picking the optimal endocrine adjuvant treatment for pre menopausal women

Endocrine treatments are key component of the adjuvant strategy for pre-menopausal patients with luminal tumors. Treatment options should be based not only upon the risk of relapse and level of endocrine responsiveness, but also on co-morbidities, preferences of the patient and degree of side effects. Tamoxifen should still be considered as an appropriate endocrine therapy in a large group of premenopausal patients (e.g. lower risk patient, presence of co-morbidities, patient preference). However, the results of the SOFT and TEXT trials, evaluating the value of ovarian function suppression (OFS) as well as the role of adjuvant aromatase inhibitor (AI), raised questions about the use of tamoxifen alone in selected higher risk patient. In the SOFT study, premenopausal patients did not benefit from the addition of OFS, but for those women at sufficient risk of recurrence to deserve adjuvant chemotherapy and who maintained pre-menopausal estradiol, the addition of OFS to tamoxifen reduced the risk of recurrence. Moreover, in the TEXT trial, adjuvant treatment with exemestane plus OFS, as compared with tamoxifen plus OFS, significantly improved disease-free survival, breast cancer-free interval and distant disease-free survival, thus representing a new treatment option. Recent available information on endocrine options for younger patients with luminal tumors support the use of tailored endocrine treatments. Issues specific for younger patients related to pregnancies desire, family planning, safety, quality of life and subjective side effects should be a priority in the therapeutic algorithm

extended adjuvant chemotherapy in endocrine non responsive disease

Abstract Introduction and aims There is a biological rationale for expecting benefit from longer duration therapy in the subpopulation of patients with endocrine non-responsive disease. Such tumors have a rapid cell proliferation and are associated with a high risk of relapse despite adjuvant chemotherapy. Moreover, prolonged duration of chemotherapy may be particularly relevant for patients with triple negative disease to inhibit the growth of tumors that are not susceptible to the effects of endocrine therapies due to lack of steroid hormone receptors, or to the effects of anti-HER2 target treatment. Methods and results The question of duration of adjuvant chemotherapy for breast cancer has been directly addressed in several trials herein presented. Most of these were small and, therefore, unsuitable for detecting differences of modest magnitude in intrinsic biological subtypes. In addition, a number of trials examine regimens which differ in duration of therapy, but also in the drugs given. In these trials the effects of duration and choice of drug are inextricably confounded. However incremental chemotherapy strategies, compared with less extensive therapies, were more effective in past studies particularly in patients with endocrine non-responsive disease. Conclusions The evidence resulting from past trials indicates that conventional-dose chemotherapy for 4–6 months is an adequate option in patients whose tumors present a low or no expression of steroid hormone receptors. These tumor subtypes are part of a highly heterogeneous subgroup (e.g., basal-like, molecular apocrine, claudin-low, HER-enriched). Tailored research through international cooperation is key to solidify consensus on how to treat individual patients with endocrine non-responsive breast cancer

Treatment selection for patients with equivocal HER2 status and in luminal versus HER2-enriched disease

Equivocal HER2 status has been variably defined in the past, and its clinical implications have long been debated. In the 2018 focused update, ASCO/CAP guidelines recommended that tumours with double-equivocal (by immunohistochemistry and in situ hybridization assays) HER2 status should be considered HER2-negative due to the lack of evidence for any benefit of HER2-targeted therapy. The biology and the response to systemic therapies of tumours co-expressing HR and HER2 is quite complex. There is an extensive bi-directional cross-talk between these 2 pathways, that may result in both intrinsic and acquired resistance to endocrine agents, as well as in lower sensitivity to HER2-targeted therapies. In fact, neoadjuvant studies indicate that pCR rates are significantly lower in HER2-positive/ER-positive than ER-negative tumours, regardless the type of HER2 targeted treatment. The recent identification of different subtypes of HER2-positive breast cancer, according to the co-expression of HR and/or the molecular (intrinsic) subtyping, has prompted a renewed interest for clinical studies aimed at better tailoring the systemic therapy for these patients. A subgroup of them might not need chemotherapy if treated with dual HER2 blockade, and this option has been tested in a number of neo-adjuvant trials. In addition, triple targeting of HR, HER2, and CDK4/6 pathways simultaneously may be an effective treatment and overcome the drug resistance mechanisms that are typical of the disease. Finally, HER2-positive breast cancer may well benefit from immunotherapeutic interventions with anti-programmed cell death protein 1 (PD-1) and programmed cell death ligand 1 (PD-L1) agents

