Initiation Of Hormone Therapy Research Articles

A randomized trial of the impact of symptom monitoring using an electronic patient-reported outcome app on health-related quality of life in postmenopausal breast cancer patients receiving adjuvant endocrine therapy.

Electronic patient-reported outcomes (ePRO) monitoring is a useful communication tool for cancer patients and healthcare providers. In this study, we examined the impact of symptom monitoring using an ePRO app on quality of life (QoL) in postmenopausal breast cancer patients receiving adjuvant endocrine therapy. The free app "Welby My Carte ONC" was used in the study. Patients with breast cancer starting adjuvant endocrine therapy were randomly assigned in a 1:1 ratio to ePRO monitoring (ONC) and control groups. The ONC group reported five symptoms extracted from the Patient-Reported Outcome-Common Terminology Criteria for Adverse Events (PRO-CTCAE) (insomnia, joint pain, headache, anxiety, and hot flashes) weekly for 3months through the app. Reported symptoms were shared with medical personnel. When serious symptoms were reported, these personnel ascertained the patient's health status and provided advice over the phone. The primary endpoint was QoL measured by the Functional Assessment of Cancer Therapy-Breast (FACT-B) at 3months from enrollment. Differences between groups were tested using analysis of covariance. The study included 125 subjects with mean age of 64years in the ONC group (n = 61) and 63years in the control group (n = 64). In the ONC group, the response rate to PRO-CTCAE was about 70% or higher until week 10. The item missing rate was 0. The ONC group reported more symptoms related to joint pain and insomnia. The difference in FACT-B total score between the groups was -1.55 (95% confidence interval: -5.91, 2.81), indicating no significant difference. Symptom monitoring using ePRO early after initiation of adjuvant endocrine therapy after surgery did not improve QoL of breast cancer patients.

Validation and responsiveness of the English version of the Chemotherapy-Induced Alopecia Distress Scale (CADS) in breast cancer patients

PurposeThis study aimed to validate the Chemotherapy-Induced Alopecia Distress Scale (CADS) in a diverse English-speaking population and patients with endocrine treatment-induced alopecia (EIA).ObjectiveChemotherapy and endocrine therapy commonly cause alopecia in breast cancer patients, leading to significant psychological and social challenges. The CADS was developed to assess the psychosocial impact of alopecia, but its generalizability beyond Korean patients requires further investigation.MethodsData from the CHANCE study (NCT02530177), which focused on non-metastatic breast cancer, was used. The cohort included 256 patients, and CADS data were collected at baseline, 6 months after chemotherapy completion, or 12 months after initiating endocrine therapy. The CADS questionnaire comprised 17 items covering physical and emotional health, daily activities, and relationships. Reliability was assessed using Cronbach’s alpha, and responsiveness was measured by effect size.ResultsThe CADS exhibited good reliability, with Cronbach’s alpha of 0.91 for the overall score, indicating acceptable internal consistency in both chemotherapy (0.89) and endocrine therapy (0.86) groups. Longitudinal responsiveness was supported by an effect size of 0.49 between decreasing satisfaction with hair growth and increasing emotional distress. Cross-sectional validity was confirmed, with effect sizes of 0.91 and 0.92 for satisfaction with hair growth and emotional and activity domains, respectively.ConclusionThe CADS is a valid and responsive tool for assessing the psychosocial impact of chemotherapy-induced alopecia and endocrine treatment-induced alopecia in a diverse Western patient population.

Abstract PO4-05-04: Comparative effectiveness of Palbociclib plus Aromatase inhibitor versus fulvestrant alone as initial endocrine therapy for HR+/HER2- advanced breast cancer in Chinese clinical practice: a real-world study

