Recurrent and functional regulatory mutations in breast cancer.

Genomic analysis of tumours has led to the identification of hundreds of cancer genes on the basis of the presence of mutations in protein-coding regions. By contrast, much less is known about cancer-causing mutations in non-coding regions. Here we perform deep sequencing in 360 primary breast cancers and develop computational methods to identify significantly mutated promoters. Clear signals are found in the promoters of three genes. FOXA1, a known driver of hormone-receptor positive breast cancer, harbours a mutational hotspot in its promoter leading to overexpression through increased E2F binding. RMRP and NEAT1, two non-coding RNA genes, carry mutations that affect protein binding to their promoters and alter expression levels. Our study shows that promoter regions harbour recurrent mutations in cancer with functional consequences and that the mutations occur at similar frequencies as in coding regions. Power analyses indicate that more such regions remain to be discovered through deep sequencing of adequately sized cohorts of patients.

Sequence analysis of mutations and translocations across breast cancer subtypes.

Breast carcinoma is the leading cause of cancer-related mortality in women worldwide, with an estimated 1.38 million new cases and 458,000 deaths in 2008 alone. This malignancy represents a heterogeneous group of tumours with characteristic molecular features, prognosis and responses to available therapy. Recurrent somatic alterations in breast cancer have been described, including mutations and copy number alterations, notably ERBB2 amplifications, the first successful therapy target defined by a genomic aberration. Previous DNA sequencing studies of breast cancer genomes have revealed additional candidate mutations and gene rearrangements. Here we report the whole-exome sequences of DNA from 103 human breast cancers of diverse subtypes from patients in Mexico and Vietnam compared to matched-normal DNA, together with whole-genome sequences of 22 breast cancer/normal pairs. Beyond confirming recurrent somatic mutations in PIK3CA, TP53, AKT1, GATA3 and MAP3K1, we discovered recurrent mutations in the CBFB transcription factor gene and deletions of its partner RUNX1. Furthermore, we have identified a recurrent MAGI3-AKT3 fusion enriched in triple-negative breast cancer lacking oestrogen and progesterone receptors and ERBB2 expression. The MAGI3-AKT3 fusion leads to constitutive activation of AKT kinase, which is abolished by treatment with an ATP-competitive AKT small-molecule inhibitor.

Complete sequence of the ATP6 and ND3 mitochondrial genes in breast cancer tissue of postmenopausal women with different body mass indexes.

Due to the fact that mitochondrial defects and oxidative stress have been related with obesity and breast cancer is more aggressive in women with obesity, we investigated if postmenopausal Mexican-Mestizo women with breast cancer presented somatic mutations in the sequence of the ATP6 and/or ND3 genes. Twenty one postmenopausal Mexican-Mestizo women with breast cancer who underwent mastectomy or breast conserving surgery were studied. Height and weight were used to calculate body mass index. DNA from tumor tissue samples and blood leukocytes was amplified by polymerase chain reaction and sequenced the ATP6 and ND3 mitochondrial genes. Ages ranged from 46 to 82. According to World Health Organization criteria among the 21 women, 7 had a normal BMI, 7 were overweight and 7 had obesity. In regard to the molecular study, after sequencing the coding region of ATP6 and ND3 genes of the DNA obtained from both leukocytes and tumor tissue, we did not find somatic mutations. All of the changes that we found in both genes were polymorphisms: in ATP6, we identified in ten patients 3 non-synonymous nucleotide changes and in ND3 we observed that six patients presented polymorphisms, three of them were synonymous and two non-synonymous. To our knowledge, this constitutes the first report where the complete sequence of the ATP6 and ND3 genes has been analyzed in postmenopausal Mexican-Mestizo women with breast cancer and diverse BMI. Our results differ with those reported in Caucasian and Asian populations, possibly due to ethnic differences.

A microRNA signature associated with pathological complete response to novel neoadjuvant therapy regimen in triple-negative breast cancer.

