scholarly journals Is There a Correlation between Multiparametric Assessment in Ultrasound and Intrinsic Subtype of Breast Cancer?

2021 ◽  
Vol 10 (22) ◽  
pp. 5394
Author(s):  
Magdalena Gumowska ◽  
Joanna Mączewska ◽  
Piotr Prostko ◽  
Katarzyna Roszkowska-Purska ◽  
Katarzyna Dobruch-Sobczak

Molecular profile of breast cancer provides information about its biological activity, prognosis and treatment strategies. The purpose of our study was to investigate the correlation between ultrasound features and molecular subtypes of breast cancer. From June 2019 to December 2019, 86 patients (median age 57 years; range 32–88) with 102 breast cancer tumors were included in the study. The molecular subtypes were classified into five types: luminal A (LA), luminal B without HER2 overexpression (LB HER2−), luminal B with HER2 overexpression (LB HER2+), human epidermal growth factor receptor 2 positive (HER2+) and triple negative breast cancer (TNBC). Histopathological verification was obtained in core biopsy or/and post-surgery specimens in all cases. Univariate logistic regression analysis was performed to assess the association between the subtypes and ultrasound imaging features. Experienced radiologists assessed lesions according to the BIRADS-US lexicon. The ultrasound scans were performed with a Supersonic Aixplorer and Supersonix. Based on histopathological verification, the rates of LA, LB HER2−, LB HER2+, HER2+, and TNBC were 33, 17, 17, 16, 19, respectively. Both LB HER2+ and HER2+ subtypes presented higher incidence of calcification (OR = 3.125, p = 0.02, CI 0.0917–5.87) and HER2+ subtype presented a higher incidence of posterior enhancement (OR = 5.75, p = 0.03, CI 1.2257–32.8005), compared to other subtypes. The calcifications were less common in TNBC (OR = 0.176, p = 0.0041, CI 0.0469–0.5335) compared to other subtypes. There were no differences with regard to margin, shape, orientation, elasticity values and vascularity among five molecular subtypes. Our results suggest that there is a correlation between ultrasonographic features assessed according to BIRADS-US lexicon and BC subtypes with HER2 overexpression (both LB HER2+ and HER2+). It may be useful for identification of these aggressive subtypes of breast cancer.

Mastology ◽  
2020 ◽  
Vol 30 (Suppl 1) ◽  
Author(s):  
Vanessa Monteiro Sanvido ◽  
Morgana Domingues da Silva ◽  
Patricia Zaideman Charf ◽  
Gil Facina ◽  
Afonso Celso Pinto Nazário

Introduction: Invasive breast carcinoma represents a heterogeneous group of lesions that differ in their molecular and histological characteristics. Perou et al. evaluated breast tumors using the DNA microarray technique and classified them into four molecular subtypes: Luminal A (LA), Luminal B (LB), HER2 overexpression (HER2), and triple-negative (TN). Immunohistochemistry approximately identifies the subtypes. The TN subtype is negative for estrogen and progesterone receptors and HER2 protein. This subgroup is comprehensive, with 75% of them being basaloid, that is, cells with a molecular profile similar to that of myoepithelial cells and a high expression 5, 6, 14, and 17 cytokeratins, vimentin, and P-cadherin. These tumors tend to be more aggressive, have higher rates of cell proliferation, and, therefore, a worse prognosis. Clinically, triple-negative carcinomas are more strongly associated with younger patients, early local and distant recurrence. Given their rapid progression, they can be clinically diagnosed in the interval of screening tests. Objective: To compare clinical and radiological aspects of TN and other molecular subtypes of breast cancer at diagnosis. Method: The study retrospectively evaluated data collected from medical records of patients diagnosed with breast cancer and treated at the Hospital São Paulo from 2013 to 2016. Results: In the study period, 235 cases of breast cancer were diagnosed. The incidence in patients under 39 years was 4.2% for LA, 4.9% for LB, and 8.3% for TN. At diagnosis, 83% of patients with TN tumors had clinical complaints, of which 96% were nodules. In mammographies, TN presented as nodules in 100% of cases, LA in 68%, LB in 71%, and HER2 in 50%. Microcalcifications were identified in 14% of LA cases, 21% of LB, and 50% of HER2. TN had no cases of microcalcifications or asymmetries. Among the other subtypes, the diagnosis by physical examination represented 35% to 53% of cases. As to the staging at diagnosis, TN cases presented ≤2 cm tumors in 25% of cases. The LA, LB, and HER2 subtypes presented as ≤2 cm tumors, respectively, in 61%, 49.4%, and 43% of patients. Lymph node involvement by neoplasm at diagnosis occurred in 3.35%, 17.5%, 14.3%, and 33.3% of LA, LB, HER2, and TN cases, respectively. Conclusion: TN carcinomas affect a greater number of young patients, outside the screening age group. In our sample, TN tumors were diagnosed based on clinical complaints and showed no association with non-palpable breast lesions. TN is the subtype with the highest probability of interval tumors, untraceable by conventional exams, and, as a result, other screening options, such as serum assays, have been discussed.


Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3146
Author(s):  
Patricia Fernández-Nogueira ◽  
Gemma Fuster ◽  
Álvaro Gutierrez-Uzquiza ◽  
Pere Gascón ◽  
Neus Carbó ◽  
...  

Breast cancer (BrCa) is the leading cause of death among women worldwide, with about one million new cases diagnosed each year. In spite of the improvements in diagnosis, early detection and treatment, there is still a high incidence of mortality and failure to respond to current therapies. With the use of several well-established biomarkers, such as hormone receptors and human epidermal growth factor receptor-2 (HER2), as well as genetic analysis, BrCa patients can be categorized into multiple subgroups: Luminal A, Luminal B, HER2-enriched, and Basal-like, with specific treatment strategies. Although chemotherapy and targeted therapies have greatly improved the survival of patients with BrCa, there is still a large number of patients who relapse or who fail to respond. The role of the tumor microenvironment in BrCa progression is becoming increasingly understood. Cancer-associated fibroblasts (CAFs) are the principal population of stromal cells in breast tumors. In this review, we discuss the current understanding of CAFs’ role in altering the tumor response to therapeutic agents as well as in fostering metastasis in BrCa. In addition, we also review the available CAFs-directed molecular therapies and their potential implications for BrCa management.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 572-572
Author(s):  
Yunan Han ◽  
Shuai Xu ◽  
Graham A. Colditz ◽  
Adetunji T. Toriola

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.


2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Charity Ameh-Mensah ◽  
Babatunde Moses Duduyemi ◽  
Kweku Bedu-Addo ◽  
Elijah Atta Manu ◽  
Francis Opoku ◽  
...  

Background. Little is known about the role of apoptosis in the tumorigenesis and prognosis of breast cancer in Ghana. Chemotherapeutic drug efficacy partially relates to apoptosis induction, rendering it a vital target in cancer therapy with unique biomarker opportunities that have not been exploited. Aberrations in this pathway are central to tumorigenesis, tumor progression, overall tumor growth, and regression during treatment therapies. Antiapoptotic bcl-2 (gene) and p53 are known to play roles in apoptosis while Ki-67 is a proliferative marker. The aim of our study is to determine the association of bcl-2 (protein) with p53 and Ki-67 in 203 consecutive breast cancer cases over a 10-year period. Method. A retrospective cross-sectional study on archival FFPE tissue blocks over a 9-year period with abstraction of clinicopathologic data. Two hundred and three consecutive and suitable FFPE blocks were selected for tissue microarray (TMA) construction, and IHC (bcl-2 (protein), Ki-67, p53, cyclin D, pan cytokeratins A and E, ER, PR, and HER2/neu) was done. Expressions of bcl-2 (protein), p53, and Ki-67 were related to histological grade, lymphovascular invasion, and molecular subtypes. SPSS version 23 was used to analyze results. Results. Most of our cases were in the fifth decade of life (31%); invasive carcinoma of no special type (NST) was predominant (87%); histological grade III (38%) was the highest; and Luminal A (19.8%), Luminal B (9.9%), HER2 (16%), and TNBC (54.3%) constituted the molecular classes. bcl-2 expression was found in 38% of the cases. Our cases also showed mutation in p53 (36.7%) and ki-67 expression (62.5%). bcl-2 (protein) and p53 significantly correlated with Luminal B and TNBC ( p < 0.01 ). Ki-67 also correlated significantly with Luminal A and B and HER2 overexpression ( p < 0.01 ). Premenopausal age (40–49) and histological grade inversely correlated with bcl-2 (protein) expression. p53 statistically correlated with Ki-67 ( p < 0.05 ). Conclusion. Our results show high expression of bcl-2 (protein) suggesting an important role of apoptosis in Ghanaian breast cancer cases. bcl-2 (protein), p53, and Ki-67 expressions emerged interdependently from this research and can thus be manipulated in prediction and prognosis of breast cancers in our setting.


