Physicians' attitudes and perceived barriers to adherence to the national breast cancer clinical practice guidelines in Mexico: a survey study.

BACKGROUND: Adherence to clinical practice guidelines improves outcomes for patients with breast cancer. However, their implementation may not be feasible in low- and middle-income countries. This study aimed to evaluate physicians' adherence, attitudes, and barriers towards the Colima Consensus, which is the Mexican national breast cancer clinical practice guideline. METHODS: A cross-sectional, 31-item survey was e-mailed to Consensus attendees and members of the Mexican Society of Oncology and Mexican Mastology Association. Descriptive statistics, univariate, and multivariate analysis were used to analyze the associations between participants' characteristics, adherence, attitudes, and barriers. RESULTS: Of 439 respondents, 78% percent adhered to Consensus recommendations and 94% believed it was applicable to their clinical practice. Forty percent reported using the Consensus as their sole breast cancer guideline. This was associated with being a surgical oncologist (OR 3.3, 95% CI 2.0-5.3) and practicing at a public hospital (OR 2.1, 95% CI 1.2-3.7). The most common barriers to adherence were lack of resources and logistical problems. Regarding attitudes towards the Consensus, 90% considered it a good educational tool, 89% considered it a reliable source of information, and 90% thought it improved quality of care. CONCLUSIONS: We showed high levels of adherence and positive attitudes towards the Colima Consensus, with a significant proportion of physicians using it as their only guideline. Lack of resources and logistical issues were the main barriers to adherence. Our results highlight the relevance of local breast cancer guidelines and suggest a need for the creation of resource-stratified guidelines.

The Evolution of Clinically Aggressive Triple-Negative Breast Cancer Shows a Large Mutational Diversity and Early Metastasis to Lymph Nodes.

In triple-negative breast cancer (TNBC), only 30% of patients treated with neoadjuvant chemotherapy achieve a pathological complete response after treatment and more than 90% die due to metastasis formation. The diverse clinical responses and metastatic developments are attributed to extensive intrapatient genetic heterogeneity and tumor evolution acting on this neoplasm. In this work, we aimed to evaluate genomic alterations and tumor evolution in TNBC patients with aggressive disease. We sequenced the whole exome of 16 lesions from four patients who did not respond to therapy, and took several follow-up samples, including samples from tumors before and after treatment, as well as from the lymph nodes and skin metastases. We found substantial intrapatient genetic heterogeneity, with a variable tumor mutational composition. Early truncal events were MCL1 amplifications. Metastatic lesions had deletions in RB1 and PTEN, along with TERT, AKT2, and CCNE1 amplifications. Mutational signatures 06 and 12 were mainly detected in skin metastases and lymph nodes. According to phylogenetic analysis, the lymph node metastases occurred at an early stage of TNBC development. Finally, each patient had three to eight candidate driving mutations for targeted treatments. This study delves into the genomic complexity and the phylogenetic and evolutionary development of aggressive TNBC, supporting early metastatic development, and identifies specific genetic alterations associated with a response to targeted therapies.

Comprehensive Genomic Profile of Heterogeneous Long Follow-Up Triple-Negative Breast Cancer and Its Clinical Characteristics Shows DNA Repair Deficiency Has Better Prognostic.

Triple-negative breast cancer (TNBC) presents a marked diversity at the molecular level, which promotes a clinical heterogeneity that further complicates treatment. We performed a detailed whole exome sequencing profile of 29 Mexican patients with long follow-up TNBC to identify genomic alterations associated with overall survival (OS), disease-free survival (DFS), and pathologic complete response (PCR), with the aim to define their role as molecular predictive factors of treatment response and prognosis. We detected 31 driver genes with pathogenic mutations in TP53 (53%), BRCA1/2 (27%), CDKN1B (9%), PIK3CA (9%), and PTEN (9%), and 16 operative mutational signatures. Moreover, tumors with mutations in BRCA1/2 showed a trend of sensitivity to platinum salts. We found an association between deficiency in DNA repair and surveillance genes and DFS. Across all analyzed tumors we consistently found a heterogeneous molecular complexity in terms of allelic composition and operative mutational processes, which hampered the definition of molecular traits with clinical utility. This work contributes to the elucidation of the global molecular alterations of TNBC by providing accurate genomic data that may help forthcoming studies to improve treatment and survival. This is the first study that integrates genomic alterations with a long follow-up of clinical variables in a Latin American population that is an underrepresented ethnicity in most of the genomic studies.

