Received Hormone Therapy Research Articles

Low Corticosterone Response to Stress in a Perimenopausal Rat Model Is Associated with the Hypoactivation of PaMP Region of the Paraventricular Nucleus and Can Be Corrected by Exogenous Progesterone Supplementation

Introduction: The transition to menopause is characterized by mood, behavioral and metabolic changes. However, little is known about the changes in adrenal response to stress. Aims: The aim of the study was to evaluate, in an animal model of perimenopause induced by 4-vinylcyclohexene diepoxide (VCD), (1) the endocrine and neuronal stress system activity in response to acute restraint stress and (2) the effect of hormonal therapy in this response. Methods: Prepubertal female Wistar rats received daily injections (s.c) of oil or VCD (160 mg/kg) for 15 days. On 56th–66th days after treatment onset, the groups to be stressed received s.c implants containing placebo (PL), 17β-estradiol (E2), progesterone (P4), or E2P4. At 80 ± 5 days after VCD/oil injections, stress was applied for 30 min. Blood samples were collected immediately after and 60 min after the end of stress session from the tail tip followed by transcardial perfusion with PFA 4% for the assessment of c-Fos expression in the medial and posterior parvocellular (PaMP and PaPo) subdivisions of the paraventricular nucleus (PVN) and c-Fos/tyrosine hydroxylase in the locus coeruleus (LC) using immunohistochemistry. Control groups were not stressed nor received hormone therapy. Results: While basal corticosterone levels were similar between VCD-periestropausal and control rats, the secretion in response to stress in the VCD group was lower. This effect was prevented by P4 therapy. Inversely, basal levels of P4 were lower in VCD-periestropausal rats than in the controls, and no differences were found in response to stress between the groups. As expected, 30-min restraint stress increased c-Fos immunoreactivity in all brain areas studied in both control and VCD-periestropausal rats. However, the c-Fos increase in the PaMP region was attenuated. In all areas examined, there were no significant differences in the number of c-Fos-positive neurons across hormonal therapies. Discussion/Conclusion: This is the first study to demonstrate in a perimenopausal rat model that reproductive aging is accompanied by inadequate secretion of corticosterone in response to acute stress in association with the hypoactivation of the PaMP region of the PVN, while adrenal P4 response is preserved. Moreover, P4 therapy was shown to attenuate the effects of progressive ovarian failure on adrenal functioning during stress.

Abstract 1415: Triple combination targeting ER, CDK4/6, and PI3K inhibits tumor growth in ER+ breast cancer resistant to combined fulvestrant and CDK4/6 or PI3K inhibitor

Abstract Despite the improved outcome of ER+ advanced breast cancer patients treated with combined CDK4/6 inhibitor (CDK4/6i) and endocrine therapy, the disease will eventually progress. Furthermore, the recently approved combined therapy with the α-specific PI3K inhibitor (PI3Ki) alpelisib and fulvestrant in PIK3CA-mutated ER+ metastatic breast cancer patients who had previously received endocrine therapy demonstrated a clinically meaningful benefit in clinical trials, but drug resistance is inevitable. Thus, novel and more effective treatment combinations are urgently needed, as well as defining the subsequent optimal sequence of treatment following progression on combined treatment with either CDK4/6i or Pi3Ki and endocrine therapy. We developed 4 PIK3CA-mutated ER+ breast cancer cell models resistant to combined fulvestrant and CDK4/6i or PI3Ki, derived from MCF-7 (MPFR and MPiFR) and T47D (TPFR and TPiFR) cells, and 2 orthotopic cell line xenograft models (MPFR and MPiFR). We used these models to investigate whether ER+ breast cancer cells resistant to combined fulvestrant and CDK4/6i or PI3Ki would benefit from switching between these combined therapies, or whether triple combination of these agents would be required. We observed that triple inhibition of CDK4/6, PI3K and ER significantly reduced growth of breast cancer cells and xenografts models resistant to combined fulvestrant and CDK4/6i or PI3Ki. The triple combination also induced apoptosis and cell cycle arrest and reduced the expression of key proteins of the ER, PI3K/AKT/mTOR and cyclin D-CDK4/6-Rb pathways, including ER, p-PRAS40 and p-S6, in cell lines resistant to combined fulvestrant and CDK4/6i or PI3Ki. Finally, the triple inhibition significantly prevented and/or delayed the acquisition of resistance in cells resistant to combined fulvestrant and CDK4/6i or PI3Ki. Importantly, switching between combined fulvestrant and CDK4/6i to fulvestrant and PI3Ki or vice versa upon resistance did not prevent disease progression, suggesting that simultaneous blockage of the 3 pathways is required in these tumors. Finally, we found high CDK2 levels in cells resistant to combined fulvestrant and PI3Ki, and targeting ER, PI3K, and CDK2 offered an additional treatment option for ER+ breast cancer resistant to combined fulvestrant and PI3Ki. Evaluation of the efficacy of these different targeted therapy combinations in patient-derived xenografts models is ongoing. Our data supports the use of combined therapy with either PI3Ki or CDK4/6i and fulvestrant following progression on or after an endocrine-based regime. However, following disease progression on combined therapy with fulvestrant and either CDK4/6i or PI3Ki, triple combination targeting ER, PI3K and either CDK4/6 or CDK2 is needed to inhibit tumor progression. Citation Format: Leena Karimi, Carla L. Alves, Mikkel G. Terp, Martina Tuttolomondo, Henrik J. Ditzel. Triple combination targeting ER, CDK4/6, and PI3K inhibits tumor growth in ER+ breast cancer resistant to combined fulvestrant and CDK4/6 or PI3K inhibitor [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1415.

