A new genomic approach to describe the natural history of node negative breast cancer patients

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 10058-10058
Author(s):  
M. Saghatchian ◽  
R. Lidereau ◽  
S. Delaloge ◽  
S. Koscielny ◽  
A. Kauffmann ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Prediction Accuracy ◽  
Complex Disease ◽  
Statistical Significance ◽  
Normal Breast ◽  
Benign Tumors ◽  
Consecutive Series ◽  
Breast Cancers ◽  
Node Negative ◽  
Breast Cancer Outcome

10058 Background: Breast cancer is a heterogeneous and complex disease beyond good/bad prognosis groups. Previous studies identified prognostic tools that are undergoing inter-group validation. Our present study aims at better defining pre-malignant vs. malignant lesions and tumors that will give local vs. distant metastases (DM) or early vs. late DM. Methods: We selected 3 groups of patients (pts) in a consecutive series of node-negative breast cancers with a very long follow-up (>10 years (y)) and available frozen tumor samples. Pts who did not receive any adjuvant treatment were selected: 60 with no relapse after 10 y, 29 with early DM before 5 y and 18 with late DM after 5y. Genomic profiling on 44K Agilent pangenomic arrays taking as reference non-relapsing pts (after 10y) or normal breast (Clonetech) allowed us to select specific genes related to DM occurrence or tumorigenesis. Random permutations were performed to assess the statistical significance of our prediction accuracy. Results: 1- we identified a 141 gene-profile and related genes distinguishing tumors with early DM from tumors with late DM (71% prediction accuracy). 2- Similarly, we identified a 285-gene signature for late DM vs. no relapse at 10 y (80% prediction accuracy). Genes were further classified according to family clusters allowing description of genes involved in DM occurrence. 3- a total of 435 genes were also significantly over-expressed in at least 90% of 148 tumours (compared to normal breast). Among those, a selection of the most significant genes were analysed for RT-PC expression throughout the various steps of tumour development (normal breast, benign tumors, in situ carcinomas, invasive carcinomas). Among the 15 most upregulated genes listed, 3 unknown genes appear, that are overexpressed in 98% of the tumors with an average fold change > 11 and are currently explored. Discussion: In this unique series of untreated node-negative breast cancers, identification of molecular profiles of early and late DM could be useful in better early prediction of breast cancer outcome. Based on genomic analysis, a molecular gene based classification of progression from benign tissue to aggressive tumors allows to dissect pathways towards malignancy and to identify early diagnostic markers or targets for prevention. No significant financial relationships to disclose.

scholarly journals Differential Genomic Interactions Drive Progesterone Receptor Isoform Specific Functions in Breast Cancer

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A821-A821
Author(s):  
Tram B Doan ◽  
J Dinny Graham ◽  
Mariah Tehan ◽  
Barbara J Guild ◽  
Christine L Clarke
Keyword(s):  
Breast Cancer ◽  
Progesterone Receptor ◽  
Hormone Replacement ◽  
Breast Cancer Incidence ◽  
Normal Breast ◽  
Breast Development ◽  
Integrated Analysis ◽  
Breast Cancers ◽  
Multiple Cancer ◽  
Breast Cancer Outcome

Abstract Progesterone is critical for normal breast development and function, and has been shown to stimulate proliferation of normal breast epithelial cells by increasing stem and progenitor cell numbers. Breast cancer incidence is increased in women exposed to progesterone analogues in combined estrogen plus progestin hormone replacement therapy, but not in women taking estrogen alone. Classical progesterone signaling is mediated through the nuclear progesterone receptor (PR), which occurs as two related but functionally different isoforms, PRA and PRB. PRA and PRB are co-expressed equally in normal breast tissue but become dysregulated in breast cancer where PRA often becomes predominant. PRA predominance in breast cancer is associated with poorer outcome and higher risk of distant metastasis in tamoxifen treated patients. We show using integrated analysis of ChIP-seq, ATAC-seq and transcriptomic profiling in a breast cancer cell line model of acquired PRA predominance that: 1) PRA and PRB have different requirements with regard to chromatin accessibility; 2) PRA predominance reshapes the PR cistrome and the associated transcriptome to affect genes not normally regulated by PR when PRA and PRB are equivalently expressed, possibly through assisted loading with multiple other transcription factors; 3) Genes regulated by PR only when PRA is predominant are associated with poorer breast cancer outcome and involved in multiple cancer-associated pathways including those that regulate cell proliferation and adhesion. Our data suggest a mechanism for the poorer disease outcome seen in breast cancers with a predominance of PRA.

