Endocrine Therapy For Breast Cancer Research Articles

Is the extension of adjuvant hormone therapy for breast cancer justified?

In practice, all patients with ER (+) primary breast cancer should conduct adjuvant hormone therapy to suppress the growth of tumors stimulated by estrogens. Five-year tamoxifen treatment reduces breast cancer mortality for 30%, and aromatase inhibitors (for postmenopausal women) reduces it by up to 40%. After five years, long-term relapses still occurred, the risk of which can be reduced by the expansion of adjuvant hormone therapy for more than 5 years. At the population level, the treatment can show relatively moderate and sometimes toxic effects; therefore, it is extremely important for modern clinical practice to identify patients with risk of relapse within the first five years small enough for the therapy to be safely canceled for this period, as well as patients with a risk of relapse high enough to justify a longer treatment. Currently, little data is available from clinical trials regarding the second problem. Recent EBCTCG studies have consistently shown a risk of relapse within 5–20 years in all patient groups. However, the risk varies greatly depending on the size of the tumor and the status of the lymph nodes. The tumor grade (G) and the proliferation index (Ki67), supplementing the information on the TN stage, demonstrate a high degree of correlation between each other. The only patients who have a relatively low frequency of long-term recurrence (which allows them to be assigned to a very low risk group) are patients with a low tumor grade pT1N0. Prognostic molecular signatures have been proven to be clinically useful (in addition to clinical and morphological characteristics) in identifying patients with an extremely low risk of relapse who can safely avoid chemotherapy. In clinical trials of adjuvant hormone therapy with a long follow-up period (up to 20 years), a delayed (over five years) recurrence of estrogen-receptor-positive (ER+) breast cancer was noted. Based on these observations, a number of researchers offer longer hormone therapy (exceeding the five-year standard).

90 YEARS OF PROGESTERONE: Progesterone and progesterone receptors in breast cancer: past, present, future.

Progesterone and progesterone receptors (PR) have a storied albeit controversial history in breast cancers. As endocrine therapies for breast cancer progressed through the twentieth century from oophorectomy to antiestrogens, it was recognized in the 1970s that the presence of estrogen receptors (ER) alone could not efficiently predict treatment responses. PR, an estrogen regulated protein, became the first prognostic and predictive marker of response to endocrine therapies. It remains today as the gold standard for predicting the existence of functional, targetable ER in breast malignancies. PRs were subsequently identified as highly structured transcription factors that regulate diverse physiological processes in breast cancer cells. In the early 2000s, the somewhat surprising finding that prolonged use of synthetic progestin-containing menopausal hormone therapies was associated with increased breast cancer incidence raised new questions about the role of PR in 'tumorigenesis'. Most recently, PR have been linked to expansion of cancer stem cells that are postulated to be the principal cells reactivated in occult or dormant disease. Other studies establish PR as dominant modulators of ER activity. Together, these findings mark PR as bona fide targets for progestin or antiprogestin therapies, yet their diverse actions have confounded that use. Here we summarize the early history of PR in breast cancer; debunk the theory that progesterone causes cancer; discuss recent discoveries that PR regulate cell heterogeneity; attempt to unify theories describing PR as either good or bad actors in tumors; and discuss emerging areas of research that may help explain this enigmatic hormone and receptor.

Symptom Profiles of Latina Breast Cancer Survivors: A Latent Class Analysis.

