Diagnosis Of Metastatic Breast Cancer Research Articles

Quality of working life can protect against cognitive and emotional vulnerability in women living with metastatic breast cancer: a cross-sectional study.

PurposeResearch focusing on the cognitive and emotional health of women with metastatic breast cancer (MBC) is limited. The focal aim of the current study was to explore how quality of working life was related to global health, perceived cognitive function, anxiety and depression. To this end, women’s experience of employers after MBC diagnosis and its relationship to quality of working life was also explored.MethodsWomen living with MBC (N = 88) completed online questionnaires assessing their global health status, perceived cognitive and emotional vulnerability and their experience of employers following diagnosis. Women working at the time of the study also reported on their quality of working life.ResultsWomen’s experience of employers after MBC diagnosis was positively related to their quality of working life. Importantly, greater quality of working life met with better perceived cognitive function and global health, as well as lower levels of depression in working women.ConclusionsOur study is the first to establish the role of quality of working life in protecting against levels of cognitive vulnerability and emotional vulnerability to depression in women with MBC. We also highlight the importance of having a positive experience with employers. Our findings suggest that educational programmes can be provided to employers to enhance their understanding and awareness of the needs of women with MBC.Implications for Cancer SurvivorsWomen with MBC may benefit from employers accessing educational (or support) programmes that can increase their awareness of the treatment-related sequelae and needs of women with MBC in the workplace.Supplementary InformationThe online version contains supplementary material available at 10.1007/s11764-022-01169-0.

The diagnostic accuracy of PIK3CA mutations by circulating tumor DNA in breast cancer: an individual patient data meta-analysis.

Background:The circulating tumor DNA (ctDNA) diagnostic accuracy for detecting phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) mutations in breast cancer (BC) is under discussion. We aimed to compare plasma and tissue PIK3CA alterations, encompassing factors that could affect the results.Methods:Two reviewers selected studies from different databases until December 2020. We considered BC patients with matched tumor tissue and plasma ctDNA. We performed meta-regression and subgroup analyses to explore sources of heterogeneity concerning tumor burden, diagnostic technique, sample size, sampling time, biological subtype, and hotspot mutation. Pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and the related area under the curve (AUC) were elaborated for the overall population and each subgroup.Results:The pooled analysis was carried out on 25 cohorts for a total of 1966 patients. The overall ctDNA sensitivity and specificity were 0.73 (95% CI: 0.70–0.77) and 0.87 (95% CI: 0.85–0.89). The AUC was 0.93. Pooled concordance, negative predictive value and positive predictive value values were 0.87 (95% CI: 0.82–0.92), 0.86 (95% CI: 0.81–0.90), and 0.89 (95% CI: 0.81–0.95) with pooled PLR, NLR, and DOR of 7.94 (95% CI: 4.90–12.86), 0.33 (95% CI: 0.25–0.45), and 33.41 (95% CI: 17.23–64.79), respectively. The pooled results consistently favored next-generation sequencing (NGS)- over polymerase chain reaction-based methodologies. The best ctDNA performance in terms of sensitivity, specificity, and AUC (0.85, 0.99, and 0.94, respectively) was observed in the low-time sampling subgroup (⩽18 days between tissue and plasma collection). Meta-regression and subgroup analyses highlighted sampling time as a possible major cause of heterogeneity.Conclusions:These findings reliably estimate the high ctDNA accuracy for the detection of PIK3CA mutations. A ctDNA-first approach for the assessment of PIK3CA mutational status by NGS may accurately replace tissue tumor sampling, representing the preferable strategy at diagnosis of metastatic BC in patients who present with visceral involvement and at least two metastatic lesions, primarily given low clinical compliance or inaccessible metastatic sites.

Clinical outcomes and metastatic behavior between de novo versus recurrent HER2-positive metastatic breast cancer: A 17-year single-institution cohort study at Taipei Veterans General Hospital.

To assess the clinical outcomes and metastatic behavior between de novo versus recurrent human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC) based on a single-institution database in Taiwan. We retrospectively identified patients diagnosed between January 2000 and December 2017 with de novo stage IV or recurrent HER2-positive MBC. Several variables were recorded in patients with recurrent disease: age at diagnosis, metastatic site, hormone receptor (HR) status, HER2 status, and disease-free interval (DFI). Treatments and metastatic patterns were compared between de novo stage IV and recurrent MBC cohorts. Post-metastasis survival (PMS) was estimated using the Kaplan-Meier method with log-rank tests. Hazard ratios and 95% CIs were estimated using Cox regression analysis. In total, 1360 patients were diagnosed with breast cancer with HER2 overexpression. At baseline, de novo stage IV patients were older than recurrent MBC patients (median age 58 vs 53). The majority of the de novo stage IV patients were diagnosed after 2010, while most of the recurrent MBC patients were diagnosed during 2000-2009. An increased number of de novo stage IV patients underwent targeted therapy than recurrent MBC patients was also noted. PMS in patients with de novo stage IV and recurrent MBC was 79.2 months and 61.8 months, respectively, which indicated significant better survival in de novo stage IV than those with recurrent MBC disease. Longer survival was also noted in de novo stage IV and recurrent MBC with DFI >24 months than in those with recurrent MBC with DFI <24 months and in patients receiving HER2-targeted therapy after MBC diagnosis than in those not receiving the therapy. However, median PMS showed no significant difference between patients with the luminal B2 (HR-positive, HER2-negative) and HER2-enriched (HR-negative, HER2-positive) subtypes. After adjustment in multivariate analysis, a low risk of BC-specific death was observed in patients aged >50 years, those receiving HER2-targeted therapy for MBC, and those with oligometastasis, while patients with first metastases to the liver or brain showed a higher risk of BC-specific death than those without metastases. De novo and recurrent MBC have distinct characteristic, metastatic patterns and outcomes in Asian HER2-positive breast cancer patients. The age distribution and survivals between HR+/- status were different to non-Asian group. These differences should be further investigated in the future considering ethnic factor.