Abstract Background: In the real world, there are still a large number of HR+/HER2- advanced breast cancer patients receiving initial endocrine therapy with fulvestrant monotherapy in China, especially patients with bone metastases only. It is due to lack of data comparing the effective between Palbociclib combined with AI and fulvestrant monotherapy as initial endocrine therapy. On the other hand, there are economic factors and access issues. According to the National Cancer Center's previous clinical experience, Palbociclib combined with AI is superior to fulvestrant monotherapy in HR+/HER2- advanced breast cancer patients receiving initial endocrine therapy. Therefore, we collected and summarized the previous clinical data in our center to compare the effective of Palbociclib combined with AI and fulvestrant monotherapy for HR+/HER2-advanced breast cancer patients receiving initial endocrine therapy in China. Patients and methods: This is a retrospective real-world study of multicenter studies. It aimed at verifying the effective of Palbociclib combined with AI and fulvestrant monotherapy for HR+/HER2-advanced breast cancer patients receiving initial endocrine therapy in China. A total of 392 patients with ≥3 months of follow-up received Palbociclib plus AI or fulvestrant alone in the first-line setting between April 1, 2015 and February 1, 2023. Stabilized inverse probability treatment weighting (sIPTW) was used to balance baseline demographic and clinical characteristics. Real-world progression-free survival (rwPFS) and overall survival (OS) were analyzed. Results: After sIPTW adjustment, a median follow-up of 37 months (range 34-40) in the Palbociclib group and 59 months (range 56-61) in those taking fulvestrant alone. Palbociclib combination regiment was associated with significantly longer median rwPFS compared to fulvestrant alone (22.0 vs 14.0 months; HR,0.469;95% CI 0.370–0.594, p< 0·0001). Median OS was not reached in the Palbociclib group and was 57 months (95% CI 54.0–66.0) in the fulvestrant group(HR,0.666; 95% CI 0.437–1.017, p< 0·94). Conclusion: In the real-world population of patients, palbociclib combined with AI endocrine therapy is superior to fulvestrant monotherapy in HR+/HER2- advanced breast cancer patients receiving initial endocrine therapy. PFS and OS before IPTW PFS and OS after IPTW Table patient characteristics Citation Format: Jian Yue, Xue Wang, Jie Ju, Zixiang Yang, Tong Wei, Peng Yuan, Min Gao, Ling Xu, Yin Guan. Comparative effectiveness of Palbociclib plus Aromatase inhibitor versus fulvestrant alone as initial endocrine therapy for HR+/HER2- advanced breast cancer in Chinese clinical practice: a real-world study [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-05-04.

A Qualitative Study of Transgender and Nonbinary Perspectives Regarding the Desired Properties of a Peer Support Intervention for the Initiation of Gender-Affirming Hormone Therapy [ID 2683451

INTRODUCTION: Transgender and nonbinary (TNB) people experience significant mental health disparities and challenges accessing gender-affirming care. Peer support interventions have been shown to improve mental health in other populations and contexts but have not been uniquely tailored to the initiation of gender-affirming hormones. This study aims to identify the desired properties of a peer support intervention for TNB people initiating gender-affirming hormones. METHODS: We conducted semistructured interviews with TNB adults who had initiated or attempted to initiate gender-affirming hormones (IRB: HUM00203630: approved/exempt; gender-affirmation: off-label). Participants were selected by snowball and purposive sampling methods. Interview questions focused on the participants' experiences with peer support and their vision for ideal peer support while initiating hormones. Interviews were transcribed and analyzed using reflective thematic analysis with inductive and deductive coding. A TNB community advisory board collaborated in the study design and interviews were conducted by TNB research team members. RESULTS: The ages of the participants ranged from 20 to 52 years (mean=32); 8/18 identified as men or trans men; 4/18 identified as nonbinary; 3/18 identified as women or trans women; 3/18 identified as genderqueer or genderfluid; 10/18 identified as a person of color. Themes include the importance of 1) trans community knowledge in guiding hormone therapy decisions, 2) having support structures attend to intersectional identities, and 3) recognizing barriers to peer engagement, including anxieties about fitting in and internalized transphobia. CONCLUSION: Centering TNB voices is essential in designing a peer support intervention for hormone initiation. Our participants offered nuanced approaches for how to share information about hormones, attend to intersectional identities, and navigate barriers to peer engagement.

The Women's Health Initiative Randomized Trials and Clinical Practice: A Review.

