Adherence to oral endocrine therapy by menopausal status: post hoc insights from a remote monitoring randomized trial.

Breast cancer, menopause, and long-term survivorship: critical issues for the 21st century

e24086 Background: Oral adjuvant endocrine therapy (AET) is an effective treatment for hormone receptor positive breast cancer to decrease recurrence and mortality. However, adherence to AET is poor, with 1/3 of patients not completing the recommended 5-year treatment course. Studies have shown that symptoms of the medication, such as joint pain, hot flashes, and fatigue, are associated with AET discontinuation. While previous studies have focused on symptoms post-AET initiation, preliminary evidence suggests that pre-AET symptoms may be an important predictor of early AET discontinuation. We used qualitative interviews to explore adherence to AET and patients’ attribution of symptoms to AET to provide context for a larger quantitative study on the role of patient-reported distress pre-AET as a predictor of AET discontinuation. Methods: Participants were recruited from the Froedtert/MCW Cancer Center registry, stratified by high (≥4) and low pre-AET Distress Thermometer scores and adherence to/discontinuation of AET. Semi-structured phone interviews followed an interview guide focused on constructs previously identified in the literature as having strong associations with AET adherence. Interviews were recorded and transcribed. A multidisciplinary team developed a codebook based on the conceptual framework describing AET discontinuation by AlOmeir et al. as well as other themes that emerged from the data. Results: Interviews were conducted with 31 participants; ages ranged from 57-86 years. Participants were diverse with respect to race/ethnicity (55% white, 26% Black, 13% Latina, and 6% other racial/ethnic groups). Participants who reported symptoms described hot flashes, joint pain, low appetite, memory loss, depression, and fatigue. We saw support for previous findings by AlOmeir et al in which ability to deal with symptoms affected the decision to continue AET. We uncovered additional nuance related to attribution of symptoms, in that some participants attributed their symptoms to a side effect of AET, while others attributed symptoms to other factors including older age, recent completion of other cancer treatments, and psychological burden associated with a cancer diagnosis and treatment. Those who did not attribute symptoms to AET focused on AET as necessary treatment to increase survival, while those who attributed symptoms to AET reported a more negative AET experience in general, with AET described as an additional burden after cancer. Conclusions: Symptom attribution rather than experience of specific symptoms may be a key factor leading to discontinuation of AET. Patient-reported symptoms and associated distress pre-AET may be a viable way to identify patients at high-risk for AET nonadherence, allowing for timely intervention. This will be quantitatively tested in a large sample.

Oral adjuvant endocrine therapy (AET) reduces the risk of cancer recurrence and death for women with hormone receptor-positive (HR+) breast cancer. Because of adverse symptoms and socioecologic barriers, AET adherence rates are low. We conducted post hoc analyses of a randomized trial of a remote symptom and adherence monitoring app to evaluate characteristics associated with higher app use, satisfaction, and how app use was associated with AET adherence. Patients prescribed AET were randomly assigned to receive one of three intervention conditions: app, app + feedback, or enhanced usual care. Baseline and 6-month follow-up surveys, app use, and pillbox-monitored AET adherence data for app and app + feedback participants were used. Logistic regression evaluated the association between sociodemographic/clinical characteristics and app utilization and satisfaction, and how app use was associated with AET adherence (>80%). Overall, 163 women with early-stage HR+ breast cancer were included; 35.0% had high app use (≥75% of weeks enrolled). No sociodemographic characteristics were associated with app use. Satisfaction with the app was higher among those who were younger (88.9% for age 31-49 years v 54.9% for age 65+ years, P < .001), identified as White (76.8% v 60.1% for Black, P = .045), had lower health literacy (85.4% v 68.2% with higher health literacy, P = .017), or were nonurban residents (85.7% v 68.6% for urban, P = .021). Most participants (90.3%) with high app use were AET-adherent compared with 66.8% for those with lower app use (P < .001). Use of a remote monitoring app was similar across sociodemographic characteristics, and more frequent app use was associated with a higher likelihood of 6-month AET adherence. Encouraging women to monitor medication adherence and communicate adverse symptoms could improve AET adherence.

