scholarly journals VGLL1 expression is associated with a triple-negative basal-like phenotype in breast cancer

2014 ◽  
Vol 21 (4) ◽  
pp. 587-599 ◽  
Author(s):  
María Ángeles Castilla ◽  
María Ángeles López-García ◽  
María Reina Atienza ◽  
Juan Manuel Rosa-Rosa ◽  
Juan Díaz-Martín ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative ◽  
Tissue Microarrays ◽  
The Cancer Genome Atlas ◽  
Luminal Progenitor ◽  
Breast Carcinomas ◽  
Luminal A ◽  
Her2 Positive ◽  
Cancer Subtypes ◽  
Grade 3

Vestigial-like 1 (VGLL1) is a poorly characterized gene encoding a transcriptional co-activator structurally homologous toTAZandYAPthat modulates the Hippo pathway inDrosophila. In this study, we examined the expression ofVGLL1and its intronic miRNA, miR-934, in breast cancer.VGLL1and miR-934 expression miRNA profiling was carried out on frozen samples of grade 3 invasive ductal carcinomas. VGLL1 protein was also examined in 433 sporadic andBRCA1-associated breast carcinomas on tissue microarrays. RNA-seq data from The Cancer Genome Atlas (TCGA) was used to confirm differences inVGLL1and miR-934 expression in different breast cancer subtypes, and to correlate their expression with that of other genes and miRNAs. Of 28 miRNAs differentially expressed in estrogen receptor (ER)-positive and ER-negative grade 3 breast carcinomas, miR-934 was most strongly upregulated in ER-negative carcinomas, and its expression was correlated with that ofVGLL1. NuclearVGLL1expression was observed in 13% of sporadic breast carcinomas, and whileVGLL1was only occasionally found in luminal A (0.70%) and B (5.60%) carcinomas, it was often expressed in HER2-positive (17%), triple-negative (TN) breast carcinomas (>40%) andBRCA1-associated TN carcinomas (>50%). These findings were confirmed in the TCGA dataset, which revealed positive associations with luminal progenitor genes (GABRP,SLC6A14,FOXC1,PROM1, andBBOX1) and strong negative correlations with ER-associated genes (ESR1,C6ORF211,GATA3, andFOXA1). Moreover,VGLL1expression was associated with reduced overall survival. In conclusion,VGLL1and miR-934 are mainly expressed in sporadic andBRCA1-associated TN basal-like breast carcinomas, and their coordinated expression, at least partially mediated by the direct modulation ofESR1, might be involved in the maintenance of a luminal progenitor phenotype.

scholarly journals Identification of Long Noncoding RNAs as Predictors of Survival in Triple-Negative Breast Cancer Based on Network Analysis

2020 ◽  
Vol 2020 ◽  
pp. 1-15 ◽  
Author(s):  
Xiao-Xiao Li ◽  
Li-Juan Wang ◽  
Jie Hou ◽  
Hong-Yang Liu ◽  
Rui Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Network Analysis ◽  
Molecular Mechanisms ◽  
Triple Negative ◽  
Noncoding Rnas ◽  
Long Noncoding Rnas ◽  
Breast Cancers ◽  
Luminal A ◽  
Her2 Positive ◽  
Cancer Subtypes

Breast cancer is the most common cancer observed in adult females, worldwide. Due to the heterogeneity and varied molecular subtypes of breast cancer, the molecular mechanisms underlying carcinogenesis in different subtypes of breast cancer are distinct. Recently, long noncoding RNAs (lncRNAs) have been shown to be oncogenic or play important roles in cancer suppression and are used as biomarkers for diagnosis and therapy. In this study, we identified 134 lncRNAs and 6,414 coding genes were differentially expressed in triple-negative (TN), human epidermal growth factor receptor 2- (HER2-) positive, luminal A-positive, and luminal B-positive breast cancer. Of these, 37 lncRNAs were found to be dysregulated in all four subtypes of breast cancers. Subtypes of breast cancer special modules and lncRNA-mRNA interaction networks were constructed through weighted gene coexpression network analysis (WGCNA). Survival analysis of another public datasets was used to verify the identified lncRNAs exhibiting potential indicative roles in TN prognosis. Results from heat map analysis of the identified lncRNAs revealed that five blocks were significantly displayed. High expressions of lncRNAs, including LINC00911, CSMD2-AS1, LINC01192, SNHG19, DSCAM-AS1, PCAT4, ACVR28-AS1, and CNTFR-AS1, and low expressions of THAP9-AS1, MALAT1, TUG1, CAHM, FAM2011, NNT-AS1, COX10-AS1, and RPARP-AS1 were associated with low survival possibility in TN breast cancers. This study provides novel lncRNAs as potential biomarkers for the therapeutic and prognostic classification of different breast cancer subtypes.

