Regulation of estradiol synthesis by aromatase interacting partner (AIPB)

2021 ◽  
Author(s):  
Himangshu S. Bose ◽  
Randy M. Whittal ◽  
Curtis E. Lanier ◽  
Brendan Marshall ◽  
Maheshinie Rajapaksha ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Sex Characteristics ◽  
Early Event ◽  
Aromatase Activity ◽  
Breast Cancer Patients ◽  
Over Expression ◽  
Increased Risk ◽  
Binding Antibody ◽  
Estradiol Synthesis ◽  
Breast Tissues

Estradiol is essential for the development of female sex characteristics and fertility. Postmenopausal women and breast cancer patients have high estradiol. Aromatase catalyzes estradiol synthesis; however, the factors regulating aromatase activity are unknown. We identified a new 22-kDa protein, aromatase interacting partner in breast (AIPB), from the endoplasmic reticulum of human breast tissue. AIPB expression is reduced in tumorigenic breast and further reduced in triple negative tumors. Like aromatase, AIPB expression is induced by nonsteroidal estrogen. We found that AIPB and aromatase interact in nontumorigenic and tumorigenic breast tissues and cells. Conditional AIPB over expression decreased estradiol and blocking AIPB availability with an AIPB binding antibody increased estradiol in tumorigenic cells. Estradiol synthesis is highly increased in AIPB knockdown cells, suggesting that the newly identified AIPB protein is important for aromatase activity and a key modulator of estradiol synthesis. Thus, a change in AIPB protein expression may represent an early event in tumorigenesis and be predictive of an increased risk of developing breast cancer.

scholarly journals Local Biomarkers Involved in the Interplay between Obesity and Breast Cancer

Cancers ◽  
2021 ◽  
Vol 13 (24) ◽  
pp. 6286
Author(s):  
Jonas Busk Holm ◽  
Ann H. Rosendahl ◽  
Signe Borgquist
Keyword(s):  
Breast Cancer ◽  
Adipose Tissue ◽  
Current Knowledge ◽  
Local Environment ◽  
Aromatase Activity ◽  
Breast Cancer Patients ◽  
Increased Risk ◽  
Breast Adipose Tissue ◽  
Breast Adipose ◽  
Inflammatory State

Obesity is associated with an increased risk of breast cancer, which is the most common cancer in women worldwide (excluding non-melanoma skin cancer). Furthermore, breast cancer patients with obesity have an impaired prognosis. Adipose tissue is abundant in the breast. Therefore, breast cancer develops in an adipose-rich environment. During obesity, changes in the local environment in the breast occur which are associated with breast cancer. A shift towards a pro-inflammatory state is seen, resulting in altered levels of cytokines and immune cells. Levels of adipokines, such as leptin, adiponectin, and resistin, are changed. Aromatase activity rises, resulting in higher levels of potent estrogen in the breast. Lastly, remodeling of the extracellular matrix takes place. In this review, we address the current knowledge on the changes in the breast adipose tissue in obesity associated with breast cancer initiation and progression. We aim to identify obesity-associated biomarkers in the breast involved in the interplay between obesity and breast cancer. Hereby, we can improve identification of women with obesity with an increased risk of breast cancer and an impaired prognosis. Studies investigating mammary adipocytes and breast adipose tissue in women with obesity versus women without obesity are, however, sparse and further research is needed.

Prognostic significance of HER-2/neu over-expression on the incidence of brain metastasis in newly diagnosed breast cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 649-649 ◽  
Author(s):  
B. S. Abdulkarim ◽  
Z. Gabos ◽  
R. Sinha ◽  
J. Hanson ◽  
N. Chauhan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Tumor Size ◽  
Univariate Analysis ◽  
Prognostic Significance ◽  
Newly Diagnosed ◽  
Breast Cancer Patients ◽  
Over Expression ◽  
Increased Risk ◽  
Her 2

