Endocrine Therapy For Breast Cancer Research Articles

Everolimus and exemestane for the treatment of metastatic hormone receptor-positive breast cancer patients previously treated with CDK4/6 inhibitor based therapies.

1058 Background: The combination of everolimus (EVE) and exemestane (EXE) is approved as second line endocrine therapy for metastatic hormone receptor positive breast cancer (mHRBC) patients who progressed on non-steroidal aromatase inhibitor (NSAI) therapy based on the BOLERO-2 trial. However, none of the patients in BOLERO-2 received prior CDK4/6 inhibitors, which have since become standard of care for metastatic HRBC. As such, the clinical benefit of EVE + EXE in mHRBC patients previously treated with CDK4/6 inhibitors remains unknown. Methods: We reviewed patients ≥18yo with mHRBC treated with EVE + EXE following NSAI alone or NSAI + CDK 4/6 inhibitor at our institution between 2012-2018. Data collected included patient and tumor characteristics, therapies in the metastatic setting, special interest adverse events, and clinical outcomes. The primary objective was comparing PFS for EVE + EXE therapy between patients who received prior CDK4/6 inhibitor therapy and those who did not. Secondary endpoints included overall survival (OS). Patient features were summarized with descriptive statistics and time-to-event measures were estimated using the Kaplan-Meier method. Differences between groups were tested with Fisher’s exact, Kruskal-Wallis, or log-rank test. Results: Thirty-three patients were included in the study; 17 had prior CDK4/6 inhibitor therapy and 16 did not. Subjects that took EVE + EXE for < 28 days were excluded. Patient characteristics, including prior therapies and sites of metastatic disease, were not significantly different. There was no significant difference in PFS (median 5.7 vs 4.7 months, p = 0.890) or OS (median 17.8 vs 11.4 months, p = 0.177) between patients who received prior CDK4/6 inhibitors and those who did not, respectively. Steroid mouthwash use was associated with a reduced incidence of stomatitis. Conclusions: EVE + EXE is well tolerated and shows similar efficacy in metastatic HRBC patients who received CDK4/6 inhibitor therapy and those who did not. There was a non-significant trend towards improved OS in the CDK4/6 inhibitor group that needs to be further evaluated in larger patient cohorts.

Assessing adherence to hormone therapy (HT) in breast cancer (BC) patients receiving care at BC unit in a Uruguayan university of Hospital de Clínicas.

e12026 Background: Adjuvant HT in Hormone Receptors (HR) + BC increases overall survival (OS). Adherence to therapy is a complex and multifaceted issue that can alter outcomes; however, not much of it is known abouth this in routine clinical practice. Methods: This was a retrospective study that enrolled patients treated with HT because of HR+ BC (stages I-III) at the BC unit in the 2002-2012 period. Methods: The proportion remaining on endocrine therapy was analysed by Kaplan-Meier curve. Univariate analysis (log rank test) was used to identify the factors that might independently impact on such discontinuation. The study was approved by the Ethics Committee of the Hospital de Clínicas. Results: 139 (73.1%) of the 190 patients enrolled were postmenopausal; their median age being 61 years. Most patients were single or divorced or widowed (121, 63.7%) and resided in the capital (125, 65.7%). Most tumors (166, 87.3%) were ductal carcinomas and most presented at a low histological grade: HG 2-3: 112 (58.9%). The distribution by stage was: SI: 63 (33.1%); SII: 82 (43.1%); SIII 39 (20.5%); S0 6 (3.1%). At the end of their first, second, third, fourth and fifth years of treatment; 95.3%, 87.9%, 80.6%, 76.4% and 69.5% of the patients still adhered, respectively. Adherence was not associated with either age (p = 0.687), menopausal status (p = 0.449), marital status (p = 0.221), origin (p = 0.5640), or stage (p = 0.168). The patients who received combined HT (tamoxifen followed by AI) adhered better than those who received one drug alone (p = 0.017). Conclusions: we assessed the adherence to HT in real life and found that it was reduced by 30.5% in 5 years, despite patients were well informed about the well-known benefit in terms of OS, of being a well-tolerated treatment and of being provided for free. These results are similar to or even better than those reported in several international studies. Further investigation is needed to understand why patients interrupt HT. We need to work harder to increase compliance, given the potential impact this may have on the patients’ OS.

