subgroup. Conclusions: The novel experimental combo-strategies in the first line setting showed an improvement in PFS in
the subgroup of elderly patients. Adding CDK4/6 inhibitors to ET significantly prolongs PFS as compared to ET alone. The
magnitude of PFS benefit due to addition of CDK4/6 inhibitors to ET is age-independent
Sans norme ni sanction : l'homosexualité dans un état postmoraliste
No full textIreland is discovering its gays. The Spring of 1994 saw several people «coming out», but public opinion was not particularly moved. Momentous socio-moral changes had just taken place : in 1993, queers' became legal ; in 1994 Ireland adopted the UN definition of the family, acknowledging the multiplicity of family types. From the only openly gay politician's campaigns to the latest changes in the law and public policy, this article retraces the legalisation of homosexuality in Ireland in a wider framework : the author argues that a new moral order has emerged in Ireland, whereby the individual's moral choice and subjective rights have won out in face of the Catholic Church's diktats. A tradition of tolerance and the legitimization of the « liberal agenda » have contributed to the emergence of a new identity : Irish and gay.Récemment affichée a l'échelle nationale, l'homosexualité d'un certain nombre de personnes et personnalités n'a pas provoqué l'émoi. Et cela à peine un an après la légalisation des rapports homosexuels, et au moment ou une nouvelle définition officielle de la famille, reconnaissant toutes les formes qu'elle peut prendre, rentre en vigueur sous l'égide des Nations Unies. Cet article se propose de retracer les grands moments de la campagne pour les droits civiques des homosexuels irlandais, tout en la replaçant dans son contexte. Nous ne sommes pas témoins de la faillite des valeurs, ni de la fin de la morale, mais de l'avènement d'une éthique minimale, sanctionnée par l'Etat, basée sur les droits fondamentaux des individus. Une longue tradition de tolérance et la légitimation d'un programme libéral ont favorisé l'émergence d'une nouvelle identité : homosexuel et irlandais.Hug Chrystel. Sans norme ni sanction : l'homosexualité dans un état postmoraliste. In: Études irlandaises, n°20-1, 1995. L'État en Irlande, sous la direction de Claude Fierobe et Emile-Jean Dumay. pp. 205-216
Clinical and Pathological Features of Breast Cancer in Systemic Sclerosis: Results from the Sclero-Breast Study
No full textSystemic Sclerosis (SSc) is a chronic disease associated with a 1.5-fold increase in cancer risk, including lung cancer, hematological malignancies, and breast cancer (BC). This is a retrospective study aiming to explore the clinical and pathological features of BC developed by SSc patients. A total of 54.5% of patients developed BC before SSc (median interval: 5 years), whereas 45.5% of patients developed BC after SSc (median delay: 8 years). A total of 93.1% of patients were diagnosed with an early stage tumor. Among invasive carcinomas, 70.8% presented with a low Mib1, 8.3% with a tubular histotype, and 42.8% with a Luminal A-like phenotype. A total of 66.6% of patients underwent breast-conserving surgery and 55.5% RT. A total of 40% of patients developed interstitial lung disease after RT and 20% diffuse cutaneous SSc. The cause of death of the six deceased patients was PAH. A significant association was observed between the use of immunosuppressive therapy and diffuse skin extension, negative ACA, positive Anti-Scl-70, and interstitial lung disease, but not BC status. SSc patients developed BC at a good prognosis, suggesting a de-escalation strategy of cancer therapies. In particular, ionizing radiation and chemotherapeuticals should be limited to higher-risk cases. Finally, proper screening is mandatory in order to allow for early cancer detection in SSc patients
CLINICAL AND PATHOLOGICAL FEATURES OF BREAST CANCER IN PATIENTS WITH SYSTEMIC SCLEROSIS: PRELIMINARY DATA FROM THE SCLERO-BREAST STUDY
