Treatment patterns for metastatic colorectal cancer in Spain.

PURPOSE: The primary aim of this retrospective study was to describe the treatment patterns according to the type of treatment received by patients with metastatic colorectal cancer (mCRC) in Spain. METHODS: This was a retrospective, observational, multicenter study performed by 33 sites throughout Spain that included consecutive patients aged 18 years or older who had received or were receiving treatment for mCRC. RESULTS: At the time of inclusion, of the 873 evaluable patients, 507 (58%) had received two lines, 235 (27%) had received three lines, 106 (12%) had received four lines, and the remaining patients had received up to ten lines. The most frequent chemotherapy schemes were the FOLFOX or CAPOX regimens (66%) for first-line treatment, FOLFOX, CAPOX or FOLFIRI (70%) for second-line treatment, and FOLFOX, FOLFIRI or other fluoropyrimidine-based regimens for third- and fourth-line (over 60%) treatment. Sixty percent of patients received targeted therapy as part of their first-line treatment, and this proportion increased up to approximately 70% of patients as part of the second-line of treatment. A relevant proportion of patients were treated with unknown KRAS, and especially the BRAF, mutation statuses. CONCLUSIONS: This study reveals inconsistencies regarding adherence to the recommendations of the ESMO guidelines for the management of mCRC in Spain. Improved adherence to the standard practice described in such guidelines for the determination of RAS and BRAF mutation statuses and the use of targeted therapies in first-line treatment should be considered to guarantee that patients can benefit from the best therapeutic approaches available.

A retrospective, multicenter study of the efficacy of lapatinib plus trastuzumab in HER2-positive metastatic breast cancer patients previously treated with trastuzumab, lapatinib, or both: the Trastyvere study.

PURPOSE: To evaluate the efficacy and safety of lapatinib (L) and trastuzumab (T) combination in HER2-positive metastatic breast cancer (MBC) patients previously treated with T and/or L. MATERIALS AND METHODS: We conducted a retrospective, post-authorized, multicenter study including patients with HER2-positive MBC or locally advanced breast cancer (ABC) treated with the combination of L-T. Concomitant endocrine therapy, as well as brain metastasis and/or prior exposure to L, were allowed. RESULTS: One hundred and fifteen patients from 14 institutions were included. The median age was 59.8 years. The median number of prior T regimens in the advanced setting was 3 and 73 patients had received a prior L regimen. The clinical benefit rate (CBR) was 34.8% (95% CI 26.1-43.5). Among other efficacy endpoints, the overall response rate was 21.7%, and median progression-free survival (PFS) and overall survival were 3.9 and 21.6 months, respectively. Heavily pretreated and ≥ 3 metastatic organ patients showed lower CBR and PFS than patients with a low number of previous regimens and < 3 metastatic organs. Moreover, CBR did not significantly change in L-pretreated compared with L-naïve patients (31.5% versus 40.5% for L-pretreated versus L-naïve). Grade 3/4 adverse events were reported in 19 patients (16.5%). CONCLUSION: The combination of L-T is an effective and well-tolerated regimen in heavily pretreated patients and remains active among patients progressing on prior L-based therapy. Our study suggests that the L-T regimen is a safe and active chemotherapy-free option for MBC patients previously treated with T and/or L.

Evolution of older patients diagnosed with early breast cancer in Spain between 1998 and 2001 included in El Alamo III project.

INTRODUCTION: An increase in the number of cancer cases is expected in the near future. Breast cancer (BC) mortality rates increase with age even when adjusted for other variables. Here we analyzed BC disease-free survival (BCDFS) and BC specific survival (BCSS) in the El Alamo III BC registry of GEICAM Spanish Breast Cancer Group. MATERIALS AND METHODS: El Alamo III is a retrospective registry of BC patients diagnosed between 1998 and 2001. Patients with stage I-III invasive BC of age groups 55-64 years (y), 70-74 years and ≥ 75 years were included. Patients and tumors characteristics, treatments and recurrences and deaths were analyzed. RESULTS: 4343 patients were included within the following age intervals: 2288 (55-64 years), 960 (70-74 years), and 1095 (≥ 75 years). Older patients (≥ 70 years) were diagnosed with more advanced tumors (stage III) than younger patients (21.5% versus 13.4%, p < 0.0001). Mastectomies were performed more on older patients and they received less chemotherapy than younger patients (66.6% versus 43.1%, p < 0.00001 and 30.8% versus 71.6%, p < 0.0001, respectively). With a median follow-up of 5.9 years, 17.7% patients had BCDFS events in the younger group and 19.8% in the older group (p < 0.0001). A decrease in BCSS was also observed in older patients, either when analyzing patients ≥ 70y (p < 0.0001) and when differentiating by the two older groups (p < 0.0001). CONCLUSIONS: Our study suggests that older BC patients have worse outcomes what can be a consequence of receiving inadequate adjuvant treatments. Specific trials for these patients are warranted to allow us to treat them with the same scientific rigor than younger patients.

