scholarly journals Medullary breast carcinoma: a pathologic review and immunohistochemical study using tissue microarray

2021 ◽  
Author(s):  
L Ming ◽  
AR Jara-Lazaro ◽  
PY Cheok ◽  
AA Thike
Keyword(s):  
Lymphovascular Invasion ◽  
Ductal Carcinoma ◽  
Tumour Size ◽  
Growth Factor Receptor ◽  
Disease Free Survival ◽  
Good Prognosis ◽  
Clinicopathological Parameters ◽  
Nodal Stage ◽  
Singapore General Hospital

Introduction: Medullary breast carcinomas (MBCs) are distinguished by circumscribed, high-grade morphology with dense chronic inflammation; they are associated with the basal phenotype but have a relatively good prognosis. Methods: This study aimed to review the clinicopathological features of MBCs diagnosed at the Department of Pathology, Singapore General Hospital and correlate them with immunohistochemical expression of hormonal markers and c-erbB-2, the basal markers p53, cytokeratin (CK) 14, epidermal growth factor receptor (EGFR) and 34BE12, and the follow-up outcome. Results: Using Ridolfi’s criteria for histologic reviews, 62 patients previously diagnosed as having ‘typical MBC’ (n = 26), ‘atypical MBC’ (n = 32) and ‘invasive carcinoma with focal medullary-like features’ (n = 4) were re-classified as follows: ‘typical MBC’ (n = 6; 9.7%), ‘atypical MBC’ (n = 46; 74.2%), and ‘non-medullary infiltrating carcinoma’ (n = 10; 16.1%). Clinicopathological parameters, including ethnicity, age, tumour size and concurrent ductal carcinoma in situ (DCIS), showed no statistically significant correlation with review diagnoses and immunohistochemical findings. Presence of lymphovascular invasion and nodal stage were significantly correlated with recurrence and breast cancer-related deaths, respectively. ER negativity was significantly correlated with triple positivity for basal markers CK14, EGFR and 34BE12, which comprised patients who showed a significantly decreased disease-free survival rate within a 10–15-year follow-up period. Conclusions: Lymphovascular invasion and high nodal stage as well as triple negativity among typical and atypical MBCs that have basal-like phenotype represent a portion of invasive carcinomas with medullary features that may have poor outcomes in this otherwise relatively good prognostic group.

Co-expression of ER-beta and HER2 associated with poorer prognosis in primary breast cancer

2009 ◽  
Vol 32 (3) ◽  
pp. 250 ◽  
Author(s):  
Wen-sheng Qui ◽  
Lu Yue ◽  
Ai-ping Ding ◽  
Jian Sun ◽  
Yang Yao ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Differentiation ◽  
Primary Breast Cancer ◽  
Tumour Size ◽  
Univariate Analysis ◽  
Growth Factor Receptor ◽  
Disease Free Survival ◽  
Breast Cancer Patients ◽  
Her2 Positive ◽  
Er Alpha

Purpose: To assess the prognostic value of co-expression of estrogen receptor (ER)-beta and human epidermal growth factor receptor 2 (HER2) in primary breast cancer patients in China. Methods: Tumour specimens from 308 patients undergoing surgery for primary breast cancer were evaluated. Expression of ER-beta and HER-2 was investigated by the immunohistochemistry. Results: 123 patients (40%) were ER-beta positive and 58 (18.5 %) were HER2 positive. Among the 58 HER2 positive patients, 44 were ER-beta positive and 14 were ER-beta negative. ER-beta positive was associated with HER2 positive (75.9%, P=0.018) as well as ER-alpha positive (79.7%, P=0.023), poor cell differentiation (77.2% grade 2 or 3, P=0.010) and menopause age < 45 yr (55.3%, P=0.031). HER2 positive was associated with poor cell differentiation (93.1%, P=0.001), ?3cm tumour size (67.2%, P=0.011). Conclusion: Both ER-beta positive and HER2 positive status was associated with poorer overall survival (OS) by univariate analysis. In both HER2 positive and HER2 negative subgroups, ER-beta positive was associated with poorer distant disease free survival (DDFS) but not OS, which implied that ER-beta might relate to metastasis in breast cancer.