Approximately 55 million people in the US and approximately 1.1 billion people worldwide are postmenopausal women. To inform clinical practice about the health effects of menopausal hormone therapy, calcium plus vitamin D supplementation, and a low-fat dietary pattern, the Women's Health Initiative (WHI) enrolled 161 808 postmenopausal US women (N = 68 132 in the clinical trials) aged 50 to 79 years at baseline from 1993 to 1998, and followed them up for up to 20 years. The WHI clinical trial results do not support hormone therapy with oral conjugated equine estrogens plus medroxyprogesterone acetate for postmenopausal women or conjugated equine estrogens alone for those with prior hysterectomy to prevent cardiovascular disease, dementia, or other chronic diseases. However, hormone therapy is effective for treating moderate to severe vasomotor and other menopausal symptoms. These benefits of hormone therapy in early menopause, combined with lower rates of adverse effects of hormone therapy in early compared with later menopause, support initiation of hormone therapy before age 60 years for women without contraindications to hormone therapy who have bothersome menopausal symptoms. The WHI results do not support routinely recommending calcium plus vitamin D supplementation for fracture prevention in all postmenopausal women. However, calcium and vitamin D are appropriate for women who do not meet national guidelines for recommended intakes of these nutrients through diet. A low-fat dietary pattern with increased fruit, vegetable, and grain consumption did not prevent the primary outcomes of breast or colorectal cancer but was associated with lower rates of the secondary outcome of breast cancer mortality during long-term follow-up. For postmenopausal women, the WHI randomized clinical trials do not support menopausal hormone therapy to prevent cardiovascular disease or other chronic diseases. Menopausal hormone therapy is appropriate to treat bothersome vasomotor symptoms among women in early menopause, without contraindications, who are interested in taking hormone therapy. The WHI evidence does not support routine supplementation with calcium plus vitamin D for menopausal women to prevent fractures or a low-fat diet with increased fruits, vegetables, and grains to prevent breast or colorectal cancer. A potential role of a low-fat dietary pattern in reducing breast cancer mortality, a secondary outcome, warrants further study.

Tumor lysis syndrome following letrozole for locally advanced breast cancer: a case report

BackgroundLetrozole, an aromatase inhibitor, is used to treat breast cancer in postmenopausal women. Tumor lysis syndrome (TLS) is a complication that can trigger multiple organ failure caused by the release of intracellular nucleic acids, phosphate, and potassium into the blood due to rapid tumor cell disintegration induced by drug therapy. TLS is uncommon in solid tumors and occurs primarily in patients receiving chemotherapy. Herein, we report a rare occurrence of TLS that developed in a patient with locally advanced breast cancer following treatment with letrozole.Case presentationAn 80-year-old woman with increased bleeding from a fist-sized left-sided breast mass presented to our hospital. Histological examination led to a diagnosis of invasive ductal carcinoma of the luminal type. The patient refused chemotherapy and was administered hormonal therapy with letrozole. Seven days after letrozole initiation, she complained of anorexia and diarrhea. Blood test results revealed elevated blood urea nitrogen (BUN) and creatinine (Cr) levels, and she was admitted to our hospital for intravenous infusions. On the second day after admission, marked elevations of LDH, BUN, Cr, potassium, calcium, and uric acid levels were observed. Furthermore, metabolic acidosis and prolonged coagulation capacity were observed. We suspected TLS and discontinued letrozole, and the patient was treated with hydration, febuxostat, and maintenance hemodialysis. On the third day after admission, her respiratory status worsened because of acute respiratory distress syndrome associated with hypercytokinemia, and she was intubated. On the fourth day after admission, her general condition did not improve, and she died.ConclusionsAlthough TLS typically occurs after chemotherapy initiation, the findings from the present case confirm that this syndrome can also occur after hormonal therapy initiation and should be treated with caution.

Association between trajectories of adherence to endocrine therapy and risk of treated breast cancer recurrence among US nonmetastatic breast cancer survivors.

Endocrine therapy is the mainstay treatment for breast cancer (BC) to reduce BC recurrence risk. During the first year of endocrine therapy use, nearly 30% of BC survivors are nonadherent, which may increase BC recurrence risk. This study is to examine the association between endocrine therapy adherence trajectories and BC recurrence risk in nonmetastatic BC survivors. This retrospective cohort study included Medicare beneficiaries in the United States (US) with incident nonmetastatic BC followed by endocrine therapy initiation in 2010-2019 US Surveillance, Epidemiology, and End Results linked Medicare data. We calculated monthly fill-based proportion of days covered in the first year of endocrine therapy. We applied group-based trajectory models to identify distinct endocrine therapy adherence patterns. After the end of the first-year endocrine therapy trajectory measurement period, we estimated the risk of time to first treated BC recurrence within 4 years using Cox proportional hazards models. We identified 5 trajectories of adherence to endocrine therapy in BC Stages 0-I subgroup (n = 28,042) and in Stages II-III subgroup (n = 7781). A trajectory of discontinuation before 6 months accounted for 7.0% in Stages 0-I and 5.8% in Stages II-III subgroups, and this trajectory was associated with an increased treated BC recurrence risk compared to nearly perfect adherence (Stages 0-I: adjusted hazard [aHR] = 1.84, 95% CI = 1.46-2.33; Stages II-III: aHR = 1.38, 95% CI = 1.07-1.77). Nearly 7% of BC survivors who discontinued before completing 6 months of treatment was associated with an increased treated BC recurrence risk compared to those with nearly perfect adherence among Medicare nonmetastatic BC survivors.

