Discontinuation Of Hormone Therapy Research Articles

Abstract PS9-14: Feasibility of monitoring symptoms during endocrine therapy with patient reported outcomes collected via smart phone app

Abstract Background: Despite known benefits in reducing breast cancer (BC) recurrence and death, up to 50% of patients discontinue endocrine therapy (ET) early. Symptoms are often cited as a reason for early ET discontinuation (DC). The symptom burden during ET captured by patient reported outcomes (PRO) exceeds that captured by clinicians. Methods: We initiated a single arm pilot trial evaluating symptom monitoring during ET with PRO collected via smart phone app. Eligible patients are women starting ET for stage 0-III BC. Participants receive text message reminders to complete surveys at baseline (BL), 1, 3, 6 and 12 months (mo). Participants who do not complete 2 sequential surveys may opt out of further surveys. Surveys include PROMIS measures for anxiety, depression, fatigue and the vaginal discomfort domain of sexual function plus PRO-CTCAE measures for concentration, memory, hot flashes, joint pain and vaginal dryness. PROMIS measures are scored by T-score look up tables. PRO-CTCAE responses are reported on a 5 point scale (0-4). Severe or worsening scores trigger email alerts to clinicians as follows: T-scores ≥70 or ≥5 points worse than BL for anxiety, depression, and fatigue; T-score ≥65 or ≥5 points worse than BL for sexual function; scores ≥3 or ≥2 points worse than BL on PRO-CTCAE measures. Recommended management pathways are provided to clinicians upon alert acknowledgement. The primary endpoint is feasibility, with success defined as ≥65% of participants completing the BL survey and ≥65% of participants completing ≥1 follow-up (FU) survey during the first 6 mo of ET. Secondary endpoints include patient-reported symptoms and pathway-concordant symptom management based on chart review. We report here descriptive statistics of the observed data to date and multivariate logistic regression analysis of factors associated with BL survey completion. Results: From Feb 2019 to May 2020, 213 of 250 planned participants enrolled. Median FU is 5.7 mo. Mean age is 58.3 years (SD 11.7). 154 (72.3%) participants are white (W) and 32 (15%) are black (B). 189 (88.7%) participants have stage I-II BC. Prior to initiating ET, 82 (39%) had mastectomy, 75 (35.2%) had chemotherapy and 135 (63.4%) had radiation. 138 (64.8%) initiated an aromatase inhibitor and 72 (33.8%) initiated tamoxifen. BL survey completion rate is 73.7% (95% confidence interval (CI) 67.3-79.5%). To date, 69.3% (95% CI 60.5-77.2%) of participants completed ≥1 FU survey during the first 6 mo of ET. 25.2% of participants opted out of participation within 6 mo. On multivariate analysis, race was associated with BL survey completion. By race, BL survey completion rate was: 77.9% (W) and 62.5% (B). Mean scores on PROMIS depression, anxiety, fatigue, and sexual function measures at BL, 1 mo, and 3 mo were +/- 0.5 SD of population means. Compared to BL, mean PRO-CTCAE scores for joint pain severity and hot flash frequency worsened at 1 and 3 mo and mean PRO-CTCAE score for vaginal dryness severity worsened at 3 mo (p<0.05). 28% of participants had alerts at BL. Most common BL alerts were joint pain and hot flashes. To date, 79.7% of participants had ≥1 alert on a FU survey. Most common FU alerts were joint pain, hot flashes and fatigue. Median number of alerts per participant per FU survey is 1 (range 0-5). To date, clinicians acknowledged 29.8% of alerts within 7 days and made pathway-concordant management recommendations within 30 days for 39.4% of alerts. Conclusion: Monitoring symptoms during ET using PRO collected via smart phone app is feasible. Symptoms are common during ET. Updated data, including factors associated with survey completion, clinician response to alerts and the association between PRO scores and early ET DC, will be reported at the conference. These data will be used to design a randomized trial to evaluate symptom monitoring via smart phone app to reduce early ET DC. Citation Format: Karen L Smith, Chenguang Wang, David Lim, Amanda Montanari, Raquel Nunes, Mary J. Wilkinson, Jennifer Y. Sheng, Rima Couzi, John Fetting, Carol Riley, Antonio C. Wolff, Cesar A. Santa-Maria, Katie Papathakis, Lauren Collins-Chase, Christie Hilton, Claire Snyder, Elissa Thorner, Dara Z. Ikejiani, Molly Steimer, Vered Stearns. Feasibility of monitoring symptoms during endocrine therapy with patient reported outcomes collected via smart phone app [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS9-14.

Patient-Reported Outcomes Bridge an Important Gap in Identifying Risk for Early Endocrine Therapy Discontinuation.

Patient-Reported Outcomes Bridge an Important Gap in Identifying Risk for Early Endocrine Therapy Discontinuation.

Endocrine therapy and radiotherapy use among older women with hormone receptor-positive, clinically node-negative breast cancer.