Pregnancy outcomes after maternal Zika virus infection in a non-endemic region: prospective cohort study.

OBJECTIVES: The aim was to describe pregnancy outcomes after Zika virus (ZIKV) infection in a non-endemic region. METHODS: According to the Spanish protocol issued after the ZIKV outbreak in Brazil in 2015, all pregnant women who had travelled to high-burden countries were screened for ZIKV. Serological and molecular tests were used to identify ZIKV-infected pregnant women. They were classified as confirmed ZIKV infection when reverse transcription (RT) PCR tested positive, or probable ZIKV infection when ZIKV immunoglobulin M and/or immunoglobulin G and ZIKV plaque reduction neutralization tests were positive. Women found positive using molecular or serological tests were prospectively followed-up with ultrasound scans and neurosonograms on a monthly basis until delivery; magnetic resonance imaging and amniotic fluid testing were performed after signed informed consent. Samples of placenta, and fetal and neonatal tissues were obtained. RESULTS: Seventy-two pregnant women tested positive for ZIKV infection: ten were confirmed by RT-PCR, and 62 were probable cases based on serological tests. The prevalence of adverse perinatal outcomes was 33.3% (three out of nine, 95% CI 12.1-64.6%): two cases of congenital ZIKV syndrome (CZS) and one miscarriage, all born to women infected in the first trimester of gestation. All ZIKV-confirmed women had persistent viraemias beyond 2 weeks (median 61.50 days; IQR 35.50-80.75). Amniotic fluid testing was only positive in the two fetuses with anomalies. CONCLUSION: The prevalence of perinatal adverse outcomes for women with ZIKV-confirmed infection was 33.3%. Amniocentesis for ZIKV RT-PCR is recommended when fetal abnormalities are found. Intensive prenatal and postnatal follow-up of ZIKV-infected pregnancies is advised in confirmed cases.

Activity of weekly paclitaxel-cetuximab chemotherapy in unselected patients with recurrent/metastatic head and neck squamous cell carcinoma: prognostic factors.

BACKGROUND: Standard treatment for recurrent/metastatic head and neck squamous cell carcinoma (RM-SCCHN) is based in on platinum and cetuximab combination therapy. Unfortunately, not all patients are candidates to receive platinum-based treatment, because of different conditions as comorbidity and poor performance status. Weekly paclitaxel and cetuximab (WPC) is an active therapeutic alternative, based on a phase II study, with less toxicity. Our main objective is to confirm its activity in unselected patients, mostly unfit for aggressive therapies, analysing also some clinically relevant prognostic factors (PFs). METHODS: Retrospective data was collected for RM-SCCHN patients, treated at our institution between January 2008 and July 2014 with weekly paclitaxel (80 mg/m2) and cetuximab (400/250 mg/m2). RESULTS: 148 patients were treated. The objective response rate (OR) was as follows: 13 patients (8.78%) complete response (CR); 57 patients (38.51%) partial response (PR) and 30 patients (20.3%) stable disease (SD). Median overall survival (OS) was 10 months (95% CI 8.31-11.69) and median progression free survival (PFS) was 7 months (95% CI 5.88-8.12). Response to treatment showed independent prognosis relevance as PF in multivariate analysis for PFS and OS. Furthermore, decline in serum magnesium during the treatment was also an independent PF for OS. CONCLUSIONS: WPC activity was confirmed as a useful therapy on real-life unselected RM-SCCHN patients, with similar benefit to that obtained in the phase II study, and comparable to platinum and cetuximab based treatment, confirming its value in unfit patients. In addition to treatment response, a change in serum magnesium values during treatment was proved as independent PF on OS.

