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.

Stem cell-like transcriptional reprogramming mediates metastatic resistance to mTOR inhibition.

Inhibitors of the mechanistic target of rapamycin (mTOR) are currently used to treat advanced metastatic breast cancer. However, whether an aggressive phenotype is sustained through adaptation or resistance to mTOR inhibition remains unknown. Here, complementary studies in human tumors, cancer models and cell lines reveal transcriptional reprogramming that supports metastasis in response to mTOR inhibition. This cancer feature is driven by EVI1 and SOX9. EVI1 functionally cooperates with and positively regulates SOX9, and promotes the transcriptional upregulation of key mTOR pathway components (REHB and RAPTOR) and of lung metastasis mediators (FSCN1 and SPARC). The expression of EVI1 and SOX9 is associated with stem cell-like and metastasis signatures, and their depletion impairs the metastatic potential of breast cancer cells. These results establish the mechanistic link between resistance to mTOR inhibition and cancer metastatic potential, thus enhancing our understanding of mTOR targeting failure.

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.

Effect of a diet and physical activity intervention on body weight and nutritional patterns in overweight and obese breast cancer survivors.

Energy restriction from a low-calorie diet and increased energy expenditure induced by physical activity (PA) could promote weight loss/maintenance and be important determinants of breast cancer (BC) prognosis. The aim of this study was to assess participation and adherence of overweight and obese BC survivors to a lifestyle intervention and to demonstrate the capacity of this intervention to induce weight loss and nutritional changes. This single-arm pre-post study, which involved one-hourly weekly diet sessions delivered by a dietician and 75-min bi-weekly PA sessions of moderate-to-high intensity led by PA monitors, was offered to overweight and obese BC survivors shortly after treatment. Before and after the intervention, anthropometry, dietary information, quality of life (QoL) and cardiorespiratory fitness (CRF) were collected. A total of 112 BC survivors were invited to participate: 42 of them started the intervention and 37 completed it. Participants attended more than 90 % of the sessions offered and showed a significant weight loss of 5.6 ± 2.0 kg, as well as significant decreases in body mass index, fat mass and waist circumference. Significant decreases in total energy (-25 %), fat (-35 %), saturated fat (-37 %) and carbohydrate (-21 %) intakes were observed while QoL and CRF showed significant increases. This feasibility study demonstrated the success of a short-term diet and PA intervention to induce weight loss and promote healthful changes in BC survivors. Assessing the long-term effects of these changes, and in particular their possible impact of BC prognosis, and designing interventions reaching a wider number of BC survivors are still issues to be addressed.

[Efficiency of oncologic treatments for solid tumours in Spain]. / Eficiencia de tratamientos oncológicos para tumores sólidos en España.

OBJECTIVE: To provide estimates of the efficiency for chemotherapy strategies used in Spain. METHODS: Published reports of the phase-III clinical trials for chemotherapies used for the most prevalent solid tumours in Spain were retrieved. The incremental cost-effectiveness ratio (ICER) was calculated for each strategy compared to the control group in the clinical trial, with the National Health System perspective. The total cost (?, 2012) including only drug cost (exfactory price) was estimated based on the total units of each drug required for administration (no vial wastage), with the dosification and number of cycles specified in the publication for each treatment arm. Effectiveness was measured as month of overall survival (OS) and/or month of progression free survival (PFS). RESULTS: A total of 40 chemotherapies for 13 different advanced or metastatic tumours were assessed. OS ranged from 5.3 to 33.3 months for the 34 therapies that included the information with hazard ratios (HR) values from 0.49 to 1.15 when compared with its control group. PFS ranged, from 39 therapies with these data, between 1.5 to 12.4 months, with HR from 0.33 to 1.52. ICERs were between ?2,142.57 and ?60,996.37 per each OS month gained, and from ?2,102.54 to ?661,845.27 per PFS month gained. CONCLUSION: The variety and heterogenicity of survival and ICERs results, suggest disparity of criteria in the price and reimbursement process of drugs in Spain. The continuous advances in oncology seem to require economic revaluations of drugs.

