Role of boost radiotherapy for local control of pure ductal carcinoma in situ after breast-conserving surgery: a multicenter, retrospective study of 622 patients.

PURPOSE: To evaluate the effect of boost radiotherapy on ipsilateral breast tumor recurrence (IBTR) for ductal carcinoma in situ (DCIS) after breast-conserving surgery and whole breast radiotherapy (WBRT) with or without boost. METHODS AND MATERIALS: Retrospective, multicentre study of 622 patients (624 tumors) diagnosed with pure DCIS from 1993-2011. RESULTS: Most tumors (377/624; 60.4%) received a boost. At a median follow-up of 8.8 years, IBTR occurred in 64 cases (10.3%). A higher percentage of patients with risk factors for IBTR received a boost (p < 0.05). Boost was not associated with lower rates of IBTR than WBRT alone (HR 0.75, 95% CI 0.42-1.35). On the univariate analyses, IBTR was significantly associated with tumor size (11-20 mm, HR 2.32, 95% CI 1.27-4.24; and > 20 mm, HR 2.10, 95% CI 1.14-3.88), re-excision (HR 1.76, 95% CI 1.04-2.96), and tamoxifen (HR 2.03, 95% CI 1.12-3.70). Boost dose > 16 Gy had a protective effect (HR 0.39, 95% CI 0.187-0.824). Multivariate analyses confirmed the independent associations between IBTR and 11-20 mm (p = 0.02) and > 20 mm (p = 0.009) tumours, and re-excision (p = 0.006). On the margin-stratified multivariate analysis, tamoxifen was a poor prognostic factor in the close/positive margin subgroup (HR 4.28 95% CI 1.23-14.88), while the highest boost dose ( > 16 Gy) had a significant positive effect (HR 0.34, 95% CI 0.13-0.86) in the negative margin subgroup. CONCLUSIONS: Radiotherapy boost did not improve the risk of IBTR. Boost radiotherapy was more common in patients with high-risk disease. Tumor size and re-excision were significant independent prognostic factors.

Situation, challenges, and SEOM recommendations for the future of undergraduate education in Oncology in Spain.

PURPOSE: The Spanish Society of Medical Oncology (SEOM, for its Spanish acronym) would like to attest to the relevance of training in Oncology as part of the undergraduate education in Medicine program and issue recommendations to improve said training, with the aim of responding better to the challenges that cancer poses to our society. MATERIALS AND METHODS: The curricula of 42 schools of medicine were reviewed with interviews with at least one teaching medical oncologist from each faculty. The qualitative and opinion analysis was completed by means of an online questionnaire targeting lecturers, resident tutors, and residents in Medical Oncology (MO), enabling the detection of needs and areas for improvement at an organizational level and in terms of skill acquisition. RESULTS: While the number of medical schools with a specific, mandatory program in MO has grown by up to 90%, it has not been accompanied by an increase in independent programs. Instead, they largely consist of programs shared with other specialties (61% of the medical faculties). In most of the undergraduate education programs, Oncology contents are fragmented and approached from the perspective of each organ system. CONCLUSIONS: Despite the positive evolution in recent years, the heterogeneity in Oncology contents during undergraduate education training continues to be remarkable. Cross-sectional programs with an integral vision, taught in the final years of undergraduate medical education would be desirable. Among the recommendations for improvement of training in Medical Oncology, the SEOM proposes that updated, theoretical content be incorporated and clinical practice in Medical Oncology departments be promoted.

SEOM clinical guideline on unknown primary cancer (2017).

Cancer of unknown primary site is a histologically confirmed cancer that manifests in advanced stage, with no identifiable primary site following standard diagnostic procedures. Patients are initially categorized based on the findings of the initial biopsy: adenocarcinoma, squamous-cell carcinoma, neuroendocrine carcinoma, and poorly differentiated carcinoma. Appropriate patient management requires understanding several clinical and pathological features that aid in identifying several subsets of patients with more responsive tumors.

Evaluation and management of chemotherapy-induced cardiotoxicity in breast cancer: a Delphi study.