GPER1 influences cellular homeostasis and cytostatic drug resistance via influencing long chain ceramide synthesis in breast cancer cells.

The G protein-coupled estrogen receptor 1 (GPER1) is involved in the regulation of physiological processes such as cellular growth and proliferation, but also in pathophysiological processes such as tumor development. The role of GPER1 in breast cancer is contradictory. Therefore, we investigated the influence of GPER1 overexpression on cellular processes in MCF-7 breast cancer cells. GPER1 overexpression leads to a cell cycle arrest in the G1 phase, induction of autophagy and reduced proliferation. Reduced proliferation was accompanied by a reduced basal respiration and reduced glycolysis rate in GPER1 overexpressing cells. This is presumably ascribable to mitophagy induction following GPER1 overexpression. However, GPER1 overexpressing cells were less sensitive against doxorubicin as compared to control cells. In previous work we showed the effect of transient GPER1 overexpression on the synthesis of several ceramide synthases (CerS) thereby influencing the sphingolipid pathway. Therefore, we investigated CerS expression and sphingolipid level in stable GPER1 overexpressing and control cells. Stable GPER1 overexpression strongly reduced CerS4, CerS5 and CerS6 promoter activity and CerS5 and CerS6 mRNA expression, whereas CerS2 mRNA expression was upregulated. The GPER1 effect on CerS5 promoter is mediated by GSK-3β signaling. In addition, other enzymes of the sphingolipid pathway were upregulated. Our study provides new insights into the role of GPER1 and the activated sphingolipid pathways and how GPER1 may influence cellular processes such as cancer cell survival following chemotherapy. Further studies are needed to investigate the molecular mechanisms leading to these cellular effects. Finding new therapeutic targets for modulating specifically GPER1 in breast tumors may improve endocrine breast cancer therapy.

PCN268 ASSOCIATION BETWEEN ADHERENCE TO ORAL HORMONE THERAPY AND TYPE OF ORAL HORMONE THERAPY IN MEDICARE BENEFICIARIES WITH HORMONE RECEPTOR POSITIVE BREAST CANCER

Use of oral hormone therapy for hormone receptor positive breast cancer has increased and newer aromatase inhibitor drugs have been incorporated into therapy. However, there is limited data on adherence to oral hormone therapy, or on any differences among drug classes in adherence. The objectives of this study were to 1) determine levels of adherence to oral hormone therapy for breast cancer in the Medicare population, and 2) assess association between hormone therapy type and adherence. Data used were from 2010-2014 SEER-Medicare files. Inclusion criteria were female sex, diagnosis of hormone receptor positive breast cancer, and at least 2 Medicare Part D claims for tamoxifen or aromatase inhibitors. Exclusion criteria were not being continuously enrolled in Medicare. Claim-based medication adherence was calculated as proportion of days covered (PDC) in a one-year period following start of oral hormone therapy. Individuals with PDCs of 0.80 or higher were considered adherent. Multivariate logistic regression was used to assess associations between hormone therapy type and adherence, after controlling for patient demographic characteristics (age, race, income, insurance and marital status). Among 19,200 individuals who met selection criteria, 16,340 (85.1%) took aromatase inhibitors and 2,860 (14.9%) took tamoxifen. The overall proportion (95% confidence interval) of adherent patients was 76.3%, (75.2% - 78.1%). Adherent proportion among aromatase inhibitor users was 78.3%, (77.7% - 78.9%), while 64.7%, (62.9% - 66.4%) of tamoxifen users were adherent to their medication. Age, race, household income, insurance type, and marital-status were not significantly associated with adherence. Based on multivariate logistic regression, patients on an aromatase inhibitor were 1.9 times (1.8-2.1) more likely to be adherent than patients on tamoxifen (p<0.0001), after controlling for age, race, household income, insurance, and marital-status. Women with hormone receptor positive breast cancer were 1.9 times more likely to be adherent to aromatase inhibitors as compared to tamoxifen.