649 Background: As systemic therapy improves, brain metastases (BM) from breast cancer are becoming increasingly evident. An increased risk of BM in HER-2/neu over-expressing metastatic breast cancer patients has been suggested. However, the relationship between HER-2/neu over-expression and the risk of BM in newly diagnosed breast cancer patients is unknown. Methods: To determine incidence of BM in HER-2/neu over-expressing breast cancer patients, a cohort of patients between 01/1998 and 12/2003 with uniform HER-2/neu testing were identified from a cancer registry. A total of 460 patients with HER-2/neu over-expression and 500 patients with HER-2/neu negative disease were reviewed. Patients were excluded if there was breast cancer diagnosed before 01/1998 or others cancer. A total of 301 HER-2/neu over-expressing and 363 HER-2/neu negative patients were included for this analysis. The association between histological features and the occurrence of BM were evaluated with univariate and multivariate analyses. Results: BM were identified in 8% (24 patients) of HER-2/neu over-expressing breast cancer patients compared to only 1.7% (6 patients) in the HER-2/neu negative patients (hazard ratio 5.15 [2.079–12.78], p=0.0001). In patients with recurrent disease, the proportion of BM for HER-2/neu over-expressing patients was 24% compared to 10% in HER-2/neu negative patients. HER-2/neu over-expression, tumor size >2cm, ≥ 4 nodes positive and grade 2/3 were predictors of BM in univariate analysis. In multivariate analysis, HER-2/neu over-expression and tumor size>2cm were an independent prognostic factors for the development of BM, while hormone receptors expressions was protective (p=0.02). Conclusions: Our population based study show that newly diagnosed HER-2/neu over-expressing breast cancer patients are at significantly increased risk for BM. As most BM occur in HER-2/neu over-expressing patients with systemic metastatic disease, these findings could prompt consideration of brain prophylaxis strategies and/or serial radiologic screening to detect asymptomatic BM. No significant financial relationships to disclose.

ER, PR & HER2 Receptor status in recurrent breast cancer: Its relation to age & time of recurrence

2020 ◽  
Vol 22 (1) ◽  
pp. 16-20
Author(s):  
Abu Khaled Muhammad Iqbal ◽  
Nasima Akhter ◽  
Hasan Shahrear Ahmed ◽  
Md Rassell ◽  
AMM Yahia ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Treatment Approach ◽  
Recurrent Breast Cancer ◽  
Breast Cancer Patients ◽  
Her2 Receptor ◽  
Younger Patients ◽  
Receptor Status ◽  
Increased Risk ◽  
Neoplastic Lesions ◽  
Recurrent Breast

Background: Malignant neoplastic lesions of the breast are one of the main causes of cancer death among women. In tumor cells the expression status of Estrogen receptor (ER), progesterone receptor (PR), and c-ERBB2 (HER2/neu) are therapeutically and prognostically important markers affecting the treatment approach, management and prognosis of breast carcinoma. Objective: To explore the relation of receptor status in recurrent breast cancer to age and time of recurrence. Methods: This study was conducted in National Institute of Cancer Research and Hospital (NICRH) and included 81 female patients between 20 to 75 years with recurrent breast cancer. Detection of receptor status of ER +ve/-ve, PR +ve/-ve, Her-2+ve/-ve was based on the immunohistochemistry staining of tissue samples of malignant neoplastic lesions prepared from tissue biopsies of patients with recurrent breast cancer. All the information were recorded through the pre-structured data collection sheet and analyzed. Results: This study showed that most of the recurrent breast cancer patients were Triple negative breast cancer (TNBC) (39.5%) and among them most of them were younger patients. Younger patients with TNBC had increased risk of recurrence. Most of the recurrence occurred within 1-2 years. Conclusion: It can be concluded that the assessment of the expression of these biornarkers in recurrent tumors provides reliable information for the treatment approach of locoregional tumors. Journal of Surgical Sciences (2018) Vol. 22 (1): 16-20

scholarly journals An Exploration of Heart Failure Risk in Breast Cancer Patients Receiving Anthracyclines with or without Trastuzumab in Thailand: A Retrospective Study

