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1.
Int J Mol Sci ; 25(15)2024 Jul 24.
Article in English | MEDLINE | ID: mdl-39125649

ABSTRACT

lncRNAs are noncoding transcripts with tissue and cancer specificity. Particularly, in breast cancer, lncRNAs exhibit subtype-specific expression; they are particularly upregulated in luminal tumors. However, no gene signature-based laboratory tests have been developed for luminal breast cancer identification or the differential diagnosis of luminal tumors, since no luminal A- or B-specific genes have been identified. Particularly, luminal B patients are of clinical interest, since they have the most variable response to neoadjuvant treatment; thus, it is necessary to develop diagnostic and predictive biomarkers for these patients to optimize treatment decision-making and improve treatment quality. In this study, we analyzed the lncRNA expression profiles of breast cancer cell lines and patient tumor samples from RNA-Seq data to identify an lncRNA signature specific for luminal phenotypes. We identified an lncRNA signature consisting of LINC01016, GATA3-AS1, MAPT-IT1, and DSCAM-AS1 that exhibits luminal subtype-specific expression; among these lncRNAs, GATA3-AS1 is associated with the presence of residual disease (Wilcoxon test, p < 0.05), which is related to neoadjuvant chemotherapy resistance in luminal B breast cancer patients. Furthermore, analysis of GATA3-AS1 expression using RNA in situ hybridization (RNA ISH) demonstrated that this lncRNA is detectable in histological slides. Similar to estrogen receptors and Ki67, both commonly detected biomarkers, GATA3-AS1 proves to be a suitable predictive biomarker for clinical application in breast cancer laboratory tests.


Subject(s)
Biomarkers, Tumor , Breast Neoplasms , Drug Resistance, Neoplasm , Gene Expression Regulation, Neoplastic , Neoadjuvant Therapy , RNA, Long Noncoding , Humans , RNA, Long Noncoding/genetics , Breast Neoplasms/genetics , Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , Breast Neoplasms/metabolism , Female , Drug Resistance, Neoplasm/genetics , Biomarkers, Tumor/genetics , Cell Line, Tumor , Gene Expression Profiling , GATA3 Transcription Factor/genetics , GATA3 Transcription Factor/metabolism , Transcriptome
2.
Int J Mol Sci ; 24(8)2023 Apr 18.
Article in English | MEDLINE | ID: mdl-37108589

ABSTRACT

Given their tumor-specific and stage-specific gene expression, long non-coding RNAs (lncRNAs) have demonstrated to be potential molecular biomarkers for diagnosis, prognosis, and treatment response. Particularly, the lncRNAs DSCAM-AS1 and GATA3-AS1 serve as examples of this because of their high subtype-specific expression profile in luminal B-like breast cancer. This makes them candidates to use as molecular biomarkers in clinical practice. However, lncRNA studies in breast cancer are limited in sample size and are restricted to the determination of their biological function, which represents an obstacle for its inclusion as molecular biomarkers of clinical utility. Nevertheless, due to their expression specificity among diseases, such as cancer, and their stability in body fluids, lncRNAs are promising molecular biomarkers that could improve the reliability, sensitivity, and specificity of molecular techniques used in clinical diagnosis. The development of lncRNA-based diagnostics and lncRNA-based therapeutics will be useful in routine medical practice to improve patient clinical management and quality of life.


Subject(s)
Breast Neoplasms , RNA, Long Noncoding , Humans , Female , Breast Neoplasms/diagnosis , Breast Neoplasms/genetics , Breast Neoplasms/metabolism , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , Quality of Life , Reproducibility of Results , Biomarkers , Biomarkers, Tumor/genetics , Gene Expression Regulation, Neoplastic
3.
Cancer Epidemiol ; 84: 102366, 2023 06.
Article in English | MEDLINE | ID: mdl-37086645

ABSTRACT

BACKGROUND: The present study assesses the time intervals from symptom discovery to treatment start and describes the health service use experiences of uninsured patients with cancer of the breast, cervix uteri, testicle, and prostate before their arrival to the cancer hospital. METHODS: This cross-sectional study included 1468 patients who were diagnosed between June 2016 and May 2017 and received treatment for the selected cancers in two of the largest public cancer hospitals in Mexico City, financed through Seguro Popular. Data was collected through a survey administered via face-to-face interviews with patients and a review of their medical files. RESULTS: The median time between detection (symptom discovery or first abnormal screening test) and treatment start was 6.6 months. For all types of cancer, the longest interval was the diagnostic interval -between the first use of healthcare services and the confirmation of cancer. Less than 20% cancer patients were diagnosed in the earliest stages that are associated with the best chances of long-term survival. The participants described a high use of private services for their first consultation, the use of several different types of health services and multiple consultations before arrival to the cancer centers, and 35% perceived being misdiagnosed by the first doctor they consulted. CONCLUSIONS: Most cancer patients treated in the two largest public institutions available for the uninsured faced long delays to get diagnosed and started treatment at advanced stages. Strengthening quality and access for effective early cancer diagnosis and treatment is key to improve patient outcomes in low and middle-income settings.


