Diagnosis Of Metastatic Breast Cancer Research Articles

Clinical and radiographic characteristics of patients with metastatic breast cancer and pseudocirrhosis: A single-center retrospective cohort study.

1101 Background: Pseudocirrhosis is a term used to describe changes in hepatic contour that mimic cirrhosis radiographically, but lack the classic pathologic features of cirrhosis. This radiographic finding is frequently found in patients with metastatic breast cancer (MBC); the pathophysiology and clinical consequences are poorly understood. The objective of this study is to describe the patient, tumor, and treatment characteristics associated with pseudocirrhosis, and to assess associated clinical outcomes. Methods: In this retrospective study, we identified patients with MBC and imaging findings consistent with pseudocirrhosis (diffuse liver contour abnormalities) who were treated at the University of California San Francisco from 2002-2021. We used chart extraction and radiology review to determine demographic characteristics, treatment history, response to treatment, imaging features, and complications of pseudocirrhosis. Comparisons between groups were made using the unpaired t-test or two-sided Fisher’s exact test. Results: 120 patients with MBC and radiographic evidence of pseudocirrhosis were identified with the following BC subtypes: Hormone receptor (HR) positive, HER2 negative (n = 99, 82.5%), HR+/HER2+ (n = 14, 11.7%), HR-/HER2+ (n = 3, 2.5%), and triple negative (TNBC; n = 4, 3.3%). All patients with pseudocirrhosis had liver metastases (n = 120, 100.0%) and 82.5% (n = 99) had > 15 lesions. Median time from diagnosis of MBC to radiographic evidence of pseudocirrhosis was 29.2 months. Most patients received chemotherapy for MBC prior to the finding of pseudocirrhosis (n = 111, 92.5%) with median 2.0 lines. Pseudocirrhosis was observed in the setting of stable or responding disease in 50% of patients (n = 60). Patients received a median of 1.0 line of additional therapy after pseudocirrhosis diagnosis, with a median overall survival of 7.9 months from pseudocirrhosis to death. Sequelae of pseudocirrhosis included the radiographic finding of ascites (n = 97, 80.8%), gastric/esophageal varices (n = 68, 56.7%), splenomegaly (n = 26, 21.7%), GI bleeding (n = 12, 10.0%), or hepatic encephalopathy (n = 11, 9.2%). Radiographic evidence of ascites was associated with a shorter survival from MBC diagnosis compared to no ascites (42.8 vs. 76.2 months, p = < 0.001). GI/Hepatology consultation was uncommon (n = 9, 7.5%). Conclusions: To our knowledge, this is the largest reported case series of patients with MBC and pseudocirrhosis. Nearly all patients had HR+ disease and extensive liver metastases. Pseudocirrhosis was frequently observed in the setting of responding or stable disease, creating complexity in management. Survival was short in all patients, particularly patients with radiographic evidence of ascites. Further understanding of the pathogenesis of and risk factors for pseudocirrhosis could help improve outcomes for this condition.

Real world incidence and management of adverse events in patients with HR+, HER2− metastatic breast cancer receiving CDK4 and 6 inhibitors in a United States community setting

Objective To examine the real-world incidence and management of select adverse events (AEs) among female patients with hormone receptor positive (HR+), human epidermal growth factor receptor 2-negative (HER2−) metastatic breast cancer (MBC), receiving a cyclin-dependent kinase 4 and 6 (CDK4 and 6) inhibitor (palbociclib, abemaciclib, or ribociclib). Methods This retrospective study analyzed data from the US Oncology Network iKnowMed electronic health record database for 396 patients with an initial MBC diagnosis on/after 1 January 2014 and receipt of first CDK4 and 6 regimen between 1 January 2017 and 31 December 2018. In this descriptive study, the proportion of patients who experienced select AEs and associated dose modifications or discontinuations were reported. The occurrence of select healthcare resource utilization categories was also reported. Results Median follow-up time was 451, 262, and 355 days for patients in the palbociclib, abemaciclib, and ribociclib cohorts, respectively. The most common AEs were neutropenia (palbociclib, 44.8%; abemaciclib, 10.6%; ribociclib, 36.3%), diarrhea (palbociclib, 8.0%; abemaciclib, 43.0%; ribociclib, 8.8%), and fatigue (palbociclib, 12.9%; abemaciclib, 17.6%; ribociclib, 16.5%). AEs resulted in a treatment hold among 91 (23.0%), a dose reduction among 86 (21.7%), and permanent discontinuation among 48 (12.1%) patients overall. Conclusions This real-world study provides insight into the occurrence of AEs which varied by CDK4 and 6 inhibitor. Compared to clinical trials, frequencies of AEs were numerically lower but dose reductions due to AEs were numerically higher. It is possible these differences reflect proactive management of AEs on the part of clinicians to help patients remain on therapy.

Cancer treatment-specific medication beliefs among metastatic breast cancer patients: a qualitative study.

Over 168,000 women are living with metastatic breast cancer (MBC) in the USA. More efficacious treatments have lengthened overall survival, but these treatments often result in a myriad of symptoms and financial burden that may negatively impact perceptions of cancer treatment and medication-taking behavior. To explore cancer treatment-specific medication beliefs among women undergoing cancer treatment for MBC. A qualitative study was conducted using semi-structured interviews that were audio recorded and transcribed verbatim. A thematic analysis was conducted using ATLAS.ti 8.0 software. Inter-rater reliability was set at a threshold of 0.80. Participants were recruited from a National Cancer Institute-designated comprehensive care center. Eligibility included ≥18 years old, English speaking, confirmed MBC diagnosis, and able/willing to complete interviews via telephone or Zoom. Participants (n = 16) were largely Caucasian (86.7%) and non-Hispanic (93.3%). Mean age was 55.62 years. Three major themes were revealed, with corresponding subthemes: (1) positive cancer treatment-specific medication beliefs highlighting the benefit of treatment (relief of cancer-related symptoms and medication efficacy: delayed disease progression/extended survival); (2) negative cancer treatment-specific medication beliefs that caused concern for cancer treatment (medication symptoms, side effects and drug-drug interactions, financial toxicity, lack of guarantee medication would work); and (3) dialectical cancer treatment-specific medication beliefs indicating the benefits of cancer treatment outweigh the risks. Overall, participants noted that the benefits of cancer treatment outweighed the risks in the context of metastatic disease. Participants understood their prognosis and that they depended on their cancer treatment for survival. Oncology providers should continue to assess and address medication beliefs over the treatment trajectory and assist MBC patients with the decisional balance between the risk and benefit of continued cancer treatment.

