Neratinib + fulvestrant + trastuzumab for HR-positive, HER2-negative, HER2-mutant metastatic breast cancer: outcomes and biomarker analysis from the SUMMIT trial.

BACKGROUND: HER2 mutations are targetable alterations in patients with hormone receptor-positive (HR+) metastatic breast cancer (MBC). In the SUMMIT basket study, patients with HER2-mutant MBC received neratinib monotherapy, neratinib + fulvestrant, or neratinib + fulvestrant + trastuzumab (N + F + T). We report results from 71 patients with HR+, HER2-mutant MBC, including 21 (seven in each arm) from a randomized substudy of fulvestrant versus fulvestrant + trastuzumab (F + T) versus N + F + T. PATIENTS AND METHODS: Patients with HR+ HER2-negative MBC with activating HER2 mutation(s) and prior cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) therapy received N + F + T (oral neratinib 240 mg/day with loperamide prophylaxis, intramuscular fulvestrant 500 mg on days 1, 15, and 29 of cycle 1 then q4w, intravenous trastuzumab 8 mg/kg then 6 mg/kg q3w) or F + T or fulvestrant alone. Those whose disease progressed on F + T or fulvestrant could cross-over to N + F + T. Efficacy endpoints included investigator-assessed objective response rate (ORR), clinical benefit rate (RECIST v1.1), duration of response, and progression-free survival (PFS). Plasma and/or formalin-fixed paraffin-embedded tissue samples were collected at baseline; plasma was collected during and at end of treatment. Extracted DNA was analyzed by next-generation sequencing. RESULTS: ORR for 57 N + F + T-treated patients was 39% [95% confidence interval (CI) 26% to 52%); median PFS was 8.3 months (95% CI 6.0-15.1 months). No responses occurred in fulvestrant- or F + T-treated patients; responses in patients crossing over to N + F + T supported the requirement for neratinib in the triplet. Responses were observed in patients with ductal and lobular histology, 1 or ≥1 HER2 mutations, and co-occurring HER3 mutations. Longitudinal circulating tumor DNA sequencing revealed acquisition of additional HER2 alterations, and mutations in genes including PIK3CA, enabling further precision targeting and possible re-response. CONCLUSIONS: The benefit of N + F + T for HR+ HER2-mutant MBC after progression on CDK4/6is is clinically meaningful and, based on this study, N + F + T has been included in the National Comprehensive Cancer Network treatment guidelines. SUMMIT has improved our understanding of the translational implications of targeting HER2 mutations with neratinib-based therapy.

Phosphoproteomic analysis of neoadjuvant breast cancer suggests that increased sensitivity to paclitaxel is driven by CDK4 and filamin A.

Precision oncology research is challenging outside the contexts of oncogenic addiction and/or targeted therapies. We previously showed that phosphoproteomics is a powerful approach to reveal patient subsets of interest characterized by the activity of a few kinases where the underlying genomics is complex. Here, we conduct a phosphoproteomic screening of samples from HER2-negative female breast cancer receiving neoadjuvant paclitaxel (N = 130), aiming to find candidate biomarkers of paclitaxel sensitivity. Filtering 11 candidate biomarkers through 2 independent patient sets (N = 218) allowed the identification of a subgroup of patients characterized by high levels of CDK4 and filamin-A who had a 90% chance of achieving a pCR in response to paclitaxel. Mechanistically, CDK4 regulates filamin-A transcription, which in turn forms a complex with tubulin and CLIP-170, which elicits increased binding of paclitaxel to microtubules, microtubule acetylation and stabilization, and mitotic catastrophe. Thus, phosphoproteomics allows the identification of explainable factors for predicting response to paclitaxel.

Palbociclib in combination with endocrine therapy versus capecitabine in hormonal receptor-positive, human epidermal growth factor 2-negative, aromatase inhibitor-resistant metastatic breast cancer: a phase III randomised controlled trial-PEARL.

