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 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.

Impact of loco-regional treatment including radiotherapy in patients presenting with metastatic breast cancer

2021 ◽  
pp. 1-6
Author(s):  
Budhi Singh Yadav ◽  
Rubu Sunku ◽  
Divya Dahiya
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Cox Regression ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Hormone Treatment ◽  
Rank Test ◽  
Factors Affecting ◽  
The Impact ◽  
Regional Treatment

Abstract Background: The impact of loco-regional treatment (LRT) with radiotherapy (RT) in patients presenting with metastatic breast cancer (MBC) has not been widely studied. The aim of this study was to review the treatment outcomes of LRT including RT in patients with MBC. Materials and methods: Patients who presented with MBC were included in this retrospective study. Analysis was undertaken to determine the difference in local disease control, overall survival (OS) and progression-free survival (PFS) with systemic treatment alone, surgery alone, surgery plus RT and RT alone with long-rank test. Multivariate analysis was done, using the cox regression for factors affecting PFS and OS. Results: From 2007 to 2014, data of 257 patients with MBC were collected. Totally, 185 patients received LRT and 72 did not. LRT was surgery plus RT, surgery only and RT only in 113, 47 and 25 patients, respectively. Cytotoxic chemotherapy and hormone therapy were received by 205 and 166 patients, respectively. Median follow-up was 36 months (6–120 months). PFS and OS at 3 years with and without LRT were 31% versus 6% (p < 0·001) and 41% versus 17% (p < 0·001), respectively. PFS at 3 years with surgery plus RT, RT alone and surgery was 40, 33 and 6%, respectively. OS at 3 years with surgery plus RT, RT alone and surgery was 50, 38 and 17%, respectively. Patients without LRT had worse PFS and OS, 6 and 17%, respectively. RT had significant impact on PFS and OS along with chemotherapy and hormone treatment. Conclusion: In patients with MBC, improved local control, PFS and OS were achieved with loco-regional RT. Loco-regional RT along with chemotherapy and hormones were significant factors for PFS and OS irrespective of surgery.

Resistance to CDK4/6 inhibitors (CDK4/6i): The clinical usefulness of liquid biopsy in metastatic breast cancer (mBC).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 1053-1053
Author(s):  
Lucrezia Raimondi ◽  
Laura Di Benedetto ◽  
Giuseppe Naso ◽  
Filippo Maria Raimondi ◽  
Arianna Di Rocco ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Kras Mutation ◽  
Liquid Biopsy ◽  
Molecular Mechanisms ◽  
Cox Regression ◽  
Objective Response ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Rank Test

1053 Background: Palbociclib (P) in combination with fulvestrant (F) or letrozole (L), is used globally to treat metastatic breast cancer but despite therapeutic improvements most patients acquire resistance to CDK4/6i. KRAS tumor mutations (mutKRAS) have been associated with worse PFS in several tumor types but have not been analysed extensively in breast cancer. To understand the molecular mechanisms of resistance to CDK4/6i and their clinical behavior, using liquid biopsy, we evaluated the opportunity to reveal the onset of resistance to CDK4/6i detecting mutKRAS ctDNA. Methods: We studied the KRAS mutation status of 211 patients with mBC treated with CDK4/6i plus L or F as first-line metastatic therapy. Using Bio-Rad QX200 droplet digital polymerase chain reaction (ddPCR) system we determined KRAS ctDNA levels in plasma. Using logistic and Cox regression, a predictive model for objective response (OR), progression-free survival (PFS) and overall survival (OS) was constructed. The PFS and the OS were estimated by the Kaplan–Meier method and compared with use of the log-rank test. Results: In 38% (81 patients, 24 in treatment with L and 57 in treatment with F) we observed mutKRAS ctDNA before starting CDK4/6i: the detection of mutKRAS significantly correlated with the onset of resistance to CDK4/6i within 6months from the evidence of KRAS mutation and worse PFS ( p<0.001). OR was seen in 84 of 130 KRAS wild-type (WT) patients versus 0 of 81 in KRAS mutants. At 24-month follow up, median PFS was significantly better in KRAS WT versus mutants (3.1 [range: 1-6months,95%CI 0.9-3.6] versus NA months; p<0.001). Correlating the results of liquid biopsy both to tumoral burden and patients clinical features, we observed a higher mutKRAS circulating copies-number in those patients with two or more metastatic sites( p<0.001). Conclusions: Despite the study’s limitations, our data suggest mutKRAS ctDNA status leads to CDK4/6i resistance acquisition within 6 months from the detection and provide critical information for the prediction of therapeutic responses in mBC. Monitoring KRAS status with liquid biopsy, we could predict who will take advantage from CDK4/6i, decreasing wastes of resources ensuring the best patients’ quality of life.

