scholarly journals Prognostic Significance of Low Claudin3 Expression in Luminal Breast Cancers

2017 ◽  
Vol 11 ◽  
pp. 117822341774585
Author(s):  
Lakmini Mudduwa ◽  
Harshini Peiris ◽  
Shania Gunasekara ◽  
Deepthika Abeysiriwardhana ◽  
Thusharie Liyanage
Keyword(s):  
Breast Cancer ◽  
Prognostic Significance ◽  
Molecular Classification ◽  
Rank Test ◽  
Recurrence Free Survival ◽  
Breast Cancers ◽  
Luminal A ◽  
Cancer Specific Survival ◽  
Free Survival ◽  
Luminal B

Aim: To study the prognostic value of immunohistochemically detected low Claudin3 expression in breast cancers. Methods: This retrospective study included patients with breast cancer who were investigated at our unit from 2006 to 2015. Tissue microarrays were constructed, and immunohistochemical staining was done to assess the Claudin3 expression and to classify breast cancers according to the immunohistochemical surrogates for molecular classification. Kaplan-Meier model and log-rank test were used for recurrence-free survival and breast cancer–specific survival analysis. Results: Of the 853 patients, overall low expression of Claudin3 was seen in 18.4%. Recurrence-free survival of patients with overall low Claudin3 breast cancers was poor in luminal A ( P = .006) and luminal B (Her2−) ( P = .009) subtypes compared with those who had Claudin3 expression in each group. Conclusions: Assessment of Claudin3 expression by immunohistochemistry is suggested for luminal A and luminal B (Her2−) subtypes to identify patients with poor prognosis.

scholarly journals Assessment of Long-term Distant Recurrence-Free Survival Associated With Tamoxifen Therapy in Postmenopausal Patients With Luminal A or Luminal B Breast Cancer

JAMA Oncology ◽  
2019 ◽  
Vol 5 (9) ◽  
pp. 1304 ◽  
Author(s):  
Nancy Y. Yu ◽  
Adina Iftimi ◽  
Christina Yau ◽  
Nicholas P. Tobin ◽  
Laura van ’t Veer ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Distant Recurrence ◽  
Tamoxifen Therapy ◽  
Recurrence Free Survival ◽  
Luminal A ◽  
Free Survival ◽  
Luminal B

Luminal and basal subtyping of prostate cancer.

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 3-3 ◽  
Author(s):  
Felix Yi-Chung Feng ◽  
Shuang Zhao ◽  
Seiwon Laura Chang ◽  
Nicholas Erho ◽  
Jonathan Lehrer ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Prostate Cancer ◽  
Cancer Biology ◽  
Microarray Platform ◽  
Luminal A ◽  
Cancer Specific Survival ◽  
Free Survival ◽  
Luminal B ◽  
Clinical Tools ◽  
Prostate Cancers

3 Background: There is a clear need to develop a clinically relevant molecular subtyping approach for prostate cancer. We hypothesized that prostate cancer can be subtyped based on luminal versus basal lineage. Methods: We applied the PAM50 classifier, which is used clinically to identify luminal and basal cancers in breast cancer, to subtype a total of 3,782 prostate cancer samples using a high-density microarray platform run in a CLIA-certified laboratory. We examined the associations of these subtypes and clinical outcomes. Results: We demonstrate that PAM50 segregates prostate cancer into three reproducible subtypes in both retrospective cohorts and on prospective validation: luminal A (33.3%-34.3%), luminal B (28.5%-32.6%), and basal (34.1%-37.1%). Luminal B prostate cancers exhibited the worst clinical prognoses, followed by basal and luminal A subtypes (10-year biochemical recurrence-free survival: 29/39/41%; distant metastasis-free survival: 53/73/73%; prostate cancer-specific survival: 78/86/89%; overall survival: 69/80/82% respectively) on both univariable and multivariable analyses accounting for standard clinicopathologic prognostic factors. Known luminal lineage markers, such as NKX3.1 and KRT18, and the basal lineage CD49f signature, were enriched in luminal- and basal-like cancers respectively, demonstrating the connection between these subtypes and established prostate cancer biology. While both luminal-like subtypes were associated with increased AR expression and signaling, only luminal B prostate cancers were significantly associated with post-operative response to androgen deprivation therapy (ADT) in a subset analysis matching patients based on clinicopathologic variables (interaction p = 0.006, luminal B 10-year metastasis: 33% (treated) vs. 55% (untreated), non-luminal B: 37% (treated) vs. 21% (untreated)). Conclusions: These findings contribute novel insight into the biology of prostate cancer, and provide translatable clinical tools for personalizing post-operative ADT for patients with prostate cancer. Similar to breast cancer, these findings suggest that luminal/basal subtyping may be useful in treatment selection in prostate cancer.