No full textSystemic Sclerosis (SSc) is a chronic disease associated with a 1.5-fold increase in cancer risk, including lung cancer, hematological malignancies, and breast cancer (BC). This is a retrospective study aiming to explore the clinical and pathological features of BC developed by SSc patients. A total of 54.5% of patients developed BC before SSc (median interval: 5 years), whereas 45.5% of patients developed BC after SSc (median delay: 8 years). A total of 93.1% of patients were diagnosed with an early stage tumor. Among invasive carcinomas, 70.8% presented with a low Mib1, 8.3% with a tubular histotype, and 42.8% with a Luminal A-like phenotype. A total of 66.6% of patients underwent breast-conserving surgery and 55.5% RT. A total of 40% of patients developed interstitial lung disease after RT and 20% diffuse cutaneous SSc. The cause of death of the six deceased patients was PAH. A significant association was observed between the use of immunosuppressive therapy and diffuse skin extension, negative ACA, positive Anti-Scl-70, and interstitial lung disease, but not BC status. SSc patients developed BC at a good prognosis, suggesting a de-escalation strategy of cancer therapies. In particular, ionizing radiation and chemotherapeuticals should be limited to higher-risk cases. Finally, proper screening is mandatory in order to allow for early cancer detection in SSc patients
First-line treatment for endocrine sensitive bone-only metastatic breast cancer: Is more always better?
No full textThe standard first-line for endocrine sensitive metastatic breast cancer (BC) is represented by endocrine therapy. Several phase III clinical trials searched for more effective endocrine strategies. Nevertheless, the use of combinations for the first-line treatment of bone-only disease (BoD) is widely discussed, due to its indolent course. Our meta-analysis aims to explore the role of new endocrine strategies in BoD.
A systematic review of electronic databases was conducted to identify the phase III clinical trials comparing the standard AI to novel experimental strategies. The hazard ratios (HR) for PFS were pooled in a meta-analysis. The heterogeneity of the data was evaluated by Chi-square Q test and I2 statistic.
8 studies were included in the analyses. 4 trials explored the role of CDK4/6 inhibitors (Monaleesa2 and 7, Monarch3 and Paloma2), 2 trials analyzed Fulvestrant + AI (SWOG and FACT), one trial studied Fulvestrant monotherapy (FALCON), while one trial evaluated the association between Bevacizumab and Letrozole (ALLIANCE). 6 trials reported data regarding the BoD, while 2 trials included the BoD in the non-visceral disease. Overall, the meta-analyses showed a PFS advantage for the experimental arms [HR 0.70 p 0.012], with a significant moderate/high heterogeneity [I2 66.48% p 0.004]. Only the FALCON and Paloma2 showed a significant improvement in PFS, respectively for Fulvestrant and Palbociclib + Letrozole. Considering only trials reporting data for BoD, the experimental arms significantly improved the PFS [HR 0.66 p 0.005], with a low/moderate non-significant heterogeneity [I2 44.95% p 0.106].
The novel strategies showed to be able to improve the PFS of BoD. Nonetheless, only Palbociclib + Letrozole provided statistically significant data of advantage in this setting. In clinical trials, BoD is often included in the non-visceral disease subgroup. Future clinical trials should take into account the differences in natural history and better prognosis of BoD, in order to define the best approach to these patient
"Learned Chaucer" : The evolution of Chaucer's reputation as the author of A Treatise on the Astrolabe
No full textIn 1532, William Thynne printed the first edition of the complete works of Geoffrey Chaucer. It was also the first time his astronomical prose text, A Treatise on the Astrolabe, appeared in print.
In his treatise, Chaucer describes the use of an astronomical instrument called the astrolabe. To be able to use such an instrument required knowledge of the Ptolemaic model of the universe.
In Thynne's edition, Chaucer aqcuired the soubriquet "learned scientist" and subsequent comments seem to indicate that it was thanks to A Treatise on the Astrolabe.
In my thesis, I explore all the editions of Chaucer where the Astrolabe has appeared and give an account of the editors's views and evaluations of the text and of its author.
Most importantly, I attempt to determine how historical factors may have affected these views