Breast Cancer With Synchronous Metastases: Trends in Survival During a 14-Year Period

2004 ◽  
Vol 22 (16) ◽  
pp. 3302-3308 ◽  
Author(s):  
Fabrice Andre ◽  
Khemaies Slimane ◽  
Thomas Bachelot ◽  
Arianne Dunant ◽  
Moise Namer ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Cancer Patients ◽  
Cox Regression ◽  
Metastatic Breast ◽  
New Drugs ◽  
Rank Test ◽  
Breast Cancer Patients ◽  
Cox Regression Analysis ◽  
Over Time

Purpose Although new drugs were approved during the 1990s for the treatment of metastatic breast cancer, it is not clear whether their use has changed the outcome of patients in daily practice. This study sought to determine whether survival has improved over time for breast cancer patients who had metastases at diagnosis. Patients and Methods A total of 724 patients have been treated in three French cancer centers for an initially metastatic breast cancer between 1987 and 2000; 343 were diagnosed between 1987 and 1993, and 381 were diagnosed between 1994 and 2000. Tumor characteristics, treatments, and outcomes of these patients were compared by χ2 test, log-rank test, and Cox regression analysis. Results Characteristics were not different between the patients diagnosed from 1987 to 1993 and those diagnosed from 1994 to 2000. Ten percent of patients treated from 1987 to 1994 and 58% of patients treated from 1994 to 2000 have received either a taxane or a new aromatase inhibitor. The 3-year overall survival rates were 27% for patients treated from 1987 to 1993 and 44% for patients treated from 1994 to 2000 (P < .001). The treatment period (1994 to 2000 v 1987 to 1993) was a prognostic factor in multivariate analysis (relative risk, 0.6; P < .001). Conclusion The survival of breast cancer patients presenting with metastases at diagnosis has improved over time. This study strongly suggests that this improvement is related to treatment.

scholarly journals Real-world Treatment Patterns and Outcomes in HR+/HER2+ Metastatic Breast Cancer Patients: A National Cancer Database Analysis

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Abby B. Statler ◽  
Brian P. Hobbs ◽  
Wei Wei ◽  
Annie Gupta ◽  
Cassann N. Blake ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Hormonal Therapy ◽  
Propensity Scores ◽  
Cox Regression ◽  
Metastatic Breast ◽  
Treatment Patterns ◽  
Rank Test ◽  
National Cancer Database ◽  
Breast Cancer Patients

AbstractTreatment patterns and outcomes are unclear for metastatic breast cancer (MBC) patients diagnosed with hormone receptor-positive (HR+), human epidermal growth factor 2-positive (HER2+) disease. This study aimed to: (1) examine the utilization of first-line therapy among HR+/HER2+/MBC patients and (2) compare overall survival (OS) between the identified regimens. We analyzed National Cancer Database patients (HR+/HER2+/MBC) who were treated between 2010 and 2015. Multivariable logistic and Cox regression were used to: (1) identify independent predictors of treatment receipt and (2) determine significant prognostic factors for OS. Kaplan-Meier method and log-rank test were used to estimate and evaluate OS, respectively. Propensity scores were added to all multivariate OS models, thereby accounting for bias in treatment receipt. Of 6,234 patients analyzed, 3770 (60.5%) received hormonal therapy and 2464 (39.5%) received chemotherapy. Receipt of hormonal therapy was associated with older age, grade 1/grade 2 disease, no visceral involvement, higher comorbidity scores, and being white. Multivariate analysis suggest patients receiving hormonal therapy + anti-HER2 experienced improved OS, when compared to chemotherapy + anti-HER2 (HR: 0.74, p = 0.004). Overall, the cohort receiving hormonal therapy + anti-HER2 reported the highest 5-year OS (hormonal + anti-HER2: 47.5% vs. chemotherapy + anti-HER2: 39.8% vs. hormonal: 38.5% vs. chemotherapy: 36.3%, p < 0.001). Our findings suggest de-escalated therapy may be the preferred and potentially more effective care path for HR+/HER2+/MBC patients, signaling a need for randomized studies.

