Tryfonidis K.,European Organization for Research and Treatment of Cancer EORTC Headquarters |
Zardavas D.,Breast International Group Headquarters BIG Aisbl |
Cardoso F.,Breast Unit
Cancer Treatment Reviews | Year: 2014
Small (T1a, b), lymph node negative breast tumors represent an entity diagnosed with increasing frequency due to the implementation of wide-scale screening programs. Patients bearing such tumors usually exhibit favorable long-term outcomes, with low breast cancer mortality rates at 10. years, even in the absence of adjuvant chemotherapy. However, most available data derive from retrospective studies. Additionally, a subset of patients with these tumors experience recurrence of the disease, indicating that early tumor stage itself is not a sufficient prognosticator. It is of paramount importance to refine the prognosis of this population, identifying patients with high risk of recurrence, for whom adjuvant treatment is needed. The underlying biology of the disease provides relevant information, such as grade and status of hormone receptors and HER-2 (human epidermal growth factor receptor 2), with high grade, triple negative and HER-2-positive tumors having worse prognosis. Additionally, multigene signatures may improve further the prognostication of patients with small, node negative breast cancers. Further research for this increasingly frequent group of patients is urgently needed, so that better informed clinical decision making, in particular regarding adjuvant chemotherapy, can occur. © 2014 Elsevier Ltd.
Cuzick J.,Queen Mary, University of London |
Sestak I.,Queen Mary, University of London |
Forbes J.F.,University of Newcastle |
Knox J.,Queen Mary, University of London |
And 10 more authors.
The Lancet | Year: 2014
Background Aromatase inhibitors eff ectively prevent breast cancer recurrence and development of new contralateral tumours in postmenopausal women. We assessed the effi cacy and safety of the aromatase inhibitor anastrozole for prevention of breast cancer in postmenopausal women who are at high risk of the disease. Methods Between Feb 2, 2003, and Jan 31, 2012, we recruited postmenopausal women aged 40-70 years from 18 countries into an international, double-blind, randomised placebo-controlled trial. To be eligible, women had to be at increased risk of breast cancer (judged on the basis of specifi c criteria). Eligible women were randomly assigned (1:1) by central computer allocation to receive 1 mg oral anastrozole or matching placebo every day for 5 years. Randomisation was stratifi ed by country and was done with blocks (size six, eight, or ten). All trial personnel, participants, and clinicians were masked to treatment allocation; only the trial statistician was unmasked. The primary endpoint was histologically confi rmed breast cancer (invasive cancers or non-invasive ductal carcinoma in situ). Analyses were done by intention to treat. This trial is registered, number ISRCTN31488319. Findings 1920 women were randomly assigned to receive anastrozole and 1944 to placebo. After a median follow-up of 5.0 years (IQR 3.0-7.1), 40 women in the anastrozole group (2%) and 85 in the placebo group (4%) had developed breast cancer (hazard ratio 0.47, 95% CI 0.32-0.68, p<0.0001). The predicted cumulative incidence of all breast cancers after 7 years was 5.6% in the placebo group and 2.8% in the anastrozole group. 18 deaths were reported in the anastrozole group and 17 in the placebo group, and no specifi c causes were more common in one group than the other (p=0.836). Interpretation Anastrozole eff ectively reduces incidence of breast cancer in high-risk postmenopausal women. This fi nding, along with the fact that most of the side-eff ects associated with oestrogen deprivation were not attributable to treatment, provides support for the use of anastrozole in postmenopausal women at high risk of breast cancer. Funding Cancer Research UK, the National Health and Medical Research Council Australia, Sanofi -Aventis, and AstraZeneca.
Awada A.,Free University of Colombia |
Garcia A.A.,University of Southern California |
Chan S.,University of Nottingham |
Jerusalem G.H.M.,CHU Sart Tilman |
And 14 more authors.