Symptom research among Latinas with breast cancer is limited-especially as it relates to multiple co-occurring symptoms. The aim of the study was to identify subgroups (latent classes) of Latinas who have distinct symptom profiles while receiving radiation, chemotherapy, and/or hormonal therapy for breast cancer. This secondary analysis included intake data from three randomized trials of supportive care psychosocial interventions for Latinas treated for breast cancer (n = 290). Prevalence of 12 symptoms-measured using the General Symptom Distress Scale-was entered into the latent class analysis to identify classes of women with different symptom profiles. Most of the participants had Stage II or III disease, and 81% reported receiving chemotherapy. On average, women reported 4.2 (standard deviation [SD] = 3) symptoms with an overall symptom distress score of 6.4 (SD = 2.5) on a 1-10 scale, with 10 being most distressing. Latent class analysis resulted in three classes that were labeled based on symptoms with the highest prevalence. Class 1 (n = 192) was "Disrupted Sleep and Tired," Class 2 (n = 74) was "Tired," and Class 3 (n = 24) was "Pain, Disrupted Sleep, and Tired." Depression, anxiety, and difficulty concentrating had moderate prevalence in each of the three classes. Beyond the core six symptoms (depression, anxiety, fatigue, pain, disrupted sleep, difficulty concentration), the classes differed in the prevalence of other burdensome symptoms (e.g., nausea, vomiting, constipation), which provide implications for treatment. Thus, it is important to assess for the full range of symptoms so that supportive care interventions can be tailored for the distinct symptom profiles of Latinas with breast cancer.

Tamoxifen maculopathy: The importance of screening and long follow-up

We report a case of a patient treated with tamoxifen 20mg daily as hormone therapy for breast cancer. On regular ophthalmological follow-up, tamoxifen maculopathy was detected on SD-OCT (Spectral Domain Optic Coherence Tomography, Carl Zeiss Meditec®), so the medication was discontinued. Despite discontinuation of the medication, the maculopathy progressed over time. We have been following our patient for seven years. Tamoxifen may produce a toxic maculopathy which may progress despite discontinuation of the medication. We consider our case interesting, given the lengthy follow-up of the patient with sequential SD-OCT images. To the best of our knowledge, our case represents the longest follow-up period for a patient with tamoxifen maculopathy. Moreover, we would like to stress the importance of screening in asymptomatic patients on this medication, in order to detect early pathological signs.

The association between endocrine therapy use and dementia among post-menopausal women treated for early-stage breast cancer in Ontario, Canada

PurposeThe association between endocrine therapy and risk of dementia remains uncertain. We investigated the association between adjuvant endocrine therapy for breast cancer and risk of developing dementia in a real-world, population-based study. MethodsWe used health administrative data collected from post-menopausal women (aged ≥66 years) who were diagnosed with breast cancer and started on adjuvant endocrine therapy from 2005 to 2012 with follow-up until 2017. Patients were classified by the use of either an aromatase inhibitor or tamoxifen and followed to estimate the unadjusted cumulative incidence of developing dementia. A multivariable Cox proportional hazards model was created adjusting for age, income quintile, medical co-morbidities, and duration of endocrine therapy. ResultsWe identified 12,077 patients of whom 73% were treated with an aromatase inhibitor and 27% with tamoxifen. Our multivariable analysis showed a lower rate of dementia in patients treated with an aromatase inhibitor as compared to tamoxifen [Hazard ratio (HR) = 0.88, 95% confidence interval (CI): 0.78–0.98, p-value = .02) at a median follow-up of 5.9 years. The 5-year dementia rate among patient treated with either an aromatase inhibitor or tamoxifen was 7.4% and 9.2% respectively. Older age, previous history of ischemic heart disease, diabetes, hypertension and history of stroke were all significantly associated with the development of dementia. ConclusionAromatase inhibitor therapy was associated with a decreased incidence of dementia as compared to treatment with tamoxifen among post-menopausal women with early stage breast cancer. Further prospective studies with longer-term follow-up investigating the neurocognitive effects of endocrine therapy are warranted.

Potential insights from population kinetic assessment of progression-free survival curves.

Progression-free survival (PFS) curves follow first order kinetics on exponential decay nonlinear regression analysis (EDNLRA). Some exhibit 1-phase-decay, some have 2-phase-decay, some are convex. We digitized, performed EDNLRA and generated log-linear plots for 887 published PFS curves for incurable solid tumors treated with various systemic therapies. Proportion of curves fitting 2-phase-decay varied by therapy (p < 0.0001). For 13 therapies, >64 % of PFS curves had 2-phase-decay. This included epidermal growth factor receptor inhibitors in unselected lung cancer patients (some with, some without mutations), immune checkpoint inhibitors, interferon, breast cancer hormonal therapies, and selected others, suggesting 2 distinct, potentially identifiable subpopulations with differing progression rates. For 22 other therapies, <25 % of PFS curves had 2-phase-decay. Only 1 therapy was in the mid-range. Small cell lung and colon carcinomas were particularly likely to yield highly convex curves (p < 0.006), probably from discontinuation of effective therapies. PFS curve shape may yield biological and clinical insights.