Women with short survival after diagnosis of metastatic breast cancer: a population-based registry study

PurposeDespite therapeutic advances, overall survival of metastatic breast cancer (MBC) at the population level has seen little improvement over the past decades. Aggressive tumor biology or delay in access to cancer care might be contributing factors. With this retrospective population-based study we aimed to quantify and characterize patients with very short survival time following MBC diagnosis.MethodsWomen diagnosed with MBC between Jan 1st, 2005 and Dec 31st, 2016 were identified using the population-based Stockholm–Gotland breast cancer registry. Data regarding demographic and clinicopathological characteristics, survival, and treatment were extracted retrospectively from the registry and from patient charts. Patients who died within 90 days following diagnosis of MBC were identified and their characteristics were compared with all other patients diagnosed with MBC during the same period.ResultsBetween 2005 and 2016, 3124 patients were diagnosed with MBC, of whom 498 (16.2%) died within 90 days of diagnosis. Nearly half (N = 233) did not receive any antitumoral treatment. Patients with short survival were older (p < 0.001), had higher primary tumor grade (p < 0.001), higher clinical stage at primary diagnosis (p = 0.002), and more often estrogen receptor (ER)-negative breast cancer (p < 0.001). Visceral metastases were more frequent (p < 0.001) and patients with short survival received adjuvant chemotherapy (p < 0.001) to a lesser extent compared to patients with a better prognosis. In multivariable analysis older age, time period of diagnosis, metastasis site, adjuvant chemotherapy, and primary tumor grade were independent predictors for short survival, whereas ER status was not.ConclusionNearly one out of six patients with MBC survive less than 3 months after diagnosis. Our findings demonstrate a different spectrum of MBC at population level and can potentially inform on individualized follow-up strategies and treatment algorithms.

Coping With Changes to Sex and Intimacy After a Diagnosis of Metastatic Breast Cancer: Results From a Qualitative Investigation With Patients and Partners.

Objective:Prior research examining sexual and intimacy concerns among metastatic breast cancer (MBC) patients and their intimate partners is limited. In this qualitative study, we explored MBC patients’ and partners’ experiences of sexual and intimacy-related changes and concerns, coping efforts, and information needs and intervention preferences, with a focus on identifying how the context of MBC shapes these experiences.Methods:We conducted 3 focus groups with partnered patients with MBC [N = 12; M age = 50.2; 92% White; 8% Black] and 6 interviews with intimate partners [M age = 47.3; 83% White; 17% Black]. Participants were recruited through the Fox Chase Cancer Center Tumor Registry and the Cancer Support Community. Qualitative data were analyzed using the Framework Method and Dedoose software.Results:Qualitative analyses revealed several key themes reflecting ways in which MBC shapes experiences of sex/intimacy: (1) the heavy disease/treatment burden leads to significant, long-term sexual concerns (e.g., loss of interest and vaginal dryness/discomfort) and consequent heightened emotional distress for both patients (e.g., guilt around not being able to engage in intercourse) and partners (e.g., guilt around pressuring the patient to engage in sexual activity despite pain/discomfort); (2) viewing the relationship as having “an expiration date” (due to expected earlier mortality) influences patients’ and partners’ concerns related to sex/intimacy and complicates coping efforts; and (3) information needs extend beyond managing sexual side effects to include emotional aspects of intimacy and the added strain of the life-limiting nature of the disease on the relationship. The heightened severity of sexual concerns faced by patients with MBC, compounded by the terminal nature of the disease, may place patients and partners at risk for significant adverse emotional and interpersonal consequences.Conclusion:Findings suggest unique ways in which sex and intimate relationships change after a diagnosis of metastatic breast cancer from both patients’ and partners’ perspectives. Consideration of the substantial physical and emotional burden of MBC and the broader context of the relationship and intimacy overall is important when developing a sexuality-focused intervention in this population. Addressing sexual concerns is a critical part of cancer care with important implications for patients’ health and quality of life.

Low social and family well-being is associated with greater RAGE ligand s100A8/A9 and interleukin-1 beta levels in metastatic breast cancer patients

Greater inflammatory signaling has been shown to promote breast cancer disease progression and poorer clinical outcomes. Lower social support and social well-being have been related to greater inflammatory signaling and poorer clinical outcomes in women with non-metastatic breast cancer, and this appears to be independent of depression. However, little is known about these associations in women with metastatic disease. s100A8/A9 and interleukin 1 beta (IL-1β) proteins are widely studied in breast cancer and are considered as biomarkers of cancer progression or as having a causal role in carcinogenesis and cancer progression and metastasis via inflammatory signaling. The aim of this study was to examine the associations between less social/family well-being (SWB) and S100A8/A9 and IL-1β levels in women diagnosed with metastatic breast cancer. Sixty women (Mean age 58.95 ​± ​1.49) with a diagnosis of metastatic breast cancer participated in the study. The Functional Assessment of Cancer Therapy (FACT) social and family well-being (SWB) subscale and the Hospital Anxiety Depression Scale (HADS) were administered to patients undergoing a first- or second-line endocrine or oral chemotherapy treatment and who were not experiencing brain metastasis or visceral crisis. Salivary s100A8/A9 and IL-1β levels were assessed at 5PM on two consecutive days and averaged. Multiple regression tested the independent contribution of SWB on s100 A8/A9 and IL-1b while controlling for depression. Lower levels of SWB were associated with greater S100A8/A9 (ß ​= ​−0.345, p ​= ​0.007) and IL-1β (ß ​= ​−0.286, p ​= ​0.027) levels and these associations remained significant after controlling for depression. This work provides new evidence for the role of decreased SWB and greater s100A8/A9 and IL-1b levels in patients diagnosed with metastatic breast cancer. Psychosocial interventions that promote social support and positive social interactions through interpersonal skills may help metastatic breast cancer patients to improve their SWB. This may have salutary effects on cancer-promoting processes, which could provide psychological and physical health benefits.