BACKGROUND: Palbociclib plus endocrine therapy (ET) is the standard treatment of hormone receptor-positive and human epidermal growth factor receptor 2-negative, metastatic breast cancer (MBC). However, its efficacy has not been compared with that of chemotherapy in a phase III trial. PATIENTS AND METHODS: PEARL is a multicentre, phase III randomised study in which patients with aromatase inhibitor (AI)-resistant MBC were included in two consecutive cohorts. In cohort 1, patients were randomised 1 : 1 to palbociclib plus exemestane or capecitabine. On discovering new evidence about estrogen receptor-1 (ESR1) mutations inducing resistance to AIs, the trial was amended to include cohort 2, in which patients were randomised 1 : 1 between palbociclib plus fulvestrant and capecitabine. The stratification criteria were disease site, prior sensitivity to ET, prior chemotherapy for MBC, and country of origin. Co-primary endpoints were progression-free survival (PFS) in cohort 2 and in wild-type ESR1 patients (cohort 1 + cohort 2). ESR1 hotspot mutations were analysed in baseline circulating tumour DNA. RESULTS: From March 2014 to July 2018, 296 and 305 patients were included in cohort 1 and cohort 2, respectively. Palbociclib plus ET was not superior to capecitabine in both cohort 2 [median PFS: 7.5 versus 10.0 months; adjusted hazard ratio (aHR): 1.13; 95% confidence interval (CI): 0.85-1.50] and wild-type ESR1 patients (median PFS: 8.0 versus 10.6 months; aHR: 1.11; 95% CI: 0.87-1.41). The most frequent grade 3-4 toxicities with palbociclib plus exemestane, palbociclib plus fulvestrant and capecitabine, respectively, were neutropenia (57.4%, 55.7% and 5.5%), hand/foot syndrome (0%, 0% and 23.5%), and diarrhoea (1.3%, 1.3% and 7.6%). Palbociclib plus ET offered better quality of life (aHR for time to deterioration of global health status: 0.67; 95% CI: 0.53-0.85). CONCLUSIONS: There was no statistical superiority of palbociclib plus ET over capecitabine with respect to PFS in MBC patients resistant to AIs. Palbociclib plus ET showed a better safety profile and improved quality of life.

Review of concepts in therapeutic decision-making in HER2-negative luminal metastatic breast cancer.

PURPOSE: Hormone receptor (HR)-positive, Human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (MBC) requires a therapeutic approach that takes into account multiple factors, with treatment being based on anti-estrogen hormone therapy (HT). As consensus documents are valuable tools that assist in the decision-making process for establishing clinical strategies and optimize the delivery of health services, this consensus document has been created with the aim of developing recommendations on cretiera for hormone sensitivity and resistance in HER2-negative luminal MBC and facilitating clinical decision-making. METHODS: This consensus document was generated using a modification of the RAND/UCLA methodology, which included the definition of the project and identification of issues of interest, a non-exhaustive systematic review of the literature, an analysis and synthesis of the scientific evidence, preparation of recommendations, and external evaluation with a panel of 64 medical oncologists specializing in breast cancer. RESULTS: A Spanish panel of experts reached consensus on 32 of the 32 recommendations/conclusions presented in the first round and were accepted with an approval rate of 100% about definition of metastatic disease not susceptible to local curative treatment, definition of hormone sensitivity and hormone resistance in metastatic luminal disease and therapeutic decision-making. CONCLUSION: We have developed a consensus document with recommendations on the treatment of patients with HER2-negative luminal MBC that will help to improve therapeutic benefits.

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.

Prospective, multicenter study on the economic and clinical impact of gene-expression assays in early-stage breast cancer from a single region: the PREGECAM registry experience.

INTRODUCTION: The aim of this study is to evaluate the cost-effectiveness and impact of gene-expression assays (GEAs) on treatment decisions in a real-world setting of early-stage breast cancer (ESBC) patients. METHODS: This is a regional, prospective study promoted by the Council Health Authorities in Madrid. Enrolment was offered to women with estrogen receptor-positive, human epidermal growth factor receptor 2-negative, node-negative or micrometastatic, stage I or II breast cancer from 21 hospitals in Madrid. Treatment recommendations were recorded before and after knowledge of tests results. An economic model compared the cost-effectiveness of treatment, guided by GEAs or by common prognostic factors. RESULTS: 907 tests (440 Oncotype DX® and 467 MammaPrint®) were performed between February 2012 and November 2014. Treatment recommendation changed in 42.6% of patients. The shift was predominantly from chemohormonal (CHT) to hormonal therapy (HT) alone, in 30.5% of patients. GEAs increased patients' confidence in treatment decision making. Tumor grade, progesterone receptor positivity and Ki67 expression were associated with the likelihood of change from CHT to HT (P < 0.001) and from HT to CHT (P < 0.001). Compared with current clinical practice genomic testing increased quality-adjusted life years by 0.00787 per patient and was cost-saving from a national health care system (by 13.867€ per patient) and from a societal perspective (by 32.678€ per patient). CONCLUSION: Using GEAs to guide adjuvant therapy in ESBC is cost-effective in Spain and has a significant impact on treatment decisions.

