Endocrine Therapy For Breast Cancer Research Articles

148P Phase III study of everolimus or placebo in addition to adjuvant hormone therapy for high risk early breast cancer: Subgroup analysis of the UCBG UNIRAD trial

The double blind randomized UNIRAD trial (NCT01805271) showed that adding Everolimus (EVE) to adjuvant endocrine therapy (ET) for high-risk early breast cancer (BC) does not improve 3-year disease-free survival (iDFS) compared with ET alone. We report the subgroup analysis focusing on the pre-specified stratification factors.

Review of the Literature on Ocular Complications Associated With Aromatase Inhibitor Use.

Aromatase inhibitors (AIs), such as anastrozole, letrozole, and exemestane, are commonly used as adjuvant endocrine therapy in hormone-receptive breast cancer in postmenopausal women. Their adverse effects are well documented, except for visual disturbances. The purpose of this study was to review the current literature on ocular disease linked to AI use. Due to the scarcity of published data, any suggested ophthalmic adverse events were included to increase awareness of these drugs. The ocular side effects of tamoxifen use are well documented and were not included. Cases of rare side effects such as papilloedema, macular oedema, and uveitis associated with anastrozole and letrozole have been reported. Studies demonstrating retinopathy, in the form of crystalline retinopathy, hemicentral retinal artery occlusion, and retinal haemorrhages, are also noted. All three third-generation AIs can also lead to ocular surface diseases such as corneal epithelial changes, blepharitis, and keratitis. There is slightly more literature available regarding anastrozole-related ocular diseases. Although these are likely rare side effects, we recommend a high level of clinical suspicion when assessing patients with visual symptoms and on AIs. Larger prospective studies are necessary to further investigate these complications.

Breast Cancer Endocrine Therapy Promotes Weight Gain With Distinct Adipose Tissue Effects in Lean and Obese Female Mice.

Breast cancer survivors treated with tamoxifen and aromatase inhibitors report weight gain and have an elevated risk of type 2 diabetes, especially if they have obesity. These patient experiences are inconsistent with, preclinical studies using high doses of tamoxifen which reported acute weight loss. We investigated the impact of breast cancer endocrine therapies in a preclinical model of obesity and in a small group of breast adipose tissue samples from women taking tamoxifen to understand the clinical findings. Mature female mice were housed at thermoneutrality and fed either a low-fat/low-sucrose (LFLS) or a high-fat/high-sucrose (HFHS) diet. Consistent with the high expression of Esr1 observed in mesenchymal stem cells from adipose tissue, endocrine therapy was associated with adipose accumulation and more preadipocytes compared with estrogen-treated control mice but resulted in fewer adipocyte progenitors only in the context of HFHS. Analysis of subcutaneous adipose stromal cells revealed diet- and treatment-dependent effects of endocrine therapies on various cell types and genes, illustrating the complexity of adipose tissue estrogen receptor signaling. Breast cancer therapies supported adipocyte hypertrophy and associated with hepatic steatosis, hyperinsulinemia, and glucose intolerance, particularly in obese females. Current tamoxifen use associated with larger breast adipocyte diameter only in women with obesity. Our translational studies suggest that endocrine therapies may disrupt adipocyte progenitors and support adipocyte hypertrophy, potentially leading to ectopic lipid deposition that may be linked to a greater type 2 diabetes risk. Monitoring glucose tolerance and potential interventions that target insulin action should be considered for some women receiving life-saving endocrine therapies for breast cancer.

Finding the “Sweet Spot” with Adjuvant Endocrine Therapy for Breast Cancer

One dilemma in treating breast cancer is how long to continue adjuvant endocrine therapy. Late recurrences can occur in patients with estrogen receptor

Hormonal Therapy in Breast Cancer

Hormonal Therapy in Breast Cancer

Retraction.