Real-world evidence of the management and prognosis of young women (⩽40 years) with de novo metastatic breast cancer.

Background:Breast cancer (BC) in young women merits a specific approach given the associated fertility, genetic and psychosocial issues. De novo metastatic breast cancer (MBC) in young women is an even more serious condition, with limited data available.Methods:We evaluated management of women aged ⩽40 years with de novo MBC in a real-life national multicentre cohort of 22,463 patients treated between 2008 and 2016 (NCT0327531). Our primary objective was to compare overall survival (OS) in young women versus women aged 41–69 years. The secondary objectives were to compare first-line progression-free survival (PFS1) and to describe treatment patterns.Results:Of the 4524 women included, 598 (13%) were ⩽40 years. Median age at MBC diagnosis was 36 years (range = 20–40). Compared with women aged 41–69 years, young women had more grade III tumours (49% versus 35.7%, p < 0.0001), human epidermal growth factor receptor 2 amplified (HER2+) disease (34.6% versus 26.4%, p < 0.0001) and HR–/HER2– disease known as “triple negative breast cancer” (TNBC) (17.1% versus 12.7%, p < 0.0001). BRCA testing was performed for 260 young women, with a BRCA1/2 mutation in 44 (17% of those tested) In young HR+/HER2– patients, chemotherapy (CT) was given as the frontline treatment more frequently compared with older ones (89.6% versus 68.8%, respectively, p < 0.0001). After median follow-up of 49.7 months (95% confidence interval, CI = 48.0–51.7), the median OS of young women was 58.5 months, 20.7 months and not attained in HR+/HER2–, TNBC and HER2+ subgroups, respectively. After adjustment for histological subtype, tumour grade, and number and type of metastasis, young women had significantly better OS compared with older ones, except for the TNBC subgroup, for which the outcome was similar. PFS1 was statistically different only in the TNBC subgroup, with 7.8 months for young women and 6.3 months for older women (p = 0.0015).Conclusion:De novo MBC affects a significant proportion of young women. A subgroup of these patients achieves long OS and merits multidisciplinary care.

Clinicopathological characteristics and prognosis of breast cancer patients with isolated central nervous system metastases in the multicentre ESME database.

Background:As a result of progress in diagnosis and treatment, there is a growing prevalence of metastatic breast cancer (MBC) with isolated CNS metastases. This study describes the largest-to-date real-life cohort of this clinical setting and compares it to other clinical presentations.Methods:We retrospectively analysed the French Epidemiological Strategy and Medical Economics (ESME) MBC database including patients who initiated treatment for MBC between 2008 and 2016. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan–Meier method. Descriptive statistics and multivariate Cox model were used.Results:Of 22,266 patients, 647 (2.9%) and 929 (4.2%) patients had isolated first-site CNS metastases or combined with extra-CNS metastases, with longer OS for the group with isolated CNS metastases (16.9 versus 13.9 months, adjusted HR = 1.69 (95% CI: 1.50–1.91), p < 0.001). Among the 541 (2.4%) patients with isolated CNS metastases and no intrathecal therapy (excluding leptomeningeal metastases), HER2+ cases were preponderant over TN or HR+ /HER2− cases (41.6% versus 26.1% versus 28.5%, respectively, p < 0.01). The treatment strategy consisted of a combination of local treatment and systemic therapy (49.2%), local treatment only (35.5%) or systemic therapy only (11.4%), or symptomatic therapy only (3.9%). Median PFS was 6.1 months (95% CI: 5.7–6.8). Median OS was 20.7 months (95% CI: 17.3–24.3), reaching 37.9 months (95% CI: 25.9–47.6) in the HR+ /HER2+ subgroup. Older age, TN subtype, MBC-free interval of 6–12 months, lower performance status, and WBRT were associated with poorer survival. Patients who received systemic therapy within 3 months from MBC diagnosis had longer OS (24.1 versus 16.1 months, p = 0.031), but this was not significant on multivariate analysis [HR = 1.0 (95% CI: 0.7–1.3), p = 0.806].Conclusions:Patients with isolated CNS metastases at MBC diagnosis represent a distinct population for which the role of systemic therapy needs to be further investigated in prospective studies.