Neoadjuvant chemotherapy aims to improve the outcome of breast cancer patients, but only few would benefit from this treatment. Pathological complete response has been proposed as a surrogate marker for the prediction of long-term clinical benefits; however, 50%-85% patients have an unfavorable pathological complete response to chemotherapy. MicroRNAs are known biomarkers of breast cancer progression; nevertheless, their potential to identify patients with pathological complete response remains poorly understood. Here, we investigated whether a microRNA profile could be associated with pathological complete response in triple-negative breast cancer patients receiving 5-fluorouracil, adriamycin, cyclophosphamide-cisplatin/paclitaxel as a novel neoadjuvant chemotherapy. In the discovery cohort, the expression of 754 microRNAs was examined in tumors from 10 triple-negative breast cancer patients who achieved pathological complete response and 8 without pathological complete response using TaqMan Low-Density Arrays. Unsupervised hierarchical cluster analysis identified 11 microRNAs with significant differences between responder and no-responder patients (fold change ≥ 1.5; p < 0.05). The differential expression of miR-30a, miR-9-3p, miR-770, and miR-143-5p was validated in an independent group of 17 patients with or without pathological complete response. Moreover, Kaplan-Meier analysis showed that expression of these four microRNAs was associated with an increased disease-free survival. Gene ontology classification of predicted microRNA targets indicated that numerous genes are involved in pathways related to chemoresistance, such as vascular endothelial growth factor, focal adhesion kinase, WNT, ERbB, phosphoinositide 3-kinase, and AKT signaling. In summary, we identified a novel microRNA expression signature associated with pathological complete response in breast cancer. We propose that the four validated microRNAs could be used as molecular biomarkers of clinical response in triple-negative breast cancer patients with pathological complete response to neoadjuvant therapy.

Suppression of cell migration is promoted by miR-944 through targeting of SIAH1 and PTP4A1 in breast cancer cells.

BACKGROUND: Aberrant expression of microRNAs has been associated with migration of tumor cells. In this study, we aimed to investigate the biological significance of miR-944 whose function is unknown in breast cancer. METHODS: MiR-944 expression in breast cancer cells and tumors was evaluated by Taqman qRT-PCR assays. Transcriptional profiling of MDA-MB-231 cells expressing miR-944 was performed using DNA microarrays. Cell viability, migration and invasion were assessed by MTT, scratch/wound-healing and transwell chamber assays, respectively. The luciferase reporter assay was used to evaluate targeting of SIAH1, PTP4A1 and PRKCA genes by miR-944. SIAH1 protein levels were measured by Western blot. Silencing of SIAH1 gene was performed by RNA interference using shRNAs. RESULTS: Our data showed that miR-944 expression was severely repressed in clinical specimens and breast cancer cell lines. Suppression of miR-944 levels was independent of hormonal status and metastatic potential of breast cancer cells. Gain-of-function analysis indicated that miR-944 altered the actin cytoskeleton dynamics and impaired cell migration and invasion. Genome-wide transcriptional profiling of MDA-MB-231 cells that ectopically express miR-944 showed that 15 genes involved in migration were significantly repressed. Notably, luciferase reporter assays confirmed the ability of miR-944 to bind the 3´UTR of SIAH1 and PTP4A1 genes, but not PRKCA gene. Congruently, an inverse correlation between miR-944 and SIAH1 protein expression was found in breast cancer cells. Moreover, SIAH1 was upregulated in 75 % of miR-944-deficient breast tumors. Finally, SIAH1 gene silencing by RNA interference significantly impaired cell migration of breast cancer cells. CONCLUSIONS: Our results pointed out that miR-944 is a novel upstream negative regulator of SIAH1 and PTP4A1 genes and provided for the first time evidence for its functional role in migration and invasion of breast cancer cells. They also suggest that miR-944 restoration may represent a potential strategy for breast cancer therapy.

[Neoadjuvant Chemotherapy (NC) Response in Patients with Breast Cancer According to Immunohistochemical Intrinsic Subtypes (IHC)]. / Respuesta a la quimioterapia neoadyuvante (QTneo) según los subtipos intrínsecos determinados por inmunohistoquímica (IHQ) en pacientes con cáncer de mama.