Lymphoepithelioma-like carcinoma of breast: A case report and review of the literature.

Lymphoepithelioma is a rare clinical entity, first was described in nasopharynx, and have been reported in another organs. Lymphoepithelioma-like carcinoma (LEC) of the breast is an undifferentiated carcinoma. Approximately 32 cases have been described, and differential diagnoses include primary breast lymphoma and medullary carcinoma. We present a 57-year-old woman, diagnosed with LEC of the breast, treated with mastectomy, followed by adjuvant chemotherapy, radiotherapy, and hormone therapy, with a disease-free interval of 2 years. There is scarce evidence related to the best treatment choice in this histological type.

Ki67 Changes Identify Worse Outcomes in Residual Breast Cancer Tumors After Neoadjuvant Chemotherapy.

BACKGROUND: Several breast cancer (BC) trials have adopted pathological complete response (pCR) as a surrogate marker of long-term treatment efficacy. In patients with luminal subtype, pCR seems less important for outcome prediction. BC is a heterogeneous disease, which is evident in residual tumors after neoadjuvant-chemotherapy (NAC). This study evaluates changes in Ki67 in relation to disease-free survival (DFS) and overall survival (OS) in patients without pCR. SUBJECTS, MATERIALS, AND METHODS: Four hundred thirty-five patients with stage IIA-IIIC BC without pCR after standard NAC with anthracycline and paclitaxel were analyzed. We analyzed the decrease or lack of decrease in the percentage of Ki67-positive cells between core biopsy samples and surgical specimens and correlated this value with outcome. RESULTS: Twenty-five percent of patients presented with luminal A-like tumors, 45% had luminal B-like tumors, 14% had triple-negative BC, 5% had HER2-positive BC, and 11% had triple-positive BC. Patients were predominantly diagnosed with stage III disease (52%) and high-grade tumors (46%). Median Ki67 level was 20% before NAC, which decreased to a median of 10% after NAC. Fifty-seven percent of patients had a decrease in Ki67 percentage. Ki67 decrease significantly correlated with better DFS and OS compared with no decrease, particularly in the luminal B subgroup. Multivariate analysis showed that nonreduction of Ki67 significantly increased the hazard ratio of recurrence and death by 3.39 (95% confidence interval [CI] 1.8-6.37) and 7.03 (95% CI 2.6-18.7), respectively. CONCLUSION: Patients without a decrease in Ki67 in residual tumors after NAC have poor prognosis. This warrants the introduction of new therapeutic strategies in this setting. IMPLICATIONS FOR PRACTICE: This study evaluates the change in Ki67 percentage before and after neoadjuvant chemotherapy (NAC) and its relationship with survival outcomes in patients with breast cancer who did not achieve complete pathological response (pCR). These patients, a heterogeneous group with diverse prognoses that cannot be treated using a single algorithm, pose a challenge to clinicians. This study identified a subgroup of these patients with a poor prognosis, those with luminal B-like tumors without a Ki67 decrease after NAC, thus justifying the introduction of new therapeutic strategies for patients who already present a favorable prognosis (luminal B-like with Ki67 decrease).

68Ga-DTPA Anti-HER2 positron emission tomography/CT successfully predicts the overexpression of human epidermal growth factor receptor in lung metastases from breast cancer.

Molecular identification of a metastatic tumour without the inconvenience of a biopsy and the time required for pathological characterization is possible using molecular imaging. Here, we present the case of a patient with breast cancer in whom 68Ga-diethylenetriamine pentaacetic acid anti-human epidermal growth factor receptor 2 positron emission tomography-CT was successfully employed to characterize the expression of human epidermal growth factor receptor 2 in metastatic sites.

An Uncommon Case of Bilateral Breast Enlargement Diagnosed as Tumoral Pseudoangiomatous Stromal Hyperplasia: Imaging and Pathological Findings.

