EUSOMA position regarding breast implant associated anaplastic large cell lymphoma (BIA-ALCL) and the use of textured implants.

During the last two decades the number of breast implants used in aesthetic, oncologic and risk reducing surgery has increased substantially mainly due to the improvement and confirmed safety of these devices. Since identification of the first case of anaplastic large cell lymphoma associated with a breast implant (BIA-ALCL) 20 years ago, there has been an increase in the number of reports of this very rare disease, demonstrating a clear association with breast implants. Whilst the majority of cases are localised and cured by implant removal and full capsulectomy, a small percentage require chemotherapy and the mortality rate is very low. The evidence linking BIA-ALCL to implant surface texturing, as the majority of cases were diagnosed in patients with textured implants, has raised concerns about the long term safety of these devices resulting in patient and regulatory authority concerns globally. We hereby present the current published knowledge about the link between BIA-ALCL and implant surface texture and a review of current regulatory and professional body advice across Europe, which may enable a better understanding of this rare disease, how to manage and ultimately prevent it. We conclude by giving EUSOMA recommendation, towards the unnecessary change in attitudes towards implant based surgery, according to the most recent available published evidence as long as patients are properly informed about the risk of BIA-ALCL.

Variability in breast cancer surgery training across Europe: An ESSO-EUSOMA international survey.

BACKGROUND: At present there is a lack of standardization of training in breast cancer surgery across Europe. The aim of this survey was to assess current practice in Europe regarding training in breast cancer (BC) surgery. MATERIAL AND METHODS: General surgeons, surgical oncologists, gynecologist, and plastic surgeons in Europe were invited to participate in this bespoke survey including 19 questions. RESULTS: The survey was sent to 3.000 surgical oncologists across Europe. A total of 671 physicians (387 general surgeons, 152 gynecologists, 126 surgical oncologist, 31 plastic surgeons) answered the survey (23% response rate). Four hundred and sixty-eight physicians devoted between 50% -100% of their job to treating breast cancer. 45% worked in a community/University hospital within a dedicated Breast Unit. Specific additional breast surgery training was not universal: 20% had undertaken an accredited breast fellowship, 30% in a Breast Unit as a trainee, 21% had done additional courses, masters or diploma and 8% had not done any additional training. The majority (61%) of respondents worked in Units treating >150 BC cases per year, while 26% of the responders treat >120 new primary cases per year, and 23% less than 50 new cases a year. Multivariate analysis showed that breast surgeons working in a Breast Unit and treating more than 50 cases/year significantly performed oncoplastic procedures. CONCLUSION: There is a great variability in breast cancer surgery training in Europe. It is imperative to develop quality standards for breast cancer surgery training to ensure that patients get standardized and certified surgical management regardless of the country in which they are treated.

Adjuvant endocrine therapy in premenopausal patients with hormone receptor-positive early breast cancer: evidence evaluation and GRADE recommendations by the Italian Association of Medical Oncology (AIOM)

Premenopausal women with hormone receptor-positive early breast cancer are candidates for adjuvant endocrine therapy, as recommended by the major international guidelines. To date, adjuvant endocrine options for premenopausal women include tamoxifen with or without ovarian function suppression (OFS) or an aromatase inhibitor with OFS. Multiple strategies for endocrine treatment of premenopausal women with hormone-responsive breast cancer have been assessed, and the results of randomised clinical trials have been reported over the last years. Despite this evidence, the optimal algorithm for endocrine therapy for premenopausal women with hormone receptor-positive early stage invasive breast cancer shows open questions regarding the role of OFS in addition to tamoxifen and the optimal use of hormonal agents. The panel of the Italian Association of Medical Oncology (AIOM) Clinical Practice Guidelines on Breast Cancer applied the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) methodology on three critical questions on the choice of the adjuvant hormonal therapy in premenopausal breast cancer patients to summarise available evidence and to create recommendations to help physicians in their clinical practice.

Palbociclib as single agent or in combination with the endocrine therapy received before disease progression for estrogen receptor-positive, HER2-negative metastatic breast cancer: TREnd trial.

Background: The activity of palbociclib as a single agent in advanced breast cancer has not been extensively studied, with the only available clinical data limited to heavily pretreated patients. Preclinical data suggests palbociclib may partially reverse endocrine resistance, though this hypothesis has not been evaluated in previous clinical studies. This phase II, open-label, multicenter study examined the activity of palbociclib monotherapy, as well as palbociclib given in combination with the same endocrine therapy (ET) that was received prior to disease progression, in postmenopausal women with moderately pretreated, estrogen receptor-positive, HER2 negative advanced breast cancer. Patients and methods: Eligible women with advanced disease which had progressed on one or two prior ETs were randomized 1 : 1 to receive either palbociclib alone, or palbociclib in combination with the ET as previously received. Primary end point was clinical benefit rate (CBR); secondary end points included progression-free survival (PFS). Results: Between October 2012 and July 2016, a total of 115 patients were randomized. The CBR was 54% [95% confidence interval (CI): 41.5-63.7] for combination therapy, and 60% (95% CI: 47.8-72.9) for monotherapy. Median PFS was 10.8 months (95% CI: 5.6-12.7) for combination therapy, and 6.5 months (95% CI: 5.4-8.5) for monotherapy [hazard ratio (HR) 0.69; 95% CI: 0.4-1.1, exploratory P-value = 0.12]. Exploratory analyses revealed the PFS advantage for combination therapy was seen in the subgroup of patients who received prior ET for >6 months (HR 0.53; 95% CI: 0.3-0.9, exploratory P-value = 0.02), but not in those who received prior ET for ≤6 months. Conclusion: Palbociclib has clinical activity as a single agent in women with moderately pretreated, oestrogen receptor-positive, HER2-negative advanced breast cancer. Palbociclib may have potential to reverse endocrine resistance in patients with a history of previous durable response to ET. Clinical trial information: NCT02549430.

