Expression of BCRP/ABCG2 Protein in Invasive Breast Cancer and Response to Neoadjuvant Chemotherapy

2021 ◽  
Author(s):  
Yan Shou Zhang ◽  
Chao Yang ◽  
Lei Han ◽  
Lei Liu ◽  
Yun Jiang Liu
Keyword(s):  
Breast Cancer ◽  
Breast Carcinoma ◽  
Neoadjuvant Chemotherapy ◽  
Tumor Size ◽  
Hormone Receptor ◽  
Molecular Subtypes ◽  
Therapy Response ◽  
Luminal A ◽  
Luminal B ◽  
Response To Neoadjuvant Chemotherapy

Background: Breast cancer resistance protein (BCRP), or ABCG2 (ATP-binding cassette sub-family G member 2), is an ATP-binding cassette (ABC) transporter that mediates energy-dependent transport of substrate drugs out of the cell. Its overexpression may contribute to intrinsic drug resistance in vitro. However, the current literature has not yet clarified the clinical significance of BCRP/ABCG2 in invasive breast carcinoma. Objectives: The purpose of this study was to validate the expression of BCRP/ABCG2 in invasive breast carcinoma and its role in response to neoadjuvant chemotherapy. Methods: In this study, a pretherapeutic core biopsy was performed in 222 patients. BCRP/ABCG2 expression in carcinoma tissue was measured by immunohistochemistry. BCRP/ABCG2 expression correlations with clinicopathological features, molecular subtypes, and therapy response after neoadjuvant chemotherapy were investigated. Results: The results showed that BCRP/ABCG2 was expressed in different molecular subtypes. The proportions of patients with high BCRP/ABCG2 expression were similar in luminal A and luminal B tumors (Luminal B, 80%; Luminal A, 78%), compared with other molecular subtypes (Triple-negative, 63%; HER-2+, 58%. P=0.05). BCRP/ABCG2 expression and the number of lymphatic metastases (𝑃=0.001) and tumor size (𝑃=0.011) demonstrated a statistically significant correlation. Low BCRP/ABCG2 expression was associated with an increased pathological complete response (pCR) rate of 38%, higher than the 19% in tumors with high BCRP/ABCG2 expression (P=0.002). In multivariable analysis, BCRP/ABCG2 and hormone receptor (HR) expression were identified as independent risk factors of pCR (P=0.003, P=0.013. respectively). Conclusions: BCRP/ABCG2 is highly expressed in hormone receptor-positive breast cancer. High BCRP/ABCG2 expression is associated with lymphatic metastasis, tumor size, and poor pCR. BCRP/ABCG2 may be a novel potential biomarker that can predict clinical progression and therapy response after neoadjuvant chemotherapy.

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

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.

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

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.

scholarly journals Unraveling Immune-Related lncRNAs in Breast Cancer Molecular Subtypes

2021 ◽  
Vol 11 ◽  
Author(s):  
Carolina Mathias ◽  
João Carlos Degraf Muzzi ◽  
Bruna Borba Antunes ◽  
Daniela F. Gradia ◽  
Mauro A. A. Castro ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Immune Response ◽  
Molecular Subtypes ◽  
Expression Profiles ◽  
Therapy Response ◽  
The Cancer Genome Atlas ◽  
Luminal A ◽  
Specific Expression ◽  
Luminal B ◽  
Response Activation

Breast cancer (BRCA) is the most leading cause of cancer worldwide. It is a heterogeneous disease with at least five molecular subtypes including luminal A, luminal B, basal-like, HER2-enriched, and normal-like. These five molecular subtypes are usually stratified according to their mRNA profile patterns; however, ncRNAs are increasingly being used for this purpose. Among the ncRNAs class, the long non-coding RNAs (lncRNAs) are molecules with more than 200 nucleotides with versatile regulatory roles; and high tissue-specific expression profiles. The heterogeneity of BRCA can also be reflected regarding tumor microenvironment immune cells composition, which can directly impact a patient’s prognosis and therapy response. Using BRCA immunogenomics data from a previous study, we propose here a bioinformatics approach to include lncRNAs complexity in BRCA molecular and immune subtype. RNA-seq data from The Cancer Genome Atlas (TCGA) BRCA cohort was analyzed, and signal-to-noise ratio metrics were applied to create these subtype-specific signatures. Five immune-related signatures were generated with approximately ten specific lncRNAs, which were then functionally analyzed using GSEA enrichment and survival analysis. We highlighted here some lncRNAs in each subtype. LINC01871 is related to immune response activation and favorable overall survival in basal-like samples; EBLN3P is related to immune response suppression and progression in luminal B, MEG3, XXYLT1-AS2, and LINC02613 were related with immune response activation in luminal A, HER2-enriched and normal-like subtypes, respectively. In this way, we emphasize the need to know better the role of lncRNAs as regulators of immune response to provide new perspectives regarding diagnosis, prognosis and therapeutical targets in BRCA molecular subtypes.

