Does the Sequence of Anthracycline and Taxane Matter? The NeoSAMBA Trial.

BACKGROUND: Taxanes usually follow anthracyclines in breast cancer neo/adjuvant treatment, likely because of their later introduction into clinical practice. However, there is no biological rationale that justifies this current standard of care. We compared a taxane followed by an anthracycline-based regimen with the reverse sequence in the neoadjuvant setting. PATIENTS AND METHODS: In a randomized, open-label, single-center phase II trial, women with inoperable, locally advanced, HER2-negative breast cancer were stratified by hormone receptor status and randomized to three cycles of docetaxel (T) followed by three cycles of fluorouracil, doxorubicin, and cyclophosphamide (FAC) versus three cycles of FAC followed by three cycles of docetaxel. Surgery, radiotherapy, and adjuvant hormonal therapy were administered as per local guidelines. The primary endpoint was pathological complete response (pCR), and secondary endpoints included toxicity, event-free survival (EFS), and overall survival (OS). RESULTS: Treatment sequence did not improve pCR, which was 7% with T-FAC and 3% with FAC-T. However, after a median follow-up of 79 months, the 5-year EFS rate was 75.7% (95% confidence interval [CI], 65.4%-87.7%) with T-FAC and 48.2% (95% CI, 37.0%-62.7%) with FAC-T (hazard ratio [HR], 0.46; 95% CI, 0.26-0.81; log-rank p = .0054), and the 5-year OS rate was 89.7% (95% CI, 82.2%-97.8%) with T-FAC and 64.7% (95% CI, 53.6%-78.1%) with FAC-T (HR, 0.41; 95% CI, 0.22-0.78; p = .0052). There were no unexpected toxicities. CONCLUSION: We showed for the first time an improvement in EFS and OS with taxane-first compared with anthracycline-first sequencing chemotherapy in HER2-negative, locally advanced breast cancer. Confirmation of these results may have implications for clinical practice. This trial was registered with Clinicatrials.gov identifier NCT01270373. IMPLICATIONS FOR PRACTICE: The NeoSAMBA trial showed a benefit for taxane-first sequencing chemotherapy consistent with the systematic review of the literature as well as the larger Neo-tAnGo study. Many recent and current ongoing clinical trials have already followed this treatment strategy. As a taxane-before-anthracycline sequence carries neither an incremental cost nor an increased toxicity, and given the available literature on this issue, reinforced that taxane-first regimen can be easily incorporated into daily clinical practice while awaiting confirmation of these findings from larger trials.

The Challenge of Evaluating Adnexal Masses in Patients With Breast Cancer.

This narrative literature review addresses the problem of an adnexal mass discovered during the course of breast cancer (BC) care, which may represent a benign condition, a metastatic process, or a primary ovarian cancer (OC), clinical scenarios associated with distinct physiopathology and prognosis. Furthermore, the coexistence of BC and OC in the same patient may be owing to a hereditary disorder, deserving specific management strategies and counseling. The initial detection and evaluation of an adnexal mass in a patient with BC requires a high index of suspicion, and the initial workup should include a thorough medical history and physical examination, measurement of tumor markers, complete blood count, and imaging tests. Transvaginal ultrasonography remains the standard tool, and findings suggestive of malignancy include bilateral tumors, thick septations, predominance of a solid component, Doppler flow to the solid component, and ascites. From the pathology point of view, features that are suggestive of metastatic disease include bilaterality, mild ovarian enlargement, vascular emboli, no omental deposits, and the absence of transition from benign to malignant epithelium. Although there is a considerable overlap in OC and BC immunohistochemical profiles, BC usually stain positive for GCDFP-15 and negative for vimentine, PAX8, and WT1, and OC often stain positive for CK7, PAX8, WT1, and to mesothelin. Genetic counselling should always be indicated in this clinical scenario. In conclusion, diagnostic spectrum of an ovarian mass in a patient with BC is broad, and a systematic multi-professional strategy is necessary to conduct these challenging cases.

T cells induce pre-metastatic osteolytic disease and help bone metastases establishment in a mouse model of metastatic breast cancer.

