Prognostic subset of metastatic and non-metastatic luminal B breast cancer (LBBC) subtype based on Ki67 index.

e12570 Background: Gene expression profiling for breast cancer has classified ER positive subtype into luminal A and luminal B. Luminal B breast cancer (LBBC) have a higher proliferation and poorer prognosis than luminal A tumors. Ki-67 index is the commonly used proliferation marker in breast cancer; however Ki67 expression can also be used to identify a subset of patients among LB with a favorable prognosis. This study attempts to verify this subset of LBBC patients based on DFS and PFS in non-metastatic and metastatic patients respectively. Methods: We retrospectively analyzed 80 IDC breast cancer patients diagnosed in 2013-2016 with complete follow-up till January-2021. We defined LBBC as ER+, PR+ or PR- , HER2+ or HER2- with a Ki67 index >20%. PFS was considered as the endpoint in patients presenting with metastatic disease whereas DFS was used in non-metastatic disease. The cut-off for ki67 was calculated using an X-tile plot (version 3.6.1, Yale University) by dividing Ki67 data into two populations: low and high, with randomized 1:1 “training” and “validation” cohorts. Results: Median age was 51.5 years. 18.7% (n=15) presented with metastasis at the time of diagnosis and their overall median PFS was found to be 25.8 months. The incidence of HER2 positive LBBC was found to be 15% (n=12) and none of them were found to be presented with metastasis. Survival and frequency of various sub groups in our study are enlisted in the given table. We estimated a Ki67 cut-off of 30% in patients with upfront metastatic disease and PFS was found to be higher in <30% compared to a Ki67 index >30% (38.9 months vs 19.7 months, p-0.002). Overall median DFS was not achieved in non-metastatic group (Mean DFS: 64.7 months) where as a statistically significant difference was observed in the survival of HER2 positive (median DFS: 53.5 months, mean DFS: 50.9) than HER2 negative patients (median DFS not achieved, mean: 66.97 months) ( p-0.021). We obtained a Ki67 cut-off of 32% in non- metastatic group and mean DFS was found to be higher in Ki67<32% (69 months) compared to Ki67>32% (61.4 months), however it failed to exhibit a statistically significant relationship ( p-0.373). Conclusions: Our study indicates that a subset of patients exists within metastatic and non-metastatic LBBC with differing prognosis based on Ki67. Larger studies are further required to confirm the findings and therapeutic implications.[Table: see text]

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Inflammatory Breast Cancer: Clinical Characteristics and Influence of Molecular Subtypes on Treatment Response

Tumori Journal ◽

10.1177/03008916211012341 ◽

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.

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Comparison of Clinico-Pathological Presentations of Triple-Negative versus Triple-Positive and HER2 Iraqi Breast Cancer Patients

Open Access Macedonian Journal of Medical Sciences ◽

10.3889/oamjms.2019.808 ◽

2019 ◽

Vol 7 (21) ◽

pp. 3534-3539

Author(s):

Nada A. S. Alwan ◽

Furat N. Tawfeeq

Keyword(s):

Breast Cancer ◽

Triple Negative ◽

Molecular Subtype ◽

Clinical Stage ◽

Lymph Node Involvement ◽

Breast Cancer Patients ◽

Luminal A ◽

Her2 Positive ◽

Cancer Subtypes ◽

Significant Difference

BACKGROUND: Breast cancer remains the most common malignancy among the Iraqi population. Affected patients exhibit different clinical behaviours according to the molecular subtypes of the tumour. AIM: To identify the clinical and pathological presentations of the Iraqi breast cancer subtypes identified by Estrogen receptors (ER), Progesterone receptors (PR) and HER2 expressions. PATIENTS AND METHODS: The present study comprised 486 Iraqi female patients diagnosed with breast cancer. ER, PR and HER2 contents of the primary tumours were assessed through immunohistochemical staining; classifying the patients into five different groups: Triple Negative (ER/PR negative/HER2 negative), Triple Positive (ER/PR positive/HER2 positive), Luminal A (ER/PR positive/HER2 negative), HER2 enriched ((ER/PR negative/HER2 positive) and all other subtypes. RESULTS: The major registered subtype was the Luminal A which was encountered in 230 patients (47.3%), followed by the Triple Negative (14.6%), Triple Positive (13.6%) and HER2 Enriched (11.5%). Patients exhibiting the Triple Negative subtype were significantly younger than the rest of the groups and presented with larger size tumours. A significant difference in the distribution of the breast cancer stages was displayed (p < 0.05); the most advanced were noted among those with HER2 enriched tumours who exhibited the highest frequency of poorly differentiated carcinomas and lymph node involvement. CONCLUSION: The most significant variations in the clinicopathological presentations were observed in the age and clinical stage of the patients at diagnosis. Adoption of breast cancer molecular subtype classification in countries with limited resources could serve as a valuable prognostic marker in the management of aggressive forms of the disease.

