scholarly journals Landscape of HER2-low metastatic breast cancer (MBC): results from the Austrian AGMT_MBC-Registry

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Simon Peter Gampenrieder ◽  
Gabriel Rinnerthaler ◽  
Christoph Tinchon ◽  
Andreas Petzer ◽  
Marija Balic ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Survival Data ◽  
Triple Negative ◽  
Cox Regression ◽  
Tumor Therapy ◽  
Multivariable Analysis ◽  
Metastatic Breast ◽  
World Population ◽  
Her2 Expression

Abstract Background About 50% of all primary breast cancers show a low-level expression of HER2 (HER2-low), defined as immunohistochemically 1+ or 2+ and lack of HER2 gene amplification measured by in situ hybridization. This low HER2 expression is a promising new target for antibody–drug conjugates (ADCs) currently under investigation. Until now, little is known about the frequency and the prognostic value of low HER2-expression in metastatic breast cancer (MBC). Patients and methods The MBC-Registry of the Austrian Study Group of Medical Tumor Therapy (AGMT) is a multicenter nationwide ongoing registry for MBC patients in Austria. Unadjusted, univariate survival probabilities of progression-free survival (PFS) and overall survival (OS) were calculated by the Kaplan–Meier method and compared by the log-rank test. Multivariable adjusted hazard ratios were estimated by Cox regression models. In this analysis, only patients with known HER2 status and available survival data were included. Results As of 11/15/2020, 1,973 patients were included in the AGMT-MBC-Registry. Out of 1,729 evaluable patients, 351 (20.3%) were HER2-positive, 608 (35.2%) were HER2-low and 770 (44.5%) were completely HER2-negative (HER2-0). Low HER2-expression was markedly more frequent in the hormone-receptor(HR)+ subgroup compared to the triple-negative subgroup (40% vs. 23%). In multivariable analysis, low HER2 expression did not significantly influence OS neither in the HR+ (HR 0.89; 95% CI 0.74–1.05; P = 0.171) nor in the triple-negative subgroup (HR 0.92; 95% CI 0.68–1.25; P = 0.585), when compared to completely HER2-negative disease. Similar results were observed when HER2 IHC 2+ patients were compared to IHC 1+ or 0 patients. Conclusion Low-HER2 expression did not have any impact on prognosis of metastatic breast cancer in this real-world population.

The association of HER2 low expression with the efficacy of CDK4/6 inhibitor in hormone receptor positive HER2 negative metastatic breast cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 1052-1052
Author(s):  
Kelvin K H Bao ◽  
Leone Sutanto ◽  
Shirley S W Tse ◽  
Ka Man Cheung ◽  
Jeffrey C H Chan
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Cox Regression ◽  
Endocrine Resistance ◽  
Metastatic Breast ◽  
Rank Test ◽  
Her2 Expression ◽  
Disease Extent ◽  
Potential Marker ◽  
Low Expression

