scholarly journals Optimal Endocrine Therapy in Premenopausal Women: A Pragmatic Approach to Unanswered Questions

2021 ◽  
Author(s):  
Tal Sella ◽  
Kathryn J. Ruddy ◽  
Lisa A. Carey ◽  
Ann H. Partridge
Keyword(s):  
Breast Cancer ◽  
Endocrine Therapy ◽  
Ovarian Function ◽  
Growth Factor Receptor ◽  
Cancer Recurrence ◽  
Premenopausal Women ◽  
Ovarian Function Suppression ◽  
Hormone Receptor Positive ◽  
Disease Biology ◽  
Age Related

Recent epidemiologic data show an increasing incidence of breast cancer among premenopausal women in many higher-income countries. Among premenopausal women, those diagnosed under age 40 years experience inferior long-term outcomes, particularly in the setting of hormone receptor–positive, human epidermal growth factor receptor 2–negative disease. In addition to more advanced disease presentation and/or less favorable disease biology, suboptimal adjuvant endocrine therapy (ET) has emerged as an important driver of this age-related disparity. Historically, young women have been excluded from treatment with aromatase inhibitors (AIs), attained low rates of chemotherapy-related amenorrhea, and exhibited low adherence to ET. Recently, several studies have demonstrated treatment with ovarian function suppression (OFS) during the first 5 years postdiagnosis to be associated with improvements in breast cancer recurrence and mortality, with additional benefits achieved from pairing OFS with an AI. As the first 5 years of ET for premenopausal women has been transformed, extended ET, administered in years 5-10 postdiagnosis, has also become more common. However, the only studies of extending ET in premenopausal women have tested an additional 5 years of tamoxifen following an initial 5 years of tamoxifen and studies of AIs in the second 5 years have been limited to postmenopausal women. Herein, we review available data concerning potential benefits and risks to be considered when counseling premenopausal women on extended ET, including the continuation of OFS. We offer a pragmatic framework to support decision making given the current body of knowledge and call out the need for additional research into this issue.

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.

Endocrine therapy adherence of premenopausal Mexican breast cancer patients.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e12510-e12510
Author(s):  
Cynthia Villarreal-Garza ◽  
Fernanda Mesa-Chavez ◽  
Ana Sofia Ferrigno ◽  
Cynthia De la Garza-Ramos ◽  
Karen Villanueva-Tamez ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Adverse Effects ◽  
Endocrine Therapy ◽  
Ovarian Function ◽  
Hot Flashes ◽  
Self Report ◽  
Categorical Variables ◽  
Considerable Proportion ◽  
Ovarian Function Suppression ◽  
Age Related

e12510 Background: Among premenopausal women with breast cancer (BC), adherence to endocrine therapy (ET) has often been reported suboptimal due to age-related adverse effects, lack of understandable information and inadequate social support. The current increased use of ovarian function suppression (OFS) may lead to even lower adherence rates in this group due to its high adverse effects profile. This study aims to assess the extent to which premenopausal patients comply with ET and to identify factors that hinder optimal adherence in Mexico. Methods: Women aged ≤50 years with primary stage I-III hormone receptor-positive BC receiving adjuvant ET for ≥1year were invited to fill a survey regarding their attitude towards ET and self-reported adherence. Fisher’s exact test was used to explore associations between categorical variables. This study was funded by AstraZeneca Mexico. Results: From Sep 2019 to Jan 2020, 127 patients with a median age of 45 years (range: 25-50) were included. Most had at least high school education (64%) and were unemployed (61%). ET distribution was: 69% tamoxifen (TMX) alone; 2% TMX switch to aromatase inhibitor (AI); 29% OFS plus TMX/AI. All patients recognized ET as a necessary part of their treatment and 97% believed it reduced their recurrence risk, yet 14% considered they had not received enough information about ET. Adverse effects were reported by 98%, predominantly hot flashes (82%), arthralgias (59%) and fatigue (58%). A statistically significant higher proportion of patients treated with a switch strategy or OFS experienced hot flashes, headache, insomnia, decreased libido and dyspareunia than those with TMX alone. Only 59% claimed their physician had taken measures to reduce these symptoms. Overall, 93% reported complete ET adherence. Nonetheless, 22% of them subsequently acknowledged missing 1-6 doses in the last month, the most common reasons being forgetfulness (78%), adverse effects (27%) and unwillingness to take the medication (11%). Unemployed patients were more likely to report daily compliance than students/employees (79% vs 60%; p = 0.02). No significant differences in adherence were found according to other factors, including type of ET. Conclusions: Premenopausal Mexican women self-report remarkably high rates of ET adherence. However, a considerable proportion misses ≥1 doses/month, with forgetfulness as the most common cause particularly in students/employees. Interventions aimed at reminding this group to take their ET and managing adverse effects could be crucial to improve adherence and, consequently, disease outcomes.