The incidence of reported pseudoangiomatous stromal hyperplasia (PASH), as well as the variability and severity of clinical presentations, is increasing in the literature. In parallel, several authors posit the need for an improved classification of PASH to avoid possible variables associated with this diagnosis. Here, we present a 25-year-old woman with PASH accompanied by severe bilateral and symmetrical breasts enlargement, highlighting an uncommon clinical presentation of PASH as much as the careful interdisciplinary review and correlation of histology and all available imaging studies to confirm the definitive diagnosis.

Cost-effectiveness of the 21-gene breast cancer assay in Mexico.

INTRODUCTION: The 21-gene breast cancer assay (Oncotype DX(®); Genomic Health, Inc.) is a validated diagnostic test that predicts the likelihood of adjuvant chemotherapy benefit and 10-year risk of distant recurrence in patients with hormone-receptor-positive, human epidermal growth receptor 2-negative, early-stage breast cancer. The aim of this analysis was to evaluate the cost-effectiveness of using the assay to inform adjuvant chemotherapy decisions in Mexico. METHODS: A Markov model was developed to make long-term projections of distant recurrence, survival, and direct costs in scenarios using conventional diagnostic procedures or the 21-gene assay to inform adjuvant chemotherapy recommendations. Transition probabilities and risk adjustment were taken from published landmark trials. Costs [2011 Mexican Pesos (MXN)] were estimated from an Instituto Mexicano del Seguro Social perspective. Costs and clinical benefits were discounted at 5% annually. RESULTS: Following assay testing, approximately 66% of patients previously receiving chemotherapy were recommended to receive hormone therapy only after consideration of assay results. Furthermore, approximately 10% of those previously allocated hormone therapy alone had their recommendation changed to add chemotherapy. This optimized therapy allocation led to improved mean life expectancy by 0.068 years per patient and increased direct costs by MXN 1707 [2011 United States Dollars (USD) 129] per patient versus usual care. This is equated to an incremental cost-effectiveness ratio (ICER) of MXN 25,244 (USD 1914) per life-year gained. CONCLUSION: In early-stage breast cancer patients in Mexico, guiding decision making on adjuvant therapy using the 21-gene assay was projected to improve life expectancy in comparison with the current standard of care, with an ICER of MXN 25,244 (USD 1914) per life-year gained, which is within the range generally considered cost-effective.

A study of the impact of the 21-gene breast cancer assay on the use of adjuvant chemotherapy in women with breast cancer in a Mexican public hospital.

BACKGROUND: The majority of breast cancer patients in Mexico are treated through the public health system and >80% receive adjuvant chemotherapy. The aim of this prospective study was to characterize the impact of the Oncotype DX assay on adjuvant therapy decision making and the confidence in those decisions amongst public sector physicians in Mexico. METHODS: Ninety-eight consecutive patients with ER+, HER2-, stage I-IIIa, N0/N1-3 node-positive breast cancer from the Instituto Nacional de Cancerología were eligible for the study. The primary endpoint was the overall change in treatment recommendations after receiving the assay results. RESULTS: Of 96 patients, 48% received a chemohormonal therapy recommendation prior to testing. Following receipt of results, treatment decisions changed for 31/96 (32%) patients, including 17/62 (27%) node-negative patients and 14/34 (41%) node-positive patients. The proportion of patients with a chemotherapy-based recommendation decreased from 48% pre- to 34% post-assay (P=0.024). 92% of physicians agreed that they were more confident in their treatment recommendation after ordering the assay. CONCLUSIONS: These results suggest that use of the 21-gene assay in the Mexican public health system has a meaningful impact on adjuvant treatment recommendations that may reduce the overall use of chemotherapy.

SIP1/NHERF2 enhances estrogen receptor alpha transactivation in breast cancer cells.

