Single-Stage Immediate Breast Reconstruction with Acellular Dermal Matrix after Breast Cancer: Comparative Study and Evaluation of Breast Reconstruction Outcomes.

We evaluate postoperative complications, aesthetic results and satisfaction outcomes in patients with breast cancer after intervening with a skin-sparing or nipple-sparing mastectomy with an immediate prosthetic reconstruction with or without a biological mesh. Patients with multifocal breast cancer, ductal carcinoma in situ with an indication for a mastectomy and cT2 tumors with no response to primary systemic treatment were included, whereas patients aged >75 years, with inflammatory carcinoma, and severe circulatory disorders were excluded. Patients in the control group were reconstructed using a prosthesis, whereas the study group included patients reconstructed using a prosthesis and biological acellular porcine dermal mesh (Strattice™). In both groups, the result was assessed using the BREAST-Q instrument. A total of 51 patients (62 intervened breasts) were included in the study group and 38 patients (41 intervened breasts) in the control group. Implant loss and removal occurred in three patients in the study group (5.9%) and nine patients in the control group (24.3%; p = 0.030). Infections appeared in three patients in the study group (4.8%) and three patients in the control group (7.3%; p = 1.00). Skin necrosis appeared in 5 patients in the study group (12.2%) and 11 patients in the control group (21.6%; p = 0.367). Seroma appeared in five patients in the study group (12.2%) and five patients in the control group (8.1%; p = 0.514). The BREAST-Q questionnaire is a comparison between both groups regarding "satisfaction with breasts after surgery" (p = 0.026), "sexual well-being after intervention" (p = 0.010) and "satisfaction with the information received" (p = 0.049). We have noted a statistically significant decrease in implant loss in women receiving an implant with a biological mesh. A higher satisfaction was observed in patients reconstructed using Strattice™, with statistically significant differences in three items.

Circulating levels of ß-endorphin and cortisol in breast cancer.

Neurobehavioral stress can promote the growth and progression of different types of cancer because psychological factors can alter immune and endocrine function. ß-endorphin is one of the hormones involved in the bidirectional connection between the immune and neuroendocrine systems that explains the effects of stress on the immune capacity against cancer. Breast cancer (BC) is the most common type of cancer in women and one of the best known to influence the different stressors involved in coping with the disease. Here we evaluated the circulating levels of ß-endorphin and cortisol in premenopausal and postmenopausal women with BC treated or not with neoadjuvant chemotherapy, to understand the neuroendocrine basis that explain the relationship between stress and the development of the disease. In our hands, healthy women show elevated levels of ß-endorphin, levels that are even higher in postmenopausal women. In women with BC, however, significantly lower levels appear, with no differences between premenopausal and postmenopausal women. These data correlate with cortisol levels, which are much higher in women with BC regardless of their hormonal status. Neoadjuvant chemotherapy treatment only improves ß-endorphin levels in postmenopausal women, without recovering the levels of healthy women. In women treated with neoadjuvant chemotherapy, both premenopausal and postmenopausal maintain elevated cortisol levels that are indicative of the stressful situation. Regulation of stress levels by modulation with ß-endorphin could be an alternative pharmacological therapy against tumor growth and development, as well as its ability to promote in patients feelings of well-being that improve the development of their disease.

Insulin-Regulated Aminopeptidase in Women with Breast Cancer: A Role beyond the Regulation of Oxytocin and Vasopressin.