A definition for aggressive disease in patients with HER-2 negative metastatic breast cancer: an expert consensus of the Spanish Society of Medical Oncology (SEOM).

PURPOSE: To converge on an expert opinion to define aggressive disease in patients with HER2-negative mBC using a modified Delphi methodology. METHODS: A panel of 21 breast cancer experts from the Spanish Society of Medical Oncology agreed upon a survey which comprised 47 questions that were grouped into three sections: relevance for defining aggressive disease, aggressive disease criteria and therapeutic goals. Answers were rated using a 9-point Likert scale of relevance or agreement. RESULTS: Among the 88 oncologists that were invited to participate, 81 answered the first round (92%), 70 answered the second round (80%), and 67 answered the third round (76%) of the survey. There was strong agreement regarding the fact that identifying patients with aggressive disease needs to be adequately addressed to help practitioners to decide the best treatment options for patients with HER2-negative mBC. The factors that were considered to be strongly relevant to classifying patients with aggressive HER2-negative mBC were a high tumor burden, a disease-free interval of less than 12-24 months after surgery, the presence of progressive disease during adjuvant or neoadjuvant chemotherapy and having a triple-negative phenotype. The main therapeutic goals were controlling symptoms, improving quality of life and increasing the time to progression and overall survival. CONCLUSIONS: High tumor burden, time to recurrence after prior therapy and having a triple-negative phenotype were the prognostic factors for which the greatest consensus was found for identifying patients with aggressive HER2-negative mBC. Identifying patients with aggressive disease leads to different therapeutic approaches.

Biliary tract cancers: SEOM clinical guidelines.

Biliary tract cancer (BTC) is an uncommon and highly fatal malignancy. It is composed of three main different entities; Gall bladder carcinoma (GBC), intrahepatic cholangiocarcinoma (iCC) and extrahepatic cholangiocarcinoma (eCC) sharing different genetic, risk factors and clinical presentation. Multidetector-row computed tomography (MDCT) and magnetic resonance cholangio-pancreatography (MRCP) are the more important diagnostic techniques. Surgery is the only potentially curative therapy but disease recurrence is frequent. Treatment with chemotherapy, radiotherapy or both has not demonstrated survival benefit in the adjuvant setting. Cisplatin plus gemcitabine constitutes the gold standard in metastatic disease. New ongoing studies mainly in the adjuvant and neoadjuvant setting along with molecular research will hopefully help to improve survival and quality of life of this disease.

Adjuvant regimens with trastuzumab administered for small HER2-positive breast cancer in routine clinical practice.

PURPOSE: Trastuzumab has proven to improve the prognosis of HER2-positive breast cancer, but the information available about its administration for small tumors is still limited. Therefore, we assessed the use of adjuvant regimens with trastuzumab for the treatment of small HER2-positive breast cancer in routine clinical practice. METHODS: This observational study was conducted in patients with HER2-positive breast adenocarcinoma ≤1.5 cm who received trastuzumab-based adjuvant treatment in clinical practice. Clinical/histopathological data were retrieved from patients' medical charts. RESULTS: A total of 101 evaluable patients were enrolled (median age [range], 56.7 [49.0-64.8] years; ECOG 0, 98.0 %; ductal carcinoma, 88.1 %; lymph nodes N0, 79.2 %). Only five (5.0 %) patients received neoadjuvant treatment, while all patients underwent tumor surgery. Adjuvant trastuzumab was administered at a mean (±SD) dose of 5.9 ± 1.5 mg/kg/cycle, and mostly in a three-weekly schedule (89 [89.0 %] patients). The most frequent adjuvant therapy used with trastuzumab was chemotherapy (87 [86.1 %] patients), followed by radiotherapy (63 [62.4 %] patients) and hormone therapy (52 [51.5 %] patients). Chemotherapy regimens mainly included doxorubicin, cyclophosphamide and paclitaxel/docetaxel (n = 30), docetaxel and cyclophosphamide (n = 15), docetaxel and carboplatin (n = 13). Hormone therapy mainly included letrozole (n = 17) and tamoxifen (n = 17). Nine (8.9 %) patients reported trastuzumab-related adverse events; only one allergic reaction reached grade 3 toxicity. CONCLUSION: This study shows that trastuzumab-based adjuvant treatment of small HER2-positive breast cancer is mostly based on chemotherapy-mainly paclitaxel/docetaxel. Adjuvant administration of trastuzumab for small HER2-positive breast cancer seems to be similar to that used for larger tumors.