The Lancet Oncology | Year: 2013
Background: New therapeutic options are needed for patients with heavily pretreated breast cancer. Etirinotecan pegol is a long-acting topoisomerase-I inhibitor designed to provide prolonged tumour-cell exposure to SN38, the active metabolite. We aimed to assess the efficacy and safety of two etirinotecan pegol dosing schedules in patients with previously treated metastatic breast cancer to determine an optimum dosing schedule for phase 3 trials. Methods: In this randomised, two-stage, open-label phase 2 trial, we recruited patients aged 18 years or older who had received taxane therapy and undergone two or fewer previous chemotherapy regimens for metastatic breast cancer, with an Eastern Cooperative Oncology Group performance status of 0 or 1, from 18 sites in three countries. Eligible patients were randomly assigned (1:1) to etirinotecan pegol 145 mg/m2 every 14 days or every 21 days. The primary endpoint was the proportion of patients with a confirmed objective response as defined by Response Evaluation Criteria in Solid Tumors version 1.0, analysed by intention to treat. Safety was assessed in all patients who received at least one dose of study drug. This trial is registered at ClinicalTrials.gov, number NCT00802945. Findings: 70 patients (35 in each group) were randomly assigned to treatment between Feb 17, 2009 and April 13, 2010. Of the 70 patients, 20 (29%; 95% CI 18·4-40·6) achieved an objective response (two [3%] had a complete response and 18 [26%] had a partial response). Ten patients on the 14-day schedule achieved an objective response (29%; 95% CI 14·6-46·3; eight partial responses, two complete responses) as did ten on the 21-day schedule (29%; 95% CI 14·6-46·3; all partial responses). The most common grade 3 or worse adverse events were delayed diarrhoea (seven [20%] of 35 patients on the 14-day schedule vs eight [23%] of 35 patients on the 21-day schedule), fatigue (five [14%] vs three [9%]), neutropenia (four [11%] vs four [11%]), and dehydration (three [9%] vs four [11%]); 14 [20%] patients discontinued treatment because of drug-related toxicity. There were two possible drug-related deaths (acute renal failure and septic shock) in the 14-day group; other drug-related serious adverse events reported by more than one patient included ten [14%] patients with diarrhoea (six [17%] patients on the 14-day schedule vs four [11%] on the 21-day schedule), six [9%] with dehydration (two [6%] vs four [11%]), two [3%] with nausea (two [6%] vs none), and two [3%] with vomiting (two [6%] vs none). Interpretation: On the basis of the overall clinical data, pharmacokinetics, and tolerability profile, etirinotecan pegol 145 mg/m2 every 21 days has been selected for a phase 3 trial against treatment of physician's choice in patients with advanced breast cancer. Funding: Nektar Therapeutics. © 2013 Elsevier Ltd.
Eterno V.,IRCCS Salvatore Maugeri Foundation |
Zambelli A.,IRCCS Salvatore Maugeri Foundation |
Pavesi L.,IRCCS Salvatore Maugeri Foundation |
Villani L.,IRCCS Salvatore Maugeri Foundation |
And 5 more authors.
Oncotarget | Year: 2014
Adipose tissue is a reservoir of Mesenchymal Stem Cells (Adipose-derived Mesenchymal Stem Cells, ASCs), endowed with regenerative properties. Fat graft was proposed for breast reconstruction in post-surgery cancer patients achieving good aesthetic results and tissues regeneration. However, recent findings highlight a potential tumorigenic role that ASCs may have in cancer recurrence, raising some concerns about their safety in clinical application. To address this issue, we established a model where autologous ASCs were combined with primary normal or cancer cells from breast of human donors, in order to evaluate potential effects of their interactions, in vitro and in vivo. Surprisingly, we found that ASCs are not tumorigenic per sè, as they are not able to induce a neoplastic transformation of normal mammary cells, however they could exhacerbate tumorigenic behaviour of c-Met-expressing breast cancer cells, creating an inflammatory microenvironment which sustained tumor growth and angiogenesis. Pharmacological c-Met inhibition showed that a HGF/c-Met crosstalk between ASCs and breast cancer cells enhanced tumor cells migration, acquiring a metastatic signature, and sustained tumor self-renewal. The master role of HGF/c-Met pathway in cancer recurrence was further confirmed by c-Met immunostaining in primary breast cancer from human donors, revealing a strong positivity in patients displaying a recurrent pathology after fat grafts and a weak/moderate staining in patients without signs of recurrence. Altogether our findings, for the first time, suggest c-Met expression, as predictive to evaluate risk of cancer recurrence after autologous fat graft in post-surgery breast cancer patients, increasing the safety of fat graft in clinical application.
Tryfonidis K.,Eur Organization For Research And Treat Of Cancer Eortc Headq And Breast Cancer Gro |
Senkus E.,Medical University of Gdańsk |
Cardoso M.J.,Breast Unit |
Cardoso F.,Breast Unit
Nature Reviews Clinical Oncology | Year: 2015
Locally advanced breast cancer (LABC) constitutes a heterogeneous entity that includes advanced-stage primary tumours, cancers with extensive nodal involvement and inflammatory breast carcinomas. Although the definition of LABC can be broadened to include some large operable breast tumours, we use this term to strictly refer to inoperable cancers that are included in the above-mentioned categories. The prognosis of such tumours is often unfavourable; despite aggressive treatment, many patients eventually develop distant metastases and die from the disease. Advances in systemic therapy, including radiation treatment, surgical techniques and the development of new targeted agents have significantly improved clinical outcomes for patients with this disease. Notwithstanding these advances, LABC remains an important clinical problem, particularly in developing countries and those without widely adapted breast cancer awareness programmes. The optimal management of LABC requires a multidisciplinary approach, a well-coordinated treatment schedule and close cooperation between medical, surgical and radiation oncologists. In this Review, we discuss the current state of the art and possible future treatment strategies for patients with LABC. © 2015 Macmillan Publishers Limited.