Randomized clinical trial of tamoxifen alone or combined with fluoxymesterone in postmenopausal women with metastatic breast cancer.

1988 ◽  
Vol 6 (5) ◽  
pp. 825-831 ◽  
Author(s):  
J N Ingle ◽  
D I Twito ◽  
D J Schaid ◽  
S A Cullinan ◽  
J E Krook ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Trial ◽  
Metastatic Breast Cancer ◽  
Side Effects ◽  
Postmenopausal Women ◽  
Randomized Clinical Trial ◽  
Statistical Significance ◽  
Metastatic Breast ◽  
Rank Test ◽  
Breast Cancer Patients

A randomized clinical trial was performed to determine if combination hormonal therapy with tamoxifen (TAM) and fluoxymesterone (FLU) was more efficacious than TAM alone for the treatment of postmenopausal women with metastatic breast cancer. Patients failing TAM could subsequently receive FLU. The dose of both drugs was 10 mg orally twice daily. Objective responses were seen in 50 of 119 TAM patients (42%) and 63 of 119 TAM plus FLU patients (53%) (one-sided P = .05). Time to disease progression distributions were better for TAM plus FLU (median, 350 days v 199 days), but the log rank test only approached statistical significance (one-sided P = .07). Duration of response and survival distributions were similar between the two treatment arms. Toxicities, in terms of androgenic side effects, were greater on the TAM plus FLU regimen. Fifty-two patients are evaluable for response with FLU following TAM and 21 (40%) have achieved a response. We conclude that the advantages in terms of response rate and time to progression observed with TAM plus FLU probably represent a biological effect, but are not of sufficient magnitude to justify the routine clinical use of this combination given the lack of survival advantage and side effects encountered.

scholarly journals Survival impact of primary tumor resection in de novo metastatic breast cancer patients (GEICAM/El Alamo Registry)

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Sara Lopez-Tarruella ◽  
M. J. Escudero ◽  
Marina Pollan ◽  
Miguel Martín ◽  
Carlos Jara ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Cancer Patients ◽  
Primary Tumor ◽  
Cox Regression ◽  
De Novo ◽  
Histological Grade ◽  
Tumor Resection ◽  
Metastatic Breast ◽  
Breast Cancer Patients

AbstractThe debate about surgical resection of primary tumor (PT) in de novo metastatic breast cancer (MBC) patients persists. We explored this approach’s outcomes in patients included in a retrospective registry, named El Álamo, of breast cancer patients diagnosed in Spain (1990–2001). In this analysis we only included de novo MBC patients, 1415 of whom met the study’s criteria. Descriptive, Kaplan-Meier and Cox regression analyses were carried out. Median age was 63.1 years, 49.2% of patients had single-organ metastasis (skin/soft tissue [16.3%], bone [33.8%], or viscera [48.3%]). PT surgery (S) was performed in 44.5% of the cases. S-group patients were younger, had smaller tumors, higher prevalence of bone and oligometastatic disease, and lower prevalence of visceral involvement. With a median follow-up of 23.3 months, overall survival (OS) was 39.6 versus 22.4 months (HR = 0.59, p < 0.0001) in the S- and non-S groups, respectively. The S-group OS benefit remained statistically and clinically significant regardless of metastatic location, histological type, histological grade, hormone receptor status and tumor size. PT surgery (versus no surgery) was associated with an OS benefit suggesting that loco-regional PT control may be considered in selected MBC patients. Data from randomized controlled trials are of utmost importance to confirm these results.

scholarly journals High-Dose Toremifene as a Promising Candidate Therapy for Hormone Receptor-Positive Metastatic Breast Cancer with Secondary Resistance to Aromatase Inhibitors