Evaluating the addition of bevacizumab to endocrine therapy as first-line treatment for hormone receptor-positive metastatic breast cancer: a pooled analysis from the LEA (GEICAM/2006-11_GBG51) and CALGB 40503 (Alliance) trials.

BACKGROUND: Randomised trials comparing the efficacy of standard endocrine therapy (ET) versus experimental ET + bevacizumab (Bev) in 1st line hormone receptor-positive patients with metastatic breast cancer have thus far shown conflicting results. PATIENTS AND METHODS: We pooled data from two similar phase III randomised trials of ET ± Bev (LEA and Cancer and Leukemia Group B 40503) to increase precision in estimating treatment effect. Primary end-point was progression-free survival (PFS). Secondary end-points were overall survival (OS), objective response rate (ORR), clinical benefit rate (CBR) and safety. Exploratory analyses were performed within subgroups defined by patients with recurrent disease, de novo disease, prior endocrine sensitivity or resistance and reported grades III-IV hypertension and proteinuria. RESULTS: The pooled sample consisted of 749 patients randomised to ET or ET + Bev. Median PFS was 14.3 months for ET versus 19 months for ET + Bev (unadjusted hazard ratio [HR] 0.77; 95% confidence interval [CI] 0.66-0.91; p < 0.01). ORR and CBR with ET and ET + Bev were 40 versus 61% (p < 0.01) and 64 versus 77% (p < 0.01), respectively. There was no difference in OS (HR 0.96; 95% CI 0.77-1.18; p = 0.68). PFS was superior for ET + Bev for endocrine-sensitive patients (HR 0.68; 95% CI 0.53-0.89; p = 0.004). Grade III-IV hypertension (2.2 versus 20.1%), proteinuria (0 versus 9.3%), cardiovascular (0.5 versus 4.2%) and liver events (0 versus 2.9%) were significantly higher for ET + Bev (all p < 0.01). Hypertension and proteinuria were not predictors of efficacy (interaction test p = 0.33). CONCLUSION: The addition of Bev to ET increased PFS overall and in endocrine-sensitive patients but not OS at the expense of significant additional toxicity. TRIALS REGISTRATION: ClinicalTrial.Gov NCT00545077 and NCT00601900.

Breast cancer PAM50 signature: correlation and concordance between RNA-Seq and digital multiplexed gene expression technologies in a triple negative breast cancer series.

BACKGROUND: Full RNA-Seq is a fundamental research tool for whole transcriptome analysis. However, it is too costly and time consuming to be used in routine clinical practice. We evaluated the transcript quantification agreement between RNA-Seq and a digital multiplexed gene expression platform, and the subtype call after running the PAM50 assay in a series of breast cancer patients classified as triple negative by IHC/FISH. The goal of this study is to analyze the concordance between both expression platforms overall, and for calling PAM50 triple negative breast cancer intrinsic subtypes in particular. RESULTS: The analyses were performed in paraffin-embedded tissues from 96 patients recruited in a multicenter, prospective, non-randomized neoadjuvant triple negative breast cancer trial (NCT01560663). Pre-treatment core biopsies were obtained following clinical practice guidelines and conserved as FFPE for further RNA extraction. PAM50 was performed on both digital multiplexed gene expression and RNA-Seq platforms. Subtype assignment was based on the nearest centroid classification following this procedure for both platforms and it was concordant on 96% of the cases (N = 96). In four cases, digital multiplexed gene expression analysis and RNA-Seq were discordant. The Spearman correlation to each of the centroids and the risk of recurrence were above 0.89 in both platforms while the agreement on Proliferation Score reached up to 0.97. In addition, 82% of the individual PAM50 genes showed a correlation coefficient > 0.80. CONCLUSIONS: In our analysis, the subtype calling in most of the samples was concordant in both platforms and the potential discordances had reduced clinical implications in terms of prognosis. If speed and cost are the main driving forces then the preferred technique is the digital multiplexed platform, while if whole genome patterns and subtype are the driving forces, then RNA-Seq is the preferred method.