Bone metastases, present in 70% of patients with metastatic breast cancer, lead to skeletal disease, fractures and intense pain, which are all believed to be mediated by tumor cells. Engraftment of tumor cells is supposed to be preceded by changes in the target tissue to create a permissive microenvironment, the pre-metastatic niche, for the establishment of the metastatic foci. In bone metastatic niche, metastatic cells stimulate bone consumption resulting in the release of growth factors that feed the tumor, establishing a vicious cycle between the bone remodeling system and the tumor itself. Yet, how the pre-metastatic niches arise in the bone tissue remains unclear. Here we show that tumor-specific T cells induce osteolytic bone disease before bone colonization. T cells pro-metastatic activity correlate with a pro-osteoclastogenic cytokine profile, including RANKL, a master regulator of osteoclastogenesis. In vivo inhibition of RANKL from tumor-specific T cells completely blocks bone loss and metastasis. Our results unveil an unexpected role for RANKL-derived from T cells in setting the pre-metastatic niche and promoting tumor spread. We believe this information can bring new possibilities for the development of prognostic and therapeutic tools based on modulation of T cell activity for prevention and treatment of bone metastasis.

[Underestimation of malignancy of core needle biopsy for nonpalpable breast lesions]. / Grau de subestimação histopatológica por core biopsy de lesões não palpáveis da mama.

PURPOSE: To determine the rate of underestimation of an image-guided core biopsy of nonpalpable breast lesions, with validation by histologic examination after surgical excision. METHODS: We retrospectively reviewed 352 biopsies from patients who were submitted to surgery from February 2000 to December 2005, and whose histopathologic findings were recorded in the database system. Results were compared to surgical findings and underestimation rate was determined by dividing the number of lesions that proved to be carcinomas at surgical excision by the total number of lesions evaluated with excisional biopsy. Clinical, imaging, core biopsy and pathologic features were analyzed to identify factors that affect the rate of underestimation. The degree of agreement between the results was obtained by the percentage of agreement and Cohen's kappa coefficient. The association of variables with the underestimation of the diagnosis was determined by the chi-square, Fisher exact, ANOVA and Mann-Whitney U tests. The risk of underestimation was measured by the relative risk (RR) together with the respective 95% confidence intervals (95%CI). RESULTS: Inconclusive core biopsy findings occurred in 15.6% of cases. The histopathological result was benign in 26.4%, a high-risk lesion in 12.8% and malignant in 45.2%. There was agreement between core biopsy and surgery in 82.1% of cases (kappa=0.75). The false-negative rate was 5.4% and the lesion was completely removed in 3.4% of cases. The underestimation rate was 9.1% and was associated with BI-RADS® category 5 (p=0,01), microcalcifications (p CONCLUSIONS: The core breast biopsy under image guidance is a reliable procedure but the recommendation of surgical excision of high-risk lesions detected in the core biopsy remains since it was not possible to assess clinical, imaging, core biopsy and pathologic features that could predict underestimation and avoid excision. Representative samples are much more important than number of fragments.

Grau de subestimação histopatológica por core biopsy de lesões não palpáveis da mama / Underestimation of malignancy of core needle biopsy for nonpalpable breast lesions