scholarly journals The Biological and Clinical Significance of Glutaminase in Luminal Breast Cancer

Cancers ◽  
2021 ◽  
Vol 13 (16) ◽  
pp. 3963
Author(s):  
Brendah K. Masisi ◽  
Rokaya El Ansari ◽  
Lutfi Alfarsi ◽  
Madeleine L. Craze ◽  
Natasha Jewa ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Patient Outcome ◽  
Ductal Carcinoma ◽  
Tumour Size ◽  
Prognostic Significance ◽  
Disease Free Survival ◽  
Glutamine Metabolism ◽  
Gene Copy ◽  
Luminal Breast Cancer ◽  
Potential Biomarker

The glutamine metabolism has a key role in the regulation of uncontrolled tumour growth. This study aimed to evaluate the expression and prognostic significance of glutaminase in luminal breast cancer (BC). The glutaminase isoforms (GLS/GLS2) were assessed at genomic/transcriptomic levels, using METABRIC (n = 1398) and GeneMiner datasets (n = 4712), and protein using immunohistochemistry in well-characterised cohorts of Oestrogen receptor-positive/HER2-negative BC patients: ductal carcinoma in situ (DCIS; n = 206) and invasive breast cancer (IBC; n = 717). Glutaminase expression was associated with clinicopathological features, patient outcome and glutamine-metabolism-related genes. In DCIS, GLS alone and GLS+/GLS2- expression were risk factors for shorter local recurrence-free interval (p < 0.0001 and p = 0.001, respectively) and remained prognostic factors independent of tumour size, grade and comedo necrosis (p = 0.0008 and p = 0.003, respectively). In IBC, GLS gene copy number gain with high mRNA expression was associated with poor patient outcome (p = 0.011), whereas high GLS2 protein was predictive of a longer disease-free survival (p = 0.006). Glutaminase plays a role in the biological function of luminal BC, particularly GLS in the early non-invasive stage, which could be used as a potential biomarker to predict disease progression and a target for inhibition. Further validation is required to confirm these observations, and functional assessments are needed to explore their specific roles.

Analysis of Conservative Surgical Treatment and Prognosis of Microinvasive Squamous Cell Carcinoma of the Cervix Stage IA1: Results of Follow-Up to 20 Years

2017 ◽  
Vol 27 (2) ◽  
pp. 357-363 ◽  
Author(s):  
Caio Augusto Hartman ◽  
Julio Cesar Teixeira ◽  
Sergio Bruno Barbosa ◽  
Stephanye Mariano Figueiredo ◽  
Liliana Aparecida Lucci De Angelo Andrade ◽  
...  
Keyword(s):  
Residual Disease ◽  
Disease Free Survival ◽  
Cervical Neoplasia ◽  
Good Prognosis ◽  
Positive Cone ◽  
Definitive Treatment ◽  
Younger Women ◽  
Grade 3 ◽  
Almost All

ObjectiveThe aim of this study was to evaluate the prognosis and recurrence of microinvasive squamous cervical (MIC) cancer stage IA1 in women treated conservatively or by hysterectomy, and followed-up to 20 years.MethodsIt was studied in a cohort of 139 women with MIC, 41 definitively managed by conization and 98 by hysterectomy from January 1994 to December 2003 and followed-up until 2013. The definitive treatment, age, conization technique (loop electrosurgical excision procedure or cold knife conization), cone margin, residual disease in hysterectomy specimen, and the association with recurrence (intraepithelial cervical neoplasia grade 3/intraepithelial vaginal neoplasia grade 3 or worse, and microinvasive or worse) were analyzed.ResultsThere were 2.5 times more conservative treatment in younger women than older (>40 years), and high proportion of residual disease in hysterectomy specimens (67% of intraepithelial cervical neoplasia grade 3 or worse), more common if positive cone margin (74% vs 35%, P < 0.002). There were 2.3% (3/133) recurrences detected as microinvasive or worse, and 6% (8/133) recurrences detected as intraepithelial cervical neoplasia grade 3/intraepithelial vaginal neoplasia grade 3 or worse: 7.3% (3/41) in the conization group and 5.4% (5/92) in the hysterectomy group (P = 0.701). Almost all recurrences (88%, 7/8) were diagnosed until 36 months after treatment, and they were not associated with conization technique. There were no differences in risk of recurrence and overall disease-free survival time related to type of treatment.ConclusionsThis study demonstrates the good prognosis of MIC, regardless the treatment. When fertility is not a concern, hysterectomy should be considered as definitive treatment to avoid the risk of residual disease. Regular follow-up for a long period should be maintained.

