Assessment of Breast Cancer Immunohistochemical Properties with Demographics and Pathological Features; A Retrospective Study

Background: Breast cancer is considered the most common malignant disease in the female population. It is known as an emerging epidemy with a great burden on women's health, which can be associated with poor outcomes. Some factors including histological type, immunohistochemistry (IHC), tumor grade, and tumor size can have effects on breast cancer. Objectives: This study aimed at assessing the effects of mentioned factors on IHC type of breast cancer. Methods: This retrospective cross-sectional study was conducted on 142 patients, who were referred to one of the referral centers for breast cancer in Mashhad. Information including age, histological type, familial history, menopause status, tumor grade, tumor size, and IHC properties was collected from the patient’s medical records. Allred score was used for reporting hormonal status. The data were analyzed by version 26 of SPSS software. Results: The mean age of patient was 50.2 ± 12.7. The frequency of luminal A and luminal B type was calculated as 29.7 and 18.9%, respectively. In addition, triple-negative IHC type has a prevalence of 24.3% and HER2 had a prevalence of 27%. There were no significant differences between age (P = 0.34), familial history (P = 0.42), menopause (P = 0.36), histological type (invasive: P = 0.11, in situ: P = 0.45), and IHC properties. However, tumor diameter (P = 0.0001) and tumor grading (P = 0.002) had significant association with IHC properties. Conclusions: Factors including tumor size and pathological grade can have effects on the gene expression properties of breast cancers. Luminal IHC type A is more common in breast cancer and is associated with better outcomes. However, age, histological type, familial history, and menopause status had no effects on the IHC properties of breast cancer.

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Androgen Receptor Expression in Triple-Negative Breast Cancer

Archives of Breast Cancer ◽

10.32768/abc.20196290-94 ◽

2019 ◽

pp. 90-94

Author(s):

Samane Jam ◽

Alireza Abdollahi ◽

Sanaz Zand ◽

Zahra Khazaeipour ◽

Ramesh Omranipour ◽

...

Keyword(s):

Breast Cancer ◽

Androgen Receptor ◽

Triple Negative Breast Cancer ◽

Lymphovascular Invasion ◽

Triple Negative ◽

Tumor Grade ◽

Receptor Expression ◽

Breast Cancers ◽

Breast Cancer Patients ◽

Cross Sectional

Background: Triple-negative breast cancer (TNBC) accounts for 15 to 20% of all breast cancers. These patients do not benefit from hormone therapy and other targeted treatments of breast cancer. Recently, researchers proposed the use of androgen receptor (AR)-targeted therapies in this subset of patients. The rate of AR expression in TNBC patients varies from 0 to 53%. AR positivity is associated with a better outcome for breast cancer patients. The purpose of this study was to evaluate AR status in TNBC patients and its association with other demographic and pathologic features.Methods: This cross-sectional study was conducted in the Cancer Institute of Iran, affiliated with Tehran University of Medical Sciences, in 2015. Archived formalin-fixed, paraffin-embedded breast tumor blocks were evaluated to determine the AR status of the tumors. Demographic and pathologic characteristics of the patients were retrieved from the department of pathology database. Data were analyzed with SPSS 18.0.Results: Seventy-seven TNBC patients with the mean age of 45.3 ± 11.5 were assessed. Twenty-six patients (34%) showed AR expression, and 51 patients (56%) did not have AR expression. There was no significant correlation between AR status and age, tumor size, histopathologic type of tumor, or lymph node involvement. However, AR positivity had a statistically significant association with a lower tumor grade and lymphovascular invasion (P = 0.029 and P = 0.01, respectively).Conclusion: TNBC patients with AR expression tend to have lower tumor grades and higher rates of lymphovascular invasion.

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Histological Aspects and Quantitative Assessment of Ki67 as Prognostic Factors in Breast Cancer Patients: Result from a Single-Center, Cross Sectional Study

Medicina ◽

10.3390/medicina56110600 ◽

2020 ◽

Vol 56 (11) ◽

pp. 600

Author(s):

Irina Niță ◽

Cornelia Nițipir ◽

Ștefania Andreea Toma ◽

Alexandra Maria Limbău ◽

Edvina Pîrvu ◽

...

