Basal-Like Breast Cancer; Clinicopathological, Molecular, and Prognostic Features

Background: Molecular classification of breast tumors has identified the basal-like subtype, with high heterogeneity and very poor prognosis. These tumors are mainly triple negative, characterized by the expression of basal markers CK5/6 and EGFR. In this study, we sought to investigate the features, outcome, and therapeutic modalities of basal-like breast cancers (BLBC).Methods: We retrospectively identified 90 BLBC patients diagnosed at the Department of Surgical Oncology of Salah Azaiez Institute between January 2009 and December 2013. Results: The mean age of our patients was 50 years, and 15.5% had a family history of breast cancer. The mean tumor size was 43.8 mm. Histological examination revealed invasive ductal carcinoma in 88.9% of the cases, metaplastic carcinoma in 5.6%, and medullary carcinoma and adenoid cystic carcinoma in 2.2%. BLBC was most often associated with a high tumor grade (55.3% had a grade 3 tumor) and a high Ki-67 proliferative index. Vascular invasion was found in 31.1% of the cases. Regarding lymph node involvement, 42.9% had positive lymph nodes and 7.9% featured distant metastases. Surgical treatment was provided for 85 patients. It consisted of conservative surgery in 40 cases and radical surgery in 45 cases. Neoadjuvant chemotherapy was administrated to 23 patients, with a 13% complete pathologic response. The rates of overall survival and disease-free survival at 3 years for localized BLBC were 74.4% and 75.9%, respectively. Conclusion: BLBCs are aggressive tumors associated with poor prognosis. Thus, to identify novel prognostic factors and therapeutic targets, prospective studies should investigate the epidemiological and evolutive profile of these tumors.

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Claudin 1, 3, 4, and 7 expression in triple-negative breast cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.1070 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. 1070-1070

Author(s):

Beom Seok Ko ◽

Hee Jeong Kim ◽

Jong Han Yu ◽

jong Won Lee ◽

Byung Ho Sohn ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Progression ◽

Triple Negative Breast Cancer ◽

Poor Prognosis ◽

Triple Negative ◽

Disease Free Survival ◽

Endocrine Treatment ◽

Lymph Node Status ◽

High Recurrence Rate ◽

Breast Cancers

1070 Background: Triple negative breast cancer (TNBC) often grows rapidly and has poor prognosis, with a high recurrence rate. Because conventional endocrine treatment and HER2 targeted therapy for TNBC is invalid, chemotherapy is the only systemic treatment for TNBC. It is known that several subtypes within the TNBC show different responses to chemotherapy, depending on the subtypes. Recently, a claudin (CLDN) low breast cancer has been identified, exhibiting low expressions of CLDNs 1, 3, 4 and 7. CLDNs are transmembrane proteins that seal tight junctions and are critical for maintaining cell-to-cell adhesion in epithelial cell sheets. However, their role in cancer progression remains largely unexplored. Methods: Surgically removed, formalin-fixed, paraffin-embedded breast cancers from 341 TNBC patients were analyzed to identify CLDN expression.They underwent wide local excision or mastectomy between March, 2004 and December, 2007 at the breast surgery unit of Asan Medical Central Hospital. Results: In our tumor series, we found 45.0% (153/339) of high expressing cases for CLDN1, 57.0% (192/337) for CLDN3, 57.6% (194/337) for CLDN4 and 44.0% (149/339) for CLDN7. Overall, we found 20.5% (70/341) of cases were within the low CLDN expression group and 79.5% (271/341) of tumors were within the high expression group of CLDN1, 3, 4 ,7. Although the high CLDN expression group was significantly associated with positive lymph node status and higher stage, there were no significant differences between CLDN low and high groups in disease free survival (p=0.477) or overall survival (p=0.253). Conclusions: CLDN high tumors are associated with poor prognosis features, but they are not an independent prognostic factor in TNBC patients. However, the mechanisms underlying the different roles of CLDNs in tumorigenesis are largely unclear. Studying the associations of these CLDNs with the TNBC subgroup of breast cancers might provide us with potential diagnostic biomarkers or therapeutic targets for cancer cells.

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Comparison of the Distribution Pattern of 21-Gene Recurrence Score between Mucinous Breast Cancer and Infiltrating Ductal Carcinoma in Chinese Population: A Retrospective Single-Center Study

Cancer Research and Treatment ◽

10.4143/crt.2019.387 ◽

2020 ◽

Vol 52 (3) ◽

pp. 671-679

Author(s):

Jiayi Wu ◽

Shuning Ding ◽

Lin Lin ◽

Xiaochun Fei ◽

Caijin Lin ◽

...