Inflammation as a Potential Mechanism Contributing to Sexual Functioning Following Initiation of Gender-Affirming Hormone Therapy

Inflammation as a Potential Mechanism Contributing to Sexual Functioning Following Initiation of Gender-Affirming Hormone Therapy

85. Use of Telemedicine Services is Associated With Longer Time to Initiation of Hormone Therapy in Transgender Teens and Young Adults

85. Use of Telemedicine Services is Associated With Longer Time to Initiation of Hormone Therapy in Transgender Teens and Young Adults

A polygenic score associated with fracture risk in breast cancer patients treated with aromatase inhibitors

Identifying women at high risk of osteoporotic fracture from aromatase inhibitor (AI) therapy for breast cancer is largely based on known risk factors for healthy postmenopausal women, which might not accurately reflect the risk in breast cancer patients post-AI therapy. To determine whether a polygenic score associated with fracture in healthy women is also significant in women treated with AIs for breast cancer, we used data from a prospective observational cohort of 2152 women diagnosed with hormonal receptor positive breast cancer treated with AIs as the initial endocrine therapy and examined a polygenic score of heel quantitative ultrasound speed of sound (gSOS) in relation to incident osteoporotic fracture after AI therapy during a median 6.1 years of follow up after AI initiation. In multivariable models, patients with the second and third highest tertiles (T) versus the lowest tertile of gSOS had significantly lower risk of fracture (T2: adjusted HR = 0.61, 95% CI: 0.46-0.80; T3: adjusted HR = 0.53, 95% CI: 0.40-0.70). The lower risk of fracture in patients with the highest tertile of gSOS remained significant after further adjustment for BMD at the hip (T3: adjusted HR = 0.62, 95% CI: 0.42-0.91). In conclusion, our analysis showed gSOS as a novel genetic predictor for fracture risk independent of BMD among breast cancer patients treated with AIs. Future studies are warranted to evaluate the performance of incorporating gSOS in prediction models for the risk of AI-related fracture in breast cancer patients.

Lipid changes during endocrine therapy in early-stage breast cancer patients: A real-world study

BackgroundEndocrine drugs may affect lipid metabolism in breast cancer (BC) patients. This study explores lipid changes in early-stage BC patients taking different endocrine drugs.MethodsThe changing trend of blood lipid during endocrine therapy in 2756 BC patients from January 2013 to December 2021 was retrospectively analyzed. The changes in four lipid parameters were assessed by the Generalized Linear Mixed Model, including total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL-C), and high-density lipoprotein (HDL-C). These parameters were quantified at baseline and at 6, 12, 18, 24, 36, 48, 60, and 72 months after endocrine therapy initiation. Furthermore, a subgroup analysis according to menopausal status or medication types was conducted.ResultsA total of 1201 patients taking aromatase inhibitors (AIs), including anastrozole (ANA), letrozole (LET), or exemestane (EXE), and 1555 patients taking toremifene (TOR) were enrolled. TC and TG levels showed a significantly elevated trend during 5 years of treatment (P < 0.05). HDL-C levels increased from baseline in the TOR group (P < 0.05). Compared with the postmenopausal AI group, the increasing trends of TC, TG, and LDL-C in the premenopausal AI group were more evident with the extension of time (β = 0.105, 0.027, 0.086, respectively). Within 3 years, TC, TG, and LDL-C levels in the ANA and LET groups were significantly higher than baseline (P < 0.05). Moreover, the levels of TG in the EXE group were significantly lower than that in the ANA or LET group (P < 0.05), but this significant difference disappeared after 3 years.ConclusionsAIs significantly influenced lipid profiles more than TOR. AIs had a greater effect on blood lipids in premenopausal patients. Steroidal AIs (EXE) may affect lipid levels less than nonsteroidal AIs (ANA and LET).

