Glucocorticoid receptors are expressed in diverse molecular subtypes of breast cancer and in peri tumoral stroma: luminal A, luminal B HER+, luminal B HER–, and triple-negative breast cancers

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.

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Diffusion-Weighted Imaging of Different Breast Cancer Molecular Subtypes: A Systematic Review and Meta-Analysis

Breast Care ◽

10.1159/000514407 ◽

2021 ◽

pp. 1-8

Author(s):

Hans-Jonas Meyer ◽

Andreas Wienke ◽

Alexey Surov

Keyword(s):

Breast Cancer ◽

Systematic Review ◽

Diffusion Weighted Imaging ◽

Triple Negative ◽

Molecular Subtypes ◽

Luminal A ◽

Diagnose Breast Cancer ◽

Luminal B ◽

Diffusion Weighted ◽

Adc Values

Background: Magnetic resonance imaging can be used to diagnose breast cancer (BC).Diffusion-weighted imaging (DWI) and the apparent diffusion coefficient (ADC) can be used to reflect tumor microstructure. Objectives: This analysis aimed to compare ADC values between molecular subtypes of BC based on a large sample of patients. Method: The MEDLINE library and Scopus database were screened for the associations between ADC and molecular subtypes of BC up to April 2020. The primary end point of the systematic review was the ADC value in different BC subtypes. Overall, 28 studies were included. Results: The included studies comprised a total of 2,990 tumors. Luminal A type was diagnosed in 865 cases (28.9%), luminal B in 899 (30.1%), human epidermal growth factor receptor (Her2)-enriched in 597 (20.0%), and triple-negative in 629 (21.0%). The mean ADC values of the subtypes were as follows: luminal A: 0.99 × 10–3 mm2/s (95% CI 0.94–1.04), luminal B: 0.97 × 10–3 mm2/s (95% CI 0.89–1.05), Her2-enriched: 1.02 × 10–3 mm2/s (95% CI 0.95–1.08), and triple-negative: 0.99 × 10–3 mm2/s (95% CI 0.91–1.07). Conclusions: ADC values cannot be used to discriminate between molecular subtypes of BC.

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

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.572 ◽

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.

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Breast cancer in Angola, molecular subtypes: The first preliminary study.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.e13075 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. e13075-e13075

Author(s):

Lúcio Lara Santos ◽

Fernando Miguel ◽

Lygia Vieira Lopes ◽

Julio Oliveira ◽

Eduardo Ferreira ◽

...

Keyword(s):

Breast Cancer ◽

Triple Negative ◽

Molecular Subtypes ◽

Molecular Subtype ◽

Locally Advanced ◽

Luminal A ◽

Her2 Positive ◽

Luminal B ◽

Therapeutic Decisions ◽

Ihc Markers

e13075 Background: Women in sub-Saharan African countries, as Angola, are experiencing an increasing burden of aggressive breast cancer. Breast cancer molecular subtypes may enable more accurate diagnoses and support therapeutic decisions, however several studies have suggested that African breast cancers are predominantly hormone receptor poor. We conduct a study, to correlate the clinical pathological profiles and molecular subtypes, according its surrogate immunohistochemistry (IHC) markers, of breast cancer in Luanda, Angola. Methods: From Jan. 2011 to Dec. 30, 2014, 179 consecutive cases of microscopically confirmed invasive breast carcinoma that were evaluable for histology and IHC (ER, PR, HER2, and Ki-67) were classified. However, 21.8% (n = 39) of cases were poorly preserved, therefore it was only possible to study IHC in 140 cases. Results: All patients were female, the median age was 47 years (24-84 years). Invasive ductal carcinoma was the most common type, 91.4% (n = 128), grade 2 (moderately differentiated) was prevalent, 67.1%. Most of the tumours were locally advanced, stage III 65% (n = 91) and stage IV 3.6% (n = 5). In 140 cases studied, 53.2% (n = 74 ) of malignancies were hormone receptors positive, whence 25.7% were luminal A like, 19.3% luminal B like/ HER2 negative, 7.9% luminal B like/HER2 positive, 15.7% HER2 positive and 31,4% were triple-negative. Conclusions: Woman with breast cancer in Luanda-Angola were caracterized by advance stage and younger age at diagnosis of disease. The two predominant molecular subtypes are triple negative and luminal A like. Therefore, determining the molecular subtype using surrogate IHC markers has important treatment and prognostic implications for Angola women with breast cancer.

