Breast Cancer Risk After Ovarian Stimulation for In Vitro Fertilization

The study by Dr van den Belt-Dusebout and colleagues1 investigated a debated aspect of reproductive medicine: breast cancer risk following ovarian stimulation for in vitro fertilization (IVF).2-5 The authors concluded that “these findings are consistent with absence of a significant increase in long-term risk of breast cancer among IVF-treated women”.1 However, some important points should be discussed. For about 23 % of women, sub-fertility diagnosis and number of IVF cycles were collected using a questionnaire since medical records were not available. This high rate threatens the reliability of results. It is not possible to compare a detailed report of official medical records with data deriving from subjective memory of treatments received many years before. This may be a strong bias, because reproductive medicine, IVF strategies and the pharmacological protocols have changed rapidly in the last decades. Dates of diagnosis and histology were reported but unfortunately not disease staging. It would be interesting to investigate if ovarian stimulation with the use of IVF techniques can promote the occurrence of biologically different types of breast cancer, as in the case of tamoxifen-related endometrial cancer, a neoplasia with better prognostic profile and outcome. Also, the authors reported that breast cancer risk decreased with more IVF cycles (7 or more compared with 1-2). They suggested as potential explanations that women treated with more IVF cycles received more hCG or had longer periods of down-regulation with low estradiol and progesterone levels, or the women requiring more IVF cycles were inherently different. It is difficult to provide a definitive conclusion since the clinical outcomes of IVF cycles were not reported. The decreased risk in women treated with many IVF cycles also could be related to the improvement of ovarian function after repeated endocrine stimulations. Infertility and infertility-related nulliparity must be considered as risk factors for breast cancer, and prolonged treatment of anovulatory or poor ovulatory cycles could be one approach for restoring normal ovarian activity and reducing breast cancer risk

Update on Poly-ADP-ribose polymerase inhibition for ovarian cancer treatment

Background: Despite standard treatment for epithelial ovarian cancer (EOC), that involves cytoreductive surgery followed by platinum-based chemotherapy, and initial high response rates to these, up to 80 % of patients experience relapses with a median progression-free survival of 12–18 months. There remains an urgent need for novel targeted therapies to improve clinical outcomes in ovarian cancer. Of the many targeted therapies currently under evaluation, the most promising strategies developed thus far are antiangiogenic agents and Poly(ADP-ribose) polymerase (PARP) inhibitors. Particularly, PARP inhibitors are active in cells that have impaired repair of DNA by the homologous recombination (HR) pathway. Cells with mutated breast related cancer antigens (BRCA) function have HR deficiency, which is also present in a significant proportion of non-BRCA-mutated ovarian cancer (“BRCAness” ovarian cancer). The prevalence of germline BRCA mutations in EOC has historically been estimated to be around 10–15 %. However, recent reports suggest that this may be a gross underestimate, especially in women with high-grade serous ovarian cancer (HGSOC). Main body of the abstract: The emergence of the DNA repair pathway as a rational target in various cancers led to the development of the PARP inhibitors. The concept of tumor-selective synthetic lethality heralded the beginning of an eventful decade, culminating in the approval by regulatory authorities both in Europe as a maintenance therapy and in the United States treatment for advanced recurrent disease of the first oral PARP inhibitor, olaparib, for the treatment of BRCA-mutated ovarian cancer patients. Other PARP inhibitors are clearly effective in this disease and, within the next years, the results of ongoing randomized trials will clarify their respective roles. Conclusion: This review will discuss the different PARP inhibitors in development and the potential use of this class of agents in the future. Moreover, combination strategies involving PARP inhibitors are likely to receive increasing attention. The utility of PARP inhibitors combined with cytotoxic chemotherapy is of doubtful value, because of enhanced toxicity of this combination; while, more promising strategies include the combination with antiangiogenic agents, or with inhibitors of the P13K/AKT pathway and new generation of immunotherapy