Objetivo: Proporcionar estimadores de la eficiencia de esquemas oncológicos empleados en España. Métodos: Se seleccionaron las publicaciones de ensayos clínicos en fase III usados para indicación de las terapias oncológicas de alto impacto empleadas para tratamiento de tumores sólidos en estadíos III-IV. Para cada esquema se calculó la relación costeeficacia incremental (RCEI) respecto al comparador del ensayo, con la perspectiva del Sistema Nacional de Salud. El coste (?, 2012) farmacológico, en PVL, de cada esquema y comparador se estimó con las unidades de medicamento requeridas en cada administración (aprovechamiento máximo de viales) considerando la posología y el número de ciclos especificado en el ensayo para cada una de las ramas. La efectividad se expresó en meses de supervivencia global (SG) y/o supervivencia libre de progresión (SLP). Resultados: Se analizaron 40 esquemas oncológicos para trece tumores metastásicos. La SG osciló entre 5,3 y 33,3 meses para las 34 terapias que incluían esa información, con valores de Hazard ratio (HR) respecto a sus comparadores de 0,49 a 1,15. La SLP osciló entre 1,5 y 12,4 meses para las 39 terapias con este dato, con HR de 0,33 a 1,52. Los valores de RCEI oscilaron entre 2.142,57 ?-60.996,37 ?/mes de SG adicional y entre 2.102,54 ?-661.845,27 ?/mes de SLP adicional. Conclusión: La dispersión y heterogeneidad de la supervivencia y RCEI estimadas, sugieren disparidad de criterios en la decisión de precio y financiación de las terapias, en España. Los continuos avances en terapias oncológicas parecen requerir reevaluaciones económicas de los medicamentos.

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.

Finding the right dose of fulvestrant in breast cancer.

Fulvestrant is a selective estrogen receptor downregulator, behaving as a complete antagonist. It was initially approved, at a dose of 250 mg, to treat hormone dependant breast cancer in second line setting. However, a series of pharmacological and pre-clinical studies have suggested that a higher dose of 500 mg may be more effective. The present work summarizes and discusses clinical trials that have aimed to test the benefits of administering fulvestrant at a higher dose. The data support the use of a higher, and more possibly, effective dose of the agent.

A randomized phase II trial of platinum salts in basal-like breast cancer patients in the neoadjuvant setting. Results from the GEICAM/2006-03, multicenter study.

Chemotherapy remains as the only systemic treatment option available for basal-like breast cancer (BC) patients. Preclinical models and several phase II studies suggested that platinum salts are active drugs in this BC subtype though there is no randomized study supporting this hypothesis. This study investigates if the addition of carboplatin to a combination of an alkylating agent together with anthracyclines and taxanes is able to increase the efficacy in the neoadjuvant treatment context. Patients with operable breast cancer and immunophenotypically defined basal-like disease (ER-/PR-/HER2- and cytokeratin 5/6+ or EGFR+) were recruited. Patients were randomized to receive EC (epirubicin 90 mg/m(2) plus cyclophosphamide 600 mg/m(2) for 4 cycles) followed either by D (docetaxel 100 mg/m(2) × 4 cycles; EC-D) or DCb (docetaxel 75 mg/m(2) plus carboplatin AUC 6 × 4 cycles; EC-DCb). The primary end point was pathological complete response (pCR) in the breast following the Miller and Payne criteria. Ninety-four patients were randomized (46 EC-D, 48 EC-DCb). pCR rate in the breast was seen in 16 patients (35 %) with EC-D and 14 patients (30 %) with EC-DCb (P value = 0.61). pCR in the breast and axilla was seen in 30 % of patients in both arms. The overall clinical response rate was 70 % (95 % CI 56-83) in the EC-D arm and 77 % (95 % CI 65-87) in the EC-DCb arm. Grade 3/4 toxicity was similar in both arms. The addition of carboplatin to conventional chemotherapy with EC-D in basal-like breast cancer patients did not improve the efficacy probably because they had already received an alkylating agent. These findings should be taken into consideration when developing new agents for this disease.

Prescription refill, patient self-report and physician report in assessing adherence to oral endocrine therapy in early breast cancer patients: a retrospective cohort study in Catalonia, Spain.

AIMS: To compare different methods in order to assess adherence and persistence with oral endocrine therapy in women diagnosed with breast cancer (BC) in Catalonia. MATERIALS AND METHODS: This study covered all women newly diagnosed with stage I, II or IIIa BC and positive hormone receptors at six hospitals in Catalonia (Spain) in 2004. Adherence was assessed on the basis of physician report and patient self-report using a telephone questionnaire. Persistence was measured by refill prescriptions. We used the Kappa index to compare adherence measures and logistic regression to evaluate adherence-related risk factors. RESULTS: The study covered a total of 692 women. Adherence ranged from 92% (self-report) to 94.7% (physician report), depending on the measure used; persistence was 74.7% at 5 years of follow-up. Low concordance between measures was observed (Kappa range: 0.018-0.267). Patients aged 50-74 years showed higher adherence than those aged <50 years. Adherence was also associated with: adjuvant chemotherapy and sequential hormonal therapy. CONCLUSIONS: Concordance between the different measures was remarkably low, indicating the need for further research. Adherence is an issue in the management of BC patients taking oral drugs, and should be assessed in clinical practice.