Abstract P1-16-03: Response pattern to chemotherapy in metastatic breast cancer (MBC): Real-word data from the Austrian AGMT_MBC-Registry

Abstract Background: Despite the advances by targeted therapies, particularly in HER2-positive and hormone receptor (HR)-positive metastatic breast cancer (MBC), chemotherapy remains a mainstay of the treatment in all breast cancer subtypes. Response probabilities to chemotherapy seem to decrease with increasing lines of treatment, but little is known about the response dependency on the previous therapy line. Here, we present data from the MBC registry of the Austrian Study Group for Medical Tumor Therapy (AGMT-MBC-Registry). Methods: The AGMT-MBC-Registry is an ongoing multicenter registry for MBC patients in Austria. Patients with available hormone receptor and negative HER2 status, at least two consecutive lines of chemotherapy and sufficient progression-free survival (PFS) data were included in this analysis. Multivariable adjusted hazard ratios (HR) for PFS were estimated by Cox regression models and included the following parameters: age, HR status, disease-free survival (de novo metastatic or ≥ 24 months vs. &amp;lt; 24 months), visceral disease, number of involved metastatic sites at diagnosis of MBC, chemotherapy treatment line, and response in previous treatment line. Response was defined as PFS &amp;gt; 4 month and non-response as a PFS ≤ 4 month. Cox model was extended as proposed by Andersen and Gill due to possibility of multiple events per patient and thereby resulting dependencies (Sousa-Ferreira &amp; Abreu, 2019). Results: As of 15/04/2021, 2024 patients were included in the registry. Out of them, 405 patients (20.0%) had documented HER2 negative disease with at least two lines of consecutive chemotherapy. Median PFS for first-, second-, third-, and forth-line chemotherapy were 6.0 months (95% CI 5.5-6.5), 3.7 months (95% CI 3.1-4.3), 2.9 months (95% CI 2.5-3.2), and 2.8 months (95% CI 2.6-3.2), respectively. Median overall survival was 31.8 months (95% CI 27.2-34.8). Median number of chemotherapy lines was 3 (range 2-8). The most commonly used cytotoxic agents were paclitaxel and capecitabine in first- and second-line, and eribulin in third-, and fourth-line chemotherapy. Combinations of more than one cytotoxic drug were given in 36%, 29%, 28% in first-, second-, and third/fourth-line. Patients who did not respond to the previous therapy line, had a response in 43% (95% CI 33-53), 34% (95% CI 25-43), and 30% (95% CI 21-39) to second-, third-, and fourth-line. In those patients, investigator assessed overall response rate (partial remission or complete remission) was 27% (95% CI 13-40), 23% (95% CI 9-37), and 33% (95% CI 16-51), respectively. A response to third-line chemotherapy in patients who did not respond to first- and second-line therapy, was seen in 16.7% of patients. Ratios between PFS of interest and PFS of the previous treatment line were 0.63 (95% CI 0.55-0.68), 0.57 (95% CI 0.41-0.62), and 0.76 (95% CI 0.58-0.9) in second-, third-, and forth-line therapy. In multivariable analysis, responses in second- to fourth-line therapy were statistically significant associated with disease-free survival (HR 0.75, P=0.022), and treatment line (HR 1.17 per increasing treatment line, P=0.004), but not for the response to the previous treatment line (HR 0.85, P=0.068). Conclusion: A continuously decreasing PFS for cytotoxic drugs from treatment line to treatment line was confirmed in our analysis. However, in multivariable analysis, response, defined as PFS &amp;gt; 4 months, was not statistically associated with response to the previous treatment line. Therefore, a lack of response to first, second-, - or third-line chemotherapy should not trigger discontinuation of anticancer therapy in case of further available treatment options. Citation Format: Gabriel Rinnerthaler, Simon P Gampenrieder, Christoph Tinchon, Andreas Petzer Petzer, Marija Balic, Heibl Sonja, August F Zabernigg, Daniel Egle, Margit Sandholzer, Florian Roitner, Johannes Andel, Petra Pichler, Christophe Hager, Michael Hubalek, Michael Knauer, Christian F Singer, Richard Greil. Response pattern to chemotherapy in metastatic breast cancer (MBC): Real-word data from the Austrian AGMT_MBC-Registry [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-16-03.

Abstract P4-11-14: Importance of work and work-related needs among survivors living with metastatic breast cancer