SEOM clinical guidelines in early stage breast cancer (2018).

Breast cancer is the most common cancer in women in our country and it is usually diagnosed in the early and potentially curable stages. Nevertheless, around 20-30% of patients will relapse despite appropriate locoregional and systemic therapies. A better knowledge of this disease is improving our ability to select the most appropriate therapy for each patient with a recent diagnosis of an early stage breast cancer, minimizing unnecessary toxicities and improving long-term efficacy.

Correction to: Persistent major alopecia following adjuvant docetaxel for breast cancer: incidence, characteristics, and prevention with scalp cooling.

In the original publication of the article, Table 1 was published with incorrect caption and values. The Table 1 with corrected caption and values is given in this Correction.

Persistent major alopecia following adjuvant docetaxel for breast cancer: incidence, characteristics, and prevention with scalp cooling.

BACKGROUND: Persistent alopecia (PA) after docetaxel has been recently described. The aim of our study is to establish the incidence and characteristics of PA following adjuvant docetaxel for breast cancer (BC) and to test the ability of scalp cooling in prevention. PATIENTS AND METHODS: BC patients receiving adjuvant chemotherapy followed or not by endocrine therapy (and a control group receiving only endocrine therapy) were interviewed in a single institution at 1.5 to 5 years following primary diagnosis searching for PA. A confirmatory prevalence study was later performed in other two institutions. Finally, a prevention study using prophylactic scalp cooling (PSC) with ELASTO-GEL hypothermia caps in patients receiving adjuvant docetaxel was performed. RESULTS: In the initial prevalence study (492 patients), minor forms of PA (grade 1) were recorded with all chemotherapy regimens and aromatase inhibitors. Patients receiving docetaxel regimens at cumulative dose (CD) ≥ 400 mmg/m2 presented a significantly higher prevalence of grades 1 PA (33-52%) and 2 PA (5-12%). Prevalence of grade 2 PA with docetaxel CD ≥ 400 mmg/m2 was confirmed in two other institutions. Overall, grade 2 PA was seen in 10.06% (95% CI 7.36-13.61) of 358 patients with docetaxel regimens reaching CD ≥ 400 mmg/m2, but not in patients with lower docetaxel CD, other chemotherapy regimens, or endocrine therapy alone. In prevention trial, no grade 2 PA occurred among 116 patients receiving adjuvant docetaxel (≥ 400 mmg/m2) and PSC followed-up after a 96 months median time. PSC was well tolerated. No scalp relapses were seen among 30 patients (22% of all inclusions) having disease relapse. CONCLUSION: Adjuvant treatment with docetaxel (CD ≥ 400 mmg/m2) is associated with a significant rate of grade 2 PA, leading to wearing a wig, in around 10% of patients. This toxicity was completely prevented with scalp cooling. Clinical Trial Reference: NCT00515762.

Safety of everolimus plus exemestane in patients with hormone-receptor-positive, HER2-negative locally advanced or metastatic breast cancer: results of phase IIIb BALLET trial in Spain.

BACKGROUND: Everolimus with exemestane has shown promising activity in patients with hormone-receptor (HR)-positive HER2-negative endocrine-resistant advanced breast cancer. It is necessary, therefore, to characterize the safety profile of this new combination in the real-world clinical setting and in the broadest possible population. PATIENTS AND METHODS: Post-menopausal women with HR-positive HER2-negative advanced breast cancer progressing after prior non-steroidal aromatase inhibitors (NSAIs) were included. The objectives of this analysis were to evaluate the safety profile of this combination in a subset of Spanish patients in the BALLET trial and to characterize grade 3 and 4 adverse events (AEs) in routine clinical practice in Spain. RESULTS: Between September 2012 and July 2013, 429 patients (20% of the overall study population) were included in the BALLET study in 52 hospitals in Spain, of whom 100 (23%) were ≥ 70 years. The median treatment duration was 3.14 and 3.03 months for exemestane and everolimus, respectively. The most common reasons for discontinuation of treatment were local reimbursement of everolimus (43%), followed by disease progression (31%) and the incidence of AEs (15%). The most frequent AEs causing permanent discontinuation were pneumonitis (4%), asthenia (2%) and stomatitis (2%). Overall, 87% of patients experienced at least one AE of any grade, 30% of patients at least one grade 3 AE and 2% of patients a grade 4 AE. CONCLUSION: The safety profile in Spanish patients of the BALLET trial is consistent with the results obtained in the overall population of the trial, as well as in previous clinical trials.

