Manuel Fraile

Survival and clinicopathological characteristics of breast cancer patient according to different tumour subtypes as determined by hormone receptor and Her2 immunohistochemistry. A single institution survey spanning 1998 to 2010

As far as recent breast cancer molecular subtype classification is concerned, much work has dealt with clinical outcomes for triple negative and Her2 patients. Less is known about the course of patients in the remaining subtypes. Molecular classification based on immunohistochemistry is widely available and correlates well with genetic microarray assessment, but at a lower cost. The aim of our investigation was to correlate immunohistochemical subtypes of breast cancer with clinical characteristics and patient outcomes. Since 1998, 1167 patients operated for 1191 invasive breast tumours were included in our database. Patients were regularly followed up until March 2010. Disease-free survival, overall mortality, and breast cancer-specific mortality at 5 years were calculated for the cohort. 72% of tumours were ER+PR±HER2- group, 13% triple negative (ER-PR-HER2-), 10% ER+PR±HER2+ group, and 5% Her2 (ER-PR-HER2+). Cancer-specific survival was 94.2% for the ER+PR+HER2- subtype, 84.8% for the Her2 subtype, 83.3% for the ER+PR-HER2- subtype, and 78.6% for triple negatives. Distant metastases prevalence ranged from 7% to 22% across subtypes, increasing stepwise from ER+PR+HER2-, ER+PR+HER2+, ER+PR-HER2-, ER+PR-HER2+, ER-PR-HER2+ through triple negative. Small, low-grade tumours with low axillary burden were more likely to belong to the ER+PR±HER2- group. Conversely, larger high-grade tumours with significant axillary burden were more likely to belong to Her2 or triple negative groups. ER+PR±HER2- group patients with negative PR receptors performed more like Her2 or triple negative than like the rest of ER+PR±HER2± groups patients. Molecular classification of breast tumours based only on immunohistochemistry is quite useful on practical clinical grounds, as expected. ER+PR±HER2- group patients with negative PR receptors seem to be at high risk and deserve further consideration.

Radiolocalización de lesiones mamarias no palpables combinada con la biopsia del ganglio centinela en mujeres con cáncer de mama

Resumen Introduccion La modalidad intralesional de inyeccion de los radiocoloides en la biopsia del ganglio centinela (BGC) permite la localizacion de tumors mamarios primitivos no palpables, en un mismo acto quirurgico, mediante la tecnica conocida como ROLL. Pacientes y metodo Presentamos nuestra experiencia con la combinacion de ambas tecnicas (BGC y ROLL). Se analizo retrospectivamente a 233 pacientes: en 65 pacientes se practico ROLL y en 168 la lesion fue localizada mediante la insercion de guias metalicas (grupo control). Ambos grupos eran comparables en cuanto a sus variables anatomorradiologicas. Resultados La reseccion de la lesion se llevo a cabo en un solo tiempo en 169 pacientes. No se observaron diferencias significativas entre ambos grupos en cuanto a la afeccion de los margenes quirurgicos (margenes correctos del 80% con ROLL frente al 69,9% sin ROLL) ni en el diametro maximo de la pieza (6,85 frente a 6,52 cm, respectivamente). Conclusion En pacientes sometidas a la BGC con lesiones mamarias no palpables, la tecnica ROLL es una alternativa a las guias metalicas que ofrece una mayor facilidad para la exeresis y mas comodidad para la paciente.

Positive versus negative sentinel nodes in early breast cancer patients: Axillary or loco-regional relapse and survival. A study spanning 2000–2012

Sentinel Node Biopsy (SNB) is a minimally invasive alternative to elective axillary lymph node dissection (ALND) for nodal staging in early breast cancer. The present study was conducted to evaluate prognostic implications of a negative sentinel node (SN) versus a positive SN (followed by completion ALND) in a closely followed-up sample of early breast cancer patients. We studied 889 consecutive breast cancer patients operated for 908 primaries. Patients received adjuvant therapy with chemotherapy, hormone therapy and eventually trastuzumab. Radiation therapy was based on tangential radiation fields that usually included axillary level I. Median follow-up was 47 months. Axillary recurrence was seen in 1.2% (2/162) of positive SN patients, and 0.8% (5/625) of negative SN patients (p = n.s.). There was an overall 3.2% loco-regional failure rate (29/908). Incidence of distant recurrence was 3.3% (23/693) for negative SN patients, and 4.6% (9/196) for positive SN patients (p = n.s.). Overall mortality rate was 4% (8/198) for positive SN patients, while the corresponding specific mortality rate was 2.5% (5/198). For patients with negative SNs, overall mortality was 4.9% (34/693), and the specific mortality was 1.4% (19/693) (p = n.s.). We did not find significant differences in axillary/loco-regional relapse, distant metastases, disease-free interval or mortality between SN negative and SN positive patients, with a follow-up over 4 years.

