Breast cancer subtypes in Chinese Americans: A study from the Mount Sinai Health System.

39 Background: Breast cancer has been increasing in many Asian countries, as well as among Asian Americans. While many studies have examined breast cancer subtypes in African American and Caucasian populations, few have looked at tumor subtypes in the Asian population. We aimed to examine breast cancer subtypes in Chinese Americans. Methods: We identified all Chinese patients diagnosed with invasive breast cancers between 2005 and 2012 from the Cancer Registry of Mount Sinai Beth Israel, Mount Sinai St. Luke’s, and Roosevelt Hospitals. The following clinical data were collected for each patient: age at diagnosis, year of diagnosis, largest tumor size (cm), lymph node status, estrogen receptor (ER), progesterone receptor (PR) and HER2 status. Based on ER, PR, and HER2, patients were categorized into three molecular subtypes: 1) Hormone receptor (HR)+ (ER and/or PR positive, HER2 negative), HER2+ and triple negative (TN) (ER, PR, and HER2 negative). Descriptive variables were analyzed using one-way Anova test. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated from logistic regression models. Results: There were 175 Chinese patients diagnosed with invasive breast cancers from 2005 to 2012. Median age at diagnosis was 54 (range 27-90). One hundred fourteen (65%) were HR+, 41 (23%) were HER2+, and 20 (11%) were TN. There were 59 (34%) patients diagnosed at age ≤ 50 and twelve patients (7%) were diagnosed at age < 40. There were more HER2+ and TN breast cancers diagnosed in women age ≤ 50 compared to age > 50, but the difference was not statistically significant. Women in the HR+ group were diagnosed at an older age compared to the other two subgroups (57 ± 12, 52 ± 8, and 52 ± 10 for HR+, HER2+, and TN, respectively, p = 0.036). Patients with TN breast cancers were more likely to have lymph node involvement compared to HR+ or HER2+ patients (p = 0.02). There was a trend of increasing prevalence of HER2+ breast cancer observed in recent years: 18.5% in 2005-2006, 23.8% in 2007-2008, 18.4% in 2009-2010, and 29.8% in 2011-2012. Conclusions: We observed a high proportion of breast cancer among young Chinese Americans as well as an increasing prevalence of HER2+ breast cancer in this population in recent years. Further studies are warranted.

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Crosstalk between HER2 and PD-1/PD-L1 in Breast Cancer: From Clinical Applications to Mathematical Models

Cancers ◽

10.3390/cancers12030636 ◽

2020 ◽

Vol 12 (3) ◽

pp. 636 ◽

Cited By ~ 10

Author(s):

Regina Padmanabhan ◽

Hadeel Shafeeq Kheraldine ◽

Nader Meskin ◽

Semir Vranic ◽

Ala-Eddin Al Moustafa

Keyword(s):

Breast Cancer ◽

Mathematical Models ◽

Immune Checkpoint ◽

Checkpoint Inhibitors ◽

Breast Cancers ◽

Treatment Protocols ◽

Cancer Subtypes ◽

Cancer Management ◽

Her2 Breast Cancer ◽

Programmed Death

Breast cancer is one of the major causes of mortality in women worldwide. The most aggressive breast cancer subtypes are human epidermal growth factor receptor-positive (HER2+) and triple-negative breast cancers. Therapies targeting HER2 receptors have significantly improved HER2+ breast cancer patient outcomes. However, several recent studies have pointed out the deficiency of existing treatment protocols in combatting disease relapse and improving response rates to treatment. Overriding the inherent actions of the immune system to detect and annihilate cancer via the immune checkpoint pathways is one of the important hallmarks of cancer. Thus, restoration of these pathways by various means of immunomodulation has shown beneficial effects in the management of various types of cancers, including breast. We herein review the recent progress in the management of HER2+ breast cancer via HER2-targeted therapies, and its association with the programmed death receptor-1 (PD-1)/programmed death ligand-1 (PD-L1) axis. In order to link research in the areas of medicine and mathematics and point out specific opportunities for providing efficient theoretical analysis related to HER2+ breast cancer management, we also review mathematical models pertaining to the dynamics of HER2+ breast cancer and immune checkpoint inhibitors.

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Ki67 index in intrinsic breast cancer subtypes and its association with prognostic parameters

BMC Research Notes ◽

10.1186/s13104-019-4653-x ◽

2019 ◽

Vol 12 (1) ◽

Cited By ~ 5

Author(s):

Atif Ali Hashmi ◽

Kashif Ali Hashmi ◽

Muhammad Irfan ◽

Saadia Mehmood Khan ◽

Muhammad Muzzammil Edhi ◽

...