Trastuzumab emtansine (T-DM1) plus docetaxel with or without pertuzumab in patients with HER2-positive locally advanced or metastatic breast cancer: results from a phase Ib/IIa study.

BACKGROUND: Trastuzumab emtansine (T-DM1) exhibited enhanced antitumor activity when combined with docetaxel or pertuzumab in preclinical studies. This phase Ib/IIa study assessed the feasibility of T-DM1 + docetaxel in patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC) and T-DM1 + docetaxel ± pertuzumab in patients with HER2-positive locally advanced breast cancer (LABC). PATIENTS AND METHODS: Phase Ib (part 1) explored dose escalation, with T-DM1 + docetaxel administered for greater than or equal to six cycles in patients with MBC. Phase Ib (part 2) began with the maximum tolerated dose (MTD) identified in part 1. Patients with LABC were administered less than or equal to six cycles of T-DM1 + docetaxel or T-DM1 + docetaxel + pertuzumab. Phase IIa explored the MTDs identified in phase Ib. RESULTS: Administered with T-DM1 (3.6 mg/kg), the docetaxel MTD was 60 mg/m(2) in MBC. In LABC, the MTD was 100 mg/m(2) docetaxel in combination with T-DM1 (3.6 mg/kg), given with granulocyte colony-stimulating factor (G-CSF). Administered with T-DM1 (3.6 mg/kg) + pertuzumab (840 mg, cycle 1; 420 mg, subsequent cycles), the docetaxel MTD in LABC was 75 mg/m(2) with G-CSF support. Neutropenia was the most common grade 3-4 adverse event (AE; MBC, 72% and LABC, 29%). In total, 48% (12/25) of MBC patients and 47% (34/73) of LABC patients experienced AEs requiring dose modification. In MBC (median prior systemic agents = 5), the objective response rate was 80.0% (20/25; 95% confidence interval [CI] 59.3-93.2) and the median progression-free survival was 13.8 months (range, 1.6-33.5). The pathologic complete response (ypT0/is, ypN0) rate in LABC was 60.3% (44/73; 95% CI 48.1-71.5). Pharmacokinetic analyses indicated a low risk of drug-drug interaction between T-DM1 and docetaxel. CONCLUSIONS: T-DM1 combined with docetaxel ± pertuzumab appeared efficacious in MBC or LABC; however, nearly half of patients experienced AEs requiring dose reductions with these T-DM1 combinations. CLINICALTRIALSGOV IDENTIFIER: NCT00934856.

Prognostic value of metabolic tumour volume and total lesion glycolysis in 18F-FDG PET/CT scans in locally advanced breast cancer staging. / Papel pronóstico del volumen metabólico tumoral y de la glucólisis tumoral total en los estudios 18F-FDG PET/TC de estadificación del cáncer localmente avanzado de mama.