scholarly journals Comparison of Clinico-Pathological Presentations of Triple-Negative versus Triple-Positive and HER2 Iraqi Breast Cancer Patients

2019 ◽  
Vol 7 (21) ◽  
pp. 3534-3539
Author(s):  
Nada A. S. Alwan ◽  
Furat N. Tawfeeq
Keyword(s):  
Breast Cancer ◽  
Triple Negative ◽  
Molecular Subtype ◽  
Clinical Stage ◽  
Lymph Node Involvement ◽  
Breast Cancer Patients ◽  
Luminal A ◽  
Her2 Positive ◽  
Cancer Subtypes ◽  
Significant Difference

BACKGROUND: Breast cancer remains the most common malignancy among the Iraqi population. Affected patients exhibit different clinical behaviours according to the molecular subtypes of the tumour. AIM: To identify the clinical and pathological presentations of the Iraqi breast cancer subtypes identified by Estrogen receptors (ER), Progesterone receptors (PR) and HER2 expressions. PATIENTS AND METHODS: The present study comprised 486 Iraqi female patients diagnosed with breast cancer. ER, PR and HER2 contents of the primary tumours were assessed through immunohistochemical staining; classifying the patients into five different groups: Triple Negative (ER/PR negative/HER2 negative), Triple Positive (ER/PR positive/HER2 positive), Luminal A (ER/PR positive/HER2 negative), HER2 enriched ((ER/PR negative/HER2 positive) and all other subtypes. RESULTS: The major registered subtype was the Luminal A which was encountered in 230 patients (47.3%), followed by the Triple Negative (14.6%), Triple Positive (13.6%) and HER2 Enriched (11.5%). Patients exhibiting the Triple Negative subtype were significantly younger than the rest of the groups and presented with larger size tumours. A significant difference in the distribution of the breast cancer stages was displayed (p < 0.05); the most advanced were noted among those with HER2 enriched tumours who exhibited the highest frequency of poorly differentiated carcinomas and lymph node involvement. CONCLUSION: The most significant variations in the clinicopathological presentations were observed in the age and clinical stage of the patients at diagnosis. Adoption of breast cancer molecular subtype classification in countries with limited resources could serve as a valuable prognostic marker in the management of aggressive forms of the disease.

Breast cancer subtype and screening sensitivity in the Quebec Mammography Screening Program

2018 ◽  
Vol 26 (3) ◽  
pp. 154-161
Author(s):  
Linda Perron ◽  
Sue-Ling Chang ◽  
Jean-Marc Daigle ◽  
Nathalie Vandal ◽  
Isabelle Theberge ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Mammography Screening ◽  
Triple Negative ◽  
Screening Program ◽  
Luminal A ◽  
Her2 Positive ◽  
Cancer Subtypes ◽  
Luminal B ◽  
Mammography Screening Program ◽  
Screening Sensitivity