Neoadjuvant versus adjuvant chemotherapy with taxanes and anthracycline-based regimen: Which leads to better outcome in patients with different subtype breast cancer?

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 1084-1084
Author(s):  
Houpu Yang ◽  
Shu Wang ◽  
Lixin Zhou ◽  
Jiajia Guo ◽  
Yingming Cao ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Adjuvant Chemotherapy ◽  
Neoadjuvant Chemotherapy ◽  
Adjuvant Therapy ◽  
Molecular Subtypes ◽  
Disease Free Survival ◽  
Luminal A ◽  
Luminal B ◽  
Survival Difference ◽  
Response To Chemotherapy

1084 Background: Neoadjuvant chemotherapy was reported to lead to equal outcome with adjuvant therapy in operable breast cancer. However, different molecular subtypes show variant response to chemotherapy, which is associated with different long-term prognosis. This study was to clarify whether molecular subtypes lead to different outcome between neoadjuvant and adjuvant chemotherapy. Methods: We identified 406 patients with stage II-III breast cancer who were treated with neoadjuvant or adjuvant chemotherapy between 2000 and 2008. To minimize the confounding bias, only patients received taxanes and anthracycline based regimen (TA) were included. Cases were divided according to receipt of neoadjuvant and adjuvant therapy. Data were compared using χ2test and analysis of variance. Kaplan-Meier Curves were generated. Results: Of the 406 patients, 201(49.5%) received neoadjuvant chemotherapy and 205(50.5%) received adjuvant TA regimen. The pCR rate was 12.9%(26/201) in total, and 7%, 14%, 33.3%, 19.4% for Luminal A, Luminal B, HER2+ and Triple negative breast cancer(TNBC), respectively. The HER2+ and TNBC have significantly higher rates of pCR than Luminal type (p<0.05). In general the two groups showed little survival variance (p=0.073 for DFS and p=0. 601 for OS). In Luminal B, neoadjuvant settings led to worse disease free survival (DFS) and overall survival (OS) than adjuvant settings after controlling for the covariates associated with survival in unadjusted tests (HR=0.41, p=0.028 for DFS; HR=0.32, p=0.020 for OS). In HER2+ subtype, neoadjuvant group corresponded to better DFS and OS (HR=5.65, p=0.024 for DFS; HR=10.52, p=0.010 for OS). On the contrary, patients with TNBC and Luminal A undergoing neoadjuvant chemotherapy had equal DFS and OS compared with patients receiving adjuvant therapy (p>0.05). Conclusions: The results demonstrate survival difference between patients receiving neoadjuvant and adjuvant cytotoxic therapy in variant subtypes. Prospective studies are necessary to determine if the finding is durable and optimize the timing of chemotherapy for breast cancer with different molecular background.

scholarly journals Diffusion-Weighted Imaging of Different Breast Cancer Molecular Subtypes: A Systematic Review and Meta-Analysis

Breast Care ◽  
2021 ◽  
pp. 1-8
Author(s):  
Hans-Jonas Meyer ◽  
Andreas Wienke ◽  
Alexey Surov
Keyword(s):  
Breast Cancer ◽  
Systematic Review ◽  
Diffusion Weighted Imaging ◽  
Triple Negative ◽  
Molecular Subtypes ◽  
Luminal A ◽  
Diagnose Breast Cancer ◽  
Luminal B ◽  
Diffusion Weighted ◽  
Adc Values