Abstract Background: Survivors living with metastatic cancer may continue to work. Up to 35% report working at least part-time. 1 There is a knowledge gap regarding the reasons and priorities driving the decisions about continuing to work while living with metastatic cancer. By 2020, the US population of individuals living with metastatic breast cancer (MBC) was projected to exceed 165,000. 2 Thus, it is necessary to understand and to explore the importance of work and information needs, in order to develop interventions to address MBC survivors’ employment-related needs. Objective: To explore the importance of work and characterize the information needs among survivors living with MBC. Methods: We conducted an online survey assessing work-related needs and motivations, between November 2014 and February 2015, using a MBC listserv and clinic flyers. Respondents who worked at the time of MBC diagnosis were divided into “stably-working” and “no-longer-working” based on employment status at the time of the survey. Comparisons between the two groups were made with chi-square or two-tailed t-test. A p-value &amp;lt;0.05 was considered statistically significant. The study obtained Institutional Review Board approval. Results: Respondents (n=133) were predominantly non-Hispanic White (93.2%), with a college degree (72.7%). The majority of stably-working women (80.5%) considered work to be important due to financial and/or insurance reasons (80.4%), the importance of staying busy (67.9%), and the desire to support themselves and family (64.3%). Among those no-longer-working who stated that work was unimportant (47,6%), the work became less important since the diagnosis of MBC. The stably-working group valued information on how to talk with employers or co-workers about diagnosis, legal rights in the workplace, when to think about stopping work, and applying for disability. Among those no-longer-working, information on Medicare and/or Medicaid and spirituality were deemed important. Conclusion: Assessing the employment needs of survivors with MBC is important. It can be a continuous process as the disease progresses, and maintenance of employment and priorities may change. Thus, offering resources to empower survivors living with MBC to manage their employment issues earlier in the disease trajectory is needed, particularly considering that unemployment and financial burden can adversely affect health-related quality of life and increase distress. 3 Table 1.Sociodemographic and importance of work among women with MBCStably-workingNo-longer-working(n=72)(n=61)Age, Mean (SD) **49.5 (8.3)54.0 (8.1)Time from MBC diagnosis (yr), Mean (SD) **3.3 (3.4)4.6 (4.0)Highest level of education, %Less than college23.931.2College graduate29.637.7Post-graduate or professional degree46.531.2Household income, %≤$75,00047.242.6$75,001-150,00029.237.7≥ $150,00118.19.8Unknown or prefer not to answer5.69.8RaceWhite98.693.4Black03.3Asian00Other1.43.3Prefer not to answer1.41.6Ethnicity (Spanish/Hispanic/Latino origin) %Yes03.3No97.296.7Prefer not to answer2.80Current importance of work, %**Extremely important33.31.6Very important47.227.9Neither important nor unimportant5.623Somewhat unimportant8.314.8Not at all important5.632.8Reasons why work is important %(n=56)(n=18)Success is important to me30.438.9It means a lot for me to be able to support myself/my family64.350It is important that I have a worthwhile job60.772.2It is necessary for financial and/or insurance reasons80.461.1Work is an important part of my social life48.266.7Staying busy is important to me67.972.2Other14.316.7Reasons why work is unimportant %(n=10)(n=29)Work has never been very important to me03.5Work is less important to me since being diagnosed with metastatic breast cancer*10055.2Work is not important because I do not need to work for financial reasons1037.9Work is not important because I do not need to work for insurance reasons3034.5Work is not important because it does not provide social support06.9Other5041.4Comparison between stably-working and no-longer-working groups using t-test for continuous variables and chi-square test for categorical variables; *p&amp;lt;0.05; **p&amp;lt;0.01. Citation Format: Cibele B. Carroll, Mary E. Sesto, Xiao Zhang, Karen B. Chen, Abigail Terhaar, Athena S. Wilson, Amye J. Tevaarwerk. Importance of work and work-related needs among survivors living with metastatic breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P4-11-14.

Abstract P4-05-02: Impact of hormone receptor status on clinicopathological characteristics and outcomes among HER2-positive metastatic breast cancer patients in the ESME database

Abstract Introduction. Evidence suggests that human epidermal growth factor receptor 2-positive (HER2+) metastatic breast cancer (MBC) patients have different clinical characteristics and outcomes according to the hormone receptor (HR) status. We aimed to evaluate the impact of HR status in this population extracted from a large real-world database. Methods. We performed a retrospective analysis of HER2+ MBC patients (pts) included in the real world ESME MBC database (NCT03275311) between 2008 and 2017. Descriptive statistics, the Kaplan-Meier method and Cox proportional hazards models were used to report characteristics, outcomes and prognostic factors. Results. Of 4,145 HER2+ MBC pts eligible for our analysis, 1,449 (35%) had HR-negative (HR-), while 2,696 (65%) had HR-positive (HR+) tumors. Pts with HR- tumors had metastases earlier (median 9.3 vs 28.0 mo from primary cancer), had more often de novo MBC (47.6% vs 38.1%), grade III tumors (50.9% vs 33.6%), visceral metastases (70.9% vs 60.8%) and less often bone only disease (8.4% vs 21.1%) compared to those with HR+ tumors, all p&amp;lt;0.001. Pts with HR+ MBC received less frequently an anti-HER2+ targeted therapy during first line of treatment than pts with HR- tumors (74.9% vs 90.8%, p&amp;lt;0.001). Pts with HR- MBC had significantly worse outcomes than those with HER2+/HR+ MBC, with median overall survival (OS) 42.0 mo [95% CI 38.8-45.2] vs 55.9 mo [95% CI 53.7-59.4], p&amp;lt;0.001, and median progression-free survival (PFS) 9.8 mo [95%CI 9.2-11] vs 12.2 mo [95%CI 11.5-12.9], p=0.012, respectively. The independent prognostic value of HR status was confirmed in a multivariable analysis for OS (HR- versus HR+, hazard ratio=1.25 [1.13-1.39], p&amp;lt;0.001) but not for PFS (hazard ratio=1.03 [95%CI 0.95-1.13], p=0.8) (Table 1 for OS). The multivariable analysis also included tumor grade, age at and time to MBC diagnosis, presence of visceral metastases, number of metastatic sites and performance status as prognostic factors. In the HR+ population, ER and PR statuses were not prognostic. Conclusions. These data confirm the remaining strong and independent adverse prognostic effect of negative hormone receptors among pts with HER2+ MBC treated in the past 12 years. Cox multivariable model for overall survival in patients with HER2-positive MBCCategoriesNHazard ratio95% CIp valueTumor gradeGrade I/II17711&amp;lt;0.001Grade III15741.13[1.03-1.25]NA5811.15[1.01-1.31]ER/PR statusER+/PR+14571&amp;lt;0.001ER+/PR-9711.03[0.92-1.16]ER-/PR+1021.03[0.77-1.36]ER-/PR-13961.25[1.13-1.39]Age at MBC diagnosis&amp;lt;55 years17561&amp;lt;0.001≥55 years21701.26[1.16-1.38]Time to MBC diagnosis&amp;lt;6 months16351&amp;lt;0.0016-24 months5082.53[2.22-2.89]24-60 months8721.75[1.56-1.96]≥60 months9111.19[1.06-1.35]Visceral metastasesNo14061&amp;lt;0.001Yes25201.54[1.38-1.71]No of metastatic sites&amp;lt;330911&amp;lt;0.001≥38351.65[1.48-1.84]ECOG PSPS 010101&amp;lt;0.001PS 18021.62[1.4-1.87]PS 2-43923.34[2.83-3.95]NA17222.34[2.07-2.64] Citation Format: Luc Cabel, Matthieu Carton, Veronique Dieras, Thierry Petit, Severine Guiu, Corinne Veyret, Anthony Goncalves, Lionel Uwer, Paule Augereau, Jean-Marc Ferrero, Christelle Levy, Florence Dalenc, Isabelle Desmoulins, Marie Ange Mouret-Reynier, Marc Debled, Thomas Bachelot, Jean-Christophe Eymard, Barbara Pistilli, Jean Sebastien Frenel, Michael Chevrot, Audrey Mailliez, Marcela Carausu. Impact of hormone receptor status on clinicopathological characteristics and outcomes among HER2-positive metastatic breast cancer patients in the ESME database [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P4-05-02.