To examine patterns of radiotherapy (RT) and endocrine therapy (ET) use, associations between RT omission and ET adherence, and associations among ET and RT use and disease recurrence in older women with early-stage, estrogen receptor-positive breast cancer. Women age 65 and older diagnosed with hormone receptor-positive, clinically node-negative breast cancer between 2005 and 2018 and who did not undergo mastectomy were included. Multinomial logistic regression was used to examine the trends in practice patterns over time and by age. Kaplan-Meier estimates were used to estimate the probability of ET discontinuation. Cox proportional hazards models were constructed to assess associations between recurrence and ET/RT. Of the 484 enrolled patients, 47.9% patients underwent RT and initiated ET, 27.4% received ET alone, 10.2% received RT alone, and 13.8% patients received neither. Older patients had a higher probability of receiving ET alone or neither ET nor RT (both p < 0.001). The probability of initiating ET was greater among patients who underwent RT than those who omitted RT (p < 0.001). Regardless of RT status (RT or no RT), initiation and continuation of ET may be associated with reduced risk of recurrence. Patients who opt for no adjuvant therapy, or who do not tolerate ET, are at increased risk of disease recurrence if they omit RT. Clinicians should consider the likelihood a patient will adhere to ET prior to recommending omission of RT.

Hormone therapy for postmenopausal women

Hormone therapy is recommended for relief from hot flashes or night sweats in women younger than age 60 years or those who entered menopause within 10 years of seeking treatment. Hormone therapy also can reduce bone loss and the risk of fractures; offer a potential cardioprotective benefit; and alleviate the genitourinary symptoms of menopause, including dysfunction of the bladder and irritation of the vagina and vulva.For women with early menopause without contraindications, hormone therapy is recommended until at least the average age of natural menopause. Observational studies suggest that the risk of thromboembolism and stroke is lower with transdermal therapy than with oral hormone therapy. Compounded bioidentical hormone therapies that have not been approved by the Food and Drug Administration are not recommended owing to safety concerns. Hormone therapy is not recommended for primary or secondary prevention of coronary heart disease or dementia. Nonhormone therapies that have been shown to reduce hot flashes include low-dose selective serotonin-reuptake inhibitors and serotonin–norepinephrine reuptake inhibitors, gabapentinoids, weight loss, hypnosis, and cognitive behavioral therapy. For women with only genitourinary symptoms, local vaginal hormone therapies are recommended.The treatment is not without its risks, including concerns about cognitive decline and breast cancer. More research is warranted, to determine the long-term benefits and risks of menopausal hormone therapy, to gauge the effects of prolonged use in women initiating therapy close to menopause, to inform the timing of and approach to hormone therapy discontinuation, and to answer additional unknowns. As scientists work to address these questions, technology can help identify women likely to benefit from hormone therapy. The MenoPro mobile app, backed by the North American Menopause Society, provides a free algorithm to flag the strongest candidates.

Dynamic Impact of Hormone Therapy on Laboratory Values in Transgender Patients over Time.

Known physiological changes occur while transgender patients are taking hormone therapy (HT). However, knowledge is limited about when laboratory values stabilize and if there are any long-term impacts, making it challenging for physicians to provide adequate gender-affirming care. We aim to analyze laboratory values with HT use over 5 years and after discontinuation of HT to define when values achieve stability. We performed a multicenter retrospective analysis of 126 transgender women (TW) and 91 transgender men (TM) at consecutive clinic visits. Labs included complete metabolic panel, complete blood count, lipids, and hormone levels and were monitored for 5 years. Absolute measurement and percentage change from baseline were calculated for each analyte value. We collected the laboratory studies described from patients off HT and the duration of discontinuation to determine the time to return to baseline levels. During HT, red blood cell (RBC; erythrocyte) indexes reach stable levels within 6 months (P < 0.001) and are unchanged long term. Some analytes such as HDL and platelets showed increases beyond the first year of HT in TW (P = 0.001 and P < 0.001, respectively). LDL and alanine aminotransferase increased beyond 1 year in TM (P < 0.005 and P < 0.001, respectively), whereas HDL decreased beyond 1 year (P < 0.001). Time for laboratory values to return to baseline occurred around 10 weeks. Most analytes reach stable levels within 6 months (RBC and creatinine), whereas others change in the long term (LDL, HDL, platelets). This information can be used to guide physicians as they monitor their transgender patients in all stages of their progress through HT.

Treatment interruption and discontinuationof hormonal therapy in hormone receptor-positive breast cancer patients.

