Biopsia del ganglio centinela en pacientes con cáncer de mama operable tratadas con quimioterapia neoadyuvante / Sentinel lymph node biopsy in patients with operable breast cancer treated with neoadjuvant chemotherapy

Objetivo. Validar la biopsia selectiva del ganglio centinela (BGC) en pacientes con cáncer de mama tratadas con quimioterapia neoadyuvante. Materiales y métodos. Estudio prospectivo de enero de 2008 a enero de 2011, 88 pacientes con una edad media de 49,4 años, con cáncer de mama infiltrante T1-3, N0-1, M0, tratadas con epirrubicina/ciclofosfamida, docetaxel y trastuzumab en Her2/neu positivas. El estatus axilar se estableció por exploración física, ecografía axilar y punción ecoguiada de ganglios sospechosos. El día antes de la cirugía se inyectaron periareolarmente 74-111 MBq de 99mTc-nanocoloide de albúmina. En todas se realizó cirugía mamaria, BGC y linfadenectomía axilar. El ganglio centinela (GC) se analizó por cortes de congelación, hematoxilina-eosina, inmunohistoquímica u OSNA. Resultados. El tamaño medio del tumor fue de 3,5 cm. Según el tipo histológico, 69 se clasificaron como ductal infiltrante, 16 como lobulillar infiltrante y 3 como de otro tipo. Treinta y siete pacientes tenían axila clínica/ecográfica positiva al diagnóstico. La respuesta clínica del tumor primario fue: 38 completa, 45 parcial, 5 no respuesta. En todas las pacientes la axila fue clínica/ecográfica negativa después del tratamiento. En 25 casos hubo respuesta patológica completa en el tumor primario. El porcentaje de identificación del GC fue del 92,0%, 6 de las 7 pacientes sin migración eran axila clínica/ecográfica positiva al diagnóstico. En el 96,3% de los casos el GC determinó correctamente el estatus axilar. La tasa de falsos negativos fue del 8,3%. En el 69,4% de los casos el GC era el único afectado de la axila. El número medio de GC identificados fue 1,7 y el de ganglios axilares extirpados fue 13,2. Conclusión. La BGC es una técnica factible en pacientes con cáncer de mama tratadas con quimioterapia neoadyuvante, pudiendo evitar linfadenectomías innecesarias(AU)

Aim. To evaluate the accuracy of sentinel lymph node biopsy (SLNB) in operable breast cancer patients treated with neoadjuvant chemotherapy (NAC). Materials and methods. Between January 2008-2011, 88 women, mean age 49.4 years, with infiltrating breast carcinoma, were studied prospectively. Patients were T1-3, N0-1, M0. Prior to surgery, the patients received chemotherapy (epirubicin/cyclophosphamide, docetaxel), and trastuzumab in Her2/neu-positive patients. Axillary status was established by physical examination, ultrasound-guided core needle biopsy of any suspicious lymph node. The day before surgery, 74-111 MBq of 99mTc-albumin nanocolloid was injected periareolarly. All patients underwent breast surgery, with SLNB, followed by complete axillary lymph node dissection (ALND). Sentinel lymph node (SLN) were examined by frozen sections, hematoxylin-eosin staining and immunohistochemical analysis or One Step Nucleic Acid Amplification (OSNA). Results. Mean tumor size: 3.5 cm. Histologic type: 69 invasive ductal, 16 invasive lobular and 3 others. Thirty seven patients had clinical/ultrasound node-positive at presentation. Clinical response of primary tumor to NAC: complete in 38, partial in 45, and stable disease in 5 patients. A pathological complete response was achieved in 25. All patients were clinically node-negative after NAC. SLN identification rate was 92.0%. Six of 7 patients in whom SLN was not found had clinical/ultrasound positive axilla before NAC. SLN accurately determined the axillary status in 96.5%. False negative rate was 8.3%. In 69.4% of patients, SLN was the only positive node. The mean number of SLN removed was 1.7 and nodes resected from the ALND were 13.2. Conclusion. SLN biopsy after NAC can predict the axillary status with a high accuracy in patients with breast cancer, avoiding unnecessary ALND(AU)

Sentinel lymph node biopsy in patients with operable breast cancer treated with neoadjuvant chemotherapy.