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Luminal A and Luminal B subtypes in patients with breast cancer 65 years of age and older.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.549 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. 549-549

Author(s):

Robert Konigsberg ◽

Georg Pfeiler ◽

Nicole Hammerschmid ◽

Tatjana Klement ◽

Christian Dittrich

Keyword(s):

Breast Cancer ◽

Lymph Node ◽

Endocrine Therapy ◽

Tumor Size ◽

Lymph Node Status ◽

Primary Therapy ◽

Luminal A ◽

Ki 67 ◽

Luminal B ◽

Significant Difference

549 Background: In 2011, the St. Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer (bc) suggested the distinction between Luminal A and Luminal B subtypes. In Luminal A patients (pts) endocrine therapy seems to be sufficiently effective, whereas in Luminal B pts the additional application of chemotherapy should be considered. It is currently unknown, whether the risk stratification into Luminal A and B is comparably or more discriminatory than the established pathologic tumor size (pT) and lymph node (pN) status in pts ≥ 65 years. This analysis evaluates the discriminatory capacity of the new distinction between Luminal A and B and the established prognostic factors in bc pts ≥ 65 years treated with endocrine therapy only. Methods: Clinico-pathological data of 190 bc pts ≥ 65 years diagnosed between 1998 and 2004 were retrospectively analyzed. Pts were classified as Luminal A [ER (+) and/ or PR (+) and Her/2neu (-) and Ki-67 < 14%] or Luminal B [ER (+) and/ or PR (+) and Her2 (-) and Ki-67 ≥ 14%]. The Kaplan-Meier method was used to assess the progression-free survival (PFS) and overall survival (OS) estimates. Differences in survival between groups were tested for significance by the log-rank test. Results: Median age was 74 years (65–92 years) and median time of follow-up was 69 months (0–134 months). 68.9% and 31.1% pts had Luminal A and B subtypes, respectively. 73.3% and 26.7% of pts had pT1 and pT2 tumors, respectively. 79.7% and 20.3% of pts had pN0 and pN1 status, respectively. Overall, median PFS was 33 months. No significant difference regarding PFS could be detected between Luminal A and B pts, between pT1 and pT2 tumors and between pN0 and pN1 status (p=0.458; 0.172; 0.156), respectively. Overall, median OS was not reached. No significant difference regarding OS could be detected between Luminal A and B pts, between pT1 and pT2 tumors and between pN0 and pN1 status (p=0.328; 0.951; 0.976), respectively. Conclusions: In bc pts ≥ 65 years treated with endocrine therapy only, neither the recently consented dichotomization into Luminal A and B subtypes nor pathologic tumor size and lymph node status could be confirmed to be discriminative as propagated in the 2011 St. Gallen Consensus for the overall bc population.

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Neoadjuvant Chemotherapy Exerts Selection Pressure Towards Luminal Phenotype Breast Cancer

Breast Care ◽

10.1159/000479582 ◽

2017 ◽

Vol 12 (6) ◽

pp. 391-394 ◽

Cited By ~ 3

Author(s):

Giulia Galli ◽

Giacomo Bregni ◽

Stefano Cavalieri ◽

Luca Porcu ◽

Paolo Baili ◽

...

