Use of comprehensive next-generation sequencing to identify pathogenic germline variants with therapeutic relevance in metastatic breast cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 10527-10527
Author(s):  
Nicole Margo Grogan ◽  
Yi-Mi Wu ◽  
Dan R. Robinson ◽  
James M. Rae ◽  
Norah Lynn Henry ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Genetic Testing ◽  
Early Stage ◽  
Metastatic Breast ◽  
Exome Capture ◽  
Sample Collection ◽  
Direct Role ◽  
Early Stage Disease ◽  
Therapeutic Relevance

10527 Background: Among patients with early-stage breast cancer, approximately 6-10% have a pathogenic germline variant (PGV) conferring inherited cancer predisposition. In contrast, few studies have explored the frequency and types of PGVs identified in patients with metastatic breast cancer (MBC); therefore, additional data is needed. Methods: From 2011-2020, 278 patients with MBC underwent fresh tumor biopsy and blood sample collection for paired tumor/normal DNA (targeted exome capture with analysis of 1700 genes) and RNA (tumor transcriptome) sequencing through the Michigan Oncology Sequencing (Mi-ONCOSEQ) program. Somatic and germline alterations were annotated and classified according to degree of clinical actionability with results returned to treating oncologists. Retrospective chart review was performed to determine if: 1) a PGV was identified prior to Mi-ONCOSEQ testing, 2) patients met National Comprehensive Cancer Network (NCCN) guideline criteria for genetic testing on the basis of personal or family cancer history and 3) patients received subsequent therapy informed by a PGV. Results: Forty-eight of the 278 patients (17.3%) had at least one PGV identified, with a total of 50 PGVs identified in this cohort. Only twelve of these PGVs (24%) had been identified prior to Mi-ONCOSEQ testing. The most frequent PGVs identified were in CHEK 2 (n = 9, 18%), MUTYH (n = 6, 12%), BRCA 1 (n = 5, 10%), BRCA2 (n = 5, 10%), ATM (n = 4, 8%) and PALB2 (n = 4, 8%). Somatic loss of heterozygosity events (LOH) occurred in 30 of the 50 cases with PGVs identified (60%). LOH events were observed in 83.3% of BRCA1, BRCA2, ATM and PALB2 PGVs, but were less frequently observed with CHEK2 (33.3%) and MUTYH (66.7%). Two hundred sixteen out of 278 patients (77.7%) in this cohort met NCCN criteria for genetic testing, although six patients with a PGV identified (CHEK2: n = 5; MUTYH: n = 1) did not meet NCCN criteria. Twenty-nine PGVs identified (58%) had potential therapeutic relevance and 11 patients (22.9%) received targeted therapy based on the PGV. Conclusions: The frequency of PGVs identified in this cohort is nearly double the frequency reported for patients with early-stage disease, suggesting that certain PGVs may confer worse prognosis. CHEK2, the most frequently identified PGV, was less likely to have an identifiable LOH event. The direct role of CHEK2 PGVs in tumor pathogenesis is uncertain, but other mechanisms of silencing the wild type allele must be considered. Despite the majority of patients meeting NCCN criteria for genetic testing, those with PGVs in CHEK2 were less reliably identified by this mechanism. The majority of PGVs identified were of potential therapeutic relevance, supporting the recommendation for genetic testing in all patients with MBC.

scholarly journals Among the Metavivors: Social Media and Illness Narratives of Stage IV Breast Cancer Patients

2018 ◽  
Vol 4 (1) ◽  
pp. 1-24
Author(s):  
Susan Jacobson
Keyword(s):  
Breast Cancer ◽  
Social Media ◽  
Metastatic Breast Cancer ◽  
Civil Rights ◽  
Early Stage ◽  
Metastatic Breast ◽  
Stage Iv ◽  
Breast Cancer Patients ◽  
Early Stage Disease ◽  
Stage Iv Breast Cancer

Dominant breast cancer narratives equate early detection and screening with “cure,” advocate for “awareness,” and identify women who undergo treatment for early stage disease as “survivors.” Left out of these narratives are the “metavivors”: women and men diagnosed with “incurable” metastatic breast cancer, also known as Stage IV. This article uses case studies to profile four women living with metastatic breast cancer who turn to social media to tell their stories: Sally, a former civil rights attorney turned breast cancer activist, who uses social media platforms to organize and mobilize Stage IV patients to advocate on their own behalf; Jane, who plows through databases of dense medical research to find treatments to save her own life; Jenny, a young mother dying of metastatic breast cancer who shares her experiences on a YouTube channel; and Grace, who participates in an early-stage clinical trial that she believes “cured” her, a term eschewed by both the medical establishment and fellow metavivors.