scholarly journals Sequential Versus Concurrent Trastuzumab in Adjuvant Chemotherapy for Breast Cancer

2011 ◽  
Vol 29 (34) ◽  
pp. 4491-4497 ◽  
Author(s):  
Edith A. Perez ◽  
Vera J. Suman ◽  
Nancy E. Davidson ◽  
Julie R. Gralow ◽  
Peter A. Kaufman ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Adjuvant Chemotherapy ◽  
Growth Factor Receptor ◽  
Disease Free Survival ◽  
Standard Of Care ◽  
Phase Iii ◽  
P Value ◽  
Sequential Administration ◽  
Taxane Chemotherapy

Purpose NCCTG (North Central Cancer Treatment Group) N9831 is the only randomized phase III trial evaluating trastuzumab added sequentially or used concurrently with chemotherapy in resected stages I to III invasive human epidermal growth factor receptor 2–positive breast cancer. Patients and Methods Patients received doxorubicin and cyclophosphamide every 3 weeks for four cycles, followed by paclitaxel weekly for 12 weeks (arm A), paclitaxel plus sequential trastuzumab weekly for 52 weeks (arm B), or paclitaxel plus concurrent trastuzumab for 12 weeks followed by trastuzumab for 40 weeks (arm C). The primary end point was disease-free survival (DFS). Results Comparison of arm A (n = 1,087) and arm B (n = 1,097), with 6-year median follow-up and 390 events, revealed 5-year DFS rates of 71.8% and 80.1%, respectively. DFS was significantly increased with trastuzumab added sequentially to paclitaxel (log-rank P < .001; arm B/arm A hazard ratio [HR], 0.69; 95% CI, 0.57 to 0.85). Comparison of arm B (n = 954) and arm C (n = 949), with 6-year median follow-up and 313 events, revealed 5-year DFS rates of 80.1% and 84.4%, respectively. There was an increase in DFS with concurrent trastuzumab and paclitaxel relative to sequential administration (arm C/arm B HR, 0.77; 99.9% CI, 0.53 to 1.11), but the P value (.02) did not cross the prespecified O'Brien-Fleming boundary (.00116) for the interim analysis. Conclusion DFS was significantly improved with 52 weeks of trastuzumab added to adjuvant chemotherapy. On the basis of a positive risk-benefit ratio, we recommend that trastuzumab be incorporated into a concurrent regimen with taxane chemotherapy as an important standard-of-care treatment alternative to a sequential regimen.

Post IORT seroma complication in breast cancer surgery

2020 ◽  
pp. 1-7
Author(s):  
Maha Abdel Hadi ◽  
Afnan Al-Muhanna ◽  
Lina Abu Arida ◽  
Dina Lutfi
Keyword(s):  
Breast Cancer ◽  
Lymphovascular Invasion ◽  
Tumour Size ◽  
Nodal Status ◽  
Histological Diagnosis ◽  
Tumour Grade ◽  
Receptor Status ◽  
Life Threatening ◽  
Radiotherapy Treatment