Role of axillary ultrasound, magnetic resonance imaging, and ultrasound-guided fine-needle aspiration biopsy in the preoperative triage of breast cancer patients.

PurposeRoughly two-thirds of early breast cancer cases are associated with negative axillary nodes and do not benefit from axillary surgery at all. Accordingly, there is an ongoing search for non-surgical staging procedures to avoid lymph-node dissection or sentinel node biopsy (SNB). Non-invasive imaging techniques with very high sensitivity (Se) and negative predictive value (NPV) could eventually replace SNB. We aimed to establish the role of axillary US and MRI, alone or in combination, associated with ultrasound-guided fine-needle aspiration biopsy (US-FNAB) in the prediction of axillary node involvement.Methods/patientsBetween January 2003 and September 2015, we included 1505 of the 1538 breast cancer patients attending our centres. All patients had been referred from a single geographical area. Axillary US, magnetic resonance imaging and ultrasound-guided fine-needle aspiration biopsy (US-FNAB) were performed if required.Results1533 axillary US examinations and 1351 axillary MRI studies were analyzed. For axillary US, Se, Specificity (Sp), Positive Predictive Value (PPV), and NPV were 47.5, 93.6, 82.5, and 73.8%, respectively. For axillary MRI, corresponding values were 29.8, 96.6, 84.9, and 68.4%. When both tests were combined, Sp and PPV slightly improved over individual tests alone. US-FNAB showed a 100% Sp and PPV, with a Se of 80%.ConclusionWe may confidently state that axillary US and US-FNAB have to be included in the preoperative work-up of breast cancer patients.

Prognostic value of hematogenous dissemination and biological profile of the tumor in early breast cancer patients: A prospective observational study

BackgroundThe aim of this study was to investigate the incidence and prognostic value of disseminated tumor cells in bone marrow of breast carcinoma patients with early disease, and to analyze this finding in relation to lymph node involvement, determined by sentinel lymph node (SLN) biopsy analysis, and to prognostic factors of interest.Methods104 patients with operable (T < 3 cm) breast cancer and clinically- and sonographically-negative axillary lymph nodes were scheduled for SLN biopsy. Bone marrow aspirates were collected before the start of surgery from both iliac crests, and mononuclear cell layers were separated by density centrifugation (Lymphoprep). Slide preparations were then examined for the presence of disseminated tumor cells by immunocytochemistry with anti-cytokeratin antibodies (A45-B/B3). Lymphoscintigraphy was performed 2 hours after intratumor administration of 2 mCi (74 MBq) of 99mTc colloidal albumin. The SLN was evaluated for the presence of tumor cells by hematoxylin-eosin staining and, when negative, by immunocytochemistry using anti-cytokeratin antibody (CAM 5.2). Survival analyses and comparative analyses were performed on the results of bone marrow determinations, SLN biopsy, and known prognostic factors, including breast cancer subtypes according to the simplified classification based on ER, PR and HER2.ResultsLymph node and hematogenous dissemination occur in one-third of patients with early-stage breast cancer, although not necessarily simultaneously. In our study, disseminated tumor cells were identified in 22% of bone marrow aspirates, whereas 28% of patients had axillary lymph node involvement. Simultaneous lymph node and bone marrow involvement was found in only 5 patients (nonsignificant). In the survival study (60 months), a higher, although nonsignificant rate of disease-related events (13%) was seen in patients with disseminated tumor cells in bone marrow, and a significant association of events was documented with the known, more aggressive tumor subtypes: triple negative receptor status (21%) and positive ERBB2 status (29%).ConclusionsTumor cell detection in bone marrow can be considered a valid prognostic parameter in patients with early disease. However, the classic prognostic factors remain highly relevant, and the newer breast cancer subtypes are also useful for this purpose.

Detection of disseminated tumor cells in locally advanced breast cancer patients before primary systemic therapy