Abstract P3-09-11: Clinical characteristics associated withBRCA1/2mutations identified on routine tumor tissue genotyping in metastatic breast cancer

Abstract Background: Tumor tissue genotyping (TG) can identify actionable mutations for potential therapeutic intervention. PARP inhibitors are approved for the treatment of metastatic breast cancer (MBC) in germline BRCA1/2 carriers, and may have efficacy in somatic BRCA1/2-mutant MBC. We studied the clinical features of BRCA1/2 mutations detected on routine TG of tumors in patients with MBC. Methods: Consecutive patients with MBC at an academic medical center who underwent TG (institutional next generation sequencing (NGS), 91 gene assay; coverage includes BRCA1 exons 2-23 and BRCA2 exons 2-27) as part of routine clinical care from June 2016 to September 2020 were identified. The subset with BRCA1/2 mutations underwent further chart review to determine demographics, coexisting genomic landscape, germline genetic testing results, cell-free DNA (cfDNA) results, and treatment with a PARP inhibitor. Variant classification and presumed germline/somatic status was determined by pathologists, using a combination of automated bioinformatics tools and manual review of NGS read pile-ups, allele frequency, variant annotation, and by querying publically-available genomic databases including ClinVar, COSMIC, and gnomAD. Pathogenic status of mutations was determined via manual review by a molecular genetic pathologist using online genomic resources (ClinVar, mycancergenome, ARUP, and pubmed). Concordance between cfDNA and TG was assessed. Results: Of 372 patients with MBC who underwent TG, 46 (12.4%) had BRCA1/2 mutations identified on TG (85% on metastatic specimens), 15 (33%) BRCA1 and 31 (67%) BRCA2, with 1 patient having both BRCA1 and BRCA2 mutations. Of these, 26 (57%) were hormone receptor (HR)+/HER2-, 14 (30%) were triple negative (TNBC), 3 (6.5%) were HR-/HER2+, and 3 (6.5%) had HR+/HER2+ MBC. Thirty-four mutations (74%) were pathogenic. Median age at MBC diagnosis was 61 years (range 31-82). Common co-existing mutations found in TG included TP53 (37%), PI3KCA (22%), NF1 (8.6%), ESR1 (8.6%), MAP3K1 (6.5%), ATM (6.5%), and PTEN (6.5%). Of 22 patients with BRCA1/2 mutations on TG who had cfDNA testing results available, 10 (45%) had concordant BRCA1/2 mutations seen in TG and cfDNA. On expert review, 29 (63%) BRCA1/2 mutations were presumed germline mutations, and 17 (37%) were presumed somatic mutations. Eighteen patients with germline genetic testing results available had confirmed germline BRCA1/2 mutations. Fourteen patients with presumed germline BRCA1/2 mutations received a PARP inhibitor with a median duration of response (DOR) of 6 months (range 2-28). Two patients with presumed somatic BRCA1/2 mutations received a PARP inhibitor with median DOR of 13 months (range 10-16). Conclusions: TG can identify both germline and somatic BRCA1/2 mutations in a proportion of patients with MBC, especially HR+/HER2- and TNBC, and in conjunction with TP53 mutations. Some of these mutations in TG are concordant with cfDNA. The identification of BRCA1/2 mutations on TG may lead to consideration of genotype-directed therapy with a PARP inhibitor in germline and somatic BRCA1/2-mutant cancers. Citation Format: Neelima Vidula, Erica Blouch, Alexander Farahani, Hetal Marble, Andrzej Niemierko, Kathleen Hesler, Elyssa Denault, Dejan Juric, Leif W. Ellisen, Beverly Moy, Steven Isakoff, Jochen Lennerz, Aditya Bardia. Clinical characteristics associated withBRCA1/2mutations identified on routine tumor tissue genotyping in metastatic breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-09-11.

Abstract OT2-16-01: The SMILE study: A phase 2 trial of onapristone in combination with fulvestrant for patients with ER+ and HER2- metastatic breast cancer after progression on endocrine therapy and CDK4/6 inhibitors