Changes in systemic cancer therapy in Australia during the Delta and Omicron waves of the COVID-19 pandemic (2021-2022): a controlled interrupted time series analysis.

Australian lockdowns in response to the initial coronavirus disease 2019 (COVID-19) outbreak in 2020 were associated with small and transient changes in the use of systemic cancer therapy. We aimed to investigate the impacts of the longer and more restrictive lockdowns in the Australian states of New South Wales (NSW) and Victoria during both the Delta subvariant lockdowns in mid-2021 and the Omicron subvariant outbreak in late 2021/early 2022. Population-based, controlled interrupted time series analysis. We conducted a national observational study using de-identified records of government-subsidised cancer medicines dispensed to a random 10% sample of Australians between July 2018 and July 2022. We used controlled interrupted time series analysis to investigate changes in the dispensing, initiation and discontinuation of all cancer medicines dispensed to residents of NSW and Victoria, using the rest of Australia as a control series. We used quasi-Poisson regression to model weekly counts and estimate incidence rate ratios (IRRs) for the effect of (each) the Delta phase lockdown and the Omicron outbreak on our systemic cancer therapy outcomes. Between July 2018 and July 2022, cancer medicines were dispensed 592 141 times to 33 198 people in NSW and Victoria. Overall, there were no changes to the rates of dispensing, initiation or discontinuation of antineoplastics during the Delta phase lockdowns. In both states during the Omicron outbreak, there were significant decreases in the dispensing of antineoplastics (NSW IRR 0.89; 95% confidence interval [CI] 0.84, 0.93. Victoria IRR 0.92; 95% CI 0.88, 0.96) and in the initiation of endocrine therapy (NSW IRR 0.85; 95% CI 0.74, 0.99. Victoria IRR 0.78; 95% CI 0.65, 0.94), and no changes in the discontinuation of any systemic cancer therapy. The 2021 lockdowns and 2021/2022 Omicron outbreaks in NSW and Victoria had significant impacts on the dispensing, initiation and discontinuation of systemic cancer therapies, however, the overall effects were minimal. The impacts of lockdowns were less significant than the Omicron outbreaks, suggesting COVID-19 infection, health system capacity, and patient and community concerns were important factors for treatment changes.

Systematic Review on Gender-Affirming Testosterone Therapy and the Risk of Breast Cancer: A Challenge for Physicians Treating Patients from Transgender and Gender-Diverse Populations.

Conflicting evidence exists about the risk of breast cancer in transgender and gender-diverse (TGD) patients treated with testosterone. This review aimed to summarize current knowledge regarding the risk of breast cancer associated with gender-affirming testosterone treatment (GATT). A systematic literature search using the Preferred Reporting Items for Systematic Review and Meta-Analysis checklist was conducted in January 2023 through Ovid, Scopus, and Web of Science databases. English-language, peer-reviewed articles evaluating breast cancer in TGD patients after GATT that met the inclusion criteria were included. This review included 22 articles, with 14 case reports, 4 case series, and 4 retrospective cohort studies. The review identified 26 TGD patients who developed breast cancer post-GATT therapy, with inconclusive evidence on the relationship between testosterone and the risk of breast cancer in TGD patients. This uncertainty in part arises from the mechanisms governing testosterone's effects within breast tissue, with contrasting theories proposing both proliferative and antiproliferative impacts. Considering this ambiguity, it is imperative for healthcare providers to engage in informed discussions with patients prior to initiating hormone therapy to discuss potential adverse effects, including the possibility of breast cancer development in TGD individuals. Patient education and shared decision-making are essential components of responsible care in this context.

Treatment Goals of Adolescents and Young Adults for Gender Dysphoria.

With this study, we aim to describe transgender and nonbinary adolescents and young adults' stated gender treatment goals at the time of initial presentation to medical care. This is a retrospective chart review of transgender and nonbinary patients aged 10 to 24 seeking specific gender-affirming health care. Charts were reviewed for specifically stated goals of future hormonal or surgical care for gender and analyzed by the experienced or asserted gender (man, woman, nonbinary, eclectic) of participants. In total, 176 patient encounters were reviewed. Of these, 71% were assigned female at birth. Most participants experienced a masculine gender (46.6%), identified as white (65.3%), and had private health insurance (73.3%). Most patients had a goal of initiating hormone therapy (97.4%) and eventual surgery (87.1%). Of those who had a surgical goal, most (87.5%) desired surgery of the chest or breast, and a minority (29.3%) desired eventual genital surgery. The second-largest gender group was patients who either declined to state an asserted gender or felt unable to describe their gender experience (eclectic, 23.3%), and this group's treatment goals did not mirror any other group's goals. At the time of initial presentation to medical care for gender-specific needs, many adolescents are capable of asserting specific treatment goals. Most do not desire genital surgery. A large minority of patients decline to state an asserted gender or feel unable to assert a specific gender, and this population appears distinct from more traditional genders in terms of treatment goals.