Retraction: "Inhibitory role of large intergenic noncoding RNA-ROR on tamoxifen resistance in the endocrine therapy of breast cancer by regulating the PI3K/Akt/mTOR signaling pathway," by Peng-Wei Lu, Lin Li, Fang Wang, Yuan-Ting Gu, J Cell Physiol. 2019; 1904-1912: The above article, published online on 26 August 2018 in Wiley Online Library (https://onlinelibrary.wiley.com/doi/full/10.1002/jcp.27066), has been retracted by agreement between the journal's Editor in Chief, Prof. Dr. Gregg Fields, and Wiley Periodicals LLC. The retraction has been agreed following an investigation based on allegations raised by a third party. Several flaws and inconsistencies between results presented and experimental methods described were found. Thus, the editors consider the conclusions of this article to be invalid.

Does the Time of Day at Which Endocrine Therapy Is Taken Affect Breast Cancer Patient Outcomes?

Background: Non-compliance and non-persistence with endocrine therapy for breast cancer is common and usually related to treatment-induced side effects. There are anecdotal reports that simply changing the time of day when taking endocrine therapy (i.e., changing morning dosing to evening dosing or vice versa) can reduce side effects. Literature review: We conducted a literature review to evaluate whether changing the timing of tamoxifen and/or aromatase inhibitor administration impacted patient outcomes. No randomized control trials or prospective cohort studies that looked at time of day of endocrine therapy were identified through our review of literature from 1947 until August 2020. Conclusions: Given the rates of endocrine therapy non-compliance and non-persistence reported in the literature, ranging from 41–72% and 31–73%, respectively, simply changing the time of day when medications are taken could be an important strategy. We could identify no trials evaluating the effect of changes in timing of administration of endocrine therapy on breast cancer patient outcomes. Randomized control trials are clearly indicated for this simple and cost-effective intervention.

Abstract 406: Development of a gene signature assessing ER modulation by SERMs and SERDs as a target engagement biomarker for endocrine therapy in breast cancer

Abstract Hormone or endocrine therapy is the primary treatment for estrogen receptor-positive (ER+) breast cancer. Selective Estrogen Receptor Modulators (SERMs) have been used for women with ER+ invasive cancer in the adjuvant setting. However, they do not fully inhibit ER transcriptional activity. Therefore, selective estrogen receptor degraders (SERDs) such as fulvestrant have been developed to overcome the partial modulation of ER transcriptional activity by SERMs. However, the clinical benefit of fulvestrant is limited by its pharmaceutical properties, and burden of intramuscular administration. We developed amcenestrant (SAR439859), a novel, orally bioavailable SERD to improve drug properties and is under clinical investigation.To assess the relative ER modulating activity, we developed a gene signature by transcriptional profiling of multiple ER+ cell lines. We identified 87 genes that were either up- or down-regulated by estradiol and reversed by SERM and SERD compounds or differentially expressed between a SERM/SERD compound and estradiol. We assessed ER activity scores by applying Gene Set Variation Analysis (GSVA) method to the ER gene signature and evaluated the effect of 6 SERD compounds. Amcenestrant and fulvestrant illuminated a deeper inhibition of ER activity compared to the other compounds. In addition, these ER activity scores could potentially be utilized in clinics as pharmacodynamic (PD) biomarker to assess target engagement. We applied this ER signature to RNA-seq data from paired pre- and post-treatment tumor biopsies from patients of NCT03284957 study (AMEERA-1), an open-label, phase 1/2 study of amcenestrant in postmenopausal women with ER+/HER2- metastatic breast cancer. The results of our analysis showed that ER activity is down-regulated by amcenestrant (oral SERD) for 3 out of 5 patients, in parallel with clinical benefit. Validation in a larger patient cohort is needed. Citation Format: Joon Sang Lee, Maysoun Shomali, Monsif Bouaboula, Emma Wang, Wilson Dos-Santos-Bele, Colette Dib, Eric Boitier, Vasiliki Pelekanou, Nils Ternes, Alice Gosselin, Patrick Cohen, Marina Celanovic, Christopher Soria, Alexei Protopopov, Jack Pollard. Development of a gene signature assessing ER modulation by SERMs and SERDs as a target engagement biomarker for endocrine therapy in breast cancer [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 406.

