ABSTRACT
Neoadjuvant chemotherapy (NAT) in breast cancer (BC) has been used to reduce tumor burden prior to surgery. However, the impact on prognosis depends on the establishment of Pathological Complete Response (pCR), which is influenced by tumor-infiltrating lymphocyte levels and the activation of the antitumor immune response. Nonetheless, NAT can affect immune infiltration and the quality of the response. Here, we showed that NAT induces dynamic changes in the tumor microenvironment (TME). After NAT, an increase of regulatory T cells and a decrease of CD8+ T cells was found in tumor, correlated with the presence of metastatic cells in lymph nodes. In addition, an increase of polymorphonuclear myeloid-derived suppressor like cells was found in luminal patients post-NAT. pCR patients showed a balance between the immune populations, while non-pCR patients presented an inverse relationship in the frequency of CD68+ versus CD3+, CD8+, and CD20+ cells. Moreover, activated T cells were found in peripheral blood, as well as an increase in T cell clonality with a lower diversity post-NAT. Overall, these results shown that NAT induces an activation of immune response, however, a balance in the TME seems to be related to a better antigenic presentation and therefore a better response to treatment.
Subject(s)
Breast Neoplasms , Neoadjuvant Therapy , Breast Neoplasms/pathology , CD8-Positive T-Lymphocytes , Female , Humans , Lymphocytes, Tumor-Infiltrating , Neoadjuvant Therapy/methods , Tumor MicroenvironmentABSTRACT
The main cause of death by cancer is metastasis rather than local complications of primary tumors. Recent studies suggest that breast cancer stem cells (BCSCs), retains the ability to self-renew and differentiate to repopulate the entire tumor, also, they have been associated with resistance to chemotherapy and tumor recurrence, even after tumor resection. Chemotherapy has been implicated in the induction of resistant phenotypes with highly metastatic potential. Naturally occurring compounds, especially phytochemicals such as P2Et, can target different populations of cancer cells as well as BCSC, favoring the activation of immune response via immunogenic tumor death. Here, we evaluated the presence of BCSC as well as markers related to drug resistance in tumors obtained from 78 patients who had received (or not) chemotherapy before surgery. We evaluated the ex vivo response of patient tumor-derived organoids (or mammospheres) to chemotherapy alone or in combination with P2Et. A xenotransplant model engrafted with MDA-MB-468 was used to evaluate in vivo the activity of P2Et, in this model P2Et delay tumor growth. We show that patients with luminal and TNBC, and those who received neoadjuvant therapy before surgery have a higher frequency of BCSC. Further, the treatment with P2Et in mammospheres and human breast cancer cell lines improve the in vitro tumor death and decrease its viability and proliferation together with the release of immunogenic signals. P2Et could be a good co-adjuvant in antitumor therapy in patients, retarding the tumor growth by enabling the activation of the immune response.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/pharmacology , Breast Neoplasms/drug therapy , Caesalpinia/chemistry , Neoplasm Recurrence, Local/drug therapy , Neoplastic Stem Cells/drug effects , Phytochemicals/pharmacology , Plant Extracts/pharmacology , Adult , Aged , Animals , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Cell Line, Tumor , Drug Resistance, Neoplasm/drug effects , Female , Humans , Mice, Inbred NOD , Middle Aged , Neoadjuvant Therapy/methods , Neoplasm Recurrence, Local/metabolism , Neoplasm Recurrence, Local/pathology , Neoplastic Stem Cells/metabolism , Xenograft Model Antitumor AssaysABSTRACT
PURPOSE: Clinical breast examination (CBE) is an important step in the assessment of patients with breast-related complaints. We developed a standardized simulation and multimedia-based (SSMBI) curriculum using current evidenced-based recommendations. This study aimed to determine if SSMBI training resulted in better performance (examination scores and detection of abnormal findings) than the traditional teaching method. METHODS: Novice fourth-year medical students were exposed to the SSMBI curriculum (n = 68) or traditional (n = 52) training. The traditional group was taught by a lecture and attending weekly clinics where they had hands-on experience. The SSMBI group underwent a structured lecture followed by an instructional video and dedicated simulated teaching. Both groups were assessed through a written knowledge exam and an objective structured clinical examination (OSCE). Student's t test and χ2 tests were used to assess differences in CBE technique and knoweldge. RESULTS: Students who underwent SSMBI training had significantly higher numbers of correct answers describing the different steps and justifications of CBE. OSCE performance was significantly higher in the SSMBI group. SSMBI-trained students were more likely to complete all the necessary CBE steps compared to traditionally-trained students (88.2% vs. 28.2%, p < 0.00001). The SSMBI group was also more systematic and more likely to perform adequate inspection, palpation, examination of the nipple-areolar complex, and identify and characterize a palpable lesion (p < 0.05). CONCLUSIONS: Formal SSMBI training is an important asset when teaching medical students how to perform a CBE. Real clinical experience is still necessary to refine this skill and the physician-patient interaction.