Gold nanoparticle uptake is enhanced by estradiol in MCF-7 breast cancer cells.

Purpose: In the present study, we investigated the effects of 17β-estradiol (E2) on membrane roughness and gold nanoparticle (AuNP) uptake in MCF-7 breast cancer cells.Methods: Estrogen receptor (ER)-positive breast cancer cells (MCF-7) were exposed to bare 20 nm AuNPs in the presence and absence of 1×10−9 M E2 for different time intervals for up to 24 hrs. The effects of AuNP incorporation and E2 incubation on the MCF-7 cell surface roughness were measured using atomic force microscopy (AFM). Endocytic vesicle formation was studied using confocal laser scanning microscopy (CLSM). Finally, the results were confirmed by hyperspectral optical microscopy.Results: High-resolution AFM images of the surfaces of MCF-7 membranes (up to 250 nm2) were obtained. The incubation of cells for 12 hrs with AuNP and E2 increased the cell membrane roughness by 95% and 30% compared with the groups treated with vehicle (ethanol) or AuNPs only, respectively. This effect was blocked by an ER antagonist (7α,17β-[9-[(4,4,5,5,5-Pentafluoropentyl)sulfinyl]nonyl]estra-1,3,5(10)-triene-3,17-diol [ICI] 182,780). Higher amounts of AuNPs were localized inside MCF-7 cells around the nucleus, even after 6 hrs of E2 incubation, compared with vehicle-treated cells. Endolysosome formation was induced by E2, which may be associated with an increase in AuNP-uptake.Conclusions: E2 enhances AuNP incorporation in MCF-7 cells by modulating of plasma membrane roughness and inducing lysosomal endocytosis. These findings provide new insights into combined nanotherapies and hormone therapies for breast cancer.

Evaluation of binding and antagonism/downregulation of brilanestrant molecule in estrogen receptor-α via quantum mechanics/molecular mechanics, molecular dynamics and binding free energy calculations

The resistance to the endocrine therapy of breast cancer leads to the emergence of new class of drugs that downregulates the estrogen receptor action known as selective estrogen receptor downregulators (SERDs). The first approved SERD is fluvestrant; after this, there are several downregulators evolved and are in clinical trials, in which the brilanestrant (BRI) molecule shows nM range of binding affinity and efficacy. In the present study, to understand the binding nature of BRI molecule in the active site of ERα, the molecular docking analysis has been performed. Further, the QM/MM calculations were performed for the BRI–ERα complex to analyze the charge density distribution of intermolecular interactions. The molecular dynamics (MD) simulation was employed to understand the stability and binding mechanism of BRI molecule through root-mean-square deviation (RMSD), root-mean-square fluctuation (RMSF) and binding free energy calculations. From the MD simulation trajectory analysis, the alterations of Helix12 conformation and the key residue (Lys529), which is responsible for the ERα downregulation, have been identified. Further, the interaction between the H3 and H12 regions was identified for the antagonism of BRI molecule. The current study led us to understand the binding mechanism, antagonism and downregulation of BRI molecule, and this knowledge is essential to design novel SERDs for the treatment of endocrine-resistant positive breast cancer.Communicated by Ramaswamy H. Sarma

SAT-341 Pharmacology and Metabolism of GLL398 an Oral Selective Estrogen Receptor Degrader for Endocrine Therapy of Breast Cancer

