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.

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

BACKGROUND: The 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. METHODS: 104 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. RESULTS: Lymph 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%). CONCLUSIONS: Tumor 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.

Effects of two variants of Roux-en-Y Gastric bypass on metabolism behaviour: focus on plasma ghrelin concentrations over a 2-year follow-up.

BACKGROUND: To study the effects of two variants of Roux-en-Y gastric bypass (RYGBP) on plasma ghrelin concentrations according to different exposure of gastric fundus to the nutrient pathway. METHODS: A prospective longitudinal 2-year follow-up study was conducted. Ninety-six morbidly obese (MO) patients (age range: 41.6 +/- 9.6 years, body mass index: 53 +/- 9.5 kg/m(2)) were assigned to two bariatric surgical (BS) procedures: one that preserves food contact with gastric fundus (ringed RYGBP, n = 50) and the other that avoids it (modified RYGBP, n = 46). Different anthropometric and biochemical parameters were studied, focusing on ghrelin concentrations at baseline and 6, 12, and 24 months post-BS. RESULTS: At 24 months post-BS, all metabolic parameters studied had improved in all patients compared with those at 1-year follow-up and baseline (p < 0.05). However, high-density lipoprotein cholesterol concentrations took 2 years to normalise in 80% of patients, interleukin-6 decreased significantly in relation to baseline only after 2 years from BS (p < 0.001), and tumour necrosis factor alpha concentrations did not significantly decrease during the 2 years of follow-up. Plasma ghrelin concentrations increased in both surgical groups compare to baseline during the first year (24.6% in modified RYGBP and 36.62% in ringed RYGBP) and remained stable at the second year of follow-up, with no statistical differences between groups. CONCLUSIONS: In the second year of follow-up after BS, morbidity continued to improve in MO patients despite a lesser weight loss in relation to the first year. An increase in plasma ghrelin concentrations was found, regardless of nutrient contact with gastric fundus. Furthermore, changes in plasma ghrelin concentrations appeared to be independent of weight loss.

Is it possible to refine the indication for sentinel node biopsy in high-risk ductal carcinoma in situ?

BACKGROUND: The indication for sentinel node biopsy (SNB) has not been fully established yet for patients with ductal carcinoma in situ (DCIS). AIM: To relate the conversion rate to invasive carcinoma with sentinel node positivity in high risk DCIS, and to refine the clinical presentation analysis in order to better select patients for SNB. For this purpose, a risk score was devised. METHODS: From 1998 to 2005, 151 high-risk DCIS patients from six clinical centres were included in a prospective sentinel node database. The conversion rate to invasive carcinoma was 39%. Ten of 142 (7%) successful SNBs showed a positive sentinel node (eight micrometastatic). The sentinel node was positive in 1% of pure DCIS, in 5.5% of DCIS with micro-invasion, and in 19.5% of invasive carcinoma. RESULTS: Both clinical presentation and corresponding risk score were closely related to conversion to invasive carcinoma. The association of risk score and sentinel node positivity approached but did not reach statistical significance (P=0.06); therefore a subset of further selected higher risk patients could not be defined. CONCLUSION: The relevance of SNB positivity cannot be overlooked in high-risk DCIS patients, however, because SNB is not free from morbidity and cost, more studies are needed to refine its final indication.

Radiolocalización de lesiones mamarias no palpables combinada con la biopsia del ganglio centinela en mujeres con cáncer de mama / Radio-guided occult lesion localization combined with sentinel node biopsy in women with breast cancer

Introducción. La modalidad intralesional de inyección de los radiocoloides en la biopsia del ganglio centinela (BGC) permite la localización de tumores mamarios primitivos no palpables, en un mismo acto quirúrgico, mediante la técnica conocida como ROLL. Pacientes y método. Presentamos nuestra experiencia con la combinación de ambas técnicas (BGC y ROLL). Se analizó retrospectivamente a 233 pacientes: en 65 pacientes se practicó ROLL y en 168 la lesión fue localizada mediante la inserción de guías metálicas (grupo control). Ambos grupos eran comparables en cuanto a sus variables anatomorradiológicas. Resultados. La resección de la lesión se llevó a cabo en un solo tiempo en 169 pacientes. No se observaron diferencias significativas entre ambos grupos en cuanto a la afección de los márgenes quirúrgicos (márgenes correctos del 80% con ROLL frente al 69,9% sin ROLL) ni en el diámetro máximo de la pieza (6,85 frente a 6,52 cm, respectivamente). Conclusión. En pacientes sometidas a la BGC con lesiones mamarias no palpables, la técnica ROLL es una alternativa a las guías metálicas que ofrece una mayor facilidad para la exéresis y más comodidad para la paciente (AU)