Insulin-regulated aminopeptidase (IRAP) is the only enzyme known to cleave oxytocin and vasopressin; however, it is also the high-affinity binding site for angiotensin IV (AngIV) receptor type 4 (AT4) ligands and it is related to insulin-dependent glucose transporters through the translocation of the glucose transporter type 4 (GLUT4). Previous studies have demonstrated an association between IRAP activity and the number and size of mammary tumors in an animal model of breast cancer (BC). Also, a highly significant increase in IRAP activity has been found in BC tissue from women patients. Here, we found no changes in circulating IRAP in premenopausal (preMP) women, but it increased significantly in postmenopausal (postMP) women not treated with neoadjuvant chemotherapy (NACH). However, in women treated with NACH, IRAP activity increased in both preMP and postMP women. Two years of follow-up indicated lower levels of IRAP activity in untreated preMP women, but a return to control levels in untreated postMP women, while IRAP activity returned to control levels in women treated with NACH. Circulating oxytocin decreased in both preMP and postMP women during the follow-up period. Differences in Oxytocin appeared between preMP and postMP women treated with NACH, but not in women who were not treated with NACH. On the contrary, circulating vasopressin increased in untreated and treated preMP and postMP women, with most of the differences related to the hormonal status as well as the neoadjuvant treatment during the two year follow-up We propose that IRAP is involved in mechanisms related not only to oxytocin and/or vasopressin regulation, but also to the local mammary RAS through AngIV and its role in glucose transportation through the IRAP/GLUT4 system.

Neoadjuvant chemotherapy modifies serum pyrrolidone carboxypeptidase specific activity in women with breast cancer and influences circulating levels of GnRH and gonadotropins.

PURPOSE: Functional studies have demonstrated that gonadotropin-releasing hormone (GnRH) regulates cell proliferation, apoptosis, and tissue remodeling. GnRH is metabolized by the proteolytic regulatory enzyme pyrrolidone carboxypeptidase (Pcp) (E.C. 3.4.19.3), which is an omega peptidase widely distributed in fluids and tissues. We previously reported a decrease in both rat and human Pcp activity in breast cancer, suggesting that GnRH may be an important local hormonal factor in the pathogenesis of breast cancer. Recently, we have described that postmenopausal women with breast cancer show lower levels of serum Pcp activity than control postmenopausal women. To determine the effect of neoadjuvant chemotherapy (NACT) on serum Pcp specific activity and circulating levels of GnRH, luteinizing hormone (LH), follicle-stimulating hormone (FSH) and steroid hormones 17-ß-estradiol and progesterone in pre- and postmenopausal women diagnosed with infiltrating ductal carcinoma. METHODS: Serum Pcp activity was measured fluorometrically using pyroglutamyl-ß-naphthylamide. Circulating GnRH levels were dosed using a commercial RIA kit. Circulating LH and FSH levels were measured by enzyme immunoassays. Levels of steroid hormones were measured in serum samples by dissociation-enhanced lanthanide fluorescence immunoassay. RESULTS AND CONCLUSION: Our results show the effect of NACT on the hypothalamic-pituitary axis, with the consequent alteration of circulating gonadotropins in premenopausal women with breast cancer. However, the results obtained in postmenopausal women with breast cancer treated with NACT, that is, the significant decrease in the concentration of GnRH and FSH compared to control postmenopausal women, differ from those obtained for premenopausal women. The only difference between pre- and postmenopausal women is their hormonal profile at the beginning of the study, that is, the presence of menopause and the consequent alteration of the hypothalamic-pituitary-gonadal axis.

Redox status in the sentinel lymph node of women with breast cancer.