Objective In mammography screening, interval cancers present a problem. The metric ‘screening sensitivity’ monitors both how well a programme detects cancers and avoids interval cancers. To our knowledge, the effect of breast cancer surrogate molecular subtypes on screening sensitivity has never been evaluated. We aimed to measure the 2-year screening sensitivity according to breast cancer subtypes. Methods We studied 734 women with an invasive breast cancer diagnosed between 2003 and 2007 after participating in one regional division of Quebec’s Mammography Screening Program. They represented 83% of all participating women with an invasive BC diagnosis in that region for that period. Tumours were categorized into ‘luminal A-like’, ‘luminal B-like’, ‘triple-negative’ and ‘HER2-positive’ subtypes. We used logistic regression and marginal standardization to estimate screening sensitivity, sensitivity ratios (SR) and sensitivity differences. We also assessed the mediating effect of grade. Results Adjusted 2-year screening sensitivity was 75.4% in luminal A-like, 66.1% in luminal B-like, 52.9% in triple-negative and 45.3% in HER2-positive, translating into sensitivity ratios of 0.88 (95% confidence interval [CI] = 0.78–0.98) for luminal B-like, 0.70 (CI = 0.56–0.88) for triple-negative and 0.60 (CI = 0.39–0.93) for HER2-positive, when compared with luminal A-like. Grade entirely mediated the subtype-sensitivity association for triple negative and mediated it partly for HER2-positive. Screening round (prevalent vs. incident) did not modify results. Conclusion There was substantial variation in screening sensitivity according to breast cancer subtypes. Aggressive phenotypes showed the lowest sensitivity, an effect that was mediated by grade. Tailoring screening according to women’s subtype risk factors might eventually lead to more efficient programs.

scholarly journals Breast Cancer Subtypes among Iraqi Patients: Identified By Their ER, PR and HER2 Status

2018 ◽  
Vol 59 (4) ◽  
pp. 303-307
Author(s):  
Nada A.S. Alwan ◽  
Furat N. Tawfeeq ◽  
Faisal H. Muallah
Keyword(s):  
Breast Cancer ◽  
Triple Negative ◽  
Molecular Subtypes ◽  
Progesterone Receptors ◽  
Breast Cancer Subtypes ◽  
Breast Carcinomas ◽  
Luminal A ◽  
Cancer Subtypes ◽  
Luminal B ◽  
Her 2