Phase II clinical trial of liposomal-encapsulated doxorubicin citrate and docetaxel, associated with trastuzumab, as neoadjuvant treatment in stages II and IIIA HER2-overexpressing breast cancer patients. GEICAM 2003-03 study.

BACKGROUND: we previously reported a phase I trial of liposome-encapsulated doxorubicin citrate (LD), docetaxel and trastuzumab as neoadjuvant in stages II and IIIA human epidermal growth factor receptor 2-overexpressing breast cancer patients. This study evaluates the efficacy of this regimen in a phase II trial. PATIENTS AND METHODS: patients were treated with LD 50 mg/m(2) and docetaxel 60 mg/m(2) every 21days associated with standard trastuzumab dose and pegfilgrastim support. RESULTS: fifty-nine patients were enrolled; median age: 48 years (range 24-71 years); premenopausal patients: 36 (61%); 19 patients (32%) presented stage IIIA disease and 40 patients (67%) stage II; histological grades 2-3 tumors: 50 patients (84%) and estrogen receptor-progesterone receptor negative: 28 patients (47%). In all, 27% achieved a pathological complete response in breast and axilla (grade 5-Miller and Payne classification); 15% of patients achieved grade 4. Clinical and radiological response rates were 86% and 81%, respectively. Forty-two patients (71%) underwent breast-conserving surgery. The main grades 3-4 toxic effects were non-febrile neutropenia (29%) and fatigue (8%). Grade 2 left ventricular ejection fraction decline was observed in nine patients. No congestive heart failure was observed. CONCLUSIONS: LD plus docetaxel combination associated with trastuzumab as neoadjuvant is active in breast cancer and entails a favorable cardiotoxicity profile. This regimen is a new treatment option in these patients.

Cost-effectiveness analyses of docetaxel versus paclitaxel once weekly in patients with metastatic breast cancer in progression following anthracycline chemotherapy, in Spain

OBJECTIVES: Our aim was to evaluate the cost-effectiveness of docetaxel versus weekly paclitaxel regimen in patients with metastatic breast cancer previously treated with anthracycline from the Spanish National Health Service (NHS) perspective. METHODS: A Markov model with a 21-day cycle duration was developed to estimate total treatment-related costs and clinical benefits over 5 years of docetaxel (100 mg/m²) and weekly paclitaxel (80 mg/m²). Patient data were obtained from the Randomized Phase III Study of Docetaxel Compared with Paclitaxel in Metastatic Breast Cancer (TAX- 311) and Anglo-Celtic IV trials. Utilities were obtained from literature, and unitary costs (€2009) from a Spanish health-cost database and the Catalogue of Medicines. Cost and benefits [life-years gained (LYG) and quality-adjusted life years (QALY)] were discounted at 3%. Sensitivity analyses were performed. RESULTS: Docetaxel yields higher health benefits (1.83 LYG; 1.08 QALY) than paclitaxel (1.46 LYG; 0.84 QALY). Global costs (treatment, concomitant medication, adverse events management, progression, best supportive care, and end of life phase) per patient were €20,052 and €9,982 with docetaxel and paclitaxel, respectively. Incremental cost-effectiveness ratio (ICER) of docetaxel versus paclitaxel was €190/LYG and €295/QALY. Based on a €30,000/QALY threshold, docetaxel has 99% probability of being cost-effective. ICER was mostly sensitive to hazard ratio (HR) (when varied from 1.46 to 1.09; €3,517/ QALY), discount over the ex-lab price of Taxol® (75%; €6,396/QALY) and granulocyte colony-stimulating factor (G-CSF) prophylactic treatment (when administered in 60% of cycles instead of 100%; cost saving). Variations in other inputs, such as time horizon (3-10 years), discount rate (0-5%), or adverse event cost (± 25%) were shown not to have relevant influence on the results. CONCLUSION: Compared to weekly paclitaxel, docetaxel therapy is cost effective for treating metastatic breast cancer patient (AU)

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'.

Supportive care for patients with early breast cancer

Breast cancer treatment currently requires the joint efforts of a multidisciplinary team to effectively combine chemotherapy, hormone therapy, biological agents, surgery and radiation therapy when needed. To develop such a treatment plan, it is important to know the benefits as well as the potential toxic effects of each therapy. Thus, many patients with early breast cancer complain of collateral adverse events such as fatigue, nausea, vomiting, loss of libido, hot flashes, night sweats or neuropathy due to the complex therapies they are receiving. To date, the treatment of such symptoms is an important issue that greatly affects the quality of life of these patients. In this review, we report the content of a multi-expert meeting where the incidence of and medical approach to some of the most common adverse events encountered during the treatment of patients with early breast cancer were analysed (AU)

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.

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 (AU)

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