Adjustments, extinction, and remains of selenocysteine incorporation machinery in the nematode lineage.

Selenocysteine (Sec) is encoded by an UGA codon with the help of a SECIS element present in selenoprotein mRNAs. SECIS-binding protein (SBP2/SCBP-2) mediates Sec insertion, but the roles of its domains and the impact of its deficiency on Sec insertion are not fully understood. We used Caenorhabditis elegans to examine SBP2 function since it possesses a single selenoprotein, thioredoxin reductase-1 (TRXR-1). All SBP2 described so far have an RNA-binding domain (RBD) and a Sec-incorporation domain (SID). Surprisingly, C. elegans SBP2 lacks SID and consists only of an RBD. An sbp2 deletion mutant strain ablated Sec incorporation demonstrating SBP2 essentiality for Sec incorporation. Further in silico analyses of nematode genomes revealed conservation of SBP2 lacking SID and maintenance of Sec incorporation linked to TRXR-1. Remarkably, parasitic plant nematodes lost the ability to incorporate Sec, but retained SecP43, a gene associated with Sec incorporation. Interestingly, both selenophosphate synthetase (SPS) genes are absent in plant parasitic nematodes, while only Cys-containing SPS2 is present in Sec-incorporating nematodes. Our results indicate that C. elegans and the nematode lineage provide key insights into Sec incorporation and the evolution of Sec utilization trait, selenoproteomes, selenoproteins, and Sec residues. Finally, our study provides evidence of noncanonical translation initiation in C. elegans, not previously known for this well-established animal model.

Oncological translational research in the Spanish national health system: the INTRO study.

OBJECTIVES: Under the auspices of the Foundation for Excellence and Quality in Oncology (ECO), the Translational Research in Oncology Medical Services Study (INTRO) was conducted with the aim of describing the current state of, and future expectations for translational cancer research in Spanish medical centres. The first step in the investigation was intended to analyse the current condition of the national Medical Oncology Services network by examining different aspects of the oncology research field. METHODS: A descriptive and observational multicentre study was performed at a statewide level; information was collected by surveying a cross-section of all those responsible for Medical Oncology Services in Spain. RESULTS: The survey was completed by key informants, who were selected independently by each service, between September 2010 and April 2011. We were able to gather comprehensive data from a total of 27 Spanish hospitals. These data enabled us to describe the allocation of human and material resources devoted to clinical and translational research across the Medical Oncology Services and to describe the organisational and functional components of these services and units. These data included information pertaining to the activities developed, their funding sources, and their functional dependence on other internal or external bodies. Finally, we explored the degree of dissemination and use of some specific techniques used for the genetic diagnosis of cancer, which have recently been introduced in Medical Oncology within the Spanish healthcare system. CONCLUSIONS: A wide range of variability exists between different oncology services in Spanish hospitals. Time should be spent reflecting on the need and opportunities for improvement in the development of translational research within the field of oncology.

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.

Panitumumab and irinotecan every 3 weeks is an active and convenient regimen for second-line treatment of patients with wild-type K-RAS metastatic colorectal cancer.

PURPOSE: To evaluate the efficacy and safety profile of the combination of panitumumab and irinotecan every 3 weeks in a phase II trial as second-line treatment in patients with advanced wild-type (WT) K-RAS colorectal cancer (CRC). METHODS: Fifty-three patients received 9 mg/kg of panitumumab followed by 350 mg/m(2) of irinotecan every 21 days until disease progression, unacceptable toxicity or consent withdrawal. RESULTS: Median age of patients included was 67 years. All patients had previously received 5-fluorouracil, 84 % oxaliplatin and 8 % irinotecan as first-line treatment. Patients received a median of five infusions of panitumumab and irinotecan. On an intention-to-treat analysis, 12 patients (23 %) achieved partial responses and 22 patients (41 %) achieved disease stabilization. Median progression-free survival and overall survival were 4.5 and 15.1 months, respectively. The most frequent treatment-related severe toxicities per patient were diarrhoea (35.8 %), followed by skin rash (32.1 %), asthenia (18.9 %) and neutropenia (13.2 %). A significant association between clinical response and incidence and grade of skin toxicity was observed (p = 0.0032). CONCLUSION: This study shows that the administration of panitumumab plus irinotecan every 3 weeks is safe, active and feasible as second-line treatment in patients with advanced WT K-RAS CRC.