Abstract A083: Initiation and persistence of hormone therapy in endocrine positive breast cancer at an urban safety-net hospital

Abstract Background: Evidence demonstrates inequities in receipt and persistence of hormone therapy among breast cancer patient populations based on race, ethnicity, insurance, and language. Institutions where patients seek cancer care may have an impact on receipt of treatment. It is unknown whether safety net hospitals, servicing a vulnerable patient population, exhibit inequities in receipt of hormone therapy for breast cancer. Study Design: We performed a retrospective study of patients diagnosed with all stages of hormone positive (ER+ and/or PR +) breast cancer treated at a safety net institution over the five year period from January 1, 2009 to December 31, 2013. The initiation of and persistence of hormone therapy were assessed by race, ethnicity, insurance status, and primary language. Persistence of therapy was defined as defined as at least 3 prescriptions (90 day supply) or more than 1 visit after start of treatment documenting taking treatment. Results: A total of 599 women were identified. The median age was 59 years, 58% were non-White, 32% were non-English-speaking, and 35% had Medicaid or no insurance. A total of 506 (84%) were started on hormone therapy. In multivariate regression analysis, the rate of endocrine therapy initiation was associated with higher stage at diagnosis, post-menopausal status, and HER2 negative status. Non-white race, Hispanic/Latino ethnicity, non-English-language, and Medicaid/no insurance were not significantly associated with or without initiation of hormone therapy. 93% of patients started on hormone therapy had evidence of continued treatment, 91% had evidence of continued treatment at 1 year, 75% finished their recommended course of hormone therapy. Conclusion: At an urban safety-net hospital, we do not observe inequities in the initiation of endocrine therapy for breast cancer by race, ethnicity, insurance, or language. Persistence of therapy was similar to nationally reported data. Additional research by hospital type, and granular reasons for non-adherence are warranted. Citation Format: Quinn S. Solfisburg, Brendin R. Beaulieu-Jones, Michael R. Cassidy, Naomi Y. Ko. Initiation and persistence of hormone therapy in endocrine positive breast cancer at an urban safety-net hospital [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr A083.

Contralateral prophylactic mastectomy: Weighing the risks of delayed chemotherapy, radiotherapy, and hormonal therapy

Many patients with unilateral breast cancer opt for contralateral prophylactic mastectomy (CPM) at the time of therapeutic mastectomy (immediate CPM) or following completion of adjuvant therapy. Studies show that immediate CPM increases the risk of surgical complications related to unilateral mastectomy (UM) alone, which may lead to delays in adjuvant therapy initiation. However, it is unclear if these complications cause clinically significant delays in initiating adjuvant chemotherapy, radiotherapy, or hormonal therapy. A retrospective chart review was conducted on patients with breast cancer who underwent immediate CPM versus UM alone at Columbia University Medical Center from January 2000 to December 2020. Patient demographic and oncologic characteristics; complications; and timing of adjuvant chemotherapy, radiotherapy, and/or hormonal therapy relative to therapeutic mastectomy were collected. In this study, 239 UM alone patients were propensity score matched to 239 immediate CPM patients. No significant difference in complication rates was found between the index and contralateral breasts in CPM patients. A similar percentage of CPM and UM patients experienced postoperative complications (19% vs. 17%, p = 0.64). No significant difference in time to adjuvant chemotherapy, radiotherapy, or hormonal therapy was found between CPM patients with complications and all CPM patients or all UM patients. There is a lack of clear guidance for clinical decision-making regarding timing of CPM relative to adjuvant therapy. Our study suggests that immediate CPM does not significantly increase the risks of postoperative complications or complication-related delays in the initiation of adjuvant chemotherapy, radiotherapy, or hormonal therapy. This information may help patients and providers to plan, select, and schedule breast cancer treatment options.