INTRODUCTION: Breast cancer is heterogeneous, with different responses to NC even within similar histology and stages. OBJECTIVE: To evaluate clinical/pathological response to NC according to different tumor subtypes in Mexican breast cancer patients. PATIENTS AND METHODS: Retrospective study of patients with breast cancer stages II-III, and complete immunohistochemistry (IHC), such as hormonal receptors HER2 and Ki67, treated with NC and surgery. Descriptive and comparative analyses between different intrinsic subtypes were performed. RESULTS: A total of 117 patients were included with 48.6 ± 10.6 years of age, stage II (24%), and III (76%). We identified 20 (17.1%) cases of luminal A, 37 (31.6%) luminal B HER2-, 13 (11.1%) luminal B HER2+, 12 (10.3%) HER2+, and 35 (29.9%) triple negative. Clinical complete response (tumor and lymph nodes) in luminal A was 10%, in luminal B HER2- 10.8%, luminal B HER2+ 15.4%, HER2+ 25%, and in triple negative 14.3%. Conservative surgeries were done in 9 (7.7%) patients. There is a weak positive association between Ki67 expression and tumor clinical response. Pathological complete response occurred in 8 (6.83%) cases, being more frequent in luminal B HER2+ patients (23%). CONCLUSIONS: Pathological complete responses were more often in luminal B HER2+ cases.

[Impact on quality of life with breast reconstructive surgery after mastectomy for breast cancer]. / Impacto en la calidad de vida con cirugía reconstructiva posterior al tratamiento de cáncer de mama.

BACKGROUND: Breast cancer treatment leads mutilation and destruction of breast shape, with negative effects on body image and self-esteem. OBJECTIVES: Assessment on quality of life after breast reconstruction surgery, impact on sexuality, the cosmetic outcome experienced by the patient, and compare result with patients who refused breast reconstruction. MATERIAL AND METHODS: Retrospective, observational, descriptive, analytic study. We included breast cancer patients treated between April 15 2010 to April 15, 2011. Application of "The Survey Questionnaire short form Health 36" (SF-36) with valid use on Mexican population was conducted to measure quality of life, which uses 8 concepts: physical functioning, physical role, body pain, general health, vitality, social function, emotional role and mental health, the results are transferred to a scale 0 (worst health) to 100 (best health). RESULTS: 37 patients whit breast reconstruction had the inclusion criteria, mean age was 48.4 years. The score of SF-36 questionnaire in reconstructed patients was 76.8, in control group was 85.19 and mastectomy patients without reconstruction was 72.6. Among the items studied those with the greatest difference was the mental health, emotional role and social function, this means that patients with breast reconstruction are less affected in their social and sexual interaction. CONCLUSIONS: The reconstructed patients have a positive impact on quality of life slightly higher, sexuality is significantly worse in patients without breast reconstruction, it is important to inform and offer breast reconstruction because many do not require these procedures for fear or lack of information.

MetastamiRs: non-coding MicroRNAs driving cancer invasion and metastasis.

MicroRNAs (miRNAs) are small non-coding RNAs of ~22 nucleotides that function as negative regulators of gene expression by either inhibiting translation or inducing deadenylation-dependent degradation of target transcripts. Notably, deregulation of miRNAs expression is associated with the initiation and progression of human cancers where they act as oncogenes or tumor suppressors contributing to tumorigenesis. Abnormal miRNA expression may provide potential diagnostic and prognostic tumor biomarkers and new therapeutic targets in cancer. Recently, several miRNAs have been shown to initiate invasion and metastasis by targeting multiple proteins that are major players in these cellular events, thus they have been denominated as metastamiRs. Here, we present a review of the current knowledge of miRNAs in cancer with a special focus on metastamiRs. In addition we discuss their potential use as novel specific markers for cancer progression.

[Breast cancer in Mexican women under 40]. / Cancer de mama en mujeres mexicanas menores de 40 años.