Abstract Background Antiprogestins, including selective progesterone receptor (PgR) modulators (SPRMs) that act as PgR antagonists, are a promising class of therapeutics for overcoming endocrine resistance including in patients who develop activating estrogen receptor 1 (ESR1) mutations after prior endocrine therapy (ET). The SMILE study (NCT04738292) is a multi-institutional phase II clinical trial to determine the efficacy and safety of an antiprogestin, onapristone in combination with fulvestrant as second-line therapy for patients with ER+,PgR+, HER2 -metastatic breast cancer (MBC). Methods Patients with locally advanced or MBC who progress on ≥2 lines of prior therapy with ET as a single agent or in combination with CDK4/6 inhibitors, mTOR inhibitors and one line of chemotherapy in the metastatic setting are eligible. Other criteria include ECOG performance status ≤ 2, measurable disease per RECIST 1.1 criteria, adequate organ function, availability of an archived tumor biopsy block confirming the diagnosis of MBC, optional biopsy at disease progression on trial, and optional 18F-fluorofuranylnorprogesterone (18F-FFNP) PET/CT imaging. Ovarian suppression is allowed. Prior ET with tamoxifen or aromatase inhibitor therapy in the adjuvant or metastatic setting is allowed. Patients with prior exposure to fulvestrant, antiprogestins, or CDK inhibitors in the adjuvant setting are ineligible. Following consent, all subjects will receive fulvestrant at the recommended dosing schedule plus onapristone 50 mg orally, twice daily, until disease progression, unacceptable toxicity, or discontinuation for any other reason. Using the Simon Two-Stage design, a total of 39 patients will be enrolled over two years from 6-8 sites within Wisconsin Oncology Network (WON). In the first stage of the trial, 21 subjects will be enrolled; if ≥2 responses are observed, then 18 additional subjects will be enrolled in the second stage. This design yields a one-sided type I error rate of 5% if the ORR is 7% and power of 80% when the combination's true response rate is 20%. The primary objective is to evaluate the objective response rate; secondary objectives include safety and tolerability, progression-free survival, disease control rate, and duration of response. Other correlates include optional functional imaging of PgR binding with 18F-FFNP PET/CT and biomarker analysis (ER, total PgR, HER2, Ki67, CD24, CD44, LDH1, KLF4, CK 5/6, PhosphoSer294-PgR on tissue samples, ESR1 mutations, and circulating tumor DNA analysis). The study was approved in January 2021, and enrollment is active at the time of this submission. Citation Format: Sailaja Kamaraju, Amy Fowler, Chung Yee Cheng, Lubna N Chaudhary, John Burfeind, Janet Retseck, Amye J Tevaarwerk, Mark Burkard, Elisavet Paplomata, Amanda M Parkes, Julie M Jorns, Sergey Tarima, Douglas Yee, Hallgeir Rui, Carol Lange, Tarek Sahmoud, Kari B Wisinski. The SMILE study: A phase 2 trial of onapristone in combination with fulvestrant for patients with ER+ and HER2- metastatic breast cancer after progression on endocrine therapy and CDK4/6 inhibitors [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr OT2-16-01.

Abstract OT1-18-05: A multicenter, open-label, phase 2 study of Imprime PGG and pembrolizumab in patients with metastatic breast cancer who have progressed through prior hormonal therapy

Abstract Immune checkpoint inhibitors (ICI) have shown limited response in breast cancers, especially the hormone receptor (HR) positive/human epidermal growth factor receptor 2-negative (Her2-) subtype that is considered to be ‘immunologically cold’ in comparison to the TNBC and Her2+ subtypes. Results from Keynote-028 study showed a ORR of 12% to anti-PD1 antibody, pembrolizumab (KEYTRUDA®; PEM) in previously treated HR+/HER2-/programmed death ligand 1-positive (PD-L1-positive) advanced breast cancer patients. With limited options available for these patients, there is a significant unmet need to expand the clinical benefit from ICI to increased numbers of patients. Imprime PGG (Imprime) is a novel beta glucan acting as a pathogen-associated molecular pattern (PAMP) that drives a cascade of immune activating events. Imprime treatment repolarizes the immunosuppressive microenvironment, activates the maturation of antigen presenting cells, and has significantly enhanced the efficacy of ICI therapy in several preclinical tumor models. Imprime has been studied in combination with PEM, in metastatic TNBC and advanced melanoma in a recently completed Ph2 trial (IMPRIME 1) where in TNBC pts the objective response rate (ORR) = 15.9%, disease control rate (DCR) = 54.5%, median duration of response (mDoR)=12.7mo, median progression free survival (mPFS) =2.86 mo, 12-month overall survival (OS) rate = 57.6%, and median OS= 16.4 months. Clinical benefit in IMPRIME 1 was particularly evident in a subset of pts, mTNBC “converters” (12/44 total TNBC pts) who had originally been diagnosed with ER/PR+ disease and progressed through endocrine therapies +/- CDK4/6 inhibitors. In these 12 TNBC converters, the ORR = 50%, DCR = 83%, mDoR=11.2, mPFS=5.6 mo, 12-month OS rate=64.8%, and mOS= 17.4 months. Imprime is now being explored in pts with hormone-resistant metastatic breast cancer (MBC) in combination with PEM. This is a phase 2, Simon’s 2-Stage study of pts with MBC who have progressed through prior hormonal therapy with at least one CDK4/6 inhibitor. All pts will receive Imprime 4 mg/kg/wk + PEM 200 mg Q3wk. A total of 23 pts will be enrolled into Stage 1. If ≥4 pts in Stage 1 have an objective response after 12 wks of treatment, the study will proceed into Stage 2. Twenty-four (24) pts will be enrolled in Stage 2 for a total combined population of 47 pts. Rejection of the null hypothesis will require documenting at least 10 objective responses in the total population. Main eligibility criteria include a diagnosis of MBC having failed prior hormonal therapy with at least one CDK4/6 inhibitor, ≤1 prior line of chemotherapy, serum ABA level of ≥20 µg/mL, and no prior ICI exposure. The primary endpoint is ORR (per RECIST v1.1); secondary endpoints are mPFS, PFS, mOS, OS, DCR, DoR, and safety. Exploratory objectives will assess the impact of the treatment combination on immune activating events in peripheral blood and at the tumor level, and correlate changes in PD-L1 status, the tumor microenvironment, and serum ABA with response. Point estimates with the exact 95% confidence intervals of ORR and DCR will be computed. For mPFS, PFS, mOS, OS, and DoR, medians, first, and third quartiles with 95% confidence intervals (CIs) will be estimated using Kaplan-Meier method. Safety parameters will be summarized. The trial is sponsored by HiberCell, Inc. in collaboration with Merck Sharp &amp; Dohme Corp., a subsidiary of Merck &amp; Co., Inc., Kenilworth, NJ, USA. Approximately 25 US sites will participate in the study. For information, contact Nick Niles nniles@hibercell.com. 612.230.5846. Citation Format: Alison Stopeck, Michele Gargano, Nandita Bose, Nick Niles, Michael Chisamore, Jose Iglesias. A multicenter, open-label, phase 2 study of Imprime PGG and pembrolizumab in patients with metastatic breast cancer who have progressed through prior hormonal therapy [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr OT1-18-05.

