International Guidelines for Management of Metastatic Breast Cancer: Can Metastatic Breast Cancer Be Cured?

A distinctive subset of metastatic breast cancer (MBC) is oligometastatic disease, which is characterized by single or few detectable metastatic lesions. The existing treatment guidelines for patients with localized MBC include surgery, radiotherapy, and regional chemotherapy. The European School of Oncology-Metastatic Breast Cancer Task Force addressed the management of these patients in its first consensus recommendations published in 2007. The Task Force endorsed the possibility of a more aggressive and multidisciplinary approach for patients with oligometastatic disease, stressing also the need for clinical trials in this patient population. At the sixth European Breast Cancer Conference, held in Berlin in March 2008, the second public session on MBC guidelines addressed the controversial issue of whether MBC can be cured. In this commentary, we summarize the discussion and related recommendations regarding the available therapeutic options that are possibly associated with cure in these patients. In particular, data on local (surgery and radiotherapy) and chemotherapy options are discussed. Large retrospective series show an association between surgical removal of the primary tumor or of lung metastases and improved long-term outcome in patients with oligometastatic disease. In the absence of data from prospective randomized studies, removal of the primary tumor or isolated metastatic lesions may be an attractive therapeutic strategy in this subset of patients, offering rapid disease control and potential for survival benefit. Some improvement in outcome may also be achieved with optimization of systemic therapies, possibly in combination with optimal local treatmen

Cistadenoma mucinoso retroperitoneal primário - relato de caso

Universidade Federal de São Paulo (UNIFESP), Escola Paulista de Medicina (EPM)UNIFESP, EPMSciEL

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

The goods and bads of state intervention : three empirical essays in political economy

Defence date: 09 December 2024Examining Board: Prof. Andrea Mattozzi (University of Bologna; European University Institute, supervisor); Prof. David Levine (Royal Holloway; University of London); Prof. Roberto Galbiati (Sciences Po); Prof. Giacomo De Luca (Libera Università di Bolzano)Institutions concurring to overcome market failures and coordination issues are relevant contributors to economic growth and development. Nonetheless, public interventions may incentivise corruptive behaviour or a distorted allocation of resources, if the state apparatus is not adequately regulated in turn. These different implications of the involvement of the public sector in the economy are the object of my thesis. In Chapter 1, I propose a historical and economic analysis of the heterogeneous institutional setting defined by the British in Central India after winning the third Anglo-Maratha war in 1818. Owing to institutional quality, the positive synergies between the private and public sectors in the treated group have enabled the construction of the railway infrastructure, which drove diverging development paths with the control group. In fact, a relevant difference in nutrition and wealth indicators is still measured in 2015. Instead, the public offices under study in Chapter 2 seem to be engaging in a self-interested vote-buying strategy by making the discretionary hirings of local workforce depend on the local electoral timing. In this analysis, the outcome of interest proxies the ratio of new employees who are entitled to vote in the Italian regional elections. It outlines a drop of nearly 30 percentage points after the mandated deferral due to Covid, and a surge close to the same magnitude after the new election announcement, vis-à-vis the regions that were not meant to vote in the same period. These effects are consistent across two different empirical strategies, involving DID and RD estimation. Similarly, Chapter 3 - joint with Giacomo De Luca and Jahen Rezki - uses a combination of RD and DID techniques to understand if the emergence of dynasties of politicians has an impact on local development and public expenditures in Indonesia. There, the phenomenon has become widespread and is considered as a possible threat to the democratisation process. To this purpose, our data cover the island of Java at the district level during the period 2005-2020. We do not find general evidence of worse outcomes immediately attributable to dynastic rulers.-- 1. The long-term welfare effects of colonial institutions : evidence from Central India -- 2. Targeted spending : the effect of the electoral timing on the distribution of discretionary jobs within the Italian bureaucracy -- 3. Political dynasties, development, and corruption : a study on the island of Java -- 4. AppendicesChapter 1 'The long-term welfare effects of colonial institutions : evidence from Central India' of the PhD thesis draws upon an earlier version published as an article 'The long-term welfare effects of colonial institutions : evidence from Central India' (2024) in the 'Journal of development economics'

The long-term welfare effects of colonial institutions : evidence from Central India

Published online: 13 October 2023In Central India, the Narmada River separates two regions that have been ruled by different types of government only during the colonial period, and for reasons independent of their initial economic development. I implement a spatial RDD on village population in the Nineteenth Century as well as in 1901, and I run the same model on proxies of welfare in 2015. My results highlight that divergence has realised where the river overlapped with the colonial border, but not in a neighbouring area where the same Narmada River separates two shores with the same type of former colonial institution. I discuss the following transmission mechanism. The treated group was directly administered by the British with more modern state tools - such as the enforcement of property rights and a transparent taxation system - that made it easier to develop private investment. The most prominent example is the mixed-capital enterprise in charge of the construction of the first trans-continental railway. Infrastructure endowment seems to be crucial for the long-term transmission of the colonial institutional characteristics to the outcomes measured in 2015, which show better average welfare outcomes, as well as higher wealth inequality in the treated group. My work provides an explanation of how the improvement in the quality of the institutions of an embryonic state may sustain the growth of the local markets it deems relevant.This article was published Open Access with the support from the EUI Library through the CRUI - Elsevier Transformative Agreement (2023-2027)

lessons on responsiveness to adjuvant systemic therapies learned from the neoadjuvant setting

Summary Aims Recommended principles for the choice of therapies in operable breast cancer include the recognition of diverse subtypes of breast cancer and, based on genetic signature and immunohistochemistry, the identification of targets and related factors predictive of response. We review recent developments in the knowledge of established predictive factors in the neo-adjuvant setting. Methods and Results Experimental and clinical studies have shown that the degree of expression of estrogen receptor (ER) and progesterone receptor (PgR) of the primary tumor defines distinct biological entities that require a differentiated approach to neoadjuvant treatment and clinical trial investigation. In particular, tumors that express high levels of both steroid hormone receptors in a majority of cells derive no or low benefit from preoperative chemotherapy, while the absence of expression of ER and PgR was significantly correlated with the probability of pathologic complete remission (pCR). It was also demonstrated that the pCR rate to primary chemotherapy is significantly lower in invasive lobular carcinoma, frequently characterized by a high expression of steroid hormone receptors, if compared with the ductal histotype. Direct or indirect measures of high cell proliferation (elevated Ki-67 labeling index and high grade) identified patients with tumors responsive to chemotherapy in the preoperative setting. These factors might therefore assist in the identification of patients who might benefit from chemotherapy, in particular those patients with endocrine responsiveness. HER2 overexpression or amplification represents a target for neoadjuvant treatment with the humanised monoclonal antibody against its extracellular domain, but is also a factor predictive of response to neoadjuvant systemic therapies. A statistically significant positive correlation between HER2 positivity and pCR rate in patients treated with neoadjuvant chemotherapy was recently shown. Conclusions Results from studies in the neoadjuvant setting indicate that the use of factors predictive of response may permit a more effective application of therapies identifying patients likely to obtain substantial benefit from treatment