Keyword(s):

Breast Cancer ◽

Overall Survival ◽

Progression Free Survival ◽

Tumor Grade ◽

Cross Sectional Study ◽

Histological Type ◽

Breast Cancer Patients ◽

Cross Sectional ◽

Free Survival ◽

Prognostic Assessment

Background and objectives: Our aim is to explore the relationship between the levels of protein encoded by Ki67 and the histopathological aspects regarding the overall survival and progression-free survival in a single university center. A secondary objective was to examine other factors that can influence these endpoints. New approaches to the prognostic assessment of breast cancer have come from molecular profiling studies. Ki67 is a nuclear protein associated with cell proliferation. Together with the histological type and tumor grade, it is used to appreciate the aggressiveness of the breast tumors. Materials and Methods: We conducted a retrospective single-institution study, at Elias University Emergency Hospital, Bucharest, Romania, in which we enrolled women with stage I to III breast cancer. The protocol was amended to include the immunohistochemistry determination of Ki67 and the histological aspects. The methodology consisted in using a Kaplan–Meier analysis for the entire sample and restricted mean survival time up to 36 months. Results: Both lower Ki67 and low tumor grade are associated with better prognosis in terms of overall survival (OS) and progression-free survival (PFS) for our patients’ cohort. In our group, the histological type did not impact the time to progression or survival. Conclusions: Both overall survival and progression-free survival may be influenced by the higher value of Ki67 and less differentiated tumors. Further studies are needed in order to establish if the histologic type may impact breast cancer prognostic, probably together with other histologic and molecular markers.

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MCM6 Versus Ki-67 in Diagnosis of Luminal Molecular Subtypes of Breast Cancers

10.21203/rs.3.rs-934232/v1 ◽

2021 ◽

Author(s):

Dorsay Sadeghian ◽

Hana Saffar ◽

Pouya Mahdavi Sharif ◽

Vahid Soleimani ◽

Behnaz Jahanbin

Keyword(s):

Breast Cancer ◽

Cellular Proliferation ◽

Molecular Subtypes ◽

Surrogate Marker ◽

Breast Cancers ◽

Luminal A ◽

Ki 67 ◽

Cross Sectional ◽

Luminal B ◽

Prognostic Features

Abstract Background: Currently, breast cancers are divided into four major molecular subtypes. The distinction between the luminal A and luminal B subtypes is mainly based on the cellular proliferation indices and is assessed by the Ki-67 scoring. Due to the limitations in the assessment and expression of Ki-67, we hypothesized that minichromosome maintenance protein 6 (MCM6) can be taken as a surrogate marker to differentiate molecular subtypes and aid in more precise grading of tumors. Methods: We performed a retrospective, cross-sectional study on 124 samples of breast cancer and 40 samples of normal breast tissue. Relevant clinical information was retrieved from the relevant Cancer Institute database.Results: MCM6 could discriminate between different histologic grades. The luminal B subtype exhibited a higher MCM6 score in comparison to luminal A (P=0.01). There were significantly higher MCM6 scores in the hormone receptor (HR) negative, in comparison to luminal breast cancers (P<0.001). MCM6 score had a significant correlation with the mitotic count (P<0.001).Conclusion: MCM6 can reliably differentiate luminal A and luminal B subtypes and was correlated with the mitotic counts. More studies are needed to standardize its assessment methods, determine more robust cut-off values, and evaluate its associations with prognostic features of breast cancer.

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Tumor size estimation of the breast cancer molecular subtypes using imaging techniques

Medicine and Pharmacy Reports ◽

10.15386/mpr-1476 ◽

2020 ◽

Author(s):

Gulten Sezgın ◽

Melda Apaydın ◽

Demet Etıt ◽

Murat Kemal Atahan

Keyword(s):

Breast Cancer ◽

Tumor Size ◽

Molecular Subtypes ◽

Imaging Techniques ◽

Breast Cancers ◽

Size Estimation ◽

Luminal A ◽

Luminal B ◽

Cancer Management ◽

Underestimation Rate

Background and aim. In medical practice the classification of breast cancer is most commonly based on the molecular subtypes, in order to predict the disease prognosis, avoid over-treatment, and provide individualized cancer management. Tumor size is a major determiner of treatment planning, acting on the decision-making process, whether to perform breast surgery or administer neoadjuvant chemotherapy. Imaging methods play a key role in determining the tumor size in breast cancers at the time of the diagnosis. We aimed to compare the radiologically determined tumor sizes with the corresponding pathologically determined tumor sizes of breast cancer at the time of the diagnosis, in correlation with the molecular subtypes. Methods. Ninety-one patients with primary invasive breast cancer were evaluated. The main molecular subtypes were luminal A, luminal B, HER-2 positive, and triple-negative. The Bland–Altman plot was used for presenting the limits of agreement between the radiologically and the pathologically determined tumor sizes by the molecular subtypes. Results. A significantly proportional underestimation was found for the luminal A subtype, especially for large tumors. The p-values for the magnetic resonance imaging, mammography, and ultrasonography were 0.020, 0.030, and <0.001, respectively. No statistically significant differences were observed among the radiologic modalities in determining the tumor size in the remaining molecular subtypes (p > 0.05). Conclusion. The radiologically determined tumor size was significantly smaller than the pathologically determined tumor size in the luminal A subtype of breast cancers when measured with all three imaging modalities. The differences were more prominent with ultrasonography and mammography. The underestimation rate increases as the tumor gets larger.