Oral adjuvant endocrine therapy (AET) is an effective treatment for hormone receptor positive breast cancer to decrease recurrence and mortality, but adherence is poor. This study explored post-menopausal women's experiences with AET, with a particular focus on adherence to AET as well as distress and symptoms experienced prior to and during AET treatment. Participants were recruited from a hospital registry, stratified by adherence to/discontinuation of AET. Telephone interviews followed a semi-structured interview guide and were recorded and transcribed verbatim. Transcripts were systematically coded using team-based coding, with analysis of themes using a grounded theory approach. Thirty-three participants were interviewed; ages ranged from 57 to 86years. Participants included 10 discontinued patients and 23 patients who completed their AET course or were adherent to AET at the time of interviewing. Both adherent and discontinued patients reported symptoms throughout their AET treatment course, and both attributed symptoms to factors other than AET (e.g., older age and pre-existing comorbidities). However, discontinued patients were more likely to attribute symptoms to AET and to describe difficulty managing their symptoms, with some directly citing symptoms as the reason for discontinuing AET therapy. Conversely, adherent patients were more likely to describe the necessity of taking AET, despite symptoms. AET adherence was associated with beliefs about AET, symptom attribution, and symptom management. Routine symptom monitoring during AET and addressing both symptoms and patients' understanding of their symptoms may promote adherence to AET.

Adjuvant endocrine therapy for premenopausal ER+breast cancer had a relatively challenging initial pathway. The earliest trials testing adjuvant ovarian ablation in premenopausal breast cancer were hampered by the lack of ability to test for the relevant target, namely the estrogen receptor (ER). Therefore, trials testing adjuvant ovarian ablation and subsequently ovarian suppression with gonadotropin releasing hormone agonists (GnRHa) were diluted by the inclusion of women with estrogen receptor negative tumors. The subsequent demonstration of the effectiveness of adjuvant chemotherapy, initially with the CMF regimen, diverted some attention away from adjuvant endocrine therapy in premenopausal women, notwithstanding the fact that CMF, initially given for 12 months, resulted in permanent ovarian function suppression in many premenopausal women. Use of adjuvant CMF made it even more challenging to discern the added value of ovarian ablation or suppression. Oral adjuvant endocrine therapy with the selective estrogen receptor modulator tamoxifen became recommended for postmenopausal women, subsequently refined to only those with ER+ breast cancer, but the value of tamoxifen in premenopausal women was initially considered uncertain. Eventually, 5 years of adjuvant tamoxifen became a standard recommendation for premenopausal ER+ early breast cancer, although it took some time for evidence to emerge on the value of adding tamoxifen in women who received chemotherapy. The value of extending adjuvant endocrine therapy beyond 5 years was subsequently studied. More recent randomized premenopausal adjuvant endocrine therapy trials have focused of delineating the value of ovarian function suppression (OFS) added to tamoxifen or to an aromatase inhibitor. There are now a range of options for adjuvant endocrine therapy for premenopausal ER+ breast cancer, and identifying the clinical-pathologic features most appropriate for intensification of adjuvant endocrine therapy can assist with optimizing recommendations for an individual patient. Citation Format: Carlos Arteaga, Prudence Francis. Plenary Lecture 2: Premenopausal ER+ Breast Cancer: Past, Present, and Future [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr PL2.

Oral adjuvant endocrine therapy (OAET) substantially improves the survival of women with hormone receptor-positive (HR) breast cancer. However, we reported previously that at 3 to 4 years after diagnosis, 18% of affected women are not using OAET primarily because of estrogen deficiency symptoms. The aim of this study was to determine the use of OAET in women with HR breast cancer 5 to 6 years from diagnosis.Analysis was carried out using data from the Bupa Health Foundation's Health and Wellbeing After Breast Cancer Study, a cohort study of 1,683 women with breast cancer who were recruited in Victoria, Australia between 2004 and 2006. All women completed an enrollment questionnaire within 12 months of diagnosis and an annual follow-up questionnaire (FQ) for 5 years. The fifth FQ was completed 5.7 years from the time of diagnosis. Use of OAET was self-reported in response to a series of questions.A minimal exposure to OAET of at least 5 years (OAET in all six FQs) was reported by 19.7% of the women (n = 212), and another 46.7% (n = 503) received a minimal exposure of at least 4 years (OAET in five questionnaires). In total, 82.1% (n = 883) of the women would have received at least 3 years of treatment (OAET in at least four questionnaires). Only 7.8% (n = 84) reported never using OAET.Most women with HR breast cancer who survive at least 5 years have persisted with OAET despite the adverse effects of estrogen depletion.