Selective estrogen receptor degrader (SERD) has proven clinically effective in treating advanced or metastatic breast cancer since the approval of fulvestrant by FDA in 2002. Recent expansion of indications as a first line monotherapy and as combination therapy with CDK4/6 inhibitors further demonstrates its clinical utility as an efficacious breast cancer endocrine regimen. However, the poor pharmacokinetic properties of fulvestrant and its injection-only administration route has driven continued efforts to develop orally bioavailability SERD that could potentially improve clinical response to SERD treatment. Our laboratory has developed a boron-modified GW5638 analog, GLL398 that showed superior oral bioavailability while retaining both antiestrogenic activity and ER degrading efficacy at a potency level comparable to the more active metabolite of GW5638, GW7604. Here we report further studies on the pharmacology, pharmacokinetics, and metabolism of GLL398. Given GLL398’s robust activities in breast cancer cells that are either tamoxifen resistant or express constitutively active, mutant ESR1 (Y537S), we first measured its binding behavior towards ERY537S. To better understand the mode of action we next performed molecular modeling of the binding of GLL398 and found its molecular interactions consistent with the experimentally determined high binding affinity towards WT ER and ERY537S. To test if the superior oral bioavailability can be translated to potent efficacy in vivo, mice bearing MCF-7 derived xenograft breast tumors and patient derived xenograft tumors harboring ERY537S were treated with GLL398 which potently inhibited tumor growth in mice. Finally, the metabolism of GLL398 was also investigated to elucidate the biotransformation of the drug and its potential contribution to the superior oral bioavailability over GW7604.

OCT Angiography Findings of Tamoxifen Retinopathy: Similarity with Macular Telangiectasia Type 2

We aimed to describe the vascular changes in eyes associated with tamoxifen retinopathy using OCT angiography (OCTA) and to compare these changes with abnormalities in macular telangiectasia type 2 (MacTel 2) previously reported in the literature. Retrospective, observational study. Seventeen eyes with tamoxifen retinopathy and 17 eyes of age-matched healthy control participants. The medical records of patients who visited the ophthalmology department with a history of taking tamoxifen were reviewed. Tamoxifen retinopathy was diagnosed based on typical spectral-domain (SD) OCT findings, such as intraretinal cavitation, photoreceptor disruption, or both. Multimodal imaging, particularly focused on OCTA, was analyzed. To compare vessel density in OCTA, age-matched normal control participants also were enrolled. Descriptive appraisal of the vascular abnormalities and objective quantification of vessel density associated with tamoxifen retinopathy. Among 292 patients who were screened, 26 were diagnosed with tamoxifen retinopathy. Of these, 17 eyes of 10 patients who were evaluated using OCTA were included. All patients were women, with a median patient age of 65.0 years. They were treated with tamoxifen as adjuvant endocrine therapy for breast cancer. All eyes showed intraretinal cavitation, and 8 eyes showed focal photoreceptor disruption as well, on OCT. On OCTA imaging, 14 eyes (82.4%) showed saccular capillary telangiectasia at the deep capillary plexus and 6 eyes (35.3%) showed right-angled vessels. Foveal vessel density of the superficial plexus was significantly lower in eyes with tamoxifen retinopathy than in control participants (P= 0.003). Crystalline deposits on fundus photographs (12 eyes [70.6%]) and increased autofluorescence on fundus autofluorescence (16 eyes [94.1%]) also were noted as characteristic findings of tamoxifen retinopathy. In addition to morphologic changes of tamoxifen retinopathy in SD OCT, its vascular changes on OCTA, such as telangiectatic vascular change at the deep capillary plexus and right-angled vessels, are similar to those observed in the early stages of MacTel2.

Use of Guarana for Hot Flashes after Breast Cancer: Randomized, Double-Blind, Placebo-Controlled Phase II Trial