Abstract 733: Significance of PELP1/SETDB1 axis in endocrine therapy resistance

Abstract BACKGROUND: PELP1 is commonly overexpressed in breast cancer (BCa) and is implicated in endocrine therapy resistance. However, the mechanism by which PELP1 contributes to therapy resistance remains elusive. Our ongoing studies using yeast two hybrid screen identified histone methyltransferase SETDB1 as a novel interactor of PELP1. The objective of this study is to determine the significance of PELP1 interaction with SETDB1 in BCa endocrine therapy resistance. METHODS: We used two ER+ BCa cell lines (MCF7 and ZR75) and three endocrine therapy resistant cell lines (Tamoxifen resistant MCF7-TamR, Fulvestrant resistant MCF7-FR, Tamoxifen resistant MCF7-PELP1-cyto). Additional BCa models with stable overexpression and under expression of SETDB1 and PELP1 (MCF7-SETDB1-PELP1shRNA, ZR75-SETDB1-PELP1shRNA, ZR75-SETDB1, MCF7-SETDB1, MCF7-TamR-SETDB1shRNA, MCF7-FR-SETDB1shRNA) were generated using lentiviral transduction. Functional significance of cross-talk was tested using MTT, soft agar, and colony formation assays. Mechanistic studies were conducted using immunoprecipitation, Western blotting, and RT-qPCR. RESULTS: Analyses of TCGA databases showed that SETDB1 expression is positively correlated with PELP1 expression in ER+ BCa (r=0.30, p<0.0001). Immunoprecipitation assays using multiple ER+ BCa cell lysates confirmed the interaction of SETDB1 with PELP1. Using ER+ BCa models with overexpression of SETDB1 or knockdown, we provided evidence that SETDB1 plays an important role in the proliferation of BCa cells. PELP1 knockdown attenuated SETDB1 mediated BCa cells proliferation. SETDB1 upregulation contributed to tamoxifen resistance, while PELP1 knockdown re-sensitized cells to tamoxifen therapy. Further, endocrine therapy resistant model cells (MCF7-TamR, MCF7-FR, MCF7-PELP1-cyto) showed increased expression of SETDB1, and its knockdown sensitized them to endocrine therapy. Mechanistic studies revealed that PELP1 is needed for SETDB1 mediated Akt phosphorylation and activation of its downstream targets such as S6, and Cyclin D1. CONCLUSIONS: The results of study suggest that the PELP1/SETDB1 interactions contribute to endocrine therapy resistance via aberrant activation of Akt signaling. Targeting PELP1/SETDB1 axis could represent a new therapeutic avenue to mitigate endocrine resistance. Supported by VA grant I01BX004545 (R.K. Vadlamudi) Citation Format: Zexuan Liu, Junhao Liu, Weiwei Tang, Uday P. Pratap, Kristin A. Altwegg, Behnam Ebrahimi, Xiaonan Li, Gangadhara R. Sareddy, Suryavathi Viswanadhapalli, Ratna K. Vadlamudi. Significance of PELP1/SETDB1 axis in endocrine therapy resistance [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 733.

Patient-derived scaffolds as a drug-testing platform for endocrine therapies in breast cancer