OBJETIVO: Determinar o grau de subestimação de core biopsy, guiada por imagem, de lesões impalpáveis da mama subsequentemente submetidas à exérese cirúrgica. MÉTODOS: Foram revisados retrospectivamente 352 casos com biópsias de fragmento que foram submetidos à cirurgia entre fevereiro de 2000 e dezembro de 2005, cujo laudo histopatológico estava registrado no sistema interno de informação. Os resultados foram comparados com os da cirurgia e a taxa de subestimação foi calculada dividindo-se o número de carcinoma in situ e/ou invasivo à cirurgia pelo número de lesões de alto risco ou carcinoma in situ que foram submetidas à cirurgia. O grau de concordância entre os resultados foi obtido pelo percentual de concordância e pelo coeficiente kappa de Cohen. A associação das variáveis estudadas com a subestimação do diagnóstico foi verificada pelos testes do c2 exato de Fisher, ANOVA e Mann-Whitney U. O risco de subestimação foi medido por meio do risco relativo acompanhado dos respectivos intervalos com 95 por cento de confiança (IC95 por cento). RESULTADOS: Core biopsy foi inconclusiva em 15,6 por cento. O laudo histopatológico foi benigno em 26,4 por cento, sugestivo de lesão de alto risco em 12,8 por cento e maligno em 45,2 por cento. A concordância entre a core biopsy e a cirurgia foi de 82,1 por cento (kappa=0,75). A taxa de falso negativo foi de 5,4 por cento e a lesão foi completamente removida em 3,4 por cento. A taxa de subestimação foi de 9,1 por cento e esteve associada com BI-RADS® categoria 5 (p=0,01), microcalcificações (p < 0,001) e estereotaxia (p= 0,002). Todos os casos subestimados apresentavam diâmetro menor que 20 mm e em todos foram retirados pelo menos cinco fragmentos. A taxa de subestimação para lesões de alto risco foi de 31,1 por cento, 41,2 por cento, para hiperplasia ductal atípica, 31,2 por cento para lesões papilíferas, 16,7 por cento para tumor filóides e 41,9 por cento para carcinoma ductal in situ. CONCLUSÕES: Core biopsy guiada por imagem é um procedimento confiável, contudo permanece a recomendação de ressecção cirúrgica de lesões de alto risco detectadas à biópsia de fragmento já que não foi possível estabelecer características clínicas, imaginológicas, do procedimento e patológicas que pudessem predizer subestimação e evitar a cirurgia. Amostras representativas da lesão são mais importantes que o número de fragmentos.

PURPOSE: To determine the rate of underestimation of an image-guided core biopsy of nonpalpable breast lesions, with validation by histologic examination after surgical excision. METHODS: We retrospectively reviewed 352 biopsies from patients who were submitted to surgery from February 2000 to December 2005, and whose histopathologic findings were recorded in the database system. Results were compared to surgical findings and underestimation rate was determined by dividing the number of lesions that proved to be carcinomas at surgical excision by the total number of lesions evaluated with excisional biopsy. Clinical, imaging, core biopsy and pathologic features were analyzed to identify factors that affect the rate of underestimation. The degree of agreement between the results was obtained by the percentage of agreement and Cohen's kappa coefficient. The association of variables with the underestimation of the diagnosis was determined by the chi-square, Fisher exact, ANOVA and Mann-Whitney U tests. The risk of underestimation was measured by the relative risk (RR) together with the respective 95 percent confidence intervals (95 percentCI). RESULTS: Inconclusive core biopsy findings occurred in 15.6 percent of cases. The histopathological result was benign in 26.4 percent, a high-risk lesion in 12.8 percent and malignant in 45.2 percent. There was agreement between core biopsy and surgery in 82.1 percent of cases (kappa=0.75). The false-negative rate was 5.4 percent and the lesion was completely removed in 3.4 percent of cases. The underestimation rate was 9.1 percent and was associated with BI-RADS® category 5 (p=0,01), microcalcifications (p CONCLUSIONS: The core breast biopsy under image guidance is a reliable procedure but the recommendation of surgical excision of high-risk lesions detected in the core biopsy remains since it was not possible to assess clinical, imaging, core biopsy and pathologic features that could predict underestimation and avoid excision. Representative samples are much more important than number of fragments.

Carcinoma medular da mama: correlação anátomo-radiológica / Medullary breast carcinoma: anatomo-radiological correlation", "_i": "en

OBJETIVO: Avaliar as características radiológicas do câncer de mama medular em pacientes submetidas atratamento cirúrgico no Instituto Nacional de Câncer (INCA) û Ministério da Saúde, Rio de Janeiro, RJ, correlacionando os achados com estudo histopatológico. MATERIAIS E MÉTODOS: Foi realizado estudo descritivo retrospectivo de mulheres submetidas a tratamento cirúrgico no INCA, no período de janeiro de 1997 adezembro de 2006, para identificação das pacientes com carcinoma medular e análise dos achados radiológicos.RESULTADOS: Foram identificadas 21.287 pacientes com diagnóstico de carcinoma neste período, sendo 76 pacientes com diagnóstico de carcinoma medular típico (0,357%). Nessas pacientes selecionadas, a idade média foi de 51,9 anos (32 a 81 anos). Dezenove pacientes apresentavam lesão na mamografia, sendo 17 (89,5%) nódulos e 2 assimetrias focais (10,5%). Entre as pacientes com nódulo, 15 (88,1%) apresentavam alta densidade e 2 eram isodensos (11,9%). Doze pacientes apresentavam achados ultra-sonográficos e, destas, 11 (91,6%) apresentavam nódulos hipoecóicos. Foi observada uma paciente com nóduloanecóico com áreas de degeneração cística. CONCLUSÃO: O nódulo foi o achado radiológico dominante (89,5%), dos quais 88,1% apresentaram nódulos com alta densidade e margens circunscritas. Apesar das características radiológicas de benignidade, um nódulo com alta densidade, sólido, margens circunscritas e crescimento rápido deve ser investigado para confirmar o diagnóstico.