Interventions to Improve Sexual Health in Women Living with and Surviving Cancer: Review and Recommendations.

Simple SummarySexual health, both physical and psychological, is a common concern and unmet need among women with and surviving cancer. To guide clinical care and future research to improve sexual function and satisfaction in women with cancer, we performed a narrative review of interventions for sexual health concerns including sexual function, body image, genitourinary symptoms, and hot flashes. Relevant investigations conducted in the US and abroad published between 2005 and 2020 were reviewed (n = 91). Recommendations for future research in this area are also offered.Sexual health concerns, both physical and psychological, are common and represent an unmet need among women with and surviving cancer. Sexual challenges and conditions negatively impact body image, satisfaction, relationships, well-being, and quality of life, yet are widely reported to be under-recognized and undertreated. To guide clinical care and future research on sexual function in women with cancer, we performed a scoping review of interventions for sexual health concerns, including sexual function, body image, genitourinary symptoms, and hot flashes. Relevant publications between 2005 and 2020 were identified by searching PubMed with a combination of medical subject headings and keywords. Articles were included if they focused on the aforementioned topics, were primary research publications, and included female cancer survivors. Studies focusing on women receiving hormone therapy for breast cancer were also included. A total of 91 investigations conducted in the US and abroad were reviewed. Most commonly, interventions included a component of psychoeducation, although pharmacologic, exercise, and other approaches have been evaluated. Many studies have focused on survivors of breast or gynecologic cancer, among other sampling and methodological limitations. These limitations underscore the need for more work on this vital survivorship issue. Recommendations for future research in this area are also offered.

1010-P: Prevalence of Acute Diabetes Complications following Cancer Diagnosis and Treatment

Introduction: Multiple case studies have reported diabetic ketoacidosis (DKA) in recently-diagnosed cancer patients, especially those taking immune checkpoint inhibitors. The prevalence of DKA and other acute diabetes complications (ADC), including hypoglycemia and hyperosmolarity, and their relationship with the onset of systemic cancer therapy is unclear. Methods: This study utilized data from n=9,588 cancer patients from the Huntsman Cancer Institute, UT. Data on clinicodemographic characteristics, biomarkers, and cancer diagnoses were extracted from electronic medical records (EMR) and tumor registry. Patients included in this analysis received an ICD diagnosis of hypoglycemia, hyperosmolarity with or without coma, and/or DKA with or without coma. Systemic therapy was defined as any chemotherapy, immunotherapy or hormone therapy resulting from a specific first primary cancer diagnosis. Results: There were 243 instances of ADC within this cohort, occurring in 211 (2.2%) unique patients. Of these 211 unique patients with an ADC, 106 (50.0%) experienced their first ADC within one year after cancer diagnosis, with a median time to ADC diagnosis of 88 days. Forty-seven (44%) of these patients experienced the ADC following the onset of systemic therapy, with a median time from systemic therapy onset to ADC diagnosis of 120 days. In these 47 patients who received an ADC diagnosis following the onset of systemic therapy, 40 (85.1%) received chemotherapy (n=20 as monotherapy), 20 (42.6%) received immunotherapy (n=4 as monotherapy) and 12 (25.5%) received hormone therapy (n=2 as monotherapy). Only 54% of patients experiencing an ADC after cancer diagnosis had a history of diabetes prior to cancer, and on average their first diabetes diagnosis was 5.4 ± 4.4 years prior to their cancer diagnosis. Discussion: ADCs may be common following a cancer diagnosis, however a substantial number occurred prior to the onset of systemic cancer therapy and in patients with no prior history of diabetes. Disclosure R. Viskochil: None. S. Hardikar: None. S. Pauleck: None. M. Winn: None. K. Funai: None. M. L. Litchman: Research Support; Self; Abbott Diabetes. W. Akerley: None. H. Colman: Advisory Panel; Self; Adastra Pharmaceuticals, Orbus Therapeutics, Consultant; Self; Best Doctors/Teladoc. C. M. Ulrich: None. M. C. Playdon: None. Funding University of Utah Health/Larry H. Miller Family Wellness Initiative

Mat pilates method improve postural alignment women undergoing hormone therapy adjunct to breast cancer treatment. Clinical trial

The purpose of the study is to analyze the effects of a mat Pilates intervention on the postural alignment and balance of breast cancer women receiving hormone therapy. A two-arm randomized clinical trial included 34 breast cancer survivors divided randomly between a mat Pilates group (n = 18), that performed 16 weeks of mat Pilates exercises, and a control group (n = 16), who were invited to maintain their daily routine activities and received three educational sessions. Data collection occurred at baseline and at post-intervention time. The postural alignment was assessed using the Postural Assessment Software (SAPO) and the balance was assessed by the MINIBESTest. When the two-way ANOVA was performed on postural alignment results, a significant statistical difference was found in the angle between acromions and the anterior-superior iliac spines of the mat Pilates group (p = 0.036). When compared to the post-intervention period, the mat Pilates method had an improved horizontal alignment of the anterior-superior iliac spines (p = 0.039) and vertical alignment of the acromion head on the right side (p = 0,016). Also, the participants of the Pilates group showed a significant statistical difference in the balance (p = 0.034). The control group had an improved vertical trunk alignment on the left side (p = 0,048). The control group and the mat Pilates method group improved in some aspects, however the mat Pilates method was effective in improving the postural alignment and the balance of breast cancer survivors receiving hormone therapy and may be recommended in oncological rehabilitation as a type of complementary therapy.