AIM: To evaluate the accuracy of sentinel lymph node biopsy (SLNB) in operable breast cancer patients treated with neoadjuvant chemotherapy (NAC). MATERIALS AND METHODS: Between January 2008-2011, 88 women, mean age 49.4 years, with infiltrating breast carcinoma, were studied prospectively. Patients were T1-3, N0-1, M0. Prior to surgery, the patients received chemotherapy (epirubicin/cyclophosphamide, docetaxel), and trastuzumab in Her2/neu-positive patients. Axillary status was established by physical examination, ultrasound-guided core needle biopsy of any suspicious lymph node. The day before surgery, 74-111 MBq of (99m)Tc-albumin nanocolloid was injected periareolarly. All patients underwent breast surgery, with SLNB, followed by complete axillary lymph node dissection (ALND). Sentinel lymph node (SLN) were examined by frozen sections, hematoxylin-eosin staining and immunohistochemical analysis or One Step Nucleic Acid Amplification (OSNA). RESULTS: Mean tumor size: 3.5 cm. Histologic type: 69 invasive ductal, 16 invasive lobular and 3 others. Thirty seven patients had clinical/ultrasound node-positive at presentation. Clinical response of primary tumor to NAC: complete in 38, partial in 45, and stable disease in 5 patients. A pathological complete response was achieved in 25. All patients were clinically node-negative after NAC. SLN identification rate was 92.0%. Six of 7 patients in whom SLN was not found had clinical/ultrasound positive axilla before NAC. SLN accurately determined the axillary status in 96.5%. False negative rate was 8.3%. In 69.4% of patients, SLN was the only positive node. The mean number of SLN removed was 1.7 and nodes resected from the ALND were 13.2. CONCLUSION: SLN biopsy after NAC can predict the axillary status with a high accuracy in patients with breast cancer, avoiding unnecessary ALND.

Seguridad farmacológica y ambiental: disrupción endocrina / Drug and environmental safety: hyroid endocrine disruption

La exposición humana a compuestos químicos que interfieren con la homeostasis hormonal es bien conocida, a pesar de que la evidencia sea muy desigual para los distintos sistemas hormonales. Mientras que la disrupción endocrina de los esteroides (estrógenos y andrógenos) ha merecido gran atención, la de la homeostasis de las hormonas tiroideas está mal entendida, si se exceptúa lo que se refiere a la captación de yodo. La lista de disruptores endocrinos que interfieren con la síntesis, la circulación, la unión a receptores específicos, el metabolismo y la degradación de las hormonas tiroideas crece día a día. A los bifenilospoliclorados (PCB), las dioxinas y los furanos, se unen ahora los compuestos bromados retardadores de la llama, los bisfenoles y losftalatos. Cambios sutiles en las concentraciones de las hormonas tiroideas pueden ocasionar efectos adversos en períodos esenciales del desarrollo, de tal manera que se empieza a ver los efectos de tal exposición ahora, una vez que los mecanismos que ligan hormonastiroideas y neurodesarrollo son cada vez más evidentes ( AU)

Human exposure to environmental chemicals that disrupt endocrine homeostasis has been related to several hormone systems. Sex hormones (estrogen sand androgens) have received special attention, but thyroid hormone disruption is not so well known except in the special case of iodine intake deficiency. The list of chemicals that alter synthesis, circulation, binding to specific receptors, metabolism and degradation of thyroid hormones increases daily. Brominated flameretardants, bisphenols and phthalates are now included alongside polychlorinated biphenyls (PCBs), dioxins and furans. Subtle changes in circulating thyroid hormones may have undesirable effects during development. As our understanding of the role of thyroid hormones in neurodevelopment improves, exposure to environmental thyroid disruptors becomes a matter of increasing concern (AU)

Estrogen conjugates and serum factors mediating the estrogenic trophic effect on MCF-7 cell growth.