Challenges in Treating Premenopausal Women with Endocrine-Sensitive Breast Cancer

2016 ◽  
pp. 23-32 ◽  
Author(s):  
Hatem A. Azim ◽  
Nancy E. Davidson ◽  
Kathryn J. Ruddy
Keyword(s):  
Breast Cancer ◽  
Decision Making ◽  
Side Effects ◽  
Sexual Dysfunction ◽  
Aromatase Inhibitor ◽  
Endocrine Therapy ◽  
Ovarian Function ◽  
Hot Flashes ◽  
Premenopausal Women ◽  
Ovarian Function Suppression

For the hundreds of thousands of premenopausal women who are diagnosed annually with endocrine-sensitive breast cancer, treatment strategies are complex. For many, chemotherapy may not be necessary, and endocrine therapy decision making is paramount. Options for adjuvant endocrine regimens include tamoxifen for 5 years, tamoxifen for 10 years, ovarian function suppression (OFS) plus tamoxifen for 5 years, and OFS plus an aromatase inhibitor for 5 years. There are modest differences in efficacy between these regimens, with a benefit from OFS most obvious among patients with higher-risk disease; therefore, choosing which should be used for a given patient requires consideration of expected toxicities and patient preferences. An aromatase inhibitor cannot be safely prescribed without OFS in this setting. Additional research is needed to determine whether genomic tests such as Prosigna and Endopredict can help with decision making about optimal duration of endocrine therapy for premenopausal patients. Endocrine therapy side effects can include hot flashes, sexual dysfunction, osteoporosis, and infertility, all of which may impair quality of life and can encourage nonadherence with treatment. Ovarian function suppression worsens menopausal side effects. Hot flashes tend to be worse with tamoxifen/OFS, whereas sexual dysfunction and osteoporosis tend to be worse with aromatase inhibitors/OFS. Pregnancy is safe after endocrine therapy, and some survivors can conceive naturally. Still, embryo or oocyte cryopreservation should be considered at the time of diagnosis for patients with endocrine-sensitive disease who desire future childbearing, particularly if they will undergo chemotherapy.

scholarly journals Absolute Benefit of Adjuvant Endocrine Therapies for Premenopausal Women With Hormone Receptor–Positive, Human Epidermal Growth Factor Receptor 2–Negative Early Breast Cancer: TEXT and SOFT Trials

2016 ◽  
Vol 34 (19) ◽  
pp. 2221-2231 ◽  
Author(s):  
Meredith M. Regan ◽  
Prudence A. Francis ◽  
Olivia Pagani ◽  
Gini F. Fleming ◽  
Barbara A. Walley ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Hormone Receptor ◽  
Ovarian Function ◽  
Growth Factor Receptor ◽  
Premenopausal Women ◽  
Recurrence Risk ◽  
Hormone Receptor Positive ◽  
Epidermal Growth ◽  
Composite Risk