Subject(s)
Medically Uninsured , Neoplasms , Male , Female , Humans , Mexico , Cross-Sectional Studies , Health Services , Patient Acceptance of Health Care , Financing, Government , Health Services Accessibility
4.
Clin Transl Oncol ; 25(1): 151-159, 2023 Jan.
Article in English | MEDLINE | ID: mdl-35986133

ABSTRACT

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.


Subject(s)
Breast Neoplasms , Physicians , Humans , Female , Breast Neoplasms/therapy , Cross-Sectional Studies , Mexico , Attitude of Health Personnel , Guideline Adherence , Practice Patterns, Physicians' , Surveys and Questionnaires
7.
Cancers (Basel) ; 13(20)2021 Oct 12.
Article in English | MEDLINE | ID: mdl-34680239

ABSTRACT

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.

8.
Breast Cancer Res Treat ; 188(2): 489-500, 2021 Jul.
Article in English | MEDLINE | ID: mdl-34132938

ABSTRACT

PURPOSE: Pregnancy-associated breast cancer (PABC) poses a clinical challenge and its prognosis remains controversial. During the pregnancy and postpartum periods, the breast undergoes biological events that may uniquely influence disease behavior and treatment response. This study aimed to assess if a PABC diagnosis influences survival compared to non-PABC. METHODS: A single-center record review was performed to identify PABC patients diagnosed from January 2007 through June 2018. Two controls were matched to each PABC case by stage, immunohistochemical (IHC) subtype, age (± 3) and year of diagnosis (± 2). Disease-free survival (DFS) and overall survival (OS) were estimated with the Kaplan-Meier method and compared with the log-rank test. Multivariate analysis was used to assess the impact of PABC on outcomes. RESULTS: 125 PABC patients (pregnant: 62; postpartum: 63) and 250 controls were included. Median follow-up was 67.7 and 73.4 months, respectively. 4-year DFS was 62% in pregnant vs 78% in controls (p = 0.010), and 63% in postpartum vs 83% in controls (p = 0.034). Subanalysis by IHC subtype revealed a significantly inferior DFS in PABC with hormone receptor-positive/HER2-negative (p = 0.032) and HER2-positive disease (p = 0.005) compared to corresponding non-PABC patients. 4-year OS was similar between case groups and controls. Multivariate analysis supported the independent impact of pregnant and postpartum status on DFS (p < 0.05). CONCLUSION: Patients diagnosed during pregnancy and early postpartum are at high risk of recurrence. Further research is warranted to better characterize PABC tumor biology and enable the identification of novel therapeutic interventions to improve treatment outcomes.


Subject(s)
Breast Neoplasms , Pregnancy Complications, Neoplastic , Breast Neoplasms/diagnosis , Case-Control Studies , Female , Humans , Neoplasm Recurrence, Local , Postpartum Period , Pregnancy , Pregnancy Complications, Neoplastic/diagnosis , Prognosis
9.
J Natl Compr Canc Netw ; : 1-8, 2021 Jun 21.
Article in English | MEDLINE | ID: mdl-34153944