PURPOSE: While much progress has been made in the treatment of breast cancer, cardiac complications resulting from therapy remain a significant concern. Both anthracyclines and novel targeted agents can inflict cardiac damage. The present study aimed to evaluate the difference between what it is currently done and what standards of care should be used to minimizing and managing cardiac toxicity in breast cancer survivors. METHODS: A two-round multicenter Delphi study was carried out. The panel consisted of 100 oncologists who were asked to define the elected therapies for breast cancer patients, the clinical definition and patterns of cancer drug-derived cardiac toxicity, and those protocols focused on early detection and monitoring of cardiovascular outcomes. RESULTS: Experts agreed a more recent definition of cardiotoxicity. Around 38 % of patients with early-stage disease, and 51.3 % cases with advanced metastatic breast cancer had preexisting risk factors for cardiotoxicity. Among risk factors, cumulative dose of anthracycline ≥450 mg/m2 and its combination with other anticancer drugs, and a preexisting cardiovascular disease were considered the best predictors of cardiotoxicity. Echocardiography and radionuclide ventriculography have been the proposed methods for monitoring changes in cardiac structure and function. Breast cancer is generally treated with anthracyclines (80 %), so that the panel strongly stated about the need to plan a strategy to managing cardiotoxicity. A decline of left ventricular ejection fraction (LVEF) >10 %, to an LVEF value <53 % was suggested as a criterion for changing the dose schedule of anthracyclines, or suspending the treatment of chemotherapy plus trastuzumab until the normalization of the left ventricular function. The use of liposomal anthracyclines was strongly suggested as a treatment option for breast cancer patients. CONCLUSIONS: The present report is the first to produce a set of statements on the prevention, evaluation and monitoring of chemotherapy-induced cardiac toxicity in breast cancer patients.

SEOM Clinical Guideline for bone metastases from solid tumours (2016).

Bone metastases are common in many advanced solid tumours, being breast, prostate, thyroid, lung, and renal cancer the most prevalent. Bone metastases can produce skeletal-related events (SREs), defined as pathological fracture, spinal cord compression, need of bone irradiation or need of bone surgery, and hypercalcaemia. Patients with bone metastases experience pain, functional impairment and have a negative impact on their quality of life. Several imaging techniques are available for diagnosis of this disease. Bone-targeted therapies include zoledronic acid, a potent biphosfonate, and denosumab, an anti-RANKL monoclonal antibody. Both reduce the risk and/or delay the development of SREs in several types of tumours. Radium 233, an alpha-particle emitter, increases overall survival in patients with bone metastases from resistant castration prostate cancer. Multidisciplinary approach is essential and bone surgery and radiotherapy should be integrated in the treatment of bone metastases when necessary. This SEOM Guideline reviews bone metastases pathogenesis, clinical presentations, lab tests, imaging techniques for diagnosis and response assessment, bone-targeted agents, and local therapies, as radiation and surgery, and establishes recommendations for the management of patients with metastases to bone.

SEOM Clinical Guideline of fertility preservation and reproduction in cancer patients (2016).

Chemotherapy and radiotherapy often result in reduced fertility in cancer patients. With increasing survival rates, fertility is an important quality-of-life concern for many young cancer patients. Around 70-75% of young cancer survivors are interested in parenthood but the numbers of patients who access fertility preservation techniques prior to treatment are significantly lower. Moreover, despite existing guidelines, healthcare professionals do not address fertility preservation issues adequately. There is a critical need for improvements in clinical care to ensure patients are well informed about infertility risks and fertility preservation options and to support them in their reproductive decision-making prior to cancer treatment.

Bevacizumab plus preoperative chemotherapy in operable HER2 negative breast cancer: biomarkers and pathologic response.