Purpose Risk of recurrence is the primary consideration in breast cancer adjuvant therapy recommendations. The TEXT (Tamoxifen and Exemestane Trial) and SOFT (Suppression of Ovarian Function Trial) trials investigated adjuvant endocrine therapies for premenopausal women with hormone receptor–positive breast cancer, testing exemestane plus ovarian function suppression (OFS), tamoxifen plus OFS, and tamoxifen alone. We examined absolute treatment effect across a continuum of recurrence risk to individualize endocrine therapy decision making for premenopausal women with human epidermal growth factor receptor 2 (HER2) –negative disease. Patients and Methods The TEXT and SOFT hormone receptor–positive, HER2-negative analysis population included 4,891 women. The end point was breast cancer–free interval (BCFI), defined as time from random assignment to first occurrence of invasive locoregional, distant, or contralateral breast cancer. A continuous, composite measure of recurrence risk for each patient was determined from a Cox model incorporating age, nodal status, tumor size and grade, and estrogen receptor, progesterone receptor, and Ki-67 expression levels. Subpopulation treatment effect pattern plot methodology revealed differential treatment effects on 5-year BCFI according to composite risk. Results SOFT patients who remained premenopausal after chemotherapy experienced absolute improvement of 5% or more in 5-year BCFI with exemestane plus OFS versus tamoxifen plus OFS or tamoxifen alone, reaching 10% to 15% at intermediate to high composite risk; the benefit of tamoxifen plus OFS versus tamoxifen alone was apparent at the highest composite risk. The SOFT no-chemotherapy cohort—for whom composite risk was lowest on average—did well with all endocrine therapies. For TEXT patients, the benefit of exemestane plus OFS versus tamoxifen plus OFS in 5-year BCFI ranged from 5% to 15%; patients not receiving chemotherapy and with lowest composite risk did well with both treatments. Conclusion Premenopausal women with hormone receptor–positive, HER2-negative disease and high recurrence risk, as defined by clinicopathologic characteristics, may experience improvement of 10% to 15% in 5-year BCFI with exemestane plus OFS versus tamoxifen alone. An improvement of at least 5% may be achieved for women at intermediate risk, and improvement is minimal for those at lowest risk.

scholarly journals Impact on disease-free survival of the duration of ovarian function suppression, as postoperative adjuvant therapy, in premenopausal women with hormone receptor-positive breast cancer: a retrospective single-institution study

Breast Cancer ◽  
2018 ◽  
Vol 25 (3) ◽  
pp. 343-349 ◽  
Author(s):  
Yukinori Ozaki ◽  
Yuko Tanabe ◽  
Nobuko Tamura ◽  
Takuya Ogura ◽  
Chihiro Kondoh ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Hormone Receptor ◽  
Ovarian Function ◽  
Disease Free Survival ◽  
Premenopausal Women ◽  
Ovarian Function Suppression ◽  
Hormone Receptor Positive ◽  
Significant Difference ◽  
Premenopausal Patients ◽  
Positive Breast Cancer

Abstract Introduction Although tamoxifen (TAM) plus ovarian function suppression (OFS) is considered as a standard adjuvant treatment for premenopausal women with hormone receptor-positive breast cancer, the optimal duration of OFS has not yet been established. This retrospective study was designed to assess the duration of OFS and the impact of the duration of OFS on the DFS in these patients. Methods We retrospectively reviewed the data of premenopausal patients with breast cancer who received TAM + OFS (goserelin or leuprorelin) as adjuvant therapy between February 2004 and June 2015. The primary analysis was a comparison of the disease-free survival (DFS) between patients who received OFS for 3 years or less (OFS ≤ 3 years group) and those who received OFS for longer than 3 years (OFS > 3 years group). Results We analyzed the data of 215 premenopausal patients diagnosed as having hormone receptor-positive breast cancer. A propensity score-matched model showed the absence of any significant difference in the DFS between the OFS ≤ 3 years group and OFS > 3 years group (6-year DFS rate, 93.2 vs. 94.0%; log-rank test p = 0.767). Conclusions Our data showed that among premenopausal women with hormone receptor-positive breast cancer who received TAM + OFS as adjuvant endocrine therapy, there was no significant difference in the DFS between the OFS ≤ 3-year group and OFS > 3-year group. A randomized trial is needed to establish the optimal duration of OFS for these patients.

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