To investigate predictors of treatment interruption and early discontinuation of adjuvant hormonal therapy (HT) in a retrospective cohort of women with newly diagnosed hormone receptor-positive (HR +) breast cancer. Eligible cases were identified from a single institutional tumor registry from 2009 to 2015. Patients were followed from initiation of adjuvant HT for a minimum of one year through December 1, 2016. Predictors of treatment interruption or early discontinuation were analyzed with Cox proportional hazards regression models. With a median follow-up time of 3.0years (IQR 1.5-4.5), 22 women (10.9%) discontinued HT early and 47 (23.4%) had at least one treatment interruption of > 14days. Adjusted Cox proportional hazards regression models showed that women with pre-existing affective disorders were more likely to discontinue therapy early (HR 3.15; 95% CI 1.35-7.37), while those with pre-existing chronic pain disorders were at increased risk for treatment interruption (HR 2.24; 95% CI 1.20-4.19). HT-related symptoms were the most commonly reported reason for HT interruption or discontinuation. Women who experienced severe treatment-related symptoms were at increased risk for both HT interruption (HR 2.64; 95% CI 1.07-6.50) and HT discontinuation (HR 3.48; 95% CI 1.20-10.1). This study showed that HT interruptions and discontinuation were common, often associated with HT-related symptoms. Clinicians caring for breast cancer patients on HT should monitor closely for treatment-emergent symptoms, especially women with pre-existing disorders, and support them to continue therapy through aggressive symptom management and other patient-centered approaches.

Early discontinuation to adjuvant endocrine therapy in the ECOG-ACRIN TAILORx Trial.

7004 Background: The TAILORx study demonstrated women with an intermediate Oncotype DX score receive the same benefit with endocrine therapy (ET) compared to chemoendocrine therapy (CET). However, early discontinuation of adjuvant ET is problematic among breast cancer survivors, with previous studies suggesting that up to 50% of women do not adhere to the full 5 years of recommended ET treatment. The aim of this study was to identify patient-level risk factors associated with early discontinuation of ET in the TAILORx study. Methods: TAILORx was coordinated by the ECOG-ACRIN Cancer Research Group. Participants were a subgroup of 954 women who completed additional measures on health-related quality of life (HRQoL) including endocrine symptoms (ES) physical well-being (PWB) and social well-being (SWB) prior to initiating ET, which categorized into three groups by tertile for analysis. All participants were diagnosed with hormone-receptor–positive, human epidermal growth factor receptor 2–negative, axillary node–negative breast cancer who started ET within a year of study entry. Early discontinuation of ET, defined as discontinuation less than 4 years from initiation for reasons other than death or recurrence, was assessed by clinician report. Rate of discontinuation was calculated using Kaplan-Meier estimates, and Cox-proportional hazards joint models were used to analyze the association between rates of adherence to ET with patient-level factors. Results: In a joint model, receipt of CET therapy (vs receipt of ET only; HR = .59, 95% CI .38-.94, p = .02) and age above 40 (versus age &lt; = 40; HR = .30, 95% CI .14-.66, p = .003) were associated with a lower probability of early discontinuation of ET. Adjusted for these factors, a history of depression compared to no history of depression (HR 1.82, 95% CI 1.19-2.77, p = 0.005), worse ES compared to better ES (HR 1.70, 95% CI 1.06-2.74, p = 0.03), worse PWB compared to better PWB (HR 2.12, 95% CI 1.30-3.45,p = 0.003), and worse SWB compared to better SWB (HR 1.94, 95% CI 1.20-3.13, p = 0.007) were individually and significantly associated with a higher probability of early discontinuation of ET, although none reached statistical significance when all were included in a joint model. Conclusions: Younger women are at risk for early discontinuation and modifiable characteristics such as HRQoL and history of depression are potential risk factors for early discontinuation of ET. These results support systematic screening for HRQoL and depressive symptoms to identify women at risk for discontinuation of ET. Clinical trial information: NCT00310180 .

Breast cancer patients’ insurance status correlates with their adherence to endocrine therapy: Analysis of ECOG-ACRIN TAILORx trial.

7041 Background: Cancer patients spend substantial amounts on their healthcare services, and are at high risk for financial toxicity, a patient-reported outcome shown to be associated with care non-adherence. Even with insurance, cancer patients often face unpredictable or unmanageable costs. In women with breast cancer enrolled in TAILORx trial, we investigated the association between study entry insurance status and adherence to endocrine therapy (ET). Methods: Women with hormone-receptor–positive, human epidermal growth factor receptor 2–negative, axillary node–negative breast cancer enrolled in TAILORx clinical trial who started ET within a year of study entry were included. Early discontinuation was defined as stopping ET within 4 years of start for reasons other than distant recurrence or death, and the rate was calculated using Kaplan-Meier estimates. Cox proportional hazards model was used to analyze association between the patients’ insurance status at study entry and early discontinuation of ET incorporating patients’ treatment, age, race and Recurrence Score in the model. Results: A total of 9,475 patients were included (mean age: 55.6; 84% white; 9% Hispanic). A total of 58.0% had private insurance, while 11.7% had Medicare; 5.8% had Medicaid; 0.98% had military/VA insurance; 3.8% were self-pay, and 19.1% were patient recruited from international sites. The rates of 4-year early discontinuation were highest among self-pay (18.7%) and Medicaid patients (18%) and lowest among patients with military/VA insurance (8.6%) and international sites (9.8%). In multivariable analysis, compared to private insurance patients with Medicaid (HR 1.6; 95% CI 1.3-2.0) and self-pay (HR 1.6; 95% CI 1.3-2.1) had higher probability of discontinuing ET within 4 years of start and those at international sites had lower probability of early discontinuation (HR 0.8; 95% CI 0.7-0.9) (All p values &lt; 0.05). Conclusions: Patients’ insurance status plays an important role in adherence to ET with uninsured and underinsured having a high rate of treatment non-adherence. Early identification of patients at risk and enrollment in insurance optimization programs may improve adherence to therapy. Clinical trial information: NCT00310180 .