Optimal management of breakthrough cancer pain (BCP).

Breakthrough cancer pain (BCP) is common in patients with cancer, causing a negative impairment in quality of life. Recent diagnostic criteria allow for differentiation of background chronic pain and BCP, for which proportion of unpredictable episodes is very high. Five characteristics define BCP: rapid onset, high intensity, maximum intensity (minutes), mean duration 30 min, and unpredictable onset. Fentanyl is a synthetic opioid characterized by rapid absorption and start of the analgesic effects. In addition to comparing some of the marked differences between the four pharmaceutical forms of fentanyl marketed in Spain, this paper discusses the data collected in a comprehensive clinical trial program with fentanyl pectin nasal spray (FPNS), a formulation that takes advantage of the intranasal route and the PecSys™ technology. The FPNS formulation achieves analgesic action 5 min after application and significant pain relief at 10 min. FPNS, therefore, has key features to be an optimal treatment for BCP.

Novel antiangiogenic therapies against advanced hepatocellular carcinoma (HCC).

Angiogenesis is a cornerstone in the process of hepatocarcinogenesis. In the sorafenib era, other antiangiogenic targeted drugs, such as monoclonal antibodies and a new generation of tyrosine kinase inhibitors, have been shown in phase II trials to be safe and effective in the treatment of advanced hepatocellular carcinoma. Several currently active phase III trials are testing these drugs, both in first- and second-line settings. Strategies to overcome primary and acquired resistance to antiangiogenic therapy are urgently needed. Novel biomarkers may help in improving the efficacy of drugs targeting angiogenesis.

Chromosome number in South American species of Bothriochloa (Poaceae: Andropogoneae) and evolutionary history of the genus.

Mitotic chromosome number of 14 taxa of Bothriochloa native to Argentina, Brazil and Uruguay were surveyed. Chromosome numbers of B. eurylemma, B. meridionalis and B. velutina are reported for the first time, with 2n = 6x = 60, and this ploidy level is the most common among the studied taxa. In addition, new cytotypes were found for B. alta (2n = 60), B. barbinodis (2n = 60), B. exaristata (2n = 80), B. laguroides var. torreyana (2n = 80), B. longipaniculata (2n = 60 and 80), B. perforata (2n = 60) and B. springfieldii (2n = 60). These numbers differ from those reported in the literature.

Effectiveness of whole grain consumption in the prevention of colorectal cancer: meta-analysis of cohort studies.

The present work aimed to evaluate the effectiveness of whole grain consumption in preventing colorectal cancer. A systematic review with meta-analysis of 11 cohort studies was carried out. The age group of the population studied (1,719,590 participants) was between 25 and 76 years of age. The review evaluated the relative risks with the Cox proportional hazard model. The period of study varied from 6 to 16 years, where 7,745 persons developed colorectal cancer during the follow-up period. In the multivariate analysis, the highest quintile relative risk was 0.94 (95% confidence interval, 0.85-1.03), whereas that for the lowest quintile was 0.96 (95% confidence interval, 0.88-1.04). The location of tumors was also evaluated, with tumors in the colon demonstrating a relative risk of 0.93 (95% confidence interval, 0.83-1.02) and tumors in the recto a relative risk equal to 0.89 (95% confidence interval, 0.79-1.00). In this multivariate analysis, consumption of whole grains was inversely associated with the risk of developing colorectal cancer.

Platyhelminth mitochondrial and cytosolic redox homeostasis is controlled by a single thioredoxin glutathione reductase and dependent on selenium and glutathione.