Abstract Background: Intraoperative radiotherapy (IORT) has gained popularity over recent years due to its impact on shortening the radiotherapy treatment time for early breast cancer. It has certainly proven effective as an exclusive treatment or when combined with whole breast irradiation (WBIR). Seroma is a common non-life-threatening complication that may delay treatment and impose challenges on radiological diagnostic follow-up. Aim: To review and compare the occurrence of seroma in patients who received exclusive IORT or when combined with WBIR and to outline the diagnostic challenges encountered during radiological follow-up. Materials and methods: Based on strict selection criteria, all eligible patients who received IORT ± WBIR treatment between 2012 and 2019 in a university hospital setting were included. Demographic data, histological diagnosis, tumour size, tumour grade, lymphovascular invasion, nodal status, receptor status, treatment with neoadjuvant hormonal chemotherapy, applicator size, dose used, duration of radiotherapy treatment, timing of seroma development and duration of seroma were documented. Both clinical and radiological follow-up were exercised in all patients. Results: The total number of patients treated with breast conserving surgery (BCS) and IORT was 86. Age ranged between 31 and 75 years with the median age of 51 years. Patients treated exclusively with IORT were 39 (45%) while those who received the IORT as a boost were 47 (55%). Seroma was observed in 39(45%) of both IORT and IORT\WBIR patients. Those included 15(38%) of the exclusive IORT treated patients and 24 (62%) of those treated as a boost. Duration of asymptomatic seroma ranged from 6 months to 6 years. Repeated aspiration was performed in 2 (5%) patients. Postoperative seroma occurred independent of age histological diagnosis, tumour size, tumour grade, lymphovascular invasion, nodal status, receptor status, treatment with neoadjuvant hormonal\chemotherapy, applicator size, dose used or duration of radiotherapy treatment. All reviewed patients have shown increased risk of developing seroma; however, an increased incidence of seroma in the IORT + WBIR treated patients was higher than those who received exclusive IORT treatment. Conclusion: Postoperative seroma is a common non-life-threatening entity that occasionally may lead to delay in the subsequent treatment plan. IORT is a safe modality with many benefits; however, it may increase the risk of seroma formation independent of the clinical parameters. Promoting the expertise in post IORT breast imaging aids in overcoming diagnostic challenges.

scholarly journals Clinical Development of the E75 Vaccine in Breast Cancer

Breast Care ◽  
2016 ◽  
Vol 11 (2) ◽  
pp. 116-121 ◽  
Author(s):  
Guy T. Clifton ◽  
Victor Gall ◽  
George E. Peoples ◽  
Elizabeth A. Mittendorf
Keyword(s):  
Breast Cancer ◽  
Ductal Carcinoma ◽  
Protein A ◽  
Growth Factor Receptor ◽  
Disease Free Survival ◽  
Initial Step ◽  
Recurrence Risk ◽  
Phase Iii ◽  
Breast Cancer Patients ◽  
Gm Csf

E75 is an immunogenic peptide derived from the human epidermal growth factor receptor 2 (HER2) protein. A large amount of preclinical work evaluated the immunogenicity of E75, after which phase I trials investigated using E75 mixed with an immunoadjuvant as a vaccine. Those studies showed the vaccine to be safe and capable of stimulating an antigen-specific immune response. Subsequent to that, our group conducted trials evaluating E75 + granulocyte macrophage colony-stimulating factor (GM-CSF) in the adjuvant setting. The studies enrolled node-positive and high-risk node-negative breast cancer patients, with the goal being to determine if vaccination could decrease the recurrence risk. The studies included 187 evaluable patients: 108 vaccinated ones and 79 controls. The 5-year disease-free survival for the vaccinated patients was 89.7% compared to 80.2% for the control patients, a 48% reduction in relative risk of recurrence. Based on these data, E75 + GM-CSF, now known as NeuVax™, is being evaluated in a phase III trial. In this article, we review preclinical data and results of the early-phase trials and provide an update on the ongoing phase III study. We also present additional strategies for employing the vaccine to be included as a component of combination immunotherapy as well as in the setting of ductal carcinoma in situ as an initial step towards primary prevention.