2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Atsushi Fushimi ◽  
Isao Tabei ◽  
Azusa Fuke ◽  
Tomoyoshi Okamoto ◽  
Hiroshi Takeyama
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Liver Metastasis ◽  
Hormone Receptor ◽  
Metastatic Breast ◽  
Postmenopausal Breast Cancer ◽  
Rank Test ◽  
High Dose ◽  
Secondary Resistance ◽  
Hormone Receptor Positive

There are currently no established second- and later-line therapies for postmenopausal women with hormone receptor-positive advanced or metastatic breast cancer. We examined the efficacy of high-dose toremifene (HD-TOR) for this patient group and whether aromatase inhibitor (AI) resistance influences HD-TOR treatment outcome. This retrospective analysis investigated the outcomes of 19 women with postmenopausal hormone-sensitive recurrent or metastatic breast cancer who received HD-TOR, defined as 120 mg daily from 2012 to 2016. The median follow-up duration was 9.67 months. The overall response rate (ORR) and clinical benefit rate (CBR) were compared between various clinical subgroups, including patients exhibiting primary or secondary AI resistance as defined by the timing of recurrence or progression. Time to treatment failure (TTF) was estimated by the Kaplan–Meier method and compared between subgroups by the log-rank test. The overall ORR was 21.1%, and the CBR was 31.6%. CBR was significantly higher for patients without liver metastasis (50% vs. 0%, p=0.044). Nine cases exhibited primary and eight cases secondary AI resistance. Both ORR and CBR were higher in patients with secondary AI resistance (25% vs. 0%, p=0.087; 38% vs. 11%, p=0.29). The median TTF was 6.2 months in the entire AI-resistant group (n=17) and was longer in the secondary resistance subgroup than in the primary resistance subgroup (8.40 vs. 4.87 months; log-rank: p=0.159). High-dose TOR appears to be most effective for postmenopausal breast cancer cases with secondary resistance to AIs, cases without prior AI treatment, and cases without liver metastasis. The detailed mechanisms of AI resistance and the clinical features of responsive cases need to be further clarified to identify the best candidates for HD-TOR.

scholarly journals The Lack of Evidence for an Association between Cancer Biomarker Conversion Patterns and CTC-Status in Patients with Metastatic Breast Cancer

2020 ◽  
Vol 21 (6) ◽  
pp. 2161
Author(s):  
Stefan Stefanovic ◽  
Thomas M. Deutsch ◽  
Sabine Riethdorf ◽  
Chiara Fischer ◽  
Andreas Hartkopf ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Metastatic Breast ◽  
Metastatic Tumor ◽  
Circulating Tumor Cell ◽  
Her2 Expression ◽  
Change Pattern ◽  
Kaplan Meier ◽  
Prognostic Importance ◽  
Genetic Profiles

Circulating tumor cell (CTC) detection is a prognostic factor in the metastatic breast cancer (MBC) setting. Discrepancies in primary (PT) and metastatic tumor (MT) genetic profiles are also of prognostic importance. Our study aimed to compare the CTC statuses and prognoses between those with subtype stable MBCs and MBCs with specific biomarker conversions. The study enrolled 261 MBC patients, treated at the National Center for Tumor Diseases, Heidelberg, Germany in a five-year period. All underwent PT and MT biopsies and subsequent CTC enumeration before the initiation of systemic therapy. ER and HER2 statuses of the PTs and MTs were determined and progression free survivals (PFSs) and overall survivals (OSs) were recorded. We compared CTC statuses, CTC counts, PFSs and OSs between subgroups of patients with different receptor change patterns. Patients who had tumors that converted to triple negative MTs had the shortest median OSs, while HER2 expression was not associated with a shorter median OS. No significant differences in PFSs and OSs have been demonstrated by Kaplan-Meier curve comparisons in any of the subgroup analyses. CTC counts were similar in all subgroups. CTCs were comparably less frequently detected in patients with a stable HER2 expression. Similar proportions of CTC positives were observed in all other subtype change pattern subgroups, barring the aforementioned HER2 stable subgroup. The detection of CTCs was of no appreciable prognostic value in different receptor change pattern subgroups in our cohort.

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