Keyword(s):

Breast Cancer ◽

Distribution Pattern ◽

Ductal Carcinoma ◽

Molecular Subtype ◽

Disease Free Survival ◽

Recurrence Score ◽

Chinese Patients ◽

Ki 67 ◽

Infiltrating Ductal Carcinoma ◽

Mucinous Breast Cancer

PurposeThis retrospective study aimed to evaluate the distribution pattern and prognostic value of 21-gene recurrence score (RS) in Chinese patients with mucinous breast cancer (MC) and compared with infiltrating ductal carcinoma (IDC).Materials and MethodsPatients diagnosed with MC or IDC from January 2010 to January 2017 were retrospectively recruited. Reverse transcriptase–polymerase chain reaction assay of 21 genes was conducted to calculate the RS. Univariate and multivariate analyses were performed to assess the association between RS and clinicopathological factors. Survival outcomes including disease-free survival (DFS) and overall survival (OS) were estimated by Kaplan-Meier method and compared by log-rank test.ResultsThe MC cohort included 128 patients and the IDC cohort included 707 patients. The proportions of patients with a low (RS < 18), intermediate (18-30), or high risk (RS > 30) were 32.0%, 48.4%, and 19.5% in MC cohort, and 26.9%, 46.8% and 26.3% in IDC cohort. The distribution of RS varied significantly according to different Ki-67 index and molecular subtype in both cohorts. Moreover, the receipt of chemotherapy was associated with RS in both cohorts. Among patients with MC, tumor stage was related to the DFS (p=0.040). No significant differences in DFS and OS were found among MC patients in different RS risk groups (OS, p=0.695; DFS, p=0.926).ConclusionRS was significantly related to Ki-67 index and molecular subtypes in MC patients, which is similar in IDC patients. However, RS was not able to predict DFS and OS in patients with MC.

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Ki-67 is a Luminal B marker that identifies a high-risk subgroup in hormone receptor positive and node negative breast cancer

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.10521 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 10521-10521

Author(s):

M. Cheang ◽

D. Voduc ◽

S. Leung ◽

D. Turbin ◽

P. S. Bernard ◽

...

Keyword(s):

Breast Cancer ◽

Hormone Receptor ◽

Poor Prognosis ◽

Cox Regression ◽

Breast Cancers ◽

Ki 67 ◽

Node Negative ◽

Luminal B ◽

Poor Outcome ◽

Hormone Receptor Positive

10521 Background: Gene expression profiling studies have revealed prognostically significant intrinsic breast cancer subtypes, designated Luminal A, Luminal B, Basal and Her2. Expression of ER and associated genes characterizes the luminal breast cancers. The Lum B subgroup is associated with poor outcome, but we lack immunohistochemical (IHC) markers to distinguish Lum A and Lum B subgroups. MKI67 is one gene known to be highly expressed in Lum B tumors, encoding the Ki-67 protein, a robust marker of cell proliferation. In this study, we perform IHC analysis of Ki-67 in a large breast cancer tissue microarray. Methods: Our patient cohort consists of 2222 consecutive cases of invasive breast cancer referred to the BC Cancer Agency from 1986 to 1992. Archival paraffin tissue blocks were used to construct a tissue microarray that was then stained for Ki-67 using a commercially available mouse monoclonal antibody. Ki-67 staining was scored quantitatively by automated image analysis and a tumor was positive if the percent positive nuclei was >30%’ Results: Of the 2,222 patients, there are 1,437 Luminal tumors as defined by IHC (ER or PR positive). As Her2 positive status is an established marker of poor prognosis, we excluded these tumors from our analysis. Of the remaining tumors, 9% were Ki-67 positive when using a ki-67 cut off of 30% positive nuclei. In survival analysis of patients ER/PR positive and Her2 negative, we found that Ki-67 identifies a population with poor prognosis (10-yr BCSS 60% vs. 80%). In a multivariate Cox regression we found that Ki-67 is independently prognostic. We repeated Cox regression analysis including only node negative patients and again found that Ki-67 is an independent predictor of poor outcome. Conclusions: Ki-67 has prognostic significance on multivariate survival analysis. Hormone receptor positive and node negative status is typically associated with a favorable outcome for breast cancer. However, Ki-67 is able to identify a small, but clinically significant subgroup with a particularly poor outcome. Defining the Luminal B subtype as (ER or PR) positive and (HER2 or Ki-67) positive, results in a subgroup that contains 18% of hormone receptor positive breast cancers with 10-yr BCSS of 61%. No significant financial relationships to disclose.