Three-dimensional cell culture platforms based on decellularised patient-based microenvironments provide in vivo-like growth conditions allowing cancer cells to interact with intact structures and components of the surrounding tissue. A patient-derived scaffold (PDS) model was therefore evaluated as a testing platform for the endocrine therapies (Z)-4-Hydroxytamoxifen (4OHT) and fulvestrant as well as the CDK4/6-inhibitor palbociclib, monitoring the treatment responses in breast cancer cell lines MCF7 and T47D adapted to the patient-based microenvironments. MCF7 cells growing in PDSs showed increased resistance to 4OHT and fulvestrant treatment (100- and 20-fold) compared to 2D cultures. Quantitative PCR analyses of endocrine treated cancer cells in PDSs revealed upregulation of pluripotency markers further supported by increased self-renewal capacity in sphere formation assays. When comparing different 3D growth platforms including PDS, matrigel, gelatin sponges and 3D-printed hydrogels, 3D based cultures showed slightly varying responses to fulvestrant and palbociclib whereas PDS and matrigel cultures showed more similar gene expression profiles for 4OHT treatment compared to the other platforms. The results support that the PDS technique maximized to provide a multitude of smaller functional PDS replicates from each primary breast cancer, is an up-scalable patient-derived drug-testing platform available for gene expression profiling and downstream functional assays.

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.

LncRNA-42060 Regulates Tamoxifen Sensitivity and Tumor Development via Regulating the miR-204-5p/SOX4 Axis in Canine Mammary Gland Tumor Cells.

Tamoxifen is the drug of choice for endocrine therapy of breast cancer. Its clinical use is limited by the development of drug resistance. There is increasing evidence that long non-coding RNAs (lncRNAs) are associated with tumor drug resistance. Therefore, we established two TAM-resistant cell lines, CHMpTAM and CHMmTAM. The different expression levels of lncRNA and miRNA in CHMmTAM and CHMm were screened by RNA sequencing, and the lncRNA-miRNA interactions were analyzed. LncRNA ENSCAFG42060 (lnc-42060) was found to be significantly upregulated in drug-resistant cells and tumor tissues. Further functional validation revealed that the knockdown of lnc-42060 inhibited proliferation, migration, clone formation, restoration of TAM sensitivity, and reduction of stem cell formation in drug-resistant cells, whereas overexpression of lnc-4206 showed opposite results. Bioinformatics and dual-luciferase reporter gene assays confirmed that lnc-42060 could act as a sponge for miR-204-5p, further regulating SOX4 expression activity and thus influencing tumor cell progression. In conclusion, we screened lncRNAs and miRNAs associated with TAM resistance in canine mammary gland tumor cells for the first time. lnc-42060 served as a novel marker that may be used as an important biomarker for future diagnosis and treatment.

Identification of Ten Mitosis Genes Associated with Tamoxifen Resistance in Breast Cancer

BackgroundEndocrine therapy is the backbone therapy in estrogen receptor α (ER)-positive breast cancer, and tamoxifen resistance is a great challenge for endocrine therapy. Tamoxifen-resistant and sensitive samples from the international public repository, the Gene Expression Omnibus (GEO) database, were used to identify therapeutic biomarkers associated with tamoxifen resistance.Materials and MethodsIn this study, integrated analysis was used to identify tamoxifen resistance-associated genes. Differentially expressed genes (DEGs) were identified. Gene ontology and pathway analysis were then analyzed. Weighted correlation network analysis (WGCNA) was performed to find modules correlated with tamoxifen resistance. Protein–protein interaction (PPI) network was used to find hub genes. Genes of prognostic significance were further validated in another GEO dataset and cohort from Shanghai Ruijin Hospital using RT-PCR.ResultsA total of 441 genes were down-regulated and 123 genes were up-regulated in tamoxifen-resistant samples. Those up-regulated genes were mostly enriched in the cell cycle pathway. Then, WGCNA was performed, and the brown module was correlated with tamoxifen resistance. An overlap of 81 genes was identified between differentially expressed genes (DEGs) and genes in the brown module. These genes were also enriched in the cell cycle. Twelve hub genes were identified using PPI network, which were involved in the mitosis phase of the cell cycle. Finally, 10 of these 12 genes were validated to be up-regulated in tamoxifen-resistant patients and were associated with poor prognosis in ER-positive patients.ConclusionOur study suggested mitosis-related genes are mainly involved in tamoxifen resistance, and high expression of these genes could predict poor prognosis of patients receiving tamoxifen. These genes may be potential targets to improve efficacy of endocrine therapy in breast cancer, and inhibitors targeted these genes could be used in endocrine-resistant patients.