Older age and comorbidity in breast cancer: is RT alone the new therapeutic frontier?

To assess the impact of age, comorbidities and endocrine therapy (ET) in older breast cancer (BC) patients treated with hypofractionated radiotherapy (Hypo-RT). From June 2009 to December 2017, we enrolled in this study 735 ER-positive BC patients (stage pT1-T2, pNx-1, M0 and age ≥ 65years) receiving hypo-RT and followed them until September 2019. Baseline comorbidities included in the hypertension-augmented Charlson Comorbidity Index were retrospectively retrieved. Logistic regression model estimated adjusted-odds ratios (ORs) of ET prescription in relation to baseline patient and tumor characteristics. Competing risk analysis estimated 5-year cumulative incidence function (CIF) of ET discontinuation due to side effects (with BC progression or death as competing events), and its effect on locoregional recurrence (LRR) and distant metastasis (DM) (with death as competing event). ET has been prescribed in 89% patients. In multivariable analysis, the odds of ET prescription was significantly reduced in older patients (≥ 80years, OR 0.08, 95% CI 0.03-0.20) and significantly increased in patients with moderate comorbidity. Patients ≥ 80years discontinued the prescribed therapy earlier and more frequently than younger (65-69years) patients (p = 0.060). Five-year CIF of LLR, DM and death from causes other that BC were 1.7%, 2.2% and 7.5%, respectively. Patients who discontinued ET had higher chance of LRR (p = 0.004). ET use did not impact on OS in any of the analyzed groups. In older patients, ET did not show a benefit in terms of overall survival. Further studies focusing on tailored treatment approaches are warranted to offer the best care in terms of adjuvant treatment to these patients.

Voice Change Following Testosterone Supplementation in Women: A Multi-Institutional Case Series

To describe voice changes as a result of the off-label use of androgen supplementation in women. A multi-institutional retrospective consecutive case series identified women taking androgen supplementation who presented to voice clinics at two institutions with a chief complaint of voice change between 2014 and 2019. Age, occupation, hormone therapy, indication, Voice Handicap Index-10, fundamental frequency, semitone pitch range, testosterone blood level, treatment undertaken, and long-term outcome were collected. Nine women presented with voice change after initiation of androgen hormone supplementation. The mean age was 55 and three patients were performers. All patients underwent hormone therapy with testosterone supplementation, most commonly subcutaneous testosterone pellets. Six patients (67%) were being treated for menopause symptoms, one patient for decreased libido, one patient for breast cancer, and one patient who desired additional muscle gain. Time of symptom onset after hormone therapy initiation was highly variable, ranging from 0 to 48 months with a mean of 15 months. Mean Voice Handicap Index-10 was 21, mean fundamental frequency at comfortable speaking level was 155 Hz and mean semitone pitch range was 22 semitones. Two patients had markedly elevated serum total testosterone levels. Hormone therapy discontinuation and voice therapy were recommended in six (67%) patients each. Five patients returned for follow-up after treatment and noted some subjective benefit. Female patients treated with androgen supplementation may experience unintended voice changes, most prominently reduction in fundamental frequency. Although some benefit may be obtained from voice therapy and cessation of hormone therapy, voice changes may be permanent. Caution should be exercised when prescribing these medications to women.

Abstract P2-18-04: Endocrine therapy (ET) and radiotherapy (RT) use among elderly women with hormone receptor positive (HR+), clinically node negative (cN-) breast cancer