scholarly journals ER81 Expression in Breast Cancers and Hyperplasia

2011 ◽  
Vol 2011 ◽  
pp. 1-6 ◽  
Author(s):  
YuanYuan Wang ◽  
Li Wang ◽  
Yue Chen ◽  
Lin Li ◽  
XuanTao Yang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Early Stage ◽  
Statistical Significance ◽  
Normal Breast ◽  
Breast Development ◽  
Breast Cancers ◽  
Breast Carcinogenesis ◽  
Cancer Tissues ◽  
Breast Tissues

ER81 is a transcription factor that may contribute to breast cancer; however, little known about the role of ER81 in breast carcinogenesis. To investigate the role of ER81 in breast carcinogenesis, we examined ER81 expression in IDC, DCIS, ADH, HUT, and normal breast tissues by immunohistochemical staining. We found that ER81 overexpression was detected in 25.7% (9/35) of HUT, 41.2% (7/17) of ADH, 54.5% (12/22) of DCIS, and 63.0% (51/81) of IDC. In 20 of breast cancer tissues combined with DCIS, ADH, and HUT, ER81 expression was found in 14/20 (70%) IDC. In these 14 cases all cases were ER81 positive expression in DCIS, 13 of 14 cases were positively expressed of ER81 in ADH and 8 of 14 were positive for ER81 in HUT components. A statistical significance was found between NBT and HUT () and HUT and ADH (). Clinical-pathological features analysis of breast cancer revealed that ER81 expression was significantly associated with Her2 amplification and was negatively associated with ER and PR expression. Our results demonstrated that ER81 overexpression was present in the early stage of breast development that suggested that ER81 overexpression may play an important role in breast carcinogenesis.

scholarly journals Classical Cyclophosphamide, Methotrexate, and Fluorouracil Chemotherapy Is More Effective in Triple-Negative, Node-Negative Breast Cancer: Results From Two Randomized Trials of Adjuvant Chemoendocrine Therapy for Node-Negative Breast Cancer

2010 ◽  
Vol 28 (18) ◽  
pp. 2966-2973 ◽  
Author(s):  
Marco Colleoni ◽  
Bernard F. Cole ◽  
Giuseppe Viale ◽  
Meredith M. Regan ◽  
Karen N. Price ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Endocrine Therapy ◽  
Triple Negative ◽  
Alkylating Agents ◽  
Growth Factor Receptor ◽  
Breast Cancers ◽  
Her2 Positive ◽  
Node Negative ◽  
Tumor Subtypes ◽  
Node Negative Breast Cancer

Purpose Retrospective studies suggest that primary breast cancers lacking estrogen receptor (ER) and progesterone receptor (PR) and not overexpressing human epidermal growth factor receptor 2 (HER2; triple-negative tumors) are particularly sensitive to DNA-damaging chemotherapy with alkylating agents. Patients and Methods Patients enrolled in International Breast Cancer Study Group Trials VIII and IX with node-negative, operable breast cancer and centrally assessed ER, PR, and HER2 were included (n = 2,257). The trials compared three or six courses of adjuvant classical cyclophosphamide, methotrexate, and fluorouracil (CMF) with or without endocrine therapy versus endocrine therapy alone. We explored patterns of recurrence by treatment according to three immunohistochemically defined tumor subtypes: triple negative, HER2 positive and endocrine receptor absent, and endocrine receptor present. Results Patients with triple-negative tumors (303 patients; 13%) were significantly more likely to have tumors > 2 cm and grade 3 compared with those in the HER2-positive, endocrine receptor–absent, and endocrine receptor–present subtypes. No clear chemotherapy benefit was observed in endocrine receptor–present disease (hazard ratio [HR], 0.90; 95% CI, 0.74 to 1.11). A statistically significantly greater benefit for chemotherapy versus no chemotherapy was observed in triple-negative breast cancer (HR, 0.46; 95% CI, 0.29 to 0.73; interaction P = .009 v endocrine receptor–present disease). The magnitude of the chemotherapy effect was lower in HER2-positive endocrine receptor–absent disease (HR, 0.58; 95% CI, 0.29 to 1.17; interaction P = .24 v endocrine receptor–present disease). Conclusion The magnitude of benefit of CMF chemotherapy is largest in patients with triple-negative, node-negative breast cancer.