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ER, PR, HER2, Ki-67 and CK5 in Early and Late Relapsing Breast Cancer—Reduced CK5 Expression in Metastases

Breast Cancer Basic and Clinical Research ◽

10.4137/bcbcr.s10701 ◽

2013 ◽

Vol 7 ◽

pp. BCBCR.S10701 ◽

Cited By ~ 10

Author(s):

Kristiina Joensuu ◽

Marjut Leidenius ◽

Mia Kero ◽

Leif C. Andersson ◽

Kathryn B. Horwitz ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Progression ◽

Triple Negative ◽

Significant Risk ◽

Growth Factor Receptor ◽

Primary Therapy ◽

Breast Cancers ◽

Luminal A ◽

Ki 67 ◽

Luminal B

Breast cancer can recur even decades after the primary therapy. Markers are needed to predict cancer progression and the risk of late recurrence. The estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor-2 (HER2), proliferation marker Ki-67, and cytokeratin CK5 were studied to find out whether their expression or occurrence in subgroups of breast cancers correlated with the time of recurrence. The expression of HER2, ER, PR, Ki-67, and CK5 was studied by IHC in 72 primary breast cancers and their corresponding recurrent/metastatic lesions. The patients were divided into three groups according to the time of the recurrence/metastasis: before two years, after 5 years, and after 10 years. Based on their IHC profiles, the tumors were divided into surrogates of the genetically defined subgroups of breast cancers and the subtype definitions were as follows: luminal A (ER or PR+HER2–), luminal B (ER or PR+HER2+), HER2 overexpressing (ER–PR–HER2+), triple-negative (ER–PR–HER2–), basal-like (ER–PR–HER2–CK5+), non-classified (ER–PR–HER2–CK5–) and luminobasal (ER or PR+CK5+). In multivariate analysis, tumor size and HER2 positivity were a significant risk of early cancer relapse. The metastases showed a significantly lower CK5 expression. CK5 positivity distinguished triple negative tumors into rapidly and slowly recurring cancers. The IHC subtype ER or PR+HER2– luminal A presented a significantly lower risk of early tumor recurrence. Ki-67 expression denoted early-relapsing tumors and correlated linearly with tumor progression, since Ki-67 positivity declined gradually from early-relapsing toward late-recurring cancers.

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Diffusion Weighted Imaging of Different Breast Cancer Molecular Subtypes. A Systematic Review and Meta Analysis.

10.21203/rs.3.rs-57672/v1 ◽

2020 ◽

Author(s):

Hans-Jonas Meyer ◽

Andreas Wienke ◽

Alexey Surov

Keyword(s):

Breast Cancer ◽

Systematic Review ◽

Diffusion Weighted Imaging ◽

Triple Negative ◽

Molecular Subtypes ◽

Luminal A ◽

Adc Value ◽

Luminal B ◽

Adc Values ◽

Her 2

Abstract Background: Magnetic resonance imaging can be used to diagnose breast cancer (BC)s. Diffusion weighted imaging and the apparent diffusion coefficient (ADC) can be used to reflect tumor microstructure. The present analysis sought to compare ADC values between molecular subtypes of BC based upon a large patient sample.Methods: MEDLINE library and SCOPUS databases were screened for the associations between ADC and molecular suptype of BC to April 2020. Primary endpoint of the systematic review was the ADC value in different BC. Overall, 28 studies were suitable for the analysis and included into the present study.Results: The included studies comprised a total of 2990 tumors. Luminal A type was diagnosed in 865 cases (28.9%), Luminal B in 899 cases (30.1%), Her-2 enriched in 597 cases (20.0%) and triple negative in 629 cases (21.0%). The mean ADC value of the Luminal A type was 0.99 × 10− 3 mm2/s [95% CI 0.94-1.04], of the Luminal B type was 0.99 × 10− 3 mm2/s [95% CI 0.89-1.05], of Her 2-enriched type was 1.02 × 10− 3 mm2/s [95% CI 0.95-1.08] and of the triple negative type was 0.99 × 10− 3 mm2/s [95% CI 0.91-1.07].Conclusions: ADC values cannot be used to discriminate between molecular subtypes of BC.

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Radiomic signatures with contrast-enhanced magnetic resonance imaging for the assessment of breast cancer receptor status and molecular subtypes: initial results

Breast Cancer Research ◽

10.1186/s13058-019-1187-z ◽

2019 ◽

Vol 21 (1) ◽

Cited By ~ 11

Author(s):

Doris Leithner ◽

Joao V. Horvat ◽

Maria Adele Marino ◽

Blanca Bernard-Davila ◽

Maxine S. Jochelson ◽

...