Examining religious/spiritual change among women with metastatic breast cancer

AbstractTo what extent and how does religion/spirituality change after a terminal breast cancer diagnosis? Utilizing a nationwide survey and semistructured interviews, I examine how prayer, meditation, religious service attendance, importance of religion, and religiosity may change after a metastatic breast cancer diagnosis. Results from the survey show that most people experienced change on at least one religious/spiritual indicator. “No change” is the most common response for religiosity, importance of religion, and religious service attendance, while prayer and meditation increased. Themes from the interviews shed light on coping mechanisms, such as the increased consumption of religious texts and writings, leaning on God, (re)commitment to religious institutions, prayer, and meditation. Religion (or lack thereof) remained consistent for some of the participants. A decrease in religion was less common. The results of this study have important implications for how women with a terminal disease use religious coping to manage their illness experiences.

Clinicopathological characteristics and survival outcomes in patients with synchronous lung metastases upon initial metastatic breast cancer diagnosis in Han population

BackgroundWe investigated the clinicopathological characteristics and survival of breast cancer lung metastases (BCLM) patients at initial diagnosis of metastatic breast cancer (MBC) in the Han population.MethodsWe attained clinical data of 3155 MBC patients initially diagnosed between April 2000 and September 2019 from the China National Cancer Center and finally included 2263 MBC patients in this study, among which 809 patients presented with lung metastases at first MBC diagnosis. The risk factors for BCLM were determined using multivariate logistic regression analysis and the prognostic factors of BCLM patients were assessed by univariate and multivariate Cox regression analyses.ResultsPatients with triple-negative subtype (42.3%) harbored the highest incidence proportions of lung metastases. Age ≥ 50 years, Eastern Cooperative Oncology Group (ECOG) 2, M1, hormone receptor-negative (HR-)/human epidermal growth factor receptor 2-positive (HER2) + subtype, triple-negative subtype and disease-free survival (DFS) > 2 years were remarkably associated with higher incidence of lung metastases, while invasive lobular carcinoma (ILC) and bone metastases were significantly correlated with lower odds of lung metastases at diagnosis. The median survival of BCLM patients was 41.7 months, with triple-negative subtype experiencing the worst prognosis of 26.8 months. ECOG 2, triple-negative subtype, liver metastases, multi-metastatic sites and DFS ≤ 2 years were significantly correlated with poor survival of BCLM patients.ConclusionsOur study provides essential information on clinicopathological features and survival outcomes of BCLM patients at initial diagnosis of MBC in China.

Cardiotoxicity of trastuzumab emtansine (T-DM1): a single-center experience.

ObjectiveNew anti-cancer drugs promise to increased survival benefits and reduce adverse events. Trastuzumab emtansine (T-DM1) is a novel anti-human epidermal growth factor receptor 2 agent that has shown minimal cardiotoxicity in clinical trials. However, data on real-life outcomes are required.MethodsA retrospective review of our center’s medical records was performed, including female patients aged ≥18 years with a diagnosis of metastatic breast cancer who were treated with T-DM1. Descriptive statistics were used to investigate clinical features that could increase the risk of cardiotoxicity. Cardiotoxicity was determined by comparing pre and post-T-DM1 echocardiogram results and was defined as a decrease in the left ventricular ejection fraction (LVEF) >10% to below 55%.ResultsData from 41 female patients with a mean age of 52 ± 11.5 years were evaluated. A significant LVEF decrease (from 59% to 33%) was observed in one patient during T-DM1 treatment. Further investigation showed that this decrease was due to underlying coronary artery disease, and LVEF recovered to the baseline value after coronary revascularization.ConclusionT-DM1 seems to be safe in terms of cardiotoxicity. Real-life data with a larger sample size are still needed to confirm the cardiac safety of T-DM1.

Treatment Patterns and Overall Survival in HER2+ Metastatic Breast Cancer at US Community Oncology Practices

Aim: To describe real-world treatment patterns/outcomes among patients with HER2+ metastatic breast cancer (MBC). Materials &amp; methods: Real-world treatments and overall survival (OS) were evaluated among adult women diagnosed with HER2+ MBC, with and without brain metastases (BMs), between 1 June 2012 and 31 May 2018 using electronic medical records from the Definitive Oncology Dataset. Results: Among 372 patients, 69% initiated first-line trastuzumab plus pertuzumab-based therapy; many therapy combinations were utilized in the second- to fourth-line. During follow-up (median 24.8 months), 18% of patients died (22% with and 16% without BMs). Mean OS was shortest among patients with BMs at MBC diagnosis in the third- and fourth-line. Conclusion: OS was poor, and no clear standard of care was observed among patients with HER2+ MBC progressing on trastuzumab-based therapies.