Senkus E.,Medical University of Gdańsk |
Cardoso F.,Breast Unit |
Pagani O.,Institute of Oncology of Southern Switzerland and Breast Unit of Southern Switzerland
Cancer Treatment Reviews | Year: 2014
Treatment of metastatic breast cancer has substantially changed in the last decades. Availability of new cytotoxics and targeted therapies as well as changes in treatment philosophy and strategy have all contributed to a significant improvement in both survival and patients' quality of life. The multidisciplinary approach, personalised treatments based on tumour characteristics, patient's and disease history, as well as re-definition of treatment goals, aiming at the lowest possible impact on patients' life by replacing aggressive multidrug chemotherapy with single-agent cytotoxic treatment or endocrine. ±. targeted therapies, have all been the bases of the new treatment paradigm. More recently the development of the international advanced breast cancer (ABC) consensus guidelines have further contributed to this improvement. This review will focus on the major achievements and challenges in the different tumour subtypes and sites, with a focus on future research topics and trends. © 2013 Elsevier Ltd.
Cardoso F.,Breast Unit |
Senkus E.,Medical University of Gdańsk
Nature Reviews Gastroenterology and Hepatology | Year: 2015
In 2014, no major breakthroughs were made in understanding the biology of breast cancer or its management; few novel practice-changing studies were presented or published. Nevertheless, important negative results from studies that challenge some of the current concepts, particularly in drug development, underline 2014 as a year of 'failed surrogates and precocious expectations'. © 2015 Macmillan Publishers Limited.
Schiavon G.,Breast Unit |
Schiavon G.,The Institute of Cancer Research |
Smith I.E.,Breast Unit |
Smith I.E.,The Institute of Cancer Research
Hematology/Oncology Clinics of North America | Year: 2013
First-line endocrine therapy by estrogen antagonism or suppression of estrogen achieves objective responses (ORs) and clinical benefit (CB) in around 30% and 50% of estrogen receptor-positive metastatic breast cancer patients, respectively. Aromatase inhibitors (AIs) are the most effective treatment in previously untreated postmenopausal women. Tamoxifen is an effective alternative. The optimal endocrine therapy on relapse remains uncertain. Tamoxifen and fulvestrant achieve CB in around 50% of patients and ORs of 10%. CB of exemestane after nonsteroidal AIs is 30% to 50% but ORs are rare. Targeted agents (eg, everolimus) plus endocrine therapy are likely to become increasingly important in overcoming endocrine resistance. © 2013 Elsevier Inc.
Cardoso M.J.,Breast Unit |
Oliveira H.,INESC Porto |
Cardoso J.,INESC Porto
Journal of Surgical Oncology | Year: 2014
"Taking less treating better" has been one of the major improvements of breast cancer surgery in the last four decades. The application of this principle translates into equivalent survival of breast cancer conserving treatment (BCT) when compared to mastectomy, with a better cosmetic outcome. While it is relatively easy to evaluate the oncological results of BCT, the cosmetic outcome is more difficult to measure due to the lack of an effective and consensual procedure. The assessment of cosmetic outcome has been mainly subjective, undertaken by a panel of expert observers or/and by patient self-Assessment. Unfortunately, the reproducibility of these methods is low. Objective methods have higher values of reproducibility but still lack the inclusion of several features considered by specialists in BCT to be fundamental for cosmetic outcome. The recent addition of volume information obtained with 3D images seems promising. Until now, unfortunately, no method is considered to be the standard of care. This paper revises the history of cosmetic evaluation and guides us into the future aiming at a method that can easily be used and accepted by all, caregivers and caretakers, allowing not only the comparison of results but the improvement of performance. © 2014 Wiley Periodicals, Inc.
Oliveira H.P.,INESC Porto |
Cardoso J.S.,INESC Porto |
Magalhaes A.,University of Porto |
Cardoso M.J.,Breast Unit
Current Medical Imaging Reviews | Year: 2013
Breast-conserving approaches aim to attain better aesthetic results in addition to local control and achieving survival rates equivalent to mastectomy in patients with breast cancer. While the oncologic outcome of breast conservation procedures is easily estimated objectively by disease-free and overall survival rates, the cosmetic outcome has no standard of evaluation. Although breast conservation techniques have been widely studied, different forms of evaluation and heterogeneous working practices have contributed to different aesthetic results. As this scenario suggests, the evaluation of aesthetic results should be mandatory in any institution performing breast cancer treatment, contributing to the improvement of current strategies by enabling the identification of variables which have a significant impact on the final aesthetic result. In the process of assessing cosmetic outcomes there are several important issues that should be considered: which factors have a crucial impact on the cosmetic outcome of Breast Cancer Conservation Treatment (BCCT); which parameters or features should be evaluated in the cosmetic assessment of BCCT; how patients are evaluated; which scales are used in this evaluation; which methods and technological solutions are available for the evaluation of cosmetic results of BCCT. In this paper we try to discuss all these questions, with an emphasis on the objective methods and corresponding technologies used in the aesthetic evaluation of BCCT. The most relevant publications related to the mentioned topics are presented, critically analysed and put in chronological perspective. Current and future trends are also discussed. © 2013 Bentham Science Publishers.