scholarly journals Among the Metavivors: Social Media and Illness Narratives of Stage IV Breast Cancer Patients

2018 ◽  
Vol 4 (1) ◽  
pp. 1-24
Author(s):  
Susan Jacobson
Keyword(s):  
Breast Cancer ◽  
Social Media ◽  
Metastatic Breast Cancer ◽  
Civil Rights ◽  
Early Stage ◽  
Metastatic Breast ◽  
Stage Iv ◽  
Breast Cancer Patients ◽  
Early Stage Disease ◽  
Stage Iv Breast Cancer

Dominant breast cancer narratives equate early detection and screening with “cure,” advocate for “awareness,” and identify women who undergo treatment for early stage disease as “survivors.” Left out of these narratives are the “metavivors”: women and men diagnosed with “incurable” metastatic breast cancer, also known as Stage IV. This article uses case studies to profile four women living with metastatic breast cancer who turn to social media to tell their stories: Sally, a former civil rights attorney turned breast cancer activist, who uses social media platforms to organize and mobilize Stage IV patients to advocate on their own behalf; Jane, who plows through databases of dense medical research to find treatments to save her own life; Jenny, a young mother dying of metastatic breast cancer who shares her experiences on a YouTube channel; and Grace, who participates in an early-stage clinical trial that she believes “cured” her, a term eschewed by both the medical establishment and fellow metavivors.

HTAPP_Acquisition and allocation of fresh metastatic breast cancer samples v1

2021 ◽  
Author(s):  
Karla Helvie ◽  
Laura DelloStritto ◽  
Lori Marini ◽  
Nelly Oliver ◽  
Miraj Patel ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Single Cell ◽  
Rna Sequencing ◽  
Cancer Genomics ◽  
Metastatic Breast ◽  
Standard Operating Procedure ◽  
Quality Data ◽  
Sample Collection ◽  
Spatial Profiling

This standard operating procedure was established by the Center for Cancer Genomics at Dana-Farber Cancer Institute, the Brigham and Women's Hospital and the Klarman Cell Observatory at the Broad Institute, to standardize the collection of fresh metastatic breast cancer biopsies and their allocation to various bulk and single cell assays, including whole exome and bulk RNA-sequencing, single-cell RNA sequencing, and spatial profiling of RNA and protein. The use of a well defined workflow has allowed us to generate high quality data from these different assays, by implementing efficient modes of communication, minimizing the time elapsed from sample collection to preservation or processing, and ensuring optimal transportation conditions. Visual Abstract

Patient preferences for treatment of metastatic breast cancer: a study of women with early-stage breast cancer.

1995 ◽  
Vol 13 (4) ◽  
pp. 858-868 ◽  
Author(s):  
R P McQuellon ◽  
H B Muss ◽  
S L Hoffman ◽  
G Russell ◽  
B Craven ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Quality Of Life ◽  
Metastatic Breast Cancer ◽  
Life Expectancy ◽  
Metastatic Disease ◽  
Patient Preferences ◽  
Early Stage ◽  
Metastatic Breast ◽  
High Dose

PURPOSE The purpose of this study was to elicit preferences for the treatment of metastatic breast cancer in women with early-stage breast cancer who were given hypothetical treatment scenarios. We predicted that quality of life, demographic, and treatment variables would have an impact on patient preferences. PATIENTS AND METHODS One hundred fifteen patients with stage 1-IIIA breast cancer were interviewed. All patients had either mastectomy or lumpectomy plus radiotherapy as primary treatment. Sixty-seven (58%) had prior adjuvant chemotherapy. Patients were given four clinical scenarios that described a woman with metastatic breast cancer who was stated to have a life expectancy of 18 months. Side effects of the treatment options were systematically varied from low (hormonal therapy) to life-threatening (high-dose experimental therapy) and were consistent with common clinical situations. Patients were asked to select which treatment, with its associated toxicity, they would accept and prefer for a 50% chance of specified increments in life expectancy, ie, 5 years, 18 months, 1 year, 6 months, 1 month, and 1 week. RESULTS Quality of life at the time of interview, previous chemotherapy treatment, and degree of difficulty of previous treatments did not predict patient preferences. The greater the toxicity potential of the treatment, the less likely patients were to accept the treatment, although approximately 15% of patients would prefer high-risk treatment for as little as 1 month of added life expectancy. Between 34% and 82% of patients would prefer different therapies for a 6-month addition to life expectancy, whereas almost all patients would accept treatment for a 5-year increase in length of survival. Younger patients were more willing to assume the risks of treatment for a small increase in life expectancy. Of note, between 54% and 78% of patients would elect to start the different treatments even without symptoms related to metastatic disease. Moreover, 76% of patients would prefer standard treatment or an experimental agent to reduce symptoms or pain, even if such treatment did not prolong life. Additionally, only 10% of patients would allow randomization to a clinical trial comparing high-dose with standard chemotherapy. Participation in the study was not distressing to most patients. CONCLUSION Patients showed clear preferences for specific treatments for metastatic disease when given hypothetical scenarios. There was a wide range of patient preferences for treatment based on risk-benefit assessment, but a substantial percentage of patients would accept the risk of major toxicity for minimal increase in overall survival.