Effects of Primary Tumor Resection on Metastatic Breast Cancer Survival and the Predictive Power of Neutrophil: Lymphocyte Ratio on Prognosis.

The aim was to investigate the effect of primary tumor resection (PTR) on survival in metastatic breast cancer patients and to assess the power of the neutrophil-to-lymphocyte ratio (NLR) regarding the prediction of prognosis in this patient group. Female patients diagnosed with and starting treatment for metastatic breast cancer from 2003 to 2016 in the general surgery and oncology clinics at a single center were retrospectively reviewed. Pre-treatment NLR value and survival situations were evaluated. A total of 117 patients were enrolled. The disease-specific survival (DSS) of the patients was 41.4 months. When stratified into PTR and systemic treatment (ST) groups, there was no difference in the survival (p = 0.054); 43.5 months in the PTR group vs 30.7 months in the ST group. When hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative subgroups were analyzed, DSS was significantly longer (p = 0.02) in the PTR group (55.4 months) compared to the ST group (41.8 months). Finally, in patients with an NLR of <2.3, DSS was significantly longer (p = 0.03) in the PTR group (56.1 months) compared to the ST group (25.2 months). These results suggest that DSS can be increased with PTR in selected patients with a diagnosis of metastatic breast cancer. NLR may be useful in selecting patients for appropraite treatment modality.

S2960 Incidental Diagnosis of a Rare Metastatic Neuroendocrine Breast Cancer During Routine Screening Mammogram Which Eventually Revealed Primary Small Intestine Carcinoid Tumor

Introduction: Neuroendocrine neoplasms (NENs), defined as epithelial neoplasms with predominant neuroendocrine differentiation, typically occur in the pancreas, tubular gastrointestinal tract, or lung with or without secretory syndromes. Neuroendocrine breast carcinoma (NEBC) is a rare tumor which accounts for 1-2% of all invasive breast carcinoma. When NENs are found on a biopsy of a breast nodule it is considered either primary NEBC or metastatic if another primary organ is discovered. NEBC usually presents as a breast lump on exam without neuroendocrine symptoms. Therefore, making a diagnosis of NEBC prior to biopsy is difficult. We present a case of an incidentaloma discovered on routine mammography that turned out to be NEBC on biopsy and further evaluation discovered an asymptomatic primary small bowel NEN, thus confirming the breast as metastatic NEBC. Case Description/Methods: A routine mammogram in 60 yo. female revealed an abnormal 4 mm solid nodule in the right breast. A core needle biopsy found a low grade, well differentiated NEN, with positive staining for synaptophysin and chromogranin. She felt well and denied any symptoms. Medical history was notable for immune hepatitis with liver cirrhosis managed by her hepatologist. An abdominal MRI/MRCP revealed thickening in the small bowel wall consistent with a primary carcinoid tumor and demonstrated hepatic surface metastases. Plasma and 24 hr. urine 5 HIAA and chromogranin A plasma levels were normal. A lumpectomy was performed and therapy with lanreotide i.m. monthly injections begun. At 6 months follow-up, she remains asymptomatic, with stable disease. Discussion: Metastasis to the breast from a primary NEN is infrequently reported in the literature. If discovered in a patient without a history of known primary NEN in another organ, imaging is warranted to seek asymptomatic and non-secreting tumors elsewhere, as in the GI tract of our patient. No proven effective chemotherapy or RT for either primary or metastatic NEBC exists. No proven effective chemotherapy regimen exists for NENs, but therapy with long-acting somatostatin analogs are the preferred first-line option for NENs associated with several hormonal syndromes as well as for growth control in well-differentiated unresectable or metastatic gastroenteropancreatic NENs as in our case.

Study of the automated synthesis of the radiopharmaceutical fluoroestradiol-18F

Approximately 75% of breast cancer cells express estrogen receptor positive, being the second leading cause of cancer death among women worldwide with an incidence of 25% per year. 16α-[18F]-fluoro-17β-estradiol, FES-18F, is a radiopharmaceutical that binds to estrogen receptors enabling the acquisition of molecular images for non-invasive diagnosis of primary and metastatic breast cancer using PET-CT. The objective of this work was to study the synthesis of FES-18F in the GE TRACERlab® MXFDG module, using the chemical kit and the ABX® disposable cassette, and to determine the process yield and the analytical parameters to be used in the routine production of this radiopharmaceutical. Automated synthesis occurs in 75 minutes and includes percolation of [18F-] fluoride into an anion exchange cartridge, cartridge elution, 3-step azeotropic drying, labeling using precursor 3-methoxymethyl-16β,17β-epiestriol-O-cyclic sulfone (MMSE) and a hydrolysis step. Product purification is done in the module using solid phase extraction (SPE) cartridges. The radiochemical yield was reproductive, regardless of fluor-18 activity at entry into the module, and the results of quality control tests suggest that the radiopharmaceutical meets the criteria established for other fluor-18-labelled radiopharmaceuticals that have monographs in official compendiums. In vivo biodistribution studies in healthy animals and with a tumor model developed with MCF-7 cells, demonstrated radiopharmaceutical uptake in excretory organs and specificity for breast tumor cells.