ABSTRACT

BACKGROUND: Despite the risk of treatment-related infertility, implementation of fertility-preservation (FP) strategies among young patients with breast cancer is often suboptimal in resource-constrained settings such as Mexico. The "Joven & Fuerte: Program for Young Women With Breast Cancer" strives to enhance patient access to supportive care services, including FP measures through alliances with assisted-reproduction units and procurement of coverage of some of these strategies. This study describes patients from Joven & Fuerte who have preserved fertility, and assesses which characteristics were associated with the likelihood of undergoing FP. METHODS: Women aged ≤40 years with recently diagnosed breast cancer were prospectively accrued. Sociodemographic and clinicopathologic data were collected from patient-reported and provider-recorded information at diagnosis and 1-year follow-up. Descriptive statistics, chi-square test, and simple logistic regression were used to compare patients who preserved fertility with those who did not. RESULTS: In total, 447 patients were included, among which 53 (12%) preserved fertility, representing 38% of the 140 women who desired future biologic children. Oocyte/embryo cryopreservation was the most frequently used method for FP (59%), followed by temporary ovarian suppression with gonadotropin-releasing hormone agonists (GnRHa) during chemotherapy (26%), and use of both GnRHa and oocyte/embryo cryopreservation (15%). Younger age, higher educational level, being employed, having private healthcare insurance, and having one or no children were associated with a significantly higher likelihood of preserving fertility. CONCLUSIONS: By facilitating referral and seeking funds and special discounts for underserved patients, supportive care programs for young women with breast cancer can play a crucial role on enhancing access to oncofertility services that would otherwise be prohibitive because of their high costs, particularly in resource-constrained settings. For these efforts to be successful and widely applied in the long term, sustained and extended governmental coverage of FP options for this young group is warranted.

11.
Genes (Basel) ; 11(11)2020 11 19.
Article in English | MEDLINE | ID: mdl-33227964

ABSTRACT

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.


Subject(s)
Mutation , Triple Negative Breast Neoplasms/genetics , Triple Negative Breast Neoplasms/mortality , Adult , Aged , DNA Repair-Deficiency Disorders/genetics , Female , Humans , Kaplan-Meier Estimate , Lymphocytes, Tumor-Infiltrating/pathology , Middle Aged , Triple Negative Breast Neoplasms/drug therapy , Triple Negative Breast Neoplasms/pathology , Exome Sequencing
12.
Clin Breast Cancer ; 20(4): 307-316.e1, 2020 08.
Article in English | MEDLINE | ID: mdl-32305297

ABSTRACT

PURPOSE: Neutrophils are among the key cellular players in the inflammatory milieu produced in patients with breast cancer (BC), and strong evidence exists in terms of the prognostic value of assessing the neutrophil-to-lymphocyte ratio (NLR) in patients with BC. In this study we sought to determine whether the baseline NLR correlates with pathological complete response (pCR), disease-free survival (DFS), and overall survival (OS) in patients with locally advanced BC in the neoadjuvant chemotherapy (NAC) setting. METHODS: We analyzed the pretreatment NLR from the first blood count of patients treated from 2007 to 2015 in terms of pCR, DFS, and OS in patients with locally advanced BC. Patients received standard medical care based on national guidelines. RESULTS: A total of 1519 patients were included in the study. Median age was 49 years (22-88). The cutoff point for NLR was 2.0. NLR was not associated with pCR or DFS. However, patients with high NLR had worse OS in the presence of triple-negative BC (105.9 months; 95% confidence interval [CI], 100.2-111.5] vs. 98.7 months; 95% CI, 91.1-106.3; P = .029), Her2 overexpression (114.0 months; 95% CI, 110.5-118.0 vs. 100.8 months; 95% CI 95.7-105.9; P = .019), and residual disease after NAC for both phenotypes. Multivariate analysis showed that NLR was independently associated with OS (hazard ratio, 1.4; 95% CI, 1.02-1.95; P = .037). CONCLUSIONS: Pretreatment NLR in patients with locally advanced BC correlates with OS as an independent prognostic factor. This influence depends on phenotype and residual disease. Routine assessment of this parameter could be an easy and affordable tool for defining prognosis.


Subject(s)
Breast Neoplasms/therapy , Lymphocytes , Neoadjuvant Therapy/methods , Neoplasm Recurrence, Local/epidemiology , Neutrophils , Adult , Aged , Aged, 80 and over , Breast/pathology , Breast/surgery , Breast Neoplasms/blood , Breast Neoplasms/mortality , Breast Neoplasms/pathology , Chemotherapy, Adjuvant/statistics & numerical data , Disease-Free Survival , Female , Humans , Kaplan-Meier Estimate , Longitudinal Studies , Lymphocyte Count , Mastectomy , Middle Aged , Neoadjuvant Therapy/statistics & numerical data , Neoplasm Recurrence, Local/prevention & control , Prognosis , Receptor, ErbB-2/analysis , Receptor, ErbB-2/metabolism , Receptors, Estrogen/analysis , Receptors, Estrogen/metabolism , Receptors, Progesterone/analysis , Receptors, Progesterone/metabolism , Retrospective Studies , Young Adult
13.
Support Care Cancer ; 28(10): 4943-4951, 2020 Oct.
Article in English | MEDLINE | ID: mdl-32020358