BACKGROUND: Breast cancer is the leading cause of death from malignancy in women. The incidence increases with age, but the relationship between age and survival of breast cancer patients is not well defined. It is observed that young women with breast cancer have patterns more aggressive biological. OBJECTIVE: To determine the frequency, sociodemographic, clinical and histopathological features of breast cancer in women under 40 years attending a specialist breast unit in Mexico City. PATIENTS AND METHOD: Transversal, descriptive and retrospective study of patients under 40 years of age with breast cancer treated between 2005 and 2010. RESULTS: 1430 cases were diagnosed with breast cancer five years with a mean age of 53.64 +/- 11.87 years (range 23 to 93 years), 142 cases were women under 40 years of age (10%). The auto-detection of a breast lump was the most frequent clinical manifestation (50%). CONCLUSION: The prevalence of clinical stage III in this age group suggests the difficulty of diagnosis, the high breast density, which is one factor limiting studies of screening with mammography, it diminishes their effectiveness in early detection of breast cancer.

First breast cancer mammography screening program in Mexico: initial results 2005-2006.

Breast cancer is the most frequent malignant neoplasia worldwide. In emergent countries as Mexico, an increase has been shown in frequency and mortality, unfortunately, most cases in advanced loco-regional stages developed in young women. The success of breast screening in mortality reduction has been observed since 1995 in Western Europe and the United States, where as many as 40% mortality reduction has been achieved. Most countries guidelines recommends an annual or biannual mammography for all women >40 years of age. In 2005, FUCAM, a nonlucrative civil foundation in Mexico join with Mexico City government, initiated the first voluntary mammography screening program for women >40 years of age residing in Mexico City's Federal District. Mammographies were carried out with analogical mammographs in specially designed mobile units and were performed in the area of women's domiciles. This report includes data from the first 96,828 mammographies performed between March 2005 and December 2006. There were 1% of mammographies in Breast Imaging Reporting and Data System 0, 4, or 5 and 208 out of 949 women with abnormal mammographies (27.7%) had breast cancer, a rate of 2.1 per thousand, most of them in situ or stage I (29.4%) or stage II (42.2%) nevertheless 21% of those women with abnormal mammography did not present for further clinical and radiologic evaluation despite being personally notified at their home addresses. The breast cancer rate of Mexican women submitted to screening mammography is lower than in European or North American women. Family history of breast cancer, nulliparity, absence of breast feeding, and increasing age are factors that increase the risk of breast cancer. Most cancers were diagnosed in women's age below 60 years (68.5%) with a mean age of 53.55 corroborating previous data published. It is mandatory to sensitize and educate our population with regard to accepting to visit the Specialized Breast Centers.

[Radiological control intraoperatory of a surgical piece in non palpable breast lesions]. / Control radiológico intraoperatorio de una pieza quirúrgica en lesiones mamarias no palpables.

BACKGROUND: nonconcrete the mammary injuries are frequent in programs of detection of breast cancer, estereotaxic or ecographic marking is required to realize its split. The intrasurgical radiation control of the surgical piece is indispensable to evaluate the margins of the mammary cancer. OBJECTIVE: to determine the effectiveness of the intrasurgical radiation control of the surgical piece in nonconcrete mammary injuries to diminish the surgical reinterventions to extend margins. PATIENTS AND METHOD: women with nonconcrete mammary injuries to those who biopsy by split became, previous marking and intraoperating radiation control of the surgical piece to value margins (suitable margin the same or major of 10 mm, smaller inadequate margin of 10 mm). Intrasurgical reesicion in inadequate radiological margins became. The demographic characteristics, masto-ecographics images, histopathology of the injuries and the radiological-histopatol6gica correlation of the margins studied. Cross-sectional, prospective and descriptive study. RESULTS: 103 patients with 113 nonconcrete mammary injuries included themselves, with age average of 51,35 (32-73) years. In all the injuries the intrasurgical radiation control became of the surgical piece. The prevalence of mammary cancer was of 28.3% (32/113), that corresponds to stellar images (42.8%), suspicious microcalcifications with density (39.2%), microcalcifications (31.2%) and nodules (20%). Of the 32 cancers, 16 had inadequate radiological margins that required intraoperating reescision; suitable histopatologic margins in 100% were obtained (16/16). The 16 (62.5%) cancers without intraoperating reescisi6n by suitable radiological margins had suitable histopatologic margins and 37.5% (6/16) inadequate ones that required surgical reinterventionn to control the margins. The discrepancy between margins was related to microcalcifications in 83.3% of the injuries. CONCLUSIONS: the intrasurgical radiation control of the surgical piece is effective to evaluate margins; the intrasurgical reescisión changed inadequate margins to suitable in 50% (16/32) of the cancers; only 18.7% (6/32) of the total of cases required another surgery to control the margins.