Background: Magnetic resonance imaging can be used to diagnose breast cancer (BC).Diffusion-weighted imaging (DWI) and the apparent diffusion coefficient (ADC) can be used to reflect tumor microstructure. Objectives: This analysis aimed to compare ADC values between molecular subtypes of BC based on a large sample of patients. Method: The MEDLINE library and Scopus database were screened for the associations between ADC and molecular subtypes of BC up to April 2020. The primary end point of the systematic review was the ADC value in different BC subtypes. Overall, 28 studies were included. Results: The included studies comprised a total of 2,990 tumors. Luminal A type was diagnosed in 865 cases (28.9%), luminal B in 899 (30.1%), human epidermal growth factor receptor (Her2)-enriched in 597 (20.0%), and triple-negative in 629 (21.0%). The mean ADC values of the subtypes were as follows: luminal A: 0.99 × 10–3 mm2/s (95% CI 0.94–1.04), luminal B: 0.97 × 10–3 mm2/s (95% CI 0.89–1.05), Her2-enriched: 1.02 × 10–3 mm2/s (95% CI 0.95–1.08), and triple-negative: 0.99 × 10–3 mm2/s (95% CI 0.91–1.07). Conclusions: ADC values cannot be used to discriminate between molecular subtypes of BC.

Association between molecular subtype of local advanced breast cancer with Ca 15-3 level

2021 ◽  
pp. 1-4
Author(s):  
Dony Ruswendro ◽  
Salman Ardi Syamsu ◽  
Rudy Thabry ◽  
Arifin Seweng ◽  
Andi Nilawati Usman
Keyword(s):  
Breast Cancer ◽  
Advanced Breast Cancer ◽  
Tumor Marker ◽  
Molecular Subtypes ◽  
Locally Advanced Breast Cancer ◽  
Locally Advanced ◽  
Tissue Growth ◽  
Advanced Breast ◽  
Luminal A ◽  
Luminal B

BACKGROUND: Neoplasm is an abnormal mass of tissue that grows excessively and not coordinated with normal tissue growth and continues to do so even though the stimulation that triggered the change has stopped. Breast cancer can be known by using tumor marker, which has been used is mucin-like glycoprotein Carcinoma Antigen (CA 15-3) which is a tumor marker that is specific to breast cancer. METHOD: This study is a cross-sectional study to determine the association between molecular subtypes of locally advanced breast cancer with CA 15-3 level at Abdul Wahab Sjahranie Samarinda Hospital. The population in this study were all breast cancer patients that were confirmed by histopathological examination. RESULTS: A total of 75 patients were included for this study, 29 patients (38.7%) known as Overexpression HER2, 18 patients (24.0%) were Luminal B with HER2 (+), 11 patients (14.7%) were Luminal B with HER2 (−), 11 patients (14.7%) were Basal-like/TNBC, and 6 patients (8,0%) were Luminal A. From the ANOVA test, the value of p = 0.045 (p < 0.05) means there was an association between Ca 15-3 level and molecular subtypes in patients with locally advanced breast cancer at the Abdul Wahab Sjahranie Hospital in Samarinda 2017. In this study Ca 15-3 levels were obtained on average for Luminal A 16.98 U/mL, Luminal B with HER2 (−) 42.41 U/mL, Luminal B with HER2 (+) 73.75 U/mL, Overexpression HER2 47.73 U/mL, and Basal Like /TNBC 63.50 U/mL. CONCLUSION: Statistically, it was found that there was an association between Ca 15-3 levels and molecular subtypes in patients with locally advanced breast cancer at the Abdul Wahab Sjahranie Hospital in Samarinda 2017.

Trends in breast cancer mortality according to molecular subtypes: A population-based study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 572-572
Author(s):  
Yunan Han ◽  
Shuai Xu ◽  
Graham A. Colditz ◽  
Adetunji T. Toriola
Keyword(s):  
Breast Cancer ◽  
Cancer Mortality ◽  
Triple Negative ◽  
Molecular Subtypes ◽  
Breast Cancer Mortality ◽  
Treatment Strategies ◽  
Luminal A ◽  
Her2 Positive ◽  
Mortality Trends ◽  
Luminal B