Background: Breast cancer ranks the first among the Iraqi population since three decades and is currently forming a major public health problem being the second cause of death women. Novel management of breast cancer depends upon precise evaluation of their molecular subtypes; identified by Hormone (Estrogen and Progesterone) receptors and HER2 contents of the primary tumor.Objective: To assess the rates of the different molecular breast cancer subtypes in the examined tissue specimens belonging to females diagnosed with breast cancer in Iraq; correlating the findings with those reported in the literature at the regional and global levels.Patients and Methods: This retrospective study documented the findings of tissue biopsy examination belonging to 686 female patients diagnosed with breast cancer. Formalin fixed paraffin-embedded blocks were utilized to assess the availability of Estrogen receptors (ER), Progesterone receptors (PR) and HER2 expressions through semi quantitative immuno-histochemical staining technique. Breast carcinomas were classified into four main molecular subtypes: Luminal A: ER/PR(+) / HER2(-), Luminal B/Triple Positive: ER/PR(+) / HER2(+), Non-Luminal HER-2 enriched: ER/PR(-) / HER2(+) and Non-Luminal/Triple Negative: ER/PR(-) and HER2(-). Other phenotypes included: ER(+)/PR(-) / HER2(+), ER(-)/PR(+) / HER2 (+), ER (+)/PR (-) / HER2 (-) and ER (-)/PR (+) / HER2 (-).Results: Out of the exanimated cases of breast carcinomas, the registered rates of positive ER, PR and HER2 tumor contents in this study were 67.8%, 65.3% and 29.4% respectively. The main identified phenotype was the Luminal A in 309 cases (45%). That was followed by the Triple Negative in 107 cases (15.6%) and Triple Positive/Luminal B (96 cases, 14%), while 71 cases (10.3%) were HER2 enriched. The corresponding rates of the (E+/P-/H+), (E-/P+/H+), (E+/P-/H-) and (E-/P+/H-) subtypes were 3.1%, 2.0%., 5.7% and 4.2% respectively. Differences in in the expressions of these IHC molecular markers are illustrated among different countries.Conclusions: Due to the displayed variations in the socio-demographic characteristics and biological risk factors among patients in different populations, it is mandatory to identify the molecular marker subtypes of breast cancer expressions in order to assess the impact of management and response to therapy. The routine documentation of their patterns in the cancer registry reports and published research ensures the validity and reliability of the presented clinical data. الخلفية: سرطان الثدي يحتل المرتبة الأولى بين السكان العراقيين منذ ثلاثة عقود، ويشكل حاليا مشكلة صحية رئيسية حيث يعتبر السبب الثاني للوفاة عند النساء. تعتمد أسس العلاج الجديدة لسرطان الثدي على التقييم الدقيق لأنواعها الفرعية الجزيئية و التي تحددها مستويات مستقبلات هرمون (الاستروجين والبروجسترون) ومحتويات  HER2 في الورم الرئيسي. الهدف من الدراسة: تقييم معدلات مختلف الأنواع الفرعية لسرطان الثدي الجزيئي في عينات الأنسجة التي تم فحصها والتي تخص الإناث المصابات بسرطان الثدي في العراق؛ وربط النتائج مع تلك المسجلة على الصعيدين الإقليمي والعالمي المرضى والطرق: وثقت هذه الدراسة بأثر رجعي نتائج فحص خزعة الأنسجة التي تنتمي إلى 686 مريضة مشخصة بسرطان الثدي. واستخدمت لتقييم توافر مستقبلات الاستروجين (ER)، مستقبلات البروجسترون (PR) والتعبيرات HER2 من خلال تقنية الطيخ المناعي شبه الكمي. تم تصنيف سرطان الثدي إلى أربعة أنواع فرعية جزيئية رئيسية: Luminal A:  ER/PR(+) / HER2(-), Luminal B/Triple Positive:    ER/PR(+) / HER2(+), Non-Luminal HER-2 enriched: ER/PR(-) / HER2(+) and Non-Luminal/Triple Negative:   ER/PR(-) and HER2(-). و انواع اخرى ER(+)/PR(-) / HER2(+), ER(-)/PR(+) / HER2 (+), ER (+)/PR (-)  / HER2 (-) and ER (-)/PR (+) / HER2 (-). النتائج: من بين حالات سرطان الثدي المهددة، كانت المعدلات المسجلة لمحتوى الأورام الموجبة ER, PR و   HER2 في هذه الدراسة 67.8٪ و 65.3٪ و 29.4٪ على التوالي. وكان النمط الظاهري المحدد الرئيسي اللمعية A في 309 حالات (45٪). وأعقب ذلك السلبي الثلاثي في 107 حالات (15.6٪) وثلاثية إيجابية / لومينال B (96 حالة، 14٪)، في حين أن 71 حالة (10.3٪) كانت HER2 المخصب. وكانت المعدلات المقابلة من (E + / P- / H +)، (E / P + / H +)، (E + / P- / H-) و (E / P + / H-) فرعية 3.1٪، 2.0٪. ،   و 5.7٪ و 4.2٪ على التوالي. وتظهر الاختلافات في التعبير عن هذه العلامات الجزيئية بين مختلف البلدان. الاستنتاجات والتوصيات: نظرا للاختلافات المعروضة في الخصائص الاجتماعية الديموغرافية وعوامل الخطر البيولوجية بين المرضى في مختلف السكان، فمن الضروري تحديد الأنواع الفرعية الجزيئية من تعبيرات سرطان الثدي من أجل تقييم تأثير الاستجابة للعلاج . ان التوثيق الروتيني لأنماط سرطان الثدي في تقارير سجل السرطان والبحوث المنشورة يضمن صحة ودقة البيانات السريرية ذات العلاقة.

Definition and Impact of Pathologic Complete Response on Prognosis After Neoadjuvant Chemotherapy in Various Intrinsic Breast Cancer Subtypes

2012 ◽  
Vol 30 (15) ◽  
pp. 1796-1804 ◽  
Author(s):  
Gunter von Minckwitz ◽  
Michael Untch ◽  
Jens-Uwe Blohmer ◽  
Serban D. Costa ◽  
Holger Eidtmann ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative ◽  
Pathologic Complete Response ◽  
Complete Response ◽  
Invasive Disease ◽  
Luminal A ◽  
Her2 Positive ◽  
Cancer Subtypes ◽  
Luminal B