Introduction. The practice of intratumoral radiocolloid injection for sentinel node biopsy (SNB) allows localization of nonpalpable breast tumors in the same surgical intervention, using the technique known as radio-guided occult lesion localization (ROLL). Patients and method. We present our experience with the combined use of both techniques (SNB and ROLL). A total of 233 patients were retrospectively analyzed: 65 patients underwent ROLL and 168 patients underwent wire-guided localization (control group) as the excision modality. Both groups had comparable pathologic and radiologic features. Results. Complete excision of the lesion was achieved at the first attempt in only 169 patients. There were no significant differences among groups in surgical margin status (margins were adequate in 80% of ROLL patients vs 69.9% of non-ROLL patients) or in maximum specimen diameter (6.85 cm vs 6.52 cm, respectively). Conclusion. We conclude that ROLL is an acceptable alternative to wire-guided localization in patients with nonpalpable breast tumors undergoing SNB, leading to easier lesion excision and greater patient comfort (AU)

[Radio-guided occult lesion localization combined with sentinel node biopsy in women with breast cancer]. / Radiolocalización de lesiones mamarias no palpables combinada con la biopsia del ganglio centinela en mujeres con cáncer de mama.

INTRODUCTION: The practice of intratumoral radiocolloid injection for sentinel node biopsy (SNB) allows localization of nonpalpable breast tumors in the same surgical intervention, using the technique known as radio-guided occult lesion localization (ROLL). PATIENTS AND METHOD: We present our experience with the combined use of both techniques (SNB and ROLL). A total of 233 patients were retrospectively analyzed: 65 patients underwent ROLL and 168 patients underwent wire-guided localization (control group) as the excision modality. Both groups had comparable pathologic and radiologic features. RESULTS: Complete excision of the lesion was achieved at the first attempt in only 169 patients. There were no significant differences among groups in surgical margin status (margins were adequate in 80% of ROLL patients vs 69.9% of non-ROLL patients) or in maximum specimen diameter (6.85 cm vs 6.52 cm, respectively). CONCLUSION: We conclude that ROLL is an acceptable alternative to wire-guided localization in patients with nonpalpable breast tumors undergoing SNB, leading to easier lesion excision and greater patient comfort.

Intraoperative assessment of sentinel lymph nodes in patients with breast carcinoma: accuracy of rapid imprint cytology compared with definitive histologic workup.

BACKGROUND: As sentinel lymph node biopsy (SNB) becomes a new surgical standard in the treatment of patients with breast carcinoma, there is an emergent need for a fast and accurate method with which to assess the SN intraoperatively, so a decision can be made regarding whether to perform axillary lymph node dissection during primary surgery. In the current study, the authors performed a prospective investigation of the relative merits of imprint cytology for that purpose. METHODS: Seventy-six patients with T1-T2 breast carcinoma were included after undergoing successful SNB. SNs were freshly sectioned at 2-mm intervals and imprint smears were obtained from all cut surfaces. The smears were examined using a rapid May-Grünwald-Giemsa stain variation, and the SNs were judged to be positive or negative for metastases. SNs later were submitted for paraffin embedding and serial sectioning. Both hematoxylin and eosin stained and cytokeratin (CK) immunostained sections were examined. The postoperative evaluation of the SNs was taken as the gold standard. RESULTS: Intraoperative cytology showed a sensitivity of 67.7%, a specificity of 100%, an accuracy of 86.8%, and a negative predictive value of 81.8%. The majority of false-negative cases (8 of 10 cases) were due to micrometastasis in the SNs that were discovered only after exhaustive examination with serial sectioning and CK immunostaining. CONCLUSIONS: The results of the current study demonstrate that the accuracy of imprint cytology is high enough to warrant its use for intraoperative SN assessment. If the findings are negative, axillary lymph node dissection can be omitted. Only a few patients with SN micrometastasis may require reoperation.