A new clinically-relevant rat model of letrozole-induced chronic nociceptive disorders

Among postmenopausal women with estrogen receptor-positive breast cancer, more than 80% receive hormone therapy including aromatase inhibitors (AIs). Half of them develop chronic arthralgia - characterized by symmetric articular pain, carpal tunnel syndrome, morning stiffness, myalgia and a decrease in grip strength - which is associated with treatment discontinuation. Only a few animal studies have linked AI treatment to nociception, and none to arthralgia. Thus, we developed a new chronic AI-induced nociceptive disorder model mimicking clinical symptoms induced by AIs, using subcutaneous letrozole pellets in ovariectomized (OVX) rats. Following plasma letrozole dosage at the end of the experiment (day 73), only rats with at least 90 ng/ml of letrozole were considered significantly exposed to letrozole (OVX + high LTZ group), whereas treated animals with less than 90 ng/ml were pooled in the OVX + low LTZ group. Chronic nociceptive disorder set in rapidly and was maintained for more than 70 days in the OVX + high LTZ group. Furthermore, OVX + high LTZ rats saw no alteration in locomotion, myalgia or experimental anxiety during this period. Bone parameters of the femora were significantly altered in all OVX rats compared to Sham+vehicle pellet. A mechanistic analysis focused on TRPA1, receptor suspected to mediate AI-evoked pain, and showed no modification in its expression in the DRG. This new long-lasting chronic rat model, efficiently reproduces the symptoms of AI-induced nociceptive disorder affecting patients' daily activities and quality-of-life. It should help to study the pathophysiology of this disorder and to promote the development of new therapeutic strategies.

EVALUATION OF THE TUMOR PROLIFERATIVE ACTIVITY INDEX PCNA IN A VARIETY OF ROUTES OF DELIVERY OF CHEMOTHERAPEUTIC DRUGS IN PATIENTS WITH LOCALLY ADVANCED BREAST CANCER

Introduction. Breast cancer is one of the most live issue of the modern oncology, as it holds the leading position among the causes of female mortality and disability. A special place in the structure of this pathology is occupied by locally advanced forms of malignant tumor in which the effectiveness of the treatments used is unfortunately very low, therefore the prognosis is rather unfavorable. This determines there levance of them search for new methods of diagnosis and treatment in such patients. In the context of this research, we identified the role of neoadjuvant selective intra-arterial polychemotherapy in adverse primary inoperable forms of breast cancer. To determine and predict the effectiveness of this treatment, we used tumor proliferative activity. The research examined the expression of a PCNA nuclear proliferation marker for prognostic and diagnostic evaluation in the light of unsatisfactory literature on the subject in the context of determining similar parameters by other criteria. PCNA level was taken as the main dichotomous point of prognostic assessment of neoadjuvant therapy based on the results of retrospective analysis of the efficacy of preoperative treatment and determination of statistically significant difference between the results in the subgroups with lower and higher marker levels, which in our study were divided according to the median value of the immunohistochemical parameter level in the total sample of 25 %. Objective. Evaluation of the effectiveness of neoadjuvant treatment using systemic and selective intraarterial routes of chemotherapy administration in patients with locally advanced breast cancer using the tumor proliferative index based on the PCNA marker. Materials and methods. A retrospective analysis of the results of a comprehensive treatment of patients with initially inoperable locally advanced breast cancer based on selective and systemic routes of administration of chemotherapy was performed. The study included 63 patients. The sample was divided into 2groups depending on the selected type of neoadjuvant polychemotherapy: 1st group – control group were formed (based on systemic therapy) and 2nd group – study group (the selective intraarterial delivery route was used). The control group consisted of 22 patients, the study – 41 patients. All patients revealed stage IIIb of the disease. In accordance with the clinical manifestations, the patients were distributed as follows: control group include 12 patients with сT4bN1M0, 6 patients with сT4aN1M0 and 4 patients with сT4cN1M0; study group include 23 patients with сT4bN1M0, 7 patients with сT4aN1M0 and 11 patients with сT4cN1M0. All patients included in the study had luminal type B. In parallel with routine methods, the dynamics of proliferative activity of the tumor by the PCNA nuclear antigen was additionally studied in all patients. This study demonstrates the level of the PCNA marker at the start of treatment and after the completion of polychemotherapy (PCT). After PCT, all patients underwent surgical intervention. Taking into account the pathological examination, the patients were reassigned as follows: in the control group, 4 patients has pT4aN0M0, 2 patients – pT4aN1M0, 4 patients – pT4bN0M0, 8 patients – pT4bN1M0, 1 patient – pT4cN0M0 and 3 patients – pT4cN1M0; in the study group, 3 patients has PT4aN1M0, 4 patients – PT4aN0M0, 15 patients – PT4bN1M0, 8 patients – PT4bN0M0, 6 patients – PT4cN1M0 and 5 patients – PT4cN0M0. Since the patients belonged to the group with Luminal type of tumor, each of them received hormone therapy in an adjuvant regimen. Patients of reproductive age were treated with the group of estrogen antagonists, while postmenopausal patients received aromatase inhibitors. Targeted therapy was not used in the study. A statistical analysis was performed between the comparison groups; the median marker level in 25 % was taken as the critical value. Results. According to the degree of PCNA regression, it was determined that selective intra-arterial chemotherapy for breast cancer with a low proliferative activity index has a statistical advantage in overall survival and average life expectancy (p < 0.05) compared with control group. Conclusions. Using the PCNA indicator, one can reliably evaluate the proliferative activity of the tumor, thus predicting the effect of neoadjuvant chemotherapy and choosing the optimal tactics of complex treatment. Keywords: locally advanced breast cancer, proliferative activity index, marker of nuclear antigen of proliferating cells, systemic polychemotherapy, selective intra-arterial polychemotherapy.

