scholarly journals Extended endocrine therapy in early breast cancer: how long and who for?

2020 ◽  
Vol 16 (1) ◽  
pp. 4327-4336
Author(s):  
John R Benson ◽  
Ismail Jatoi

Endocrine therapy for early stage breast cancer is currently in a state of flux with much uncertainty about choice of agents and duration of therapy. The standard treatment span of 5 years usually incorporates an aromatase inhibitor in the majority of postmenopausal patients. Hormonal therapy has a cytostatic action that provides a biological rationale for continuing treatment for more prolonged periods to reduce risk of late recurrence in estrogen receptor-positive disease. Several trials of extended endocrine therapy for periods varying from 7.5 to 10 years have shown mixed results for gains in disease-free survival. The challenge is to assimilate available data and apply clinical judgment to tailor therapies taking account of intrinsic risk of disease recurrence, patient preference, tolerability to date, and co-morbidities.

2018 ◽  
Vol 10 ◽  
pp. 175883591877743 ◽  
Author(s):  
Elisabetta Munzone ◽  
Marco Colleoni

Patients with early estrogen receptor-positive breast cancer are at continuous risk of relapse even after more than 10 years of follow up. Currently, no biomarker that identifies patients for early versus late recurrence, or one that selects patients or tumors for longer versus shorter durations of endocrine therapy (ET) is available and a crucial question is how to properly select patients who could be spared extended ET or those who require it. In the last 20 years more than 40,000 women were enrolled in randomized trials to answer the question of optimal duration of ET. According to the results of these studies extended adjuvant ET is more effective than standard 5 years of adjuvant ET. Extended ET in patients who remain premenopausal after 5 years of adjuvant tamoxifen is still tamoxifen for another 5 years. Extended ET with aromatase inhibitors (AIs) should be offered to postmenopausal women with substantial residual risk of relapse after completing 5 years of tamoxifen therapy. Extension of AI treatment to 10 years resulted in significantly better 5-year disease-free survival including disease recurrence local/distant or the occurrence of contralateral breast cancer events. Currently, new therapeutic targets are under investigation, but the beneficial effect of prolonged treatment for high-risk patients, identified by using multigenomic tests, remains unclear. Thus, further studies need to be performed to confirm the advantage of extended adjuvant ET in selected patients.


Breast Care ◽  
2017 ◽  
Vol 12 (3) ◽  
pp. 146-151 ◽  
Author(s):  
Ivana Sestak

Postmenopausal women with early oestrogen receptor-positive breast cancer who have received 5 years of endocrine therapy are at increased risk of developing a recurrence. An important clinical question is how to identify women who are at highest (or lowest) risk of a recurrence. The use of prognostic biomarkers allows individualised breast cancer therapy but correct identification of patients who will benefit most from extended endocrine therapy is essential. Several multigene assays have been developed to determine the likelihood of overall recurrence but so far none exist specifically for the prediction of late recurrence. Recent results from large clinical trials have shown that biomarker assays that include clinical information in their tests might be useful to predict and risk stratify patients for late recurrence. However, further research is needed to specifically offer multigene assays for the identification of late recurrence and thus justify routine use of these tests in the clinical setting.


2017 ◽  
Vol 35 (11) ◽  
pp. 1179-1188 ◽  
Author(s):  
Signe Borgquist ◽  
Anita Giobbie-Hurder ◽  
Thomas P. Ahern ◽  
Judy E. Garber ◽  
Marco Colleoni ◽  
...  

Purpose Cholesterol-lowering medication (CLM) has been reported to have a role in preventing breast cancer recurrence. CLM may attenuate signaling through the estrogen receptor by reducing levels of the estrogenic cholesterol metabolite 27-hydroxycholesterol. The impact of endocrine treatment on cholesterol levels and hypercholesterolemia per se may counteract the intended effect of aromatase inhibitors. Patients and Methods The Breast International Group (BIG) conducted a randomized, phase III, double-blind trial, BIG 1-98, which enrolled 8,010 postmenopausal women with early-stage, hormone receptor–positive invasive breast cancer from 1998 to 2003. Systemic levels of total cholesterol and use of CLM were measured at study entry and every 6 months up to 5.5 years. Cumulative incidence functions were used to describe the initiation of CLM in the presence of competing risks. Marginal structural Cox proportional hazards modeling investigated the relationships between initiation of CLM during endocrine therapy and outcome. Three time-to-event end points were considered: disease-free-survival, breast cancer–free interval, and distant recurrence–free interval. Results Cholesterol levels were reduced during tamoxifen therapy. Of 789 patients who initiated CLM during endocrine therapy, the majority came from the letrozole monotherapy arm (n = 318), followed by sequential tamoxifen-letrozole (n = 189), letrozole-tamoxifen (n = 176), and tamoxifen monotherapy (n = 106). Initiation of CLM during endocrine therapy was related to improved disease-free-survival (hazard ratio [HR], 0.79; 95% CI, 0.66 to 0.95; P = .01), breast cancer–free interval (HR, 0.76; 95% CI, 0.60 to 0.97; P = .02), and distant recurrence–free interval (HR, 0.74; 95% CI, 0.56 to 0.97; P = .03). Conclusion Cholesterol-lowering medication during adjuvant endocrine therapy may have a role in preventing breast cancer recurrence in hormone receptor–positive early-stage breast cancer. We recommend that these observational results be addressed in prospective randomized trials.