Factors associated with weight gain during endocrine therapy for breast cancer.

12076 Background: Weight gain is common after a breast cancer diagnosis. The incidence of and risk factors for weight gain during adjuvant endocrine therapy (ET) are poorly described. Limited data support an association between emergent symptoms and weight gain after a breast cancer diagnosis. Methods: We enrolled women with stage 0-III breast cancer initiating ET in a prospective clinic-based cohort. We assessed symptoms with the FACT-ES and PROMIS pain interference, depression, anxiety, fatigue, sleep disturbance and physical function measures at baseline (BL), 3, 6, 12, 24, 36, 48 and 60 months (mo). We defined emergent symptoms at 3 and/or 6 mo as worsening of 4 points from BL on PROMIS measures and 5 points from BL on the FACT-ES. We abstracted weight and menopausal status from charts. The primary outcome of this secondary analysis was weight gain (dichotomized as ≥5% vs < 5% of body weight compared to BL) through 60 mo. We evaluated the association between weight gain during ET and menopausal status. We also evaluated the associations between clinicodemographic factors and emergent symptoms with weight gain and if these associations differed by menopausal status. We performed logistic regression modeling with GEE to account for the longitudinal design. We identified a multivariable model for the set of factors associated with weight gain among pre-menopausal women taking ET. Results: 309 of 321 participants with BL and ≥1 follow-up (FU) weight were included. 263 (85%) had stage I-II disease, 99 (32%) were pre-menopausal, 259 (84%) were White and 32 (10%) were Black. Prior to ET, 45% had mastectomy, 66% had radiation, and 28% received chemotherapy. 4% of pre- and 82% of post-menopausal participants initiated an aromatase inhibitor (AI); all others initiated tamoxifen (Tam). 17% of pre-menopausal participants received ovarian suppression. At BL, 75% of Black and 59% of White participants were overweight/obese. With a median FU of 56 mo, 51% of pre- and 34% of post-menopausal participants gained ≥5% body weight (OR 1.09, 95% CI 1.07-1.13, p < 0.001). For each PRO measure, > 20% of participants had emergent symptoms. Worsening of physical function and pain interference scores at 3 and/or 6 mo were differentially associated with weight gain according to menopausal status (interaction p-values ≤0.05). On multivariate analysis, factors associated with weight gain among pre-menopausal participants were ET (AI vs Tam) (OR 2.8, 95% CI 0.90- 8.77, p = 0.08), prior mastectomy (OR 2.06, 95% CI 0.89-4.77, p = 0.09), emergent pain interference (OR 2.49, 95% CI 0.99-6.24, p = 0.05) and race (White vs other) (OR 7.13, 95% CI 1.29-39.4], p = 0.02). Conclusions: Weight gain during ET for breast cancer is more frequent among pre-menopausal than post-menopausal women. Worsening pain soon after ET initiation, receipt of AI, prior mastectomy and race may identify pre-menopausal women at risk for weight gain for whom prevention strategies are a priority.

Cost sharing for breast cancer hormone therapy: How do dual eligible patients' copayment impact adherence.