Improved survival supports primary endocrine therapy in patients with hormone receptor positive/ HER-2 negative metastatic breast cancer.

e13034 Background: Current ASCO guidelines recommend endocrine therapy as preferred primary treatment for hormone receptor positive (HR+) metastatic breast cancer (MBC). We assessed survival outcomes of HR+/HER2- MBC patients undergoing endocrine therapy with and without chemotherapy. Methods: The National Cancer Database was queried 2004-2016 for patients with de novo HR+/HER2- MBC. Exclusion criteria were treatment with surgery or radiation at the primary site and missing oncologic and follow up data. Overall survival was compared between systemic treatment groups using multivariable cox proportional hazards regression modes. Results: 19,317 patients met inclusion criteria, among whom 2,360 (12%) received no systemic therapy, 2,617 (14%) received chemotherapy only, 10,078 (52%) received endocrine therapy only and 4,262 (22%) received both chemotherapy and endocrine therapy. Patients treated with chemotherapy only more frequently had lung (38%, p<0.001) or liver (36%, p<0.001) metastasis while those undergoing endocrine therapy only presented primarily with bone metastasis (82%, p<0.001). Patients with multiple metastatic sites more often received endocrine therapy alone than combined therapy (44 vs. 25%, p<0.001). Median overall survival was similar after combination therapy and endocrine therapy, and poorest after chemotherapy alone (33.1 vs 31.4 vs 19.8 months, p<0.001). After controlling for patient, facility, and tumor characteristics, endocrine therapy alone provided superior survival benefit to chemotherapy only, though combination systemic therapy resulted in the greatest overall survival (p<0.001). Conclusions: Primary endocrine therapy provided significant survival benefit over chemotherapy alone for HR+/HER2- MBC. Though combination systemic therapy may be warranted in progressive disease, our results align with recommendations for endocrine therapy as first line treatment for HR+/HER2- MBC. [Table: see text]

Real-world quality of life (QoL) in black, indigenous and people of color (BIPOC) treated with palbociclib (PAL) and endocrine therapy for hormone receptor–positive (HR+)/human epidermal growth factor receptor 2–negative (HER2–) advanced breast cancer (ABC): A subgroup analysis from POLARIS.

1071 Background: Racial disparities in breast cancer incidence, mortality, and care are well documented. PAL plus endocrine therapy is indicated for patients (pts) with HR+/HER2− ABC. Findings from the PALOMA clinical trials have shown that pts receiving PAL maintained stable QoL; however, limited QoL data are available from real-world settings for BIPOC receiving PAL. Methods: POLARIS is a noninterventional, prospective, primarily US-based study in pts with HR+/HER2– ABC receiving PAL. QoL was assessed with the European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire Core 30 (EORTC QLQ-C30) at baseline, monthly for the first 3 mo of treatment (Tx) with PAL, and then every 3 mo. In this interim analysis, we report Tx patterns and QoL assessments at baseline and at 6 mo and 12 mo in BIPOC from POLARIS. Results: Of 1280 pts treated with PAL as November 10, 2020, 233 were included in the BIPOC subgroup of whom 159 (68.2%) completed PAL Tx for ≥6 mo and 112 (48.1%) for ≥12 mo. In the BIPOC cohort, 59.2% of pts were black, 35.2% Hispanic, 3.4% American Indian or Alaskan native, 2.1% Pacific Islander. PAL in combination with letrozole/anastrozole was received by 116 pts, 94 received PAL plus fulvestrant, 13 received PAL plus exemestane, and 10 received PAL plus another Tx; 175 pts (75.1%) received PAL as first-line Tx. Mean EORTC QLQ-C30 global health QoL and functional scales scores remained stable over the first 12 mo of PAL Tx, without any changes at or above the 10-point threshold considered clinically meaningful, and were similar to those previously reported in an earlier analysis of the entire POLARIS population (Table and Rocque et al SABCS 2019). Symptom scales scores, including nausea and vomiting, pain, dyspnea, insomnia, appetite loss, constipation, and diarrhea, also remained stable over 12 mo. Conclusions: In this subgroup analysis, PAL had no significant adverse impact on QOL in BIPOC with HR+/HER2– ABC, consistent with previous findings from the total POLARIS study population. Pfizer (NCT03280303). Clinical trial information: NCT03280303 .[Table: see text]

Impact of clinical trial enrollment on episode costs in the Oncology Care Model (OCM).

