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.

Evaluation of Adjuvant! Online to predict the effect of optimal endocrine therapy (ovarian function suppression plus tamoxifen) for premenopausal breast cancer patients with estrogen-receptor-positive breast cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 585-585
Author(s):  
R. J. Paridaens ◽  
S. Gelber ◽  
B. F. Cole ◽  
R. D. Gelber ◽  
B. Thürlimann ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Endocrine Therapy ◽  
Ovarian Function ◽  
Premenopausal Women ◽  
Free Survival ◽  
Ovarian Function Suppression ◽  
Estrogen Receptor Positive ◽  
Chemoendocrine Therapy ◽  
Positive Breast Cancer

585 Background: Adjuvant! Online (AOL) is a user-friendly, web-based tool that provides estimates of adjuvant therapy outcomes for individual patients. While reliable evidence underpins estimates for most patient cohorts, there is a paucity of data on the effect of adding chemotherapy to complete estrogen blockade for premenopausal women with estrogen-receptor positive breast cancer. Methods: International Breast Cancer Study Group (IBCSG) Trial 11–93 enrolled 174 premenopausal women with estrogen-receptor positive, node-positive breast cancer from 1993 to 1998. Fifty percent of patients had 1 positive axillary lymph node and 97% had between 1 and 3 positive nodes. Patients were randomized to receive ovarian function suppression plus five years of tamoxifen with or without chemotherapy. The estimated hazard rates and corresponding 10-year relapse-free survival percents obtained from Trial 11–93 data (Breast Cancer Res Treat. 2009;113:137–144) were compared with those predicted using AOL. Results: The 10-year relapse-free survival percents predicted from AOL were 64.4% (95% CI, 61.9% to 67.2%) for endocrine therapy alone and 74.9% (95% CI, 73.1% to 76.8%) for chemoendocrine therapy. By contrast, these estimates in Trial 11–93 were 76.4% (95% CI, 65.8% to 84.0%) for endocrine therapy alone and 74.9% (95% CI, 64.5% to 82.7%) for chemoendocrine therapy. The AOL estimate for the endocrine alone control group is lower than that observed in Trial 11–93 (p = 0.03), while the estimates for the two chemoendocrine therapy groups are similar. Conclusions: AOL appears to underestimate the effectiveness of adjuvant endocrine therapy alone for premenopausal women with endocrine responsive breast cancer, thus overestimating the added benefit - if any - from chemotherapy for this patient population. Prospective clinical trials addressing the question are warranted. No significant financial relationships to disclose.

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.

scholarly journals International Breast Cancer Study Group (IBCSG)

2006 ◽  
Vol 9 (S1) ◽  
pp. 226-280
Author(s):  
Keyword(s):  
Breast Cancer ◽  
Adjuvant Therapy ◽  
Endocrine Therapy ◽  
Ovarian Function ◽  
Premenopausal Women ◽  
Phase Iii ◽  
Phase Iii Trial ◽  
Node Positive ◽  
Positive Breast Cancer