What is the evidence for rechallenging with anthracyclines or taxanes in metastatic breast cancer? A review of the data

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 1072-1072
Author(s):  
J. Krell ◽  
C. Harper-Wynne ◽  
D. Miles ◽  
V. Misra ◽  
S. Cleator ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Early Stage ◽  
Safety Data ◽  
Metastatic Breast ◽  
Evidence Base ◽  
Current Evidence ◽  
Optimal Sequence ◽  
Pubmed Database ◽  
Current Evidence Base

1072 Background: Anthracyclines and taxanes are widely used in the adjuvant setting for high risk, early stage breast cancer. This raises the issue of what is the optimal therapy for those patients who relapse, and what the potential role, if any, there is for rechallenge with these agents. The current evidence base for rechallenging with anthracyclines/anthracediones and taxanes in metastatic breast cancer (MBC) is examined in this study. Methods: Medline/Pubmed database searches were performed upto October 2008 to identify studies in which patients (pts) were rechallenged with anthracyclines/anthracediones or taxanes in MBC. Results: The efficacy data, as well as the safety data relating to neurotoxicity and cardiotoxicity from these studies, are summarized in the Table. Twenty-seven studies were identified (20=anthracycline/anthracedione, 7= taxane) of which only two were prospective studies. Both were small (n= 74 & 51) and related to anthracycline rechallenging. Conclusions: Evidence exists to support rechallenging with anthracyclines and taxanes. However, there are few prospective data on reexposure to taxanes and no data comparing anthracyclines versus taxanes following adjuvant exposure to both agents, supporting the need for clinical trials in this area. Such trials should ideally incorporate a cross-over design at treatment failure, which would shed light on the optimal sequence in which these agents should be administered. [Table: see text] No significant financial relationships to disclose.

A randomised phase 2 study of 3 weekly cabazitaxel vs weekly paclitaxel chemotherapy in the first-line treatment of HER2 negative metastatic breast cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. TPS1122-TPS1122
Author(s):  
Amit Bahl ◽  
Jeremy Braybrooke
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Metastatic Breast Cancer ◽  
Metastatic Breast ◽  
Phase 2 ◽  
First Line ◽  
Phase 3 ◽  
Early Stage Disease ◽  
Phase 2 Study ◽  
Her 2

TPS1122 Background: Breast cancer (BC) represents 25% of all cancers in women. Whilst the majority have early stage disease approximately 30% will develop metastatic breast cancer (MBC). In HER2 negative MBC, palliative chemotherapy is one of the main treatment options. It remains to be seen whether the use of adjuvant taxane chemotherapy leads to an increase in taxane resistance at the onset of MBC, although for patients with a relatively short disease free interval this may be the case. Cabazitaxel (CBZ) is a novel taxoid selected for development from preclinical evidence in cell lines resistant to docetaxel and paclitaxel including activity in a HER-2 positive BC tumour xenograft, with innate resistance to docetaxel. Clinically CBZ is licensed for metastatic castration-resistant prostate cancer following progression during or after docetaxel chemotherapy. A phase 3 RCT in this patient group showed a 3 month overall survival benefit for patients receiving CBZ and prednisolone compared with mitoxantrone and prednisolone. Methods: CONCEPT is an open label randomised phase 2 trial of first line chemotherapy in patients with HER-2 negative MBC where paclitaxel would be considered the standard treatment. Patients are randomised to cabazitaxel 25 mg/m2 every 21 days for 6 cycles or paclitaxel 80 mg/m2 weekly for 18 weeks. Eligibility includes patients who are PS 0 or 1 who may have received prior docetaxel in the adjuvant setting or be taxane-naïve. The primary endpoint is progression free survival (PFS), defined as the time between the date of randomisation and progression (according to RECIST version 1.1) or death from any cause. Secondary end-points include safety, overall survival and assessment of quality of life factors by FACT-B and EQ-5D-5L. For the current phase 2 study 90 patients will be recruited, with a 1:1 randomisation, proceeding to phase 3 of 160 patients, if the interim analysis does not show futility. To date 38 patients have been recruited from 10 centres. The IDMC met in Oct 2016 and recommended the study continue recruitment.