6513 Background: Clinical trials are critical for improving outcomes for patients with cancer. However, there is some concern from health insurers that clinical trial participation can increase total cost of care for cancer patients. We investigated the impact of clinical trial participation on total costs paid by Medicare during the OCM program in a large community-based practice. Methods: Tennessee Oncology (TO) is a community oncology practice comprising over 90 oncologists across 30 sites of care. We linked TO trial data and electronic medical record data with OCM data for episodes of care from 2016-2018. To assess the impact of trial participation on total cost relative to routine care, we created matched comparator groups for each OCM episode based on cancer type, metastatic status, number of comorbidities, performance status, and age. Patients with breast cancer receiving hormone therapy only were excluded. Absolute and percent cost differences between groups were calculated for episodes that had a comparator group size of five or greater. Differences in total cost for trial episodes were compared to non-trial episodes, and significance was assessed using the Mann–Whitney U test. We also studied the impact of trial participation on receipt of active treatment in the last 14 days of life (TxEOL), hospice use, and hospitalizations. Results: During the study period, 8,026 completed OCM episodes met study criteria. Patients were enrolled in a clinical trial for 459 of these episodes. On average, episodes during which patients were on trial cost $5,973 less than matched non-trial episodes (Table), independent of early versus late-phase trial. Most savings resulted from decreased drug costs. There were no differences in rates of TxEOL (15% vs. 14% p=1.0), rates of hospitalizations (31% vs. 30% p=0.54), or hospice use (52% vs. 62% p=0.08) between trial and non-trial episodes. Median difference from comparator group average cost was significantly lower for clinical trial episodes (-18% vs. -6%, p<0.01). Conclusions: In the community setting, total costs paid by Medicare for patients participating in clinical trials during OCM episodes were lower than costs for similar patients receiving routine care. Clinical trial participation did not adversely impact end-of-life care or likelihood of hospitalization. These findings suggest that patient participation in clinical trials does not increase total cost of care nor enhance financial risk to payers.[Table: see text]

Impact of oncotype Dx score on treatment and long-term outcomes.

e12518 Background: Oncotype dx is a 21 gene breast cancer assay that helps predict benefit of chemotherapy in early-stage hormone receptor positive (HR+), HER2 negative, 0 to 3 node positive breast cancer as reported by TAILORx and RxPonder trials. Both trials found no benefit of adjuvant therapy in mid-range scores of 11-25 with the exception of some benefit in age under 50 or premenopausal status, no benefit if score was 0-10, and benefit of chemotherapy if >25. Methods: All breast cancer patients between 2019-2020 were chart checked to evaluate oncotype dx scores. Patient characteristics were analyzed between oncotype dx scores of 0-10, 11-25, and >25 using X square tests. 2000-2020 institutional cancer registry data was analyzed to understand recurrence and mortality in patients with oncotype dx testing. Results: 173 patients had oncotype dx testing between 2019-2020, and most were HR+, HER2-, and had 0-3 lymph nodes. There was no difference in race or ethnicity between the groups of oncotype dx scores (Table), and average age at diagnosis for all three groups was 58 years. More patients with lower oncotype dx score had hormone therapy, but this was not significant (0-10 at 93.6%, 11-25 at 90.8%, and >25 at 82.1%, p=0.26). Patients with a higher oncotype score were significantly more likely to have chemotherapy (0-10 at 0%, 11-25 at 17.3%, and >25 at 82.1%, p<0.01). When looking at long term outcomes, the mortality rate was highest in the 11-25 score group at 9.5%, but was not significantly higher than 0-10 at 4.7% and >25 at 2.1% (p=0.15). The recurrence was highest in the 0-10 group at 5.4%, but not significant compared to the 11-25 group at 4.1% and >25 group at 4.2% (p=0.09). Conclusions: Race, ethnicity, and age does not impact predisposition to high oncotype dx score, which is interesting since literature shows minority women have higher mortality rates. This could be because oncotype dx looks at early-stage breast cancers and many minority women have later stages at diagnosis. There was no difference in which group received hormone therapy and there was significantly higher rate of chemotherapy administration in patients with scores >25, which is consistent with prospective trial recommendations. When evaluating long term outcomes between oncotype dx groups over 20 years, there was no significant difference in recurrence of disease or mortality indicating that oncotype dx scoring accurately predicted overall benefit of chemotherapy.[Table: see text]

Increased Bone Mineral Density in Male Patients With Idiopathic Hypogonadotropic Hypogonadism Who Undergo Sex Hormone Therapy: Findings From Cross-Sectional and Longitudinal Studies

ObjectiveThis retrospective observational study assessed the long-term impact of pulsatile gonadotropin-releasing hormone, combined gonadotropin, or testosterone replacement therapy on total hip, femoral, and lumbar bone mineral density (BMD) and Z-scores in adult men with idiopathic hypogonadotropic hypogonadism (IHH). MethodsIn the cross-sectional study, 69 patients were allocated to untreated (n = 42) and treated (n = 27) groups. The untreated group included IHH patients without hormone therapy history, while the treated group included age- and body mass index-matched patients who had received hormone therapy for at least 5 years. The longitudinal study included 53 IHH patients, and their hip and lumbar BMDs were measured several times during hormone therapy. We then evaluated the changes in their BMD. ResultsOur cross-sectional study showed that the treated group had a significantly higher BMD and Z-score for total hip, femoral neck, and lumbar spine (P < 0.001 for all) than the untreated group, and the average bone mass even reached the age-matched normal range. The prevalence of low BMD was 80.95% and 11.11% in untreated and treated groups, respectively. In the longitudinal study (N = 53), the total hip, femoral neck, and lumbar spine BMD gradually increased during treatment. The lumbar spine showed a greater increment in BMD compared with the total hip and femoral neck (P < 0.05). ConclusionSex hormone therapy improved hip and lumbar spine BMD and Z-scores in patients with IHH. The lumbar spine showed a greater improvement in BMD compared with the total hip and femoral neck.