This section provides current contact details and a summary of recent or ongoing clinical trials being coordinated by International Breast Cancer Study Group (IBCSG). Clinical trials include: CMF with or without prednisone for pre/perimenopausal patients with breast cancer and 1–3 positive nodes. Ludwig/IBCSG Trial ICMF + prednisone combined with or without oophorectomy for pre/perimenopausal patients with breast cancer and 4 or more positive nodes. Ludwig/IBCSG Trial IIAdjuvant therapy for postmenopausal elderly patients (older than 65): observation versus prednisone tamoxifen. Ludwig/IBCSG Trial IIIAdjuvant therapy for postmenopausal, 65 years or younger, node-positive breast cancer patients: observation versus prednisone + tamoxifen versus CMF + prednisone + tamoxifen. Ludwig/IBCSG Trial IVAdjuvant perioperative chemotherapy. Ludwig/IBCSG Trial VAdjuvant therapy in node-positive pre/perimenopausal breast cancer patients: CMF 3 versus 6 with or without reintroduction of chemotherapy. IBCSG Trial VIAdjuvant chemotherapy in node-positive postmenopausal breast cancer patients: endocrine versus chemo-endocrine versus chemo-endocrine with delayed chemotherapy. IBCSG Trial VIIAdjuvant therapy in pre- and perimenopausal patients with node-negative breast cancer. Observation versus LH-RH analogue versus CMF versus CMF + LN-RH analogue. IBCSG Trial VIIIAdjuvant therapy in postmenopausal patients with node-negative breast cancer. Tamoxifen versus CMF followed by tamoxifen. IBCSG Trial IXSurgical therapy with or without axillary node clearance for breast cancer in elderly patients who receive adjuvant therapy with tamoxifen. IBCSG Trial 10–93Adjuvant therapy for premenopausal patients with node-positive breast cancer who are suitable for endocrine therapy alone. IBCSG Trial 11–93Adjuvant therapy for post/perimenopausal patients with node-positive breast cancer who have estrogen-receptor-positive tumors. IBCSG Trial 12–93Adjuvant therapy for premenopausal patients with node-positive breast cancer who are not suitable for endocrine therapy alone. IBCSG Trial 13–93Adjuvant therapy for post perimenopausal patients with node-positive breast cancer who are not suitable for endocrine therapy alone. IBCSG Trial 14–93High dose EC × 3 supported by PBSC versus EC/AC × 4 followed by CMF as adjuvant treatment for high-risk operable Stage II and Stage III breast cancer in premenopausal and young postmenopausal (<65 years) patients. IBCSG Trial 15–95Adjuvant therapy for postmenopausal patients with operable breast cancer who have estrogen-receptor or progesterone-receptor-positive tumors. Tamoxifen versus letrozole versus tamoxifen followed by letrozole versus letrozole followed by tamoxifen. BIG 1–98 / IBCSG Trial 18–98Maintenance chemotherapy in hormone non-responsive breast cancer: low-dose cytotoxics as “anti-angiogenesis treatment” following adjuvant induction chemotherapy for patients with ER-negative and PgR-negative breast cancer. IBCSG Trial 22–00A randomized trial of axillary dissection versus no axillary dissection for patients with clinically node-negative breast cancer and micrometastases in the sentinel node. IBCSG Trial 23–01Suppression of Ovarian Function Trial (SOFT). A Phase III trial evaluating the role of ovarian function suppression (OFS) and the role of exemestane as adjuvant therapies for premenopausal women with endocrine-responsive breast cancer. Tamoxifen versus OFS + tamoxifen versus OFS + exemestane. BIG 2–02/IBCSG Trial 24–02Tamoxifen and Exemestane Trial (TEXT). A Phase III trial evaluating the role of exemestane plus GnRH analogue as adjuvant therapy for premenopausal women with endocrine-responsive breast cancer. Ovarian function suppression + tamoxifen versus ovarian function suppression + exemestane. BIG 3–02/IBCSG Trial 25–02Premenopausal Endocrine Responsive Chemotherapy Trial (PERCHE) A Phase III trial evaluating the role of chemotherapy as adjuvant therapy for premenopausal women with endocrine-responsive breast cancer who receive endocrine therapy.Chemotherapy + OFS + tamoxifen/exemestane versus OFS + tamoxifen/ exemestane. BIG 4–02/IBCSG Trial 26–02Chemotherapy for radically resected loco-regional relapse. BIG 1-02/IBCSG Trial 27–02/NSABP Protocol B-37Chemotherapy adjuvant study for women at advanced Age (CASA) Phase III trial evaluating the role of adjuvant pegylated liposomal doxorubicin (PLD) for women (age 66 years or older) with endocrine non-responsive breast cancer who are not suitable for being offered a “standard chemotherapy regimen”. BIG 1–05/IBCSG Trial 32–05

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.

scholarly journals The Modern Landscape of Endocrine Therapy for Premenopausal Women with Breast Cancer

Breast Care ◽  
2015 ◽  
Vol 10 (5) ◽  
pp. 312-315 ◽  
Author(s):  
Lorenzo Rossi ◽  
Olivia Pagani
Keyword(s):  
Breast Cancer ◽  
Endocrine Therapy ◽  
Ovarian Function ◽  
Treatment Options ◽  
Endocrine Resistance ◽  
Premenopausal Women ◽  
New Drugs ◽  
Fine Tuning ◽  
Individual Risk ◽  
Ovarian Function Suppression

The optimal endocrine therapy for premenopausal women with early and advanced breast cancer still remains an important and controversial issue. For over 30 years, tamoxifen has been the gold standard in the adjuvant setting. New therapeutic options, such as the addition of ovarian function suppression to oral endocrine therapy (either tamoxifen or aromatase inhibitors), can improve outcomes over tamoxifen alone in well-selected patients. Treatment duration has also been revisited, and extended therapy is becoming a new standard of care, especially in high-risk patients. Endocrine therapy for advanced disease still represents a challenge and a research priority. New drugs and combinations able to overcome endocrine resistance are at the horizon, and their role in premenopausal women should be better elucidated. Side effects and quality of life (including family planning considerations) play an important role in treatment selection and in the patients' treatment adherence and should always be discussed before start of treatment. The paper will specifically focus on how to integrate all new treatment options in the current armamentarium of endocrine therapy of premenopausal women, with the aim of best fine-tuning treatment selections according to the individual risk/benefit evaluation.

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