scholarly journals Molecular biological subtypes of breast cancer in BRCA1 mutation carriers

2021 ◽  
Vol 7 (4) ◽  
pp. 29-36
Author(s):  
N. I. Pospekhova ◽  
D. A. Golovina ◽  
M. G. Filippova ◽  
A. V. Semyanikhina ◽  
S. L. Dranko ◽  
...  
Keyword(s):  
Molecular Subtypes ◽  
Molecular Subtype ◽  
Estrogen Receptor Status ◽  
Brca1 Mutation ◽  
Age Groups ◽  
Brca1 Gene ◽  
Progesterone Receptor Status ◽  
Her2 Positive ◽  
Receptor Status ◽  
Luminal B

Background. According to the literature, BRCA1-associated breast cancer (BC) most often belongs to the triple negative (TNBC) molecular subtype. The data on the contribution of other molecular subtypes to this group of patients differ among different studies.The study objective is to evaluate the frequency of different tumor molecular subtypes in BC patients with BRCA1 gene mutation treated in N. N. Blokhin National Medical Research Center of Oncology in the period from 2017 to 2020.Materials and methods. The study included BC patients with a mutation in the BRCA1 gene (n = 209) identified as a result BRCA1 mutation screening of patients with BC. DNA diagnostics was carried out on blood samples of patients using the real-time polymerase chain reaction method. After analyzing the patients primary documentation clinical and morphological data were taken into account: the age of diagnosis, the stage of the disease, the results of immunohistochemical studies (estrogen receptor status, progesterone receptor status, HER2 expression, Ki-67 proliferation index). The assignment to the particular molecular tumour subtypes was performed according to estrogen receptor status, progesterone receptor status, HER2 status and Ki67 value.Results. Clinical and pathomorphological data of 209 patients with BRCA1-associated BC were analyzed. The age at diagnosis ranged from 23 to 72 years, the median age was 40 years, the mean age was 41.46 ± 9.82 years. BC associated with BRCA1 was found to be TNBC in 71.3 % and luminal B, HER2 negative (LumB–) in 19.1 % of the cases. Other tumour subtypes were much less common: luminal B, HER2 positive (LumB+) in 7.2 %, luminal A (LumA) in 1 % and HER2-positive (HER2+) in 1.4 % of the cases. The frequency of subtypes was estimated in different age groups (1st – patients 23–34 (n = 53), 2nd – 35–49 (n = 111), and 3rd – 50–72 (n = 45) years old). TNBC frequency was 81.1 % in the 1st group, 73.9 % in the 2nd and 53.4 % in the 3rd group; LumB– frequency was 15.1, 15.3 and 33.3 % respectively. Using the Fisher test it was shown that the differences in frequencies were statistically significant between groups 1st and 3 rd, as well as between groups 2 nd and 3 rd (p <0.05).Conclusion. TNBC was the main molecular subtype in all age groups of BC patients with BRCA1 germinal mutation, TNBC frequency was lower in the older age group. LumB– subtype was also common in BRCA1-associated tumors especially in older women.

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

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.

scholarly journals Comparative analysis of the receptor status of the primary focus and synchronous axillary metastases in breast cancer patients

2020 ◽  
Vol 24 (3-6) ◽  
pp. 74-78
Author(s):  
Yu. S. Krumin’ ◽  
V. A. Khailenko ◽  
N. A. Kozlov ◽  
G. Yu. Cheremis ◽  
D. V. Khailenko ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Proliferative Activity ◽  
Molecular Subtype ◽  
Her2 Status ◽  
Breast Cancer Patients ◽  
Luminal A ◽  
Her2 Positive ◽  
Axillary Metastases ◽  
Receptor Status ◽  
Luminal B

The aim of the investigation. To study concordance of surrogate molecular subtype in the pairs of primary and synchronous axillary metastases in patients with invasive breast cancer (IBC). Materials and methods. Retrospective analysis included 80 patients aged 28 to 90 years (average age 40.35.3 years) with a first-time diagnosed IBC who underwent surgical treatment at the N.N. Blokhin National Medical Research Center of Oncology during 20162018 years. None of the patients received any neoadjuvant drug therapy. The pathological evaluation of the estrogen receptors (ER), progesterone receptor (PR), HER2 expression and estimation of proliferative activity (Ki-67 index) with subsequent assignment to surrogate subtypes were performed according to ASCO/CAP protocols and the recommendations of the 20132019 San-Gallen Conference on treatment of Early Breast Cancer. Results. Preliminary results of our study revealed therapeutically significant changes in hormone receptor status, HER2-status and proliferative activity in 12.5% of cases of Luminal A type IBC, 20% of Luminal B/HER2-positive and 4% of Luminal B/Her2-negative subtypes of IBC.

