15 Utilizing Circulating Tumor Cells to Guide HER2-Directed Therapy in IHC/FISH-Negative HER2+ Metastatic Breast Cancer

Publication
Article
Miami Breast Cancer Conference® Abstracts Supplement42nd Annual Miami Breast Cancer Conference® - Abstracts
Volume 39
Issue 4
Pages: 9-10

15 Utilizing Circulating Tumor Cells to Guide HER2-Directed Therapy in IHC/FISH-Negative HER2+ Metastatic Breast Cancer

15 Utilizing Circulating Tumor Cells to Guide HER2-Directed Therapy in IHC/FISH-Negative HER2+ Metastatic Breast Cancer

Background

The diagnosis of HER2-positive metastatic breast cancer (MBC) is complicated by tumor heterogeneity and temporal changes in HER2 expression. Circulating tumor cells (CTCs) serve as valuable noninvasive markers for HER2 expression when pathologic confirmation is infeasible, offering a potential therapeutic target in an otherwise high-risk population. We present a series of patients with HER2-negative MBC by immunohistochemistry (IHC)/ fluorescence in situ hybridization (FISH) who received adjunctive HER2-directed therapy following the detection of HER2-positive CTCs.

Materials and Methods

116 patients with HER2-positive MBC by IHC/FISH and/or HER2-positive CTCs, enrolled between 2016 and 2024 under Institutional Review Board-approved trial NU16B06 at Northwestern Medicine, were retrospectively analyzed. CTC enumerations were performed via CELLTRACKS (Menarini).

Results

Seven patients with prior HER2-negative MBC by IHC/FISH initiated HER2-directed therapy at metastatic diagnosis based on HER2-positive CTCs. Median age at metastatic diagnosis was 63 years (range, 38-68). In addition to chemotherapy, all patients received initial HER2-directed therapy with trastuzumab, which was well tolerated. The median primary CTC count was 34 (5-1143), with a median of 17 HER2-positive CTCs (5-376). Median progression-free survival was 5.2 months (0.67–13.3), and the median overall survival was 38.9 months (9.5-61.7). Among 5 patients with reported secondary CTC counts, 2 cleared HER2-positive CTCs, 1 demonstrated a decrease, and 2 exhibited an increase in HER2+ CTCs. All patients experienced progressive metastatic disease. Four patients underwent subsequent biopsies during their disease course: 2 were HER2-negative by IHC/FISH, and 2 were found to have HER2-low disease. Five patients received further HER2-directed therapy, including tucatinib, trastuzumab emtansine, and trastuzumab deruxtecan.

Conclusion

While IHC/FISH remains the standard for HER2 detection, CTCs provide a complementary metric to guide HER2-directed therapy in HER2-negative MBC by IHC/FISH. Dynamic changes in HER2+ CTCs highlight their utility as predictive biomarkers for therapeutic response and indicators of disease progression. Evidence of subsequent HER2-low disease in some patients underscores the evolving nature of HER2 expression. This limited series demonstrates that noninvasive CTC monitoring may offer a potential approach to address tumor heterogeneity and guide real-time therapeutic adjustments. Prospective studies are needed to optimize patient selection for CTC-guided HER2 therapies and validate their role in improving outcomes in MBC.