ABSTRACT

OBJECTIVE: The aim of this study was to evaluate patients' outlook and satisfaction with "Joven & Fuerte: Program for Young Women with Breast Cancer (YWBC) in Mexico" (J&F) and to determine its strengths and areas of improvement to better fulfill patients' information and supportive care needs. METHODS: Patients enrolled in J&F for ≥ 6 months at three cancer referral centers were invited via a messaging application to anonymously complete an online survey exploring their perspectives of the program's information delivery, support services, and research component. Descriptive statistics, chi2 test, Student t, and ANOVA were used for analysis. RESULTS: Of 484 eligible patients, 28% completed the survey. The program overall was useful/very useful according to 97% and aided 82% to better cope with their illness. The timing, clarity, and usefulness of the information provided were each described as good/very good by ≥ 83% for the written format and ≥ 98% for the verbal one. Eighty-four percent of patients were very satisfied (≥ 9/10) with psychological support and genetic assessment. The number of support services used was significantly associated with patients' perception of J&F's usefulness. Regarding fertility issues, 45% recalled being informed about preservation strategies and J&F financially supported 27/39 of interested patients. Fifty-eight percent were unaware of J&F's ongoing research component. CONCLUSIONS: Patients' satisfaction with J&F is very high, reflecting that the program is meeting Mexican YWBC's needs by providing useful information means and support services in a limited-resource setting. Efforts must keep up to guarantee the program's continuity and advocate for its extension to other oncologic centers.


Subject(s)
Breast Neoplasms/psychology , Breast Neoplasms/therapy , Palliative Care/methods , Patient Satisfaction , Adaptation, Psychological , Adult , Cross-Sectional Studies , Female , Humans , Mexico , Palliative Care/psychology , Palliative Care/standards , Patient Education as Topic , Socioeconomic Factors , Surveys and Questionnaires
14.
Breast Cancer Res Treat ; 176(1): 243-249, 2019 Jul.
Article in English | MEDLINE | ID: mdl-30997623

ABSTRACT

PURPOSE: The aim of this study was to compare the difference in disease-free survival (DFS) and overall survival (OS) between invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC) in our Hispanic population with breast cancer (BC). METHODS: We retrospectively analyzed a database of 4533 non-metastatic BC patients treated for BC at the National Cancer Institute in Mexico (INCan) between 2006 and 2016. We compared clinical characteristics, treatment and survival between women with invasive ductal and invasive lobular BC. We evaluated differences between survival curves with the log-rank test and used Cox's proportional hazards model for the multivariate analysis. RESULTS: Median follow-up time was 42.13 months (IQ25 25.2-IQ75 72.06). The median age was 50.9 years (IQ25 43.5-IQ75 59.8). DFS at 5 years was 80.8% for IDC versus 76.2% for ILC. 5 years OS was 88.7% for IDC versus 84.3% for ILC. Multivariate analysis showed that factors that negatively affected the 5-year DFS include: clinical stage III [hazard ratio (HR) 4.2, 95% CI 3.36-5.35; p < 0.001], triple negative phenotype (HR 1.4, 95% CI 1.08-1.81; p = 0.009), Ki67 ≥ 18 (HR 1.6, 95% CI 1.28-2.11; p < 0.001), and lobular histological type (HR 1.6, 95% CI 1.09-2.49; p = 0.017). Factors associated with a negative impact on OS were: clinical stage III (HR 4.5, 95% CI 3.15-6.54; p < 0.001), triple negative phenotype (HR 2.4, 95% CI 1.69-3.48; p < 0.001), and Ki67 ≥ 18% (HR 1.9, 95% CI 1.27-2.92; p = 0.02). CONCLUSION: Our results highlight the different biology of ILC and show that long-term prognosis in terms of DFS is not as favorable as previously reported.