How I perform fertility preservation in breast cancer patients

Ovarian suppression for adjuvant treatment of hormone receptor-positive early breast cancer.

45 Background: Despite the efficacy of oral adjuvant endocrine therapy (AET) for improving survival among women with hormone receptor-positive early-stage breast cancer, adherence rates remain low. Our THRIVE study (NCT03592771) investigated the effectiveness of a mobile health remote monitoring app with and without tailored educational messages on AET adherence among women with breast cancer and found no statistically significant treatment effects on 1-year AET adherence overall. Health literacy contributes to patients’ understanding of their treatment plans. We conducted a post hoc analysis of the THRIVE study to examine if health literacy moderates the effectiveness of this intervention. Methods: This non-blinded randomized controlled trial included women with early-stage breast cancer prescribed AET at a large cancer center with 14 clinics across three states. Participants used a pillbox to electronically monitor AET adherence for 1 year and completed surveys at enrollment. Consented participants were randomized into (1) “App”, receiving access to the study adherence and symptom monitoring app for 6 months, with increasing/severe symptoms and missed doses reported in the app triggering follow-ups from the oncology team; (2) “App+Feedback”, receiving additional weekly text messages about managing symptoms, adherence, and communication for 6 months; or (3) “Enhanced Usual Care (EUC).” The primary outcome was 1-year AET adherence captured with the pillbox (≥80% Proportion of Days Covered [PDC] vs. &lt; 80%). The enrollment survey captured participant’s sociodemographic characteristics, including race and ethnicity, education, household income, and health literacy. We used a linear probability model to measure the interaction between the study arm and health literacy on AET adherence. Results: Among 304 women randomized (104 EUC, 98 App, and 102 App+Feedback), the 12-month follow-up retention rate was 88% (n = 266) and 19.4% reported low health literacy at enrollment. Low health literacy was more prevalent among Black (29.4%) vs. White (13.4%) participants (p &lt; 0.001), those with incomes below the federal poverty level (34.4% vs. 17.2% of those with higher incomes, p = 0.02), and those with only a high school degree or lower education (31.7%) vs. with those with some college or higher education (16.4%, p &lt; 0.01). In the low health literacy group, 80.0% of App+Feedback were AET adherent vs. 42.1% of EUC, a 37.9 percentage point (ppt) difference (95% CI: 4.1 to 71.7, p = 0.03); in higher literacy group adherence, 47.1% of App+Feedback vs. 59.0% of EUC were adherent, a -11.8 ppt difference (95% CI: -27.9 to 4.3, p = 0.15). Conclusions: A remote monitoring app with tailored educational text messages led to higher 1-year AET adherence among participants with low health literacy, but not for those with high health literacy. Clinical trial information: NCT03592771 .

The Optimal Adjuvant Treatment in Older Patients with Hormone Receptor Positive Early Stage Breast Cancer (BC) is Breast Radiation (RT) not Endocrine Therapy (ET)

Background: It is well known that the young age at the diagnosis of breast cancer is a bad prognostic factor, by many previous studies. In a study of breast cancer adherence to adjuvant endocrine therapy (AET), younger patients were found to have significantly lower adherence. Therefore, the poor prognosis of young patients, with hormone receptor positive breast cancer, should be figured out whether it is due to the difference in adherence. And we aimed to analyze the effect of medication adherence for 4.5 years on subsequent prognosis, after the treatment completion. Methods: A total of 5,928 patients with stage I~III hormonal receptor positive breast cancer, who underwent surgery at Asan Medical Center from January 1997 to December 2009 were included in this retrospective analysis. Patients with no history of AET, follow-up loss, early breast cancer recurrence within 4.5 years from initial treatment were excluded. The number of days of treatment gap was estimated by subtracting the duration of medication coverage from the intervals between prescription dates. A descriptive analysis of prescription gap according to age distribution was done. And a multivariate Cox regression for the risk of distant metastasis of breast cancer by AET adherence, grouped by; no gap, gap1, gap2 (gap1: prescription gap within median, gap2: gap over median) according to age group (grouped by the age at diagnosis of &amp;lt;40, 40~59, and ≥60), was conducted. Results: The AET adherence was best in the middle-age group, showing the smallest number of days in treatment omission (130.9/4264, mean of total prescription gap/number of patients), compared with young (194.9/959) or old group (159.4/705). When adjusted with cancer stage, histologic grade, adjuvant treatment of chemotherapy or radiation therapy, type of AET agent, the risk of distant metastasis with increasing gaps tended to increase in the younger age group but it showed no significance between three gap-groups (p=0.063). The risk was significantly increased in the older age group, that the hazard ration (HR) in gap1 group was 2.534 (95% CI: 0.845~7.599, p=0.097), and 3.820 (95% CI 1.485~9.828, p=0.005) in gap2 group. With the reference of middle-age-no gap group, younger-no gap group showed significantly high HR (1.853, 95% CI: 1.008~3.407, p=0.047). In older age groups, only gap2 group showed significantly high HR (2.605, 95% CI: 1.443~4.703, p=0.001). However, in the risk of distant metastasis, the interaction between the gap and age difference was not statistically significant (p = 0.487). Conclusion: In distant metastasis after AET completion, both adherence and age at diagnosis showed a strong correlation. This suggests that survival after 4.5 years in young patients could be more affected by other factors (besides compliance with medication). This implicates that the prophylactic effect of AET after the end of the routine medication period is less significant. Further analysis including patients with early recurrence is needed in the future. Citation Format: Yura Lee, Hee Jeong Kim, Sun Ok Kim, Jong Won Lee. The effect of adjuvant endocrine therapy adherence on breast cancer prognosis according to age group [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-12-08.