Toxicity profile differences of adjuvant docetaxel/cyclophosphamide (TC) between Asian and Caucasian breast cancer patients.

AIM: For early-stage breast cancer, four cycles of docetaxel and cyclophosphamide (TC) was proven superior to doxorubicin plus cyclophosphamide in the US Oncology 9375 trial. Given primary prophylactic antibiotics, 5% febrile neutropenia was recorded in a population comprising 75.5% Caucasians. Smaller trials and retrospective studies reviewing TC use in Asian patients did not produce similar incidence rates. This study aims to discover the variable hematological toxicities with TC use in Caucasian and Asian patients. METHODS: Breast cancer data was retrospectively reviewed for patients receiving adjuvant docetaxel 60-75 mg/m2 plus cyclophosphamide 600 mg/m2 from six countries (China, Hong Kong, Japan, Taiwan, Italy, and United States). Similar number of patients with relatively balanced baseline characteristics were chosen for analysis of hematological and nonhematological toxicities and survival data. RESULTS: From March 2004 to July 2013, data of 227 patients (127 Asians and 100 Caucasian) patients were analyzed for treatment-related toxicities. During the four cycles of TC, Asians had a significantly higher rate of grade ≥2 neutropenia than Caucasians (45.7% vs 6.0%; P <0.001) and significantly more grade ≥3 neutropenia events were documented (respectively 30.7% vs 4.0%, P <0.001). The prophylactic use of G-CSF was similar; 26.0% in Asians and 28.0% in Caucasian (P = 0.764). There were no differences in nonhematological toxicities. No significant difference in disease-free survival was observed between Asians and Caucasians (log-rank P = 0.910). CONCLUSIONS: Ethnic differences in toxicity profile exist between Asian and Caucasian patients given adjuvant TC. Over 30% Asians but less than 5% Caucasians experienced grade ≥3 neutropenia.

Cardiac safety, efficacy, and correlation of serial serum HER2-extracellular domain shed antigen measurement with the outcome of the combined trastuzumab plus CMF in women with HER2-positive metastatic breast cancer: results from the EORTC 10995 phase II study.

PURPOSE: Cardiotoxicity is a side effect of trastuzumab. We assessed efficacy and cardiac safety of CMF with trastuzumab (CMF+T) in HER2-positive metastatic breast cancer patients (MBC). METHODS: In this phase II study, centrally confirmed, previously treated HER2-positive MBC patients with measurable disease (per RECIST v 1.0) were enrolled. Initially, patients were randomized between 8 CMF cycles alone or combined with trastuzumab during chemotherapy, followed by 3-weekly trastuzumab maintenance till progression. A protocol amendment dropped the CMF arm and thereafter all patients received CMF+T. Translational research for prediction of treatment benefit was performed through serial serum HER2-shed antigen assessments. RESULTS: Ninety patients (CMF: 19; CMF+T: 71) were enrolled between 2002 and 2006. Median age was 54 years. 42 patients had prior chemotherapy (33 with anthracyclines) and 41/71 patients who received CMF+T continued trastuzumab monotherapy for a median duration of 40 weeks. Overall response rate was 50% for CMF+T (35/70) and 32% for CMF (6/19). Median duration of response was 10.3 months and 5.4 months, respectively. Median progression-free survival was 9.4 months (95% CI 8.1-11.6) and 4.8 months (95% CI 2.8-7.9), respectively. In the CMF+T arm, 13(18%) patients had an absolute LVEF decline, including 3 patients developing any grade of New York Heart Association cardiac dysfunction. Patients with an increase of 30% over baseline shed antigen had a higher progression risk (95% CI 7.6, 3.9-14.8). CONCLUSIONS: CMF+T is effective, with an acceptable cardiotoxicity profile. LVEF declines were mostly asymptomatic and occurred irrespective of previous anthracycline exposure. CMF+T can be considered for these patients, if other cytotoxics are contraindicated.

Taxanes in the treatment of breast cancer: Have we better defined their role in older patients? A position paper from a SIOG Task Force.