Niraparib in ovarian cancer. results to date and clinical potential

Ovarian cancer is the first cause of death from gynaecological malignancy. Germline mutation in BRCA1 and 2, two genes involved in the mechanisms of reparation of DNA damage, are showed to be related with the incidence of breast and ovarian cancer, both sporadic and familiar. PARP is a family of enzymes involved in the base excision repair (BER) system. The introduction of inhibitors of PARP in patients with BRCA-mutated ovarian cancer is correlated with the concept of synthetic lethality. Among the PARP inhibitors introduced in clinical practice, niraparib showed interesting results in a phase III trial in the setting of maintenance treatment in ovarian cancer, after platinum-based chemotherapy. Interestingly, was niraparib showed to be efficacious not only in BRCA-mutated patients, but also in patients with other alterations of the homologous recombination (HR) system and in patients with unknown alterations. These results position niraparib as the first PARP-inhibitor with clinically and statistically significant results also in patients with no alterations in BRCA 1/2 and other genes involved in the DNA repair system. Even if the results are potentially practice-changing, the action of niraparib must be further studied and deepened

Innovations in the treatment of ovarian cancer. Analysis of the therapeutic development: from platinum to immunotherapy

Ovarian cancer is the seventh most common cancer in women. The therapeutic approach provides for an appropriate integration between surgery and chemotherapy. Surgery is an important step for diagnosis, staging and therapy, aiming at the complete cytoreduction of all macroscopic visible disease. At the moment, adjuvant and first-line chemotherapy has as a standard the carboplatin-paclitaxel combination. Further, the addition of bevacizumab in the advanced stage (IIIB-IV) is strongly recommended. Despite the initial effectiveness, however, 70-80% of patients develop relapsed disease within the first two years and require subsequent treatment lines that have palliative, rather than curative purposes and that seek to reach a chronic state for the disease. Among the causes of recurrences, one of the most studied is related to the stem cells that, due to a quiescent state, are resistant to chemotherapy. The choice of these treatments must consider several factors, including the probability of extending the PFS and OS, the residual toxicity, symptoms control, and the improvement of quality of life, and always remains subject to platinum free interval (PFI). There are not standard therapy. Pegylated liposomal doxorubicin (PLD) as a single agent or in combination with other drugs is one of several treatment modalities that may be considered for relapsed ovaria cancer. In addition, in about 15% to 20% of epithelial tumors, there is a mutation of the BRCA1 and 2 genes. This is fundamental to identify immediately a therapeutic opportunity represented by PARP inhibitors. These drugs, such as olaparib and niraparib, used in maintenance after a previous platinum-response, even partial, have also shown in upfront an activity in BRCA wild type, homologous recombination deficent (HRD) and homologous recombination proficient (HRP). Therefore, after 20 years of chemotherapy alone, new targeted therapies are emerging that will help changing the therapeutic approach, making treatments increasingly personalized

Triple negative breast cancer: new perspectives for targeted therapies

Breast cancer is a heterogeneous disease, encompassing a large number of entities showing different morphological features and having clinical behaviors. It has became apparent that this diversity may be justified by distinct patterns of genetic, epigenetic, and transcriptomic aberrations. The identification of gene-expression microarray-based characteristics has led to the identification of at least five breast cancer subgroups: luminal A, luminal B, normal breast-like, human epidermal growth factor receptor 2, and basal-like. Triple-negative breast cancer is a complex disease diagnosed by immunohistochemistry, and it is characterized by malignant cells not expressing estrogen receptors or progesterone receptors at all, and human epidermal growth factor receptor 2. Along with this knowledge, recent data show that triple-negative breast cancer has specific molecular features that could be possible targets for new biological targeted drugs. The aim of this article is to explore the use of new drugs in this particular setting, which is still associated with poor prognosis and high risk of distant recurrence and death

Primary prophylaxis of neutropenia in women affected by breast cancer undergoing adjuvant chemotherapy with fec 100+/- docetaxel. Comparison of efficacy and tolerability between lenograstim and pegfilgrastim

Objectives: evaluate safety and toxicity of a single injection of pegfilgrastim compared to daily administration of lenograstim in breast cancer patient undergoing adjuvant chemotherapy

Factors influencing choice of chemotherapy in metastatic colorectal cancer (mCRC)

Management of metastatic colorectal cancer requires a multimodal approach and must be performed by an experienced, multidisciplinary expert team. The optimal choice of the individual treatment modality, according to disease localization and extent, tumor biology, and patient clinical characteristics, will be one that can maintain quality of life and long-term survival, and even cure selected patients. This review is an overview of the different therapeutic approaches available in metastatic colorectal cancer, for the purpose of defining personalized therapeutic algorithms according to tumor biology and patient clinical features

Family history of cancer as surrogate predictor for immunotherapy with anti-PD1/PD-L1 agents: preliminary report of the FAMI-L1 study.