2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 10531-10531 ◽  
Author(s):  
V. Guillem ◽  
A. Llombart-Cussac ◽  
J. Lopez Guerrero ◽  
A. Guerrero ◽  
C. Fuster ◽  
...  

10531 Background: Letrozole (L) is more active than tamoxifen in early stage ER[+] breast cancer both as adjuvant (BIG-98 trial) or neoadjuvant (LET-024) therapy. However, complete pathological remissions to neoadjuvant endocrine therapy are anecdotal (<5%), there are no new prognostic indicators with clinical implications. Methods: We have review our series of postmenopausal patients with stage II-III breast cancer ER/PgR[+] breast cancer treated in our institution with L as neoadjuvant therapy. All patients had completed 4 months of therapy (in the absence of PD), and had measurable clinical (or radiological) disease. An independent statistical analysis was conducted for disease free (DFS) and distant disease free survival (DDFS). Results: From IV/99 to XII/04, 107 patients fulfill the criteria. Median age 76 years (range 64 to 92); median tumour size 35 mm (range 25 to 100); cT2 75 (70%), cT3/4 32 (30%); cN[-] 83 (78%). The ORR (PR + CR) at 4 months was 63% (7 CR and 60 PR), 4 patients had PD as best response (4%) and 36 a SD (34%). Surgery was done in 63 patients (59%), including all non-responders. Only 2 patients received adjuvant CT. With a median follow-up of 32 month (range 8 to 66), 12 patients had relapsed (9 distant). The 3 years DFS and DDFS were 84% and 90% respectively. In univaried analysis: cN (p < 0.02), cT3/4 (p < 0.02), and clinical response at 4 months (CR) (p = 0.003) were related to DFS; and HER2 (p < 0.05), cN (p < 0.003), and CR (p = 0.007) with DDFS. Other factors like cT, HR-levels, or surgery were not significant. Multivariate analysis showed that only OR and cN remained independently predictive both for DFS and DDFS. Conclusions: Clinical response to neoadjuvant letrozole therapy is an independent predictor of distant disease free survival and could be of value to recommend or deny more aggressive therapies in addition to endocrine therapy. [Table: see text] No significant financial relationships to disclose.


2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e14723-e14723
Author(s):  
Saranya Kodali ◽  
Eswar Tipirneni ◽  
Kim Dittus

e14723 Background: Extended endocrine therapy (EET) greater than 5 years in early stage hormone receptor positive (HR+) breast cancer (BC) patients has shown benefit. However, EET is associated with side effects and there is no validated assay to determine which group of patients would derive benefit. Breast Cancer Index (BCI) is a validated bio-marker test that incorporates 2 distinct genomic assays and is prognostic/predictive. The objective of this study is to assess patient characteristics, pathologic features and patient preferences with regards to extending endocrine therapy after reviewing the BCI results. Methods: We performed a retrospective chart review on early stage HR+ BC patients from Jan, 2016 to Jan, 2017 at the University of Vermont Medical Center. We identified 25 cases on whom BCI was submitted. Results: Median age was 68 years. Majority of the patients were stage IA (64%). 56% of the tumors were moderately differentiated. All patients were ER +ve and 12% were HER2+. Median tumor size was 1.4 cm (0.3-4). 76% had poor tolerance to the ET and preferred the test to be sent. In LN-patients, BCI identified 42% as high risk and 52% as low risk for late recurrence and 32% who derive high benefit from EET. In LN+ patients, BCI identified 75% as high risk for late recurrence and 25% as low risk for late recurrence. 40% of the entire group were identified to highly benefit from EET (70% agreed to continue ET and 30% denied due to side effects). Conclusions: BCI is a reasonable test to consider in early stage HR+ BC, especially in patients with poor tolerance to ET. This test might aid in decision making with tolerability/compliance challenges to EET. [Table: see text]


Author(s):  
Kristi Orbaugh, RN, MSN, RNP, AOCN ◽  
Val R. Adams, PharmD, FCCP, BCOP, FHOPA ◽  
Theresa W. Gillespie, PhD, MA, RN, FAAN

Cyclin-dependent kinase (CDK) 4/6 inhibitors are revolutionizing care for patients with advanced and metastatic hormone receptor–positive (HR+) and human epidermal growth factor receptor 2–negative (HER2–) breast cancer. These oral agents, often combined with other hormone-based therapy, have demonstrated considerable success in clinical trials and are used widely in oncology practices. CDK4/6 inhibitors are also being investigated for the treatment of early stage HR+, HER2– breast cancer. The addition of abemaciclib to adjuvant endocrine therapy improved invasive disease-free survival and distant relapse-free survival compared with endocrine therapy alone in patients with HR+, HER2–, node-positive, high-risk early breast cancer, and is now FDA-approved as adjuvant treatment in this setting. Here we review recent clinical data supporting the use of CDK4/6 inhibitors in both early and metastatic breast cancer. In addition, an expert faculty panel will discuss practical strategies to promote and improve adherence and side effect management in patients being treated with oral CDK4/6 inhibitors.


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