New molecular breast cancer classification with adjuvant therapy in our population

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e11624-e11624
Author(s):  
E. Richardet ◽  
B Mascheroni ◽  
I Magri ◽  
L Perelli ◽  
M Cortés
Keyword(s):  
Breast Cancer ◽  
Adjuvant Therapy ◽  
Adjuvant Treatment ◽  
Disease Free Survival ◽  
Type A ◽  
Molecular Classification ◽  
Luminal A ◽  
Free Survival ◽  
Luminal B ◽  
Disease Free

e11624 Background: The molecular classification (Perou) helped to identify new groups of patients with different biological behaviors. A retrospective, descriptive, comparative trial with adjuvant chemotherapy treatment was conducted. Objectives: Analyze the natural history of the subgroups of patients, frequency, site of relapse and Disease-free survival (DFS). Materials and Methods: 200 Medical charts of patients with breast cancer were analyzed from 1997 to 2007, who had received adjuvant treatment without Trastuzumab. The 92, 5 % of Luminal A, 91 % of Luminal B y C, the 75.9 % of Her2 (+) and the 69.2 % of Triple Negative (TN) had received adjuvant therapy with FAC, while 30% of the last two groups were treated with taxanes and anthracyclines. We evaluated the site of the first relapse after adjuvant treatment in relation to the new molecular classification. Log-rank test was used to compare the rates of Disease-free survival (DFS). Results: Frequency: Luminal A (86, 42%) Luminal B y C (65, 33%) Her2 + (33, 17%) TN: (16, 8%) The locoregional relapse in the TN group was 36.4% (P = 0.003), the average of bone relapses were 64.5% on the four groups without statically significance compared to other groups. The CNS had a greater trend in TN groups (16.7%) and Her2+ (13.6%), compared to Luminal Type A-B (0 % y 8.3 %). Disease-free survival (DFS): Luminal A 65.0 ± 5.0 months Luminal B y C 50.3 ± 4.3 months HER2 42.9 ± 5.5 months TN 31.1 ± 7.3 months In the analysis of type A luminal subgroup, a prolonged disease free time was showed when compared with the others subgroups, of major statistical significance Log rank (p = 0.002). Conclusions: Her2 negative and TN tumors have less DFS and a higher locoregional and CNS relapse. No significant financial relationships to disclose.

scholarly journals Comparison of survival in non-metastatic inflammatory and other T4 breast cancers: a SEER population-based analysis

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Dechuang Jiao ◽  
Jingyang Zhang ◽  
Jiujun Zhu ◽  
Xuhui Guo ◽  
Yue Yang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cox Model ◽  
Survival Rates ◽  
Tumor Grade ◽  
Population Based ◽  
Rank Test ◽  
Breast Cancers ◽  
Significant Independent Predictor ◽  
Cancer Specific Survival ◽  
7Th Edition

