scholarly journals Biological and clinical impact of imbalanced progesterone receptor isoform ratios in breast cancer

2018 ◽  
Vol 25 (12) ◽  
pp. R605-R624 ◽  
Author(s):  
Caroline A Lamb ◽  
Victoria T Fabris ◽  
Britta M Jacobsen ◽  
Alfredo Molinolo ◽  
Claudia Lanari
Keyword(s):  
Breast Cancer ◽  
Current Knowledge ◽  
Hormone Replacement ◽  
Progesterone Receptors ◽  
Experimental Models ◽  
Breast Carcinogenesis ◽  
Breast Cancer Patients ◽  
Cognate Receptor ◽  
Estrogen Receptor Signaling ◽  
Cancer Models

There is a consensus that progestins and thus their cognate receptor molecules, the progesterone receptors (PRs), are essential in the development of the adult mammary gland and regulators of proliferation and lactation. However, a role for natural progestins in breast carcinogenesis remains poorly understood. A hint to that possible role came from studies in which the synthetic progestin medroxyprogesterone acetate was associated with an increased breast cancer risk in women under hormone replacement therapy. However, progestins have also been used for breast cancer treatment and to inhibit the growth of several experimental breast cancer models. More recently, PRs have been shown to be regulators of estrogen receptor signaling. With all this information, the question is how can we target PR, and if so, which patients may benefit from such an approach? PRs are not single unique molecules. Two main PR isoforms have been characterized, PRA and PRB, which exert different functions and the relative abundance of one isoform with respect to the other determines the response of PR agonists and antagonists. Immunohistochemistry with standard antibodies against PR do not discriminate between isoforms. In this review, we summarize the current knowledge on the expression of both PR isoforms in mammary glands, in experimental models of breast cancer and in breast cancer patients, to better understand how the PRA/PRB ratio can be exploited therapeutically to design personalized therapeutic strategies.

scholarly journals Antioxidants for the Treatment of Breast Cancer: Are We There Yet?

Antioxidants ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 205
Author(s):  
Carmen Griñan-Lison ◽  
Jose L. Blaya-Cánovas ◽  
Araceli López-Tejada ◽  
Marta Ávalos-Moreno ◽  
Alba Navarro-Ocón ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Oxidative Stress ◽  
Cancer Progression ◽  
Redox Homeostasis ◽  
Breast Carcinogenesis ◽  
Breast Cancer Patients ◽  
Chemopreventive Agents ◽  
Low Degree ◽  
Potential Use

Breast cancer is the most frequent cancer and the leading cause of cancer death in women. Oxidative stress and the generation of reactive oxygen species (ROS) have been related to cancer progression. Compared to their normal counterparts, tumor cells show higher ROS levels and tight regulation of REDOX homeostasis to maintain a low degree of oxidative stress. Traditionally antioxidants have been extensively investigated to counteract breast carcinogenesis and tumor progression as chemopreventive agents; however, there is growing evidence indicating their potential as adjuvants for the treatment of breast cancer. Aimed to elucidate whether antioxidants could be a reality in the management of breast cancer patients, this review focuses on the latest investigations regarding the ambivalent role of antioxidants in the development of breast cancer, with special attention to the results derived from clinical trials, as well as their potential use as plausible agents in combination therapy and their power to ameliorate the side effects attributed to standard therapeutics. Data retrieved herein suggest that antioxidants play an important role in breast cancer prevention and the improvement of therapeutic efficacy; nevertheless, appropriate patient stratification based on “redoxidomics” or tumor subtype is mandatory in order to define the dosage for future standardized and personalized treatments of patients.

scholarly journals Natural product like “shikonin” might be a hope for Breast cancer cure

2019 ◽  
Vol 2 (2) ◽  
pp. 14-18
Author(s):  
Md. Niuz Morshed Khan ◽  
Maidul Islam
Keyword(s):  
Breast Cancer ◽  
Effective Treatment ◽  
Estrogen Therapy ◽  
Future Research ◽  
Breast Cancer Patients ◽  
Developed Country ◽  
Estrogen Receptor Signaling ◽  
Life Threatening ◽  
Effective Treatment Regimen ◽  
Less Developed Country