1052 Background: Markers for the efficacy of CDK4/6 inhibitor in estrogen receptor (ER) positive, HER2 negative advanced breast cancer are limited. The bidirectional crosstalks that exist between ER and HER2 pathways contribute to endocrine resistance. We investigated the association between low levels of HER2 expression and the clinical outcome of patients with ER+ HER2- metastatic breast cancer (MBC) treated with CDK4/6 inhibitors. Methods: We identified consecutive patients with ER+ HER2- MBC who received CDK4/6 inhibitor plus either letrozole or fulvestrant between Mar 2017 - Jun 2020 from an institutional cancer registry. HER2-low expression was defined as IHC score 1+, or 2+ with a negative ISH. Progression-free survival (PFS) was defined as the time from the initiation of CDK4/6 inhibitor to the date of radiological or clinical progression, or death. The relationship between HER2 expression levels and PFS was evaluated using log-rank test and multivariable Cox regression modelling. Results: 106 women with MBC were eligible for analysis. Median age at treatment was 58 (23.0-91.4). The majority received palbociclib (84%) while the rest received ribociclib. CDK4/6 inhibitor was used as first-line treatment in 50.9% of cases. Most tumors were of ductal histology (83%) and progesterone receptor (PgR) positive (84.9%), and 22.6% of the patients had bone-only disease. 77.3% of cases were considered HER2-low expressing. HER2-low expression was associated with a significantly shorter PFS compared with HER2 IHC 0 counterpart (median, 8.9 vs 18.8 months, p= 0.014). In multivariate analysis, HER-2 low expression remained significantly associated with an inferior PFS (HR 1.96, 95%CI 1.03-3.75, p= 0.041) after adjusting for the line of treatment, PgR status and disease extent (bone only vs extra-osseous disease). Conclusions: In patients with ER+ HER2- MBC treated with CDK4/6 inhibitors, HER2-low expression was associated with an inferior PFS, and may serve as a potential marker candidate for CDK4/6 inhibitor efficacy. As novel anti-HER2 antibody-drug conjugates demonstrated efficacy in HER2-low expressing MBC, coupled with the emerging evidence for the combination of CDK4/6 inhibitors with anti-HER2 agents, this HER2-low expression subgroup warrants prospective evaluations in future trials.

scholarly journals Prognostic factors and survival outcomes according to tumor subtype in patients with breast cancer lung metastases

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e8298
Author(s):  
Siying Chen ◽  
Jin Yang ◽  
Yang Liu ◽  
Haisheng You ◽  
Yalin Dong ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Prognostic Factors ◽  
Metastatic Breast Cancer ◽  
Cancer Patients ◽  
Triple Negative ◽  
Cox Regression ◽  
Lung Metastases ◽  
Metastatic Breast ◽  
Breast Cancer Patients ◽  
Metastatic Sites

Background Reports on the incidence and prognoses of lung metastases when diagnosing breast cancer patients with different subtypes are limited. Our study investigated the effect of molecular sub-typing stratification on the prognoses of lung metastatic breast caner patients. Methods Patients with breast cancer and lung metastases were identified from Surveillance, Epidemiology and End Results population-based data between 2010 and 2015. Univariate and multivariate Cox regression analyses were performed to identify risk factors and prognoses, overall survival (OS) and breast cancer-specific survival for patients with breast cancer lung metastases. Results We identified 6,516 patients with lung metastatic breast cancer, representing 1.7% of the entire cohort and 30.4% of the subset with metastatic disease. This included 2,940 hormone receptor (HR)+/HER2− patients, 852 HR+/HER2+ patients, 547 HR−/HER2+ patients and 983 triple-negative patients. The median OS for all lung metastatic patients was 13 months. Multivariate analysis revealed that those lung metastatic breast cancer patients of older age (>80), black race, with poorly differentiated tumors, carcinoma histology, triple-negative subtype, more metastatic sites and no surgery, and no chemotherapy showed significantly poor survival, both overall and breast cancer-specific. Conclusions Our findings show that molecular sub-type and more metastatic sites might have significant influence on the incidence and prognosis of breast cancer lung metastases. We also identified several prognostic factors that could guide therapy selection in the treatment of lung metastatic patients.

Metastatic breast cancer treated by chemotherapy: Trends in survival and costs in two patient cohorts treated in 1994–1998 and 2003–2006

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 6552-6552
Author(s):  
G. Galy ◽  
S. Labidi ◽  
D. Perol ◽  
C. Carol ◽  
J. Guastalla ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Metastatic Breast Cancer ◽  
Survival Data ◽  
Cox Regression ◽  
Metastatic Breast ◽  
Chemotherapeutic Agents ◽  
Cox Regression Analysis ◽  
Her 2