Keyword(s):

Breast Cancer ◽

Neoadjuvant Chemotherapy ◽

Hormone Receptors ◽

Residual Disease ◽

Luminal A ◽

Her2 Positive ◽

Ki 67 ◽

Surgical Specimen ◽

Luminal B ◽

Basal Phenotype

Background: Breast cancer (BC) phenotype after neoadjuvant chemotherapy (NAC) has not been extensively described and few data exist on whether expression of the primary tumor hormone receptors, HER2 and Ki-67 changes as a result of chemotherapy. Materials and Methods: We analyzed specimens from all BC patients treated with anthracycline/taxane-based NAC at our Institution between January 2010 and March 2015 (n = 325). The expression of estrogen receptor (ER), progesterone receptor (PR), HER2 and Ki-67 was determined in pre- and post-NAC specimens. McNemar's test was used to compare paired proportions. Results: Among patients with residual disease after NAC, basal phenotype was luminal A, luminal B, HER2 positive and triple negative in 44, 111, 74 and 27 cases, respectively. PR-positive tumors decreased from 68.0% in the initial biopsy sample to 61.7% in the surgical specimen (p = 0.024). A Ki-67 of < 20% increased from 23.6% to 45% (p < 0.001). ER expression changed from positive to negative in 5% and from negative to positive in 16.7% of cases. Overall, 30% of cases underwent subtype changes, 79% of them towards luminal differentiation. Conclusions: The switch towards luminal phenotype suggests some kind of endocrine effect of NAC. Our findings raise renewed interest in combinatorial cytotoxic chemotherapy with concomitant or rather sequential endocrine therapy, either alone or with targeted agents.

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BREAST CANCER TYPING USING RT-PCR ASSAY

Siberian Journal of Oncology ◽

10.21294/1814-4861-2019-18-5-61-67 ◽

2019 ◽

Vol 18 (5) ◽

pp. 61-67

Author(s):

V. K. Bozhenko ◽

I. D. Trotsenko ◽

E. A. Kudimnova ◽

S. G. Vardanyan ◽

M. V. Zakharenko ◽

...

Keyword(s):

Breast Cancer ◽

Systemic Therapy ◽

Breast Cancer Patients ◽

Rt Pcr ◽

Luminal A ◽

Her2 Positive ◽

Luminal B ◽

Diagnostic Measures ◽

Total Percentage ◽

Response To Chemotherapy

Introduction. Adjuvant systemic therapy remains one of the main options for treating breast cancer. Results of standard immunohistochemical studies are not always a criterion for selecting systemic therapy. Nowadays, multigene expression analysis is actively used to predict the response to chemotherapy in patients with earlystage breast cancer. We studied a 24-gene multi-gene panel for typing breast cancer.Material and Methods. A prospective analysis of 199 breast cancer patients (T1–3N0–3M0) was carried out. Surgical specimens were studied using the standard immunohistochemistry (IHC) and RT-PCR for detecting expression of 24 genes.Results. According to the IHC results, breast cancer was divided into 5 molecular subtypes: luminal A was detected in 59 (30 %) patients; luminal B (HER2-negative) in 52 (26 %); luminal B (HER2-positive) in 19 (9 %); triple-negative in 28 (14 %); HER2-positive 41 (21 %). RT-PCR showed that ST K15, MYC, MYBL2, BIRCC 5, BCL2, TERT, ESRP1, PGR, HER2, GBR7, MGB1 and MMP11 were the most significant genes in subtype distribution. The total percentage of matches between the two studies was 61.7 %.Conclusion. Studies have shown the need to add additional typing methods for breast cancer to a standard IHC study, which will undoubtedly increase the information content of diagnostic measures and will improve the effectiveness of the treatment.

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

Russian Journal of Oncology ◽

10.18821/1028-9984-2019-24-3-6-74-78 ◽

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.