The estrogen receptor alpha (ERα) is a ligand-activated transcription factor that possesses two activating domains designated AF-1 and AF-2 that mediate its transcriptional activity. The role of AF-2 is to recruit coregulator protein complexes capable of modifying chromatin condensation status. In contrast, the mechanism responsible for the ligand-independent AF-1 activity and for its synergistic functional interaction with AF-2 is unclear. In this study, we have identified the protein Na+/H+ Exchanger RegulatoryFactor 2 (NHERF2) as an ERα-associated coactivator that interacts predominantly with the AF-1 domain of the nuclear receptor. Overexpression of NHERF2 in breast cancer MCF7 cells produced an increase in ERα transactivation. Interestingly, the presence of SRC-1 in NHERF2 stably overexpressing MCF7 cells produced a synergistic increase in ERα activity. We show further that NHERF2 interacts with ERα and SRC-1 in the promoter region of ERα target genes. The binding of NHERF2 to ERα in MCF7 cells increased cell proliferation and the ability of MCF7 cells to form tumors in a mouse model. We analyzed the expression of NHERF2 in breast cancer tumors finding a 2- to 17-fold increase in its mRNA levels in 50% of the tumor samples compared to normal breast tissue. These results indicate that NHERF2 is a coactivator of ERα that may participate in the development of estrogen-dependent breast cancer tumors.

[Evaluation of breast cancer treatment at a tertiary-level institution with Popular Health Insurance in Mexico]. / Evaluación del tratamiento del cáncer de mama en una institución del tercer nivel con el Seguro Popular, México.

BACKGROUND: In our country breast cancer represents a major health problem. Only 45% of all population has access to health services, the consequence is delay in diagnosis and treatment. In Mexico, 66% of all new cases of breast cancer are diagnosed in locally advanced stages. From May 2007 the Health System Protection Against Catastrophic Expenses, called Seguro Popular (SP), breast cancer was included in covering the treatment of this neoplasm in any patient without access to social security. OBJECTIVE: To evaluate the results and impact of SP in the adjuvant and neoadjuvant treatment of a group of patients diagnosed with breast cancer at an institution of national reference. MATERIAL AND METHODS: We analyzed a group of 259 patients in stages (I-IIIC). The clinical stages I and II (55 patients) were treated with adjuvant chemotherapy FAC -T (fluorouracil 500 mg/m2, adriamycin 50 mg/m2 and cyclophosphamide 500 mg/m2 (FAC) followed by 12 weeks of paclitaxel 80 mg/m2 +/- trastuzumab loading dose of 4 mg/kg followed by 2 mg/kg); 204 patients in locally advanced stages (IIB-IIIC) received FAC-T +/- trastuzumab followed by surgery. Adjuvant treatment consisted of endocrine therapy for hormone-sensitive patients and radiotherapy 50 cGy according to international standards. RESULTS: The age at diagnosis was 47 years (range 23-68). 80% of them were locally advanced stages (IIB-IIIC) and were treated in a neoadjuvant setting, 20% was in early stages, treated with surgery and adjuvant chemotherapy The disease-free survival and overall survival at 30 months was 85.7 and 90% respectively. Overall pathologic complete response was obtained in 15% of cases. In the subgroup analysis showed that 41% of patients HER2 (+), 29% of triple-negative patients and 9% of hormone-sensitive tumors achieved complete pathological response (p = 0.0001). CONCLUSION: This is the first analysis of efficacy of adjuvant and neoadjuvant treatment in breast cancer since the introduction of popular secure non-entitled population. It is clear that treatment efficacy is similar to that reported in the literature, with 15% of pRC and survival to 30 months in 94-80%. The coverage of health expenditures treats a larger number of patients optimally. Along with this, efforts should be made to reduce the high frequency of diagnosis at advanced stage.

Triple-negative breast cancer in Hispanic patients: high prevalence, poor prognosis, and association with menopausal status, body mass index, and parity.