Keyword(s):

Breast Cancer ◽

Ductal Carcinoma ◽

Prognostic Significance ◽

Breast Cancer Subtypes ◽

Prognostic Parameters ◽

Ki67 Index ◽

Breast Cancers ◽

Cancer Subtypes ◽

Luminal B ◽

Cancer Management

Abstract Objectives Ki67 is the most commonly used marker to evaluate proliferative index in breast cancer, however no cutoff values have been clearly defined for high ki67 index. Cancer management should be according to loco-regional profile; therefore, we aimed to determine ki67 index in 1951 cases of intrinsic breast cancer subtypes and its association with other prognostic parameters in our set up. Results Triple negative breast cancers showed highest ki67 index (mean 50.9 ± 23.7%) followed by Her2neu (mean 42.6 ± 21.6%) and luminal B cancers (mean 34.9 ± 20.05%). Metaplastic and medullary breast cancers significantly showed higher ki67 index as compared to ductal carcinoma, NOS. No significant association of ki67 index was noted with any of the histologic parameters in different subtypes of breast cancer expect for tumor grade. Although, ki67 index is a valuable biomarker in breast cancer, however no independent prognostic significance of ki67 could be established in our study.

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Relationship between young age at diagnosis and disease free survival in premenopausal patients according to breast cancer subtypes.

Journal of Clinical Oncology ◽

10.1200/jco.2018.36.15_suppl.e12557 ◽

2018 ◽

Vol 36 (15_suppl) ◽

pp. e12557-e12557

Author(s):

Shuangshuang Lu ◽

Li Zhu ◽

Jiayi Wu

Keyword(s):

Breast Cancer ◽

Disease Free Survival ◽

Young Age ◽

Breast Cancer Subtypes ◽

Age At Diagnosis ◽

Free Survival ◽

Cancer Subtypes ◽

Premenopausal Patients ◽

Disease Free

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Evaluation of FGFR targeting in breast cancer through interrogation of patient-derived models

Breast Cancer Research ◽

10.1186/s13058-021-01461-4 ◽

2021 ◽

Vol 23 (1) ◽

Author(s):

Nicole J. Chew ◽

Terry C. C. Lim Kam Sian ◽

Elizabeth V. Nguyen ◽

Sung-Young Shin ◽

Jessica Yang ◽

...

Keyword(s):

Breast Cancer ◽

Therapeutic Target ◽

Breast Cancer Subtype ◽

Breast Cancer Subtypes ◽

Cancer Tissue ◽

Breast Cancers ◽

Luminal A ◽

Tissue Samples ◽

Cancer Subtypes ◽

Luminal B

Abstract Background Particular breast cancer subtypes pose a clinical challenge due to limited targeted therapeutic options and/or poor responses to the existing targeted therapies. While cell lines provide useful pre-clinical models, patient-derived xenografts (PDX) and organoids (PDO) provide significant advantages, including maintenance of genetic and phenotypic heterogeneity, 3D architecture and for PDX, tumor–stroma interactions. In this study, we applied an integrated multi-omic approach across panels of breast cancer PDXs and PDOs in order to identify candidate therapeutic targets, with a major focus on specific FGFRs. Methods MS-based phosphoproteomics, RNAseq, WES and Western blotting were used to characterize aberrantly activated protein kinases and effects of specific FGFR inhibitors. PDX and PDO were treated with the selective tyrosine kinase inhibitors AZD4547 (FGFR1-3) and BLU9931 (FGFR4). FGFR4 expression in cancer tissue samples and PDOs was assessed by immunohistochemistry. METABRIC and TCGA datasets were interrogated to identify specific FGFR alterations and their association with breast cancer subtype and patient survival. Results Phosphoproteomic profiling across 18 triple-negative breast cancers (TNBC) and 1 luminal B PDX revealed considerable heterogeneity in kinase activation, but 1/3 of PDX exhibited enhanced phosphorylation of FGFR1, FGFR2 or FGFR4. One TNBC PDX with high FGFR2 activation was exquisitely sensitive to AZD4547. Integrated ‘omic analysis revealed a novel FGFR2-SKI fusion that comprised the majority of FGFR2 joined to the C-terminal region of SKI containing the coiled-coil domains. High FGFR4 phosphorylation characterized a luminal B PDX model and treatment with BLU9931 significantly decreased tumor growth. Phosphoproteomic and transcriptomic analyses confirmed on-target action of the two anti-FGFR drugs and also revealed novel effects on the spliceosome, metabolism and extracellular matrix (AZD4547) and RIG-I-like and NOD-like receptor signaling (BLU9931). Interrogation of public datasets revealed FGFR2 amplification, fusion or mutation in TNBC and other breast cancer subtypes, while FGFR4 overexpression and amplification occurred in all breast cancer subtypes and were associated with poor prognosis. Characterization of a PDO panel identified a luminal A PDO with high FGFR4 expression that was sensitive to BLU9931 treatment, further highlighting FGFR4 as a potential therapeutic target. Conclusions This work highlights how patient-derived models of human breast cancer provide powerful platforms for therapeutic target identification and analysis of drug action, and also the potential of specific FGFRs, including FGFR4, as targets for precision treatment.