ObjectiveTo examine the different levels of copayment assistance and treatment adherence among Medicare and Medicaid dual eligible beneficiaries with breast cancer in the U.S.Research designPropensity Score methodology was adopted to minimize potential selection bias from the nonrandom allocation of the treatment group (i.e., full Medicaid beneficiaries) and control group (i.e., Medicare Savings Programs [MSPs] beneficiaries). Longitudinal hierarchical model and Cox proportional-hazard model were adopted to examine patients’ adherence over their full five-year course of adjuvant hormone therapy.ResultsOur study cohort consisted of 1,133 dual eligible beneficiaries diagnosed with hormone receptor-positive early stage breast cancer in years 2007 –mid 2009. About 80.5% of them received MSPs benefits, while the rest received full Medicaid benefits. On average for a standardized 30-day hormone therapy medication, full Medicaid beneficiaries spent $0.5-$2.0 and MSP beneficiaries spent $1.4-$4.8 in copayment. After adjusting for other factors, this copayment reduction wasn’t associated with a significantly better adherence. However, when the catastrophic coverage threshold was reached (copayments reduced to zero), significant improvement in adherence was found in both groups.ConclusionsOur study found that small amount of cost-sharing reduction did not affect Medicare and Medicaid dual eligible patients’ medication treatment adherence, however, the elimination of cost-sharing (even a minimal amount) was associated with improved adherence. Future legislative and advocacy efforts should be paid on eliminating cost sharing for dual eligibles, and possibly even a broader group of financially vulnerable patients.

Bacterial extracellular vesicles affect endocrine therapy in MCF7 cells.

Background: The microbiome is important in the development and progression of breast cancer. This study investigated the effects of microbiome derived from Klebsiella on endocrine therapy of breast cancer using MCF7 cells. The bacterial extracellular vesicles (EVs) that affect endocrine therapy were established through experiments focused on tamoxifen efficacy.Methods: The microbiomes of breast cancer patients and healthy controls were analyzed using next-generation sequencing. Among microbiome, Klebsiella was selected as the experimental material for the effect on endocrine therapy in MCF7 cells. MCF7 cells were incubated with tamoxifen in the absence/presence of bacterial EVs derived from Klebsiella pneumoniae and analyzed by quantitative real-time polymerase chain reaction and Western blot.Results: Microbiome derived from Klebsiella is abundant in breast cancer patients especially luminal A subtype compared to healthy controls. The addition of EVs derived from K pneumoniae enhances the anti-hormonal effects of tamoxifen in MCF7 cells. The increased efficacy of tamoxifen is mediated via Cyclin E2 and p-ERK.Conclusion: Based on experiments, the EVs derived from K pneumoniae are important in hormone therapy on MCF7 cells. This result provides new insight into breast cancer mechanisms and hormone therapy using Klebsiella found in the microbiome.

Breast Cancer Endocrine Therapy Exhausts Adipocyte Progenitors Promoting Weight Gain and Glucose Intolerance

Breast cancer survivors treated with anti-estrogen therapies report weight gain and have an elevated risk of type 2 diabetes. Here, we show that current tamoxifen use did not influence body mass index but associated with larger breast adipocyte diameter only in women with obesity, suggesting adipose tissue may be targeted by breast cancer therapies. To understand the mechanisms behind these clinical findings, we investigated the impact of estrogen deprivation and tamoxifen in a relevant pre-clinical murine model of obesity. Specifically, mature female mice were housed at thermoneutrality and fed either a low-fat/low-sucrose (LFLS) or a high-fat/high-sucrose (HFHS) diet. Consistent with the high expression of Esr1 observed in single-cell RNA sequencing of mesenchymal stem cells from mouse adipose tissue, endocrine therapies associated with adipose accumulation and preadipocyte expansion, but resulted in adipocyte progenitor depletion only in the context of HFHS. Consequently, 7-week endocrine therapy supported adipocyte hypertrophy and was associated with hepatic steatosis, hyperinsulinemia, insulin resistance, and glucose intolerance, particularly in HFHS fed females. We administered HFHS fed females either metformin or pioglitazone, glucose lowering drugs used to treat diabetes, or treadmill interval exercise during endocrine therapy with the goal of improving whole body metabolism. All interventions prevented the effects of tamoxifen but not estrogen deprivation on adipocyte size and insulin resistance in HFHS-fed mice. This translational study suggests that endocrine therapies may act via ER-alpha to directly disrupt adipocyte progenitors and support adipocyte hypertrophy, leading to ectopic lipid deposition that may promote hyperinsulinemia, insulin resistance and type 2 diabetes. Interventions that target insulin action should be considered for some women receiving life-saving endocrine therapies for breast cancer.