Background: Obesity is related to poor prognosis in pre- and postmenopausal patients with breast cancer. However, there is insufficient evidence regarding the optimal adjuvant hormone therapy for obese premenopausal women with hormone receptor-positive breast cancer. We examined the impact of ovarian function suppression (OFS) on the prognosis of obese women with primary hormone receptor-positive breast cancer. Methods: We retrospectively reviewed premenopausal women who received curative surgery for clinical stage I-III hormone receptor (HR)-positive breast cancer at the Cancer Institute Hospital of the Japanese Foundation for Cancer Research from January 2007 to December 2017. All patients were classified into five groups according to body mass index (BMI): underweight (UW), BMI &amp;lt;18.5 kg/m2; normal weight (NW), 18.5-24.9 kg/m2; obese 1 degree (OB1), 25.0-29.9 kg/m2; obese 2 degree (OB2), 30.0-34.9 kg/m2; and obese 3 degree (OB3), ≥35 kg/m2. The primary analysis was a comparison of breast cancer-specific survival (BCSS) according to BMI (UW/NW vs. OB1-3) and adjuvant hormonal therapy (with or without OFS). Secondary endpoints included overall survival (OS). Results: Overall, the total number of patients was 13,021 and the data of 3,380 patients were analyzed, which included patients who received adjuvant tamoxifen (TAM) without OFS (n = 1,836) or with OFS (n = 670). The median follow-up duration was 5.9 years (range, 0.2-12.9). The numbers of patients with UW, NW, OB1, OB2, and OB3 were 404 (12%), 2,482 (73%), 399 (12%), 78 (2%), and 17 (1%), respectively. Obesity was significantly associated with higher stage of breast cancer (p &amp;lt;0.0001). Nuclear grade of breast cancer in OB1-3 patients was significantly higher than that in UW/NW patients (p = 0.0323). BCSS in OB1-3 patients was significantly worse than that in patients with UW/NW (hazard ratio [HR] 2.37; 95% confidence interval [CI], 1.40-4.02: p = 0.0009). In OB1-3 patients who received TAM as adjuvant hormone therapy, BCSS was significantly worse than that in UW/NW patients (p = 0.0086); however, a significant difference was not shown in patients who received TAM and OFS (p = 0.0921). Multivariate analysis revealed that OB3 was an independent prognostic factor compared with NW in patients with stage II/III breast cancer (p = 0.0162).Conclusion: High BMI was associated with worse prognosis in premenopausal patients with HR-positive breast cancer. The negative impact of obesity might be canceled by adding OFS to TAM as adjuvant hormone therapy. Further studies are required to explore the adequate management of obese premenopausal patients. Citation Format: Yukinori Ozaki, Jun Masuda, Akemi Kataoka, Takahiro Kogawa, Tomomi Abe, Hidetomo Morizono, Lina Inagaki, Fumikata Hara, Toshimi Takano, Takayuki Ueno, Shinji Ohno. Effect of suppressed ovarian function on prognosis of premenopausal obese women with hormone receptor-positive breast cancer: A single-institute retrospective study [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P4-11-06.