Association between androgen receptor expression, Ki-67 and the 21-gene recurrence score in non-metastatic, lymph node-negative, estrogen receptor-positive and HER2-negative breast cancer

2015 ◽  
Vol 68 (10) ◽  
pp. 839-843 ◽  
Author(s):  
Francisco E Vera-Badillo ◽  
Martin C Chang ◽  
Gordana Kuruzar ◽  
Alberto Ocana ◽  
Arnoud J Templeton ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Lymph Node ◽  
Androgen Receptor ◽  
Statistical Significance ◽  
Multivariable Analysis ◽  
Recurrence Score ◽  
Receptor Expression ◽  
Ki 67 ◽  
Node Negative

BackgroundThe mechanisms underlying the favourable prognosis of androgen receptor (AR) expression in breast cancer are unknown.MethodsThe associations between the 21-gene recurrence score (RS), AR, grade, mitotic score, Ki-67 and estrogen receptor (ER) and progesterone receptor (PgR) expression were explored in sequential women with lymph node-negative, ER-positive and HER2-negative breast cancer. Statistical significance of this exploratory study was defined as p<0.10.ResultsAnalysis comprised 70 women. Most tumours had high AR expression (97% had scores >3). Median RS was 15 (range 1–53). AR expression showed a minimally significant positive correlation with ER (R=0.37), but no correlation with Ki-67 (R=−0.18). In univariable analysis, AR (p=0.01), ER (p<0.001) and PgR (p<0.001) had significant negative associations with RS. Ki-67 (p=0.16), grade (p=0.40) and mitotic score (p=0.23) showed no association with RS. Multivariable analysis showed similar associations.ConclusionsAR is associated with lower RS, but not with Ki-67.

scholarly journals Difficulties of radiological diagnosis оf small breast cancers

2021 ◽  
Vol 20 (2) ◽  
pp. 49-53
Author(s):  
Т. N. Leikht ◽  
G. I. Bratnikova ◽  
Р. S. Gomina ◽  
N. S. Kosolapova ◽  
К. A. Tihaya ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Soft Tissues ◽  
Correct Diagnosis ◽  
Screening Mammography ◽  
Diagnostic Methods ◽  
Benign Tumors ◽  
Breast Cancers ◽  
Vertical Orientation ◽  
Small Breast ◽  
Ultrasound Scanner

Introduction. Breast cancer in the structure of malignancies in women takes the 1st place. There has been an annual increase in morbidity, including due to improvements in diagnostic interventions and screening. Mammography and ultrasound of the breasts is mandatory when diagnosing breast cancer. The difficulties of diagnosis are revealed in small tumors.Methods. Breast ultrasounds were performed on the ultrasound machines of the expert class TOSHIBA APLIO 500, PHILIPS EPIQ 5 and PHILIPS EPIQ 7. Mammography and tomosynthesis were performed on mammogram MAMMOMAT INSPITATION PRIME. Core-biopsia under ultrasound control was carried out on the Logiq9 ultrasound scanner. Eighty women were selected with suspected cancer after breast core-biopsy with the category BI-RADS 3, 4 and 5. The size of the node according to ultrasound data was 6-10 mm.Results. According to core-biopsia has been identified cancer, histologically and immunohystochemically confirmed in 50 cases. In 30 women benign tumors were identified. The most informative mammograms of breast cancer were high tumor density, ray of radiibility and local deformity of soft tissues. Among the characteristic ultrasonic signs of the cancer more often noted vertical orientation, reduced echogenicity, uneven contour, other signs were not so character for the cancer.Conclusion. You can't focus on a separate sign of education! Only a combination of traits, different diagnostic methods contribute to the correct diagnosis.