[Unsual clinical signs of primary hyperparathroidism]. / Manifestaciones clínicas inusuales del hiperparatiroidismo primario.

BACKGROUND: A growing number of patients with primary hyperparathyroidism (PHPT) are diagnosed in the absence of symptoms following routine biochemical screening. However, in some countries, overt manifestations and osteitis fibrosa cystica (OFC) still dominate the clinical profile of PHPT patients. METHODS: We retrospectively studied clinical and biochemical manifestations of 47 consecutive patients with primary hyperparathyroidism who were treated with parathyroidectomy from October 1993 to June 2005. RESULTS: Mean age was of 51.3 years. Our sample included 40 women (85%) and 7 men (15%). Seventy eight percent of cases had radiological features of OFC, namely subperiosteal bone resorption, cortical cysts and osteopenia. Pathological fracture occurred in nine patients (19.1%). Fifteen (32%) patients had clinically evident bony deformities or brown tumors mostly located in the mandible and maxilla. CONCLUSIONS: Our results indicate that symptomatic osteitis fibrosa cystica and severe decrease of bone mineral density were the primary manifestations of primary hyperparathyroidism. Most patients were referred to an oncology hospital for treatment due to a suspected malignant neoplasm. A comprehensive clinical evaluation with biochemical markers, imaging studies and histological results is needed to establish a possible diagnosis of primary hyperparathyroidism.

miR­145­5p is associated with pathological complete response to neoadjuvant chemotherapy and impairs cell proliferation by targeting TGFßR2 in breast cancer.

Cancer patients who better benefit from neoadjuvant chemotherapy (NeoCh) are those who achieve a successful pathological complete response (pCR) represented by the absence of residual disease. Unfortunately, no highly sensitive and specific tumor biomarkers for predicting the clinical response to NeoCh have yet been defined. The aim of the present study was to ascertain whether miR­145­5p could discriminate between pCR and no­pCR in triple­negative breast cancer patients that received a cisplatin/doxorubicin­based neoadjuvant treatment. miR­145­5p expression was determined in breast tumors by quantitative RT­PCR. Our data showed that miR­145­5p had a significant low expression (P<0.005) in patients that achieved pCR in comparison to the non­responder group. Kaplan Meier analysis indicated that low levels of miR­145­5p were associated with increased disease­free survival. In addition, receiver operating characteristic (ROC) curve analysis suggested that miR­145­5p is a good predictor of pCR (P<0.003, AUC=0.7899, 95% CI, 0.6382­0.9416). Quantitative RT­PCR expression analysis also revealed that miR­145­5p was downregulated in four breast cancer cell lines relative to normal cells. To study the functions of miR­145­5p, its expression was restored in triple­negative MDA­MB­231 cells and its effects in cell proliferation were evaluated by MTT assays and in apoptosis using Annexin V experiments. Data revealed that ectopic expression of miR­145­5p resulted in a significant inhibition of cell proliferation and also induced apoptosis. Moreover, miR­145­5p led to sensitization of breast cancer cells to cisplatin therapy. In addition, western blot assays indicated that miR­145­5p downregulated the TGFßR2 protein. In conclusion, miR­145­5p could be a potential biomarker of clinical response to NeoCh in triple­negative breast cancer. Functionally miR­145­5p may regulate cell proliferation, at least in part, by targeting TGFßR2.