6552 Background: Although new chemotherapy agents have been approved during the past decade for the treatment of metastatic breast cancer (MBC), it is unclear whether their use has changed the outcome of patients. This study assessed the clinical and economic impacts of these drugs. Methods: We undertook a retrospective study of women diagnosed with MBC during two periods of time, 1994–1998 and 2003–2006 and compared overall survival data between the two groups. Female patients with MBC were identified from the Centre Léon Bérard (Lyon, France) database. Tumor and treatment characteristics, costs of chemotherapy, and patient outcome were compared using the X2 test, the log rank test, and Cox regression analysis. Overall survival was calculated from the date of MBC diagnosis to the date of death or last follow-up. Chemotherapy-related costs were calculated according to the 2008 pricelist of French cancer centers. Results: A total of 301 MBC cases were identified. The median follow-up of living patients was 3.87 years. No survival difference was observed between the two periods, with a median overall survival of 2.76 years for the 1994–1998 cohort (149 patients) and 2.68 years for the 2003–2006 cohort (152 patients) (HR 1.04, 95%CI 0.70–1.55; p = 0.83). The median number of lines of chemotherapy was similar in the two groups (=3). The median cost of chemotherapy per MBC patient was 3 times higher in 2003–2006 (25,320 €) than in 1994–1998 (8,865 €; p < 0.001). In multivariate analysis, prognostic factors for overall survival were the number of metastatic sites (HR 2.06; p < 0.0001), bone metastases (HR 0.67; p = 0.007), and hormone receptors (HR 0.56; p = 0.002). Survival was identical in HER-2 positive and HER-2 negative patients (HR 0.99; p = 0.99). Conclusions: Despite the implementation of numerous novel chemotherapeutic agents, the overall survival of patients with metastatic breast cancer has not improved over the last decade on the scale of our institution, whereas the costs of chemotherapy have significantly increased. No significant financial relationships to disclose.

The contribution of clinical subtype to survival differences among patients with de novo and recurrent metastatic breast cancer (dMBC).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 1030-1030
Author(s):  
Danielle Marie File ◽  
Tomas Pascual ◽  
Allison Mary Deal ◽  
Amy Wheless ◽  
Elizabeth Claire Dees ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Triple Negative ◽  
De Novo ◽  
Multivariable Analysis ◽  
Metastatic Breast ◽  
Clinical Staging ◽  
Lower Grade ◽  
Significant Difference ◽  
Metastatic Sites

1030 Background: Patients with de novo metastatic breast cancer (dMBC) have superior median overall survival (mOS) compared to recurrent metastatic breast cancer (rMBC). Whether patient characteristics, prior treatment, tumor stage and innate biological differences contribute to this observation is unknown. Methods: Clinical and pathological data from patients diagnosed with MBC from 2011 to 2017 at the University of North Carolina (UNC) was obtained from the prospective UNC Metastatic Breast Cancer Clinical Database (223 dMBC, 607 rMBC). Only patients with known survival status were included. Subtype was determined by hormone receptor (HR) and HER2 staining of the primary tumor. Pathologic staging results were used when available, otherwise clinical staging was used. Patient and tumor characteristics were compared using chi-square testing, and survival outcomes by Cox proportional hazards modeling. Results: 26.9% of patients with MBC presented with dMBC, with significant variation in the ratio of dMBC to rMBC across subtypes. In particular, there were more cases of HER2+ dMBC than rMBC (26.9% vs 14.0%) and fewer cases of triple negative dMBC (20.6% vs 35.3%)(p-value < 0.001). Nearly half of all cases of HR-/HER2+ MBC were de novo (48.2%). dMBC was significantly associated with older age (p = 0.002), lower grade (p = 0.027), higher T and N stage (p < 0.001) and African American race (30% vs 22%, p = 0.022). There was no significant difference in proportion of patients with visceral metastatic disease or in number of metastatic sites at diagnosis. Median follow up was 39 months in both cohorts. mOS was 12 months greater in dMBC than rMBC (34m vs 22m, p < 0.001). These differences were significant across all subtypes except HR+/HER2+. The difference in mOS between dMBC and rMBC was greatest in the HR-/HER2+ subgroup (45m vs 15m, p = 0.006). In multivariable analysis, dMBC remained associated with improved survival (adjusted hazard ratio 0.59, p < 0.001) independent of variables including age, race, subtype, grade and number of metastatic sites at diagnosis. Conclusions: Patients with dMBC have significantly better prognosis than those with rMBC. This improved outcome is in part due to subtype variation, with more triple negative and fewer HER2+ tumors in rMBC, however these differences largely remained when stratified by subtype. In multivariable analysis, de novo presentation of MBC remained an independently significant contributor to longer survival. Further investigation should focus on biologic differences between dMBC and rMBC.