RENATA study-Latin American prospective experience: clinical outcome of patients treated with palbociclib in hormone receptor-positive metastatic breast cancer-real-world use.

BackgroundIn hormone receptor-positive, HER-2 negative (HR+/HER2−) advanced breast cancer (ABC) endocrine therapy (ET) plus cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) in first and second line improved progression-free survival (PFS), overall response rate (ORR) and clinical benefit rate (CB) without deterioration in quality of life compared with ET alone. In addition, recent data showed improvement in overall survival (OS) for premenopausal women in first line setting and for different subgroups of patients in second line. Since 2015, in Argentina, the combination of ET with CDK4/6i is a standard of care in HR+/HER2− ABC.MethodsWe carried out a prospective analysis of real-world use of palbociclib with ET in HR+/HER2− ABC patients who received treatment between October 2015 and August 2019 in two private institutes from Buenos Aires, Argentina. The aims of the study were to determine efficacy and safety of patients treated with ET and palbociclib, describe patient profile and treatment strategy beyond progression.ResultsOne-hundred and twenty-eight patients were included in the final analysis. Main baseline characteristics include, median age 57 years, 20% were premenopausal women, 44% had visceral metastasis and 26% bone only disease. More than half of patients had two or more metastatic sites, 44.4% had performance status 1, and most of them (59.4%) were treated with palbociclib in first-line setting. Palbociclib was preferentially associated with aromatase inhibitors in 63.9% of patients, and with fulvestrant in the remaining. All premenopausal women received ovarian suppression or ovarian ablation (OS/OA). The median PFS was 36.7 months in first line and 24.2 months in second line. The ORR was 45.3% and 25.0% in first and second line, respectively. The median OS in the entire population was not reached. Half of patients did not require dose interruption and/or delay, dose reduction was required in 15% of patients and almost no patients required drug discontinuation (2.0%). With regard to safety, 55% of patients developed grade 3–4 adverse events, 20% neutropenia grade 3–4, and 7% febrile neutropenia. Infections were presented in one out of three patients, mostly uncomplicated.ConclusionsThis is the first prospective evidence of real-world use of palbociclib in a Latin American population. We found similar outcomes to the PALOMA-2 and PALOMA-3 randomised trials and Real-World Data already published, with lower incidence of side effects and treatment discontinuation, but with higher incidence of febrile neutropenia.

The maintenance effect of acupuncture on the side effects of breast cancer endocrine therapy: A protocol for systematic review and meta analysis.

Background:Breast cancer is common among women throughout the world and endocrine therapy is an established part of its treatment. But, unfortunately, this has also resulted in intolerable side effects affecting the quality of life. Acupuncture has been widely used to treat endocrine-related side effects in patients with breast cancer, but how long its effect can be maintained has not been published. The systematic review is designed to evaluate the maintenance efficacy of acupuncture for related side effects after breast cancer endocrine therapy.Methods and analysis:We will search for the following databases: PubMed, Embase, Cochrane Library, Web of Science, including China National Knowledge Infrastructure (CNKI), WanFang Data, Technology Periodical Database (VIP), and China Biology Medicine (CBM) from inception to May 2020. Two reviewers will search these databases, collect all articles, and assess the quality of studies separately, and there will be no limitations on language. The primary outcomes will be assessed using acupuncture for endocrine-related hot flashes and joint pain duration (1 month, 3 months, 6 months). Measurement tools include the Kupperman index, Brief Pain Inventory Short Form (BPI-SF), the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), the Brief Pain Inventory-Short (BPI-SF). We will use RevMan V.5.3 for meta-analysis and employ the Grading of Recommendations Assessment, Development and Evaluation System to assess the quality of evidence.Results:This systematic review will evaluate the maintenance efficacy of acupuncture on the side effects of breast cancer endocrine therapy.Conclusion:This study will provide high-quality current evidence of how long its effect can be maintained after acupuncture for related side effects after breast cancer endocrine therapy.Ethics and dissemination:Ethical committee approval is not required for this systematic review as patient data will not be collected. This study will help to inform doctors and researchers on the duration of acupuncture treatment for endocrine-related hot flashes and joint pain. The results will be published in a peer-reviewed journal and will be disseminated in relevant conferences.INPLASY registration number:INPLASY202040024

Functional genomics based on germline genome-wide association studies of endocrine therapy for breast cancer.