Articles in this issue

15 Utilizing Circulating Tumor Cells to Guide HER2-Directed Therapy in IHC/FISH-Negative HER2+ Metastatic Breast Cancer
15 Utilizing Circulating Tumor Cells to Guide HER2-Directed Therapy in IHC/FISH-Negative HER2+ Metastatic Breast Cancer
16 A Miami Hospital’s Infrastructure to Help Decrease Late-Stage Breast Cancer Diagnosis and Improve Health Equity
16 A Miami Hospital’s Infrastructure to Help Decrease Late-Stage Breast Cancer Diagnosis and Improve Health Equity
17 Salmonella and the Breast: A Literature Review of Salmonella-Induced Breast Abscesses
17 Salmonella and the Breast: A Literature Review of Salmonella-Induced Breast Abscesses
18 Tolerability of First-Line Treatment With Ribociclib for Metastatic Breast Cancer Using 2 Large US Data Sources
18 Tolerability of First-Line Treatment With Ribociclib for Metastatic Breast Cancer Using 2 Large US Data Sources
20 Impact of Ribociclib Dose Reduction on Efficacy in Patients With Hormone Receptor-Positive/Human Epidermal Growth Factor Receptor 2-Negative Early Breast
20 Impact of Ribociclib Dose Reduction on Efficacy in Patients With Hormone Receptor-Positive/Human Epidermal Growth Factor Receptor 2-Negative Early Breast
21 Distant Disease-Free Survival Across Key Subgroups From the Phase 3 NATALEE Trial of Ribociclib Plus a Nonsteroidal Aromatase Inhibitor in Patients With HR+/HER2− Early Breast Cancer
21 Distant Disease-Free Survival Across Key Subgroups From the Phase 3 NATALEE Trial of Ribociclib Plus a Nonsteroidal Aromatase Inhibitor in Patients With HR+/HER2− Early Breast Cancer
22 Efficacy and Safety of Ribociclib + Nonsteroidal Aromatase Inhibitor in Younger Patients With HR+/HER2− Early Breast Cancer in NATALEE
22 Efficacy and Safety of Ribociclib + Nonsteroidal Aromatase Inhibitor in Younger Patients With HR+/HER2− Early Breast Cancer in NATALEE
23 Clinical Outcomes in Patients With HR+/HER2− Early Breast Cancer By Prior Systemic Treatment: A Subgroup Analysis of the NATALEE Trial
23 Clinical Outcomes in Patients With HR+/HER2− Early Breast Cancer By Prior Systemic Treatment: A Subgroup Analysis of the NATALEE Trial
TPS 24 Phase Ib Dose-Finding Study of [177Lu]Lu-NeoB + Ribociclib + Fulvestrant in Patients With ER+/HER2− Advanced Breast Cancer With GRPR Expression With Early Relapse FromAdjuvant Endocrine Therapy or Progression on ET + CDK4/6i for ABC
TPS 24 Phase Ib Dose-Finding Study of [177Lu]Lu-NeoB + Ribociclib + Fulvestrant in Patients With ER+/HER2− Advanced Breast Cancer With GRPR Expression With Early Relapse FromAdjuvant Endocrine Therapy or Progression on ET + CDK4/6i for ABC
TPS 25 Phase 1/2 Study of the Novel Radioligand Therapy [177Lu]Lu-NeoB Plus Capecitabine in Patients With ER+/HER2− Advanced Breast Cancer (ABC) With GRPR Expression After Progression on Prior Endocrine Therapy Plus a CDK4/6 Inhibitor for ABC
TPS 25 Phase 1/2 Study of the Novel Radioligand Therapy [177Lu]Lu-NeoB Plus Capecitabine in Patients With ER+/HER2− Advanced Breast Cancer (ABC) With GRPR Expression After Progression on Prior Endocrine Therapy Plus a CDK4/6 Inhibitor for ABC
26 Risk of Recurrence in Real-World NATALEE- and monarchE-Eligible Populations of Patients With HR+/HER2− Early Breast Cancer in an Electronic Health Record-Derived Database
26 Risk of Recurrence in Real-World NATALEE- and monarchE-Eligible Populations of Patients With HR+/HER2− Early Breast Cancer in an Electronic Health Record-Derived Database
27 Elacestrant vs Standard of Care in ER+, HER2- Advanced or Metastatic Breast Cancer With ESR1-Mutated Tumors: ESR1 Allelic Frequencies and Clinical Activity From the Phase 3 EMERALD Trial
27 Elacestrant vs Standard of Care in ER+, HER2- Advanced or Metastatic Breast Cancer With ESR1-Mutated Tumors: ESR1 Allelic Frequencies and Clinical Activity From the Phase 3 EMERALD Trial
TPS 28 ELEGANT: Elacestrant VS Standard Endocrine Therapy in Women and Men With Node-Positive, Estrogen Receptor-Positive, HER2-Negative, Early Breast Cancer With High Risk of Recurrence in a Global, Multicenter, Randomized, Open-Label Phase 3 Study
TPS 28 ELEGANT: Elacestrant VS Standard Endocrine Therapy in Women and Men With Node-Positive, Estrogen Receptor-Positive, HER2-Negative, Early Breast Cancer With High Risk of Recurrence in a Global, Multicenter, Randomized, Open-Label Phase 3 Study
29 A Real-World Exploratory Analysis to Identify Disparities in Breast Cancer Tumor Biopsy Practice at Community Oncology Clinics in the United States
29 A Real-World Exploratory Analysis to Identify Disparities in Breast Cancer Tumor Biopsy Practice at Community Oncology Clinics in the United States
30 Imlunestrant, an Oral Selective Estrogen Receptor Degrader, as Monotherapy and Combined With Abemaciclib, for Patients with ER+, HER2– Advanced Breast Cancer, Pretreated With Endocrine Therapy: Results of the Phase 3 EMBER-3 Trial
30 Imlunestrant, an Oral Selective Estrogen Receptor Degrader, as Monotherapy and Combined With Abemaciclib, for Patients with ER+, HER2– Advanced Breast Cancer, Pretreated With Endocrine Therapy: Results of the Phase 3 EMBER-3 Trial

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