Estrogen-induced phenotype in hiPSC-derived cardiomyocytes of a woman affected by both Long QT Syndrome Type 2 and Polycystic Ovary Syndrome

Abstract Introduction Long QT Syndrome (LQTS) is an arrhythmogenic disorder caused either by genetic alteration or by exogenous factors. Polycystic Ovary Syndrome (PCOS) is a disease associated with high levels of testosterone and low levels of estrogen (E2). It has been suggested that hormones can influence the occurrence of malignant cardiac events in LQTS type 2 (LQT2) women, carriers of mutations on the potassium channel (hERG). However, the precise mechanisms governing this process still need to be clarified. Purpose We studied a patient affected by both LQT2 and PCOS who started experiencing cardiac symptoms after initiation of hormonal replacement therapy. We observed a correlation with the occurrence of arrhythmic events and the irregular assumption of the hormonal replacement therapy, thus we aim to dissect the underlying mechanism in patient-in-a-dish cardiac cellular model. Methods Induced Pluripotent Stem Cells (hiPSC) were generated from a woman affected by both LQT2 and PCOS and from a healthy donor, and then differentiated into cardiomyocytes (hiPSC-CMs). hiPSC-CMs were stimulated with E2 10nM for five time points (1, 5, 10, 15 and 30 minutes). The expression of potassium channel hERG, and of the G-coupled estrogen receptor (GPER) regulating the fast non-genomic pathway, were quantified after E2 stimulation at different time points by In Cell Western (ICW). The Unstimulated sample were used to normalize GPER and hERG expression to 100%. Electrophysiological experiments were performed using the whole-cell patch-clamp technique in current-clamp mode to record spontaneous action potentials (APs). AP duration at 30%, 50% and 90% repolarization (APD30, APD50 and APD90) was quantified. During spontaneous activity, AP duration values were rate-corrected with Bazett’s formula, thus obtaining cAPD. Results LQT2 hiPSC-CMs express higher levels of GPER (p&amp;lt;0.05) and hERG (p&amp;lt;0.01) than healthy hiPSC-CMs. A significant decrease in GPER expression was detected during 10nM E2 stimulation in healthy cardiomyocytes at the five time points (p&amp;lt;0.0001), while any difference was detected in hERG expression levels. E2 stimulation at different time points did not affect neither GPER nor hERG expression in LQT2 hiPSC-CMs. In LQT2 hiPSC-CMs, APDC values were significantly increased (p&amp;lt;0.0001) compared to healthy cells; pre-incubation with E2 for 10 minutes significantly shortened cAPD50 and increased spontaneous firing rate. In healthy hiPSC-CMs, E2 had no effect. Conclusions The hiPSC-CM model reproduces the LQT2 clinical phenotype. cAPD50 shortening by E2 was unexpected based on the proarrhythmic effect in the patient. The mechanism of LQT2-specific effects of E2 are under investigation.

Abstract 18762: Pacemaker Pocket Erosion - An Undesired Complication of Leuprolide Therapy

Introduction: Pacemaker pocket erosion is an uncommon delayed complication of the cardiac implantable electronic device (CIED) implantation that most frequently occurs in frail and elderly patients. We present a case of such a patient who developed pacemaker pocket erosion after being initiated on hormonal therapy for advanced prostate cancer. Case presentation: The patient is a ninety-three-year-old male with a history of persistent atrial fibrillation and dual chamber pacemaker in situ with last generator change two years prior presented with a two-week history of pacemaker wound dehiscence and exposed pacemaker. Six months earlier, the patient was diagnosed with advanced prostate cancer, was initiated on gonadotropin-releasing hormone agonist, leuprolide, and subsequently developed unintentional weight loss of 30 pounds. For two months prior to the current presentation, the patient noticed subjective discomfort at the site of the pacemaker pocket which he did not report to his cardiologist and eventually developed an erosive wound overlying the pacemaker pocket exposing the device (Image 1). He was admitted to the hospital and found to be hemodynamically stable, without leukocytosis and, negative blood cultures. Transthoracic and transesophageal echocardiograms showed no evidence of vegetation. He was empirically treated with daptomycin and was referred for pacing system extraction. He underwent pacing system replacement with leads and device extraction followed by leadless Micra VR (Medtronic, Minneapolis, MN) pacemaker implantation. Following a 4-week antibiotic course post pacemaker system extraction, the pacemaker pocket wound was fully healed. Conclusions: Aging and weight loss are known major risk factors for device-pocket erosion and externalization of the CIED. It highlights the importance of improving awareness of this entity and that initiation of hormonal therapy can be a contributing factor to such complications.