scholarly journals The Incidence of Brain Metastases Among Patients with Metastatic Breast Cancer: A Systematic Review and Meta-Analysis

2020 ◽  
Author(s):  
Markus Kuksis ◽  
Yizhuo Gao ◽  
William Tran ◽  
Christianne Hoey ◽  
Alex Kiss ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Systematic Review ◽  
Metastatic Breast Cancer ◽  
Brain Metastases ◽  
Triple Negative ◽  
Screening Program ◽  
Meta Analysis ◽  
Metastatic Breast ◽  
Breast Cancer Brain Metastasis

Abstract Background Patients with metastatic breast cancer (MBC) are living longer, but development of brain metastases often limits their survival. We conducted a systematic review and meta-analysis to determine the incidence of brain metastases in this patient population. Methods Articles published from January 2000 to January 2020 were compiled from four databases using search terms related to: breast cancer, brain metastasis, and incidence. The overall and per patient-year incidence of brain metastases were extracted from studies including patients with HER2+, triple negative, and hormone receptor (HR)+/HER2- MBC; pooled overall estimates for incidence were calculated using random effects models. Results 937 articles were compiled, and 25 were included in the meta-analysis. Incidence of brain metastases in patients with HER2+ MBC, triple negative MBC, and HR+/HER2- MBC was reported in 17, 6, and 4 studies, respectively. The pooled cumulative incidence of brain metastases was 31% for the HER2+ subgroup (median follow-up: 30.7 months, IQR: 24.0 – 34.0), 32% for the triple negative subgroup (median follow-up: 32.8 months, IQR: 18.5 – 40.6), and 15% among patients with HR+/HER2- MBC (median follow-up: 33.0 months, IQR: 31.9 – 36.2). The corresponding incidences per patient-year were 0.13 (95% CI: 0.10 – 0.16) for the HER2+ subgroup, 0.13 (95%CI: 0.09 – 0.20) for the triple negative subgroup, and only 0.05 (95%CI: 0.03 – 0.08) for patients with HR+/HER2- MBC. Conclusion There is high incidence of brain metastases among patients with HER2+ and triple negative MBC. The utility of a brain metastases screening program warrants investigation in these populations.

scholarly journals Staging Investigations in Asymptomatic Early Breast Cancer Patients at the Cancer Centre of Southeastern Ontario

2021 ◽  
Vol 28 (3) ◽  
pp. 2190-2198
Author(s):  
Dalia Kamel ◽  
Veronica Youssef ◽  
Wilma M. Hopman ◽  
Mihaela Mates
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Adjuvant Chemotherapy ◽  
Early Breast Cancer ◽  
Triple Negative ◽  
Metastatic Breast ◽  
Receptor Status ◽  
Cancer Centre ◽  
Radiological Staging