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Prediction of long-term survival using expression of FOXA1, a determinant of estrogen response domains in breast cancer

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.539 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 539-539

Author(s):

S. Badve ◽

D. Turbin ◽

A. Morimiya ◽

T. Nielsen ◽

C. Perou ◽

...

Keyword(s):

Breast Cancer ◽

Disease Free Survival ◽

Tumor Grade ◽

Nodal Status ◽

Breast Cancers ◽

Luminal A ◽

Term Survival ◽

Free Survival ◽

Disease Free ◽

Foxa1 Expression

539 Background: Recent studies have demonstrated cofactor dependency of estrogen receptor alpha (ERα) in defining specific pattern of estrogen (E2) response in breast cancer. FOXA1, also called HNF3α, a forkhead family transcription factor, has emerged as a major cofactor that is essential for optimum transcription of ∼50% of ERα:E2 responsive genes. FOXA1 is expressed in breast cancer cells and in cDNA microarray cluster analysis segregates with genes that characterize the luminal A subtype such as ERα, GATA3, and XBP-1. Detailed expression analysis of FOXA1 in human breast tumors has not been previously performed and it is not known whether it is an independent prognostic factor in breast cancer. Methods: A tissue microarray comprising tumors from 438 patients with 20 years follow-up was analyzed for FOXA1 expression using goat-anti-human FOXA1 antibody by immunohistochemistry. Percentage (P) and intensity (I) of expression was analyzed to generate numerical score (S= P × I). FOXA1 expression was correlated with tumor grade, nodal status, disease free survival, and expression of ER, PR, GATA3, HER2, p27kip1, phospho-AKT, and luminal A subtype (defined as ER &/or PR+, bcl-2+ and Her-2-neg). Results: FOXA1 expression (score greater than 100) was seen in 187 of 438 breast cancers and correlated with greater likelihood of survival at 20 year (p=0.0114). A significant positive correlation was observed between FOXA1 expression and expression of ERα (p= 0.000001), GATA3 (p= 0.000001), PR (p= 0.00001), phospho-AKT (p= 0.00001). Similarly, a significant correlation was noted with luminal A subtype. An inverse correlation was noted with tumor grade and mdm-2 expression (p=0.00001). HER2 or p27kip1 expression and nodal status showed no correlation with FOXA1. Conclusions: FOXA1 is good prognostic marker predicting disease free survival in patients with breast cancer. Since its expression correlates well with breast cancer of luminal A subtype, it can also be used to identify these good prognosis tumors from the rest of the ER positive breast cancers in archival paraffin embedded breast tissues. No significant financial relationships to disclose.

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Association between ultrasound findings, tumor type, grade, and biological markers in patients with breast cancer

Egyptian Journal of Radiology and Nuclear Medicine ◽

10.1186/s43055-019-0048-1 ◽

2019 ◽

Vol 50 (1) ◽

Author(s):

Yasmine Mohamed Elsaeid ◽

Dina Elmetwally ◽

Salwa Mohamed Eteba

Keyword(s):

Breast Cancer ◽

Biological Markers ◽

Tumor Grade ◽

The State ◽

Tumor Type ◽

Breast Cancers ◽

Duct Carcinoma ◽

Ultrasound Findings ◽

Her 2 ◽

And Biological Markers

Abstract Background This prospective study included 65 female patients with primary breast cancer. Ultrasound was performed for all patients. Ultrasound findings were analyzed according to the ACR BI-RADS lexicon 5th edition and correlated with tumor type, grade, and biological markers (ER, PR, HER-2/neu, and Ki67). The purpose of this study is to assess the association between ultrasound findings, tumor type, grade, and the state of biological markers in patients with breast cancer. Results Irregular shape and speculated margins are more frequently associated with invasive duct carcinoma than DCIS (p value < 0.001). There were no association between the ultrasound findings (shape, margin, orientation, echopattern, and posterior features) and the tumor grade (p value 1.0, 0, 0.544, 1.0, and 1.0), respectively. Irregular shape is more frequently seen in ER and PR positive breast cancers (p value = 0.036 and 0.026, respectively). Non-circumscribed margins were frequently seen in PR positive breast cancers (p value = 0.068). No statistically significant difference between US descriptors and HER-2/neu-positive cases. Conclusion Irregularly shaped tumors with speculated margins are frequently seen in invasive duct carcinoma and also more frequently seen in ER-, PR-, and Ki67-positive cases. No relation between ultrasound descriptors and the tumor grade of invasive duct carcinoma. Also, there were no relation between ultrasound descriptors and the state of HER-2/neu.

