The Evolving Role of the Estrogen Receptor Mutations in Endocrine Therapy-Resistant Breast Cancer

2017 ◽  
Vol 19 (5) ◽  
Author(s):  
Rinath Jeselsohn ◽  
Carmine De Angelis ◽  
Myles Brown ◽  
Rachel Schiff
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Endocrine Therapy

scholarly journals Regulatory Interplay between miR-181a-5p and Estrogen Receptor Signaling Cascade in Breast Cancer

Cancers ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 543
Author(s):  
Rosaria Benedetti ◽  
Chiara Papulino ◽  
Giulia Sgueglia ◽  
Ugo Chianese ◽  
Tommaso De Marchi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Endocrine Therapy ◽  
Mirna Expression ◽  
Estrogen Receptor Alpha ◽  
Estrogen Signaling ◽  
Integrated Analysis ◽  
Tumor Resistance ◽  
Estrogen Receptor Signaling

The efficacy and side effects of endocrine therapy in breast cancer (BC) depend largely on estrogen receptor alpha (ERα) expression, the specific drug administered, and treatment scheduling. Although the benefits of endocrine therapy outweigh any adverse effects in the initial stages of BC, later- or advanced-stage tumors acquire resistance to treatments. The mechanisms underlying tumor resistance to therapy are still not well understood, posing a major challenge for BC patient care. Epigenetic regulation and miRNA expression may be involved in the switch from a treatment-sensitive to a treatment-resistant state and could provide a valid therapeutic strategy for ERα negative BC. Here, a hybrid lysine-specific histone demethylase inhibitor, MC3324, displaying selective estrogen receptor down-regulator-like activities in BC, was used to highlight the interplay between epigenetic and ERα signaling. MC3324 anticancer action is mediated by microRNA (miRNA) expression regulation, indicating an innovative function for this molecule. Integrated analysis suggests a crosstalk between estrogen signaling, ERα interactors, miRNAs, and their putative targets. Specifically, miR-181a-5p expression is regulated by MC3324 and has an impact on cellular levels of ERα. A comparison of breast tumor versus healthy mammary tissues confirmed the important role of miR-181a-5p in ERα regulation and points to its putative predictive function in BC therapy.

The role of chemotherapy in hormone receptor-positive and HER2-positive breast cancer patients over age 70.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e12511-e12511
Author(s):  
Vincent Caggiano ◽  
Carol Parise
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Cancer Patients ◽  
Endocrine Therapy ◽  
Breast Cancer Patients ◽  
Her2 Positive ◽  
Her2 Positive Breast Cancer ◽  
Risk Of Mortality ◽  
Positive Breast Cancer

e12511 Background: Standard adjuvant therapy for HER2 positive female breast cancer patients that are estrogen receptor (ER) positive is chemotherapy, trastuzumab, and endocrine therapy. For patients older than 70 years of age, the combination of chemotherapy and trastuzumab may increase the toxicity profile. The purpose of this study was to evaluate the role of chemotherapy in for the ER+/PR+/HER- and ER+/PR+/HER+ subtypes in patients over age 70. These subtypes differ only by HER2 status. Methods: We identified 13,167 cases of patients over age 70 with stages 1-3 first primary invasive breast cancer from the California Cancer Registry diagnosed between January 1, 2000 and December 31, 2010. Of these, 9,710 were ER+/PR+/HER- and 988 were ER+/PR+/HER+. Cox regression analysis adjusted for race/ethnicity, socioeconomic status, grade, and year of diagnosis was used to compare risk of mortality for combination endocrine and chemotherapy versus endocrine therapy alone. Analyses were conducted separately for each stage. Results: For the ER+/PR+/HER- subtype, there was no difference in the risk of mortality for patients given endocrine and chemotherapy versus endocrine therapy alone for stages 1 and 2. For stage 3, there was a 57% reduced risk of mortality (HR = 0.43; 95%CI: 0.27-0.69) for patients given combination chemo and endocrine therapy. For the ER+/PR+/HER+ subtype, there were no differences in risk of mortality in any stage due to treatment. Conclusions: With the exception of stage 3 patients with the ER+/PR+/HER- subtype, chemotherapy appears to add little or no benefit to risk of mortality for patients over 70 years of age. These results support the use of endocrine therapy and anti-HER2 therapy without chemotherapy in elderly patients with early stage, estrogen receptor positive, HER2 positive breast cancer.