PURPOSE: The primary aim of this trial was to assess the rate of pathologic complete responses (pCR) of doxorubicin/cyclophosphamide (AC) followed by bevacizumab/docetaxel (BT), as neoadjuvant therapy for breast cancer (BC). Furthermore, the association between biomarkers and the pCR was explored. METHODS: Patients with HER-negative operable stage II-III BC ≥ 2 cm were enrolled. Four cycles of AC (A 60 mg/m(2) and C 600 mg/m(2), every 3 weeks) followed by 4 cycles of BT (B 15 mg/kg and T 75 mg/m(2), every 3 weeks), were planned. A core-biopsy was performed for biological markers assessment. RESULTS: Seventy-two women were included. Forty-three (63 %) patients were hormone receptor-positive. Sixty-four (89 %) completed the planned treatment, and 66 evaluable patients underwent surgery (92 %): a pCR was achieved in 16 of them (24, 95 % CI 15-36 %). pCR was significantly higher in tumors hormone receptor-negative, and in those with Angiotensin II type 1 receptor (AGTR1) protein overexpression. The overall clinical response rate was 86 % (95 % CI 76-93 %), including 42 complete responses. No unexpected toxicities or treatment-related deaths were observed. CONCLUSION: This regimen showed a remarkable clinical and pathological activity: the suggested relation between pCR and AGTR1 overexpression should be confirmed in larger trials.

Current controversies in the management of breast cancer.

The following manuscript summarises the content of the Breast Symposium that was held in May 2008 in Barcelona in which four controversies regarding the management of breast cancer were discussed. The design of the symposium included two speakers per controversy, one in favour and one diverging, and the audience had to vote before and after the presentations to assess changes in the participants' views. The four controversies included: (1) the role of non-conventional predictive factors in selecting treatment for breast cancer; (2) the role of surgery in disseminated disease; (3) are taxanes indicated in the adjuvant treatment of patients with lymph-node-negative disease?; (4) is treatment with tamoxifen (TAM) always required after surgery in patients with ductal carcinoma in situ (DCIS)? The symposium concluded with the presentation titled: 'Features of a well designed clinical trial in the adjuvant treatment of breast cancer'.

Doxorubicin and cyclophosphamide followed by weekly docetaxel as neoadjuvant treatment of early breast cancer: analysis of biological markers in a GEICAM phase II study.

INTRODUCTION: To evaluate the sequential administration of doxorubicin (A) and cyclophosphamide (C) followed by weekly docetaxel in women with stage II to IIIA breast cancer. PATIENTS AND METHODS: Patients received 60 mg/m(2) of A and 600 mg/m(2) of C every three weeks for four cycles followed by 12 infusions of weekly docetaxel at a dose of 36 mg/m(2) and with a 2-week resting period. RESULTS: Sixty-three women were included. On an intention-to- treat basis, clinical response rate was 90% (95% CI: 83-98), with 46% complete responses. Breast-conserving surgery could be performed in 43 patients (68%). Complete pathological responses in the breast were confirmed in 17% of patients. No correlations between levels of expression of topoisomerase II alpha, survivin or p27 and the pathological response were detected. The study treatment was generally well tolerated. CONCLUSION: Neoadjuvant AC followed by weekly docetaxel is a feasible regimen for patients with early-stage breast cancer.

Current controversies in the management of early breast cancer.

Medical professionals in general, and medical oncologists in particular, have highly stressful practices because they are under constant pressure to have the highest-quality, up-to-date evidence available in order to make the right decision for each individual patient. From a practical point of view, being updated on oncological and other medical specialties may seem an insurmountable task because the number of scientific publications has increased dramatically. The use of systematic reviews of randomised controlled trials or the application of results obtained from high-quality randomised controlled trials are some of the most common ways to address this need. Unfortunately, they do not cover all complex clinical situations that the majority of medical oncologists face in their outpatient consultations. In this review, we report the conclusions achieved in a multiexpert meeting where five important controversies in the treatment of breast cancer were analysed. Five highly experienced medical oncologists were required to defend an affirmative answer and another five were required to defend a negative answer for each of the clinical questions. After that, a one-day meeting was organised to debate each clinical question and to reach a consensus. We report here the content of this multi-expert meeting along with the conclusions drawn.