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Prognostic features of signal transducer and activator of transcription 3 in an ER(+) breast cancer model system

Cancer Informatics ◽

10.4137/cin.s12493 ◽

2014 ◽

Vol 13 ◽

pp. CIN.S12493 ◽

Cited By ~ 1

Author(s):

Li-Yu D. Liu ◽

Li-Yun Chang ◽

Wen-Hung Kuo ◽

Hsiao-Lin Hwa ◽

Yi-Shing Lin ◽

...

Keyword(s):

Breast Cancer ◽

Poor Prognosis ◽

Cancer Cell Line ◽

Signal Transducer ◽

Breast Cancers ◽

Luminal A ◽

Regulatory Pathways ◽

Luminal B ◽

Prognostic Features ◽

Transcription 3

The aberrantly expressed signal transducer and activator of transcription 3 (STAT3) predicts poor prognosis, primarily in estrogen receptor positive (ER(+)) breast cancers. Activated STAT3 is overexpressed in luminal A subtype cells. The mechanisms contributing to the prognosis and/or subtype relevant features of STAT3 in ER(+) breast cancers are through multiple interacting regulatory pathways, including STAT3-MYC, STAT3-ERα, and STAT3-MYC-ERα interactions, as well as the direct action of activated STAT3. These data predict malignant events, treatment responses and a novel enhancer of tamoxifen resistance. The inferred crosstalk between ERα and STAT3 in regulating their shared target gene-METAP2 is partially validated in the luminal B breast cancer cell line-MCF7. Taken together, we identify a poor prognosis relevant gene set within the STAT3 network and a robust one in a subset of patients. VEGFA, ABL1, LYN, IGF2R and STAT3 are suggested therapeutic targets for further study based upon the degree of differential expression in our model.

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Neoadjuvant chemotherapy-induced decrease of prognostic nutrition index predicts poor prognosis in patients with breast cancer

10.21203/rs.2.12820/v4 ◽

2020 ◽

Author(s):

Takaaki Oba ◽

Kazuma Maeno ◽

Daiya Takekoshi ◽

Mayu Ono ◽

Tokiko Ito ◽

...

Keyword(s):

Breast Cancer ◽

Neoadjuvant Chemotherapy ◽

Poor Prognosis ◽

Disease Free Survival ◽

Prognostic Nutritional Index ◽

Prognostic Impact ◽

Nutritional Index ◽

Significant Difference ◽

Before And After ◽

The Mean

Abstract Background: The prognostic nutritional index (PNI), which is an easily calculated nutritional index, is significantly associated with patient outcomes in various solid malignancies. This study aimed to evaluate the prognostic impact of PNI changes in patients with breast cancer undergoing neoadjuvant chemotherapy (NAC).Methods: We reviewed patients with breast cancer who underwent NAC and a subsequent surgery for breast cancer between 2005 and 2016. PNI before and after NAC were calculated using the following formula: 10 × serum albumin (g/dl) + 0.005 × total lymphocyte count/mm3. The relationship between PNI and prognosis was retrospectively analyzed. Results: In total, 191 patients were evaluated. There was no significant difference in disease-free survival (DFS) between the pre-NAC PNI high group and the pre-NAC PNI low group (cutoff: 53.1). However, PNI decreased in 181 patients (94.7%) after NAC and the mean PNI also significantly decreased after NAC from 52.6 ± 3.8 pre-NAC to 46.5 ± 4.4 post-NAC (p < 0.01). The mean ΔPNI, which was calculated as pre-NAC PNI minus post-NAC PNI, was 5.4. The high ΔPNI group showed significantly poorer DFS than the low ΔPNI group (cut off: 5.26) (p = 0.015). Moreover, high ΔPNI was an independent risk factor of DFS on multivariate analysis (p = 0.042). Conclusions: High decrease of PNI during NAC predicts poor prognosis. Thus, maintaining the nutritional status during NAC may result in better treatment outcomes in patients with breast cancer.