Abstract Background Previous studies have reported poor survival rates in inflammatory breast cancer (IBC) patients than non-inflammatory local advanced breast cancer (non-IBC) patients. However, until now, the survival rate of IBC and other T4 non-IBC (T4-non-IBC) patients remains unexplored. Methods Surveillance, Epidemiology, and End Results (SEER) database was searched to identify cases with confirmed non-metastatic IBC and T4-non-IBC who had received surgery, chemotherapy, and radiotherapy between 2010 and 2015. IBC was defined as per the American Joint Committee on Cancer (AJCC) 7th edition. Breast Cancer-Specific Survival (BCSS) was estimated by plotting the Kaplan-Meier curve and compared across groups by using the log-rank test. Cox model was constructed to determine the association between IBC and BCSS after adjusting for age, race, stage of disease, tumor grade and surgery type. Results Out of a total of 1986 patients, 37.1% had IBC and mean age was 56.6 ± 12.4. After a median follow-up time of 28 months, 3-year BCSS rate for IBC and T4-non-IBC patients was 81.4 and 81.9%, respectively (log-rank p = 0.398). The 3-year BCSS rate in HR−/HER2+ cohort was higher for IBC patients than T4-non-IBC patients (89.5% vs. 80.8%; log-rank p = 0.028), and in HR−/HER2- cohort it was significantly lower for IBC patients than T4-non-IBC patients (57.4% vs. 67.5%; log-rank p = 0.010). However, it was identical between IBC and T4-non-IBC patients in both HR+/HER2- (85.0% vs. 85.3%; log-rank p = 0.567) and HR+/HER2+ (93.6% vs. 91.0%, log-rank p = 0.510) cohorts. After adjusting for potential confounding variables, we observed that IBC is a significant independent predictor for survival of HR−/HER2+ cohort (hazards ratio [HR] = 0.442; 95% CI: 0.216–0.902; P = 0.025) and HR−/HER2- cohort (HR = 1.738; 95% CI: 1.192–2.534; P = 0.004). Conclusions Patients with IBC and T4-non-IBC had a similar BCSS in the era of modern systemic treatment. In IBC patients, the HR−/HER2+ subtype is associated with a better outcome, and HR−/HER2- subtype is associated with poorer outcomes as compared to the T4-non-IBC patients.

Molecular classification of breast cancer. Treatment and prognosis implications.

2021 ◽  
Vol 32 (2) ◽  
pp. 155-159
Author(s):  
M Alcaide Lucena ◽  
CJ Rodríguez González ◽  
S de Reyes Lartategui ◽  
R Gallart Aragón ◽  
MT Sánchez Barrón ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Treatment ◽  
Molecular Classification ◽  
Breast Cancer Treatment ◽  
Cáncer De Mama ◽  
Luminal A ◽  
Luminal B ◽  
Her 2

Resumen Los avances recientes en el campo de la biología molecular y la secuenciación del genoma se han traducido en una nueva clasificación del cáncer de mama, que busca mayor precisión y se correlaciona mejor con el riesgo de recaída de la enfermedad y la respuesta al tratamiento. Establece cuatro subtipos de cáncer de mama: luminal A, luminal B, HER 2 positivo y triple negativo, siendo el subtipo luminal A el de mejor pronóstico, y el triple negativo, el de peor pronóstico. Si combinamos la clasificación clásica histológica con la nueva molecular, nos permite encuadrar a estas pacientes de una forma más precisa en función del riesgo, definiendo así un manejo terapéutico adaptado.

scholarly journals Ki67 index in intrinsic breast cancer subtypes and its association with prognostic parameters

2019 ◽  
Vol 12 (1) ◽  
Author(s):  
Atif Ali Hashmi ◽  
Kashif Ali Hashmi ◽  
Muhammad Irfan ◽  
Saadia Mehmood Khan ◽  
Muhammad Muzzammil Edhi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Ductal Carcinoma ◽  
Prognostic Significance ◽  
Breast Cancer Subtypes ◽  
Prognostic Parameters ◽  
Ki67 Index ◽  
Breast Cancers ◽  
Cancer Subtypes ◽  
Luminal B ◽  
Cancer Management

Abstract Objectives Ki67 is the most commonly used marker to evaluate proliferative index in breast cancer, however no cutoff values have been clearly defined for high ki67 index. Cancer management should be according to loco-regional profile; therefore, we aimed to determine ki67 index in 1951 cases of intrinsic breast cancer subtypes and its association with other prognostic parameters in our set up. Results Triple negative breast cancers showed highest ki67 index (mean 50.9 ± 23.7%) followed by Her2neu (mean 42.6 ± 21.6%) and luminal B cancers (mean 34.9 ± 20.05%). Metaplastic and medullary breast cancers significantly showed higher ki67 index as compared to ductal carcinoma, NOS. No significant association of ki67 index was noted with any of the histologic parameters in different subtypes of breast cancer expect for tumor grade. Although, ki67 index is a valuable biomarker in breast cancer, however no independent prognostic significance of ki67 could be established in our study.

scholarly journals Concordance of immunohistochemistry based and gene expression-based subtyping in breast cancer