Author(s):  
Karen S Johnson ◽  
Emily F Conant ◽  
Mary Scott Soo

Abstract Gene expression profiling has reshaped our understanding of breast cancer by identifying four molecular subtypes: (1) luminal A, (2) luminal B, (3) human epidermal growth factor receptor 2 (HER2)-enriched, and (4) basal-like, which have critical differences in incidence, response to treatment, disease progression, survival, and imaging features. Luminal tumors are most common (60%–70%), characterized by estrogen receptor (ER) expression. Luminal A tumors have the best prognosis of all subtypes, whereas patients with luminal B tumors have significantly shorter overall and disease-free survival. Distinguishing between these tumors is important because luminal B tumors require more aggressive treatment. Both commonly present as irregular masses without associated calcifications at mammography; however, luminal B tumors more commonly demonstrate axillary involvement at diagnosis. HER2-enriched tumors are characterized by overexpression of the HER2 oncogene and low-to-absent ER expression. HER2+ disease carries a poor prognosis, but the development of anti-HER2 therapies has greatly improved outcomes for women with HER2+ breast cancer. HER2+ tumors most commonly present as spiculated masses with pleomorphic calcifications or as calcifications alone. Basal-like cancers (15% of all invasive breast cancers) predominate among “triple negative” cancers, which lack ER, progesterone receptor (PR), and HER2 expression. Basal-like cancers are frequently high-grade, large at diagnosis, with high rates of recurrence. Although imaging commonly reveals irregular masses with ill-defined or spiculated margins, some circumscribed basal-like tumors can be mistaken for benign lesions. Incorporating biomarker data (histologic grade, ER/PR/HER2 status, and multigene assays) into classic anatomic TNM staging can better inform clinical management of this heterogeneous disease.


BMJ Open ◽  
2018 ◽  
Vol 8 (11) ◽  
pp. e021819
Author(s):  
Qin Li ◽  
Li Li ◽  
Xiaoyue Jiang ◽  
Qi Du ◽  
Yingrui Li ◽  
...  

ObjectivesThis study investigated the characteristics and prognostic values of traditional pathological parameters and advanced molecular subtypes in women with operable breast cancer in Beijing.DesignA retrospective study through case information enquiry or telephonic follow-up.SettingBeijing Friendship Hospital.Participants1042 patients with primary operable breast cancer between 2008 and 2012 were enrolled in the study.MeasuresThe characteristics and 5-year relapse rates according to the Nottingham Prognosis Index (NPI) and molecular subtypes were analysed.ResultsIn 1042 patients, the percentages of high histological grade, N1+N2, T2+T4 were 7.3%, 24.2%, 46.9%, respectively. In patients with invasive breast cancer, the percentages of auxiliary staging, positive margins, vascular invasion and nerve infiltration were 65.0%, 2.8%, 10.5% and 1.1%, respectively. The missing percentages of auxiliary staging, margins, vascular tumour invasion and nerve infiltration were 14.2%, 31.4%, 46.5% and 97.4%, respectively. The percentages of ER-positive, PR-positive, HER2-positive and Ki-67 high expression were 64.3%, 43.8%, 18.8% and 62.7%, respectively. The percentages of luminal A, luminal B, HER2-overexpression and basal-like breast cancers were 10.5%, 54.2%, 8.2% and 11.2%, respectively. Luminal A, luminal B and basal-like breast cancer subtypes were more common in the >60 years group, the 41–60 years group and the 20–40 years group, respectively. The 5-year relapse rates according to NPI were as follows: 6.2% in the low recurrence risk group, 10.4% in the moderate recurrence risk group and 12.9% in the high recurrence risk group. The 5-year relapse rates according to molecular subtypes were as follows: luminal A 4.0%, luminal B 7.0%, HER2-overexpression14.2%, basal-like 15.6%.ConclusionsReasonable analysis of traditional pathological parameters and advanced molecular subtypes in women with operable breast cancer in Beijing may be useful to guide precise treatment and predict prognosis.


2016 ◽  
Vol 3 (2) ◽  
pp. 47-54
Author(s):  
Wissal Mahir ◽  
Lamiaa Rouas ◽  
Driss Ferhati ◽  
Brahim Rhrab ◽  
Zaitouna Alhamany ◽  
...  