Background: Hot flashes are common in menopausal women and significantly affect the quality of life of many patients diagnosed with breast cancer for which hormone replacement therapy is not indicated. In a previous uncontrolled study, guarana ( Paullinia cupana ) showed significant decreases in the amount and intensity of hot flashes in this group of women. Hypothesis/Purpose: The main objective was to reduce the intensity and frequency of hot flashes with the use of PC-18, compared with placebo in women who survived breast cancer without current evidence of disease. Study Design: The present study consists of a double-blind, randomized, placebo-controlled, uni-institutional, two-arm phase II clinical trial. Methods: The experimental group received the purified dry extract of Paullinia cupana (PC-18) at a dose of 37.5 g twice daily, while the other group received placebo, also twice daily. Results: The study included 40 patients who had completed surgical, chemotherapeutic and/or radiotherapeutic treatment for more than 3 months and who were on adjuvant hormone therapy at the time of inclusion, 20 in each arm. Both groups showed significant reductions in the number and intensity of hot flashes, with no significant difference between the arms. There was a higher intensity and frequency of hot flashes in patients receiving tamoxifen compared with those who received aromatase inhibitors. The toxicities observed were not very significant. Conclusion: This concludes that PC-18 did not demonstrate significantly greater capacity than placebo for control of hot flashes in women with a history of breast cancer and adjuvant hormone therapy.

Exploring the PROTAC degron candidates: OBHSA with different side chains as novel selective estrogen receptor degraders (SERDs)

As the mutant estrogen receptor (ER) continues to be characterized, breast cancer is becoming increasingly difficult to cure when treated with hormone therapy. In this regard, a strategy to selectively and effectively degrade the ER might be an effective alternative to endocrine therapy for breast cancer. In a previous study, we identified a novel series of 7-oxabicyclo[2.2.1]heptene sulfonamide (OBHSA) compounds as full ER antagonists while lacking the prototypical ligand side chain that has been widely used to induce antagonism of ERα. Further crystal structure studies and phenotypic assays revealed that these compounds are selective estrogen receptor degraders (SERDs) with a new mechanism of action. However, from a drug discovery point of view, there still is room to improve the potency of these OBHSA compounds. In this study, we have developed new classes of SERDs that contain the OBHSA core structure and different side chains, e.g., basic side chains, long alkyl acid side chains, and glycerol ether side chains, to simply mimic the degrons of proteolysis targeting chimera (PROTAC) and then investigated the structure-activity relationships of these PROTAC-like hybrid compounds. These novel SERDs could effectively inhibit MCF-7 cell proliferation and demonstrated good ERα degradation efficacy. Among the SERDs, compounds 17d, 17e and 17g containing a basic side chain with a N-trifluoroethyl substituent and a para methoxyl group at the phenyl group of the sulfonamide turned out to be the best candidates for ER degraders. A further docking study of these compounds with ERα elucidates their structure-activity relationships, which provides guidance to design new PROTAC degrons targeting ER for breast cancer therapy. Lastly, easy modification of these PROTAC-like SERDs enables further fine-tuning of their pharmacokinetic properties, including oral availability.

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.

P014 - Endocrine therapy in breast cancer with pulmonary embolism

P014 - Endocrine therapy in breast cancer with pulmonary embolism

Does Adding a Targeted Agent Improve Neoadjuvant Endocrine Therapy for Breast Cancer

Neoadjuvant endocrine therapy for breast cancer is less common in the U.S. than in Europe; still, this approach might merit reconsideration,

Abstract P4-14-13: Tamoxifen induced ovarian hyperstimulation during hormonal therapy for breast cancer