Abstract Background: Based on data from randomized controlled trials, women age 65 or older with HR+, cN- breast cancer can omit post-lumpectomy RT if they take ET for 5 years. However ET non-compliance is a significant challenge, especially in non-trial patients. Initiation of and persistence with ET in the setting of RT omission is poorly understood in a non-trial patient population. Methods: In this retrospective cohort study from a single institution, women age 65 and older with HR+, cN- breast cancer who were diagnosed in 2005-2018 were included. Patients who underwent mastectomy were excluded. Persistence with ET was defined as taking ET for a minimum of 57 months, until disease recurrence, or until the patient was lost to follow up. Recurrence was defined as any local, regional, or distant recurrence, and excluded contralateral breast cancer. Multinomial logistic regression was used to examine trends in practice patterns over time and by age. Kaplan-Meier estimators were used to estimate the probability of ET discontinuation. Cox proportional hazards models were constructed to assess associations between recurrence and ET/RT. Results: Of 484 patients, median age was 71.9 years old and 90% were non-Hispanic white. The majority of patients had tumor size ≤2cm (81%) and did not receive chemotherapy (92%). Approximately one third were clinically node negative but did not undergo axillary surgery (32%). The average follow-up from date of diagnosis was 34.5 months. Percentages of patients who initiated ET and/or received RT are provided in Table 1. Receipt of both ET and RT decreased with age (p&amp;lt;0.001); older patients were more likely to receive ET alone (p&amp;lt;0.001) or neither ET nor RT (p&amp;lt;0.001). Patients diagnosed since 2015 were more likely to omit RT (p&amp;lt;0.001). Of the 361 patients who initiated ET, patients who did not undergo RT were more likely to discontinue ET before 5 years compared to those who did undergo RT (Table 2). Among those who underwent lumpectomy and RT (n=276), there was no difference in risk of recurrence among those who persisted with ET, discontinued ET early, or did not initiate ET. However, among those who underwent lumpectomy but omitted RT (n=159), women did not initiate ET had a higher risk of recurrence than those who persisted with ET (HR 4.05, 95% CI 1.03-16) or discontinued ET early (HR 9.37, 95% CI 2.47-35.6). Conclusion: This real world data analysis showed that among older patients with cN- HR+ breast cancer, a substantial proportion of patients who omitted RT also did not initiate ET. Those who did not undergo RT were more likely to discontinue ET early. In addition, among women who omitted RT, those who did not initiate ET had higher risk of recurrence. Caution should be taken when omitting RT in this patient population, since concomitant omission of RT and poor compliance with ET could increase the risk of disease recurrence. Table 1. Percentage of patients who initiated ET and/or received RTTreatment % (95% CI)ET &amp; no RT27.4% (23.6-31.5%)No ET &amp; RT10.2% (7.8-13.2%)No ET &amp;no RT13.8% (11.0-17.2%)ET &amp;RT47.9% (43.5-53.4%) Table 2. Probability of ET continuation among women who initiated ET, by RT statusMonths after ET initiationProbability of ET continuation012243648Overall1.000.850.800.760.70RT1.000.860.820.780.73No RT1.000.830.770.720.63 Citation Format: Mei Wei, Xuechen Wang, Danielle Zimmerman, Lindsay M Burt, Benjamin Haaland, N. L. Henry. Endocrine therapy (ET) and radiotherapy (RT) use among elderly women with hormone receptor positive (HR+), clinically node negative (cN-) breast cancer [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 P2-18-04.

Fertility Preservation in the Transgender Population

Hormonal and surgical treatments for transgender individuals can severely impact reproductive potential. In this review, we discuss the role of fertility preservation in both male-to-female and female-to-male transgender patients. We focus on the effects of hormone replacement therapy on the gonads and discuss current methods and techniques available for fertility preservation. Moreover, we review the current literature on patient attitudes toward fertility preservation and existing barriers to care. The literature supports the notion that feminizing therapy negatively impacts spermatogenesis, as evidenced by impaired semen parameters. The degree of such decline lies on a spectrum and can be somewhat unpredictable. Similarly, masculinizing therapy with testosterone has variable effects on ovarian function, gynecologic organs, and future fertility potential. Further research is required to better elucidate the long-term effects of such therapies. Optimal timing for fertility preservation is in the postpubertal period prior to initiation of hormonal therapy. This is however not always possible. A multitude of barriers to pursuing fertility preservation exist, including lack of appropriate counseling, the potentially invasive nature of some fertility preservation methods, and the financial burden placed on the patients. Fertility preservation in the transgender population remains poorly utilized. For transgender women, cryopreservation of sperm ideally is performed prior to initiation of hormone replacement therapy. Nonetheless, studies have shown that a degree of spermatogenesis is seen in some individuals without discontinuation of hormonal therapy. This could allow for less disruption, both physically and emotionally. Fertility preservation in transgender men remains invasive with oocyte retrieval as the main technique. Cessation of therapy, ovarian stimulation, and invasive testing has potential to be traumatic and enhance dysphoria. The possibility of fertility preservation at the time of gonadectomy is promising. Prepubertal fertility preservation is also on the horizon, though still experimental. Cost of preservation techniques and storage is currently prohibitive for many patients. Recent changes to state insurance mandates may soon make fertility preservation more accessible. Future research may demonstrate that fertility preservation is possible at the time of gender confirmation surgery, with the goal of being both effective and nontraumatic to the patient.

Incidence of Hypertension Among Children Treated With Adrenocorticotropic Hormone (ACTH) or Prednisolone for Infantile Spasms.