[Multiple maxillofacial brown tumors as primary hyperparathyroidism manifestation]. / Múltiples tumores pardos maxilofaciales como manifestación de hiperparatiroidismo primario.

OBJECTIVE: In order to analyze the differential diagnosis of giant-cell lesion in facial bones, we present a case of a patient without a previously diagnosed primary hyperparathyroidism that displayed multiple maxillofacial brown tumors as the initial clinical manifestation of the disease. CASE DESCRIPTION: A 70 year-old female with amandible tumor and one year of disease progression. Tumor biopsy confirmed the presence of a giant-cell lesion. Radiologically, we confirmed the presence of another two lytic lesions in the maxillofacial region. During biochemical evaluation prior to surgery, the possibility of hyperparathyroidism was considered. Using computed tomography, we noted a parathyroid tumor in an atypical location. Surgical resection confirmed the presence of an adenoma. Postoperatively, the patient developed symptomatic hypocalcemia and was managed with calcium supplementation in addition to calcitriol. At 4 months after surgery mandibular swelling had regressed partially and serum calcium levels returned to normal levels. CONCLUSION: The detection of giant-cell bone lesions in the maxillofacial region is a strategic diagnostic finding as several entities, among these brown tumor hyperparathyroidism can display similar histologic imaging findings. Only systematic clinical, radiologic, and biochemical evaluation can allow for a definitive diagnosis. The presence of multiple simultaneous maxillofacial brown tumors in primary hyperparathyroidism is an infrequent ocurrence, and only on rare occasions can this be the first sign of the disease.

Loss of function of miR-342-3p results in MCT1 over-expression and contributes to oncogenic metabolic reprogramming in triple negative breast cancer.

Triple-negative breast cancer (TNBC) is a heterogeneous and aggressive neoplasia lacking the expression of hormonal receptors and human epidermal growth factor receptor-2. Accumulating evidence has highlighted the importance of miRNAs dysregulation in the establishment of cancer programs, but the functional role of many miRNAs remains unclear. The description of miRNAs roles might provide novel strategies for treatment. In the present work, an integrated analysis of miRNA transcriptional landscape was performed (N = 132), identifying the significant down-modulation of miR-342-3p in TNBC, probably because of the aberrant activity of estrogen receptor, which serves as a transcription factor of the miRNA, as demonstrated by a siRNA-knockdown approach. The enhanced expression of miR-342-3p significantly decreased cell proliferation, viability and migration rates of diverse TN cells in vitro. Bioinformatic and functional analyses revealed that miR-342-3p directly targets the monocarboxylate transporter 1 (MCT1), which promotes lactate and glucose fluxes alteration, thus disrupting the metabolic homeostasis of tumor cells. Optical metabolic imaging assay defined a higher optical redox ratio in glycolytic cells overexpressing miR-342-3p. Furthermore, we found that hypoxic conditions and glucose starvation attenuate miR-342-3p expression, suggesting a crosstalk program between these metabolic factors. Consistently, miR-342-3p down-modulation is associated with an increased MCT1 expression level and glycolytic score in human triple negative tumors. Overall, we described for the first time the regulatory activity of miR-342-3p on relevant metabolic carcinogenic pathways in TN breast cancers.

[Lymphatic mapping and sentinel lymph node biopsy in patients with high risk squamous cell carcinoma of the skin]. / Mapeo linfático y biopsia del ganglio centinela en pacientes con carcinoma epidermoide cutáneo de alto riesgo.