Aim: Tumors related to hereditary susceptibility seem to have an immunosensitive phenotype. Materials & methods: We conducted a multicenter retrospective study, to investigate if family history of cancer, multiple neoplasms and early onset of cancer could be related to clinical outcomes of anti-PD-1/PD-L1 therapy. Activity and efficacy data of 211 advanced cancer patients (kidney, non-small-cell lung cancer, melanoma, urothelium, colorectal and HeN), treated at seven Italian centers with anti-PD-1/PD-L1 agents, were analyzed. Results: In this preliminary report at multivariate analyses, positive family history of cancer showed a statistically significant relationship with a better objective response rate (p = 0.0024), disease control rate (p = 0.0161), median time to treatment failure (p = 0.0203) and median overall survival (p = 0.0221). Diagnosis of multiple neoplasms significantly correlates only to a better disease control rate, while interestingly non-early onset of cancer and sex (in favor of female patients) showed significant correlation with a better median overall survival (p = 0.0268 and p = 0.0272, respectively). Conclusion: This pilot study seems to individuate easily available patient's features as possible predictive surrogates of clinical benefit for anti-PD-1/PD-L1 treatments. These preliminary results need to be confirmed with a greater sample size, in prospective trials with immunotherapy

INfluenza Vaccine Indication During therapy with Immune checkpoint inhibitors: a transversal challenge. The INVIDIa study

Aim: Considering the unmet need for the counseling of cancer patients treated with immune checkpoint inhibitors (CKI) about influenza vaccination, an explorative study was planned to assess flu vaccine efficacy in this population. Methods: INVIDIa was a retrospective, multicenter study, enrolling consecutive advanced cancer outpatients receiving CKI during the influenza season 2016-2017. Results: Of 300 patients, 79 received flu vaccine. The incidence of influenza syndrome was 24.1% among vaccinated, versus 11.8% of controls; odds ratio: 2.4; 95% CI: 1.23-4.59; p = 0.009. The clinical ineffectiveness of vaccine was more pronounced among elderly: 37.8% among vaccinated patients, versus 6.1% of unvaccinated, odds ratio: 9.28; 95% CI: 2.77-31.14; p < 0.0001. Conclusion: Although influenza vaccine may be clinically ineffective in advanced cancer patients receiving CKI, it seems not to negatively impact the efficacy of anticancer therapy

Memòria Digital de Catalunya

Conté (segons GW): "Meditationes. -- e5a: Soliloquia: Agnoscam te. -- i3a: Manuale (Ausg. c). -- l2a: Pseudo-Bernardus: Meditationes. -- n1a: De perfectione vitae. -- n2b: Petrus Damiani: Sermo. -- n3b: Anselmvon Canterbury: Meditationes. -- o8a: N. Laudensis Carmina. -- o8a: Pius II, Papst: In laudem divi Augustini. -- o8b: Maphaeus Vegius: Epigramma in laudem Monicae. -- l1a: Vincentius Ferrerius: De vita spirituali. -- p1a: Pseudo-Bernardus: Sermo de passione domini"Tít. obtingut de l'epígraf del f. sign. [ ]1Tít a f. sign. a1: Meditationes diui Augustini episcopi Hypponensis, Soliloquia eiusdem, Manuale eiusdem castigatissimePeu d'impr. obtingut del colofó (f. sign.: o9v.)Marca de l'impr. amb les inicials A B al colofóEls f. sign.: o10, m12 i p8 en blancSignatures: [ ]4, a-n8, o10, l8, m12, p8 (el f. sign. l1, 1a seqüència signat: kk)Tipus gòtics de dues mides, 2 columnes i registre al colofóCaplletres xilogràfiques ornades i alguns espais en blanc per a les caplletre