BACKGROUND: Triple-negative breast cancer (TNBC) is defined as breast cancer that is negative for estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2. TNBC represents 15% of all invasive breast cancers, but some studies have suggested that its prevalence differs between races. To the authors' knowledge, no previous studies have determined the prevalence of TNBC and its risk factors among Hispanic women. METHODS: The authors identified 2074 Hispanic women with breast cancer who attended the National Cancer Institute in Mexico City from 1998 to 2008. All histopathologic and immunohistochemical diagnoses were rereviewed by a breast cancer pathologist. The prevalence of TNBC, its association with clinicopathologic characteristics, and its prognostic impact were determined. RESULTS: The median patient age at diagnosis (±standard deviation) was 50 ± 12 years. The overall prevalence of TNBC was 23.1%. Younger age (P < .001), premenopausal status (P = .002), increased parity (P = .029), hormonal contraceptive use (P = .04) high histologic grade (P < .001), and advanced disease (P < .001) were associated independently with TNBC. Postmenopausal patients who had a body mass index (BMI) <25 kg/m(2) (P = .027) or <30 kg/m(2) (P < .001) were more likely to have TNBC. In multivariate analysis, patients with TNBC had a higher risk of locoregional recurrence (LRR), lower disease-free survival (DFS) (hazard ratio, 1.62; 95% confidence interval, 1.13-2.32; P = .009), and a lower cancer-specific survival (CSS) rate (hazard ratio, 1.66; 95% confidence interval, 1.20-2.30; P = .002) than patients with non-TNBC. CONCLUSIONS: The median age at diagnosis of Hispanic women with breast cancer was 11 years younger than the average age reported in the United States. The prevalence of TNBC in this study population was higher than that reported in white women with breast cancer. TNBC was associated with a higher risk of LRR and with lower DFS and CSS than those in patients with non-TNBC.

High-risk human papillomavirus in mammary gland carcinomas and non-neoplastic tissues of Mexican women: no evidence supporting a cause and effect relationship.

Human papillomavirus (HPV) has been implicated in breast carcinogenesis. Consecutive and non-selected mastectomy specimens from Mexican patients harboring breast carcinomas were sampled in order to look for the presence of HPV DNA. HPV-16 was detected in 6 (10%) of 60 breast carcinomas. Two of these also had HPV genome in adjacent non-neoplastic mammary-tissues. Seven cases had HPV DNA only in non-neoplastic tissue specimens. HPV DNA was also detected in 4 (25%) of 10 tumor-bed specimens without residual neoplastic lesions that were obtained from patients who underwent neoadjuvant chemotherapy or neoadjuvant chemotherapy/radiotherapy. HPV-positive tumors tended to be smaller in size, than HPV-negative tumors (p=0.047). Histological distributions of HPV-positive and -negative cases showed no significant difference. Although all the HPV-16 DNA were found integrated, its low viral load rendered it difficult to incriminate this virus in breast carcinogenesis. However, the possibility that HPV infection occurred during carcinoma development cannot be ruled out.

Concurrent chemo-radiotherapy following neoadjuvant chemotherapy in locally advanced breast cancer.

BACKGROUND: Despite broad advances in multimodal treatment of locally advanced breast cancer (LABC), 30 to 40% of patients develop loco-regional relapse. The aim of this study was to analyze in a retrospective manner the effectiveness of concurrent chemo-radiotherapy (CCRTh) after neoadjuvant chemotherapy (NCT) in patients with LABC. METHODS: One hundred twelve patients with LABC (stage IIB-IIIB) were treated with NCT (5-fluorouracil 500 mg/m2, doxorubicin 50 mg/m2, and cyclophosphamide 500 mg/m2 (FAC), or doxorubicin 50 mg/m2 and cyclophosphamide 500 mg/m2 (AC) IV in four 21-day courses) followed by CCRTh (60 Gy breast irradiation and weekly mitomycin 5 mg/m2, 5-fluorouracil 500 mg/m2, and dexamethasone 16 mg, or cisplatin 30 mg/m2, gemcitabine 100 mg/m2 and dexamethasone 16 mg), and 6-8 weeks later, surgery and two additional courses of FAC, AC, or paclitaxel 90 mg/m2 weekly for 12 weeks, and in case of estrogen-receptor positive patients, hormonal therapy. RESULTS: Stages IIB, IIIA and -B were 21.4, 42.9, and 35.7%, respectively. Pathological complete response (pCR) in the breast was 42% (95% CI, 33.2-50.5%) and, 29.5% (95% CI, 21.4-37.5%) if including both the breast and the axillary nodes. Multivariate analysis showed that the main determinant of pCR was negative estrogen-receptor status (HR=3.8; 95% CI, 1.5-9; p=0.016). The 5-year disease-free survival (DFS) was 76.9% (95% CI, 68.2-84.7%). No relationship between pCR and DFS was found. Multivariate analysis demonstrated that the main DFS determinant was clinical stage (IIB and IIIA vs. IIIB, HR=3.1; 95% CI, 1.02-9.74; p=0.04). Only one patient had local recurrence. Five-year overall survival was 84.2% (95% CI, 75-93.2%). The toxicity profile was acceptable. CONCLUSION: This non-conventional multimodal treatment has good loco-regional control for LABC. Randomized clinical trials of preoperative CCRTh following chemotherapy, in patients with LABC are warranted.