Metastatic Breast Cancer Masked as Constipation

Even though screening mammography has been attributed to decreased mortality in recent decades, breast cancer is one of the leading causes of death among women in the United States. Disruption of screening protocols and variation in the presentation may alter the course of detection and management. We report a case of hormone receptor-positive breast cancer that presented as vague gastrointestinal symptoms in a patient with a delayed workup for a self-discovered breast lump during the coronavirus disease global pandemic.A 48-year-old woman with a history of gastroesophageal reflux and hypertension presented to the emergency department with primary complaints of constipation and abdominal distention with associated flatus and nausea. Vitals were within normal limits, and physical examination was notable for abdominal distention and diffuse tenderness to palpation. Labs demonstrated hypercalcemia and an unremarkable complete blood count. A chest X-ray showed a right hilar mass, and a CT chest revealed multiple lytic bone lesions diffusely scattered throughout the entire skeleton; no hilar mass was noted on the CT chest. A CT scan of the abdomen and pelvis incidentally revealed a right breast mass. A bone marrow biopsy identified invasive ductal carcinoma. Mammography and biopsy of the breast mass identified estrogen receptor/progesterone receptor-positive invasive ductal carcinoma, consistent with the bone marrow biopsy, confirming the diagnosis of metastatic breast cancer.Unpredicted disruptions in screening processes may result in delayed cancer diagnoses. This case illustrates the importance of routine self-breast examinations, screening mammography, and maintaining a broad differential diagnosis.

Cognitive function and emotional vulnerability in metastatic breast cancer: Moderating effects of age and social support.

Previous literature has established a relationship between cognitive function and symptoms of anxiety, depression, and post-traumatic stress in primary breast cancer, but not in metastatic breast cancer (MBC). The current study examined the relationship between cognitive function and symptoms of anxiety, depression, and post-traumatic stress as well as the moderating effects of age, time since MBC diagnosis, and social support. Subjective and objective measures of cognitive function as well as self-reports of emotional vulnerability were completed by 59 women diagnosed with MBC who were recruited through social media and support groups. Emotional vulnerability scores were associated with perceived measures of cognitive function. Additionally, low levels of perceived cognitive function were met with increased levels of depression with social support moderating this relationship buffering against depression. Age was found to moderate the relationship between cognitive function and post-traumatic stress with younger women at a greater risk of vulnerability. Out of all the emotional vulnerability measures, only anxiety negatively correlated with objective task performance. This study established a relationship between cognitive function and emotional vulnerability in MBC patients. It emphasised how vulnerable younger MBC women are to post-traumatic stress, and the importance of the combined effects of cognitive function and social support in buffering against depression. Our results have important implications for developing new interventions and treatment plans that consider the roles of these factors in ensuring a better quality of life in MBC.

Real-world outcomes of breast cancer patients with brain metastases treated with radiotherapy in Ontario: A population-based study.

2027 Background: Brain Metastases (BrM) are a major cause of morbidity and mortality in patients with metastatic breast cancer (MBC). Real-word data regarding time to development of breast cancer BrM and survival outcomes is lacking. Methods: We conducted a retrospective, observational population-based cohort study to assess treatment patterns and outcomes of patients with de-novo MBC who received radiotherapy for intracranial metastatic disease between January 2009 and December 2018. We used population health administrative databases in Ontario held at ICES, an independent, non-profit research institute. Primary endpoints were i) cumulative incidence of radiotherapy for BrM accounting for the competing risk of death, and ii) time from MBC diagnosis to brain radiotherapy. Secondary endpoints included overall survival (OS) and radiation therapy toxicity. Data were censored if patients were alive on the same therapy at last available follow-up with the last cut-off date being March 31, 2019. Kaplan-Meier analyses were performed for the time to event endpoints and compared using the log-rank test. Cumulative incidence of radiotherapy for BrM from the diagnosis of MBC was calculated using the Cumulative Incidence Function (CIF), accounting for the competing risk of death using a competing risk analysis. Multivariable regression models were used to account for confounding variables. Results: 3,916 patients with de-novo MBC were identified, among whom 549 (14%) developed BrM requiring radiotherapy; cumulative incidence of BrM at 7-year follow-up was highest among patients with HER2+/HR- (34.7%) and HER2+/HR+ (28.1%) disease, followed by triple negative MBC (21.9%) and HR+/HER2- (12.1%) subtypes. The median time from diagnosis of MBC to first radiotherapy treatment for BrM was 7.5 months, 15.0 months, 16.8 months and 19.8 months, in TNBC, HER2+/HR-, HR+/HER2- and HER2+/HR+ subtypes, respectively. The median OS from radiotherapy among patients with breast cancer BrM was 5.1 months in the overall cohort. When analyzed by subtype, the median OS was 2.6 months, 4.8 months, 8.7 months, and 9.4 months in TNBC, HR+/HER2, HER2+/HR+ and HER2+/HR- subtypes, respectively. In a multivariable Cox regression model, a triple negative or HR+/HER2- breast cancer subtype, treatment with WBRT, age &gt; 60 and a high-income quintile (4 or 5) were independently prognostic for shorter OS after adjustment for the index year at diagnosis. Patients treated with stereotactic radiosurgery (SRS) had lower 30-day mortality (6.4% vs. 18.9%, p = 0.003) and lower likelihood of hospitalization within 30 days of therapy (9.6% vs. 20.2%, p = 0.015) compared to patients treated with WBRT. Conclusions: Approximately 1 in 7 patients with MBC will require radiotherapy for BrM. Our data support the use of SRS when clinically indicated and provide insights regarding the time to development of BrM by breast cancer subtype.