Optimal Management of the Premenopausal Patient with Estrogen Receptor–Positive Breast Cancer

2014 ◽  
pp. e12-e15 ◽  
Author(s):  
Aleksander Chojecki ◽  
Serena Wong ◽  
Deborah Toppmeyer
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Endocrine Therapy ◽  
Ovarian Function ◽  
Premenopausal Women ◽  
Standard Of Care ◽  
Sole Source ◽  
Estrogen Receptor Positive ◽  
Function Interpretation

Tamoxifen is the standard of care in the adjuvant treatment of premenopausal women with estrogen receptor–positive (ER+) breast cancer. Ovarian suppression (OS) is another method of endocrine therapy and has been shown to decrease the risk of recurrence and confer a survival advantage when used as the sole source of hormone therapy. However, there is no evidence that OS is superior to treatment with tamoxifen. Studies comparing OS with or without tamoxifen compared with chemotherapy have demonstrated comparable effects. There does not appear to be any additional benefit when OS is combined with chemotherapy, although there is a suggestion that there may be an effect in the subgroup of young women (aged younger than 40 years) who are least likely to experience chemotherapy-induced cessation of ovarian function. Interpretation of existing data is hampered by the lack of studies incorporating modern chemotherapy regimens and the absence of molecular analyses that would allow us to better define populations most likely to benefit from endocrine therapy. Last, the role of aromatase inhibitors (AI) in the premenopausal setting remains undefined. Two recent studies, SOFT and TEXT, aim to shed light on the effect of OS and AI in premenopausal ER+ breast cancer and are pending analysis.

Endocrine Treatment of Breast Cancer: Current Perspectives, Future Directions

2017 ◽  
Vol 8 (03) ◽  
Author(s):  
Tazia Irfan ◽  
Mainul Haque ◽  
Sayeeda Rahman ◽  
Russell Kabir ◽  
Nuzhat Rahman ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Endocrine Therapy ◽  
Ovarian Function ◽  
Premenopausal Women ◽  
New Drugs ◽  
Effective Control ◽  
Endocrine Treatment ◽  
Estrogen Production ◽  
Hormone Sensitive

Breast cancer remains one of the major causes of death in women, and endocrine treatment is currently one of the mainstay of treatment in patients with estrogen receptor positive breast cancer. Endocrine therapy either slows down or stops the growth of hormone-sensitive tumors by blocking the body’s capability to yield hormones or by interfering with hormone action. In this paper, we intended to review various approaches of endocrine treatments for breast cancer highlighting successes and limitations. There are three settings where endocrine treatment of breast cancer can be used: neoadjuvant, adjuvant, or metastatic. Several strategies have also been developed to treat hormone-sensitive breast cancer which include ovarian ablation, blocking estrogen production, and stopping estrogen effects. Selective estrogen-receptor modulators (SERMs) (e.g. tamoxifen and raloxifene), aromatase inhibitors (AIs) (e.g. anastrozole, letrozole and exemestane), gonadotropin-releasing hormone agonists (GnRH) (e.g. goserelin), and selective estrogen receptor downregulators (SERDs) (e.g. fulvestrant) are currently used drugs to treat breast cancer. Tamoxifen is probably the first targeted therapy widely used in breast cancer treatment which is considered to be very effective as first line endocrine treatment in previously untreated patients and also can be used after other endocrine therapy and chemotherapy. AIs inhibit the action of enzyme aromatase which ultimately decrease the production of estrogen to stimulate the growth of ER+ breast cancer cells. GnRH agonists suppress ovarian function, inducing artificial menopause in premenopausal women. Endocrine treatments are cheap, well-tolerated and have a fixed single daily dose for all ages, heights and weights of patients. Endocrine treatments are not nearly as toxic as chemotherapy and frequent hospitalization can be avoided. New drugs in preliminary trials demonstrated the potential for improvement of the efficacy of endocrine therapy including overcoming resistance. However, the overall goals for breast cancer including endocrine therapy should focus on effective control of cancer, design personalized medical therapeutic approach, increase survival time and quality of life, and improve supportive and palliative care for end-stage disease.

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