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Prognostic factor Ki67 for breast cancer patients in each subgroup.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.565 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. 565-565

Author(s):

Naoki Niikura ◽

Shinobu Masuda ◽

Mizuho Terada ◽

Mayako Terao ◽

Nobue Kumaki ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Triple Negative ◽

Predictive Marker ◽

Rank Test ◽

Breast Cancer Patients ◽

Luminal A ◽

Her2 Positive ◽

Luminal B ◽

Er Positive

565 Background: Immunohistochemical (IHC) Ki67 has described it as a prognostic and predictive marker for breast cancer. The St. Gallen Consensus Meeting determined that Ki67 labeling index is chiefly important for distinguishing between “Luminal A” and “Luminal B (HER2 negative)” subtypes and is a predictive marker for chemotherapeutic efficacy. However, the high and low cutoff points remain controversial. Our objective is to compare survival in patients with low, intermediate, and high Ki67 levels in each subgroup. Methods: We retrospectively identified all the patients in the Tokai University breast cancer database for whom IHC Ki67 data were available between January 1, 2000, and December 31, 2010. Ki67 was defined as low if <10% Ki67 was detected, as Intermediate if 10–20% Ki67 was detected, and as high if >20% Ki67 was detected. To assess Ki67 levels and survival outcomes, survival curves were calculated using the Kaplan–Meier method and compared using the log-rank test. Results: We identified 1331 primary breast cancer patients without metastasis, of whom 686 received neoadjuvant or adjuvant chemotherapy. Patients with high Ki67 had poorer relapse-free survival (RFS) than patients with intermediate (p = 0.009) and low Ki67 (p < 0.001). Patients with intermediate Ki67 had poorer RFS than patients with low Ki67 (p < 0.001). In ER-positive cases (n = 1059), patients with high and intermediate Ki67 had poorer RFS than patients with low Ki67 (p < 0.001 and p = 0.002, respectively). In HER2-positive and ER-negative cases (n = 103), patients with high Ki67 had poorer RFS than patients with low Ki67 (p = 0.002). In triple-negative cases (n = 164), patients with high Ki67 tended to have poorer RFS than patients with low Ki67 (p = 0.064). Conclusions: Our data demonstrated that low, intermediate, and high Ki67 levels may be used to differentiate prognosis in ER-positive cancer patients as well as HER2-positive and triple-negative cancer patients.

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Protein Corona Gold Nanoparticles Fingerprinting Reveals a Profile of Blood Coagulation Proteins in the Serum of HER2-Overexpressing Breast Cancer Patients

International Journal of Molecular Sciences ◽

10.3390/ijms21228449 ◽

2020 ◽

Vol 21 (22) ◽

pp. 8449

Author(s):

María del Pilar Chantada-Vázquez ◽

Antonio Castro López ◽

María García-Vence ◽

Benigno Acea-Nebril ◽

Susana B. Bravo ◽

...

Keyword(s):

Breast Cancer ◽

Gold Nanoparticles ◽

Blood Coagulation ◽

Correct Identification ◽

Breast Cancer Patients ◽

Luminal A ◽

Her2 Positive ◽

Luminal B ◽

Coagulation Proteins ◽

Blood Coagulation Proteins

Breast cancer (BC) is a molecularly heterogeneous disease that encompasses five major molecular subtypes (luminal A (LA), luminal B HER2 negative (LB-), luminal B HER2 positive (LB+), HER2 positive (HER2+) and triple negative breast cancer (TNBC)). BC treatment mainly depends on the identification of the specific subtype. Despite the correct identification, therapies could fail in some patients. Thus, further insights into the genetic and molecular status of the different BC subtypes could be very useful to improve the response of BC patients to the range of available therapies. In this way, we used gold nanoparticles (AuNPs, 12.96 ± 0.72 nm) as a scavenging tool in combination with Sequential Window Acquisition of All Theoretical Mass Spectra (SWATH-MS) to quantitatively analyze the serum proteome alterations in the different breast cancer intrinsic subtypes. The differentially regulated proteins specific of each subtype were further analyzed with the bioinformatic tools STRING and PANTHER to identify the major molecular function, biological processes, cellular origin, protein class and biological pathways altered due to the heterogeneity in proteome of the different BC subtypes. Importantly, a profile of blood coagulation proteins was identified in the serum of HER2-overexpressing BC patients.