BACKGROUND: Some sub-groups of cutaneous squamous cell carcinoma (CSCC) display a higher risk for regional metastasis. Sentinel lymph node staging has been used successfully to evaluate nodal metastasis in selective tumors. OBJECTIVE: Assess the feasibility of sentinel node to detect occult regional lymph node metastasis in high-risk CSCC. MATERIAL AND METHODS: Between January 2002 and March 2004, a total of 20 patients received pre-operative lymphoscintigraphy and sentinel lymphadenectomy for high-risk CSCC with clinically non-palpable regional lymph nodes. RESULTS: In one of each 5 patients (20%), sentinel lymph node showed histological evidence of microinvolvement. No patients with negative sentinel node showed tumor dissemination during follow-up, with a mean of 23.5 months (range 7-44). CONCLUSIONS: Sentinel lymph node biopsy is technically feasible with low morbidity. Sentinel lymphadenectomy may play an important role in the management of high-risk CSCC with clinically non-palpable regional lymph nodes. This technique can help identify patients with regional lymph node metastases who may benefit from complete lymphadenectomy. This improved staging may allow clinicians to better stratify patients who might benefit from adjuvant therapy.

[Primary melanoma of the oral mucosa. Experience of the Oncology Hospital of Centro Médico Nacional Siglo XXI]. / Melanoma primario de la mucosa oral. Experiencia del Hospital de Oncología.

BACKGROUND: Primary intraoral melanoma is extremely rare and carries a poor prognosis. Treatment of choice remains controversial. Our aim was to define the clinical features of this disease and to evaluate treatment methods. METHODS: We retrospectively studied 14 patients with primary malignant melanoma of the oral cavity seen at the Oncology Hospital of the Mexican Institute of Social Security (IMSS), 21st Century National Medical Center (CMN-SXXI) between 1991 and 2005. The main variables studied were clinical findings, response to therapy, and outcome. RESULTS: In five males (35.7%) and nine females (64.3%) with a mean age of 65 years, tumor locations included hard palate (nine cases), maxillary gingiva (three cases), hard/soft palate (one case) and lip (one case). Pre-existing melanotic pigmentation was present in two patients. Nine patients were in stage I, four in stage II, and one was in stage III. Surgical excision was the primary treatment in 11 cases; four patients underwent simultaneous neck dissections. All patients in stage II received adjuvant radiation therapy. After a 3-year follow-up, three patients of those presenting stage I are still alive (33.3%, 3/9 cases), and all patients in stages II and III eventually died of the disease. CONCLUSIONS: Early diagnosis of pigmented lesions in the mouth along with adequate tumor resection may improve the prognosis of this disease; however, in advanced disease stage it may be reasonable to infer that major improvements in outcome after treatment of malignant melanoma of the oral cavity may not be carried out until more effective systemic therapy becomes available.

[Clinical and pathological features of breast cancer in a population of Mexico]. / Características clinicopatológicas del cáncer de mama en una población de mujeres en México.

BACKGROUND: Breast cancer is the most common among women in our country, and its treatment is based on prognostic factors to categorize patients into different risk groups. In this study, the clinical and pathological features that play a role as a prognostic factor in a representative population with breast cancer in México are described. MATERIAL AND METHODS: A descriptive analysis of the clinical and pathological features of women diagnosed with breast cancer, in a period from June 2005 to May 2014; registered in a database and calculated by simple frequencies. RESULTS: A total of 4,411 patients were included, the average age at diagnosis was 53 years, 19.7% were diagnosed by mammography screening program and 80.3% derived from any signs or symptoms. Regarding the stages at diagnosis, 6.8% were carcinoma in situ, 36% at early stages (I and IIA), 45% locally advanced (IIB to IIIC), 7.7% metastatic and 3.9% unclassifiable. A 79% were ductal histology, lobular 7.8% and the rest, other types. Of ductal carcinomas, 9.1% were grade I, 54.1% grade II, and 34.6% grade III. Regarding the biological subtypes, 65.7% were luminal, 10.9% luminal Her positive, 8.7% pure Her 2 positive and 14.6% triple negative. CONCLUSION: In the present study, we described the clinical and pathologic features of a group of Mexican women with breast cancer that might reflect a national landscape, and represent the prognostic factors to determine groups of risk and treatment decisions.