Introduction: Breast cancer remains despite the therapeutic progress, the leading cause of death by cancer among women. It represents a group of very heterogeneous clinical, histopathological and molecular diseases. Molecular heterogeneity has been demonstrated by genomic analysis, even for similar histology cancers. Four subgroups of breast carcinomas are distinguished: Luminal A, Luminal B, HER2 over expression and Basal - like. The Immuno-histo-chemical analysis useip (estrogen receptors) RE, the PR (progesterone receptors), the ((Human Epidermal Growth Factor Receptor-2), the Ki67 (proliferation marker) HER2, CK5/6) has shown a subdivision into subgroups similar to those found by genomic analysis. These subgroups are different from the point of view of clinical course and response to adjuvant treatment. Objectives: The aim of this work is to study the molecular profile of the breast cancers by immunostaining on Moroccan series to a classification with a prognostic value allowing a treatment tailored to each group of patients. Furthermore, the molecular subgroups were correlated to other clinical and histological factors. Material and methods: It is a prospective study of the laboratory of Anatomy and Pathologic cytology of the children's Hospital, the service I of the maternity hospital in Rabat and in cooperation with the United Nations Centre of pathological anatomy. To do this, 88 cases of breast cancer together were diagnosed between January 1, 2010 and December 31, 2014, taking a period of five years. All tissue samples made subject study of Immuno-histo-chemistry with the following markers: RE, PR, HER2 and Ki67. Only negative triple cases (HR and HER2 negative) benefited from an additional marking with CK5/6 and EGFR to set the basal profile. Results: Series of 88 cases of mammary carcinomas observed on operating parts, ranged in age between 28 and 84 years old, with an average of 51 ± 12, 8. Carcinoma infiltrating non-specific (DOCTORS) was the most frequent (87.5%). Ranks histo-prognostic Scarff Bloom and Richardson (SBR) 2 and 3 respectively accounted for 45.5 and 51.1% of cases and only 2, 3% of the DOCTORS were grade 1. The Luminal B (53.4%) was under the most common molecular group, followed by Luminal A (23.9%), HER2 + (15.9%) and triple negative (6.8%). The correlation of molecular type of tumors with different prognostic factors showed only one significant connection with the SBR grade.


Author(s):  
Ana Paula Almeida Miranda Reis ◽  
Cecilma Miranda de Sousa Teixeira ◽  
Adriano Rêgo Lima de Medeiros ◽  
Karlla Zolinda Cantão Chaves ◽  
Camila Rosa de Albuquerque ◽  
...  

Abstract Objective To evaluate the distribution of the main sociodemographic and clinical-pathological characteristics in women with breast cancer according to the molecular profile by immunohistochemistry. Methods A cross-sectional, retrospective, analytical and quantitative study was performed, with an analysis of 137 medical records from January 2015 to December 2018 of women attending the High Complexity in Oncology Unit of the city of Imperatriz, state of Maranhão, Brazil. The immunohistochemical profile of tumors based on the estrogen and progesterone receptor, Human Epidermal growth factor Receptor-type 2 (HER2) overexpression and Ki67 cell proliferation index was defined, from which six molecular subtypes were determined: luminal A, luminal B-HER2 negative, luminal B-HER2 positive, triple negative, overexpression of HER2 and inconclusive. Results A total of 52.6% of the patients were postmenopausal, mean age 52.1 years old, brown (56.2%), had a schooling level < 9 years (40%), staging > IIB (52.6%) and 23.4% had metastasis. Invasive ductal carcinoma accounted for 84.7%, tumor size was 2 to 5 cm (48.9%), with lymph node involvement (56.2%), axillary lymphadenectomy in 67.2%, and mastectomy in 73.7% of the patients. The most frequent molecular subtype was the luminal B-HER2 negative (36.5%), and the luminal A subtype showed characteristics of better prognosis when compared with the others. Conclusion It was concluded that in the association of molecular subtypes with sociodemographic and clinical-pathological characteristics, there were no statistically significant results obtained, except for complementary therapy, referring to hormone therapy, and there was a high index of metastasis at diagnosis, which was a worrying factor and indicative of failures in the screening and early diagnosis of this population.


2021 ◽  
Vol 11 (8) ◽  
pp. 808
Author(s):  
Anna Burguin ◽  
Caroline Diorio ◽  
Francine Durocher

Breast cancer (BC) is the most frequent cancer diagnosed in women worldwide. This heterogeneous disease can be classified into four molecular subtypes (luminal A, luminal B, HER2 and triple-negative breast cancer (TNBC)) according to the expression of the estrogen receptor (ER) and the progesterone receptor (PR), and the overexpression of the human epidermal growth factor receptor 2 (HER2). Current BC treatments target these receptors (endocrine and anti-HER2 therapies) as a personalized treatment. Along with chemotherapy and radiotherapy, these therapies can have severe adverse effects and patients can develop resistance to these agents. Moreover, TNBC do not have standardized treatments. Hence, a deeper understanding of the development of new treatments that are more specific and effective in treating each BC subgroup is key. New approaches have recently emerged such as immunotherapy, conjugated antibodies, and targeting other metabolic pathways. This review summarizes current BC treatments and explores the new treatment strategies from a personalized therapy perspective and the resulting challenges.


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