AbstractAmong all cancers, breast cancer is the most commonly occurring cancer in women and the second most common cancer overall, both in the developed and less developed country. It is a matter of concern worldwide, that there is no effective drug is available for cancer treatment. Although, Surgery, radiation, hormonal (anti-estrogen) therapy, and chemotherapy are being used for treatment of breast cancer in recent years, due to life threatening side effects, these treatment approaches becoming more vulnerable. However, researchers from across the world searching a safe and effective treatment approach that can be a breakthrough for this situation, as it is evident that natural compounds like shikonin from Lithospermum erythrorhizon can fight against aggressiveness of breast cancer by regulating apoptosis, necroptosis and estrogen receptor signaling pathway. In this review, we discussed about potential green chemical compounds with their mechanisms of actions, which can be very effective treatment regimen for breast cancer and can be more potent by their proper modifications and further molecular research. Hopefully in future, research focusing on the “shikonin” will open a new door for increasing the survival rate of breast cancer patients as well as cancer cure.

scholarly journals Pathways to Breast Cancer Recurrence

ISRN Oncology ◽  
2013 ◽  
Vol 2013 ◽  
pp. 1-16 ◽  
Author(s):  
Aamir Ahmad
Keyword(s):  
Breast Cancer ◽  
Epithelial Mesenchymal Transition ◽  
Recurrent Disease ◽  
Current Knowledge ◽  
Cancer Recurrence ◽  
Breast Cancer Recurrence ◽  
Breast Cancer Patients ◽  
Mesenchymal Transition ◽  
Number Of Factors ◽  
Prevention Of Breast Cancer

Breast cancer remains a deadly disease, even with all the recent technological advancements. Early intervention has made an impact, but an overwhelmingly large number of breast cancer patients still live under the fear of “recurrent” disease. Breast cancer recurrence is clinically a huge problem and one that is largely not well understood. Over the years, a number of factors have been studied with an overarching aim of being able to prognose recurrent disease. This paper attempts to provide an overview of our current knowledge of breast cancer recurrence and its associated challenges. Through a survey of the literature on cancer stem cells (CSCs), epithelial-mesenchymal transition (EMT), various signaling pathways such as Notch/Wnt/hedgehog, and microRNAs (miRNAs), we also examine the hypotheses that are currently under investigation for the prevention of breast cancer recurrence.

scholarly journals The GATA3 X308_Splice breast cancer mutation is a hormone context-dependent oncogenic driver

Oncogene ◽  
2020 ◽  
Vol 39 (32) ◽  
pp. 5455-5467
Author(s):  
Natascha Hruschka ◽  
Mark Kalisz ◽  
Maria Subijana ◽  
Osvaldo Graña-Castro ◽  
Francisco Del Cano-Ochoa ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Progesterone Receptors ◽  
Transcriptional Response ◽  
Molecular Data ◽  
Fine Tuning ◽  
Driver Mutations ◽  
Breast Cancer Patients ◽  
Oncogenic Driver ◽  
Functional Analyses

Abstract As the catalog of oncogenic driver mutations is expanding, it becomes clear that alterations in a given gene might have different functions and should not be lumped into one class. The transcription factor GATA3 is a paradigm of this. We investigated the functions of the most common GATA3 mutation (X308_Splice) and five additional mutations, which converge into a neoprotein that we called “neoGATA3,” associated with excellent prognosis in patients. Analysis of available molecular data from >3000 breast cancer patients revealed a dysregulation of the ER-dependent transcriptional response in tumors carrying neoGATA3-generating mutations. Mechanistic studies in vitro showed that neoGATA3 interferes with the transcriptional programs controlled by estrogen and progesterone receptors, without fully abrogating them. ChIP-Seq analysis indicated that ER binding is reduced in neoGATA3-expressing cells, especially at distal regions, suggesting that neoGATA3 interferes with the fine tuning of ER-dependent gene expression. This has opposite outputs in distinct hormonal context, having pro- or anti-proliferative effects, depending on the estrogen/progesterone ratio. Our data call for functional analyses of putative cancer drivers to guide clinical application.

scholarly journals miRNAs in Health and Disease: A Focus on the Breast Cancer Metastatic Cascade towards the Brain