Predictors of Recurrence in Patients With T2 and Early T3, N0 Adenocarcinoma of the Rectum Treated by Surgery Alone

2006 ◽  
Vol 24 (25) ◽  
pp. 4078-4084 ◽  
Author(s):  
Aviram Nissan ◽  
Alexander Stojadinovic ◽  
Jinru Shia ◽  
Axel Hoos ◽  
Jose G. Guillem ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Survival Data ◽  
Lymphovascular Invasion ◽  
Disease Free Survival ◽  
Neoadjuvant Radiotherapy ◽  
Predictors Of Recurrence ◽  
Preoperative Serum ◽  
Serum Carcinoembryonic Antigen ◽  
Disease Free

Purpose Treatment of rectal cancer with neoadjuvant radiotherapy has been shown to reduce local recurrence and improve overall survival. The role of chemoradiotherapy in patients with T2, N0 and early T3, N0 rectal cancer, treated by radical surgery with total mesorectal excision, remains controversial. The aim of this study was to identify predictors of recurrence in this group of patients to enhance treatment selection. Patients and Methods One hundred patients with primary T2-3, N0 adenocarcinoma of the rectum, uniformly treated by surgery alone, were studied. The pathology slides available for 97 patients were rereviewed. Three patients with incomplete data sets were excluded. Clinical and survival data were obtained from a prospective computerized database and updated from hospital and office charts. The study end points were disease-free survival, disease-specific survival (DSS), time to pelvic recurrence (PR), and distant recurrence. Results Complete follow-up was available for all study patients. Median follow-up was 79.5 months (range, 57.7 to 105.9 months). During this time period 30 patients (31.9%) died as a result of disease and 64 patients (68.1%) remained alive and disease free. Five-year DSS was 73%. The cumulative risk for PR was 8% at 5 years and 10% at 8 years. Lymphovascular invasion, preoperative serum carcinoembryonic antigen (CEA > 5 ng/mL) level, and age older than 70 years were all associated with adverse outcome. Conclusion Patients with T2-3, N0 rectal cancers and either lymphovascular invasion or elevated CEA levels have reduced survival and a higher incidence of PR, and should be considered for future randomized trials.

scholarly journals Loss of Villin Immunoexpression in Colorectal Carcinoma Is Associated with Poor Differentiation and Survival

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Jaudah Al-Maghrabi ◽  
Wafaey Gomaa ◽  
Abdelbaset Buhmeida ◽  
Mohmmad Al-Qahtani ◽  
Mahmoud Al-Ahwal
Keyword(s):  
Lymphovascular Invasion ◽  
Statistical Tests ◽  
Tumour Size ◽  
Disease Free Survival ◽  
Nodal Metastasis ◽  
Margin Status ◽  
Depth Of Invasion ◽  
Tumour Location

Background and Aims. Villin is a highly specialised protein and is expressed in intestinal and renal proximal tubular epithelium. It was detected in colorectal carcinomas (CRC) and other nongastrointestinal tumours. The aim of the current study is to investigate the immunohistochemical expression of villin in a subset of primary CRC and determine its relation to tumour differentiation, invasion, nodal metastasis, recurrence, and disease-free survival. Patients and Methods. Paraffin blocks of 93 cases of CRC were retrieved constituting 93 primary CRC and 58 adjacent normal mucosa. Immunohistochemistry was performed using antivillin antibody. The extent (%) of villin immunoexpression was categorised for statistical analysis. Statistical tests were used to determine the association of villin with clinicopathological characteristics: age, sex, tumour location, tumour size, depth of invasion, tumour grade, nodal metastasis, lymphovascular invasion, margin status, recurrence, and survival. Results. Villin immunostaining results showed that villin is downregulated in CRC. Villin has no association with age, sex, tumour location, depth of invasion, nodal metastasis, lymphovascular invasion, margin status, and recurrence. However, villin is expressed in higher rate in CRC less than 5 cm, well- and moderately differentiated CRC. Poor survival was associated with tumour with low villin immunoexpression. Conclusion. Villin was downregulated in CRC. Villin immunoexpression in CRC is associated with better survival, well-differentiated tumours, and small-sized tumours. Villin has no significant association with disease recurrence or nodal metastasis. More in vivo and in vitro studies are required for further elucidation of how villin may be involved in CRC.

scholarly journals RRM2 expression in different molecular subtypes of breast cancer and its prognostic significance