Children with infantile spasms are often treated with hormonal therapies including adrenocorticotropic hormone (ACTH) and prednisolone. These have numerous systemic side effects including hypertension and, rarely, fatal cardiomyopathy; however, the incidence of these side effects has not been well described. This study aims to quantify the incidence and short-term sequelae of hypertension in this population. A retrospective chart review was performed at a single institution. Children 2 months to 2 years old with newly diagnosed infantile spasms treated from 2013 to 2017 were included. Variables collected included age, sex, etiology and treatment of infantile spasms, documented or missed diagnosis of hypertension, treatment of hypertension, echocardiogram results, referrals for hypertension, and persistence of hypertension 2 to 4 months after treatment. Analyses included descriptive statistics with percentiles, means, and medians. Differences between groups were assessed using Fisher exact tests. Hypertension occurred in 34/77 children (44%) during treatment with ACTH and 4/11 children (36%) during treatment with prednisolone. No child developed hypertension during treatment with nonhormonal therapies. The incidence of hypertension between ACTH and prednisolone groups was not significantly different (P = .75). The incidence of hypertension was significantly higher in the ACTH and prednisolone groups compared to the nonhormonal group (P < .001 for each). Sixteen children received echocardiograms, with no cases of cardiomyopathy. Two children had persistent hypertension at 2 months after discontinuation of hormonal therapy. Hypertension is a very common side effect of hormonal therapy for infantile spasms; however, few developed long-term hypertension and none developed cardiomyopathy. Further study is needed to determine the role of antihypertensive treatment for hormone-related hypertension.

Is higher dose radiation necessary for positive resection margin after breast-conserving surgery for breast cancer?

BackgroundA positive resection margin after breast-conserving surgery (BCS) usually requires re-excision, which impairs cosmetic outcomes and causes considerable distress. This study aimed to evaluate the prognosis of patients with positive resection margin after BCS and the role of radiation therapy (RT) in these patients. Materials and methodsWe analyzed 297 patients who underwent BCS for breast cancer and had invasive carcinoma or ductal carcinoma in situ (DCIS) within less than 1 mm from the resection margin in Samsung Medical Center from January 2000 to June 2012. The association between RT dose and the incidence rate of ipsilateral breast tumor recurrence (IBTR) was examined. ResultsAfter a median follow-up of 78 months, the incidence rate of IBTR in all patients was 4.6% after 5 years. In the multivariate analysis, the unfavorable factors associated with IBTR were age < 40 years (p = 0.019), RT dose (<60 Gy vs. > 66 Gy, p = 0.012; 60–66 Gy vs. > 66 Gy, p = 0.017), and discontinuation of hormone therapy (p = 0.001). ConclusionsAmong the patients with invasive carcinoma or DCIS within less than 1 mm from the resection margin, adjuvant RT with higher dose > 66Gy EQD2 might improve local control. Further prospective studies are warranted to validate the benefit and risk of a high dose boost after BCS in patients with a positive resection margin.

Opioids for cancer pain: A growing quandary: Opioid prescriptions for cancer-related pain are facing greater scrutiny amid the nation's spiraling epidemic.

Opioids for cancer pain: A growing quandary: Opioid prescriptions for cancer-related pain are facing greater scrutiny amid the nation's spiraling epidemic.

Adherence and Persistence to Adjuvant Hormonal Therapy in Early-Stage Breast Cancer Patients: A Population-Based Retrospective Cohort Study in Israel

Background: Adjuvant hormonal therapy (HT) has been consistently proven to improve multiple outcomes in early breast cancer yet rates of adherence and persistence are variable. Methods: We retrospectively identified women diagnosed with nonmetastatic breast cancer and initiating HT between January 2000 and December 2007 in a large Israeli health provider. Prescription records including the drug name, date of purchase, and the quantity of pills dispensed were collected. We used Cox proportional hazards and binary logistic models to analyze factors associated with early discontinuation (<5 years) and nonadherence (proportion of days covered, PDC <80%) of HT, respectively. Results: A total of 4,178 women with breast cancer were identified with nearly 95% of patients treated with tamoxifen as the initial HT. Over the 5-year follow-up period, early discontinuation was identified in 955 (23%) patients. The mean PDC was 82.9% (SD 0.004). Younger age and low BMI were both associated with an increased risk of early discontinuation and nonadherence. A history of hypertension was associated with a higher likelihood of both outcomes. Conclusion: Adherence and persistence with HT among Israeli breast cancer survivors are comparable to those in international reports. Interventions are necessary to identify and prevent suboptimal HT adherence.