Breast cancer is the most common invasive cancer in women worldwide. Functional follow-up of breast cancer genome-wide association studieshas led to the discovery of genes that regulate endocrine therapy response in a SNP-and drug-dependent manner. Here, we will present four examples in which functional genomic studies from breast cancer clinical trials led to novel pharmacogenomic insights and molecular mechanisms of selective estrogen receptor modulatorsand aromatase inhibitors. The approach utilized for studying genetic variability described in this review offers substantial potential for meaningful discoveries that move the field toward precision medicine for patients.

Abstract B011: Changes in prescriptions for breast cancer medications after Medicaid expansion

Abstract As of summer 2018, 34 states have expanded Medicaid eligibility under the Affordable Care Act. While the Medicaid expansions decreased rates of being uninsured among women with breast cancer and increased early breast cancer detection, it is unknown whether expansions increased receipt of medications used to prevent and treat breast cancer. This study examines differences over time in receipt of two types of breast cancer hormonal therapies (tamoxifen and aromatase inhibitors) and associated payments for these medications in states that did vs. did not expand Medicaid during the period 2011-2017. The study's data source is the Medicaid State Drug Utilization Database (SDUD). This data set, compiled by the Centers for Medicaid and Medicare (CMS), is administrative data submitted by state Medicaid programs. The data comprise outpatient prescription medications that are covered under the Medicaid Drug Rebate Program for which Medicaid serves as a third-party payer; this includes aggregate numbers of prescriptions and associated payments for individuals enrolled in both fee for service and managed-care Medicaid programs. Both branded and generic prescriptions for three aromatase inhibitors (anastrozole, exemestane, and letrozole) were included in the study's analyses. Analyses used differences-in-differences and event study models (controlling for state characteristics) to compare changes in Medicaid expansion states to changes in nonexpansion states before vs. after expansion. Initial regression analyses indicate that prescriptions for all hormonal therapy medications increased by 22% (p&amp;lt;0.05) and prescriptions for aromatase inhibitors (branded and generics combined) increased by 26% (p&amp;lt;0.05) in expansion states relative to nonexpansion states. While prescriptions for tamoxifen and for generic aromatase inhibitors alone also increased in expansion states, these changes were not statistically significant. Post-expansion, both total payments and Medicaid payments for all hormonal therapies increased by 13% (p&amp;lt;0.01) in expansion states relative to nonexpansion states. The similar increases for total and Medicaid payments suggest that state Medicaid programs, not patients, financed the increased hormonal therapy prescription payments. Our findings indicate that states that expanded Medicaid with the ACA experienced increased prescriptions for breast cancer hormonal therapies relative to states that did not expand Medicaid; this effect of Medicaid expansion increased over time. The increased prescriptions were financed by Medicaid, not by patients. Citation Format: Catherine Maclean, Michael T. Halpern, Steven C. Hill, Michael Pesko. Changes in prescriptions for breast cancer medications after Medicaid expansion [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr B011.