Background: In 2012, the American Society for Clinical Oncology (ASCO) identified five key opportunities in oncology to improve patient care, recommending against imaging tests for the staging of patients with early breast cancer (EBC) at low risk for metastases. Similarly, the European Society of Medical Oncology (ESMO) guideline does not support radiological staging in asymptomatic EBC (aEBC). The purpose of this study was to assess local practice and outcomes of staging investigations (SIs) in aEBC at the Cancer Centre of Southeastern Ontario (CCSEO). Methods: A retrospective electronic and paper chart review was undertaken to identify all aEBC patients treated at our institution between January 2012 and December 2014. Patients with pathological staging of T1-T2 and N0-1 with any receptor status were included. We collected patient demographics, treatment and pathologic tumor characteristics. The use and outcomes of initial and follow-up SIs were recorded. Data were analyzed to determine associations between the use of SIs and clinical characteristics (chi-square tests, independent samples t-tests and Mann–Whitney U tests). Results: From 2012 to 2014, 295 asymptomatic EBC patients were identified. The mean age was 64, 81% were postmenopausal and 76% had breast conserving surgery. Stage distribution was as follows: stage I 42%, stage IIA 37% and stage IIB 21%. Receptor status was as follows: ER+ 84%, HER2+ 13% and triple negative 12%. Adjuvant chemotherapy was received by 36%, Trastuzumab by 10% and endocrine therapy by 76% of patients. Baseline SIs were performed in 168 patients (57%) for a total of 332 tests. Overt metastatic disease was found in five patients (one bone scan and four CT scans). Seventy-one out of the 168 patients (42%) who received initial staging imaging underwent 138 follow-up imaging tests, none of which were diagnostic for metastases. Nine patients with suspicious CT findings underwent biopsies, of which four were malignant (one metastatic breast cancer and three new primaries). Factors significantly associated with SI were as follows: younger age (p = 0.001), premenopausal status (p = 0.01), T2 stage (p < 0.001), N1 stage (p < 0.001), HER2 positive (p < 0.001), triple negative status (p = 0.007) and use of adjuvant chemotherapy (p < 0.001). Conclusions: Over a 3-year period at our institution, more than 50% of aEBC patients underwent a total of 470 initial and follow-up staging tests, yielding a cancer diagnosis (metastatic breast cancer or second primary cancer) in four patients. We, therefore, conclude that routine-staging investigations in aEBC patients have low diagnostic value, supporting current guidelines that recommend against the routine use of SI in this population.

scholarly journals Phenotypic discordance between primary and metastatic breast cancer in the large-scale real-life multicenter French ESME cohort

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Thomas Grinda ◽  
Natacha Joyon ◽  
Amélie Lusque ◽  
Sarah Lefèvre ◽  
Laurent Arnould ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Large Scale ◽  
Tumour Progression ◽  
Primary Tumour ◽  
Multivariable Analysis ◽  
Real Life ◽  
Metastatic Breast ◽  
Her2 Status ◽  
Risk Of Death

AbstractExpression of hormone receptor (HR) for estrogens (ER) and progesterone (PR) and HER2 remains the cornerstone to define the therapeutic strategy for breast cancer patients. We aimed to compare phenotypic profiles between matched primary and metastatic breast cancer (MBC) in the ESME database, a National real-life multicenter cohort of MBC patients. Patients with results available on both primary tumour and metastatic disease within 6 months of MBC diagnosis and before any tumour progression were eligible for the main analysis. Among the 16,703 patients included in the database, 1677 (10.0%) had available biopsy results at MBC diagnosis and on matched primary tumour. The change rate of either HR or HER2 was 27.0%. Global HR status changed (from positive = either ER or PR positive, to negative = both negative; and reverse) in 14.2% of the cases (expression loss in 72.5% and gain in 27.5%). HER2 status changed in 7.8% (amplification loss in 45.2%). The discordance rate appeared similar across different biopsy sites. Metastasis to bone, HER2+ and RH+/HER2- subtypes and previous adjuvant endocrine therapy, but not relapse interval were associated with an HR discordance in multivariable analysis. Loss of HR status was significantly associated with a risk of death (HR adjusted = 1.51, p = 0.002) while gain of HR and HER2 discordance was not. In conclusion, discordance of HR and HER2 expression between primary and metastatic breast cancer cannot be neglected. In addition, HR loss is associated with worse survival. Sampling metastatic sites is essential for treatment adjustment.

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