Endocrine therapy discontinuation rates in older women with early stage breast cancer who are candidates for omission of radiation.

e23018 Background: As the treatment for early-stage breast cancer continually evolves, there has been a pragmatic shift with regard to standard treatment placing a high-value on multidisciplinary management. Recent studies have shown that sentinel lymph node biopsy (SLNB) and adjuvant radiation (RT) can be omitted in a subset of older women with early-stage hormone receptor positive breast cancer who plan to take adjuvant endocrine therapy (ET). Prior analyses estimate a wide range of discontinuation rates, with studies citing 31-73%. The primary aim of this analysis is to estimate the discontinuation rate of endocrine therapy in women ages 70 and older with early stage breast cancer who omit radiation therapy at our institution. Methods: We performed a retrospective review of institutional cancer registry and EMR data to identify all women with breast cancer, ages 70 or older, AJCC 7 stage I or II, hormone receptor positive, HER2 negative, who underwent lumpectomy at the University of Michigan inclusive of years 2014 through 2017. Multiple variables of interest were collected and analyzed. Results: 174 women met initial inclusion criteria for ER/PR positive, HER2 negative, Stage I/II disease, who underwent lumpectomy. Of these, N = 10 pursued adjuvant radiation therapy with omission of ET, and N = 19 declined both ET and RT upfront. The remaining 145 women chose to pursue ET alone (N = 78) or ET+RT (N = 67). 30/145 (21%) discontinued endocrine therapy, 22% (N = 15) in the ET+RT, 19% (N = 15) in the ET alone groups. There was no statistically significant difference between groups with regard to the discontinuation of ET upon comparison, log-rank p-value 0.4. The primary reason for ET discontinuation, N = 27 (90%) was secondary to side effects. Conclusions: This review demonstrated that a significant number (54%) of older women opt to omit radiation in favor of ET alone after multidisciplinary discussion, in accordance with NCCN guidelines. Endocrine therapy discontinuation rates among older women at our institution were comparable to rates in the literature for women of all ages, and the reason for discontinuation was attributed to side effects. The pivotal clinical trials (PRIME II and CALGB 9343) exploring ET alone versus ET+RT did not report on ET discontinuation rates. In our analysis, almost 20% of women receiving ET alone discontinued ET therapy, calling into question a missed radiation treatment opportunity in a curative setting.

Patterns of endocrine therapy in a national cohort of early stage HER2‐positive breast cancer patients

Guidelines recommend ≥5years of endocrine therapy for hormone receptor-positive breast cancer patients, but nonadherence and treatment discontinuation are common. We examined adherence trajectories and early discontinuation of endocrine therapy over 5years from treatment initiation. Our retrospective cohort study used a national sample of Australian women dispensed publicly subsidised trastuzumab for early HER2-positive breast cancer. We included women initiating endocrine therapy between April 2007 and June 2011, followed until June 2016 (n=2656). We used group-based trajectory modelling and Kaplan-Meier analysis to examine patterns of adherence and time to discontinuation and restarting. We identified five adherence trajectories: quick decline (10.4%), moderate decline (8.6%), quick decline then stable (10.3%), stable with late decline (23.6%), and high and stable (47.2%). Women in the high and stable trajectory group were older and more likely to initiate therapy with anastrozole than women in other groups. Time periods after first 6months, 1.5, and 4years from initiation seemed critical in terms of remaining adherent on endocrine therapy; 45.8% of the cohort discontinued endocrine therapy with a median time to discontinuation of 2.6years (interquartile range 1.0-4.4), and 45.8% of the women discontinuing restarted treatment (median time 182.0, interquartile range 133.0-279.0days). Our study highlights evidence-practice gaps in the use of endocrine therapy, with half of our sample experiencing suboptimal adherence or persistence. Trajectory modelling provided detailed information about patterns of nonadherence and critical time periods for adherence to endocrine therapy. This information is important for developing targeted interventions to improve adherence.

3365 Treatment Interruptions and Early Discontinuation of Hormone Therapy in Hormone Receptor-Positive Breast Cancer Patients

OBJECTIVES/SPECIFIC AIMS: (1) To evaluate the association of patient and clinical factors with adherence to adjuvant hormone therapy (HT). (2) To examine the association of HT-related symptoms and the extent of remediation with early discontinuation of hormone therapy. METHODS/STUDY POPULATION: Retrospective cohort study of risk factors for interruption and early discontinuation of adjuvant hormone therapy in hormone receptor-positive nonmetastatic breast cancer patients diagnosed between 2009 and 2015. This study will include incident hormone receptor-positive breast cancer patients who initiated their HT and were followed at Tufts MC until Dec 31, 2016. Primary data source is electronic medical records (EMRs) RESULTS/ANTICIPATED RESULTS: The primary outcome of this study is early discontinuation to HT, defined as the first treatment gap of greater than or equal to 180 days following the initiation of HT. Treatment interruption, defined as any patient- or provider-initiated treatment gap of ≥ 2 weeks, will be examined as the secondary endpoint. Any HT-related symptoms occurred during a follow-up interval will be captured and categorized into five major types (i.e., vasomotor, neuropsychological, gastrointestinal, gynecological, and musculoskeletal symptoms). Onset and duration of a HT-related symptom will be recorded. Severity of the symptoms will also be rated by clinical oncologists. Remediations in response to HT- related symptoms will be collected and categorized into to two groups (pharmacological or non-pharmacological) and whether they were patient- or provider-initiated. Response to a remediation is defined as complete relief, partial relied, no relief, or with worsening symptoms. Response to a treatment change (i.e., HT switch or hold) was collected separately but using the same criteria. Analyses will be performed on the association between patient and clinical factors with rates of nonadherence (unplanned treatment interruption and/or early discontinuation) of hormone therapy, respectively. We also will explore whether patients with elevated symptoms and/or incomplete remediation will have earlier discontinuation of hormone therapy. DISCUSSION/SIGNIFICANCE OF IMPACT: Through formal chart review, we will establish a dataset that contains highly detailed information about treatment-emergent symptoms and remediations, which will enable us to quantitatively assess the impact of these treatment factors on adherence to hormone therapy for breast cancer. The in-depth analysis of risk factors associated with nonadherence to hormone therapy will inform development of interventions to improve cancer outcomes.