572 Background: Breast cancer is the second leading cause of cancer death in U.S. women. On the molecular level, breast cancer is a heterogeneous disease. Heterogeneous expressions of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) are etiologically and clinically meaningful, as they map to distinct risk factors and different treatment strategies. Although breast cancer mortality has been declining since 1990, little is known about mortality trends according to molecular subtypes at the population level. Methods: We examined the incidence-based mortality rates and trends among women who were diagnosed with invasive breast cancer from 2010 through 2017 using the Surveillance, Epidemiology, and End Results (SEER) database. We defined incidence-based mortality using a moving 5-year calendar period starting in 2014. We further assessed mortality according to breast cancer molecular subtypes: luminal A (ER and/or PR positive, HER2 negative), luminal B (ER and/or PR positive, HER2 positive), HER2-enriched (HER2 over-expressed or amplified, ER and PR negative) and triple-negative (ER and PR negative, HER2 negative) tumors. We calculated annual percent changes (APC) in incidence-based mortality using joinpoint regression models. Results: Overall, incidence-based mortality for breast cancer significantly decreased by 1.5% annually from 2014 through 2017 (APC, -1.5%; 95% coefficient interval [CI], -2.3% to -0.7%; p<0.001). Incidence-based mortality decreased annually by 2.0% for luminal A breast cancer (APC, -2.0%; 95% CI, -3.7% to -0.3%; p<0.001), 2.1% for luminal B breast cancer (APC, -2.1%; 95% CI, -5.4% to 1.4%; p=0.1), 1.1% for triple-negative breast cancer (TNBC) (APC, -1.1%; 95% CI, -2.1% to -0.0%; p<0.001). However, incidence-based mortality for HER2-enriched breast cancer increased 2.3% annually during the study period (APC, 2.3%; 95% CI, -2.4% to 7.2%; p=0.2). Conclusions: Between 2014 and 2017, incidence-based mortality for luminal A, luminal B, and TNBC decreased among U.S. women, with a larger decrease observed for luminal tumors. However, incidence-based mortality for HER2-enriched breast cancer increased. The favorable incidence-based mortality trends for luminal tumors and TNBC are likely due to the continuing improvement in treatments and early detection. The increasing trend of incidence-based mortality for HER2-enriched breast cancer constitutes a priority for cancer control activities and further research.

Relationship between tumor size and metastatic site in patients with stage IV breast cancer: A large SEER-based study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e13065-e13065
Author(s):  
Qian Dong ◽  
Mi Zhang ◽  
Da Jiang
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Tumor Size ◽  
Stage Iv ◽  
Breast Cancer Patients ◽  
Luminal A ◽  
Chi Square ◽  
Metastatic Site ◽  
Luminal B ◽  
Stage Iv Breast Cancer

e13065 Background: To analyze the correlation between tumor size and metastatic site in first-diagnosed stage IV breast cancer patients. Methods: Stage IV breast cancer patients diagnosed from 2010 to 2015 were screened by the Surveillance, Epidemiology, and End Results (SEER) database. The characteristics of clinical variables were represented by a frequency table, and the Chi-square test was used for comparison. At the same time, the Chi-square test was used to analyze the relationship between tumor size and organ metastasis. Correlation between tumor size and the prognosis of patients was contributed by KM curve and Log-rank test. Results: Regardless of tumor size, the proportion of bone metastasis was higher and brain metastasis was lower in breast cancer patients. There were significant differences in the site of metastases based on different subtype. Luminal A and Luminal B breast cancer had the highest proportion of bone metastases; brain metastasis accounted for the highest proportion in triple-negative breast cancer (TNBC); while the incidence of liver metastasis was the highest in Her-2(+) breast cancer. At the same time, the results indicated that Luminal A breast cancer with a tumor size > 5 cm was more likely to develop multi-site metastasis and lung metastasis, while Luminal B breast cancer with a tumor size ≤ 5 cm was more likely to develop liver metastasis. The results also revealed that TNBC patients with a tumor size of 0 - 2cm were more likely to develop bone metastasis than those with a tumor size > 5 cm, and the incidence of lung metastasis in triple-negative patients showed an increasing trend with the increase of tumor size. Conclusions: Based on subtype, we found that there was a significant difference between tumor size and metastatic site in patients with stage IV breast cancer, and the difference was statistically significant. This study provided evidence-based basis for decision-making of stage IV breast cancer treatment.

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