Physical Functionality of the Upper Limb after Breast Cancer Surgery in Southern Brazilian Survivors: Cross-Sectional Study

Introduction: Surgical treatment after the diagnosis of breast cancer can lead to several consequences of the survivor’s upper limb. Objective: Analyze the physical function of the upper limb after breast cancer surgery in Southern Brazilian survivors. Method: 82 breast cancer survivors (55±10 years) receiving hormone therapy were included. A questionnaire for general information, pain (Visual Analogue Scale), and upper limb functionality (DASH) were applied, followed by physical tests; the shoulder range of motion (goniometer), strength (dynamometer), proprioception (kinesimeter) and arm volume (perimeter of the arm). Results: No differences were found for any variable of physical function in relation to mastectomy or breast-conserving surgery. However, better scores of strength and the shoulder range of motion were found for the non-surgery arm. Linear regression demonstrated a relation between pain, strength, range of motion, proprioception, and arm volume with the disabilities of the upper limb, and when adjusted by surgery modality, shoulder range of motion, arm volume, and proprioception maintained significantly. Conclusion: Breast cancer survivors presented physical disabilities on the upper limb after surgery, regardless of the modality of surgery. Results elucidate the need for an efficient post-treatment program to prevent poor physical function after breast cancer surgery and provide better daily activities to these women.

Complementary and alternative medicine (CAM) in women with endometriosis

ObjectiveThis study aimed to provide an overview of the extent to which women with endometriosis are informed about, interested in, and make use of CAM, and to evaluate which of the methods are most often applied. Study DesignA retrospective, two-center cohort study was conducted using a validated questionnaire among women with laparoscopically confirmed endometriosis at two urban teaching hospitals, certified as endometriosis centres. ResultsA total of 592 patients were included in the study and received the questionnaire; 114 (19.3 %) were included in the data analysis. Most of the women were not receiving hormone therapy at the time of the study (n = 60, 52.6 %). Most (n = 75, 65.8 %) were interested in CAM, but only a minority (n = 12, 10.5 %) had detailed knowledge about it. A total of 81 patients (71.1 %) had used at least one CAM method for disease management; the five most frequently used CAM methods were exercise (n = 55, 48.2 %), vitamins (n = 40, 35.1 %), yoga (n = 38, 33.3 %), homeopathy (n = 32, 28.1 %), and trace elements (n = 27, 23.7 %). ConclusionsIn our study population, women with endometriosis are strongly interested in using CAM, but have only limited information about it. Nevertheless, a majority of the patients had used at least one CAM method to relieve symptoms associated with the disease and the most often used was exercise.

Patient Characteristics Associated With the Receipt of Hormone Therapy Among Transgender Patients in the Veterans Health Administration

Background: Many transgender patients experience gender dysphoria as a result of an incongruence between their gender identity and sex assigned at birth. Gender-affirming hormone therapy improves the quality of life for transgender patients seeking to increase alignment of their secondary sex characteristics and gender identity. However, little is known about the patient factors that are associated with receipt of this therapy which is critical to identifying areas for improvement in care for transgender patients. Objective: To evaluate patient characteristics associated with transgender patients’ receipt of hormone therapy from the Veterans Health Administration (VHA). Methods: Inpatient and outpatient data were reviewed for transgender patients, identified through ICD-9/ICD-10 diagnosis codes for gender identity disorder (GID), receiving VHA health care from January 2006 to December 2018. We evaluated receipt of hormone therapy (testosterone or estrogen +/- spironolactone) from the VHA, socio-demographics, comorbidities, social stressors, military sexual trauma, and documented suicide attempts. Adjusted Odds Ratios (aOR) and 95% Confidence Intervals (CI) were obtained from a multivariable logistic regression model used to ascertain the relationship between patient characteristics and hormone therapy. Results: Of 9,406 patients with documented GID, 5,487 (58.3%) received hormone therapy from the VHA. Compared to patients not receiving hormone therapy, a higher proportion of patients receiving hormone therapy were younger (21-29 years: 18.1% vs. 11.6%; 30-39 years: 20.0% vs. 14.6%; 40-49 years: 16.2% vs. 13.6%), had documentation of a positive military sexual trauma screening (22.2% vs. 16.2%; p<0.0001), and a suicide attempt (11.4% vs. 9.9%; p=0.0067). There were significant associations between receipt of hormone therapy and: 1) younger age (aOR: 1.33; 95% CI: 1.29-1.36; p<0.0001); 2) Black non-Hispanic patients (aOR: 0.58; 95% CI: 050-0.68; p<0.0001); 3) increasing number of comorbidities (aOR: 0.86; 95% CI: 0.84-0.88; p<0.0001); and 4) increasing number of social stressors (aOR: 0.86; 95% CI: 0.83-0.90; p<0.0001). Conclusions: Age, race/ethnicity, comorbidities, and social stressors among other factors are associated with receipt of hormone therapy among transgender patients in the VHA. Subsequent efforts should focus on understanding clinician- and site-level determinants to facilitate the design of effective quality improvement measures that optimize gender affirming hormone therapy through VHA for transgender patients.