Introduction: Deep learning tools applied to standard surveillance mammograms could serve as noninvasive pharmacodynamic biomarkers of response to adjuvant breast cancer (BC) therapies, including endocrine therapy (ET). We previously demonstrated that a convolutional neural network (CNN)-based model applied to surveillance mammograms is an accurate, independent predictor of BC risk, and that short-term change in a CNN-derived BC risk score with adjuvant ET was also associated with breast cancer relapse. We evaluated demographic and clinicopathologic characteristics associated with baseline CNN risk score and with change in CNN risk score over time on adjuvant ET among women with early-stage HR+ breast cancer. Methods: We conducted a retrospective cohort study among women diagnosed with stage I-III unilateral hormone receptor-positive (HR+) BC at Columbia University Irving Medical Center (CUIMC) from 2007-2017, who received adjuvant ET (tamoxifen, aromatase inhibitors [AIs) and had mammograms of the contralateral breast at diagnosis (baseline) and at 1-2 years on adjuvant ET (follow-up). We extracted demographics, body mass index (BMI, kg/m2), clinicopathologic characteristics including tumor stage and grade, and BC treatments from the electronic health record (EHR) and the New York-Presbyterian Hospital Tumor Registry. We applied the CNN risk model to baseline and follow-up mammograms to estimate baseline CNN BC risk score (range, 0-1, with 1 indicating highest risk), and to calculate absolute change in CNN risk score from baseline to 1-2 years on ET. We conducted multivariable linear regression models to evaluate for potential associations between baseline CNN risk score and change in CNN risk score and prognostic factors including age, race/ethnicity, BMI, tumor stage and grade, and BC treatments. Result: Among 749 evaluable women, mean age was 59.4 years (standard deviation [SD], 12.4 years), and 38% were non-Hispanic White, 14% non-Hispanic Black, 38% Hispanic, and 10% Asian. Thirty-six percent of women were obese (BMI &amp;gt;30 kg/m2), and three-quarters were postmenopausal at diagnosis. The majority of patients had stage I cancer (59.4%), and received adjuvant aromatase inhibitors (68.1%). After adjustment for covariates, baseline BMI was not significantly associated with baseline CNN risk score (regression slope estimate [ß]=0.001; p=0.424). However, increasing age (ß=0.001; p&amp;lt;0.001), Black race (ß=0.023; p&amp;lt;0.001), tumor stage III (ß=0.023, p=0.005) were associated with higher baseline CNN score, while high tumor grade was inversely associated with baseline CNN score (ß= -0.0150; p=0.028). In multivariable analysis, absolute change in CNN risk score from baseline to follow-up was inversely associated with change in BMI over that period (ß= -0.002; p=0.007) and with high tumor grade (ß -0.014; p=0.039), while older age (ß=0.001; p&amp;lt;0.001), Black race (ß=0.024; p&amp;lt;0.001), tumor stage III (ß=0.023; p&amp;lt;0.001), and low tumor grade (ß=0.022; p=0.024), had significant positive associations with change in CNN score. Conclusions: We found that poor prognostic factors such as advanced tumor stage and Black race were associated with higher baseline CNN risk score and increase in CNN score on adjuvant ET. However, factors typically associated with more favorable BC diagnosis, including lower tumor grade, older age, and a decrease in BMI on adjuvant ET, were also associated with higher baseline CNN score and an increase in CNN risk score. These associations should be further evaluated in future studies utilizing larger, diverse patient cohorts of patients with early-stage HR+ BC. Citation Format: Julia McGuinness, Juliet Rowe, Simukayi Mutasa, Vicky Ro, Samuel Pan, Jianhua Hu, Meghna S. Trivedi, Melissa K. Accordino, Kevin Kalinsky, Dawn L. Hershman, Richard S. Ha, Katherine D. Crew. Associations between demographic and clinicopathologic characteristics and convolutional neural network-derived breast cancer risk scores among women with hormone receptor-positive breast cancer [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P2-07-12.

Long-Term Adherence to Adjuvant Endocrine Therapy Following Various Radiotherapy Modalities in Early Stage Hormone Receptor Positive Breast Cancer

The influence of hormone receptors and hormonal adjuvant therapy on disease-free survival in breast cancer: a multifactorial analysis