Abstract P4-07-05: Tumor mutational profiles of extreme long-term survivors with metastatic breast cancer

Abstract Background: Extreme population sampling can discover genomic characteristics with a high likelihood of functional significance. Here, we focus on people who live for many years or decades with metastatic breast cancer (MBC). Identification of genetic markers characteristic of this population may allow long-term survival to be predicted and enable de-escalation of treatment and improved care for this subgroup of breast cancer patients. . Methods: We identified women who have MBC and have lived greater than 10 years (HR+ breast cancer) or greater than 5 years (HR- breast cancer) from initial diagnosis. A total of 14 had archived FFPE metastatic tumor specimens and matched blood available for analysis. We performed whole-exome sequencing (WES) on FFPE tumor specimens (somatic) and blood samples (germline) pairs of 14 long term survivor patients. We used Illumina DRAGEN pipeline for the read alignment and base quality calibration and GATK MuTect2 pipeline for the somatic short variant identification. Common variants were filtered using 1000 Genomes Project, Exome Sequencing Project and gnomAD and annotated using Funcotator of the GATK pipeline. Results: A cohort of 53 patients, who met criteria, with biopsy proven MBC and long survival were identified in our institution. Among them, 14 patients had sufficient archived tumor for analysis, consisting of 7 HR+/HER2-, 5 HR+/HER2+, 1 HR+/HER2- and 1 TNBC specimens. Histological type was ductal in 9 patients and lobular in 4 patients. The median age of MBC diagnosis was 53 years with 11 patients diagnosed between ages 35-64 and 3 patients diagnosed after age 65. At the time of study, 13 of these 14 patients are still living. Median time to metastasis after diagnosis was 10.2 years with metastasis occurring in less than 1 year in 2 patients, less than 5 years in 10 patients and greater than 5 years in 2 patients. Metastases to bone were present in 9 patients, to visceral organs in 8 patients and to local and regional lymph nodes in 8 patients. The most common somatic variants identified were in PIK3CA, ARID1A, and TP53. When compared with prior analyses of MBC (INSERM, MBC Project), we found that ARID1A mutations were more commonly found, whereas PTEN and ESR1 mutations were never identified, suggesting a somatic mutational profile characteristic of extreme survivors. ARID1A mutations (2 nonsense - p.R1505* and p.Q944*, 1 missense - p.L1496V, 1 frameshift - p.P729fs) occurred in 4 patients, all with ER/PR+ and all HER2- breast cancer. Median survival to date since diagnosis was 30.1 years (range 21.4-39.0). Median survival to date after metastasis was 14.9 years (range 2.7-35.0). PIK3CA mutations (5 missense - p.H1047R x2, E545K, H1047L, E545K) occurred in 5 patients, all with ER/PR+ and 2 with HER2+ breast cancer. Median survival to date since diagnosis was 23.5 years (range 20.1-39.0). Median survival to date after metastasis was 15.97 years (range 3.4-35.0). TP53 mutations (1 nonsense - p.E285*, 1 missense - p.E285K, 1 frameshift - p.N200fs) occurred in 3 patients, all with ER/PR+ and 2 with HER2+ breast cancer. Median survival to date since diagnosis was 21.7 years (range 21.7-36.2). Median survival after metastasis was 16.0 years (range 2.7-21.4). Conclusions: ARID1A mutations are overrepresented and PTEN and ESR1 are underrepresented in metastatic tumors in extreme long-term survivors with MBC. Further analyses will determine if ARID1A mutations are present at tumor inception or are acquired in metastases in this cohort with indolent disease. Additionally, it is possible that germline genomic profiles may be relevant to long-term survival. Given the variability in this cohort, a larger sample of extreme survivors will be necessary to identify characteristic genetic profiles. Citation Format: Yang Hu, Junha Shin, Sushmita Roy, Mark E Burkard. Tumor mutational profiles of extreme long-term survivors with metastatic breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P4-07-05.

Abstract P2-08-04: Progressive metastatic breast cancer with no detectable circulating tumor DNA: Evaluating limitations of this highly sensitive tool