Analysis of Low Estrogen Receptor (ER+) Breast Carcinomas in a Large Community Breast Cancer Center in Northern California

2021 ◽  
Vol 156 (Supplement_1) ◽  
pp. S26-S27
Author(s):  
G Bulusu ◽  
K Duncan ◽  
A Wheeler
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Histological Grade ◽  
Statistical Significance ◽  
Cancer Center ◽  
Pathology Report ◽  
Breast Cancers ◽  
Breast Carcinomas ◽  
Ki 67 ◽  
Er Positive

Abstract Introduction/Objective Estrogen Receptor (ER) expression in breast cancers is a crucial factor for endocrine therapy in patients with tumors expressing ER in ≥1% of tumor cells. The 2019 guidelines published by ASCO/CAP states that breast cancers that have a 1% to 10% of cells staining Estrogen Receptor (ER) positive should be reported as ER Low Positive cases. This study aims to address this subset of low-positive ER tumors and compare the clinical features to other known breast cancer subtypes. Methods/Case Report We conducted a retrospective review of a prospectively maintained breast cancer registry from 2013 to 2021 at Mills-Peninsula Medical Center, a Sutter Health Affiliate. The study reviewed patient charts with respect to the pathology report, operative report, chemotherapy regimen, and clinical outcomes. Statistical analyses were conducted using R Project for Statistical Coding, with The Student’s T-test used to compare continuous variables. Two-sided P values less than 0.05 indicate statistical significance. Results (if a Case Study enter NA) Our study identified 1316 cases of invasive breast carcinomas, of which 29 (2.16%) demonstrated ER Low-Positive expression. We aimed to evaluate the clinical and pathological features, such as histological grade, ER, PR, HER-2, Ki-67%, and patient age for these tumors. We found that ER Low-Positive tumors demonstrated higher mean histological grade morphology (2.5 out of 3, p&lt;0.001) that was similar to that of Triple Negative Breast Cancers (TNBC) (3 of 3, p&lt;0.001) than to High ER-Positive (1.6 of 3, p&lt;0.001) cancers. Further observations, through examining proliferation rates by utilizing the Ki-67 index, indicate comparative trends between the ER Low-Positive cohort and the TNBC cohort. Conclusion The results suggest that the ER Low-Positive carcinomas, despite reported as ER-positive cases, present with similar clinicopathological features to those of ER-negative tumors. Through this study and future research, we would like to emphasize a stricter set of guidelines that can be adopted to reduce variability for reporting biomarkers. This standardization will allow oncologists to provide more appropriate treatment options and improve the quality of patient care.

Adjuvant Endocrine Therapy for Women With Hormone Receptor–Positive Breast Cancer: ASCO Clinical Practice Guideline Focused Update

2019 ◽  
Vol 37 (5) ◽  
pp. 423-438 ◽  
Author(s):  
Harold J. Burstein ◽  
Christina Lacchetti ◽  
Holly Anderson ◽  
Thomas A. Buchholz ◽  
Nancy E. Davidson ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Practice ◽  
Endocrine Therapy ◽  
Clinical Practice Guideline ◽  
Practice Guideline ◽  
Cancer Recurrence ◽  
Endocrine Treatment ◽  
Breast Cancers ◽  
Node Negative ◽  
Positive Breast Cancer