Cells ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 1790 ◽  
Author(s):  
Marta Sereno ◽  
Mafalda Videira ◽  
Imola Wilhelm ◽  
István A. Krizbai ◽  
Maria Alexandra Brito
Keyword(s):  
Breast Cancer ◽  
Target Genes ◽  
Current Knowledge ◽  
Survival Rates ◽  
Breast Cancer Patients ◽  
Aberrant Expression ◽  
Metastatic Cascade ◽  
Physiological Processes ◽  
Breast Cancer Brain Metastasis ◽  
Health And Disease

MicroRNAs (miRNAs) are small non-coding RNAs that mainly act by binding to target genes to regulate their expression. Due to the multitude of genes regulated by miRNAs they have been subject of extensive research in the past few years. This state-of-the-art review summarizes the current knowledge about miRNAs and illustrates their role as powerful regulators of physiological processes. Moreover, it highlights their aberrant expression in disease, including specific cancer types and the differential hosting-metastases preferences that influence several steps of tumorigenesis. Considering the incidence of breast cancer and that the metastatic disease is presently the major cause of death in women, emphasis is put in the role of miRNAs in breast cancer and in the regulation of the different steps of the metastatic cascade. Furthermore, we depict their involvement in the cascade of events underlying breast cancer brain metastasis formation and development. Collectively, this review shall contribute to a better understanding of the uniqueness of the biologic roles of miRNAs in these processes, to the awareness of miRNAs as new and reliable biomarkers and/or of therapeutic targets, which can change the landscape of a poor prognosis and low survival rates condition of advanced breast cancer patients.

Does progesterone protect from chemotherapy-induced peripheral neuropathy? A retrospective audit of breast cancer patients.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e11552-e11552
Author(s):  
Aruna Laxman Prabhu ◽  
Akshita Singh ◽  
Rucha Vishal Kaushik ◽  
Nita S. Nair ◽  
Rohini W Hawaldar ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Peripheral Neuropathy ◽  
Cancer Patients ◽  
Neuroprotective Effect ◽  
Menopausal Status ◽  
Continuous Variable ◽  
Experimental Models ◽  
Multivariate Logistic Regression Model ◽  
Breast Cancer Patients ◽  
Retrospective Audit

e11552 Background: Paclitaxel is an integral component of chemotherapy for breast cancer but its benefit comes at the risk of peripheral neuropathy. There are experimental models of peripheral nerve injury in which progesterone is protective, possibly through remyelination and other mechanisms. Methods: We evaluated the effect of menopausal status, as a surrogate for circulating progesterone levels, on the risk of developing paclitaxel induced peripheral neuropathy, in a retrospective audit of breast cancer patients. Patients who had received paclitaxel chemotherapy for breast cancer were characterized as having CIPN or not by clinical history/examination. Results: 256 women treated with paclitaxel at our institution were assessed for CIPN. Of these 133(52%) were premenopausal and 123(48%) postmenopausal at diagnosis. 22(8.6%) had preexisting diabetes mellitus. Of the 133 premenopausal women 97(72.9%) developed chemotherapy induced amenorrhea (CIA). The incidence of CIPN was 23.1% in persistently premenopausal patients 47.4% in patients with CIA and 57.7% in postmenopausal patients. In patients with DM 81.8% had CIPN. In a multivariate logistic regression model, increasing age (continuous variable RR=1.04 95%CI 1.02-1.08 p=0.001) DM (RR=4.39 95% CI 1.42-13.38 p=0.01) and postmenopausal/CIA status (RR=2.48 95% CI 1.05-5.88 p=0.03) were risk factors for CIPN. Because patients developed CIA at variable times and circulating progesterone levels at the time of neurotoxin insult maybe variable in them such patients were excluded in the second model, which included only patients with continuing menses (n=36) and postmenopausal at diagnosis (n=123). In the latter model postmenopausal status (RR=3.5 95%CI 1.18-10.39 p=0.02) and DM (RR=6.8 95%CI 1.44-31.82 p=0.01) were associated with CIPN but increasing age (RR=1.03 95% CI 0.98-1.07 p=0.21) was not. Conclusions: These results suggest a neuroprotective effect of premenopausal status, possibly related to higher circulating levels of progesterone. We hypothesize that progesterone administration prior to taxane chemotherapy may protect against CIPN. This will be tested in a RCT.