Abstract Introduction Adjuvant endocrine therapy is an integral compo-nent of care for endocrine-dependent breast cancer. To date, international consensus statements recommend tamoxifen (20 mg/day) for five years as the standard adjuvant endocrine therapy for premenopausal women. Tamoxifen is a potent inducer of ovarian function and consequent hyper-estrogenism in premenopausal women. However, the incidence rate and risk factors associated this phenomenone were not clarified. Methods Among consecutive patients who were operated under diagnosis of breast cancer from March 2012 to December 2016 in Chung-Ang university hospital, patients who received post-operative tamoxifen therapy for endocrine-dependent breast cancer (stage 0-III) at age under 60 were selected and retrospectively analysed. Serial data on serum estradiol and follicular stimulating hormone(FSH) were collected. When the serum concentration of estradiol was higher than 400 pg/mL, which exceeds the normal estradiol production by a single preovulatory follicle, we classified them as tamoxifen induced ovarian hyperstimulation group. Clinicopathologic factors were analyzed between ovarian hyperstimulation group and non-hyperstimulation group by x2 and student t-test. Results Among 205 patients, 19 patients(9.3%) showed high values of serum estradiol during tamoxifen therapy. They showed 44 times of high estradiol level during follow up period. The serum concentrations of estradiol and FSH were 1047.97638.8pg/mL and 11.57.3 mIu/mL, respectively. The mean duration from the start of the single administration of tamoxifen to the initial detection of a high concentration of estradiol was 666.4+433.1 days. Univariate and multivariate analysis between ovarian hyperstimulation and non-hyperstimulation groups showed younger age(&amp;lt;40years) and only endocrine therapy without chemotherapy were related to higher prevalence of ovarian hyperstimulation significantly. (p &amp;lt;0.001, =0.031 each) Pathologic stages and progesterone receptor expressions on breast tumor were not related to manifestation of ovarian hyperstimulation. Conclusions The Incidence rate and occurrence time of ovarian hyperstimulation associated with adjuvant tamoxifen treatment in breast cancer patients under age 60 were 9.3% and around 2-year after treatment with tamoxifen. Young age under 40 years old and endocrine treatment without chemotherapy were risk factors predicting occurrence of ovarian hyperstimulation during tamoxifen treatment. It should be noted that tamoxifen is a potent inducer of ovarian function and close monitoring of the endocrine parameters during treatment with tamoxifen would be essential. Citation Format: Kim MK, Shin H-c. Tamoxifen induced ovarian hyperstimulation during hormonal therapy for breast cancer [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 P4-14-13.

Abstract P6-18-29: Real-world treatment patterns and clinical outcomes with palbociclib combination therapy received in US community oncology practices

Abstract Background: The treatment landscape for women with HR+/HER2- advanced and metastatic breast cancer (A/MBC) is changing as new agents are being combined with more established treatments to achieve greater efficacy in combating resistant and unresponsive disease. The present study is designed to describe patient characteristics, treatment patterns, and clinical outcomes in a cohort of women with HR+/HER2- A/MBC treated with palbociclib plus aromatase inhibitor (P+AI) or palbociclib plus fulvestrant (P+FV) in the US community oncology setting. Methods: Retrospective medical record data from adult women diagnosed with HR+/HER2- A/MBC who initiated P+AI or P+FV for treatment of A/MBC on or after February 3, 2015 were collected from the Vector Oncology Data Warehouse, a network comprised of 10 community oncology practices across the US. Descriptive analyses were performed on patient characteristics, treatment patterns, and clinical outcomes. Time to event outcomes (progression-free rate (PFR) and survival rate (SR)) at 12 (PFR-12, SR-12) and 24 (PFR-24, SR-24) months for the P+AI combination as first line endocrine therapy and 12 and 18 months for the P+FV combination as treatment following prior endocrine based therapy in either the adjuvant or metastatic setting. Results: Among 304 patients who received palbociclib combination therapy, 281 (92.4%) received it per labeled indication. Of the 281 on-label users, the focus of reporting here, 233 (82.9%) received P+AI as their initial endocrine therapy after A/MBC diagnosis; 48 (17.1%) received P+FV after prior endocrine therapy for breast cancer. Patient mean age (SD) was 63.1 (11.4) and 68.2 (10.2) years for patients receiving P+AI and P+FV, respectively. Patients were predominantly white (74.2% for P+AI and 77.1% for P+FV patients).The initial dosing for palbociclib was 125mg/day in 85.4% (n=199) of P+AI and 79.2% (n=38) of P+FV patients. Among patients who received P+AI, PFR-12 was 69.8% and PFR-24 was 46.8% with median follow up time of 10.8 months and 36.8% of progression events. The SR-12 was 89.8% and SR-24 was 71.4%. For patients who received P+FV, PFR-12 was 43.5% and PFR-18 was 39.9% with a median follow up time of 7.6 months and 50.0% of progression events. The SR-12 was 76.3% and SR-18 was 65.0%. Conclusions: This study provides real-world assessment of treatment patterns and clinical outcomes of patients with HR+/ HER2- A/MBC who received palbociclib in combination with an AI or a FV in US community oncology settings. These findings demonstrate the benefit of palbociclib combination therapy in a diverse real world population. Sponsor: Pfizer, Inc. Citation Format: Trocio J, Lin J, Fisher MD, Hu N, Davis C, McRoy L, Walker MS, Iyer S. Real-world treatment patterns and clinical outcomes with palbociclib combination therapy received in US community oncology practices [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 P6-18-29.