Clinical Experience with the Use of Neoadjuvant Hormone Therapy for Breast Cancer in a Latin American Cancer Center

Introduction: The most frequent subtype of breast cancer is the luminal one, in 70 to 80% of cases; the poor response to neoadjuvant chemotherapy of these tumors positions neoadjuvant hormone therapy as a treatment option. Materials and Methods: An observational, descriptive, historical cohort study was conducted in patients with hormone receptor (HR positive and HER2-positive breast cancer, managed with neoadjuvant hormone therapy in the INC (National Cancer Institute, for its initials in Spanish), with the aim of evaluating their clinical and pathological response. Results: 57 patients were managed with neoadjuvant hormone therapy. Most stage IIA patients (40.3%, n = 23). 86% (n = 49) had luminal A tumors. Letrozole was the most widely used drug, in 78.9% (n = 45). The overall response rate (ORR) was reached in 94.6% (n = 53); and 10.7% of the patients (n = 6) achieved complete clinical response (cCR). Complete pathological response (pCR) was achieved only in one patient. Conservative surgery was possible in 56.9% (n = 29) of the patients. There was no difference between the type of aromatase inhibitor (AI) and the duration of neoadjuvant hormonal treatment with the clinical response. With a median follow-up of 3 years (0.6 and 6 years), no disease progression was reported in any of the patients in the study. Conclusion: The results of this study support the neoadjuvant hormone therapy recommendations for postmenopausal patients older than 65 years with luminal breast cancer, with well or moderately differentiated tumors, strongly HR positive and low Ki 67.

ER, PR, and HER2 expression in Ugandan breast cancer patients: An evaluation of in-country RT-PCR compared to IHC.

e19009 Background: Breast cancer, the most common cancer in sub-Saharan Africa (SSA), is characterized by poor survival. An accurate assessment of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor 2 receptor (HER2) status, typically via immunohistochemistry (IHC), is considered essential to provide prognostic data and guide therapeutic decision-making. However, due to inaccessible IHC services, these data are often unavailable in many parts of SSA; alternate methods need to be explored. Given the lab infrastructure developed in response to the HIV pandemic, RT-PCR testing is more readily accessible and feasible in SSA. Here we assess the potential of RT-PCR in evaluating the receptor status of women with breast cancer in Uganda. Methods: We enrolled women with a new diagnosis of invasive breast cancer at the Uganda Cancer Institute. Demographic and clinical data were obtained. A formalin-fixed paraffin embedded (FFPE) specimen was utilized for quantitative RT-PCR, using a validated assay for the detection of the ER, PR and HER2. Receptor expression levels were expressed as relative quantity (RQ) compared to housekeeping genes (CALM2). HER2 IHC results were categorized as negative (score 0 or 1+) or positive (3+); 2+ results (n=6) were excluded as FISH testing was not performed. Unstained slides were sent to the Fred Hutchinson Cancer Research Center for IHC. Receiver operating characteristic (ROC) analysis was applied to compare RT-PCR to IHC (gold standard). Results: We analyzed interim data (anticipated N=100 of an ongoing study) from 32 women aged 35 to 56 years. The majority of women (25, 78%) presented with advanced stage disease. Of the 32 cancers, 18 were ER+ (56%), 10 were PR+ (31%), 9 were HER2+ (28%) and 8 were triple negative (25%) by IHC. From ROC analysis, the AUC were 0.94, 0.95, and 0.81 for ER, PR, and HER2 respectively with high sensitivity and specificity (Table). Conclusions: Despite the tremendous need, the ability to detect the ER, PR, and HER2 via IHC in SSA is limited. Here we demonstrate the favorable test characteristics of RT-PCR when compared to IHC. Given the relatively wide accessibility of RT-PCR and endocrine therapy for breast cancer, as well as the recent inclusion of trastuzumab in the WHO’s Essential Medicines List, the results of this study have both direct diagnostic and therapeutic implications. Clinical trial information: NCT03518242 . [Table: see text]

Survival outcomes in post-menopausal patients with underlying cardiovascular disease receiving endocrine therapy for the treatment of breast cancer.