Subject(s)
Breast Neoplasms/diagnosis , Curriculum , Multimedia , Palpation/methods , Simulation Training/methods , Academic Performance/statistics & numerical data , Clinical Competence , Education, Medical , Female , Humans , Students, Medical/statistics & numerical dataABSTRACT
Necrotizing fasciitis (NF) is a rare and highly lethal soft-tissue infection that involves the skin, subcutaneous tissue, and fascia. Although it can affect any part of the body, the breast is seldom involved. We describe a case of bilateral NF of the breast following elective quadrantectomy, successfully treated with antibiotics, bilateral mastectomy, and a vacuum-assisted wound closure system.
Subject(s)
Breast Neoplasms/surgery , Fasciitis, Necrotizing/therapy , Mastectomy/adverse effects , Mastectomy/methods , Adult , Fasciitis, Necrotizing/etiology , Fasciitis, Necrotizing/microbiology , Female , HumansABSTRACT
BACKGROUND: Primary neuroendocrine carcinoma of the breast is a heterogeneous group of rare tumors with positive immunoreactivity to neuroendocrine markers in at least 50% of cells. Diagnosis also requires that other primary sites be ruled out and that the same tumor show histological evidence of a breast in situ component. Primary neuroendocrine carcinoma of the breast rarely presents as locally advanced disease and less frequently with such widespread metastatic disease as described herein. The review accompanying this case report is the first to provide an overview of all the cases of primary neuroendocrine carcinoma of the breast published in the literature and encompasses detailed information regarding epidemiology, histogenesis, clinical and histologic diagnosis criteria, classification, surgical and adjuvant treatment, as well as prognosis. We also provide recommendations for common clinical and histologic pitfalls associated with this tumor. CASE PRESENTATION: We describe a case of a 51-year-old Hispanic woman initially diagnosed with locally-advanced invasive ductal carcinoma that did not respond to neoadjuvant treatment. After undergoing modified radical mastectomy the final surgical pathology showed evidence of alveolar-type primary neuroendocrine carcinoma of the breast. The patient was treated with cisplatin/etoposide followed by paclitaxel/carboplatinum. Thirteen months after surgery the patient is alive, but developed pulmonary, bone, and hepatic metastasis. CONCLUSION: The breast in situ component of primary neuroendocrine carcinoma of the breast may prevail on a core biopsy samples increasing the probability of underdiagnosing this tumor preoperatively. Being aware of the existence of this disease allows for timely diagnosis and management. Optimal treatment requires simultaneous consideration of both the neuroendocrine and breast in situ tumor features.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/diagnosis , Carcinoma, Ductal, Breast/diagnosis , Carcinoma, Neuroendocrine/diagnosis , Bone Neoplasms/secondary , Bone Neoplasms/therapy , Breast Neoplasms/therapy , Carboplatin/administration & dosage , Carcinoma, Ductal, Breast/therapy , Carcinoma, Neuroendocrine/therapy , Cisplatin/administration & dosage , Combined Modality Therapy , Diagnosis, Differential , Etoposide/administration & dosage , Female , Humans , Liver Neoplasms/secondary , Liver Neoplasms/therapy , Lung Neoplasms/secondary , Lung Neoplasms/therapy , Magnetic Resonance Imaging , Mastectomy , Middle Aged , Neoadjuvant Therapy , Neoplasm Staging , Paclitaxel/administration & dosage , Prognosis , Review Literature as TopicSubject(s)
Breast Neoplasms/pathology , Lymphatic Metastasis/diagnosis , Methylene Blue , Sentinel Lymph Node Biopsy/methods , Adult , Aged , Aged, 80 and over , Colombia , False Negative Reactions , Female , Humans , Lymphoscintigraphy/methods , Methylene Blue/adverse effects , Middle Aged , Retrospective Studies , Sentinel Lymph Node Biopsy/adverse effects , TechnetiumABSTRACT
BACKGROUND: Prophylactic antibiotics (PAs) are beneficial to breast cancer patients undergoing surgery because they prevent surgical site infection (SSI), but limited information regarding their use has been published. This study aims to determine the use of PAs prior to breast cancer surgery amongst breast surgeons in Colombia. METHODS: An online survey was distributed amongst the breast surgeon members of the Colombian Association of Mastology, the only breast surgery society of Colombia. The scope of the questions included demographics, clinical practice characteristics, PA prescription characteristics, and the use of PAs in common breast surgical procedures. RESULTS: The survey was distributed amongst eighty-eight breast surgeons of whom forty-seven responded (response rate: 53.4%). Forty surgeons (85.1%) reported using PAs prior to surgery of which >60% used PAs during mastectomy, axillary lymph node dissection, and/or breast reconstruction. Surgeons reported they targeted the use of PAs in cases in which patients had any of the following SSI risk factors: diabetes mellitus, drains in situ, obesity, and neoadjuvant therapy. The distribution of the self-reported PA dosing regimens was as follows: single pre-operative fixed-dose (27.7%), single preoperative dose followed by a second dose if the surgery was prolonged (44.7%), single preoperative dose followed by one or more postoperative doses for >24 hours (10.6%), and single preoperative weight-adjusted dose (2.1%). CONCLUSION: Although this group of breast surgeons is aware of the importance of PAs in breast cancer surgery there is a discrepancy in how they use it, specifically with regards to prescription and timeliness of drug administration. Our findings call for targeted quality-improvement initiatives, such as standardized national guidelines, which can provide sufficient evidence for all stakeholders and therefore facilitate best practice medicine for breast cancer surgery.