Subject(s)
Breast Neoplasms/mortality , Breast Neoplasms/pathology , Carcinoma, Lobular/mortality , Carcinoma, Lobular/pathology , Adult , Aged , Aged, 80 and over , Biomarkers, Tumor , Breast Neoplasms/epidemiology , Breast Neoplasms/therapy , Carcinoma, Lobular/epidemiology , Carcinoma, Lobular/therapy , Combined Modality Therapy , Female , Humans , Mexico/epidemiology , Middle Aged , Neoplasm Invasiveness , Neoplasm Staging , Population Surveillance , Young Adult
15.
BMC Cancer ; 19(1): 118, 2019 Feb 01.
Article in English | MEDLINE | ID: mdl-30709381

ABSTRACT

BACKGROUND: Heterozygous germline TP53 gene mutations result in Li-Fraumeni Syndrome (LFS). Breast cancer (BC) is the most frequent tumor in young women with LFS. An important issue related to BC in the Mexican population is the average age at diagnosis, which is approximately 11 years younger than that of patients in the United States (U.S.) and Europe. The aim of this study was to determine the prevalence of germline mutations in TP53 among young Mexican BC patients. METHODS: We searched for germline mutations in the TP53 gene using targeted next-generation sequencing (NGS) in 78 BC patients younger than 45 years old (yo) who tested negative for BRCA1/2 mutations. A group of 509 Mexican women aged 45yo or older without personal or family BC history (parents/grandparents) was used as a control. RESULTS: We identified five patients with pathogenic variants in the TP53 gene, equivalent to 6.4% (5/78). Among patients diagnosed at age 36 or younger, 9.4% (5/55) had pathogenic TP53 mutations. Three of these variants were missense mutations (c.844C > T, c.517G > A, and c.604C > T), and the other two mutations were frameshifts (c.291delC and c.273dupC) and had not been reported previously. We also identified a variant of uncertain clinical significance (VUS), c.672G > A, which causes a putative splice donor site mutation. All patients with TP53 mutations had high-grade and HER2-positive tumors. None of the 509 patients in the healthy control group had mutations in TP53. CONCLUSIONS: Among Mexican BC patients diagnosed at a young age, we identified a high proportion with germline mutations in the TP53 gene. All patients with the TP53 mutations had a family history suggestive of LFS. To establish the clinical significance of the VUS found, additional studies are needed. Pathogenic variants of TP53 may explain a substantial fraction of BC in young women in the Mexican population. Importantly, none of these mutations or other pathological variants in TP53 were found in the healthy control group.


Subject(s)
Breast Neoplasms/genetics , Genes, p53/genetics , Genetic Predisposition to Disease/genetics , Germ-Line Mutation/genetics , Adult , Age Factors , Breast Neoplasms/epidemiology , Breast Neoplasms/pathology , Female , Genetic Association Studies , Genetic Variation , Humans , Li-Fraumeni Syndrome/epidemiology , Li-Fraumeni Syndrome/genetics , Mexico/epidemiology , Pedigree , Prevalence , Young Adult
16.
Am J Nucl Med Mol Imaging ; 8(5): 341-350, 2018.
Article in English | MEDLINE | ID: mdl-30510851

ABSTRACT

Our study examines the association between two Positron Emission Mammography (PEM) semi-quantitative parameters: PUVmax (maximum uptake value) and LTB (lesion to background) baseline and the end of Neoadjuvant chemotherapy (NAC) with pathologic response in each of the following breast cancer subtype: Triple negative breast cancer (TPN), HER2-positive, and ER-positive/HER2-negative cancers. One-hundred and eight patients, 71 with invasive ductal carcinoma and 37 with infiltrating lobular carcinoma were evaluate with 18F-FDG-PEM scans before and after of NAC. We assessed the impact of 2 PEM semi-quantitative parameters for molecular subtype correlated with pathologic response according Miller-Payne grade (MPG). After NAC, an overall reduction of 2 PEM semi-quantitative parameters was found. Neither breast cancer subtypes nor Ki67 modified chemotherapy responses. Compared to PUVmax, an overall increase of LTB was found in baseline condition, independent of the expressed immunophenotype. Post-treatment values of PUVmax revealed a significant reduction compared to baseline values (4.8 ± 0.26 vs. 1.9 ± 0.18; P < 0.001) and LTB exhibited a significant decay after the first course of NAC (15.8 ± 1.36 vs. 5.5 ± 0.49; P < 0.001). Using the Kruskal-Wallis H test which showed no correlation between the different molecular subtypes and the MPG and PUVmax and LTB (P = 0.52). Two PEM semi-quantitative parameters demonstrated a statically significant correlation and equivalence across the different breast cancer subtypes correlated with pathologic response according to MPG. PEM did not allow for prediction of NAC response in terms of breast cancer biomarkers, it is not discarded that this technology might be helpful for individual treatment stratification in breast cancer.