Purpose The exact definition of pathologic complete response (pCR) and its prognostic impact on survival in intrinsic breast cancer subtypes is uncertain. Methods Tumor response at surgery and its association with long-term outcome of 6,377 patients with primary breast cancer receiving neoadjuvant anthracycline-taxane–based chemotherapy in seven randomized trials were analyzed. Results Disease-free survival (DFS) was significantly superior in patients with no invasive and no in situ residuals in breast or nodes (n = 955) compared with patients with residual ductal carcinoma in situ only (n = 309), no invasive residuals in breast but involved nodes (n = 186), only focal-invasive disease in the breast (n = 478), and gross invasive residual disease (n = 4,449; P < .001). Hazard ratios for DFS comparing patients with or without pCR were lowest when defined as no invasive and no in situ residuals (0.446) and increased monotonously when in situ residuals (0.523), no invasive breast residuals but involved nodes (0.623), and focal-invasive disease (0.727) were included in the definition. pCR was associated with improved DFS in luminal B/human epidermal growth factor receptor 2 (HER2) –negative (P = .005), HER2-positive/nonluminal (P < .001), and triple-negative (P < .001) tumors but not in luminal A (P = .39) or luminal B/HER2-positive (P = .45) breast cancer. pCR in HER2-positive (nonluminal) and triple-negative tumors was associated with excellent prognosis. Conclusion pCR defined as no invasive and no in situ residuals in breast and nodes can best discriminate between patients with favorable and unfavorable outcomes. Patients with noninvasive or focal-invasive residues or involved lymph nodes should not be considered as having achieved pCR. pCR is a suitable surrogate end point for patients with luminal B/HER2-negative, HER2-positive (nonluminal), and triple-negative disease but not for those with luminal B/HER2-positive or luminal A tumors.

scholarly journals Inflammatory Breast Cancer: Clinical Characteristics and Influence of Molecular Subtypes on Treatment Response

2021 ◽  
Vol 107 (1_suppl) ◽  
pp. 12-12
Author(s):  
D Aissaoui ◽  
M Bohli ◽  
R Ben Amor ◽  
J Yahyaoui ◽  
A Hamdoun ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Treatment Response ◽  
Inflammatory Breast Cancer ◽  
Hormone Receptor ◽  
Triple Negative ◽  
Molecular Subtypes ◽  
Luminal A ◽  
Her2 Positive ◽  
Luminal B ◽  
Significant Difference

Introduction: Inflammatory Breast Cancer (IBC) is a rare and very aggressive breast cancer with poor prognosis. The prevalence is different from a country to another. In Tunisia, it is about 5 to 7% of breast cancer. The aim of this study is to describe the epidemiological and histopathological features of patients with inflammatory breast cancer and to evaluate the treatment response according to the molecular subtypes. Methods: This retrospective review identified 31 patients with no metastatic IBC treated in our radiotherapy department between December 2019 and November 2020. IBC was confirmed using the clinical criteria. Baseline clinic-pathological and treatment information was retrieved from medical records. Statistical analysis was performed with IBM SPSS V.20. Results: Median age was 51.3 years [27-68]. 48% of tumors were grade 3. The average tumor size was 36mm [10-90]. The histological type was ductal carcinoma in 97%. Vascular invasion was noted in 24 patients (77%). Thirty patients were classified as stage IIIB and one patient was IIIC. 74% were hormone receptor positive and 45% were HER2 positive. Luminal B was the predominant subtype (52%) followed by Her2 positive (32%), Luminal A (23%), and triple negative (3%) All patients had chemotherapy: neoadjuvant for 26 patients (84%) and adjuvant for 5 patients (16%). Nine patients (29%) had tumor pathological complete response (pCR). Partial response was observed in 18 patients (58%). Lymph node pCR was noted in 16% of cases (n=5). Endocrine therapy and trastuzumab were given to 76% and 45% of patients, respectively. The influence of the molecular subtype was not statistically significant on the response to neoadjuvant treatment. The highest rate of pCR were 43% for Her2positive, then 27%, 21% and 9% for Luminal B, Luminal A and Triple negative, respectively (p=0.2). Conclusion: Our study showed a high percentage of hormone receptor and Her2+ (74% and 45% respectively) in IBC. Luminal B was the most frequent subtype. Anthracycline-based chemotherapy and trastuzumab improved the pCR rate: 44% for Her2positive. Triple negative showed poorer pCR than other breast cancer subtype without a significant difference. A larger study is warranted to confirm our findings.