Abstract P1-08-17: Pharmacy refill synchronization and oral endocrine therapy adherence

Abstract Background: One-third to one-half of patients prescribed adjuvant endocrine therapy with tamoxifen or an aromatase inhibitor either discontinue early or skip a substantial number of pills. Research to improve this has been disappointing. We investigated whether poor pharmacy synchronization of medications is an unrecognized barrier to adherence. Methods: A cohort of women aged 66-90 years old with Stage 0-3 hormone receptor-positive breast cancer were identified from the Surveillance, Epidemiology and End Result (SEER)-Medicare claims-linked cancer registry. Women with Medicare pharmacy claims documenting at least one endocrine therapy prescription fill and at least one other medication fill were identified, and the 3-month synchronization of their medication fills was calculated as the quotient of the number of pharmacy visits and the number of filled medications subtracted from one. Logistic regression was used to assess the association between synchronization stratified by the number of medications and adherence to endocrine therapy (defined as medication possession ratio &amp;gt;80%) over the subsequent year. Results: The study cohort included 3,112 women treated with endocrine therapy for breast cancer (Table 1) . Over 31% were age 70 or younger, and 38.0% had stage 2 or 3 disease. During the three months after the first endocrine therapy prescription, the mean number of unique medications was 8.0 (S.D. 6.0) and the mean number of pharmacy visits was 8.6 S.D. 4.7) for a mean synchronization of 0.3 ( (S.D. 0.2) . In adjusted model, compared with the highest synchronization, those in the lowest synchronization quantile were less likely to be adherent (MPR &amp;gt;=80%) (Odds Ratio 0.71 (95% CI 0.57, 0.88)) as were those in the second-lowest (0.81 (0.65, 0.99). Neither age nor race/ethnicity were associated with adherence, and results were unchanged with inclusion of information about duration of fills (30 vs 90 days). Conclusions: Prescription fill synchronization is strongly associated with adherence to endocrine therapy. Research into interventions to improve adherence should include prescription synchronization and other health systems barriers. Citation Format: Neuner JM, Fergestrom N, Nattinger AB, Laud PW, Pezzin L. Pharmacy refill synchronization and oral endocrine therapy adherence [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 P1-08-17.

Changes in Recurrence Score by neoadjuvant endocrine therapy of breast cancer and their prognostic implication

BackgroundNeoadjuvant endocrine therapy (NET) can improve surgical outcomes in postmenopausal patients with hormone receptor-positive breast cancer. The Ki67 labelling index after NET has a better prognostic power than that at baseline. However, it remains unknown whether a multigene assay with post-treatment samples could predict the prognosis better than that with pretreatment samples.MethodsThe prognostic value of the multigene assay Oncotype DX Recurrence Score (RS) was investigated using pretreatment and post-treatment samples from a multicentre NET trial, JFMC34-0601 (UMIN C000000345), where exemestane was given at 25 mg/day for 24 weeks.ResultsBoth pretreatment and post-treatment RSs were significantly associated with disease-free survival (DFS) (p=0.005 and 0.002, respectively). The combination of pretreatment and post-treatment RSs was also a predictor of DFS (p=0.002) and superior to preoperative endocrine prognostic index (PEPI). Furthermore, combined RS was the only independent prognostic factor in the multivariate analysis among the three RSs (p=0.04). In addition, combined RS could differentiate early recurrence in the high-risk group from mid/late recurrence in the intermediate-risk group, suggesting possible differential treatment strategies based on the risk categories indicated by the combined RS.ConclusionsThe combination of pretreatment and post-treatment RSs could provide pivotal information for predicting DFS and differentiating early recurrence in the high-risk group from mid/late recurrence in the intermediate-risk group in patients with hormone receptor-positive breast cancer. A larger study is required to validate the results.

