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Circulating tumor cells in HER2-positive metastatic breast cancer patients: a valuable prognostic and predictive biomarker.

Liu Y, Liu Q, Wang T, Bian L, Zhang S, Hu H, Li S, Hu Z, Wu S, Liu B, Jiang Z - BMC Cancer (2013)

Bottom Line: Among patients with HER2-positive CTCs, the median PFS for those receiving anti-HER2 therapy was significantly longer than those who were not (8.8 vs. 1.5 months, P=0.001).Notably, up to 52% (14/27) of the HER2-positive patients were CTC HER2-negative, and anti-HER2 therapy did not significantly improve the median PFS in these patients (2.5 vs. 0.9 months, P=0.499).Our findings underscore the necessity of a comprehensive CTC analysis, which may provide valuable prognostic and predictive information for optimizing individually tailored therapies in HER2-positive MBC patients.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Breast Cancer, Affiliated Hospital of Academy of Military Medical Sciences, No.8 Dongdajie, Beijing, 100071, China.

ABSTRACT

Background: This study was initiated to investigate the prognostic significance of circulating tumor cell (CTC) enumeration and the predictive value of CTC HER2 expression for efficient anti-HER2 therapy in HER2-positive metastatic breast cancer (MBC) patients.

Methods: Sixty HER2-positive MBC patients were enrolled in the present study. Before the initiation of systemic treatment, CTCs from 7.5 ml of blood were analyzed using the CellSearch system. The progression-free survival (PFS) of the patients was estimated using Kaplan-Meier survival curves.

Results: CTCs were detected in 45% (27/60) of the patients, who had shorter median PFS than those without CTCs (2.5 vs. 7.5 months, P=0.0125). Furthermore, referring to the standard HER2 testing that uses immunohistochemistry (IHC), we proposed a CTC HER2-positive criterion, defined as >30% of CTCs over-expressing HER2. Among patients undergoing anti-HER2 therapy, those with HER2-positive CTCs had longer PFS (8.8 vs. 2.5 months, P=0.002). Among patients with HER2-positive CTCs, the median PFS for those receiving anti-HER2 therapy was significantly longer than those who were not (8.8 vs. 1.5 months, P=0.001). Notably, up to 52% (14/27) of the HER2-positive patients were CTC HER2-negative, and anti-HER2 therapy did not significantly improve the median PFS in these patients (2.5 vs. 0.9 months, P=0.499).

Conclusions: Our findings underscore the necessity of a comprehensive CTC analysis, which may provide valuable prognostic and predictive information for optimizing individually tailored therapies in HER2-positive MBC patients. To test this idea, additional large cohort, multi-center and prospective clinical trials are needed.

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Representative images for the 0, 1+, 2+, and 3+ intensities of HER2 expression on CTCs.
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Figure 2: Representative images for the 0, 1+, 2+, and 3+ intensities of HER2 expression on CTCs.

Mentions: HER2 expression intensity in CTCs was given a score of 0, 1+, 2+, or 3+, according to the criteria described previously [28,29], and representative images are shown in Figure 2. Additional file 2: Table S2 presents the percentages of CTCs at given HER2 intensity scores in both the HER2-positive and HER2–negative groups. With the positive criterion defined as >30% of CTCs over-expressing HER2 (3+), the positive and negative coincidence rates of CTC HER2 were 48% (13/27) and 100% (9/9), respectively, compared with tumor tissue. McNemar’s test demonstrated that the HER2 status of CTCs was significantly different from that of tumor tissues (Table 2, χ2 = 12.07, P = 0.0005).


Circulating tumor cells in HER2-positive metastatic breast cancer patients: a valuable prognostic and predictive biomarker.

Liu Y, Liu Q, Wang T, Bian L, Zhang S, Hu H, Li S, Hu Z, Wu S, Liu B, Jiang Z - BMC Cancer (2013)

Representative images for the 0, 1+, 2+, and 3+ intensities of HER2 expression on CTCs.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3643882&req=5

Figure 2: Representative images for the 0, 1+, 2+, and 3+ intensities of HER2 expression on CTCs.
Mentions: HER2 expression intensity in CTCs was given a score of 0, 1+, 2+, or 3+, according to the criteria described previously [28,29], and representative images are shown in Figure 2. Additional file 2: Table S2 presents the percentages of CTCs at given HER2 intensity scores in both the HER2-positive and HER2–negative groups. With the positive criterion defined as >30% of CTCs over-expressing HER2 (3+), the positive and negative coincidence rates of CTC HER2 were 48% (13/27) and 100% (9/9), respectively, compared with tumor tissue. McNemar’s test demonstrated that the HER2 status of CTCs was significantly different from that of tumor tissues (Table 2, χ2 = 12.07, P = 0.0005).

Bottom Line: Among patients with HER2-positive CTCs, the median PFS for those receiving anti-HER2 therapy was significantly longer than those who were not (8.8 vs. 1.5 months, P=0.001).Notably, up to 52% (14/27) of the HER2-positive patients were CTC HER2-negative, and anti-HER2 therapy did not significantly improve the median PFS in these patients (2.5 vs. 0.9 months, P=0.499).Our findings underscore the necessity of a comprehensive CTC analysis, which may provide valuable prognostic and predictive information for optimizing individually tailored therapies in HER2-positive MBC patients.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Breast Cancer, Affiliated Hospital of Academy of Military Medical Sciences, No.8 Dongdajie, Beijing, 100071, China.

ABSTRACT

Background: This study was initiated to investigate the prognostic significance of circulating tumor cell (CTC) enumeration and the predictive value of CTC HER2 expression for efficient anti-HER2 therapy in HER2-positive metastatic breast cancer (MBC) patients.

Methods: Sixty HER2-positive MBC patients were enrolled in the present study. Before the initiation of systemic treatment, CTCs from 7.5 ml of blood were analyzed using the CellSearch system. The progression-free survival (PFS) of the patients was estimated using Kaplan-Meier survival curves.

Results: CTCs were detected in 45% (27/60) of the patients, who had shorter median PFS than those without CTCs (2.5 vs. 7.5 months, P=0.0125). Furthermore, referring to the standard HER2 testing that uses immunohistochemistry (IHC), we proposed a CTC HER2-positive criterion, defined as >30% of CTCs over-expressing HER2. Among patients undergoing anti-HER2 therapy, those with HER2-positive CTCs had longer PFS (8.8 vs. 2.5 months, P=0.002). Among patients with HER2-positive CTCs, the median PFS for those receiving anti-HER2 therapy was significantly longer than those who were not (8.8 vs. 1.5 months, P=0.001). Notably, up to 52% (14/27) of the HER2-positive patients were CTC HER2-negative, and anti-HER2 therapy did not significantly improve the median PFS in these patients (2.5 vs. 0.9 months, P=0.499).

Conclusions: Our findings underscore the necessity of a comprehensive CTC analysis, which may provide valuable prognostic and predictive information for optimizing individually tailored therapies in HER2-positive MBC patients. To test this idea, additional large cohort, multi-center and prospective clinical trials are needed.

Show MeSH
Related in: MedlinePlus