Endocrine therapy initiation among women diagnosed with ductal carcinoma in situ breast cancer from 2001-2016.

487 Background: Endocrine therapy (ET) initiation in people within 1 year of diagnosis of estrogen-receptor-positive (ER+) ductal carcinoma in situ (DCIS) has ranged from 21-45% in prior studies; however, these studies did not evaluate initiation post-2011 and may not reflect current patterns of use. ET use following ER+ DCIS diagnosis can reduce the relative risks of recurrence and contralateral breast cancer by 30-50%. We evaluated ET initiation over time and by demographic, tumor, and treatment characteristics in the Kaiser Permanente Breast Cancer Survivors Study between 2001-2016. Methods: We included people aged 20+ years diagnosed with unilateral DCIS with at least 1 year of cancer-free follow-up from three U.S. integrated health systems. We excluded people with ER-negative disease, no surgery, and those who received chemotherapy or unknown radiation therapy. ET dispensings (tamoxifen and aromatase inhibitors) were extracted from electronic pharmacy records within 1 year of a person’s initial DCIS breast cancer diagnosis. Using generalized linear models with a log link and Poisson distribution, we estimated relative rates (RRs) of ET use (vs none) over time and by demographic, tumor, and other treatment characteristics. Results: Among 1,782 pre- and postmenopausal people, 577 (32%) initiated ET within 1 year of diagnosis. From 2001-2016, ET use did not change over time (34% vs 36%), tamoxifen use declined slightly (34% vs 29%), and aromatase inhibitor use increased slightly (0% vs 7%). People were less likely to initiate ET if they were ≥65 years, Black, had borderline or unknown ER status, were not tested for ER, had breast conserving surgery (BCS) without radiation, or had a unilateral mastectomy. Conclusions: Only one-third of people with DCIS diagnosed in a community healthcare setting and potentially eligible for ET, initiated treatment within 1 year of their diagnosis. Previous studies have shown long-term benefits of ET use in people with DCIS; however, we saw no increase in use over time. Concerns about side-effects, overdiagnosis and overtreatment of DCIS, and confusion about treatment guidelines may explain relatively low ET initiation.[Table: see text]

The impact of 4R Care Delivery Model on timing and sequence of bone density screening among patients with breast cancer.

553 Background: Bone loss is common in patients with breast cancer and can impact treatment decisions related to endocrine therapy. Hence, bone density assessment prior to starting endocrine therapy is highly important, especially because endocrine therapy is the first line adjuvant treatment for patients with ER+ breast cancer. Implementing timely bone density assessment is challenging, particularly in the early care trajectory when there are many tests and procedures taking place. We conducted a care delivery optimization in a large health system to implement bone density testing and referral for bone health consultation prior to endocrine therapy. The optimization was conducted as part of implementing the 4R Oncology model (Right Info, Right Care, Right Patient, at the Right Time), a novel approach to improving patient-facing care planning, team-based delivery and patient self-management. Here we describe the impact of this intervention. Methods: A cohort of 278 women with breast cancer who were in the 4R intervention (the 4R cohort) was compared to a historical control cohort of 201 women who received care pre-4R. Demographic, bone health history, and oncologic care data were abstracted from chart review and clinical databases. The prevalence of bone loss and timing of bone density consultation request was compared between the 4R and historical control cohorts. Results: The age, race/ethnicity and rate of ER+ cancer were similar between cohorts. Patients in the 4R cohort were significantly more likely to have received a consultation for bone density screening prior to the start of endocrine therapy (see Table). They were also more likely to receive a bone density test result during their care (Table). These findings remained significant when data were restricted to those ≥ 50 years (as a proxy for postmenopausal status) and those with ER-positive breast cancer. The rates of osteopenia and osteoporosis were similar between the cohorts: control 47%, 24%; 4R cohort: 46%, 23% respectively (data not shown). Conclusions: Care optimization using the 4R Oncology Model was associated with a significant improvement in the timing of bone density testing before initiation of endocrine therapy. The 4R Oncology Model can lead to more informed decision making in adjuvant endocrine therapy for patients with breast cancer. Additional optimizations to improve the rates of bone density tests and referrals will be beneficial.[Table: see text]