OBJECTIVE: To determine whether metabolic tumour volume (MTV) and total lesion glycolysis (TLG) are able to predict recurrence risk in locally advanced breast cancer (LABC) patients. MATERIAL AND METHODS: Retrospective study of LABC patients who undertook neoadjuvant, local and adjuvant treatment and follow up. A 18F-FDG PET/CT study for initial staging was performed analysing in this study different metabolic parameters (MTV, TLG, SUVmax and SUVmed) both in the primary tumour (T) as well as in axillary nodes (N) and whole-body (WB). RESULTS: Forty females were included between January 2010-2011; follow up until January 2015 was completed. The average follow-up was 46 months. Twenty percent presented recurrence: local disease (n=2) and distant metastasis (n=6); 3 patients died (38% of the patients which recurred and 7.5% from the total). SUVmax, MTV and TLG, in T, N and WB, were higher in those patients with recurrence. The MTV and TLG parameters in the tumour (T) were related to the recurrence rate (P=.020 and P=.028, respectively); whereas SUVmax in the lymph nodes (N) was significantly related (P=.008) to the recurrence rate. The best cut-off points to predict recurrence where: MTV T ≥19.3cm3, TLG T≥74.4g and SUVmax N≥13.8, being 10-12 times more likely to recidivate when these thresholds where exceeded. Tumour grade was the only clinical-pathological variable which was related to recurrence probability (p=.035). CONCLUSIONS: In this study of LABC patients the metabolic parameters which have a better relationship with recurrence rate are: MTV and TLG in the primary tumour, SUVmax in the regional lymph node disease and whole-body PET data.

Review: circulating tumor cells in the practice of breast cancer oncology.

The primary cause of tumor-related death in breast cancer is still represented by distant metastasization. The dissemination of tumor cells from the primary tumor to distant sites through bloodstream cannot be early detected by standard imaging methods. Circulating tumor cells (CTCs) play a major role in the metastatic spread of breast cancer. Different analytical systems for CTCs isolation and detection have been developed and novel areas of research are directed towards developing assays for CTCs molecular characterization. This review describes the current state of art on CTCs detection techniques and the present and future clinical implications of CTCs enumeration and characterization.

SEOM clinical guidelines in early-stage breast cancer 2015.

Breast cancer is a major public health problem. Despite remarkable advances in early diagnosis and treatment, one in three women may have metastases since diagnosis. Better understanding of prognostic and predictive factors allows us to select the most appropriate adjuvant therapy in each patient. In these guidelines, we summarize current evidence for the medical management of early-stage breast cancer.

[Axillary pathologic response after neoadjuvant chemotherapy in locally advanced breast cancer with axillary involvement]. / Respuesta patológica en la axila tras quimioterapia neoadyuvante en el cáncer de mama localmente avanzado con afectación axilar.

AIM: To compare axillary involvement (N+) at initial staging in locally advanced breast cancer (LABC) with axillary lymphadenectomy histologic results after neoadjuvant chemotherapy treatment (NeoChemo). MATERIAL AND METHODS: Retrospective study between November 2011 and September 2013 of LABC cases treated with neoadjuvant chemotherapy based on docetaxel (associated with trastuzumab in HER2 positive cases and carboplatin/adriamycin in HER2 negative cases). Those clinically or radiologically suspected cases of axillary involvement were histologically confirmed. When there was no suspicion of axillary involvement, sentinel lymph node radioguided biopsy (SLNRB) was performed using intradermal injection of (99m)Tc-nanocolloid albumin prior to neoadjuvant treatment. Axillary lymphadenectomy after NeoChemo was undertaken in all cases with positive axilla. Final pathologic response was classified as complete (pCR) when there was no evidence of tumoral disease and as non-pathologic complete response (no pCR) in the opposite case. RESULTS: A total of 346 patients treated with docetaxel were reviewed, identifying 105 LABC. Axillary involvement at initial staging was detected in 70 (67%) before starting NeoChemo. From these 70, 73% (n=51) were N+ (fine needle biopsy and/or biopsy) and the remaining 19 (27%) were occult N+ detected by SLNRB. Axillary lymphadenectomy detected pCR in 56% (39/70), increasing up to 84% pCR when initial N+ status was reached using SNLB. On the other hand, when N+ was detected using fine needle biopsy/lymph biopsy, pCR was only 45%. CONCLUSION: More than 50% of women affected by locally advanced breast cancer with tumoral axillary involvement at initial diagnosis present free metastatic axilla after therapeutic neoadjuvant chemotherapy effect. This increases up to almost 90% in case of occult metastatic axilla detected with sentinel node biopsy prior starting neoadjuvant chemotherapy.

Assignment of tumor subtype by genomic testing and pathologic-based approximations: implications on patient's management and therapy selection.