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Comparison of survival in non-metastatic inflammatory and other T4 breast cancers: a SEER population-based analysis

BMC Cancer ◽

10.1186/s12885-021-07855-z ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Dechuang Jiao ◽

Jingyang Zhang ◽

Jiujun Zhu ◽

Xuhui Guo ◽

Yue Yang ◽

...

Keyword(s):

Breast Cancer ◽

Cox Model ◽

Survival Rates ◽

Tumor Grade ◽

Population Based ◽

Rank Test ◽

Breast Cancers ◽

Significant Independent Predictor ◽

Cancer Specific Survival ◽

7Th Edition

Abstract Background Previous studies have reported poor survival rates in inflammatory breast cancer (IBC) patients than non-inflammatory local advanced breast cancer (non-IBC) patients. However, until now, the survival rate of IBC and other T4 non-IBC (T4-non-IBC) patients remains unexplored. Methods Surveillance, Epidemiology, and End Results (SEER) database was searched to identify cases with confirmed non-metastatic IBC and T4-non-IBC who had received surgery, chemotherapy, and radiotherapy between 2010 and 2015. IBC was defined as per the American Joint Committee on Cancer (AJCC) 7th edition. Breast Cancer-Specific Survival (BCSS) was estimated by plotting the Kaplan-Meier curve and compared across groups by using the log-rank test. Cox model was constructed to determine the association between IBC and BCSS after adjusting for age, race, stage of disease, tumor grade and surgery type. Results Out of a total of 1986 patients, 37.1% had IBC and mean age was 56.6 ± 12.4. After a median follow-up time of 28 months, 3-year BCSS rate for IBC and T4-non-IBC patients was 81.4 and 81.9%, respectively (log-rank p = 0.398). The 3-year BCSS rate in HR−/HER2+ cohort was higher for IBC patients than T4-non-IBC patients (89.5% vs. 80.8%; log-rank p = 0.028), and in HR−/HER2- cohort it was significantly lower for IBC patients than T4-non-IBC patients (57.4% vs. 67.5%; log-rank p = 0.010). However, it was identical between IBC and T4-non-IBC patients in both HR+/HER2- (85.0% vs. 85.3%; log-rank p = 0.567) and HR+/HER2+ (93.6% vs. 91.0%, log-rank p = 0.510) cohorts. After adjusting for potential confounding variables, we observed that IBC is a significant independent predictor for survival of HR−/HER2+ cohort (hazards ratio [HR] = 0.442; 95% CI: 0.216–0.902; P = 0.025) and HR−/HER2- cohort (HR = 1.738; 95% CI: 1.192–2.534; P = 0.004). Conclusions Patients with IBC and T4-non-IBC had a similar BCSS in the era of modern systemic treatment. In IBC patients, the HR−/HER2+ subtype is associated with a better outcome, and HR−/HER2- subtype is associated with poorer outcomes as compared to the T4-non-IBC patients.

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Epidemiological and pathological characteristics of post-surgical cases of invasive breast cancer among ethnicities of Iran in 2018: A single center cross-sectional study

Archive of oncology ◽

10.2298/aoo190626007s ◽

2020 ◽

Vol 26 (1) ◽

pp. 6-9

Author(s):

Soheila Sayad ◽

Seyyed Ahmadi ◽

Reza Nekouian ◽

Mahshid Panahi ◽

Khatereh Anbari

Keyword(s):