scholarly journals Clinical implication of changes in body composition and weight in patients with early-stage and metastatic breast cancer

2018 ◽  
Vol 129 ◽  
pp. 54-66 ◽  
Author(s):  
Ilaria Trestini ◽  
Luisa Carbognin ◽  
Sara Monteverdi ◽  
Sara Zanelli ◽  
Alessandro De Toma ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Body Composition ◽  
Metastatic Breast Cancer ◽  
Clinical Implication ◽  
Early Stage ◽  
Metastatic Breast

scholarly journals It doesn’t make sense, but we do: framing disease in an online metastatic breast cancer support community

2019 ◽  
Vol 3 (2) ◽  
Author(s):  
Ariane B. Anderson
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Late Stage ◽  
Illness Perceptions ◽  
Early Stage ◽  
Metastatic Breast ◽  
Peer To Peer ◽  
Online Discussions ◽  
Breast Cancer Patients ◽  
Cancer Support

Using Weick’s sensemaking as a conceptual framework to investigate online discussions between members of a Facebook group of metastatic breast cancer patients, and using thematic analysis to examine textual threads between group members, this research examines participants’ framing of cancer survivorship. Participants in peer-to-peer disease support groups, which are not led by medical experts, communicate differently among themselves in order to cope with chronic and terminal illness. Perceptions of survivorship of late stage patients versus early stage patients differ for a variety of reasons, with late stage patients understanding their illness trajectory more often as chronic and declining. This analysis identified three properties of sensemaking used by members to manage their disease: identity, retrospective, and enactment. Results indicate that peer-to-peer online support group communication engenders distinct framing logics that members draw upon for group support as they manage a chronic and terminal disease.

Strategic integration of genetic testing and counseling in patients with breast cancer in an oncology care model (OCM) multisite community-based practice.

2021 ◽  
Vol 39 (28_suppl) ◽  
pp. 231-231
Author(s):  
Molly Mendenhall ◽  
Andrew Guinigundo ◽  
Elizabeth Burneka ◽  
Hannah Kolish ◽  
Sarah Mancini ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Genetic Testing ◽  
Cancer Patients ◽  
Metastatic Breast ◽  
Breast Cancer Patients ◽  
Brca Testing ◽  
Provider Education ◽  
Cancer Genetic ◽  
Nccn Guidelines

231 Background: Despite consensus driven recommendations, data suggests significant non-compliance in breast cancer genetic screening and testing. In the US nearly 300,000 patients are diagnosed with breast cancer annually, of whom approximately one-third are estimated to be BRCA-testing eligible by NCCN guidelines. Of this cohort of patients eligible for testing, it is estimated that again only one-third are ultimately being referred for genetic counseling and testing. Ideally, every patient who is guideline-eligible for testing should be tested, if they consent. The purpose of this project was to integrate and universally apply NCCN genetic breast cancer testing guidelines, building off current OCM processes, to all new breast and/or metastatic breast cancer patients within a large multi-site community oncology practice setting. Methods: Providers utilized directed EHR templates in the setting of an initial diagnosis visit or a treatment planning “OCM visit”. Discreet data fields were created in the EHR to streamline, prompt, and automate this process. Following provider education and uniform physician pre-approval, appropriate patients were reflexively referred to the genetics team for further evaluation and BRCA testing. Adherence to the plan was maintained and measured using data analytic reports and chart audits. Results: OHC’s pre-project eligible patient testing rate (2018) was found to be 20%. Between 1/2019 to 1/2021 1,203 new breast and/or metastatic breast cancer patients were seen and deemed eligible for inclusion, fully 1,200 were screened using NCCN guidelines (99%). Of those screened, 631 patients met the NCCN testing criteria (52.5%). 585 of the 631 were referred to a genetic specialist (92.7%), of those 449 patients were tested (76.7%), 136 patients refused (30%). 22 patients were found to have a BRCA 1 or 2 mutation (5.3%). An additional “halo” effect on other cancer diagnoses was also observed. Screening newly diagnosed breast cancer and metastatic breast cancer patients resulted in a 163% increase in genetic referrals aside from those with breast cancer. Conclusions: Our results suggest a significant overall improvement in breast cancer genetic testing rates. Implemented methods of provider education and awareness of NCCN guidelines imbedded within provider notes, together with discreet data fields in the EHR, proved to be highly effective at screening appropriate patients and ordering subsequent genetic testing; ensuring nearly 100% compliance with current NCCN guidelines for genetic testing. The workflow also resulted in a favorable increase in genetic referrals and testing across other cancers. The patient refusal rate for testing merits further investigation. This structured workflow with reflex genetics referral was effective, scalable, and financially viable to overall genetic and practice growth.

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