BACKGROUND: Breast cancer subtypes can be identified by genomic testing or pathology-based approximations. However, these classifications are not equivalent and the clinical relevance of both classifications needs to be fully explored. METHODS: Ninety-four patients were randomized to neoadjuvant single agent doxorubicin or docetaxel. Tumor subtype was assessed by pathology-based classification and by gene expression using the PAM50 plus the claudin-low predictor (CLP). Kappa Cohen's coefficient (κ) was used to test the agreement between methods. Multivariate Cox proportional hazards analyses were used to determine the significance of each methodology in the prediction of prognosis. Likelihood ratio statistics of both classifications were evaluated. RESULTS: The agreement between pathology-based classification and PAM50 was moderate [κ = 0.551, 95 % confidence interval (95 % CI) 0.467-0.641]. Tumor subtype assessed by both classifications were prognostic for overall survival (OS) and relapse-free survival (P < 0.05). However, PAM50 + CLP provided more prognostic information, in terms of OS, than the pathology-based classification (P < 0.05). Patients with triple negative tumors as well as basal-like tumors had worse OS when first treated with doxorubicin (HR = 5.98, 95 % CI 1.25-28.67, and HR = 5.02, 95 % CI 0.96-26.38, respectively). However, claudin-low tumors did not show significant differences in OS according to neoadjuvant treatment branch. Indeed, we found that claudin-low tumors treated with pre-operative doxorubicin had significantly better OS than basal-like tumors treated with neoadjuvant doxorubicin (adjusted HR = 0.16, 95 % CI 0.04-0.69, P = 0.014). CONCLUSIONS: The assignment of tumor subtype can differ depending on the methodology, which might have implications on patient's management and therapy selection.

18F-FDG PET-CT imaging in the neoadjuvant setting for stages II-III breast cancer: association of loco­regional SUVmax with classical prognostic factors.

AIM: Classical prognostic and predictive factors serve to predict outcome and response to neoadjuvant treatment in stage II and III breast cancer. The purpose is to determine the relation between the SUVmax of the locoregional disease with these classical prognostic factors. METHODS: A prospective study including 43 stage II and III breast cancer patients was performed. In all the patients, two 18F-FDG PET-CT studies were performed before and after neoadjuvant chemotherapy. After this treatment, surgery and adjuvant treatment were carried out. To combine the information of the locoregional disease, the SUVmax of the lesion (tumor or abnormal lymphnodes) with the highest uptake was used. SUVmax and prognostic factors were studied with the Kruskal-Wallis non-parametric test and with the Mann-Whitney U. RESULTS: A statistically significant association between elevated SUVmax value and absence of estrogen receptors (ER) expression (16 vs.. 10; P<0.019) was found. Locorregional disease with positive HER2 phenotype had a statistically significant SUVmax value greater than Luminal A (estrogen and/or progesterone positive receptors with Ki67<15%) and B (estrogen and/or progesterone positive receptors with Ki67≥to 15%) (13.4 vs. 7.9 and 8.9; P<0.022 and P<0.024, respectively). Triple negative phenotype disease had higher SUVmax than Luminal A and B (15.4; P<0.030 and P<0.038). Positive correlation between the percentage of the Ki67 Proliferation Index and SUVmax (P<0.007) was demonstrated. High grade disease had a higher SUVmax than low grade (P<0.004). CONCLUSION: Locorregional SUVmax is associated to prognostic and predictive factors and reaffirms the utility of PET-CT as a tool in the common clinical practice.

[New strategies to improve accessibility to laboratory tests in cancer patients]. / Nuevas estrategias de mejora en la accesibilidad a las pruebas de laboratorio de los pacientes en oncología.

OBJECTIVE: To develop models to improve accessibility of performing laboratory tests on chronic oncology patients, as well as a more flexible choice of sample collection in both primary and specialized care. MATERIAL AND METHODS: Circuit analysis of cancer patients. Patient survey to study access to laboratory tests. High Resolution Consultation Development Model (MCAR) and Patient Access Analytical Model (MAAP). RESULTS: The percentage of cancer patients on treatment has increased by 8.76% in the past two years. There was a 32% increased in the use of the MAAP model in the two years of its implementation, and has been the choice of 74% due to greater accessibility, with 8% of the patients having used both models to suit their needs. CONCLUSIONS: The implementation of optimized and preferred care systems has shown that both models improve accessibility and flexibility of the diagnostic testing laboratory in the patients studied.