Keyword(s):

Breast Cancer ◽

Triple Negative ◽

Molecular Subtypes ◽

Training Dataset ◽

Validation Dataset ◽

Resonance Imaging ◽

Luminal A ◽

Receptor Status ◽

Luminal B ◽

Contrast Enhanced

Abstract Background To evaluate the diagnostic performance of radiomic signatures extracted from contrast-enhanced magnetic resonance imaging (CE-MRI) for the assessment of breast cancer receptor status and molecular subtypes. Methods One hundred and forty-three patients with biopsy-proven breast cancer who underwent CE-MRI at 3 T were included in this IRB-approved HIPAA-compliant retrospective study. The training dataset comprised 91 patients (luminal A, n = 49; luminal B, n = 8; HER2-enriched, n = 11; triple negative, n = 23), while the validation dataset comprised 52 patients from a second institution (luminal A, n = 17; luminal B, n = 17; triple negative, n = 18). Radiomic analysis of manually segmented tumors included calculation of features derived from the first-order histogram (HIS), co-occurrence matrix (COM), run-length matrix (RLM), absolute gradient (GRA), autoregressive model (ARM), discrete Haar wavelet transform (WAV), and lesion geometry (GEO). Fisher, probability of error and average correlation (POE + ACC), and mutual information coefficients were used for feature selection. Linear discriminant analysis followed by k-nearest neighbor classification (with leave-one-out cross-validation) was used for pairwise radiomic-based separation of receptor status and molecular subtypes. Histopathology served as the standard of reference. Results In the training dataset, radiomic signatures yielded the following accuracies > 80%: luminal B vs. luminal A, 84.2% (mainly based on COM features); luminal B vs. triple negative, 83.9% (mainly based on GEO features); luminal B vs. all others, 89% (mainly based on COM features); and HER2-enriched vs. all others, 81.3% (mainly based on COM features). Radiomic signatures were successfully validated in the separate validation dataset for luminal A vs. luminal B (79.4%) and luminal B vs. triple negative (77.1%). Conclusions In this preliminary study, radiomic signatures with CE-MRI enable the assessment of breast cancer receptor status and molecular subtypes with high diagnostic accuracy. These results need to be confirmed in future larger studies.

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BRCA1/2 pathogenic variants in triple-negative versus luminal-like breast cancers: genotype–phenotype correlation in a cohort of 531 patients

Therapeutic Advances in Medical Oncology ◽

10.1177/1758835920975326 ◽

2020 ◽

Vol 12 ◽

pp. 175883592097532

Author(s):

Lorena Incorvaia ◽

Daniele Fanale ◽

Marco Bono ◽

Valentina Calò ◽

Alessia Fiorino ◽

...

Keyword(s):

Breast Cancer ◽

Triple Negative ◽

Molecular Subtypes ◽

University Hospital ◽

Sequencing Analysis ◽

Breast Cancers ◽

Luminal B ◽

Pathogenic Variants ◽

Mutational Status ◽

Phenotypic Features

Background: Several available data suggest the association between specific molecular subtypes and BRCA1/2 mutational status. Previous investigations showed the association between BRCA1/2 pathogenic variants (PVs) in specific genomic regions and phenotypic variations of cancer relative risk, while the role of PV type and location in determining the breast cancer (BC) phenotypic features remains still unclear. The aim of this research was to describe the germline BRCA1/2 PVs in triple-negative breast cancer (TNBC) versus luminal-like BC and their potential leverage on BC phenotype. Patients & methods: We retrospectively collected and analyzed all clinical information of 531 patients with BC genetically tested for germline BRCA1/2 PVs by Next-Generation Sequencing analysis at University Hospital Policlinico “P. Giaccone” of Palermo (Sicily) from January 2016 to February 2020. Results: Our results corroborate the evidence that BRCA1-related tumors often have a profile which resembles the TNBC subtype, whereas BRCA2-associated tumors have a profile that resembles luminal-like BC, especially the Luminal B subtype. Interestingly, our findings suggest that the PVs identified in TNBC were not largely overlapping with those in luminal-like tumors. Differences in the frequency of two PVs potentially associated with different molecular tumor subtypes were observed. BRCA1-633delC was detected with relatively higher prevalence in patients with TNBC, whereas BRCA2-1466delT was found mainly in Luminal B tumors, but in no TNBC patient. Conclusion: Future studies examining the type and location of BRCA1/2 PVs within different molecular subtypes are required to verify our hypothesis and could provide an interesting insight into the complex topic of genotype–phenotype correlations. Additionally, a more in-depth understanding of the potential correlations between BRCA PVs and clinical and phenotypic features of hereditary BC syndrome patients could be the key to develop better strategies of prevention and surveillance in BRCA-positive carriers without disease.