Reply to Comments on: "Preventing chemotherapy-induced alopecia: a prospective clinical trial on the efficacy and safety of a scalp cooling system in early breast cancer patients treated with anthracyclines."

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Comparative study of artificial neural network and physics-informed neural network application in sheet metal forming

Accurate prediction of the resultant geometry in sheet metal forming simulation is necessary to achieve zero-defect production. To quantify the effect of process parameters on the final geometry, numerical methods are used to simulate the process outputs for a given set of process variables. Finite element methods are employed in process optimization and design exploration. However, these computationally expensive models are unhelpful for process control applications. Surrogate models allowing fast prediction of resultant geometry or stress distribution can be plausible solutions. In the current study, we propose a sequential surrogate model to fit the stress field as a function of the process variable and the initial spatial coordinates. The framework is composed of two surrogate models. First, an artificial neural network (ANN) evaluates the displacement and the strain. Then, a second surrogate is employed to fit the stress using input strain and displacement. Here, ANN and physics-informed neural networks (PINN) are compared concerning prediction accuracy for the second surrogate model. The PINN is enhanced with the equilibrium equations. The developed method is demonstrated using a v-bending process. The results show that both surrogate models return good approximations, with ANN showing slightly better results.</p

Coordination environment of Cu(II) ions bound to N-terminal peptide fragments of angiogenin protein

Angiogenin (Ang) is a potent angiogenic factor, strongly overexpressed in patients affected by different types of cancers. The specific Ang cellular receptors have not been identified, but it is known that Ang–actin interaction induces changes both in the cell cytoskeleton and in the extracellular matrix. Most in vitro studies use the recombinant form (r-Ang) instead of the form that is normally present in vivo (“wild-type”, wt-Ang). The first residue of r-Ang is a methionine, with a free amino group, whereas wt-Ang has a glutamic acid, whose amino group spontaneously cyclizes in the pyro-glutamate form. The Ang biological activity is influenced by copper ions. To elucidate the role of such a free amino group on the protein–copper binding, we scrutinized the copper(II) complexes with the peptide fragments Ang(1–17) and AcAng(1–17), which encompass the sequence 1–17 of angiogenin (QDNSRYTHFLTQHYDAK-NH2), with free amino and acetylated N-terminus, respectively. Potentiometric, ultraviolet-visible (UV-vis), nuclear magnetic resonance (NMR) and circular dichroism (CD) studies demonstrate that the two peptides show a different metal coordination environment. Confocal microscopy imaging of neuroblastoma cells with the actin staining supports the spectroscopic results, with the finding of different responses in the cytoskeleton organization upon the interaction, in the presence or not of copper ions, with the free amino and the acetylated N-terminus peptides

metronomic administration of pegylated liposomal doxorubicin in extensively pre treated metastatic breast cancer patients a mono institutional case series report

