Identification of a subpopulation of metastatic breast cancer patients with very high HER2 expression levels and possible resistance to trastuzumab

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 1059-1059
Author(s):  
J. Sperinde ◽  
S. Ali ◽  
K. Leitzel ◽  
E. Fuchs ◽  
W. J. Köstler ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Clinical Outcomes ◽  
Metastatic Breast ◽  
Primary Breast Tumor ◽  
P Value ◽  
Her2 Expression ◽  
Abrupt Decrease ◽  
Expression Levels ◽  
Very High

1059 Background: Many HER2-positive patients with metastatic breast cancer (MBC) fail to respond to trastuzumab. We previously reported that precise quantitation of HER2 expression (H2T) by the HERmark assay identified a sub-population of IHC 3+, FISH(+) (positive) patients with low H2T levels that responded poorly to trastuzumab (Lipton, San Antonio Breast Cancer Symposium 2008, abs #32). Here we identify a sub-population of FISH(+) patients with very high H2T levels, that experience clinical outcomes that are indistinguishable from those of FISH(-) (negative) patients with low H2T levels. Methods: The HERmark assay was used to measure H2T in formalin-fixed, paraffin-embedded (FFPE) primary breast tumor specimens from 99 women treated with trastuzumab for MBC. Specimens were also tested by central FISH. A sub-population treatment effect pattern plot (STEPP) was generated to examine the progression-free survival (PFS) rate at 12 months after treatment with trastuzumab across the distribution of H2T. Kaplan-Meier (KM) analyses were performed comparing the PFS of FISH(-), H2T low (log10H2T < 1.25) patients with those of FISH(+), H2T high (log10H2T ≥ 1.95) and FISH(+), H2T intermediate (1.25 < log10H2T < 1.95) groups. Cutoffs were identified by lowest p-value in a positional scanning analysis. Results: The PFS rate improved gradually with increasing H2T in STEPP analyses. At the highest levels of H2T, an abrupt decrease in the PFS rate was observed, consistent with a reduction in susceptibility to trastuzumab. KM analyses demonstrated that patients who were FISH(+), H2T intermediate had a significantly longer PFS than patients who were FISH(-), H2T low (median PFS 12.6 vs. 4.5 mos; HR = 0.34; p < 0.0001). Patients that were FISH(+), H2T high experienced a PFS that was no better than patients that were FISH(-), H2T low (median PFS 4.6 vs. 4.5 mos; HR = 0.87; p = 0.68). Conclusions: Precise quantitation of HER2 expression levels allows the identification of multiple sub-populations of HER2(+) patients that have different clinical outcomes on trastuzumab. MBC patients with very high levels of H2T could represent a sub-group with de novo resistance to trastuzumab who may benefit from combined therapy. [Table: see text]

Correlation of trastuzumab treatment benefit with quantitative HER2 expression levels in HER2 positive metastatic breast cancer.

2015 ◽  
Vol 33 (15_suppl) ◽  
pp. 593-593
Author(s):  
Beatrice Bachmeier ◽  
Jeff Sperinde ◽  
Jodi Marie Weidler ◽  
Yolanda Lie ◽  
Ahmed Chenna ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Metastatic Breast ◽  
Her2 Expression ◽  
Her2 Positive ◽  
Treatment Benefit ◽  
Expression Levels ◽  
Trastuzumab Treatment

scholarly journals Occult Breast Carcinoma Presenting as Scalp Metastasis

2017 ◽  
Vol 10 (3) ◽  
pp. 992-997 ◽  
Author(s):  
Ricardo L.B. Costa ◽  
Rubens B. Costa-Filho ◽  
Marilin Rosa ◽  
Brian J. Czerniecki
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Breast Tumor ◽  
Rare Case ◽  
De Novo ◽  
Metastatic Breast ◽  
Primary Breast Tumor ◽  
Occult Breast Cancer ◽  
Scalp Metastasis ◽  
Occult Breast Carcinoma

Breast cancer is the most common tumor among women, and approximately 6% of the patients have de novo metastatic breast cancer. Occult breast cancer accounts for only 0.1–0.8% of the cases and most commonly presents with axillary lymphadenopathy. Scalp metastases are rare and have been described as a sign of progression or widespread metastatic disease. Here, we describe a rare case of de novo metastatic breast cancer to the scalp as the single site of spread and without an identifiable primary breast tumor.

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 Observational study of clinical outcomes of eribulin mesylate in metastatic breast cancer after cyclin-dependent kinase 4/6 inhibitor therapy

2019 ◽  
Vol 15 (34) ◽  
pp. 3935-3944 ◽  
Author(s):  
Sarah S Mougalian ◽  
Bruce A Feinberg ◽  
Edward Wang ◽  
Karenza Alexis ◽  
Debanjana Chatterjee ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Clinical Outcomes ◽  
Kinase Inhibitor ◽  
Objective Response ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Cyclin Dependent Kinase ◽  
Eribulin Mesylate ◽  
Free Survival

Aim: To examine the effectiveness of eribulin mesylate for metastatic breast cancer post cyclin-dependent kinase inhibitor (CDKi) 4/6 therapy. Materials & methods: US community oncologists reviewed charts of patients who had received eriublin from 3 February 2015 to 31 December 2017 after prior CDKi 4/6 therapy and detailed their clinical/treatment history, clinical outcomes (lesion measurements, progression, death) and toxicity. Results: Four patient cohorts were created according to eribulin line of therapy: second line, third line, per US label and fourth line with objective response rates/clinical benefit rates of 42.2%/58.7%, 26.1%/42.3%, 26.7%/54.1% and 17.9%/46.4%, respectively. Median progression-free survival/6-month progression-free survival (79.5% of all patients censored) by cohort was: 9.7 months/77.3%, 10.3 months/71.3%, not reached/70.4% and 4.0 months/0.0%, respectively. Overall occurrence of neutropenia = 23.5%, febrile neutropenia = 1.3%, peripheral neuropathy = 10.1% and diarrhea = 11.1%. Conclusion: Clinical outcome and adverse event rates were similar to those in clinical trials and other observational studies. Longer follow-up is required to confirm these findings.

Real-world clinical outcomes and toxicity in metastatic breast cancer patients treated with palbociclib and endocrine therapy

2019 ◽  
Vol 176 (2) ◽  
pp. 429-434 ◽  
Author(s):  
Leticia Varella ◽  
Akaolisa Samuel Eziokwu ◽  
Xuefei Jia ◽  
Megan Kruse ◽  
Halle C. F. Moore ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Cancer Patients ◽  
Endocrine Therapy ◽  
Clinical Outcomes ◽  
Real World ◽  
Metastatic Breast ◽  
Breast Cancer Patients

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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