2020 ◽  
Author(s):  
Johanna Holm ◽  
Nancy Yiu-Lin Yu ◽  
Annelie Johansson ◽  
Alexander Ploner ◽  
Per Hall ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Distant Recurrence ◽  
Tamoxifen Treatment ◽  
Survival Models ◽  
Recurrence Free Survival ◽  
Luminal A ◽  
Ki 67 ◽  
Treatment Benefit ◽  
Free Survival ◽  
Cancer Subtypes

Abstract Background Use of immunohistochemistry (IHC) based surrogates of molecular breast cancer subtypes is common in research and clinical practice, but information on their comparative validity and prognostic capacity is scarce. Methods Data from two PAM50-subtyped Swedish breast cancer cohorts were used; STO-3 with 561 patients diagnosed 1976-1990, and Clinseq with 237 patients diagnosed 2005-2012. We evaluated three surrogate classifications; the IHC3 surrogate classifier based on ER/PR/HER2, and the StGallen and Prolif surrogate classifiers also including Ki-67. Accuracy, kappa, sensitivity and specificity were computed as compared to PAM50. Alluvial diagrams of misclassification patterns were plotted. Distant recurrence-free survival was assessed using Kaplan-Meier plots, and tamoxifen treatment benefit for luminal subtypes was modeled using flexible parametric survival models. Results The concordance with PAM50 ranged from poor to moderate (kappa = 0.36–0.57, accuracy = 0.54-0.75), with best performance for the Prolif surrogate classification in both cohorts. Good concordance was only achieved when luminal subgroups were collapsed (kappa = 0.71- 0.69, accuracy = 0.90-0.91). The StGallen surrogate classification misclassified luminal A into luminal B, the reverse pattern was seen with the others. In distant recurrence-free survival, surrogates were more similar to each other than PAM50. The difference in tamoxifen treatment benefit between luminal A and B for PAM50 was not replicated with any surrogate classifier. Conclusions All surrogate classifiers had limited ability to distinguish between PAM50 luminal A and B, but patterns of misclassifications differed. PAM50 subtyping appeared to yield larger separation of survival between luminal subtypes than any of the surrogate classifications.

Basal-like Breast Cancer—Characteristics, Risks, and Associations

2012 ◽  
Vol 08 (01) ◽  
pp. 26
Author(s):  
Andrew Y Shuen ◽  
William D Foulkes ◽  
◽  
Keyword(s):  
Breast Cancer ◽  
Massively Parallel Sequencing ◽  
Target Identification ◽  
Response To Therapy ◽  
Breast Cancers ◽  
Luminal A ◽  
Luminal B ◽  
Predictors Of Response ◽  
Epidemiological Risk ◽  
Basal Like Breast Cancer

Breast cancer is a heterogeneous disease. Gene expression profiling has demonstrated the existence of at least five ‘intrinsic’ subtypes: luminal A, luminal B, human epidermal growth factor-2 receptor (HER2), normal-like, and basal-like. While the estrogen receptor (ER), progesterone receptor (PR), and HER2 remain the most important prognostic markers and predictors of response to therapy, interrogating thousands of genetic transcripts more accurately captures the biological complexity and clinical heterogeneity of this disease. Target identification through massively parallel sequencing is likely to bear fruit in the coming years. Attention to basal-like breast cancers has grown substantially due to their generally poor prognosis, lack of targeted therapies, and connection withBRCA1-related cancers. In this article, we discuss the basal-like subgroup with respect to its cellular origins, relationship toBRCA1, and associated epidemiological risk factors.

Evaluating the prognostic significance of JAK2 in distant breast cancer recurrence.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e22178-e22178
Author(s):  
Carl Anthony Blau ◽  
Christopher P. Miller ◽  
Amanda N. Kortum ◽  
Jason D. Thorpe ◽  
Michel Schummer ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Validation Cohort ◽  
Prognostic Significance ◽  
Cancer Recurrence ◽  
Distant Recurrence ◽  
Breast Cancer Recurrence ◽  
Mrna Levels ◽  
Recurrence Free Survival ◽  
Free Survival ◽  
Control Study