Along with anthracyclines, taxanes are the most active cytotoxics in breast cancer (BC). Balancing efficacy against toxicity in older patients with reduced physiological reserves and significant comorbidities is both important and difficult. This is especially so given the under-representation of elderly patients in major trials and a consequent lack of evidence for drug, dose and schedule. However, BC is frequent in elderly women, who are a growing proportion of the population. Careful consideration of their care is therefore imperative. Treatment that can cure or extend the duration and quality of life should not be restricted by age, but needs to be tailored to the circumstances of elderly patients. In adjuvant use, taxane toxicity in older women is greater than in their younger counterparts, limiting its sequential combination with anthracyclines for high-risk disease unless patients are in very good health. More frequently taxanes are used alone (weekly paclitaxel, three-weekly docetaxel) or combined with cytotoxics other than anthracyclines (e.g. docetaxel plus cyclophosphamide) to reduce cardiac risk, especially in HER-2-positive patients who may develop additional trastuzumab-related cardiac events. In elderly patients with metastases, weekly paclitaxel and three-weekly docetaxel are among the cornerstones of treatment, with generally acceptable toxicity. Three-weekly docetaxel at the approved dose of 100mg/m(2) is not appropriate for the elderly. Nab-paclitaxel has efficacy comparable with solvent-based taxanes without need for steroid premedication but has been little studied in older BC patients. A head-to-head comparison with weekly paclitaxel favoured the solvent-free formulation for pathologic response, but those studied were a general adult population. Compared with early stage disease, choice of taxane and regimen in the metastatic setting relies even more on availability and preferences with regard to schedule, toxicity profile and cost, especially for recently developed formulations.

Oral single-agent chemotherapy in older patients with solid tumours: A position paper from the International Society of Geriatric Oncology (SIOG).

Compared with intravenous (i.v.) chemotherapy, oral administration is convenient, requires fewer healthcare resources, is generally preferred by patients, and may be appropriate in older people with breast, colorectal and lung cancers. The effects of organ dysfunction on drug metabolism and drug interactions in patients with multiple comorbidities must be considered but are not specific to oral chemotherapy. Single-agent oral chemotherapy with capecitabine or vinorelbine is active in older patients with advanced or metastatic breast cancer. Choice of treatment is based mainly on different safety profiles. In the adjuvant treatment of colorectal cancer (CRC), single-agent oral capecitabine is an effective alternative to i.v. fluorouracil (5-FU) regimens. In metastatic CRC, oral, single-agent capecitabine has recently shown encouraging median overall survival in combination with bevacizumab. In non-small cell lung cancer, fit older patients, like their younger counterparts, benefit from platinum-based doublets, with carboplatin preferred to cisplatin. Single agent vinorelbine is an option for those less suited to combination chemotherapy, and oral may be an alternative to i.v. administration. For elderly cancer patients in general, metronomic chemotherapy combines good tolerability with acceptable activity.

Mass balance and life cycle assessment of the waste electrical and electronic equipment management system implemented in Lombardia Region (Italy).

Waste electrical and electronic equipment (WEEE) is one of the fastest growing waste streams in Europe, whose content of hazardous substances as well as of valuable materials makes the study of the different management options particularly interesting. The present study investigates the WEEE management system in Lombardia Region (Italy) in the year 2011 by applying the life cycle assessment (LCA) methodology. An extensive collection of primary data was carried out to describe the main outputs and the energy consumptions of the treatment plants. Afterwards, the benefits and burdens associated with the treatment and recovery of each of the five categories in which WEEE is classified according to the Italian legislation (heaters and refrigerators - R1, large household appliances - R2, TV and monitors - R3, small household appliances - R4 and lighting equipment - R5) were evaluated. The mass balance of the treatment and recovery system of each of the five WEEE categories showed that steel and glass are the predominant streams of materials arising from the treatment; a non-negligible amount of plastic is also recovered, together with small amounts of precious metals. The LCA of the regional WEEE management system showed that the benefits associated with materials and energy recovery balance the burdens of the treatment processes, with the sole exception of two impact categories (human toxicity-cancer effects and freshwater ecotoxicity). The WEEE categories whose treatment and recovery resulted more beneficial for the environment and the human health are R3 and R5. The contribution analysis showed that overall the main benefits are associated with the recovery of metals, as well as of plastic and glass. Some suggestions for improving the performance of the system are given, as well as an indication for a more-in-depth analysis for the toxicity categories and a proposal for a new characterisation method for WEEE.

HER2-positive metastatic breast cancer: a changing scenario.

Adjuvant trastuzumab (AT) dramatically improved HER2-positive breast cancer prognosis. Relapsed disease after AT has different patterns and information is available from observational studies. In this Review Chemotherapy regimens combined to anti-HER2 blockade are discussed, focusing in particular the role of anthracyclines, taxanes and capecitabine. The use of trastuzumab beyond progression and the role of other anti-HER2 agents like lapatinib, pertuzumab and T-DM1 are explored, as also dual blockade and in trastuzumab resistant Patients. Metastatic "de novo" HER2 Luminal (co-expression of HER2 and hormone receptors) Patients are eligible for anastrozole and trastuzumab but if pretreated with trastuzumab they are also eligible for lapatinib and letrozole. In any case endocrine treatment plays a complementary role to chemotherapy which remains pivotal. The last topic explored is treatment options for patients with brain metastases where both trastuzumab given concurrent with radiotherapy or lapatinib and capecitabine appear as potentially active.