The effect on quality of life via bio-mimetic hormone replacement therapy for breast cancer patients.

2017 ◽  
Vol 35 (7_suppl) ◽  
pp. 113-113
Author(s):  
TS Wiley ◽  
Jason T. Haraldsen
Keyword(s):  
Breast Cancer ◽  
Quality Of Life ◽  
Hormone Replacement Therapy ◽  
Replacement Therapy ◽  
Hormone Replacement ◽  
Well Being ◽  
Post Treatment ◽  
Breast Cancer Patients ◽  
Long Term Study

113 Background: Many treatments for breast cancer block the estrogen receptors to reduce the risk of relapse. However, this treatment results in massive changes to the normal hormonal milieu. When the normal rhythmic hormonal patterns are disrupted, either through treatment or normal menopause, women typically experience a multitude of harsh symptoms with little affect on relapse rate. We set out to examine and evaluate the effects of estrogen (E2) and progesterone (P4) treatments via a bio-mimetic bio-identical hormone replacement therapy (BBHRT). We theorized, through the analysis of physiological and clinical literature, that the use BBHRT in the normal physiological pattern of reproductive women will lead to an increase of overall well-being and better quality of life for post-treatment and menopausal women, but does not increase their risk of breast cancer. Methods: E2 and P4 control over 9,000 different gene products and a disruption of these processes can lead to an increase in illnesses of aging including cancer. Through an evaluation of current literature, we theorize that a BBHRT approach utilizing E2 and P4 in a bio-mimetic manner to restore a woman’s body to normal hormonal levels can be achieved through twice-daily transdermal applications of hormonal creams with peaks in serum levels on days 12 and 21. The proposed method uses compounded, bio-identical hormones dosed to mimic the female reproductive cycle. Results: While this is a proposed clinical study, it is expected that women will experience resolution of menopausal and post-treatment symptoms, including better sleep, decreased migraines and incontinence, increased focus, and increased libido. By restoring the normal hormonal rhythm, it is anticipated that the body’s natural response elements will help restore both quality of life and well being, while also protecting from possible relapse. Conclusions: We propose a method to provide better quality of life and well being for women through BHRT that combines the use of E2 and P4 in a manner that mimics a woman’s normal reproductive levels. While a small long-term study of this method has shown promising results, we conclude that further, most detailed studies are still needed.

The impact of hormone replacement therapy on breast cancer patients' quality of life and sexuality: a pilot study

2001 ◽  
Vol 7 (2) ◽  
pp. 85-91 ◽  
Author(s):  
Jo Marsden ◽  
Michael Baum ◽  
Roger A'Hern ◽  
Andrea West ◽  
Lesley Fallowfield ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Quality Of Life ◽  
Hormone Replacement Therapy ◽  
Cancer Patients ◽  
Sexual Functioning ◽  
Hormone Replacement ◽  
Sexually Active ◽  
Breast Cancer Patients ◽  
Vaginal Dryness

Objective. The effect of hormone replacement therapy (HRT) on the sexual functioning and quality of life of breast cancer patients has not received significant attention. Study design. One hundred postmenopausal women with early stage breast cancer who were experiencing vasomotor symptoms and/or vaginal dryness participated in a randomised trial of HRT. Main outcome measures. Women completed questionnaires at three and six months to determine changes in their quality of life, vaginal dryness and sexual activity. Results. At baseline, 52% (49/94) of patients were sexually active. Lack of a partner was the main reason for sexual inactivity (38% (17/45)). HRT had no significant effect on the proportion of women complaining of vaginal dryness or the severity of this symptom. HRT did not increase the proportion of women who were sexually active (53%(43/81)) but was associated with non-significant trends for improvements in pleasure and reduction of discomfort during intercourse. Non-significant trends towards improvements in physical functioning, sleep disturbance and fatigue were observed with HRT. Patient numbers were too small to determine whether the concomitant use of tamoxifen influenced any of these outcomes. Conclusions. Lack of a significant improvement in quality of life with HRT may reflect the possibility that patient concern about HRT negated its symptomatic benefits. Failure of HRT to improve vaginal dryness may partly account for a lack of improvement in sexual functioning. There is a need for evaluation of interventions to improve sexual functioning in breast cancer patients but the use of hormonal therapy should be restricted to controlled trials.

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