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Poor Biological Factors and Prognosis of Interval Breast Cancers: Long-Term Results of Bahçeşehir (Istanbul) Breast Cancer Screening Project in Turkey

JCO Global Oncology ◽

10.1200/go.20.00145 ◽

2020 ◽

pp. 1103-1113

Author(s):

Neslihan Cabioğlu ◽

Sibel Özkan Gürdal ◽

Arda Kayhan ◽

Nilüfer Özaydın ◽

Cennet Şahin ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Screening ◽

Breast Cancer Screening ◽

Triple Negative ◽

Long Term Results ◽

Breast Cancers ◽

Interval Cancers ◽

Luminal A ◽

Ki 67 ◽

Luminal B

PURPOSE The Turkish Bahçeşehir Breast Cancer Screening Project was a 10-year, organized, population-based screening program carried out in Bahçeşehir county, Istanbul. Our aim was to examine the biologic features and outcome of screen-detected and interval breast cancers during the 10-year study period. METHODS Between 2009 and 2019, 2-view mammograms were obtained at 2-year intervals for women aged 40 to 69 years. Clinicopathological characteristics including ER, PR, HER2-neu, and Ki-67 status were analyzed for those diagnosed with breast cancer. RESULTS In 8,758 screened women, 131 breast cancers (1.5%) were detected. The majority of patients (82.3%) had prognostic stage 0-I disease. Contrarily, patients with interval cancers (n = 15; 11.4%) were more likely to have a worse prognostic stage (II-IV disease; odds ratio [OR], 3.59, 95% CI, 0.9 to 14.5) and high Ki-67 scores (OR, 3.14; 95% CI, 0.9 to 11.2). Interval cancers detected within 1 year were more likely to have a luminal B (57.1% v 31.9%) and triple-negative (14.3% v 1%) subtype and less likely to have a luminal A subtype (28.6% v 61.5%; P = .04). Patients with interval cancers had a poor outcome in 10-year disease-specific (DSS) and disease-free survival (DFS) compared with those with screen-detected cancers (DSS: 68.2% v 98.1%, P = .002; DFS: 78.6% v 96.5%, P = .011). CONCLUSION Our findings suggest the majority of screen-detected breast cancers exhibited a luminal A subtype profile with an excellent prognosis. However, interval cancers were more likely to have aggressive subtypes such as luminal B subtype or triple-negative cancers associated with a poor prognosis requiring other preventive strategies.

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Expression of glutamine metabolism-related proteins according to molecular subtype of breast cancer

Endocrine Related Cancer ◽

10.1530/erc-12-0398 ◽

2013 ◽

Vol 20 (3) ◽

pp. 339-348 ◽

Cited By ~ 62

Author(s):

Sewha Kim ◽

Do Hee Kim ◽

Woo-Hee Jung ◽

Ja Seung Koo

Keyword(s):

Breast Cancer ◽

Molecular Subtypes ◽

Molecular Subtype ◽

Glutamine Metabolism ◽

Breast Cancers ◽

Breast Cancer Patients ◽

Luminal A ◽

Luminal B ◽

Related Proteins ◽

Glutaminase 1

The aim of this study was to investigate the expression of glutamine metabolism-related proteins to determine whether glutamine is metabolized differently according to breast cancer molecular subtype. We generated a tissue microarray of 702 breast cancer patients and performed immunohistochemical staining for glutamine metabolism-related proteins, including glutaminase 1 (GLS1 (GLS)), glutamate dehydrogenase (GDH (H6PD)), and amino acid transporter-2 (ASCT2 (SLC1A5)), which were separately evaluated in tumor and stroma compartments and then analyzed by breast cancer molecular subtypes. Breast cancers were classified as follows: 293 luminal A (41.7%), 166 luminal B (23.6%), 67 HER2 type (9.6%), and 176 TNBC (25.1%). HER2 type showed the highest stromal GLS1 (P=0.001), tumoral GDH (P=0.001), stromal GDH (P<0.001), and tumoral ASCT (P<0.001) expression. We identified differential expression of glutamine metabolism-related proteins according to molecular subtype of breast cancer. The highest glutamine metabolic activity was seen in HER2-type breast cancer.

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