Modeling risk assessment for breast cancer in symptomatic women: a Saudi Arabian study.

BackgroundDespite the continuing increase in the breast cancer incidence rate among Saudi Arabian women, no breast cancer risk-prediction model is available in this population. The aim of this research was to develop a risk-assessment tool to distinguish between high risk and low risk of breast cancer in a sample of Saudi women who were screened for breast cancer.MethodsA retrospective chart review was conducted on symptomatic women who underwent breast mass biopsies between September 8, 2015 and November 8, 2017 at King Abdulaziz Medical City, Riyadh, Saudi Arabia.ResultsA total of 404 (63.8%) malignant breast biopsies and 229 (36.2%) benign breast biopsies were analyzed. Women ≥40 years old (aOR: 6.202, CI 3.497–11.001, P=0.001), hormone-replacement therapy (aOR 24.365, 95% CI 8.606–68.987, P=0.001), postmenopausal (aOR 3.058, 95% CI 1.861–5.024, P=0.001), and with a family history of breast cancer (aOR 2.307, 95% CI 1.142–4.658, P=0.020) were independently associated with an increased risk of breast cancer. This model showed an acceptable fit and had area under the receiver-operating characteristic curve of 0.877 (95% CI 0.851–0.903), with optimism-corrected area under the curve of 0.865.ConclusionThe prediction model developed in this study has a high ability in predicting increased breast cancer risk in our facility. Combining information on age, use of hormone therapy, postmenopausal status, and family history of breast cancer improved the degree of discriminatory accuracy of breast cancer prediction. Our risk model may assist in initiating population-screening programs and prompt clinical decision making to manage cases and prevent unfavorable outcomes.

Factors influencing non–adherence to chemotherapy: Perspective of Nigerian breast cancer survivors

Background &amp; Aim: The use of chemotherapy for the treatment of breast cancer has experienced a rapid increase in recent years and this is expected to continue. The objectives of the study were to ascertain the patient-related factors, therapy related factors, and health care system factors that influence non-adherence to chemotherapy among breast cancer survivors at University of Nigeria Teaching Hospital (UNTH), Enugu. Methods &amp; Materials: The study design was a cross-sectional descriptive survey with a total population of 100 cancer survivors. The breast cancer questionnaire was the instrument used for data collection. Results: The result of the study showed that financial constraint 61(61.0%) was the major patient related factor that influence non-adherence to chemotherapy, medication side effects (hair loss, loss of weight) 62(62.0%) and duration of treatment 50(50.0%) were the major therapy related factors while unfavorable hour of clinic visit 40(40.0%) was the major health care related factor that influences non-adherence to chemotherapy. Conclusion: It was concluded that the federal government should re-implement the health care policy that allowed treatment free-of-charge at Nigerian government hospitals to those with malignancies and other chronic ailments to mitigate the burden of associated financial problems and encourage patients to seek orthodox medical care. Also, health education initiation on benefit of adhering to chemotherapy would be needed on the part of the nurses to foster the women intake of chemotherapy. Nurses caring for women who receive endocrine therapy for breast cancer should identify those who may be at greater risk for being non-adherent.

Induction hormotherapy as a stage of combined treatment in patients with breast cancer

At the present time, new drugs for hormone therapy for breast cancer have been investigated. The drug Faslodex - a representative of a new class of steroidal antiestrogens - has successfully undergone preclinical studies and was selected for further testing in a clinical setting, as it has a unique pharmacological profile and is promising in terms of improving the results of treatment of estrogen-sensitive forms of breast cancer.