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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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Neoadjuvant chemotherapy-induced decrease of prognostic nutrition index predicts poor prognosis in patients with breast cancer

10.21203/rs.2.12820/v2 ◽

2020 ◽

Author(s):

Takaaki Oba ◽

Kazuma Maeno ◽

Daiya Takekoshi ◽

Mayu Ono ◽

Tokiko Ito ◽

...

Keyword(s):

Breast Cancer ◽

Neoadjuvant Chemotherapy ◽

Poor Prognosis ◽

Disease Free Survival ◽

Prognostic Nutritional Index ◽

Prognostic Impact ◽

Nutritional Index ◽

Significant Difference ◽

Before And After ◽

The Mean

Abstract Background: The prognostic nutritional index (PNI), which is an easily calculated nutritional index, is significantly associated with patient outcomes in various solid malignancies. This study aimed to evaluate the prognostic impact of PNI changes in patients with breast cancer undergoing neoadjuvant chemotherapy (NAC). Methods: We reviewed patients with breast cancer who underwent NAC and a subsequent surgery for breast cancer between 2005 and 2016. PNI before and after NAC were calculated using the following formula: 10 × serum albumin (g/dl) + 0.005 × total lymphocyte count/mm3. The relationship between PNI and prognosis was retrospectively analyzed. Results: In total, 191 patients were evaluated. There was no significant difference in disease-free survival (DFS) between the pre-NAC PNI high group and the pre-NAC PNI low group (cutoff: 53.1). However, PNI decreased in 181 patients (94.7%) after NAC and the mean PNI also significantly decreased after NAC from 52.6 ± 3.8 pre-NAC to 46.5 ± 4.4 post-NAC (p < 0.01) . The mean ΔPNI, which was calculated as pre-NAC PNI minus post-NAC PNI, was 5.4. The high ΔPNI group showed significantly poorer DFS than the low ΔPNI group (cut off: 5.26) (p = 0.015). Moreover, high ΔPNI was an independent risk factor of DFS on multivariate analysis (p = 0.042). Conclusions: High decrease of PNI during NAC predicts poor prognosis. Thus, maintaining the nutritional status during NAC may result in better treatment outcomes in patients with breast cancer.

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HOXB9, a gene promoting tumor angiogenesis and proliferation, as a prognostic factor in breast cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2011.29.27_suppl.33 ◽

2011 ◽

Vol 29 (27_suppl) ◽

pp. 33-33

Author(s):

H. Seki ◽

T. Hayashida ◽

H. Jinno ◽

S. Hirose ◽

M. Takahashi ◽

...

Keyword(s):

Breast Cancer ◽

Prognostic Factor ◽

Tumor Angiogenesis ◽

Ductal Carcinoma ◽

Disease Free Survival ◽

Specific Cell ◽

Consecutive Series ◽

Positive Staining ◽

Significant Prognostic Factor ◽

Ki 67

33 Background: We demonstrated that HOXB9, a member of homeobox genes, expression promoted tumor neovascularization and metastasis in vitro and in vivo assay. These findings imply that overexpression of HOXB9 contributes to tumor progression through activation of signaling pathways that alter both tumor-specific cell fates and tumor-stromal microenvironment, leading to increased invasion and metastasis. (Hayashida et al., PNAS 2010) We sought to determine whether these results could be extended to the clinical application. In this study, we evaluated the correlation between HOXB9 expression, clinical outcomes, and the clinicopathological variables in breast cancer patients, and the contribution of HOXB9 expression to tumor cell proliferation and angiogenesis. Methods: A consecutive series of 141 patients with invasive ductal carcinoma who underwent surgical treatment were examined. HOXB9 protein expression was analyzed immunohistochemically using the anti-human HOXB9 polyclonal antibody. Immunostaining of Ki-67, CD31, and CD34 were performed to evaluate the association of proliferation and tumor angiogenesis with HOXB9 expression. Results: Of 141 tumor specimens immunostained for HOXB9, 69 specimens (48.9%) were positive staining. Univariate logistic regression revealed ER and PgR negativity, HER2 positivity, high nuclear grade, and large pathological tumor size as significant variables associated with HOXB9 expression. Moreover, 12 (92.3%) out of 13 triple negative breast cancer showed HOXB9 expression. The disease-free survival (DFS) and the overall survival were significantly different between the HOXB9 positive and negative group; HR=20.714, p=0.001, HR 9.206, p=0.003, respectively. A Multivariate analysis indicated that HOXB9 expression was the only independent prognostic factor for DFS (HR=15.532, p=0.009). In subgroup analysis, HOXB9 positive tumors showed a significant increase in the number of vasculature and the Ki-67 ratio in comparison with HOXB9 negative. Conclusions: Our results suggest that HOXB9 expression promoting the tumor proliferation and the angiogenesis is a significant prognostic factor in breast cancer.

