Evolution of Estrogen Receptor Status from Primary Tumors to Metastasis and Serially Collected Circulating Tumor Cells

Background: The estrogen receptor (ER) can change expression between primary tumor (PT) and distant metastasis (DM) in breast cancer. A tissue biopsy reflects a momentary state at one location, whereas circulating tumor cells (CTCs) reflect real-time tumor progression. We evaluated ER-status during tumor progression from PT to DM and CTCs, and related the ER-status of CTCs to prognosis. Methods: In a study of metastatic breast cancer, blood was collected at different timepoints. After CellSearch® enrichment, CTCs were captured on DropMount slides and evaluated for ER expression at baseline (BL) and after 1 and 3 months of therapy. Comparison of the ER-status of PT, DM, and CTCs at different timepoints was performed using the McNemar test. The primary endpoint was progression-free survival (PFS). Results: Evidence of a shift from ER positivity to negativity between PT and DM was demonstrated (p = 0.019). We found strong evidence of similar shifts from PT to CTCs at different timepoints (p < 0.0001). ER-positive CTCs at 1 and 3 months were related to better prognosis. Conclusions: A shift in ER-status from PT to DM/CTCs was demonstrated. ER-positive CTCs during systemic therapy might reflect the retention of a favorable phenotype that still responds to therapy.

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Detection of estrogen receptor in bone marrow from patients with metastatic breast cancer.

Journal of Clinical Oncology ◽

10.1200/jco.1987.5.11.1779 ◽

1987 ◽

Vol 5 (11) ◽

pp. 1779-1782 ◽

Cited By ~ 10

Author(s):

U Berger ◽

J L Mansi ◽

P Wilson ◽

R C Coombes

Keyword(s):

Breast Cancer ◽

Bone Marrow ◽

Endocrine Therapy ◽

Tumor Cells ◽

Epithelial Membrane Antigen ◽

Metastatic Breast ◽

Breast Cancers ◽

Double Staining ◽

Primary Tumors ◽

Er Positive

We devised a method of detecting estrogen receptors (ER) in bone marrow metastases from patients with breast cancer. The method involves a sequential double-staining immunocytochemical technique, with a monoclonal antibody to ER and a polyclonal antibody recognizing epithelial membrane antigen to confirm the epithelial nature of suspected tumor cells. Twenty-seven patients were assessed: ten were found to have ER-positive tumor cells in the bone marrow; ten had ER-negative cells; and the remaining seven patients had no tumor cells in the bone marrow smears. Of the ten patients with ER-positive cells, eight (80%) either had a response to endocrine therapy, implying that they possess ER-positive breast cancers, or had ER-positive primary tumors as determined by the dextran-coated charcoal biochemical assay (DCC). Of the ten patients with ER-negative cells in the bone marrow, eight failed to respond to endocrine therapy. This technique therefore provides a means of predicting which patients will respond to endocrine therapy, and is particularly important in those patients whose ER status is unknown.

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Abstract PD4-09: Non-invasive estrogen receptor assessment by [18F]-fluorestradiol(FES)-PET or circulating tumor cells predicts receptor status in patients with metastatic breast cancer

10.1158/1538-7445.sabcs18-pd4-09 ◽

2019 ◽

Author(s):

B Eisses ◽

L Angus ◽

B van der Vegt ◽

AM Sieuwerts ◽

J Kraan ◽

...

Keyword(s):

Breast Cancer ◽

Estrogen Receptor ◽

Metastatic Breast Cancer ◽

Tumor Cells ◽

Circulating Tumor Cells ◽

Metastatic Breast ◽

Receptor Status ◽

Non Invasive

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The Efficacy of Lapatinib in Metastatic Breast Cancer with HER2 Non-Amplified Primary Tumors and EGFR Positive Circulating Tumor Cells: A Proof-Of-Concept Study

PLoS ONE ◽

10.1371/journal.pone.0062543 ◽

2013 ◽

Vol 8 (5) ◽

pp. e62543 ◽

Cited By ~ 24

Author(s):

Justin Stebbing ◽

Rachel Payne ◽

Justine Reise ◽

Adam E. Frampton ◽

Miranda Avery ◽

...

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Tumor Cells ◽

Circulating Tumor Cells ◽

Metastatic Breast ◽

Proof Of Concept ◽

Primary Tumors ◽

Concept Study

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Prognostic Impact of Pregnancy After Breast Cancer According to Estrogen Receptor Status: A Multicenter Retrospective Study

Journal of Clinical Oncology ◽

10.1200/jco.2012.44.2285 ◽

2013 ◽

Vol 31 (1) ◽

pp. 73-79 ◽

Cited By ~ 128

Author(s):

Hatem A. Azim ◽

Niels Kroman ◽

Marianne Paesmans ◽

Shari Gelber ◽

Nicole Rotmensz ◽

...

Keyword(s):

Breast Cancer ◽

Estrogen Receptor ◽

Pregnancy Outcome ◽

Estrogen Receptor Status ◽

Disease Free Survival ◽

Prognostic Impact ◽

Er Positive ◽

The Impact ◽

Disease Free ◽

Er Status

Purpose We questioned the impact of pregnancy on disease-free survival (DFS) in women with history of breast cancer (BC) according to estrogen receptor (ER) status. Patients and Methods A multicenter, retrospective cohort study in which patients who became pregnant any time after BC were matched (1:3) to patients with BC with similar ER, nodal status, adjuvant therapy, age, and year of diagnosis. To adjust for guaranteed time bias, each nonpregnant patient had to have a disease-free interval at least equal to the time elapsing between BC diagnosis and date of conception of the matched pregnant one. The primary objective was DFS in patients with ER-positive BC. DFS in the ER-negative cohort, whole population, and overall survival (OS) were secondary objectives. Subgroup analyses included DFS according to pregnancy outcome and BC–pregnancy interval. With a two-sided α = 5% and β = 20%, 645 ER-positive patients were required to detect a hazard ratio (HR) = 0.65. Results A total of 333 pregnant patients and 874 matched nonpregnant patients were analyzed, of whom 686 patients had an ER-positive disease. No difference in DFS was observed between pregnant and nonpregnant patients in the ER-positive (HR = 0.91; 95% CI, 0.67 to 1.24, P = .55) or the ER-negative (HR = 0.75; 95% CI, 0.51 to 1.08, P = .12) cohorts. However, the pregnant group had better OS (HR = 0.72; 95% CI, 0.54 to 0.97, P = .03), with no interaction according to ER status (P = .11). Pregnancy outcome and BC–pregnancy interval did not seem to impact the risk of relapse. Conclusion Pregnancy after ER-positive BC does not seem to reduce the risk of BC recurrence.

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