BACKGROUND: Lymphatic metastasis is regulated in multiple steps including the transit of tumor cells via the lymphatic vessels and the successful seeding in draining lymph nodes. Thus, several molecular signals and cellular changes must be involved in this complex process to facilitate tumor cell entry, colonization, and survival in the lymph node. To our knowledge, the present work explores, for the first time in the literature, the redox status (oxidative stress parameters and enzymatic and non-enzymatic antioxidant defense systems) in the sentinel lymph node (SLN) of women with breast cancer. PATIENTS AND METHODS: SLNs from 75 women with breast cancer were identified using the one-step nucleic acid amplification (OSNA) method as negative (n = 43), with micrometastases (n = 13), or with macrometastases (n = 19). It will allow us to gain knowledge about the pro-oxidant/antioxidant mechanisms involved in the processes of distant metastases in breast cancer and also to assess whether these parameters may be alternative techniques for staging. RESULTS: We found different levels of lipid peroxidation in SLNs with micrometastases (increased) and macrometastases (decreased), a decrease in carbonyl group content in SLNs with macrometastases only, and an increase in total antioxidant capacity (TAC) in SNLs with micrometastases and macrometastases. A decrease in the levels of reduced glutathione (GSH) also appears in the SLNs with macrometastases only. Finally, we show increased levels of superoxide dismutase (SOD) and catalase (CAT) activity in SLNs with micrometastases and macrometastases, and decreased levels of glutathione peroxidase (GPx) activity in SNLs with macrometastases but not with micrometastases. CONCLUSIONS: Redox status of lymph node microenvironment participates in the progression of metastatic breast cancer.

Intraoperative assessment of sentinel lymph node by one-step nucleic acid amplification in breast cancer patients after neoadjuvant treatment reduces the need for a second surgery for axillary lymph node dissection.

PURPOSE: Sentinel lymph node (SLN) biopsy has been shown to be both accurate and feasible for women who receive neoadjuvant chemotherapy (NAC). Intraoperative assessment of SLN by frozen sections can produce false negative results. The aim of this study was to compare two different techniques of intraoperative assessment of SLN in breast cancer patients treated with NAC: frozen section (FS) and molecular assay (OSNA). METHODS: A multicenter cohort of 320 consecutive breast cancer patients treated with NAC between 2010 and 2014 was analyzed. FS was performed intraoperatively in 166 patients (H&E cohort) and OSNA in 154 patients (OSNA cohort). RESULTS: A mean of 2.15 SLNs by FS and 1.22 SLNs by OSNA was assessed (p = 0.03). SLN metastasis was found in 44 patients (26.5%) by FS and in 48 (31.2%) by OSNA (p = 0.4). There was no statistical significance in rates of macrometastasis (75%), micrometastasis (20.5%) or ITCs (4.5%) when assessed by FS compared to OSNA (52.3%, 36.3% and 11.4%, respectively) (p = 0.06). There were 10 patients in the H&E cohort with positive-SLN in the definitive pathology assessment with negative intraoperative FS. When OSNA and definitive pathology were compared, there were no differences in rates of macrometastasis (61.1%), micrometastasis (33.3%) nor ITCs (5.6%) (p = 0.5). Fifty-four patients in the H&E cohort and 44 in the OSNA cohort had ALND after positive-SLNs. ALND was performed in a second surgery in 10 patients (18.5%) in the H&E cohort for intraoperative FS false negative results, 90% being micrometastasis. 42 out of 44 patients (95.5%) in the OSNA cohort had an ALND in the same surgery (p = 0.03). CONCLUSIONS: OSNA assay detects SLNs metastases as accurately as conventional pathology in the NAC setting. Intraoperative definitive assessment of the SLN by OSNA reduces the need for a second surgery for ALND in 18.5% of breast cancer patients with a positive-SLN after NAC.

Estudio comparativo del uso de implante mamario únicamente o implante y malla biológica en reconstrucción inmediata tras mastectomía ahorradora de piel / Comparative study of the use of immediate implant-based breast reconstruction with or without biological dermal mesh after skin-sparing mastectomy