18.
J Geriatr Oncol ; 9(6): 620-625, 2018 11.
Article in English | MEDLINE | ID: mdl-29691196

ABSTRACT

INTRODUCTION: Although the epidemiology of breast cancer in older women has been widely described before, little is known about the clinical characteristics and prognosis of older patients living in developing countries. Here, we studied older women with breast cancer treated at a public cancer center in Mexico City, and compared their outcomes with their younger counterparts. MATERIALS AND METHODS: We retrospectively analyzed a database of 5488 women treated for breast cancer at a single institution. We compared clinical characteristics, treatment and survival between women aged <65 and ≥65 years of age. Survival analyses were performed for each molecular subtype. RESULTS: 851 women (15.5%) were ≥65 years of age, of which 45% presented with Stages III-IV disease. Compared with their younger counterparts, older women had lower grade disease, a larger proportion of hormone receptor positive tumors, and were less likely to receive both chemotherapy and radiotherapy. At 5 years, no differences in both disease free and overall survival were found between younger and older women in a multivariate model including stage, grade, tumor subtype and treatment received. CONCLUSIONS: In contrast with reports from high-income countries, older women with breast cancer in developing nations present with more advanced disease requiring more aggressive treatment. Strategies aimed at earlier detection, improved access to care, and downstaging among older adults are greatly needed in Mexico and in the rest of the developing world.


Subject(s)
Breast Neoplasms/mortality , Breast Neoplasms/therapy , Age Factors , Aged , Aged, 80 and over , Breast Neoplasms/pathology , Comorbidity , Developing Countries , Female , Humans , Mastectomy/statistics & numerical data , Mexico/epidemiology , Neoplasm Staging , Retrospective Studies , Treatment Outcome
19.
Oncologist ; 23(6): 670-678, 2018 06.
Article in English | MEDLINE | ID: mdl-29490940

ABSTRACT

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).


Subject(s)
Breast Neoplasms/complications , Ki-67 Antigen/metabolism , Neoadjuvant Therapy/adverse effects , Adult , Aged , Aged, 80 and over , Breast Neoplasms/pathology , Female , Humans , Middle Aged
20.
Cancer Treat Res Commun ; 16: 24-31, 2018.
Article in English | MEDLINE | ID: mdl-31298999

ABSTRACT

Neoadjuvant chemotherapy (NAC) has an important role in patients with locally advanced cancers, treating distant micrometastases, downstaging tumors, improving operability, and sometimes allowing breast-conserving surgery to take place. We studied the association between two Positron Emission Mammography with 18F-FDG (18F-FDG-PEM) semi-quantitative parameters in 108 patients and correlated with pathologic response in each of the following breast cancer subtype: Triple negative breast cancer (TPN), HER2-positive, and ER-positive/HER2-negative cancers. AIM: Examine the association between two Positron Emission Mammography (PEM) semi-quantitative parameters: PUVmax (maximum uptake value) and LTB (lesion to background) baseline and the end of NAC with pathologic response in each breast cancer subtype. METHODS: 108 patients, 71 with invasive ductal carcinoma and 37 with infiltrating lobular carcinoma were evaluate with 18F-FDG-PEM scans baseline and after end of NAC. We assessed the impact of 2 PEM semi-quantitative parameters for molecular subtype correlated with pathologic response according Miller-Payne grade (MPG). RESULTS: After NAC, an overall reduction of 2 PEM semi-quantitative parameters was found. Neither breast cancer subtypes nor Ki67 modified chemotherapy responses. Compared to PUVmax, an overall increase of LTB was found in baseline condition, independent of the expressed immunophenotype. Post-treatment values of PUVmax revealed a significant reduction compared to baseline values (4.8 ±â€¯0.26 vs. 1.9 ±â€¯0.18; p < 0.001) and LTB exhibited a significant decay after the first course of NACT (15.8 ±â€¯1.36 vs. 5.5 ±â€¯0.49; p < 0.001). Using the Kruskal-Wallis H test which showed no correlation between the different molecular subtypes and the MPG and PUVmax and LTB (p = 0.52), but if a correlation was found between the response rate by MPG and both semiquantitative parameters (p = 0.05). CONCLUSION: 2 PEM semi-quantitative parameters demonstrated a statically significant correlation and equivalence across the different breast cancer subtypes correlated with pathologic response according to MPG. PEM did not allow for prediction of NAC response in terms of breast cancer biomarkers, it is not discarded that this technology might be helpful for individual treatment stratification in breast cancer.

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