Abstract Background: Circulating tumor DNA (ctDNA) is being evaluated as a tool to monitor disease and guide therapy escalation and de-escalation in advanced breast cancer. The patient, disease, and treatment characteristics that influence whether tumor DNA is isolated and sequenced from the bloodstream are not well understood. We aimed to describe patient and disease characteristics of cases with undetectable ctDNA levels despite progressive metastatic breast cancer (MBC). Methods: We retrospectively identified patients (pts) with MBC who had ctDNA evaluation by the Guardant 360 assay (Redwood City, CA) as part of their routine care from 2015-2020. We correlated the ctDNA assay with the disease status at collection. We identified the patient cohort with no detectable ctDNA despite evaluation at the time of progressive disease but prior to the initiation of a new therapy (ND ctDNA/PD) and compared the clinical, pathologic, and molecular features of this group to those with detected ctDNA. Differences were tested by two proportion z-tests. Results: Of 1151 ctDNA samples collected among 473 pts with MBC, 87 (7.5%) samples had no detectable (ND) ctDNA. 54 of 87 samples with ND ctDNA were collected at a time of stable or responding disease or after a new line of therapy was started, leaving only 33 ctDNA evaluations (2.8%) among 30 pts with ND ctDNA despite collection at the time of PD prior to new therapy. Among this group there were 14 pts (47%) with HR+ HER-, 11 pts (37%) with HER2+, and 5 pts (17%) with TN MBC. This compared to 254 pts (60%) with HR+ HER2-, 82 pts (19%) with HER2+, and 85 pts (20%) with TN MBC and detectable ctDNA. HER2-positive MBC was more common in the ND ctDNA/PD group than detectable ctDNA group (p-0.02). In the ND ctDNA/PD group, the median time from MBC diagnosis to ctDNA evaluation was 7 months and pts had received a median of 0.5 prior lines of therapy for MBC. Four pts (13%) had lobular breast cancer, 24 pts (80%) had recurrent disease, 14 pts (47%) had visceral metastases, and 12 pts (40%) had oligometastatic disease. Sites of metastases at the time of ND ctDNA/PD were bone n=16 (53%), lung n=7 (23%), liver n=6 (20%), lymph node n=11 (37%), skin and soft tissue n=5 (17%), and CNS n=5 (17%). When compared to those with detectable ctDNA these differences in characteristics were not statistically significant, although numerically pts with ND ctDNA had more CNS disease (17% vs 10%) and less liver disease (20% vs 32%). At the time of ND ctDNA, the site of progression was bone n=14 (47%), CNS n=5 (17%), lymph node n=9 (30%), lung n=7 (23%), and liver n=5 (17%). There was a single site of progression in 20 pts (67%). 16 of 30 pts had repeat ctDNA analysis of which 9 pts had subsequent detectable ctDNA with a median VAF of 0.3%, a median of 1 alteration per sample, and oncogenic or likely oncogenic alterations in TP53 in 3 pts and BRCA1, CCNE1, CDH1, and PIK3CA in 1 pt each. Seven had tissue NGS, all of which showed multiple oncogenic alterations. The remaining 22 pts with ND ctDNA but no PD were responding to therapy based on imaging or had already started a new therapy since the last progression. This group also had a high proportion of HER2+ MBC (n=7, 32%) and low proportion with visceral disease (n=6, 27%) Conclusions: Although ctDNA is a highly sensitive tool to detect active MBC (&amp;lt;3% of samples had ND ctDNA), its sensitivity may be less in some clinical scenarios, including HER2+ MBC, when there are limited sites of progression, or when there is isolated CNS progression. Citation Format: Ami N Shah, Lorenzo Gerratana, Shruti Chandra, Dhruvika Mukhija, Neelima Katam, Anthony K Kang, Andrew A Davis, Millen Srivastava, Saya Jacob, Paolo D'Amico, Qiang Zhang, Carolina Reduzzi, Michael Gurley, Firas Wehbe, William J Gradishar, Amir Behdad, Massimo Cristofanilli. Progressive metastatic breast cancer with no detectable circulating tumor DNA: Evaluating limitations of this highly sensitive tool [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-08-04.

Clinical features, treatment, and prognosis of 16 breast cancer patients with ocular metastases.

The incidence of ocular metastases in patients with disseminated breast cancer is increasing. This study aimed to investigate the clinical features, treatment, and prognosis of breast cancer patients with ocular metastases. For this purpose, a total of 16 patients were diagnosed with ocular metastases. Demographic, treatment, and other clinical data were obtained from patients' charts. The estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2) statuses of the patients were obtained from the histopathologic reports. Demographic features were analyzed through descriptive statistics, and the Kaplan-Meier method was used for survival analysis. The results showed that among the 16 patients (median age: 41 years), 10 had ER-positive, 8 had PR-positive, and 3 had HER2-positive disease. The choroid was the most commonly involved structure (n = 8). Nine (56%) patients had blurred vision. Treatments for these patients included systemic therapy (six patients), radiotherapy (three patients), and combined therapy (seven patients). The median time from the diagnosis of breast cancer to the diagnosis of ocular metastasis was 52.9 months, and the median time from the diagnosis of metastatic breast cancer at any other site to the diagnosis of ocular metastasis was 21.3 months. The median overall survival (OS) was 136.5 months (95% confidence interval, 40.6-232.4 months), and the median survival duration after ocular metastasis was 32.4 months (95% confidence interval, 20.1-44.7 months). The OS of patients with unilateral eye involvement and bilateral eye involvement did not differ significantly (P = 0.573), nor did the OS of those diagnosed before 2000 and in 2000 or later (P = 0.409). In general, a breast cancer patient with ocular metastasis can have a good prognosis after therapy. However, large-scale clinical studies are needed to confirm our findings.

Unmet needs and problems related to employment and working as reported by survivors with metastatic breast cancer.

By 2020, the US population living with metastatic breast cancer (MBC) has exceeded 165,000. A knowledge gap exists regarding the factors affecting work ability for these individuals. We sought to characterize the work status, importance of work, and work-related information needs for women living with MBC. We conducted an online survey using an MBC listserv and clinic flyers in 2014-2015. Respondents working at the time of MBC diagnosis were divided into "stably-working" and "no-longer-working" based on employment status at the time of survey. Comparisons were made with chi-square or two-tailed t test. Respondents (n = 133) were predominantly non-Hispanic White (93.2%); 72 were stably-working, while 61 reported no-longer-working. Those no-longer-working were older (54.0 vs 49.5years old, p < 0.01, Cohen's d = 0.55), further from initial diagnosis of MBC (4.6 vs 3.3years, p < 0.01, Cohen's d = 0.36), and reported high rates of life interference due to MBC (n = 51, 83.6% vs n = 39, 54.2%, p < 0.01, Cramer's V = 0.32). Stably-working respondents considered work to be important (n = 58, 80.5% vs n = 18, 29.5%, p < 0.01, Cramer's V = 0.57); the top reasons cited were financial and/or insurance (80.4%), importance of staying busy (67.9%), and desire to support themselves and family (64.3%). The stably-working respondents more often valued information on how to talk with employers or co-workers about diagnosis (n = 38, 57.6% vs n = 16, 27.1%; p < 0.01), legal rights in workplace (n = 43, 65.2% vs n = 22, 36.7%; p < 0.01), when to think about stopping work (n = 45, 68.2% vs n = 18, 30%; p < 0.01), and applying for disability (n = 42, 63.6% vs n = 26, 42.6%; p < 0.05), when compared to no-longer-working. The decision to stop working may represent a subsequent event driven by cancer progression. This research highlights the ongoing need of information targeting MBC to facilitate the management of employment and financial issues early in the MBC trajectory.

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.