Trends in breast cancer mortality according to molecular subtypes: A population-based study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 572-572
Author(s):  
Yunan Han ◽  
Shuai Xu ◽  
Graham A. Colditz ◽  
Adetunji T. Toriola
Keyword(s):  
Breast Cancer ◽  
Cancer Mortality ◽  
Triple Negative ◽  
Molecular Subtypes ◽  
Breast Cancer Mortality ◽  
Treatment Strategies ◽  
Luminal A ◽  
Her2 Positive ◽  
Mortality Trends ◽  
Luminal B

572 Background: Breast cancer is the second leading cause of cancer death in U.S. women. On the molecular level, breast cancer is a heterogeneous disease. Heterogeneous expressions of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) are etiologically and clinically meaningful, as they map to distinct risk factors and different treatment strategies. Although breast cancer mortality has been declining since 1990, little is known about mortality trends according to molecular subtypes at the population level. Methods: We examined the incidence-based mortality rates and trends among women who were diagnosed with invasive breast cancer from 2010 through 2017 using the Surveillance, Epidemiology, and End Results (SEER) database. We defined incidence-based mortality using a moving 5-year calendar period starting in 2014. We further assessed mortality according to breast cancer molecular subtypes: luminal A (ER and/or PR positive, HER2 negative), luminal B (ER and/or PR positive, HER2 positive), HER2-enriched (HER2 over-expressed or amplified, ER and PR negative) and triple-negative (ER and PR negative, HER2 negative) tumors. We calculated annual percent changes (APC) in incidence-based mortality using joinpoint regression models. Results: Overall, incidence-based mortality for breast cancer significantly decreased by 1.5% annually from 2014 through 2017 (APC, -1.5%; 95% coefficient interval [CI], -2.3% to -0.7%; p<0.001). Incidence-based mortality decreased annually by 2.0% for luminal A breast cancer (APC, -2.0%; 95% CI, -3.7% to -0.3%; p<0.001), 2.1% for luminal B breast cancer (APC, -2.1%; 95% CI, -5.4% to 1.4%; p=0.1), 1.1% for triple-negative breast cancer (TNBC) (APC, -1.1%; 95% CI, -2.1% to -0.0%; p<0.001). However, incidence-based mortality for HER2-enriched breast cancer increased 2.3% annually during the study period (APC, 2.3%; 95% CI, -2.4% to 7.2%; p=0.2). Conclusions: Between 2014 and 2017, incidence-based mortality for luminal A, luminal B, and TNBC decreased among U.S. women, with a larger decrease observed for luminal tumors. However, incidence-based mortality for HER2-enriched breast cancer increased. The favorable incidence-based mortality trends for luminal tumors and TNBC are likely due to the continuing improvement in treatments and early detection. The increasing trend of incidence-based mortality for HER2-enriched breast cancer constitutes a priority for cancer control activities and further research.

scholarly journals Analysis of prolactin receptor expression in breast cancer subtypes

2020 ◽  
Vol 66 (1) ◽  
pp. 89-94
Author(s):  
T.S. Kalinina ◽  
V.V. Kononchuk ◽  
S.V. Sidorov ◽  
L.F. Gulyaeva
Keyword(s):  
Breast Cancer ◽  
Triple Negative ◽  
Prolactin Receptor ◽  
Mrna Level ◽  
Receptor Expression ◽  
Mrna Levels ◽  
Luminal A ◽  
Her2 Positive ◽  
Tissue Samples ◽  
Luminal B