2022 ◽  
Vol 17 (1) ◽  
Author(s):  
Manar Ahmed Abdel-Rahman ◽  
Mena Mahfouz ◽  
Hany Onsy Habashy
Keyword(s):  
Breast Cancer ◽  
Protein Expression ◽  
Tumour Size ◽  
Prognostic Significance ◽  
Disease Free Survival ◽  
Tissue Microarrays ◽  
Positive Lymph Node ◽  
Clinicopathological Parameters ◽  
Breast Cancer Patients ◽  
Ribonucleoside Diphosphate Reductase

Abstract Background Breast cancer is one of the most common types of cancer. Ribonucleotide reductase (RNR) is a heterodimeric tetramer consisting of two Ribonucleoside-diphosphate reductase large subunits (RRM1) and two Ribonucleoside-diphosphate reductase small subunits (RRM2). RRM2 is the building subunit of RNR that is important for synthesis of Deoxynucleoside triphosphate (dNTP) during S phase of cell cycle during DNA replication. RRM2 is associated with poor prognosis in lung and colorectal cancer. In breast cancer, increased RRM2 protein level is strongly correlated with large tumour size, positive lymph node and relapse. In this study, we aimed to study expression of RRM2 in breast cancer and to correlate it with different clinicopathological parameters in Egyptian women. Material and methods This study was performed by investigating RRM2 protein expression in breast cancer and correlating the results with other clinicopathological variables using immunohistochemistry and tissue microarrays. Results About 77% of cases were RRM2 positive. High Ki67 was observed in cases with high RRM2 score. The majority of non-luminal cases expressed RRM2, however this was statistically insignificant. In ER positive group, RRM2 expression was associated with shorter disease free survival with borderline significance. Conclusion RRM2 protein expression can help in evaluating outcome of breast cancer patients and could be a potential therapeutic target.

Tumor Characteristics and Clinical Outcome of Tubular and Mucinous Breast Carcinomas

1999 ◽  
Vol 17 (5) ◽  
pp. 1442-1442 ◽  
Author(s):  
Sami G. Diab ◽  
Gary M. Clark ◽  
C. Kent Osborne ◽  
Arlene Libby ◽  
D. Craig Allred ◽  
...  
Keyword(s):  
General Population ◽  
Clinical Outcome ◽  
Ductal Carcinoma ◽  
Growth Factor Receptor ◽  
Disease Free Survival ◽  
Axillary Node ◽  
Not Otherwise Specified ◽  
Systemic Adjuvant Therapy ◽  
Node Involvement ◽  
Epidermal Growth

PURPOSE: To comprehensively characterize the clinical and biologic features of tubular and mucinous carcinomas in a large cohort of patients and to relate this to clinical outcome and management. PATIENTS AND METHODS: The clinical and biologic features of 444 patients with tubular and 1,221 patients with mucinous carcinomas were compared with those of 43,587 patients with infiltrating ductal carcinoma, not otherwise specified (NOS). Disease-free survival (DFS) and overall survival (OS) for patients with tubular and mucinous carcinomas were compared with those of patients with NOS carcinomas and with age-matched sets from the general population. RESULTS: Tubular and mucinous carcinomas were more likely to occur in older patients, be smaller in size (tubular only), have substantially less nodal involvement, be estrogen receptor– and progesterone receptor–positive, have a lower S-phase fraction, be diploid, and be c-erbB-2– and epidermal growth factor receptor–negative compared with NOS carcinomas. Axillary node involvement was a poor prognostic feature in mucinous but not tubular carcinomas. Mucinous carcinomas ≤ 1 cm had a ≤ 5% incidence of node involvement. The 5-year DFS and OS were 94% and 88% for tubular, 90% and 80% for mucinous, and 80% and 77% for NOS carcinoma, respectively (P < .001 for differences among all three types for both DFS and OS). The 5-year OS of females from the general population age-matched to the patients with tubular and mucinous carcinomas was 89% and 82%, respectively, which is not different from the OS of patients with tubular or mucinous carcinomas. CONCLUSION: The biologic phenotype of tubular and mucinous carcinomas is quite favorable. Consistent with this observation, the survival of patients with tubular and mucinous carcinomas is similar to that of the general population. Systemic adjuvant therapy and node dissection may be avoided in many patients with these special types of carcinoma.

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