Breast Cancer ◽

Lymph Node ◽

Invasive Breast Cancer ◽

Triple Negative ◽

Cross Sectional Study ◽

Sectional Study ◽

Single Center ◽

Cross Sectional ◽

Familial History ◽

Number Of Patients

Background: Present study aimed to investigate immunohistochemical parameters in post-surgical cases of invasive breast cancer. Methods: In this single center cross-sectional study we investigated ethnicity, familial history, type of cancer, stage of cancer, lymph node positivity, bilateral involvement, metastasis and immunohistochemical parameters (estrogen and progesterone receptor, human epidermal growth factor receptor 2, as well as frequency of triple positive and triple negative patients merely based on immunohistochemical parameters). Results: Frequency of positive familial history was 27.42% (16.31-38.52%). Lymph node involvement was detected in 55.93% (43.26-68.60%) of the cases. Frequency of positive HER2 was 38.60% (25.96-51.23%). There were 17.54% (7.67-27.42%) of triple positive and 7.02% (0.39-13.65%) of triple negative cases. The most common stage at the time of diagnosis was stage 3 with 43.33% (30.79-55.87%) frequency. In Lur/Lak population higher frequency of positive HER2 cases was detected whereas in Mazani population frequency of positive HER2 cases was low (p=0.0291). Conclusions: These results could contribute to understanding of breast cancer patterns among different ethnicities. In order to draw clear conclusion future investigations have to be done in several health centers, for longer time periods and with larger number of patients.

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Microvessel Density and Mammaglobin A Expression as Prognostic Markers in Molecular Types of Breast Cancer

Revista de Chimie ◽

10.37358/rc.19.7.7403 ◽

2019 ◽

Vol 70 (7) ◽

pp. 2671-2676

Author(s):

Adriana Andreea Jitariu ◽

Amalia Raluca Ceausu ◽

Adriana Meche ◽

Cristian Nica ◽

Amelia Burlea ◽

...

Keyword(s):

Breast Cancer ◽

Tumor Cells ◽

Microvessel Density ◽

Ductal Carcinoma ◽

Hot Spot ◽

Histopathological Diagnosis ◽

Breast Cancers ◽

Breast Cancer Patients ◽

Luminal A ◽

Mean Values

Increased microvessel density (MVD) values in breast cancer correlate with tumor growth and progression while mammaglobin (MGB) expression in tumor cells is associated with a favorable prognosis. We aim to evaluate and correlate MVD values with MGB expression in molecular types of breast cancer specimens and to determine their utility as prognostic biological markers. A number of 52 breast cancer specimens were included in the study. Specimens were processed for routine histopathological diagnosis followed by the molecular classification by means of estrogen (ER), progesterone (PR) and HER2 immunohistochemical reactions. After performing immunohistochemistry for CD34 and MGB, MVD evaluation was made using the �hot spot� method for each case and MGB was scored between 0 (negative) and +3 (strong positive) depending on the intensity and distribution of the staining. MGB expression in tumor cells and MVD mean values were extremely variable. The greatest MVD mean values were obtained in luminal B followed by HER2, luminal A and triple negative breast cancer (TNBC) (95.33, 69, 62, and 40, respectively). MGB expression in the tumor cells generally ranged from mild to weak and was strong only in a few invasive ductal carcinoma cases. In cases with TNBCs the expression of MGB in tumor cells was weak and focal or negative. This variability was noticed between the molecular types of breast cancers and even within the same molecular type. In a restricted number of cases, MGB positive tumors were associated with low MVD values while the negative cases were characterized by increased MVD mean values. The variable results we obtained regarding the correlation between MVD and MGB in breast cancer specimens may indicate a rather restricted use of MVD/MGB in estimating breast cancer patients� prognosis.

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Current trends in the treatment of HR+/HER2+ breast cancer

Future Oncology ◽

10.2217/fon-2020-0504 ◽

2021 ◽

Vol 17 (13) ◽

pp. 1665-1681

Author(s):

Charlene Kay ◽

Carlos Martínez-Pérez ◽

James Meehan ◽

Mark Gray ◽

Victoria Webber ◽

...

Keyword(s):

Breast Cancer ◽

Clinical Trials ◽

Trastuzumab Emtansine ◽

Breast Cancers ◽

Newly Diagnosed ◽

Luminal A ◽

New Agents ◽

Her2 Breast Cancer ◽

Current Trends

Treatment for HR+/HER2+ patients has been debated, as some tumors within this luminal HER2+ subtype behave like luminal A cancers, whereas others behave like non-luminal HER2+ breast cancers. Recent research and clinical trials have revealed that a combination of hormone and targeted anti-HER2 approaches without chemotherapy provides long-term disease control for at least some HR+/HER2+ patients. Novel anti-HER2 therapies, including neratinib and trastuzumab emtansine, and new agents that are effective in HR+ cancers, including the next generation of oral selective estrogen receptor downregulators/degraders and CDK4/6 inhibitors such as palbociclib, are now being evaluated in combination. This review discusses current trials and results from previous studies that will provide the basis for current recommendations on how to treat newly diagnosed patients with HR+/HER2+ disease.

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