2021 ◽  
Vol 11 (3) ◽  
pp. 484-493
Author(s):  
Jukapun Yoodee ◽  
Aumkhae Sookprasert ◽  
Phitjira Sanguanboonyaphong ◽  
Suthan Chanthawong ◽  
Manit Seateaw ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Risk Factors ◽  
Cancer Patients ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Breast Cancer Patients ◽  
Ventricular Ejection Fraction ◽  
Factors Associated ◽  
Palliative Intent ◽  
Increased Risk

Anthracycline-based regimens with or without anti-human epidermal growth factor receptor (HER) 2 agents such as trastuzumab are effective in breast cancer treatment. Nevertheless, heart failure (HF) has become a significant side effect of these regimens. This study aimed to investigate the incidence and factors associated with HF in breast cancer patients treated with anthracyclines with or without trastuzumab. A retrospective cohort study was performed in patients with breast cancer who were treated with anthracyclines with or without trastuzumab between 1 January 2014 and 31 December 2018. The primary outcome was the incidence of HF. The secondary outcome was the risk factors associated with HF by using the univariable and multivariable cox-proportional hazard model. A total of 475 breast cancer patients were enrolled with a median follow-up time of 2.88 years (interquartile range (IQR), 1.59–3.93). The incidence of HF was 3.2%, corresponding to an incidence rate of 11.1 per 1000 person-years. The increased risk of HF was seen in patients receiving a combination of anthracycline and trastuzumab therapy, patients treated with radiotherapy or palliative-intent chemotherapy, and baseline left ventricular ejection fraction <65%, respectively. There were no statistically significant differences in other risk factors for HF, such as age, cardiovascular comorbidities, and cumulative doxorubicin dose. In conclusion, the incidence of HF was consistently high in patients receiving combination anthracyclines trastuzumab regimens. A reduced baseline left ventricular ejection fraction, radiotherapy, and palliative-intent chemotherapy were associated with an increased risk of HF. Intensive cardiac monitoring in breast cancer patients with an increased risk of HF should be advised to prevent undesired cardiac outcomes.

Repression of protocadherin 17 is correlated with elevated angiogenesis and hypoxia markers in female patients with breast cancer

2021 ◽  
pp. 1-10
Author(s):  
Sanaa A. El-Benhawy ◽  
Samia A. Ebeid ◽  
Nadia A. Abd El Moneim ◽  
Rabie R. Abdel Wahed ◽  
Amal R.R. Arab
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Clinical Stage ◽  
Suppressor Gene ◽  
Normal Breast ◽  
Vital Role ◽  
Control Group ◽  
Breast Cancer Patients ◽  
Cd34 Cells ◽  
Breast Tissues

BACKGROUND: Altered cadherin expression plays a vital role in tumorigenesis, angiogenesis and tumor progression. However, the function of protocadherin 17 (PCDH17) in breast cancer remains unclear. OBJECTIVE: Our target is to explore PCDH17 gene expression in breast carcinoma tissues and its relation to serum angiopoietin-2 (Ang-2), carbonic anhydrase IX (CAIX) and % of circulating CD34+ cells in breast cancer patients (BCPs). METHODS: This study included Fifty female BCPs and 50 healthy females as control group. Cancerous and neighboring normal breast tissues were collected from BCPs as well as blood samples at diagnosis PCDH17 gene expression was evaluated by RT-PCR. Serum Ang-2, CAIX levels were measured by ELISA and % CD34+ cells were assessed by flow cytometry. RESULTS: PCDH17 was downregulated in cancerous breast tissues and its repression was significantly correlated with advanced stage and larger tumor size. Low PCDH17 was significantly correlated with serum Ang-2, % CD34+ cells and serum CAIX levels. Serum CAIX, Ang-2 and % CD34+ cells levels were highly elevated in BCPs and significantly correlated with clinical stage. CONCLUSIONS: PCDH17 downregulation correlated significantly with increased angiogenic and hypoxia biomarkers. These results explore the role of PCDH17 as a tumor suppressor gene inhibiting tumor growth and proliferation.

scholarly journals Characterisation of protein-truncating and missense variants in PALB2 in 15 768 women from Malaysia and Singapore