Is nurse-led case management effective in improving treatment outcomes for cancer patients? A systematic review and meta-analysis.

To identify and synthesize the outcomes of nurse-led case management interventions for improving cancer treatment. Systematic review with meta-analysis. PubMed, MEDLINE, CINAHL, EMBASE, Cochrane Library and CEPS were searched for articles published from inception till June 2019, and search was finalized in January 2020. The review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement guidelines. The quality of evidence was assessed using Joanna Briggs Institute Critical Appraisal Tools. Outcomes were analysed by using a pool of data of 95% confidence intervals (CIs), p value and fitting model based on heterogeneity of test results. Eleven articles were included in the meta-analysis. When compared with the regular care group, the nurse-led case management group had: 1) shorter time from diagnosis to treatment by 9.07days, 2) an improved treatment completion rates (OR=2.45) and 3) more number of patients received hormone therapy. The synthesized results presented that nurse-led case management is more effective than regular care in improving treatment timeliness, treatment completion rates and hormone therapy rates.

Advances in Therapy for Hormone Receptor (HR)-Positive, Human Epidermal Growth Factor Receptor 2 (HER2)-Negative Advanced Breast Cancer Patients Who Have Experienced Progression After Treatment with CDK4/6 Inhibitors.

Approximately 70% of breast cancer (BC) cases are hormone receptor-positive (HR+) and human epidermal growth factor receptor 2-negative (HER2-) BC. Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors have acted as star drugs for reversing endocrine therapy (ET) resistance and improving the prognosis of patients with HR+ advanced breast cancer (ABC) since they were initially approved. However, progression eventually occurs. In this review, we summarize the recent treatment strategies post CDK4/6 inhibitors: 1) CDK4/6 inhibitors plus exemestane and everolimus; 2) phosphoinositide-3-kinase (PI3K) inhibitor alpelisib plus fulvestrant for patients with PIK3CA mutation; 3) poly (ADP-ribose) polymerase (PARP) inhibitor for patients with germline PALB2 mutations, somatic BRCA1/2 mutations, or germline BRCA1/2 mutations; 4) exemestane and everolimus; and (5) chemotherapy. These strategies are all supported by evidence from clinical trials and retrospective studies. We also describe potential future treatment strategies post CDK4/6 inhibitors, such as the trophoblast cell surface antigen 2 (Trop-2) directed antibody–drug conjugate, cyclin-dependent kinase 7 (CDK7) inhibitors, and B-cell lymphoma-2 (BCL-2) inhibitors.

Cardiovascular Events in Men with Prostate Cancer Receiving Hormone Therapy: An Analysis of the FDA Adverse Event Reporting System (FAERS).

The comparative cardiovascular risk profiles of available hormone therapies for the treatment of prostate cancer is not known. We queried the U.S. Food and Drug Administration Adverse Event Reporting System, a retrospective, pharmacovigilance database, for cardiovascular adverse event reports in men with prostate cancer receiving gonadotropin releasing hormone (GnRH) agonists, GnRH antagonists, androgen receptor antagonists, and/or androgen synthesis inhibitors from January 2000 to April 2020. Cardiovascular adverse events accounted for 6,231 reports (12.6%) on hormone monotherapy and 1,793 reports (26.1%) on combination therapy. Arterial vascular events were reported most commonly, followed by arrhythmias, heart failure, and venous thromboembolism. Compared to GnRH agonists, GnRH antagonists were associated with fewer cardiovascular adverse event reports as monotherapy (adjusted reporting odds ratio [ROR]=0.70 [95% CI 0.59-0.84], p <0.001) and as combination therapy (ROR=0.47 [0.34-0.67], p <0.0001), driven by reductions in arterial vascular events. Second generation androgen receptor antagonists and abiraterone were associated with more reports of hypertension requiring hospitalization (ROR=1.21 [1.03-1.41], p=0.02 and ROR=1.19 [1.01-1.40], p=0.03, respectively), and more heart failure events when used in combination with GnRH antagonists (ROR=2.79 [1.30-6.01], p=0.009 and ROR=2.57 [1.12-5.86], p=0.03). In this retrospective analysis of a pharmacovigilance database, arterial vascular events were the most commonly reported cardiovascular adverse events in men on hormone therapy for prostate cancer. GnRH antagonists were associated with fewer reports of overall cardiovascular events and arterial vascular events than GnRH agonists. Additional study is needed to identify optimal strategies to reduce cardiovascular morbidity among men with prostate cancer receiving hormone therapy.