e22178 Background: Estrogen, progesterone, and epidermal growth factor receptor ligands stimulate growth in a subset of breast cancers, however recent studies suggest roles for additional factors such as interleukins-6 and 8, prolactin, and erythropoietin. These and other growth factors act upon ligand-specific receptors to activate janus kinase 2 (JAK2), and JAK2 inhibitors are under investigation as a novel targeted therapy. We tested whether erythropoietin receptor (EPOR) or JAK2 mRNA levels are associated with distant breast cancer recurrence. Methods: We used quantitative RT-PCR to measure mRNA levels of JAK2, EPOR and a series of control genes using archival tumors from 112 women who experienced distant breast cancer recurrence (cases) and 112 tumors from women who did not (controls). Cases and controls were matched for tumor size, lymphovascular invasion, nodal status, extra-nodal extension, and ER/PR/HER2. Recurrence risks were evaluated using logistic regression. Associations between mRNA levels (via microarray data) and recurrence-free survival were validated in an independent cohort from the Netherlands Cancer Institute (n=295) using Cox proportional hazards regression. Results: Increasing JAK2 mRNA levels strongly correlated with a reduced risk of distant recurrence in our case control study (univariate p=0.0004, multivariate p=0.003), and with improved recurrence-free survival in the validation cohort (univariate p=0.0009; multivariate p=0.003). Remarkably, in the validation cohort, the ranking of the prognostic significance of JAK2 (top 3.5% of ~25,000 genes) was comparable to the known strong prognostic indicator of recurrence, ESR1 (top 1.3%). Similarly although less prominently, increasing EPORmRNA levels were significantly associated with reduced distant recurrence in our case control study (continuous model: univariate p=0.01, multivariate p=0.05) and with improved recurrence free survival in the validation cohort in univariate (p=0.03) but not multivariate analysis (p=0.35). Conclusions: JAK2 mRNA levels in breast tumors correlate with a reduced risk of recurrence. Understanding the mechanistic basis for this association is important for the rational application of JAK2 inhibitors.

Invasive micropapillary breast cancer: Single-institution experience in the modern era.

2013 ◽  
Vol 31 (26_suppl) ◽  
pp. 150-150
Author(s):  
Amy E. Voci ◽  
Camilla Boafo ◽  
Anne Eaton ◽  
Michelle Stempel ◽  
Jorge Reis- Filho ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Targeted Therapy ◽  
Hormonal Therapy ◽  
Cox Regression ◽  
Molecular Classification ◽  
Outcome Data ◽  
Rank Test ◽  
Palpable Mass ◽  
Luminal B ◽  
Factors Associated

150 Background: Invasive micropapillary breast cancer (IMPC) is a rare special histologic type of breast cancer with a propensity for nodal metastases. Molecularly, IMPCs have been classified as luminal B; however, clinical outcome data in the era of targeted therapy are limited. Here we report our institutional experience with IMPC. Methods: We retrospectively reviewed our prospective database from 1995-2009 to identify patients who had surgery for IMPC. Clinical characteristics and outcomes were abstracted from the medical record. Overall survival (OS) was estimated using Kaplan-Meier methods. Factors associated with OS and trends over time were assessed using the log-rank test and Cox regression. Results: We identified 258 patients with IMPC. Median patient age 56yrs (range 26-91), 157(61%) postmenopausal, 147(57%) presented with a palpable mass. The majority of IMPCs were grade 3 (83%), estrogen receptor (ER)-positive (86%) and HER2-neg (81%) with LVI (60%) and nodal metastasis (62%). 194 (75%) patients received chemotherapy (CTX), 204 (81%) hormonal therapy and 37/48 (77%) HER2-pos patients received trastuzumab. At a median follow-up of 55 months (range 1-173mos), 5yr OS is 89.5% with a trend towards improved survival in later yrs; 5 year OS 1995-2005 vs 2006-2009, 85% vs 91%, respectively (p=0.06) Clinical factors associated with OS are shown (Table). Among ER-pos/HER2-neg patients, progesterone receptor (PR) status was strongly associated with 5yr OS. Conclusions: In this large cohort of patients with IMPC treated at a single center, OS was associated with tumor size, PR status, use of CTX and trastuzumab but not with ER or hormonal therapy. These clinical data support the molecular classification of IMPC as luminal B cancers which have a more aggressive clinical behavior than other ER+ cancers. The trend towards improved survival in later years likely reflects the benefits of targeted therapy. [Table: see text]

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