2021 ◽  
pp. jmedgenet-2020-107471
Author(s):  
Pei Sze Ng ◽  
Rick ACM Boonen ◽  
Eldarina Wijaya ◽  
Chan Eng Chong ◽  
Milan Sharma ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Rare Variants ◽  
Embryonic Stem ◽  
Mouse Embryonic Stem Cell ◽  
Population Based ◽  
Breast Cancer Patients ◽  
Dna Double Strand Breaks ◽  
Functional Impact ◽  
Missense Variants ◽  
Increased Risk

BackgroundRare protein-truncating variants (PTVs) in partner and localiser of BRCA2 (PALB2) confer increased risk to breast cancer, but relatively few studies have reported the prevalence in South-East Asian populations. Here, we describe the prevalence of rare variants in PALB2 in a population-based study of 7840 breast cancer cases and 7928 healthy Chinese, Malay and Indian women from Malaysia and Singapore, and describe the functional impact of germline missense variants identified in this population.MethodsMutation testing was performed on germline DNA (n=15 768) using targeted sequencing panels. The functional impact of missense variants was tested in mouse embryonic stem cell based functional assays.ResultsPTVs in PALB2 were found in 0.73% of breast cancer patients and 0.14% of healthy individuals (OR=5.44; 95% CI 2.85 to 10.39, p<0.0001). In contrast, rare missense variants in PALB2 were not associated with increased risk of breast cancer. Whereas PTVs were associated with later stage of presentation and higher-grade tumours, no significant association was observed with missense variants in PALB2. However, two novel rare missense variants (p.L1027R and p.G1043V) produced unstable proteins and resulted in a decrease in homologous recombination-mediated repair of DNA double-strand breaks.ConclusionDespite genetic and lifestyle differences between Asian and other populations, the population prevalence of PALB2 PTVs and associated relative risk of breast cancer, are similar to those reported in European populations.

scholarly journals Real-world safety of palbociclib in breast cancer patients in the United States: a new user cohort study

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Daniel C. Beachler ◽  
Cynthia de Luise ◽  
Aziza Jamal-Allial ◽  
Ruihua Yin ◽  
Devon H. Taylor ◽  
...  
Keyword(s):  
Breast Cancer ◽  
United States ◽  
Pulmonary Embolism ◽  
Cohort Study ◽  
Real World ◽  
The United States ◽  
Elevated Risk ◽  
Breast Cancer Patients ◽  
Increased Risk ◽  
Serious Infections

Abstract Background There is limited real-world safety information on palbociclib for treatment of advanced stage HR+/HER2- breast cancer. Methods We conducted a cohort study of breast cancer patients initiating palbociclib and fulvestrant from February 2015 to September 2017 using the HealthCore Integrated Research Database (HIRD), a longitudinal claims database of commercial health plan members in the United States. The historical comparator cohort comprised patients initiating fulvestrant monotherapy from January 2011 to January 2015. Propensity score matching and Cox regression were used to estimate hazard ratios for various safety events. For acute liver injury (ALI), additional analyses and medical record validation were conducted. Results There were 2445 patients who initiated palbociclib including 566 new users of palbociclib-fulvestrant, and 2316 historical new users of fulvestrant monotherapy. Compared to these historical new users of fulvestrant monotherapy, new users of palbociclib-fulvestrant had a greater than 2-fold elevated risk for neutropenia, leukopenia, thrombocytopenia, stomatitis and mucositis, and ALI. Incidence of anemia and QT prolongation were more weakly associated, and incidences of serious infections and pulmonary embolism were similar between groups after propensity score matching. After adjustment for additional ALI risk factors, the elevated risk of ALI in new users of palbociclib-fulvestrant persisted (e.g. primary ALI algorithm hazard ratio (HR) = 3.0, 95% confidence interval (CI) = 1.1–8.4). Conclusions This real-world study found increased risks of several adverse events identified in clinical trials, including neutropenia, leukopenia, and thrombocytopenia, but no increased risk of serious infections or pulmonary embolism when comparing new users of palbociclib-fulvestrant to fulvestrant monotherapy. We observed an increased risk of ALI, extending clinical trial findings of significant imbalances in grade 3/4 elevations of alanine aminotransferase (ALT).

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