The effect of drug treatment on functional outcomes of hip and knee joint replacement in patients with rheumatoid arthritis

Aim – to determine the effect of drug antirheumatic therapy on the functional outcomes of hip and knee arthroplasty in patients with rheumatoid arthritis. Materials and methods. The results of 160 operations of total hip arthroplasty and 148 operations of total arthroplasty of knee joints in patients with rheumatoid joint lesions were analyzed using mathematical methods of statistical processing. Patients were divided into 4 groups: Group I – without anti-inflammatory therapy, Group II – received hormone therapy, Group III – basic therapy and Group IV – received both the basic and hormonal therapy at the time of surgery. Results. The obtained results indicated a moderate correlation between therapy and the joint range of motion of the lower extremities using basic therapy and combined nonsteroidal, hormonal and basic therapy, and the range of motion differed significantly in combination therapy from hormonal alone. The highest scores of the J. Joseph, E. E. Kaufman rating scale were observed in combination therapy with NSAIDs, hormonal and basic therapy; the lower scores – in hormonal and NSAIDs combination; and the lowest ones – in the combination of basic therapy with NSAIDs. The greatest increase in the knee joint range of motion was observed in the patients who received hormonal drugs or basic therapy compared to the patients who did not take any one or received both of these medicines in combination. Almost the same effect of antirheumatic therapy on the results of both hip and knee arthroplasty was determined with an upward trend in percentage of good and excellent results in males regardless of the lesion location and the most optimal ratio between satisfactory-unsatisfactory and good-excellent results in the patients under 40 years of age. Conclusions. The studies conducted allow to consider the combined drug therapy as a factor of weak and moderate influence on the functional outcomes of hip and knee arthroplasty in the late stages of rheumatoid arthritis and suggest that antirheumatic drug therapy should not be discontinued in the perioperative period.

Abstract S09-03: Real world data analysis of patients with genitourinary cancers receiving systemic anticancer treatment during the COVID-19 pandemic at Guy's Cancer Centre: A single centre retrospective study in the UK

Abstract Background: To understand the impact of the COVID-19 pandemic on National Health Services (NHS) cancer service delivery, care and patients, we examined the impact of changes in cancer service delivery, treatment intensity and delay by evaluating oncological outcomes of genitourinary (GU) cancer patients receiving systemic anticancer treatment (SACT) during 1st March and 8th July 2020. Methods: We used data from patients with GU cancers (i.e. prostate, urothelial, kidney and testicular) treated with SACT at Guy’s Cancer Centre during the first wave of the COVID-19 pandemic in the UK: demographics (sex, age, ethnicity, ECOG performance status (PS), comorbidities, smoking history, socio-economic status (SES)) and disease characteristics (stage, treatment type and setting, lines of treatment), as well as results from SARS-CoV-2 PCR testing. Classification of COVID-19 severity was based on the World Health Organisation (WHO) guidelines. Results: A total of 457 GU cancer patients received SACT during the study period: 68% prostate cancer, 23% renal cancer, 7% urothelial cancer, 2% testicular cancer. Mean age was 69 years (SD: 11.2). 91% were males, 82% were classified as low SES and out of the 291 patients we had ethnicity data on 199 (68%) were White British. The majority of patients had a PS of 1 and 95% of all patients had stage IV disease and hence received palliative SACT, with 58% being in the second line setting. Half of the patients received hormone therapy, 17% received chemotherapy, 20% received targeted therapy, 13% received immunotherapy (IO) and 1% received combination IO and targeted treatment. Only 5 (1%) patients tested SARS-CoV-2 positive: 2 had prostate cancer, 2 renal and 1 bladder cancer. Mean age was 66 years (SD: 5.6). They were all male, 2 White British, 1 Black African and 2 of unknown ethnicity and were all classified as low SES. Average PS was 2. Of these 5 patients 3 had at least two comorbidities (i.ehypertension, diabetes mellitus, renal impairment, frailty) and were receiving multiple medications. All had stage IV disease and received palliative SACT. 3 were on hormone therapy alone and 2 on chemotherapy. 2 of the patients presented symptoms within less than 7 days from PCR diagnosis, 1 within 7 to 14 days and 1 after 14 days. All 5 COVID-19 positive patients required hospitalization, 4 suffered severe pneumonia, 1 died from COVID-19 and 2 died from cancer related causes. In comparison, the mortality rate for the COVID-19 negative patients was 3.3%. Conclusion: Despite the impact of COVID-19 in health provision, a large number of our GU patients at Guy’s Cancer Centre safely received SACT. Our results suggest that the continuation of SACT during the COVID-19 pandemic did not increase the risk of COVID-19 in our patient cohort (SARS-CoV-2 infection rate: 1%). Of note, the infection rate was lower than observed in a similar study in our centre for gastrointestinal cancer patients (SARS-CoV-2 infection rate: 3.4%). In light of the above, decisions against SACT or SACT intensity should carefully be evaluated. Citation Format: Christina Karampera, Beth Russell, Charlotte Moss, Rushan Sylva, Kieran Palmer, Elias Pintus, Sarah Rudman, Debra Josephs, Kamarul Zaki, Mieke Van Hemelrijck, Saoirse Dolly, Deborah Enting. Real world data analysis of patients with genitourinary cancers receiving systemic anticancer treatment during the COVID-19 pandemic at Guy's Cancer Centre: A single centre retrospective study in the UK [abstract]. In: Proceedings of the AACR Virtual Meeting: COVID-19 and Cancer; 2021 Feb 3-5. Philadelphia (PA): AACR; Clin Cancer Res 2021;27(6_Suppl):Abstract nr S09-03.