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Prognostic role of lymphovascular invasion and lymph node status among breast cancer subtypes

Journal of Medical Sciences ◽

10.4103/jmedsci.jmedsci_105_17 ◽

2018 ◽

Vol 38 (2) ◽

pp. 54 ◽

Cited By ~ 1

Author(s):

Jyh-Cherng Yu ◽

Guo-Shiou Liao ◽

Huan-Ming Hsu ◽

Chi-Hong Chu ◽

Zhi-Jie Hong ◽

...

Keyword(s):

Breast Cancer ◽

Lymph Node ◽

Lymphovascular Invasion ◽

Breast Cancer Subtypes ◽

Lymph Node Status ◽

Prognostic Role ◽

Cancer Subtypes ◽

Node Status

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Differences in clinicopatholgic characteristics and risk of mortality between the triple positive and ER+/PR+/HER2− breast cancer subtypes

Cancer Causes & Control ◽

10.1007/s10552-019-01152-8 ◽

2019 ◽

Vol 30 (5) ◽

pp. 417-424

Author(s):

Carol A. Parise ◽

Vincent Caggiano

Keyword(s):

Breast Cancer ◽

Breast Cancer Subtypes ◽

Cancer Subtypes ◽

Her2 Breast Cancer ◽

Risk Of Mortality

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Omega-3 fatty acids and ERPR(-) and HER2/neu(+/-) breast cancer prevention.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.tps1589 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. TPS1589-TPS1589

Author(s):

Chidimma Kalu ◽

Sarah Woelke ◽

Jianying Zhang ◽

Martha Belury ◽

Rulong Shen ◽

...

Keyword(s):

Breast Cancer ◽

Fatty Acids ◽

Adipose Tissue ◽

Fatty Acid ◽

Corn Oil ◽

Breast Cancer Subtypes ◽

Cancer Subtypes ◽

Her2 Breast Cancer ◽

Breast Adipose Tissue ◽

Breast Adipose

TPS1589 Background: The most aggressive breast cancer subtypes tend to be estrogen and progesterone receptor negative (ERPR(-)) and human epidermal growth factor receptor type 2 positive (HER2(+)). Women with these breast cancer subtypes (triple negative, ERPR(-)HER2(+)) tend to experience worse clinical outcomes and have a relatively higher risk of recurrence. Our previous research demonstrated that dietary omega-3 (n-3) fatty acids can significantly inhibit ERPR(-) HER2(+) tumorigenesis in MMTV-HER2/neu transgenic mice fed fish oil vs corn oil-based diets. The fish oil diet group developed 30% fewer breast tumors, had lower Ki67 expression, and experienced less mammary atypia relative to the corn oil diet group. Other studies involving diet, nutrition and breast cancer point to the potentially protective effect of an anti-inflammatory diet on the risk of developing ER(-) and HER2(+) breast cancer, further supporting the evidence that the ERPR(-), HER2(±) subtypes may be highly responsive to this bioactive nutrient. Methods: This is a double-blinded, randomized clinical trial of high dose (~5.4 g EPA+DHA) vs low dose (~0.9 g EPA+DHA in fatty acid mix of the typical American diet) of n-3 fatty acids in breast cancer survivors of ERPR(-), HER2(±) breast cancer. Eligible participants will take 5 capsules/day for 12 months, with cellular samples of breast epithelial and/or adipose tissue obtained by fine needle aspirations of the contralateral breast. The study aims to determine whether n-3 fatty acid supplementation will modify fatty acid metabolite content in breast adipose tissue, modulate cytomorphology and/or cell proliferation in breast epithelial cells, affect DNA methylation patterns, and modulate pro- vs anti-inflammatory gene expression patterns in breast adipose tissue. Correlative aims will evaluate possible associations between factors such as breast adipose tissue, red cell membrane fatty acid profiles, BMI, and reported dietary intake. Sample size of 40 participants per arm was calculated to provide at least 80% power to detect a statistically significant difference for each primary endpoint. This study focuses on women survivors of high risk breast cancer subtypes, specifically triple negative or ERPR(-)HER2(+) disease, who are currently without long term adjuvant options. Eligibility criteria include prior diagnosis of ERPR(-) stage 0 to III breast cancer, ≤5 years from completion of standard therapy.The study was closed to accrual in November 2018; less than 9 months of follow-up remain for active study participants. Clinical trial information: NCT02295059.

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