Abstract Background Metronomic chemotherapy has shown efficacy in patients with metastatic breast cancer. Pegylated liposomal-doxorubicin (PLD) pharmacokinetic characteristics support the rationale for using the drug in a metronomic fashion, potentially able to combine anthracyclines efficacy to a low toxicity profile. Patients and methods In a case-series report carried out in both anthracycline-naive and pre-treated metastatic breast cancer patients, we tested feasibility, clinical efficacy and tolerability of PLD administered with a novel metronomic schedule of 20 mg/m2 i.v. every two weeks. Results 52 patients were enrolled and 45 were evaluated. Forty-four patients were assessed for either response or toxicity. Eight patients (18%) had partial responses (PR) and 17 (39%) stable disease (SD), with a clinical benefit (CB) of 45% (95% CI: 30.3%–59.7%). Nineteen patients (43%) had progressive disease (PD). Neither grade 3 nor grade 4 haematological or clinical side effects were recorded, except for 2 patients with grade 3 palmar-plantar erythrodysesthesia (PPE). No cardiac toxicity was recorded. Conclusion Metronomic administration of PLD is a feasible and active treatment for extensively pre-treated metastatic breast cancer patients, alternative to classic anthracyclines, balancing clinical efficacy with a good quality of life in terms of reduced side effects and low personal costs for the patient

Prognosis of selected triple negative apocrine breast cancer patients who did not receive adjuvant chemotherapy

Background: Triple negative breast cancer encompasses several biological entities with different outcomes and is a priority to identify which patients require more treatment to reduce the risk of recurrence and which patients need less treatment. Patients and methods: Among the 210 women with first primary invasive apocrine non metastatic breast cancer operated on between January 1998 and December 2016 at the European Institute Oncology, Milan, we identified 24 patients with a pT1-pT2, node-negative, triple negative subtype and Ki-67 64 20% who did not receive adjuvant chemotherapy (CT). We compared the outcome of this cohort with a similar group of 24 patients with ductal tumors who received adjuvant chemotherapy, matched by pathological stage and biological features and also with a similar group of 12 patients with apocrine tumors who received adjuvant chemotherapy. Results: The median age was 64 and 61 years in the apocrine (w/o CT) and ductal group, respectively. The median value of Ki-67 expression was 12% in the apocrine group (w/o CT) and 16% in the ductal group (p &lt; 0.001). After a median follow-up of 7.5 years, no patients in the apocrine group (w/o CT) experienced a breast cancer related event compared with 4 events in the ductal carcinoma group (Gray test p-value = 0.11). Conclusions: The outcome of selected apocrine triple negative breast cancer patients who did not received adjuvant chemotherapy is excellent and supports a treatment de-escalation. Multicenter projects focusing on the possibility of avoiding adjuvant chemotherapy in selected subtypes of triple negative breast cancers with favorable outcome are warranted

Development and psychometric testing of a breast cancer patient-profiling questionnaire

Introduction: The advent of \u201cpersonalized medicine\u201d has been driven by technological advances in genomics. Concentration at the subcellular level of a patient\u2019s cancer cells has meant inevitably that the \u201cperson\u201d has been overlooked. For this reason, we think there is an urgent need to develop a truly personalized approach focusing on each patient as an individual, assessing his/her unique mental dimensions and tailoring interventions to his/her individual needs and preferences. The aim of this study was to develop and test the psychometric properties of the ALGA-Breast Cancer (ALGA-BC), a new multidimensional questionnaire that assesses the breast cancer patient\u2019s physical and mental characteristics in order to provide physicians, prior to the consultation, with a patient\u2019s profile that is supposed to facilitate subsequent communication, interaction, and information delivery between the doctor and the patient. Methods: The specific validation processes used were: content and face validity, construct validity using factor analysis, reliability and internal consistency using test\u2013retest reliability, and Cronbach\u2019s alpha correlation coefficient. The exploratory analysis included 100 primary breast cancer patients and 730 healthy subjects. Results: The exploratory factor analysis revealed eight key factors: global self-rated health, perceived physical health, anxiety, self-efficacy, cognitive closure, memory, body image, and sexual life. Test\u2013retest reliability and internal consistency were good. Comparing patients with a sample of healthy subjects, we also observed a general ability of the ALGA-BC questionnaire to discriminate between the two. Conclusion: The ALGA-BC questionnaire with 29 items is a valid instrument with which to obtain a patient\u2019s profile that is supposed to help physicians achieve meaningful personalized care which supplements biological and genetic analyse