Purpose To update the ASCO clinical practice guideline on adjuvant endocrine therapy based on emerging data about the optimal duration of aromatase inhibitor (AI) treatment. Methods ASCO conducted a systematic review of randomized clinical trials from 2012 to 2018. Guideline recommendations were based on the Panel’s review of the evidence from six trials. Results The six included studies of AI treatment beyond 5 years of therapy demonstrated that extension of AI treatment was not associated with an overall survival advantage but was significantly associated with lower risks of breast cancer recurrence and contralateral breast cancer compared with placebo. Bone-related toxic effects were more common with extended AI treatment. Recommendations The Panel recommends that women with node-positive breast cancer receive extended therapy, including an AI, for up to a total of 10 years of adjuvant endocrine treatment. Many women with node-negative breast cancer should consider extended therapy for up to a total of 10 years of adjuvant endocrine treatment based on considerations of recurrence risk using established prognostic factors. The Panel noted that the benefits in absolute risk of reduction were modest and that, for lower-risk node-negative or limited node-positive cancers, an individualized approach to treatment duration that is based on considerations of risk reduction and tolerability was appropriate. A substantial portion of the benefit for extended adjuvant AI therapy was derived from prevention of second breast cancers. Shared decision making between clinicians and patients is appropriate for decisions about extended adjuvant endocrine treatment, including discussions about the absolute benefits in the reduction of breast cancer recurrence, the prevention of second breast cancers, and the impact of adverse effects of treatment. Additional information can be found at www.asco.org/breast-cancer-guidelines .

Breast cancers with stem cell-like features delineate endocrine responsiveness

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 10517-10517
Author(s):  
A. Rody ◽  
T. Karn ◽  
C. Solbach ◽  
R. Gaetje ◽  
R. Diallo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cell ◽  
Lymph Node ◽  
Survival Rates ◽  
Disease Recurrence ◽  
Normal Breast ◽  
Endocrine Treatment ◽  
Breast Cancers ◽  
Er Positive ◽  
Er Status

10517 Background: Endocrine responsiveness is one of the most important characteristics of breast cancer. The negative association between expression of the estrogen receptor (ER) and proliferation detected in normal breast is frequently lost in breast cancers leading to receptor independent growth and poor patients’ prognosis. Methods: Microarray analysis of 171 breast cancer samples allowed the discrimination of a KIT+ tumor group by using a set of genes coregulated with the “stem cell factor” receptor KIT. Validation was performed on three independent datasets encompassing 637 samples. Furthermore the response to endocrine treatment only was analyzed in a dataset of 700 patients. Results: KIT+ tumors are transcriptionally related to proposed mammary stem cells. Two types of KIT+ tumors were identified which are characterized by their positive and negative ER status, respectively. The inverse link of ER expression and proliferation is perfectly conserved within the KIT+ tumor groups, while it is uncoupled among half of the KIT-Low ER positive tumors. Those “uncoupled” ER positive tumors with altered ER response are characterized by a prognosis inferior to the ER negative cancers despite an apparent positive ER status (hazard ratio for disease recurrence, 2.07; 95% CI 1.53–2.81; P<0.001). Moreover, the 5 and 10 year survival rates of lymph node negative “uncoupled” tumors are even worse than those of lymph node positive “normal” ER positive cancers. While all ER positive patients seem to profit from endocrine treatment the relative benefit was reduced in uncoupled tumors (21.2 % vs. 31.7 %). Conclusions: The classification of breast cancers according to this biologically based model identified clinical relevant tumor groups whose further characterization will have important implications. Moreover, since the ability to recognize malfunctions in ER pathways largely depends on an appropriate reference system, the KIT+ tumors could allow a dissection of estrogen responsiveness giving crucial insights for prediction of response to endocrine therapy. No significant financial relationships to disclose.