Objetivo. Valorar las complicaciones postoperatorias en pacientes intervenidas mediante mastectomía ahorradora de piel o piel y aréola-pezón, con reconstrucción inmediata e implantación de prótesis o prótesis más malla biológica. Pacientes y métodos. Estudio prospectivo. Periodo de estudio: octubre de 2011-octubre de 2014. Criterios de inclusión: cáncer de mama multicéntrico, carcinoma ductal in situ con indicación de mastectomía y tumores cT2 que no tuvieron respuesta a tratamiento sistémico primario. Criterios de exclusión: edad > 75 años. Grupo control: pacientes reconstruidas mediante prótesis. Grupo estudio: pacientes reconstruidas mediante prótesis y malla biológica de dermis porcina acelular, no entrecruzada, de 1,6 mm e hidratada. Resultados. Se incluyeron en el grupo de estudio 34 pacientes, y en el grupo control, 38 pacientes. Extrusión de prótesis: grupo estudio uno (2,9%); grupo control 9 (23,7%) (p = 0,015). Infecciones: grupo estudio 3 (8,8%); grupo control 3 (7,9%) (p = 1). Necrosis cutánea: grupo estudio 5 (14,7%); grupo control 5 (13,2%) (p = 1). Seroma: grupo estudio 5 (14,7%); grupo control 5 (13,2%) (p = 1). Conclusión. Se ha observado una disminución significativa de la extrusión de la prótesis en las mujeres en las que se implantaron mallas biológicas. En seromas, infección y necrosis cutánea no observamos diferencias significativas (AU)

Objective. To evaluate postoperative complications after skin- or nipple-sparing mastectomy with immediate implant-based breast reconstruction with or without biological dermal mesh. Patients and methods. Prospective study. Study period: October 2011-October 2014. Inclusion criteria: multicentre breast cancer, ductal carcinoma in situ with indication for mastectomy, and cT2 tumours with no response to primary systemic treatment. Exclusion criteria: patients older than 75 years. Control group: breast reconstructions with mammary prosthesis exclusively. Study group: breast reconstructions with implant and non-crosslinked biological 1.6 mm hydrated acellular porcine dermal mesh. Results. Thirty-four patients were included in the treatment group and 38 patients in the control group. Number of prosthesis extrusions: study group one (2.9%); control group 9 (23.7%) (P = .015). Infections: study group 3 (8.8%); control group 3 (7.9%) (P = 1). Skin necrosis: study group 5 (14.7%); control group 5 (13.2%) (P = 1). Seroma: study group 5 (14.7%); control group 5 (13.2%) (P = 1). Conclusion. The number of extrusions was significantly lower in breast reconstructions with prosthesis and biological mesh. No significant differences were observed in seroma, infection, or skin necrosis (AU)

Tratamiento quirúrgico del tumor primario en pacientes con cáncer de mama en estadio IV / Surgical treatment of the primary tumor in stage iv breast cancer

INTRODUCCIÓN: El objetivo del estudio fue analizar el impacto de la cirugía locorregional en la supervivencia de pacientes con cáncer de mama estadio IV. PACIENTES Y MÉTODOS: Estudio retrospectivo que incluyó a pacientes con cáncer de mama y metástasis sincrónicas. Se excluyó a pacientes con ECOG superior a 2 y elevado riesgo anestésico-quirúrgico. Se evaluaron las siguientes variables: edad, tamaño tumoral, afectación ganglionar, tipo histológico, grado histológico, receptores hormonales, sobreexpresión de HER2, número de órganos afectos, localización de las metástasis y tratamiento quirúrgico. El impacto de la cirugía y las distintas variables clínico-patológicas sobre la supervivencia se analizó mediante un modelo de regresión de Cox. RESULTADOS: Se incluyó a 69 pacientes, de los que 36 (52,2%) fueron intervenidos quirúrgicamente (grupo estudio). Tras un seguimiento medio de 34 meses, la supervivencia media de la serie fue de 55 meses y no se encontraron diferencias significativas entre el grupo estudio y el grupo de pacientes sin intervención quirúrgica (p = 0,187). Se identificaron 2 factores relacionados con una peor supervivencia: el número de órganos con metástasis (HR = 1,69; IC 95%: 1,05- 2,71) y el cáncer triple negativo (HR = 3,49; IC 95%: 1,39-8,74). La cirugía locorregional, sin embargo, no se relacionó con la supervivencia. CONCLUSIONES: El tratamiento quirúrgico locorregional no se asoció con mayor supervivencia en pacientes con cáncer de mama en estadio IV. El número de órganos con metástasis y los tumores triple negativo fueron factores de mal pronóstico de supervivencia