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Integrative Analyses of Multilevel Omics Reveal Preneoplastic Breast to Possess a Molecular Landscape That is Globally Shared with Invasive Basal-Like Breast Cancer

Cancers ◽

10.3390/cancers12030722 ◽

2020 ◽

Vol 12 (3) ◽

pp. 722 ◽

Cited By ~ 3

Author(s):

Zhenlin Ju ◽

Anjana Bhardwaj ◽

Matthew Embury ◽

Harpreet Singh ◽

Preethi Gunaratne ◽

...

Keyword(s):

Breast Cancer ◽

Ductal Carcinoma ◽

Disease Free Survival ◽

Direct Result ◽

Mcf10a Cell ◽

Breast Cancers ◽

Breast Cancer Patients ◽

Genomic Changes ◽

Basal Like Breast Cancer ◽

Molecular Landscape

To characterize molecular changes accompanying the stepwise progression to breast cancer and to identify functional target pathways, we performed miRNA and RNA sequencing using MCF10A cell lines based model system that replicates the multi-step progression involving normal, preneoplastic, ductal carcinoma in situ, and invasive carcinoma cells, where the carcinoma most resemble the basal-like subgroup of human breast cancers. These analyses suggest that 70% of miRNA alterations occurred during the initial progression from normal to a preneoplastic stage. Most of these early changes reflected a global upregulation of miRNAs. This was consistent with a global increase in the miRNA-processing enzyme DICER, which was upregulated as a direct result of loss of miRNA let-7b-5p. Several oncogenic and tumor suppressor pathways were also found to change early, prior to histologic stigmata of cancer. Our finding that most genomic changes in the progression to basal-like breast cancer occurred in the earliest stages of histologic progression has implications for breast cancer prevention and selection of appropriate control tissues in molecular studies. Furthermore, in support of a functional significance of let-7b-5p loss, we found its low levels to predict poor disease-free survival and overall survival in breast cancer patients.

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Neoadjuvant chemotherapy-induced decrease of prognostic nutrition index predicts poor prognosis in patients with breast cancer

10.21203/rs.2.12820/v3 ◽

2020 ◽

Author(s):

Takaaki Oba ◽

Kazuma Maeno ◽

Daiya Takekoshi ◽

Mayu Ono ◽

Tokiko Ito ◽

...

Keyword(s):

Breast Cancer ◽

Neoadjuvant Chemotherapy ◽

Poor Prognosis ◽

Disease Free Survival ◽

Prognostic Nutritional Index ◽

Prognostic Impact ◽

Nutritional Index ◽

Significant Difference ◽

Before And After ◽

The Mean

Abstract Background: The prognostic nutritional index (PNI), which is an easily calculated nutritional index, is significantly associated with patient outcomes in various solid malignancies. This study aimed to evaluate the prognostic impact of PNI changes in patients with breast cancer undergoing neoadjuvant chemotherapy (NAC). Methods: We reviewed patients with breast cancer who underwent NAC and a subsequent surgery for breast cancer between 2005 and 2016. PNI before and after NAC were calculated using the following formula: 10 × serum albumin (g/dl) + 0.005 × total lymphocyte count/mm 3 . The relationship between PNI and prognosis was retrospectively analyzed. Results: In total, 191 patients were evaluated. There was no significant difference in disease-free survival (DFS) between the pre-NAC PNI high group and the pre-NAC PNI low group (cutoff: 53.1). However, PNI decreased in 181 patients (94.7%) after NAC and the mean PNI also significantly decreased after NAC from 52.6 ± 3.8 pre-NAC to 46.5 ± 4.4 post-NAC ( p < 0.01). The mean ΔPNI, which was calculated as pre-NAC PNI minus post-NAC PNI, was 5.4. The high ΔPNI group showed significantly poorer DFS than the low ΔPNI group (cut off: 5.26) ( p = 0.015). Moreover, high ΔPNI was an independent risk factor of DFS on multivariate analysis ( p = 0.042). Conclusions: High decrease of PNI during NAC predicts poor prognosis. Thus, maintaining the nutritional status during NAC may result in better treatment outcomes in patients with breast cancer.

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