Molecular characteristics and metastasis predictor genes of triple-negative breast cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 1043-1043
Author(s):  
Wen-Hung Kuo ◽  
Yao-Yin Chang ◽  
Ming-Feng Hou ◽  
Eric Y Chuang ◽  
King-Jen Chang
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Early Stage ◽  
Gene Signature ◽  
Breast Cancers ◽  
Prognostic Signature ◽  
Characteristic Analysis ◽  
Disease Etiology ◽  
Breast Cancer Outcome

1043 Background: Triple-negative breast cancer(TNBC) is a subtype of breast cancer with aggressive tumor behavior and distinct disease etiology. Due to the lack of an effective targeted medicine, treatment options for triple-negative breast cancer are few and recurrence rates are high. Although various multi-gene prognostic markers have been proposed for the prediction of breast cancer outcome, most of them were proven clinically useful only for estrogen receptor-positive breast cancers. Reliable identification of triple-negative patients with a favorable prognosis is not yet possible. Methods: Clinicopathological information and microarray data from 157 invasive breast carcinomas were collected at National Taiwan University Hospital from 1995 to 2008. Gene expression data of 51 triple-negative and 106 luminal breast cancers were generated with oligonucleotide microarrays. A prognostic 45-gene signature for triple-negative breast cancer was identified using Student’s t test and receiver operating characteristic analysis. Results: Hierarchical clustering analysis revealed that the majority (94%) of triple-negative breast cancers were tightly clustered together carrying strong basal-like characteristics. A novel 45-gene signature giving 98% predictive accuracy in distant metastasis recurrence was identified in our triple-negative patient cohort. External validation of the prognostic signature in an independent microarray dataset of 59 early-stage triple-negative patients also obtained statistical significance (hazard ratio 2.29, 95% CI 1.04-5.06, Cox P = 0.04), outperforming five other published breast cancer prognostic signatures. The prognostic signature was statistically predictive with the node-negative triple-negative patients in the validation cohort. Conclusions: The 45-gene prognostic signature identified in this study revealed that TGF-β signaling in immune/inflammatory regulation may be critically involved in distant metastatic invasion of TNBC. The 45-gene signature, if further validated, may be a clinically useful tool in risk assessment of metastasis recurrence for early-stage triple-negative patients.

Triple-negative invasive breast cancer (TNBC): Mammographic, US, and MR imaging features according to androgen receptor (AR) expression.

2014 ◽  
Vol 32 (26_suppl) ◽  
pp. 159-159
Author(s):  
Woo Kyung Moon
Keyword(s):  
Breast Cancer ◽  
Mr Imaging ◽  
Breast Imaging ◽  
Gene Signature ◽  
Irregular Shape ◽  
Consecutive Series ◽  
Imaging Features ◽  
Breast Cancers ◽  
Pathologic Features ◽  
Chi Squared

159 Background: A subset of TNBC is characterized by an androgen gene signature and early clinical trials have demonstrated clinical benefit with the use of the AR antagonist, bicalutamide, for the treatment of patients with AR+, estrogen receptor/progesterone receptor- breast cancer. Methods: AR expression was assessed immunohistochemically in 125 patients (median age; 54 years, range; 26-82 years) with TNBC from a consecutive series of 1,086 operable invasive breast cancers. Two experienced breast imaging radiologists (6 and 24 years of experience, respectively) reviewed the mammograms, US, and MR images without knowledge of clinicopathologic findings. The imaging and pathologic features of 33 AR-positive TNBCs were compared with those of 92 AR-negative TNBCs by using the Fisher’s exact or chi-squared tests. Results: AR expression in TNBC is significantly associated with mammographic findings (P < 0.001), lesion type at MR imaging (P < 0.001), and mass shape or margin at ultrasound (P < 0.001; P= 0.002). The highest PPVs for AR-positive cancer were non-mass enhancement on MR imaging (PPV, 1.00; 95% CI: 0.61, 1.00), calcifications only seen on mammography (PPV, 1.00; 95% CI: 0.37, 1.00), and spiculated masses on US (PPV, 1.00; 95% CI: 0.22, 1.00). Conclusions: AR-positive and AR-negative tumors have distinct imaging features in TNBC. The presence of calcifications or focal asymmetries at mammography, the presence of echogenic halo or non-complex hypoechoic masses at US, masses with irregular shape or indistinct margins at mammography and US, and masses with irregular shape or spiculated margins, or non-mass lesions at MR imaging were associated with AR expression in TNBC. These imaging features may be used to predict AR status, which could assist in treatment planning, prediction of response, and assessment of prognosis for patients with TNBC.

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