Changes in initiation of adjuvant endocrine therapy for breast cancer after state health reform

BackgroundSocioeconomic differences in receipt of adjuvant treatment contribute to persistent disparities in breast cancer (BCA) outcomes, including survival. Adjuvant endocrine therapy (AET) substantially reduces recurrence risk and is recommended by clinical guidelines for nearly all women with hormone receptor-positive non-metastatic BCA. However, AET use among uninsured or underinsured populations has been understudied. The health reform implemented by the US state of Massachusetts in 2006 expanded health insurance coverage and increased the scope of benefits for many with coverage. This study examines changes in the initiation of AET among BCA patients in Massachusetts after the health reform.MethodsWe used Massachusetts Cancer Registry data from 2004 to 2013 for a sample of estrogen receptor (ER)-positive BCA surgical patients aged 20–64 years. We estimated multivariable regression models to assess differential changes in the likelihood initiating AET after Massachusetts health reform by area-level income, comparing women from lower- and higher-income ZIP codes in Massachusetts.ResultsThere was a 5-percentage point (p-value< 0.001) relative increase in the likelihood of initiating AET among BCA patients aged 20–64 years in low-income areas, compared to higher-income areas, after the reform. The increase was more pronounced among younger patients aged 20–49 years (7.1-percentage point increase).ConclusionsThe expansion of health insurance in Massachusetts was associated with a significant relative increase in the likelihood of AET initiation among women in low-income areas compared with those in high-income areas. Our results suggest that expansions of health insurance coverage and improved access to care can increase the number of eligible patients initiating AET and may ameliorate socioeconomic disparities in BCA outcomes.

P041. Systematic review of surgical and patient reported outcomes of neoadjuvant endocrine therapy for breast cancer

P041. Systematic review of surgical and patient reported outcomes of neoadjuvant endocrine therapy for breast cancer

Impact of adjuvant endocrine therapy on prognosis in small hormone receptor-positive, HER2-negative early breast cancer.

The efficacy of adjuvant endocrine therapy for hormone receptor-positive breast cancer has been previously established. However, significant adverse events related to endocrine therapy cannot be ignored. T1 breast cancer is expected to have a good prognosis. Therefore, adjuvant endocrine therapy for T1a breast cancer patients is controversial. Thus, in this study, we examined the effect of endocrine therapy on the prognosis of T1N0 hormone receptor-positive, HER2-negative breast cancer patients in each tumor size group, and re-considered the application of endocrine therapy. We retrospectively obtained clinical and pathological data from medical records of 7635 patients who underwent surgery for breast cancer at Aichi Cancer Hospital between January 2000 and December 2017. The primary end point of our analysis was disease-free survival (DFS). The secondary end points were distant disease-free survival (DDFS), overall survival (OS), and breast cancer-specific survival (BCSS). The log-rank test, cumulative survival generated curves with Kaplan-Meier methods and the hazard ratio (HR) calculated with a Cox regression model were used to assess the effects of endocrine therapy on prognosis. The 5-year DFS was worse in the non-endocrine therapy (non-ET) group (78%) than the endocrine therapy (ET) group (95%) in the T1c population (p < 0.001, HR 0.25). However, there was no statistically significant difference in DFS between the ET and the non-ET groups in T1a (ET 96% vs non-ET 93%, p = 0.9314, HR 0.94) and T1b (ET 96% vs non-ET 93%, p = 0.1481HR 0.53) breast cancer. The OS, DDFS, and BCSS of the patients also showed that endocrine therapy was associated with improvement of the prognosis in the T1c group, but not in the T1a and T1b groups. Adjuvant endocrine therapy may be essential for T1c breast cancer patients. In contrast, this therapy should be discussed for T1a and T1b luminal breast cancer patients under some circumstances, such as suffering from adverse events.