e12549 Background: Breast cancer remains the number one threat to women’s health while cardiovascular disease (CVD) continues to be the leading cause of mortality in women worldwide. Adjuvant therapy with endocrine therapies (selective estrogen receptor modulators (SERM), estrogen receptor blockers (ERB), and aromatase inhibitors (AI) although known to reduce the recurrence of breast cancer in hormone receptor positive breast cancer patients, raise a concern for increased risk of cardiovascular disease. Our study aims to examine breast cancer survival outcomes on patients receiving endocrine therapy who have pre-existing CVD including heart failure. Methods: An institutional database of 478 patients with histologically confirmed hormone receptor positive breast cancer diagnosed between 01/01/2014 to 12/31/2017 was reviewed after IRB approval. Preexisting CVD included coronary artery disease (CAD), history of myocardial infarction (MI), and prior diagnosis of heart failure (HF). Patients were divided in groups depending on treatment with endocrine therapy and underlying CVD. Statistical analysis was performed with SAS v9.4. software. Survival curves were estimated using Kaplan-Meier methodology and analyzed with a log rank test. Predictors of survival were assessed with Cox proportional hazards regression analyses. All significance was assumed at the p &lt; 0.05 level. Results: Of 478 patients who met the inclusion criteria, 336 (70%) patients were postmenopausal. Out of those 336 patients, 62.2 % (n = 209) received at least one of the endocrine therapies consisting of AI, SERM or an ERB. Of these patients, 2.9 % (n = 6), 9.6% (n = 20) and 5.7% (n = 12) had a significant medical history of underlying MI, HF and CAD, respectively. Survival analysis was performed on 80% (n = 168) patients of the 209 patients with 2.3% (n = 4), 8.9% (n = 15) and 5.2% (n = 11) with underlying MI, HF and CAD respectively. There was no statistically significant difference in survival in these postmenopausal women who received endocrine therapy despite preexisting cardiovascular disease (HR 3; 95% CI, 0.5-16, p &gt; 0.05). Conclusions: A commonly known toxicity related to the adjuvant therapy including endocrine therapy of breast cancer is cardiac toxicity. Patients with history of CVD might be at the highest risk for such toxicity. Our finding is reassuring that endocrine therapy in patients with preexisting CVD including heart failure did not result in reduced survival for our patient cohort.

Use of alpelisib in the treatment of hormone receptor positive metastatic breast cancer: An institutional experience.

e15216 Background: Mutations in PI3K pathway is a known mechanism of resistance to endocrine therapy in breast cancer. Alpelisib is an alpha-specific PI3K inhibitor. Alpelisib with Fulvestrant is approved for treatment (Tx) of PIK3CA mutated HR+ metastatic breast cancer (MBC) that progress on hormonal therapy. Despite its approval by the FDA, real world data on the use of Alpelisib for the management of MBC is lacking. This abstract reviews the safety and efficacy of Alpelisib in the management of patients with MBC. Methods: A retrospective review of the tumor registry database at a single institution was conducted to identify patients with HR+ MBC. Detailed clinical and pathologic data of PIK3CA mutated patients treated with Alpelisib were obtained. Genomic profiling was done with Foundation One. Results: Table highlights the characteristics of the four patients. All were treated with Alpelisib and Fulvestrant after PIK3CA mutation was demonstrated. 3 patients were heavily pretreated with systemic Tx including CDK 4/6 inhibitors. All patients responded to Alpelisib and Fulvestrant despite treatment history. Mucositis, rash, hyperglycemia and pancytopenia were the observed adverse events (A/E). All A/E were adequately managed except in one patient that required discontinuation of Tx. None has clinically progressed. Conclusions: Our data suggests that Alpelisib and Fulvestrant is tolerated and improves outcomes in patients with HR+ MBC. Alpelisib and Fulvestrant could be an effective therapy in patients who have also progressed on systemic chemotherapy including CDK 4/6 inhibitors. Although our sample size is small, we hope that our experience could guide clinicians in the management of patients with HR+ MBC who harbor the PIK3CA mutation and are being treated with Alpelisib. [Table: see text]

CDK4/6 inhibitors and hormone therapy in hormone receptor-positive advanced breast cancer: Real-world data and intrinsic subtypes defined by PAM50.