INTRODUCTION: The aim of the study was to analyze the impact of loco-regional surgery on survival of patients with stage IV breast cancer. PATIENTS AND METHODS: Retrospective study that included patients with breast cancer and synchronous metastases. Patients with ECOG above 2 and high-risk patients were excluded. The following variables were evaluated: age, tumor size, nodal involvement, histological type, histological grade, hormone receptor status, HER2 overexpression, number of affected organs, location of metastases and surgical treatment. The impact of surgery and several clinical and pathologic variables on survival was analyzed by Cox regression model. RESULTS: A total of 69 patients, of whom 36 (52.2%) underwent surgery (study group) were included. After a mean follow-up of 34 months, the median survival of the series was 55 months and no significant differences between the study group and the group of patients without surgery (P=0.187) were found. Two factors associated with worse survival were identified: the number of organs with metastases (HR = 1.69, IC 95%: 1.05-2.71) and triple negative breast cancer (HR = 3.49, IC 95%: 1.39-8.74). Loco-regional surgery, however, was not associated with survival. CONCLUSIONS: Loco-regional surgical treatment was not associated with improved survival inpacientes with stage IV breast cancer. The number of organs with metastases and tumors were triple negative prognostic factors for survival

Angiosarcoma secundario de mama: recidiva multifocal en colgajo autólogo utilizado en la reconstrucción / Secondary breast angiosarcoma: Multifocal recurrence in a postmastectomy breast reconstruction flap

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[Surgical treatment of the primary tumor in stage IV breast cancer]. / Tratamiento quirúrgico del tumor primario en pacientes con cáncer de mama en estadio IV.

INTRODUCTION: The aim of the study was to analyze the impact of loco-regional surgery on survival of patients with stage IV breast cancer. PATIENTS AND METHODS: Retrospective study that included patients with breast cancer and synchronous metastases. Patients with ECOG above 2 and high-risk patients were excluded. The following variables were evaluated: age, tumor size, nodal involvement, histological type, histological grade, hormone receptor status, HER2 overexpression, number of affected organs, location of metastases and surgical treatment. The impact of surgery and several clinical and pathologic variables on survival was analyzed by Cox regression model. RESULTS: A total of 69 patients, of whom 36 (52.2%) underwent surgery (study group) were included. After a mean follow-up of 34 months, the median survival of the series was 55 months and no significant differences between the study group and the group of patients without surgery (P=0.187) were found. Two factors associated with worse survival were identified: the number of organs with metastases (HR=1.69, IC 95%: 1.05-2.71) and triple negative breast cancer (HR=3.49, IC 95%: 1.39-8.74). Loco-regional surgery, however, was not associated with survival. CONCLUSIONS: Loco-regional surgical treatment was not associated with improved survival inpacientes with stage IV breast cancer. The number of organs with metastases and tumors were triple negative prognostic factors for survival.

Circulating oxidative stress parameters in pre- and post-menopausal healthy women and in women suffering from breast cancer treated or not with neoadjuvant chemotherapy.

We evaluate here the redox status in pre- and post-menopausal healthy women and in women with breast cancer in order to understand the consequences of the hormonal alterations of menopause for the oxidative stress status, its modifications with breast cancer and the influence of neoadjuvant chemotherapy (NC). To that, serum oxidative stress parameters (total antioxidant capacity, lipid peroxidation and protein oxidation), non-enzyme antioxidant defenses (total glutathione, uric acid and bilirubin) and enzyme antioxidant defenses (superoxide dismutase, catalase and glutathione peroxidase activities) were measured in healthy women and in women with breast cancer divided according to their menopausal status and that received or not NC. Circulating estradiol, progesterone, FSH and LH were also analyzed. We found that menopause itself modifies the redox status of healthy women, being most of these differences also reflected in women with breast cancer. However, several changes occur as a consequence of the disease. Furthermore, NC increases oxidative damage, decreases antioxidant defenses and eliminates the differences found in menopause. We conclude that the normal redox balance is disrupted by breast cancer but is also affected by the hormonal status promoted by menopause. In fact, NC nullifies the differences found between pre- and postmenopausal women in several antioxidant defense systems.