Platyhelminth parasites are a major health problem in developing countries. In contrast to their mammalian hosts, platyhelminth thiol-disulfide redox homeostasis relies on linked thioredoxin-glutathione systems, which are fully dependent on thioredoxin-glutathione reductase (TGR), a promising drug target. TGR is a homodimeric enzyme comprising a glutaredoxin domain and thioredoxin reductase (TR) domains with a C-terminal redox center containing selenocysteine (Sec). In this study, we demonstrate the existence of functional linked thioredoxin-glutathione systems in the cytosolic and mitochondrial compartments of Echinococcus granulosus, the platyhelminth responsible for hydatid disease. The glutathione reductase (GR) activity of TGR exhibited hysteretic behavior regulated by the [GSSG]/[GSH] ratio. This behavior was associated with glutathionylation by GSSG and abolished by deglutathionylation. The K(m) and k(cat) values for mitochondrial and cytosolic thioredoxins (9.5 microm and 131 s(-1), 34 microm and 197 s(-1), respectively) were higher than those reported for mammalian TRs. Analysis of TGR mutants revealed that the glutaredoxin domain is required for the GR activity but did not affect the TR activity. In contrast, both GR and TR activities were dependent on the Sec-containing redox center. The activity loss caused by the Sec-to-Cys mutation could be partially compensated by a Cys-to-Sec mutation of the neighboring residue, indicating that Sec can support catalysis at this alternative position. Consistent with the essential role of TGR in redox control, 2.5 microm auranofin, a known TGR inhibitor, killed larval worms in vitro. These studies establish the selenium- and glutathione-dependent regulation of cytosolic and mitochondrial redox homeostasis through a single TGR enzyme in platyhelminths.

Arbuscular mycorrhizal fungi and rhizospheric bacteria diversity along an altitudinal gradient in South American Puna grassland.

Rhizospheric soil samples were taken from Puna native grasses along an altitudinal gradient. Biodiversity of arbuscular mycorrhizal fungi (AMF) and associated bacteria was analyzed considering altitude and grasses photosynthetic pathways (metabolic type C3, C4). Cultivation-dependent approaches were applied to obtain further information about the phylogeny of the dominating cultivable aerobic-heterotrophic bacteria communities present in rhizospheric soil samples. In average, the bacterial count ranged between 1.30 x 10(2) and 8.66 x 10(4) CFU g(-1) of dry weight of soil. Individual bacterial colonies of aerobic heterotrophic bacteria grown on R2A medium were morphologically grouped and identified as typical soil bacteria belonging to the genera Bacillus, Pseudomonas, and Arthrobacter. Ten AMF taxa were found: Acaulospora sp., A. laevis, A. spinosa, Gigaspora sp., Gi. ramisporophora, Glomus sp., Gl. aggregatum, Gl. ambisporum, Gl. sinuosum, and Scutellospora biornata. AMF diversity decreased with altitude.

The "El Alamo" project (1990-1997): two consecutive hospital-based studies of breast cancer outcomes in Spain.

BACKGROUND: The "Alamo" project is a retrospective analysis of 14,854 patients diagnosed of breast cancer between 1990 and 1997 in 50 Spanish hospitals. METHODS: Alamo I (AI) consisted of 4,532 patients diagnosed with breast cancer between 1990 and 1993. Data were collected in 2000. Alamo II (AII) consisted of 10,322 patients diagnosed between 1994 and 1997. Data were collected in 2003. RESULTS: At presentation, there were (AI vs. AII) 17.6% vs. 24.3% at stage I; 55.5% vs. 53.1% at stage II; 18.7% vs. 15% at stage III; 7.2% vs. 5.9 at stage IV. Median age was 57 (AI) vs. 58 years (AII) and 65.9% vs. 67.2% (AI vs. AII) were post-menopausal. Firstline treatment for disease stages I, II and III was surgery in 91% of patients in both studies. Breast conserving surgery rate increased from 20.2% (AI) to 32.7% (AII). Adjuvant systemic treatments were administered to 87.6% (AI) and 92.8% (AII) of patients. Recurrence rate diminished from 36.6% (AI) to 22.5% (AII) and the 9-year survival rate increased from 63.2% (95% CI: 61.5-64.9) to 70.1% (95% CI: 68.5-71.8). CONCLUSION: Breast cancer outcomes in Spain have improved from 1990-1993 to 1994-1997, likely because of breast cancer screening program implementation and new therapies.