HER2 expression in cervical cancer as a potential therapeutic target.

BACKGROUND: Trastuzumab, a humanized monoclonal antibody against the HER2 receptor is currently being used in breast and other tumor types. Early studies have shown that a variable proportion of cervical carcinoma tumors overexpress the HER2 receptor as evaluated by diverse techniques and antibodies. Currently it is known that a tumor response to trastuzumab strongly correlates with the level of HER2 expression evaluated by the Hercep Test, thus, it seems desirable to evaluate the status of expression of this receptor using the FDA-approved Hercep Test and grading system to gain insight in the feasibility of using trastuzumab in cervical cancer patients. METHODS: We analyzed a series of cervical cancer cell lines, the primary tumors of 35 cases of cervical cancer patients and four recurrent cases, with the Hercep Test in order to establish whether this tumor type overexpress HER2 at level of 2+/3+ as trastuzumab is currently approved for breast cancer having such level of expression. RESULTS: The results indicate that only 1 out of 35 primary tumors cases overexpress the receptor at this level, however, two out of four recurrent tumors that tested negative at diagnosis shifted to Hercep Test 2+ and 3+ respectively. CONCLUSIONS: The low frequency of expression in primary cases suggests that trastuzumab could have a limited value for the primary management of cervical cancer patients, however, the finding of "conversion" to Hercep Test 2+ and 3+ of recurrent tumors indicates the need to further evaluate the expression of HER2 in the metastatic and recurrent cases.

Carcinoma epidermoide originado en teratoma quístico maduro de ovario. Informe de dos casos y revisión de la literatura / Epidermoid carcinoma derived from mature cystic teratoma of the ovary. Two case presentation and literature review

La frecuencia del desarrollo de malignidad en un teratoma quístico maduro de ovario es de 1-2 por ciento. La mayoría de los casos informados ocurren en mujeres posmenopaúsicas. En este artículo se comunican dos casos de carcinoma epidermoide originado en un teratoma quístico maduro de ovario, uno de los cuales se presentó en una mujer joven. En el otro caso podemos sustentar que el origen del componente carcinomatoso se encuentra en el epitelio columnar y en la epidermis de los tejidos propios del teratoma

Caso anatomoclínico del Instituto Nacional de Cancerología / Anatomoclinic case of tha Instituto Nacional of Cancerologia

Se describe el caso de una mujer de 77 años que presentó datos cerebrales de un probable carcinoma con primario de origen desconocido. En el estadio final de su evolución clínica presentó datos de abdomen agudo. Se efectúan consideraciones acerca del manejo de las neoplasias de origen desconocido que eventualmente dan metástasis a sistema nervioso central. Así mismo se presenta una revisión bibliográfica de las diferentes extirpes histológicas que metastatizan a cerebro y se comenta acerca de su pronóstico. Finalmente, se efectúan comentarios de los hallazgos histopatológicos.

Higroma quístico en el hospital materno infantil de `San Bartolomé' / Cystic hygroma in the hospital materno infantil of `San Bartolomé'

Este estudio se ha hecho revisando las historias clínicas del Hospital entre los años 1963 al año 1980; se localizaron 21 casos con higroma quistico. Los puntos a discutir han sido frecuencia en la edad, localización, incidencia según la raza, el tiempo de evolución, caracteristicas del tumor, tipo de Cirugía empleado, complicaciones, sexo y mortalidad