Estrogens stimulate growth of MCF-7 breast cancer cells in monolayer culture. Possible interference of serum factors leading to an estrogen-insensitive cell growth was analyzed in various experiments carried out on serum batches producing no estradiol stimulation. Out of five estrogen conjugates, only 3-glucurono-estradiol partly suppressed the inhibition of hydroxytamoxifen; the conjugate also reduced the estrogen receptor content of the cells, probably by a down regulation process ("processing"). Moreover, prolonged subcultures in dextran-coated charcoal-treated serum attempting to remove possible intracellular estrogens produced no growth stimulation. Interference by hormone carriers of the serum was ruled out by the fact that two strong synthetic estrogens, moxestrol and diethylstilbestrol with weak binding affinity for these carriers, were unstimulatory. Reduction of the carrier concentration also failed to confer any estrogen sensitivity. This lack of effect of most estrogen conjugates and serum carriers seems to contradict the hypothesis of their interference leading to an estrogen-insensitive growth. Presence in the serum of potential inhibitors towards estrogen action was also examined. Dilution of sera inducing an estrogenic stimulated growth failed to show any growth increase, either in the absence or presence of estradiol, thus excluding the possibility of a major influence of an antagonism on growth control. Moreover, clonogenic assays in soft agar eliminated the hypothesis that a difference between "active" (stimulatory with estradiol) and "inactive" serum batches may result from distinct adherence properties rather than from real growth stimulation. All of these data are consistent with the concept that serum factors which are not of estrogenic nature mediate the trophic effect of estradiol; their absence in some serum batches may lead to an estrogen-insensitive cell growth.

Induction of progesterone receptor in an estrogen, progesterone receptor-negative breast cancer cell line.

In MCF-7 cell culture, some sera endow estradiol-17 beta with strong growth promoting properties ("active" sera) while other fail to display this property ("inactive" sera). Passage from "inactive" to "active" sera are shown here to induce the appearance of a progestin binding capacity in the receptor negative line Evsa-T. Competition with various unlabeled steroids established the specificity of this binding reaction. The induction of progesterone receptor required neither estrogens, nor ER and failed to confer major growth sensitivity to hormonal steroids: only medroxyprogesterone acetate was slightly inhibitory at high concentration. These observations disclose the influence of seric factors independent of estrogens and of ER-related mechanisms on PgR induction.

Assay for estrogen and progesterone receptors of breast cancer cell lines in monolayer culture.

A whole-cell assay for measuring estrogen (ER) and progesterone (PgR) receptors in monolayer culture of human breast cancer cell lines is described. It is based on the measurement of incorporated tritiated ligands during 50 min of incubation (i.e. [3H]estradiol for ER, [3H]ORG-2058 for PgR). The assay fulfills all criteria of specificity as shown by competitive studies and measurements of the dissociation constants of the binding reactions. Moreover, a subcellular fractionation of MCF-7 labeled cells revealed that the majority of incorporated steroids was associated with the nuclear fraction. This finding is consistent with the concept of nuclear location of steroid-receptor complexes. Cultures in the presence of 10(-8) M estradiol indicated that the methodology is adequate for detecting the well-known estrogenic induction of PgR synthesis. The assay proved suitable for the quantitative assessment of the receptor content of various neoplastic (MCF-7; ZR-75-1, Cama-1, Evsa-T) and non-neoplastic (HBL-100) cell lines. The methodology has the other advantages of being simple and rapid, of requiring small amounts of cells and of allowing histological examination of the latter before, during and after biochemical analysis.

[CEA and TPA in cancer of the breast. Findings and criteria of use]. / CEA y TPA en cáncer de mama. Hallazgos y criterios de utilización.

In breast cancer, under rigorous and normalized conditions, the blood levels of carcinoembryonic antigen (CEA) and tissue polypeptide antigen (TPA) allow us: to differentiate with enough precision, in treated patients, the presence of tumour (EP) from illness-free situation (NED); to alert about the appearance of metastases and/or local relapse in patients put under systematic postoperative evolutional control; to evaluate the systemic palliative treatment response in patients with metastatic breast cancer and to formulate, in this case, prognostic predictions. Blood levels of CEA and TPA are, otherwise, unsuitable: to detect with accuracy the primary tumour presence; to warn about the risk of subclinical tumour existence (in treated patients in NED situation); to predict, in this last case, the chemotherapeutic treatment response, and to prevent about local relapses development. The independent but combined use of both antigens, appreciably raises the diagnostic success percentage with regard to that obtained when only one tumour marker was used.