Clinicopathological characteristics of exceptional responders who achieve durable remissions beyond five years (DR5) in HER2+(H+) metastatic breast cancer (MBC).

1046 Background: The introduction of anti-H2 targeted therapies has resulted in substantially improved outcomes for patients (pts) with H+MBC, yet despite survival prolongation, most patients so-treated will still ultimately die from MBC. Some patients do however, achieved prolonged remissions. In this report we outline the long-term outcomes of patients with H+MBC who were treated in our institution, with at least five-year follow-up from the diagnosis of MBC. Methods: As part of our larger single-institution “Thousand Patient HER-2 Database”, we conducted a retrospective review of all patients in whom a diagnosis of H+MBC was made prior to December 2015 (range 2000-2015 years). The DR5 category included only those who had never experienced relapse or progression following initial anti-H2 therapy for MBC, and who were alive at 5 years. Patients were designated as (1) DR5, defined as never relapse with an overall survival (OS) &gt; 5 years; (2) nonDR, which included those who had no or shorter remission, but also included nine pts who did achieve a 5 year CR, but who subsequently relapsed. OS was calculated from the date of diagnosis of MBC. The frequency distribution was assessed by Fisher’s Exact Test or Chi-Square Test, as appropriate. OS and PFS were calculated according to Kaplan Meier method, and evaluated by Log-rank test. Univariate and multivariate Cox proportional hazards regression analysis was used to evaluate the effect of clinicopathological features on OS and PFS. Results: A total of 245 patients diagnosed with advanced H+MBC were identified. The median survival was 38 months, (range 0.3 – 248 months). Among these, 85 patients (35%) experienced an OS &gt; 5 years, with 34 designated as DR5. The median OS for DR5 was 117 months, whereas nonDR (n = 211) had median OS of 33 months. The median age was similar between groups (DR5 53 yrs vs nonDR 56 yrs). A higher incidence of visceral disease was present in nonDR compared to DR5 (69% vs 44%). Of all patients diagnosed with de novo H+MBC, 23% achieved DR5. Presence of visceral disease, number of metastases and site of metastases were statistically significant negative predictors of achieving DR5 (P &lt; 0.05). Presence of ER positive disease was not associated with OS. Conclusions: A meaningful subset of patients (14%) with advanced H+MBC achieve prolonged remission beyond five years with H2 targeted therapy. Nearly one quarter of those with de novo H+MBC achieve DR5. As de novo H+MBC now constitutes a higher proportion of all H+MBC than it did in the pre-trastuzumab era, an increasing proportion of H+MBC may now be achieving DR5. Prospective identification of variables to predict DR5 could assist in the stratification of patients for whom additional therapy is needed.

Concordance between patient-reported (PR) and physician-documented (PD) comorbidities and symptoms among Stage 4 breast cancer patients (pts).