e13035 Background: CDK 4/6 inhibitors plus hormone therapy(HT) has been approved by FDA and EMA for the treatment of hormone receptor positive HER2 negative advanced breast cancer (HR+/HER2-BC) with improvement in PFS consistently demonstrated in several clinical trials. Benefit in OS has also been demonstrated in Monaleesa3 and Monarch2 clinical trials. To date we don`t have real-world data and no single biomarker has been validated to identify subgroups that would benefit most from this new drugs. Methods: This is a multicenter, real life, observational study. From January 2015 to December 2019 we recruited 98 patients with immunohistochemical(IHC) HR+/HER2-BC treated with CDK4-6 inhibitor plus HT. All patients were classified into intrinsic molecular subtypes based on PAM50 signature done centrally in diagnostic/metastatic biopsies. Results: The clinical and treatment characteristic are in table. In IHC studies all population were classified as luminalA (40%) and LuminalB (60%) but we found HER2 enriched patients (6%) defined by PAM50. The median PFS for all population was 14 months and median PFS for Luminal A subtype was 12 months and 15 months for Luminal B with no statistically significant differences between them. Conclusions: Based on the results obtained, the intrinsic molecular subtype defined by PAM50 does not appear to be associated with differences in PFS in our study group. However, a study with a larger number of patients would be necessary. Inhibitors of CDK4/6, have established a central role in the management of HR+/HER2-BC. There is a clear benefit in PFS and OS but we still don’t know which patients will benefit from this therapy and who will not while the side effects such chronic neutropenia, QTC prolongation and diarrhea could have a negative impact on their quality of life. Its mandatory to explore a good biomarker to direct therapy. [Table: see text]

Neoadjuvant Endocrine Therapy in Breast Cancer: Current Knowledge and Future Perspectives.

In locally advanced (LA) breast cancer (BC), neoadjuvant treatments have led to major achievements, which hold particular relevance in HER2-positive and triple-negative BC. Conversely, their role in hormone receptor positive (HR+), hormone epidermal growth factor 2 negative (HER2-) BC is still under debate, mainly due to the generally low rates of pathological complete response (pCR) and lower accuracy of pCR as predictors of long-term outcomes in this patient subset. While administration of neoadjuvant chemotherapy (NCT) in LA, HR+, HER2- BC patients is widely used in clinical practice, neoadjuvant endocrine therapy (NET) still retains an unfulfilled potential in the management of these subgroups, particularly in elderly and unfit patients. In addition, NET has gained a central role as a platform to test new drugs and predictive biomarkers in previously untreated patients. We herein present historical data regarding Tamoxifen and/or Aromatase Inhibitors and a debate on recent evidence regarding agents such as CDK4/6 and PI3K/mTOR inhibitors in the neoadjuvant setting. We also discuss key issues concerning the optimal treatment length, appropriate comparisons with NCT efficacy and use of NET in premenopausal patients.

Whole-Body Characterization of Estrogen Receptor Status in Metastatic Breast Cancer with 16α-18F-Fluoro-17β-Estradiol Positron Emission Tomography: Meta-Analysis and Recommendations for Integration into Clinical Applications.

Estrogen receptor (ER) status by immunohistochemistry (IHC) of cancer tissue is currently used to direct endocrine therapy in breast cancer. Positron emission tomography (PET) with 16α-18F-fluoro-17β-estradiol (18 F-FES) noninvasively characterizes ER ligand-binding function of breast cancer lesions. Concordance of imaging and tissue assays should be established for 18 F-FES PET to be an alternative or complement to tissue biopsy for metastatic lesions. We conducted a meta-analysis of published results comparing 18 F-FES PET and tissue assays of ER status in patients with breast cancer. PubMed and EMBASE were searched for English-language manuscripts with at least 10 patients and low overall risk of bias. Thresholds for imaging and tissue classification could differ between studies but had to be clearly stated. We used hierarchical summary receiver-operating characteristic curve models for the meta-analysis. The primary analysis included 113 nonbreast lesions from 4 studies; an expanded analysis included 327 total lesions from 11 studies. Treating IHC results as the reference standard, sensitivity was 0.78 (95% confidence region 0.65-0.88) and specificity 0.98 (0.65-1.00) for the primary analysis of nonbreast lesions. In the expanded analysis including non-IHC tissue assays and all lesion sites, sensitivity was 0.81 (0.73-0.87) and specificity 0.86 (0.68-0.94). These results suggest that 18 F-FES PET is useful for characterization of ER status of metastatic breast cancer lesions. We also review current best practices for conducting 18 F-FES PET scans. This imaging assay has potential to improve clinically relevant outcomes for patients with (historically) ER-positive metastatic breast cancer, including those with brain metastases and/or lobular histology. IMPLICATIONS FOR PRACTICE: 16α-18F-fluoro-17β-estradiol positron emission tomography (18 F-FES PET) imaging assesses estrogen receptor status in breast cancer in vivo. This work reviews the sensitivity and specificity of 18 F-FES PET in a meta-analysis with reference tissue assays and discusses best practices for use of the tracer as an imaging biomarker. 18 F-FES PET could enhance breast cancer diagnosis and staging as well as aid in therapy selection for patients with metastatic disease. Tissue sampling limitations, intrapatient heterogeneity, and temporal changes in molecular markers make it likely that 18 F-FES PET will complement existing assays when clinically available in the near future.