Breast cancer (BC) is the most common cancer among women. It is known that the prolactin receptor (PRLR) may play a role in breast carcinogenesis, but the available data are often contradictory. To get a more complete picture of the relationship between the receptor and mammary gland carcinogenesis, we examined the association between changes in PRLR expression level and tumor subtype (and its main characteristics). To do this, using real-time PCR, we evaluated the level of PRLR mRNA in BC tissue samples and untransformed adjoining tissue samples (89 pairs). Since the androgen receptor (AR) has begun to be seen as a prognostic marker in breast cancer, we also evaluated the association between mRNA levels of AR and PRLR. We found a significant increase in PRLR expression in luminal subtypes; the highest level of PRLR mRNA was detected in luminal A subtype. In HER2-positive ER-, PR-negative BC, the PRLR mRNA level decreases in tumor tissues compared with untransformed tissues. High PRLR expression is also associated with smaller tumor size in luminal B HER2-negative subtype. In ER-, PR-negative tumors, PRLR expression is associated with AR expression: PRLR mRNA level is increased when AR mRNA level is reduced by more than 8 times in triple-negative tumors; in contrast, in HER2-positive subtype it decreases more significantly when AR expression is reduced by more than 3 times. A tendency towards an increase in PRLR expression with an increase in the AR mRNA level was also discovered in luminal subtypes. The level of PRLR expression depends on the age of patients. In luminal A, PRLR expression is higher in patients under 65 years. In contrast, in luminal B HER2-negative and triple-negative BC, reduced PRLR expression was observed in patients under the age of 40 years and under the age of 50 years, respectively. In this group of patients under the age of 40 years with luminal B HER2-negative BC, ER expression was also reduced (0-4 score according to the IHC assay). Thus, PRLR probably plays a different role in the development and progression of BC: in luminal A and luminal B HER2-positive subtypes PRLR may act as an oncogen, and in luminal B HER2-negative and ER-, PR-negative subtypes can play a tumor suppressor role.

scholarly journals Response to Radiotherapy After Breast-Conserving Surgery in Different Breast Cancer Subtypes in the Swedish Breast Cancer Group 91 Radiotherapy Randomized Clinical Trial

2017 ◽  
Vol 35 (28) ◽  
pp. 3222-3229 ◽  
Author(s):  
Martin Sjöström ◽  
Dan Lundstedt ◽  
Linda Hartman ◽  
Erik Holmberg ◽  
Fredrika Killander ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative ◽  
Breast Conservation ◽  
Growth Factor Receptor ◽  
Low Risk ◽  
Breast Conservation Surgery ◽  
Luminal A ◽  
Cancer Subtypes ◽  
Cancer Group ◽  
Breast Cancer Group

Purpose To evaluate the effect of adjuvant radiotherapy (RT) after breast conservation surgery in different breast cancer subtypes in a large, randomized clinical trial with long-term follow-up. Patients and Methods Tumor tissue was collected from 1,003 patients with node-negative, stage I and II breast cancer who were randomly assigned in the Swedish Breast Cancer Group 91 Radiotherapy trial between 1991 and 1997 to breast conservation surgery with or without RT. Systemic adjuvant treatment was sparsely used (8%). Subtyping was performed with immunohistochemistry and in situ hybridization on tissue microarrays for 958 tumors. Results RT reduced the cumulative incidence of ipsilateral breast tumor recurrence (IBTR) as a first event within 10 years for luminal A–like tumors (19% v 9%; P = .001), luminal B–like tumors (24% v 8%; P < .001), and triple-negative tumors (21% v 6%; P = .08), but not for human epidermal growth factor receptor 2–positive (luminal and nonluminal) tumors (15% v 19%; P = .6); however, evidence of an overall difference in RT effect between subtypes was weak ( P = .21). RT reduced the rate of death from breast cancer (BCD) for triple-negative tumors (hazard ratio, 0.35; P = .06), but not for other subtypes. Death from any cause was not improved by RT in any subtype. A hypothesized clinical low-risk group did not have a low risk of IBTR without RT, and RT reduced the rate of IBTR as a first event after 10 years (20% v 6%; P = .008), but had no effect on BCD or death from any cause. Conclusion Subtype was not predictive of response to RT, although, in our study, human epidermal growth factor receptor 2–positive tumors seemed to be most radioresistant, whereas triple-negative tumors had the largest effect on BCD. The effect of RT in the presumed low-risk luminal A–like tumors was excellent.

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