AIM To assess the prevalence and prognostic power of disseminated tumor cells (DTC) in patients with locally advanced breast cancer (LABC) before primary systemic therapy (PST). MATERIALS AND METHODS LABC patients attending our Breast Unit were studied between 2002 and 2012, all of them being considered for PST. To determine the presence of DTC, posterior iliac crest aspirates were obtained and marrow samples were processed by gradient separation with Ficoll (Lymphoprep(®)) and immunohistochemical staining using the antiCK A45-B/B3 (EPIMET) antibody. Clinicopathologic variables were recorded before and after PST to assess response. Disease-free survival (DFS) and overall survival (OS) were determined after follow-up. The presence of DTC as a predictor of response to PST and as a prognostic tool for OS and DSF was evaluated. RESULTS DTC were observed in 26% of 47 patients included in the study. PST consisted of chemotherapy in 94% and hormone therapy in 6%. Breast-conserving therapy was attained in 33%. Mean follow-up was 68 months. Complete clinical response (CR) after PST was seen in 26%, disease recurrence in 38%, and cancer-related death in 8%; tumor size and negative estrogen receptors were significant predictors of CR and mastectomy was associated with DFS. Persistent axillary disease after PST and previous recurrence were predictive of OS. DTC were detected more often in patients who did not achieve CR and those who presented recurrence. DTC detection was a significant prognostic factor for a worse OS (OR = 7.62; CI95%: 1.46-39.61; p = 0.009) and a decreased survival time (62 versus 82 months, p = 0.004). CONCLUSION Presence of DTC before PST was found in a significant number of patients with LABC. DTC were found to be a significant prognostic factor for cancer-related death. DTC could be a surrogate predictor of response to PST and also of disease recurrence in LABC patients.

A prospective study of lymphocyte subpopulations and regulatory T cells in patients with chronic hepatitis C virus infection developing interferon‐induced thyroiditis

Objective  One of the side effects of interferon‐alpha (IFN‐α) therapy is interferon‐induced thyroiditis (IIT). The role of lymphocyte subpopulations in IIT remains to be defined. The aim of this study was to assess different peripheral blood lymphocyte subpopulations, mainly CD4+CD25+CD127low/‐FoxP3+ regulatory T cells (Tregs), in patients with chronic hepatitis C virus (HCV) infection who developed IIT.

Impacto de la disponibilidad de un servicio externo de medicina nuclear en la aplicación de la biopsia del ganglio centinela en cirugía del cáncer de mama

Resumen Introduccion La realizacion de la tecnica de la biopsia selectiva del ganglio centinela (BSGC) en el tratamiento del cancer de mama requiere disponer de un servicio de medicina nuclear (SMN) y de la validacion de su tecnica. El objetivo del presente estudio es analizar la posibilidad de realizar esta tecnica con un SMN externo ya validado, y estudiar su impacto en la indicacion de la linfadenectomia axilar radical (LAR) y en la estancia postoperatoria. Pacientes y metodos Estudio prospectivo en una cohorte de pacientes con cancer de mama a partir de la implantacion en nuestro centro de la tecnica de la BSGC gracias a la colaboracion de un SMN externo que realizaba la linfogammagrafia y la deteccion del ganglio centinela (GC), en tanto que su identificacion intraoperatoria se llevaba a cabo mediante una sonda portatil. Se analiza la viabilidad del proyecto y su impacto clinico tomando como resultados finales la disminucion del numero de linfadenectomias y la estancia hospitalaria. Resultados Se ha tratado a 196 pacientes, con 201 carcinomas de mama. Las intervenciones mayoritarias fueron la tumorectomia (TC) con BSGC en 124 casos (62%), y la TC con BSGC y LAR en 62 casos (31%). La visualizacion del GC en la linfogammagrafia se obtuvo en 187 de 201 casos (93,1%) y se ha detectado el GC durante la intervencion en 182 de los 187 (97,4%) casos. La deteccion de GC en la cadena mamaria interna se ha producido en 23 de los 201 casos (11,4%). Se ha evitado la LAR en 131 de los 201 casos (65%). La diferencia de dias de ingreso postoperatorio con o sin LAR fue de una media de 1,8 dias (3,1 frente a 1,3; p Conclusiones La tecnica de BSGC ha sido factible con la colaboracion de un SMN externo; se evito el 65% de las LAR y disminuyo la estancia media en 1,8 dias.

Biopsia selectiva del ganglio centinela en pacientes con carcinoma oral: estudio piloto

Fundamento y objetivo La tecnica del ganglio centinela (GC) aparece como una alter-nativa a la linfadenectomia completa en el tratamiento quirurgico de diversos tumores. Pacientes y metodo Estudio piloto sobre 32 pacientes consecutivos con cancer oral clinicamente N0, en los que la biopsia del GC fue comparada con los resultados del vaciamiento cervical. Resultados La localizacion del GC fue posible en 31 de los 32 casos (97%) y mostro una concordancia total con el vaciamiento cervical: 16 verdaderos negativos y 15 verdaderos positivos. Entre los 15 casos positivos, el GC fue el unico ganglio afectado en 11 (73%). Conclusiones La biopsia del GC es una tecnica capaz de predecir el estado de diseminacion linfatica subclinica en el cancer oral.

Regulatory T cells and other lymphocyte subpopulations in patients with melanoma developing interferon‐induced thyroiditis during high‐dose interferon‐α2b treatment

One of the side effects of interferon‐alpha therapy is interferon‐induced thyroiditis (IIT). The role of lymphocyte subpopulations in IIT melanoma patients remains to be defined.