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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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Related in: MedlinePlus

Kaplan-Meier PFS plots of patients who have >30% or ≤30% of their CTCs with an HER2 intensity score of 3+, with or without anti-HER2 therapy. PFS was calculated from the time of the baseline blood draw. Coordinates of the dashed lines indicate median survival time.
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Figure 3: Kaplan-Meier PFS plots of patients who have >30% or ≤30% of their CTCs with an HER2 intensity score of 3+, with or without anti-HER2 therapy. PFS was calculated from the time of the baseline blood draw. Coordinates of the dashed lines indicate median survival time.

Mentions: Twenty-seven patients with a CTC count ≥1 were divided into 4 groups based on their CTC HER2 status and whether they were receiving anti-HER2 therapy. Groups 1 and 2 consisted of patients with HER2 3+ CTC >30%, and groups 3 and 4 consisted of patients with HER2 3+ CTC ≤30%. Although all patients were histologically positive for HER2 and therefore should have received anti-HER2 therapy, patients in groups 2 and 4 did not receive the treatment for economic reasons. Kaplan-Meier plots of the PFS values for all of the groups are shown in Figure 3. Statistical analysis demonstrated that among the patients who received anti-HER2 therapy (N = 18, groups 1 and 3), only those with HER2-positive CTCs have benefited (8.8 vs. 2.5 months, P = 0.002). Among the patients with HER2-positive CTCs (N = 13, groups 1 and 2), the median PFS for those receiving anti-HER2 therapy was significantly longer than that for those without anti-HER2 therapy (8.8 vs. 1.5 months, P = 0.001). Notably, up to 52% (14/27) of the patients who were histologically assessed as HER2-positive had HER2-negative CTCs (N = 14, groups 3 and 4), and anti-HER2 therapy did not significantly improve the median PFS for these patients (2.5 vs. 0.9 months, P = 0.499). In addition, we also compared the PFS of HER2 3+ >10% vs. < 10%, HER2 3+ vs. HER2 (2+ and 1+) as well as HER2 (3+ and 2+) vs. HER2 (1+ and 0), but found no significant difference (data not shown).


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)

Kaplan-Meier PFS plots of patients who have >30% or ≤30% of their CTCs with an HER2 intensity score of 3+, with or without anti-HER2 therapy. PFS was calculated from the time of the baseline blood draw. Coordinates of the dashed lines indicate median survival time.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 3: Kaplan-Meier PFS plots of patients who have >30% or ≤30% of their CTCs with an HER2 intensity score of 3+, with or without anti-HER2 therapy. PFS was calculated from the time of the baseline blood draw. Coordinates of the dashed lines indicate median survival time.
Mentions: Twenty-seven patients with a CTC count ≥1 were divided into 4 groups based on their CTC HER2 status and whether they were receiving anti-HER2 therapy. Groups 1 and 2 consisted of patients with HER2 3+ CTC >30%, and groups 3 and 4 consisted of patients with HER2 3+ CTC ≤30%. Although all patients were histologically positive for HER2 and therefore should have received anti-HER2 therapy, patients in groups 2 and 4 did not receive the treatment for economic reasons. Kaplan-Meier plots of the PFS values for all of the groups are shown in Figure 3. Statistical analysis demonstrated that among the patients who received anti-HER2 therapy (N = 18, groups 1 and 3), only those with HER2-positive CTCs have benefited (8.8 vs. 2.5 months, P = 0.002). Among the patients with HER2-positive CTCs (N = 13, groups 1 and 2), the median PFS for those receiving anti-HER2 therapy was significantly longer than that for those without anti-HER2 therapy (8.8 vs. 1.5 months, P = 0.001). Notably, up to 52% (14/27) of the patients who were histologically assessed as HER2-positive had HER2-negative CTCs (N = 14, groups 3 and 4), and anti-HER2 therapy did not significantly improve the median PFS for these patients (2.5 vs. 0.9 months, P = 0.499). In addition, we also compared the PFS of HER2 3+ >10% vs. < 10%, HER2 3+ vs. HER2 (2+ and 1+) as well as HER2 (3+ and 2+) vs. HER2 (1+ and 0), but found no significant difference (data not shown).

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