e24089 Background: Comorbidities (Co) and symptoms (Sx) in metastatic breast cancer (MBC) pts impact treatment decisions, eligibility for clinical trials, and influence prognosis and quality of life. The aim of this study was to evaluate the concordance between PR and PD Co and Sx in an electronic medical record to document pts’ health, identify Co or Sx that may be more comprehensively reported by pts vs physicians (phy), and understand if PR, PD, or concordant Co or Sx were more predictive of pt survival. Methods: New pts at UCSF’s Breast Care Center (BCC) are administered an electronic intake survey assessing PR health history, Co and Sx. Chart reviews of the initial clinic visit were conducted for PD Co and Sx. Pt and phy concordance was summarized for 54 Co and 42 Sx. Agreement was quantified using Cohen’s kappa (κ) (poor (κ &lt; 0.2), fair (0.2≤κ &lt; 0.4), moderate (0.4≤κ &lt; 0.6), substantial to high (κ ≥0.6)). Cox-proportional hazards models were used to determine hazard ratios (HR) for survival with PR, PD, and concordant Co and Sx, controlling for factors including age, sites of metastatic disease, tumor biology, etc. Results: Between Nov 2016 and Feb 2020, 168 pts with confirmed MBC seen at the BCC who consented to use of their clinical data for research were included in the analysis (median age, 56 years; median time from MBC diagnosis, 0.46 years). Highest PD Co were obesity, hypertension (HTN) and thyroid disease, while highest PR Co were HTN, depression and arthritis. 23 of 54 Co had a moderate to high level of agreement between physician and pt reports (κ≥0.40). Agreement was high for diabetes, HTN, and low for obesity, anxiety, and gastroesophageal reflux disease (GERD). After controlling for clinical covariates, of these Co, only PR GERD was significantly associated with survival (HR = 1.87, p &lt; 0.05). Only 2 of 42 Sx (shortness of breath and cough) had a moderate to high agreement between PD and PR. PR Sx were the primary drivers for predicting survival (HR &gt; 1, p &lt; 0.05 for PR Sx including vomiting, fatigue, weight loss and others). PD and PR agreement for these sx was poor (κ &lt; 0.2). Conclusions: In this review of data collected as part of routine care at an academic medical center, there was substantial variance in the concordance of Co and Sx reported by pt vs phy. Concordance was higher for Co, with phy documenting a higher number of Co that can be objectively measured by lab values (diabetes, HTN) while pts reported higher rates of Co that were more subjective (anxiety, GERD). Overall, pts reported more Sx than phy. PR Sx were also the highest predictors of survival. Intriguingly, Co such as diabetes and HTN did not predict survival in this metastatic population. This suggests that incorporating PR Sx, either secondary to their cancer or related to their Co, may provide a more informative estimate of a pt’s predicted survival, and assist phy in evaluating trial eligibility and reasonable treatment options.

Treatment-related side effects and views about dosage assessment to sustain quality of life: Results of an advocate-led survey of patients with metastatic breast cancer (MBC).

1005 Background: Metastatic breast cancer (MBC) is generally incurable and the majority of patients with MBC will remain on treatment indefinitely. Patients usually begin each new treatment at the Recommended Starting Dose (RSD) on the FDA-approved label based on results from clinical trials. However, patients’ ability to tolerate the RSD in the real-world may differ from the clinical trial setting. While the importance of patient reported outcomes is recognized, understanding tolerability from the patient’s perspective is lacking and patients’ willingness to discuss individualized doses for MBC therapy has not been evaluated. Methods: Patient advocates from the Patient-Centered Dosing Initiative distributed a confidential online survey to patients with MBC via social media groups, organizational newsletters, and online support forums. The survey was developed by patients and medical oncologists to ascertain the prevalence and impact of patients’ treatment-related side effects, quality of patient-physician communication, management of side effects, and interest in alternative approaches to the RSD when a new treatment is initiated or adverse side effects are experienced. Results: 1,221 patients with MBC completed the survey within 15 days. The median number of lines of MBC therapy was 2.5 (range 1 - ≥5) and 46% (n = 564) of patients received their MBC diagnosis within two years of taking the survey. 86% (n = 1,051) reported experiencing at least one significant treatment-related side effect, and of these, 20% (n = 213) visited the Emergency Room/hospital and 43% (n = 454) missed at least one treatment. 98% (n = 1,026) of patients with side effects discussed them with their doctors and 82% (n = 838) were helped by their physicians. The most common (non-exclusive) mitigation strategies were dosage reductions (66%, n = 556) and prescription medications (59%, n = 494). Of the 556 patients given a dosage reduction, 83% (n = 459) reported feeling better. Notably, 92% (n = 1,127) of patients expressed willingness to discuss alternative dosing options with their physicians based upon their personal characteristics and individual preferences. Conclusions: Given that 86% of patients with MBC experienced at least one significant treatment-related side effect and 83% improved after dosage reduction, innovative dosage-related strategies are warranted to sustain Quality of Life. Patient-physician discussions in which the patient’s physical attributes and circumstances are periodically assessed may determine the right dose for the patient upon treatment initiation and afterwards, and the vast majority of patients would be receptive to such discussions.

Predictors of non-receipt of first-line CDK 4/6 inhibitors (CDK4/6i) among patients with metastatic breast cancer (MBC).