Effect of Chemotherapy and Hormonal Therapy on Bone Mineral Density in Patients with Breast Cancer in Saiful Anwar Hospital Malang

Osteoporosis is an important health problem, and the number of patients who suffered from it is increasing. Breast cancer is a condition that has a high risk of osteoporosis. Cancer induced bone disease results from the primary disease, metastatic process, or from therapies against the prime condition, causing bone fragility. Therefore, there are still different opinions regarding the therapeutic effect of breast cancer on bone mineral density. Aim: to determine the effect of chemotherapy and hormonal therapy on bone mineral density in patients with breast cancer in Saiful Anwar Hospital Malang. Method: this is a case-control study conducted in 30 patients with breast cancer who had undergone chemotherapy and hormonal therapy are compared to 30 patients without breast cancer as controls. Bone Mineral Density (BMD) was measured by DEXA. Result: there are 53% of breast carcinoma patients having osteopenia and 13% having osteoporosis, with one patient has osteoporosis located in the femoral neck and three patients in lumbar (L1-L4). We obtain a significant T-score (p=0.02) in the great trochanter. Odds Ratio (OR) 0.233 with p = 0.008 showed a protective effect of chemotherapy and hormonal therapy for breast cancer to the bone density. Conclusion: the incidence of osteoporosis in the study was 13%, with the most location in the lumbar spine. Chemotherapy and hormonal therapy had a protective effect on BMD in patients with breast cancer in Saiful Anwar Hospital Malang.

110P Primary endocrine therapy of breast cancer: Is there a good radiological technique to define pathological response?

110P Primary endocrine therapy of breast cancer: Is there a good radiological technique to define pathological response?

Tumor Necrosis Factor α Blockade: An Opportunity to Tackle Breast Cancer.

Breast cancer is the most frequently diagnosed cancer and the principal cause of mortality by malignancy in women and represents a main problem for public health worldwide. Tumor necrosis factor α (TNFα) is a pro-inflammatory cytokine whose expression is increased in a variety of cancers. In particular, in breast cancer it correlates with augmented tumor cell proliferation, higher malignancy grade, increased occurrence of metastasis and general poor prognosis for the patient. These characteristics highlight TNFα as an attractive therapeutic target, and consequently, the study of soluble and transmembrane TNFα effects and its receptors in breast cancer is an area of active research. In this review we summarize the recent findings on TNFα participation in luminal, HER2-positive and triple negative breast cancer progression and metastasis. Also, we describe TNFα role in immune response against tumors and in chemotherapy, hormone therapy, HER2-targeted therapy and anti-immune checkpoint therapy resistance in breast cancer. Furthermore, we discuss the use of TNFα blocking strategies as potential therapies and their clinical relevance for breast cancer. These TNFα blocking agents have long been used in the clinical setting to treat inflammatory and autoimmune diseases. TNFα blockade can be achieved by monoclonal antibodies (such as infliximab, adalimumab, etc.), fusion proteins (etanercept) and dominant negative proteins (INB03). Here we address the different effects of each compound and also analyze the use of potential biomarkers in the selection of patients who would benefit from a combination of TNFα blocking agents with HER2-targeted treatments to prevent or overcome therapy resistance in breast cancer.