OBJECTIVE: To evaluate radiological findings in patients submitted to surgical treatment for medullary breast cancer at Instituto Nacional de Câncer (INCA), Rio de Janeiro, RJ, Brazil, correlating them with histological results. MATERIALS AND METHODS: A retrospective descriptive study was developed with patients submitted to surgery at INCA, in the period from January 1997 to December 2006, for identifying the presence of medullary breast carcinoma and analyzing radiological findings. RESULTS: Among 21,287 patients diagnosed with carcinoma, 76 (0.357%) had typical medullary breast carcinoma. The age range of these patients was 32û81 years (mean = 59.1 years). Mammography demonstrated lesions in 19 of these patients, 17 (89.5%) of them with masses, and 2 with focal asymmetry. Among the patients with masses, 15 (88.1%) presented with high density and 2 (11.9%) with isodensity. Twelve patients presented sonographic findings, 11 (91.6%) of them with hypoechoic masses, and one with an anechoic mass with areas of cystic degeneration. CONCLUSION: Nodular mass was the predominant radiological finding (89.5%), 88.1% of them corresponding to masses with high density and circumscribed margins. Despite the radiological characteristics of benignity, a solid, fastgrowing, highly dense mass with circumscribed margins should be further investigated to confirm the diagnosis.

Breast Imaging Reporting and Data System - BI-RADS®: valor preditivo positivo das categorias 3, 4 e 5. revisão sistemática da literatura / Breast Imaging Reporting and Data System - BI-RADS®: positive predictive value of categories 3, 4 and 5. A systematic literature review

OBJETIVO: Avaliar artigos, na literatura, que verificam o valor preditivo positivo das categorias 3, 4 e 5 do Breast Imaging Reporting and Data System (BI-RADS®). MATERIAIS E MÉTODOS: Foi realizada pesquisa na base de dados Medline utilizando os termos "predictive value" e "BI-RADS". Foram incluídos 11 artigos nesta revisão. RESULTADOS: O valor preditivo positivo das categorias 3, 4 e 5 variou entre 0 por cento e 8 por cento, 4 por cento e 62 por cento, 54 por cento e 100 por cento, respectivamente. Três artigos avaliaram, concomitantemente, os critérios morfológicos das lesões que apresentaram maior valor preditivo positivo na mamografia, sendo nódulo espiculado o critério com maior valor preditivo positivo. CONCLUSÃO: Houve grande variabilidade do valor preditivo positivo das categorias 3, 4 e 5 do BI-RADS® em todos os estudos, porém foram identificadas diferenças metodológicas que limitaram a comparação desses estudos.

OBJECTIVE: To review the literature about the positive predictive value of Breast Imaging Reporting and Data System (BI-RADS®) categories 3, 4 and 5. MATERIALS AND METHODS: A research was performed in the online Medline database, entering the terms "predictive value" and "BI-RADS". Eleven studies were included in this review. RESULTS: The positive predictive values ranged respectively between 0 percent and 8 percent, 4 percent and 62 percent, and 54 percent and 100 percent for BI-RADS® categories 3, 4 and 5. Three studies have also evaluated morphological criteria with higher positive predictive value in mammography, mass with spiculated margins being the finding with highest positive predictive value for malignancy. CONCLUSION: A high variability was found in the reviewed literature among positive predictive values of BI-RADS® categories 3, 4 and 5, although methodological differences have been identified, limiting the comparative analysis.