Subject(s)
Anti-Bacterial Agents/therapeutic use , Antibiotic Prophylaxis/statistics & numerical data , Breast Neoplasms/surgery , Breast/surgery , Surgical Wound Infection/prevention & control , Axilla , Colombia , Female , Health Care Surveys , Humans , Lymph Node Excision , Mammaplasty , Mastectomy , Practice Patterns, Physicians'ABSTRACT
Introducción. La instrucción en salas de cirugía tiene características particulares que requieren una evaluación, también particular. Es escasa la literatura sobre la evaluación de los cirujanos en su papel como docentes dentro y fuera del quirófano y es infrecuente la utilización en nuestro medio de procesos de evaluación estandarizados que incluyan la percepción del residente como fuente de información.Materiales y métodos. Se realizó un estudio prospectivo en el que se evaluó la totalidad de los docentes de planta participantes en la formación de residentes dentro del Hospital Universitario San Ignacio en las áreas quirúrgicas.Resultados. Las expectativas de los residentes fueron superadas, en promedio, por 59% de los docentes. En tres aspectos, más de 65% de los docentes obtuvieron una calificación en el rango superior correspondiente a excelente. Estos aspectos fueron: El docente mantiene un clima de mutuo respeto entre todos los miembros del equipo de salud, El docente demuestra habilidades técnicas con confidencia y El docente responde las preguntas clara y precisamente.El 41% de los docentes no superaron las expectativas de los residentes como docentes en el quirófano, pero sólo en 3,5% de los casos el desempeño docente en esta área fue considerado deficiente.Discusión. La evaluación integral que incluye la perspectiva de los residentes, constituye una herramienta indispensable para tener una percepción más realista sobre la enseñanza dentro y fuera del quirófano.La implementación de medidas de evaluación de la calidad de la docencia se justifica dentro de los programas académicos que buscan la excelencia en la formación de futuros cirujanos.
Subject(s)
Humans , General Surgery , Educational Measurement , Universities , TeachingABSTRACT
In South America, a high proportion of the population is of Hispanic origin with an important representation in Colombia. Since nothing is known about the contribution of BRCA1 and BRCA2 germline mutations to hereditary breast/ovarian cancer in the Hispanic population from Colombia, we conducted the first study of 53 breast/ovarian cancer families from this country. Comprehensive BRCA mutation screening was performed using a range of techniques, including DHPLC, SSCP, and PTT, followed by DNA sequencing analysis. Thirteen deleterious germline mutations (24.5%) were identified in 53 families, comprising eight in BRCA1 and five in BRCA2. The two recurrent BRCA1 mutations, 3450 delCAAG and A1708E, accounted for 100% of all BRCA1 mutations identified in this cohort and the recurrent 3034 delACAA BRCA2 mutation for 40% of all BRCA2 mutations. Haplotype analyses suggested that each of these mutations has arisen from a common ancestor. The prevalence of BRCA1 or BRCA2 mutations was 50% in multiple case breast cancer families, and was 33% for the breast-ovarian cancer families. Our findings show that BRCA mutations account for a substantial proportion of hereditary breast/ovarian cancer in Colombia. The spectrum of mutations differed completely to that previously reported in Hispanic families of predominantly Mexican origin from Southern California [1] suggesting that specific genetic risk assessment strategies for the different Hispanic populations in South America and in the United States need to be developed.
Subject(s)
Breast Neoplasms/genetics , Genes, BRCA1 , Genes, BRCA2 , Germ-Line Mutation , Hispanic or Latino/genetics , Ovarian Neoplasms/genetics , Adult , Aged , Colombia/ethnology , Female , Humans , Middle AgedABSTRACT
La obesidad constituye una patología cada vez más frecuente en el mundo occidental y los esfuerzos para controlarla han sido infructuosos en su mayoría. La cirugía bariátrica aparece como una alternativa eficaz de tratamiento que logra reducción sostenida de peso en 50 por ciento de los casos, con disminución de la morbilidad y la mortalidad asociadas con la enfermedad
Subject(s)
Obesity, Morbid/surgery , Digestive System Surgical Procedures/instrumentation , Digestive System Surgical Procedures/methodsABSTRACT
La cirugía constituye uno de los pilares fundamentales del tratamiento del cáncer de seno; las resecciones radicales han disminuido cada vez más y, paralelamente, las alternativas de tratamiento complementario han tomado mucha más fuerza. El siguiente artículo ilustra la evolución en el tiempo de conceptos básicos en la terapia del cáncer mamario y la influencia que estos nuevos conceptos han tenido sobre el tratamiento de las pacientes del Hospital Universitario San Ignacio