Abstract GS6-02: A randomized, double-blind, placebo-controlled trial of oxybutynin (Oxy) for hot flashes (HF): ACCRU study SC-1603

Abstract Background: HF occur in about 75% of midlife women and are associated with quality of life disruption and premature endocrine therapy discontinuation among breast cancer survivors. Estrogen therapy, effective for HF, is contraindicated in hormone receptor-positive breast cancer (BC). Previous studies have suggested that Oxy could be effective in managing HF. Methods: This randomized, placebo (P)-controlled trial enrolled women who had experienced HF ≥28 times per week over &amp;gt;30 days and of sufficient severity to seek treatment. Patients (pts) were randomized to receive oral Oxy at two doses: 2.5mg BID for 6 weeks (Oxy2.5), 2.5mg BID for a week with subsequent increase to 5mg BID (Oxy5), or matching P, in equal ratios. Baseline and monthly questionnaires were administered including a HF diary, the HF related daily interference scale (HFRDIS) and a symptom experience questionnaire. The primary endpoint was intra-patient change in weekly HF score and frequency from baseline to end of study compared using Kruskal-Wallis tests. Results: 150 pts were accrued between 2/23/2017-3/5/2018. 4 pts cancelled before starting treatment and were excluded from analyses. This interim report includes the first 104 pts for which at least one post-baseline evaluation was available. Baseline characteristics were well-balanced between the arms. Sixty-two percent were on tamoxifen or an aromatase inhibitor for the duration of the study. Pts on both Oxy doses had a significantly greater reduction in HF score and frequency compared to P. Pts on Oxy2.5 had a mean change in HF score of -10 (SD 7.4) vs -5.1 (SD 9.7) with P, p=0.003; and a mean change in average weekly number of HF of -4.6 (SD 3.1) vs -2.3 (SD 3.9), p=0.002. Pts on Oxy5 had a mean change in HF score of -16.2 (SD 5.1) vs -5.1 (SD 9.7) with P, p&amp;lt;0.001; and a mean change in average weekly number of HF of -7.0 (SD 4.0) vs -2.3 (SD 3.9), p&amp;lt;0.001. Repeated measures mixed models confirmed that, after adjusting for baseline values, both Oxy arms had significantly lower HF scores and frequency compared to P (p&amp;lt;0.001). HFRDIS revealed that pts in both Oxy arms experienced improvement in the following HF interference measures: work, social activities, leisure activities, sleep, relations, life enjoyment, and overall quality of life. Pts on Oxy5 also had improvement in HF interference with mood. Pts on Oxy2.5 experienced more stomach pain (p=0.031), diarrhea (p=0.007), nausea (p=0.04), headaches (0.032), episodes of confusion (0.012), dry mouth (p=0.003) and dry eyes (0.027) compared to P. Pts on Oxy5 experienced more constipation (0.004), dry mouth (0.001) and difficulty urinating (0.004) compared to P. There were no differences in study discontinuation due to adverse effects between either Oxy arm and P (Oxy2.5 vs P, p=0.653; Oxy5 vs P, p=0.483). Conclusions: Oxy is superior to P for management of HF. Oxy2.5 and 5 were both associated with significant improvements in HF scores and frequency as well as improvement in HF interference with several quality of life measures. While pts on Oxy experienced more side effects than pts on P, rates of discontinuation due to adverse events were low. This study was supported by the Breast Cancer Research Foundation. Citation Format: Leon-Ferre RA, Novotny PJ, Faubion SS, Ruddy KJ, Flora D, Dakhil C, Rowland KM, Graham ML, Le-Lindqwister N, Loprinzi CL. A randomized, double-blind, placebo-controlled trial of oxybutynin (Oxy) for hot flashes (HF): ACCRU study SC-1603 [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr GS6-02.