scholarly journals Cytokines in various molecular subtypes of breast cancer

2021 ◽  
Vol 35 ◽  
pp. 205873842110340
Author(s):  
Alexsander Autenshlyus ◽  
Kristina Davletova ◽  
Nikolay Varaksin ◽  
Igor Marinkin ◽  
Vyacheslav Lyakhovich
Keyword(s):  
Peripheral Blood ◽  
Blood Cells ◽  
Triple Negative ◽  
Molecular Subtypes ◽  
Molecular Subtype ◽  
Cytokine Secretion ◽  
Peripheral Blood Cells ◽  
Her2 Positive ◽  
Luminal B ◽  
Tnf Α

Introduction Breast cancer is a heterogeneous disease that has multiple molecular and morphological subtypes. Nonetheless, the relation between various molecular subtypes and functional characteristics of a tumor in terms of cytokine secretion remains unknown. Methods We studied spontaneous and mitogen-induced cytokine secretion by invasive breast carcinoma of no special type (IBC NST; cultured tumors and cultured peripheral blood cells), depending on a molecular tumor subtype (where “mitogens” means “polyclonal activators” (PA): phytohemagglutinin p, phytohemagglutinin M, concanavalin A, and Escherichia coli lipopolysaccharide). Enzyme-linked immunosorbent assays were used to determine concentrations of IL-6, IL-8, IL-10, IL-17, IL-18, IL-1β, IL-1Ra, TNF-α, IFN-γ, G-CSF, GM-CSF, VEGF, and MCP-1 in culture supernatants of the tumors and peripheral blood cells. Results The luminal B HER2-positive molecular subtype of IBC NST was found to feature the highest spontaneous secretion of IL-6 and IL-8 and the highest mitogen-induced secretion of IL-6, IL-8, IL-1Ra, and TNF-α by tumors; the highest mitogen-induced secretion of IL-2, IL-6, IL-8, IL-1β, TNF-α, IFN-γ, and G-CSF by peripheral blood cells; and the highest cytokine-producing potential (the ratio of mitogen-induced to spontaneous secretion) of peripheral blood cells for the secretion of IL-6, IL-8, and IL-1Ra as compared to other molecular subtypes. The triple-negative subtype of IBC NST was characterized by the lowest cytokine-producing potential of tumors for the secretion of IL-6 and IL-8 as compared to other molecular subtypes as well as a lower “stimulation index of polyclonal activators” (calculated as (cytokine secretion after incubation with PA)/(spontaneous cytokine secretion)) for IL-18 secretion as compared to luminal subtypes. The XYZ correlated with a suppressive effect of PA on cytokine secretion by tumors of the triple-negative molecular subtype. Conclusion Therefore, our findings indicate that in IBC NST of luminal B HER2-positive and triple-negative molecular subtypes, the cytokine network has distinctive functional features.

scholarly journals Prevalence of Molecular Subtypes of Breast Carcinoma and Its Comparison between Two Different Age Groups: A Retrospective Study from a Tertiary Care Center of Northeast India

2021 ◽  
Vol 10 (04) ◽  
pp. 220-224
Author(s):  
Jagannath Dev Sharma ◽  
Sachin Khanna ◽  
Shubhra Ramchandani ◽  
Lopa Mudra Kakoti ◽  
Argha Baruah ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Retrospective Study ◽  
Triple Negative ◽  
Molecular Subtypes ◽  
Molecular Subtype ◽  
Age Groups ◽  
Age Group ◽  
Luminal A ◽  
Luminal B ◽  
Her 2