1016 Background: CDK4/6i improve survival outcomes for first-line treatment of patients with hormone receptor positive (HR+), human epidermal growth factor-2 negative (HER2-) MBC. Yet, not all eligible patients (pts) receive a first-line CDK4/6i. We sought to describe factors associated with not receiving a first-line CDK 4/6i among MBC pts treated at our institution. Methods: Retrospective cohort of pts with HR+, HER2- MBC diagnosed between May 1, 2015 and June 30, 2019 treated at Johns Hopkins clinic sites in Baltimore City (BCi), Baltimore County (BCo), and Washington DC (DC). Primary outcome was receipt of a first-line CDK 4/6i. Clinical and demographic factors were abstracted from the electronic medical record. Patient zip-code was used to define a low-income neighborhood (LIN) as an area where &gt;10% of households have median income below the federal poverty level. Univariate and multivariable logistic regression models (determined using a stepwise model selection approach) were performed to identify factors associated with not receiving a first-line CDK 4/6i. Results: Of the 211 pts in the cohort, 203 (96.2%) were female, 133 (63%) were White, and 53 (25%) were Black. Median age was 58 yrs (range 25-90 yrs). 26% of pts had de novo MBC and 44% had visceral disease at diagnosis. About half, 104 (49%), were privately insured, 83 (49%) had Medicare, and 15 (7.1%) had managed care plans including Medicaid. 118 (56%), 43 (20%), and 50 (24%) pts were treated in BCi, BCo, and DC respectively. 60% (n=126) of pts received a first-line CDK 4/6i and there was a trend of increased utilization over time with 39% of pts receiving first-line CDK4/6i in 2015 and 67% in 2019. On univariate analysis, LIN, clinic site, and year of MBC diagnosis (2015-2017 vs 2018-2019) were associated with first-line CDK4/6i use. The multivariable model included age, race, clinic site, LIN, and year of MBC diagnosis. In this model, pts treated in BCi were 58% less likely to receive first-line CDK 4/6i compared to those treated in BCo (OR 0.42, 95% CI 0.18-0.95). Those diagnosed with MBC in 2017 or later were 2.6 times more likely to receive first-line CDK4/6i than those diagnosed prior (OR 2.63, 95% CI 1.45-4.83). Those who lived in a LIN were 39% less likely to receive first-line CDK4/6i vs those in a non-LIN, though this was no longer statistically significant (OR 0.61, 95% CI 0.32-1.13). Conclusions: We identified disparities in the use of CDK4/6i for first-line treatment of MBC. Lower use was observed among pts who received care at our urban Baltimore city site with a trend towards lower use among pts from lower-income neighborhoods. These findings highlight potential barriers with accessing oral cancer therapies - cost, patient distrust, and/or systemic bias. Further work is needed to delineate the multi-level factors contributing to these disparities and to develop resources to overcome these barriers and achieve equitable utilization of these drugs.

Characterizing demographics, clinical, and genomic characteristics for U.S. patients with HR+, HER2- metastatic breast cancer following progression on a CDK4 and 6 inhibitor.

1015 Background: Cyclin-dependent kinases 4 and 6 inhibitors (CDK4 &amp; 6i) have advanced the therapeutic landscape for patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (MBC). However, there is an unmet need for treatment strategies following progression on CDK4 &amp; 6i +/- endocrine therapy (ET). The objective of this analysis is to aid in the development of post-progression treatment by characterizing genomic profiles of tumor biopsies after progression on a CDK4 &amp; 6i +/- ET. Methods: This is a retrospective study comparing two cohorts of US patients (pts) diagnosed with HR+, HER2- MBC since January 2011. One cohort underwent biopsy following progression on a CDK4 &amp; 6i +/- ET (Cohortpost) while the second cohort underwent biopsy with no evidence of CDK4 &amp; 6i treatment (Cohortpre). Tumor tissue was analyzed using the next generation sequencing Tempus xT assay that analyses 595 cancer-related genes. Of 595 molecularly profiled pts, 369 had sufficient medical record data to be eligible for this analysis. Patient characteristics at metastatic diagnosis and CDK4 &amp; 6i initiation were described. For genomic profile comparison, Mann-Whitney U-test was used for continuous variables such as tumor mutation burden (TMB) with significance at P &lt; 0.05; Chi-square or Fishers' exact test was used as appropriate for categorical variables including mutation frequency, with significance at false discovery rate (FDR) &lt; 0.2. Results: Of 369 pts, 177 (48%) were in Cohortpre and 192 (52%) were in Cohortpost. Overall, the mean age at the time of MBC diagnosis was 59 and 55 years, respectively; 47% and 66% of patients had evidence of prior chemotherapy or ET; and 30% and 25% had de novo stage IV MBC. The most common biopsy site was liver, occurring in 38% of pts overall (Cohortpre, 23%; Cohortpost, 52.6%). The xT assay results indicated that pts in Cohortpost had significantly higher TMB compared to patients in Cohortpre (median 2.92 vs 1.67, P &lt; 0.0001). A subset of patients with liver mets across both cohorts (n = 141) showed a similar, but nonsignificant trend (median 2.92 vs 2.08, P = 0.0565). Additionally, pts in Cohortpost had a higher ESR1 alteration frequency compared to Cohortpre (mutations: 32.29% vs 9.60%, FDR &lt; 0.0001; fusions: 7% vs 3%, P = 0.1420). No significant differences were noted in TP53, CCNE1, CCND1, RB1, CDK4, and CDK6 between cohorts. Conclusions: These findings describe clinical characteristics and specific genomic alterations noted after progression on CDK4 &amp; 6i +/- ET. Further analyses will evaluate timing of resistance, mutational and transcriptomic signatures. This may aid in understanding mechanisms of progression associated with CDK4 &amp; 6i +/- ET, ultimately contributing to development of treatment options post progression.