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L1CAM Expression in Recurrent Estrogen Positive/HER2 Negative Breast Cancer

10.21203/rs.3.rs-56325/v1 ◽

2020 ◽

Author(s):

Ioana Moisini ◽

Huina Zhang ◽

Marcus D’Aguiar ◽

David G. Hicks ◽

Bradley M. Turner

Keyword(s):

Breast Cancer ◽

Metastatic Breast ◽

Lymph Node Status ◽

Breast Cancer Patients ◽

Breast Carcinomas ◽

Luminal A ◽

Ki 67 ◽

Luminal B ◽

Er Positive ◽

L1cam Expression

Abstract Background: We investigate L1CAM expression in ER positive/HER2 negative breast carcinomas. The finding of a potential correlation between high L1CAM expression and recurrent/metastatic disease in luminal A and B breast carcinomas may be helpful for risk stratification and open opportunities for targeted therapies.Methods: 304 cases comprising 152 cases of ER positive, PR positive/negative and HER2 negative recurrent/metastatic breast carcinomas and 152 non-recurrent controls were included. ER, PR, HER-2, Ki-67 status, Nottingham grade, tumor size, tumor stage, number of foci, lymph node status, lymphovascular invasion, phenotype, laterality, age at diagnosis and first distant or local recurrence were recorded. Results: L1CAM positive cases showed increased specificity for recurrence and these patients were significantly younger than L1CAM negative ones. Compared to L1CAM negative recurrent cases, L1CAM positive ones had a noticeably higher Ki-67, tended to be larger and recurred sooner. All L1CAM positive recurrent/metastatic cases were of the luminal B subtype compared to 67.3% of the L1CAM negative cases. Conclusions: L1CAM is highly specific for recurrence in a subset of breast cancer patients and may be associated with more aggressive behavior, particularly in luminal B breast cancers with higher Ki-67 expression. Further investigation about the prognostic value of L1CAM is warranted.

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The role of Ki-67 in molecular breast cancer classification.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.583 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. 583-583

Author(s):

George Stathopoulos ◽

Nikolaos Malamos ◽

Christos Markopoulos ◽

Athanasios Polychronis ◽

Sotirios Rigatos ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Triple Negative ◽

Progesterone Receptors ◽

Molecular Classification ◽

Breast Cancer Patients ◽

Luminal A ◽

Ki 67 ◽

Luminal B ◽

Her 2

583 Background: The Ki-67 antigen was identified the involvement in early steps of polymerase I-dependent ribosomal RNA synthesis. Although it seems that the protein has an important function in cell division, its exact role is still obscure and there is little published work on its overall function. The aim of the present study is to evaluate the contribution of Ki-67 level in respect of tumor recurrence in molecular classified groups of breast cancer patients. Methods: Breast cancer tumor samples were examined for histological confirmation and for estrogen and progesterone receptors, c-erb-B2 expression, proliferation with Grade and Ki-67. Ki-67 was divided in percentage levels, up to 20 and higher than 20%. Immunohistochemistry and Fluorescence in situ hybridization is described for the results of ER, PR, c-erb-B2, Ki-67 biomarkers. Formaldehyde – fixed breast samples were paraffin wax embedded and processed for paraffin sections. The primary antibodies used were: The monoclinal antibody ID5 (M7047, Dakocytomation, Carpinteria, CA) for the detection of ER, the monoclonal anti-PR antibody 636 was used. For the detection of Ki-67 we used monoclonal mouse anti-human Ki-67 MIB-1. The patients molecular classification was Luminal A, Luminal B, Her-2 subtype and basal cell (triple negative). Results: 847 breast cancer patients were recruited. 291 were group as Luminal A, 228 as Luminal B, 221 Her-2 subtype and 107 triple negative. Follow-up was from 3 years to 15 years since diagnosis. It was found that in Luminal A patients, none had Ki-67 higher than 20% and the recurrence was in 10.65%. In Luminal B, the Ki-67 was higher than 20% in 61% of the patients and recurrence 23.68%. In Her-2 subtype >20% Ki-67 was 78.94%, recurrence 17.19%. In triple negative > 20% Ki-67 was in 68.75% and recurrence in 29.90% of the patients. Conclusions: The data presented here indicate that Ki-67 level may be considered as one of valuable biomarkers in breast cancer patients process and recurrence.

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