Abstract Objective The aim of the study is to see the prevalence of different molecular subtypes in breast cancer patients among two different age groups: ≤40 years and >40 years. Materials and Methods Retrospective study was conducted from January 2019 to December 2019. We studied 568 cases of breast carcinoma and classified them into four molecular subtypes—luminal A, luminal B, human epidermal growth factor-2 (HER 2), and triple negative. Cases were divided into two different groups: (1) ≤40 years and (2) >40 years. Statistical Analysis was done by using SPSS software version 20.0. Results Out of 568 cases, 151 (26.6%) were ≤40 years of age and 417 (73.4%) were >40 years of age. The most common histological subtype of breast cancer was ductal carcinoma in 548 cases and the most common grade was grade III. Immunohistochemistry was done in 432 patients. In younger age group, the most common molecular subtype was luminal B (31%) followed by triple negative (20%), luminal A (14%), and then HER 2 (5.3%), while in the older age group most common molecular subtype was luminal B (27.8%) followed by triple negative (14%), HER 2 (12.2%), and then luminal A (12%). Conclusion Luminal B is found to be the most common subtype in Northeast Indian women with breast cancer, as compared with other studies in which luminal A was the most common subtype. This could be due to the reason that Ki-67 was not done in most of the other studies.

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.

Prognostic significance of the progesterone receptor status in Ki67-high and -low Luminal B-like HER2-negative breast cancers

Breast Cancer ◽  
2014 ◽  
Vol 23 (2) ◽  
pp. 310-317 ◽  
Author(s):  
Kaolu Sato ◽  
Minoru Miyashita ◽  
Takanori Ishida ◽  
Akihiko Suzuki ◽  
Hiroshi Tada ◽  
...  
Keyword(s):  
Progesterone Receptor ◽  
Prognostic Significance ◽  
Breast Cancers ◽  
Progesterone Receptor Status ◽  
Receptor Status ◽  
Luminal B

Breast cancer molecular subtypes association with clinical outcomes and race.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e12575-e12575 ◽  
Author(s):  
Ramses F. Sadek ◽  
Li fang Zhang ◽  
Houssein Talal Abdul Sater
Keyword(s):  
Breast Cancer ◽  
Black Women ◽  
Clinical Outcomes ◽  
Cox Regression ◽  
Molecular Subtypes ◽  
Molecular Subtype ◽  
Cancer Stage ◽  
Luminal A ◽  
Luminal B ◽  
Race Disparity

e12575 Background: Breast Cancer (BC) has been classified into four subtypes: Luminal A (LABC), Luminal B (LBBC), Triple negative (TNBC) and HER2-enriched (HER2e). BC mortality in Black women is significantly higher than in Whites and Asians. BC in Blacks has been characterized by higher grade and later stage. Causes of the Black-White BC survival disparity have been investigated, including differences in: diagnostic stage, socioeconomics, and comorbidities. These have led researchers to investigate the differences in tumor molecular subtype and their association with clinical outcomes and races. Methods: This study used the Surveillance, Epidemiology, and End Results – 18 (SEER-18) Registries research data between 2010 and 2013 that included over 212,000 patients. Descriptive statistics, Odds ratios (OR) and 95%Confidence intervals (CI) were used to study the association between BC stage, grade, and mortality and BC molecular subtypes across different races. We employed Cox regression models to explore the race disparity in BC mortality before and after controlling for BC molecular subtype and other clinical and social factors. Results: TNBC had more high grade cancer compared to HER2e subtype (OR, 1.5; CI, 1.3 - 1.8), LBBC (OR, 4.5; CI, 4.0 - 5.0) and LABC (OR, 12.2; CI, 11.2 – 13.3) for Black. BC mortality was higher in TNBC subtype compared to HER2e subtype (OR, 1.3; CI, 1.1 - 1.6), LBBC (OR, 2.4; CI, 2.0 - 2.9), and LABC (OR, 2.8; CI, 2.4 – 3.2) for Blacks. Results are consistent for all races. HER2e subtype had more late cancer stage compare to LBBC (OR, 1.2; CI, 1.0 - 1.4), TNBC (OR, 1.4; CI, 1.2 - 1.6) and LABC (OR, 2.1; CI, 1.8 - 2.4) in Blacks with similar results in all races. BC mortality in Blacks was higher compare with Whites (HR, 1.9; CI, 1.8 - 2.0) and Asian (HR, 2.7; CI, 2.5 - 3.0). After controlling for cancer subtype and other factors in the Cox regression model, the corresponding HRs ware significantly decreased to 1.2 (CI, 1.1 -1.3) and 1.6 (9CI, 1.5 -1.8). Blacks have heighst percent in stage IV and grade higer grade of disease. Conclusions: Molecular subtypes of BC contribute differently to risks of late cancer stage, high cancer grade and BC specific mortality. These differences are consistent in all races. The molecular subtypes and other social and clinical factors may explain part of the BC mortality race disparity.

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

2019 ◽  
Vol 21 (1) ◽  
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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