Eficacia de la biopsia intraoperatoria del ganglio centinela mediante el método one step nucleic acid amplification para evitar la linfadenectomía axilar en mujeres con cáncer de mama tratadas previamente con quimioterapia neoadyuvante / Effectiveness of intra-operative sentinel node biopsy by one-step nucleic acid amplification to avoid axillary lymphadenectomy in women with breast cancer treated with neoadjuvant chemotherapy

Objetivos. Evaluar en pacientes con ganglios axilares clínicamente negativos de inicio, la efectividad de la biopsia selectiva del ganglio centinela (BSGC) intraoperatoria mediante el método one step nucleic acid amplification (OSNA) para detectar metástasis microscópicas o celulares tras quimioterapia neoadyuvante, y evitar la duplicidad de procedimientos quirúrgicos. Pacientes y métodos. Se evaluó la efectividad de la BSGC mediante OSNA en pacientes con cáncer de mama que previamente tenían una axila clínica y ecográficamente negativa tras quimioterapia neoadyuvante (44 pacientes) o antes de la quimioterapia neoadyuvante (33 pacientes). Resultados. La tasa de identificación del ganglio centinela (GC) fue del 100% en ambos grupos. En las pacientes con BSGC previa a la quimioterapia se detectaron 13 mujeres con ganglios positivos (11 macrometástasis y 2 micrometástasis). En las pacientes tratadas primero con quimioterapia, se detectaron 10 mujeres con GC positivos, que fueron todos macrometástasis. El valor predictivo negativo de la prueba de ultrasonidos fue del 60,6% en pacientes con BSGC previa a quimioterapia y del 77,3% en pacientes con quimioterapia y posterior BSGC. Conclusiones. La BSGC mediante el método OSNA en mujeres que presentan clínicamente ganglios linfáticos negativos tras haber recibido quimioterapia neoadyuvante predice el estado axilar con gran precisión. Permite de forma inmediata tomar decisiones sobre la indicación o no de realizar una linfadenectomía axilar, evitando así el retraso en la administración de la quimioterapia y beneficiándose las pacientes de un solo procedimiento quirúrgico(AU)

Objectives. To evaluate in patients with clinically negative axillary nodes at initial presentation, the effectiveness of sentinel lymph node biopsy (SLNB) using intraoperative the one step nucleic acid amplification (OSNA) method to detect microscopic metastases or isolated tumor cells after neoadjuvant chemotherapy. Thus, axillary dissection and duplication of surgical procedures will be avoided. Patients and methods. We evaluated in patients with breast cancer and clinically negative axilla, the effectiveness of SLNB by OSNA after neoadjuvant chemotherapy (44 patients) or prior to neoadjuvant chemotherapy (33 patients). Results. The rate of SLN identification was 100% in both groups. In patients with SLNB prior to systemic treatment, 13 women showed positive nodes (11 macrometastases and 2 micrometastases), and those with SLNB after neoadjuvant chemotherapy, positive SLNB were detected in 10 women, which were all of them macrometastases. The negative predictive value of ultrasonography was 60.6% in patients with SLNB prior to neoadjuvant therapy and 77.3% in patients with chemotherapy followed by SLNB. Conclusions. Intraoperative SLNB using OSNA in women with clinically negative axillary lymph nodes at initial presentation who received neoadjuvant chemotherapy, predicts axillary status with high accuracy. Also it allows immediately make decisions about the indication or not to perform an axillary dissection, thus avoiding delay in the administration of chemotherapy and benefit the patients for a single surgical procedure(AU)