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PTK7 as a potential prognostic and predictive marker of response to adjuvant chemotherapy in breast cancer patients, and resistance to anthracycline drugs.

Ataseven B, Gunesch A, Eiermann W, Kates RE, Högel B, Knyazev P, Ullrich A, Harbeck N - Onco Targets Ther (2014)

Bottom Line: Recent studies in acute myeloid leukemia have associated PTK7 expression with resistance to anthracycline therapy.Association of PTK7 expression with clinicopathological features was seen only for age in PTT and nodal stage in LNT.High LN PTK7 was associated with poorer disease-free survival (DFS) in the total population (3-year DFS: low [81.7%] versus high [70.4%]; P=0.016) and in patients without adjuvant chemotherapy (3-year DFS: low [91.7%] versus high [22.3%]; P<0.001), but not in patients receiving adjuvant chemotherapy (P=0.552).

View Article: PubMed Central - PubMed

Affiliation: Department of Gynecology and Gynecologic Oncology, Kliniken Essen-Mitte, Essen, Germany ; Department of Gynecology and Obstetrics, Rotkreuzklinikum Munich, Munich, Germany.

ABSTRACT
Biomarkers predicting resistance to particular chemotherapy regimens could play a key role in optimally individualized treatment concepts. PTK7 (protein tyrosine kinase 7) belongs to the receptor tyrosine kinase family involved in several physiological, but also malignant, cell behaviors. Recent studies in acute myeloid leukemia have associated PTK7 expression with resistance to anthracycline therapy. PTK7 mRNA expression in primary tumor tissue (PTT) and corresponding lymph node tissue (LNT) were retrospectively measured in 117 patients with early breast cancer; PTK7 expression was available in 103 PTT and 108 LNT samples. Median age was 60 years (range, 27-87 years). At a median follow-up of 28.5 months, 6 deaths and 16 recurrences had occurred. PTK7 expression correlations with clinicopathological features were computed and PTK7 expression effects on patient outcome were analyzed in three cohorts defined by adjuvant treatment: anthracycline-based treatment, other chemotherapy regimens (including taxane or other substances), or no chemotherapy. Association of PTK7 expression with clinicopathological features was seen only for age in PTT and nodal stage in LNT. High LN PTK7 was associated with poorer disease-free survival (DFS) in the total population (3-year DFS: low [81.7%] versus high [70.4%]; P=0.016) and in patients without adjuvant chemotherapy (3-year DFS: low [91.7%] versus high [22.3%]; P<0.001), but not in patients receiving adjuvant chemotherapy (P=0.552). DFS stratified by PTK7 expression was compared in treatment cohorts: In patients with low LN PTK7 expression, neither chemotherapy cohort showed significantly better survival than the no-chemotherapy cohort. In patients with high LN PTK7 expression, those receiving chemotherapy, including substances other than anthracyclines, but not those receiving only anthracycline-based chemotherapy, showed significantly better DFS than those receiving no chemotherapy (P=0.001). Our results support earlier findings that PTK7 may be a prognostic and predictive marker associated with resistance to anthracycline-based chemotherapy. Further investigations are needed to validate these findings in breast cancer.

No MeSH data available.


Related in: MedlinePlus

Kaplan–Meier curves for disease-free survival (DFS). (A) DFS in patients with and without adjuvant chemotherapy. (B) DFS in patients without adjuvant chemotherapy based on PTK7 expression. (C) DFS in patients with adjuvant chemotherapy based on PTK7 expression.
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f1-ott-7-1723: Kaplan–Meier curves for disease-free survival (DFS). (A) DFS in patients with and without adjuvant chemotherapy. (B) DFS in patients without adjuvant chemotherapy based on PTK7 expression. (C) DFS in patients with adjuvant chemotherapy based on PTK7 expression.

Mentions: PTK7 mRNA expression in PTT and corresponding LNT were retrospectively measured in 117 early BC patients. Median age at diagnosis was 60 years (range, 27–87 years). At a median follow-up period of 28.5 months, there were 16 recurrences (13 distant, 3 local) and 6 deaths. For analysis, we defined cohort A as patients receiving exclusively anthracycline-based chemotherapy, cohort B as those receiving chemotherapy including agents other than anthracyclines (eg, taxane-based and others), and cohort C as patients receiving no chemotherapy. Table 1 describes and compares key parameters by cohort: Patients receiving no chemotherapy (cohort C) were older (median age, 72 years) than in cohorts A and B (60 and 49 years, respectively). Significant differences among the three cohorts occurred in nodal status, histological type, and HER2 status. Neither in paired comparisons among the three treatment cohorts nor in comparisons of chemotherapy versus no chemotherapy (P=0.340; Figure 1A) were significant differences in DFS or OS observed.


PTK7 as a potential prognostic and predictive marker of response to adjuvant chemotherapy in breast cancer patients, and resistance to anthracycline drugs.

Ataseven B, Gunesch A, Eiermann W, Kates RE, Högel B, Knyazev P, Ullrich A, Harbeck N - Onco Targets Ther (2014)

Kaplan–Meier curves for disease-free survival (DFS). (A) DFS in patients with and without adjuvant chemotherapy. (B) DFS in patients without adjuvant chemotherapy based on PTK7 expression. (C) DFS in patients with adjuvant chemotherapy based on PTK7 expression.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4199823&req=5

f1-ott-7-1723: Kaplan–Meier curves for disease-free survival (DFS). (A) DFS in patients with and without adjuvant chemotherapy. (B) DFS in patients without adjuvant chemotherapy based on PTK7 expression. (C) DFS in patients with adjuvant chemotherapy based on PTK7 expression.
Mentions: PTK7 mRNA expression in PTT and corresponding LNT were retrospectively measured in 117 early BC patients. Median age at diagnosis was 60 years (range, 27–87 years). At a median follow-up period of 28.5 months, there were 16 recurrences (13 distant, 3 local) and 6 deaths. For analysis, we defined cohort A as patients receiving exclusively anthracycline-based chemotherapy, cohort B as those receiving chemotherapy including agents other than anthracyclines (eg, taxane-based and others), and cohort C as patients receiving no chemotherapy. Table 1 describes and compares key parameters by cohort: Patients receiving no chemotherapy (cohort C) were older (median age, 72 years) than in cohorts A and B (60 and 49 years, respectively). Significant differences among the three cohorts occurred in nodal status, histological type, and HER2 status. Neither in paired comparisons among the three treatment cohorts nor in comparisons of chemotherapy versus no chemotherapy (P=0.340; Figure 1A) were significant differences in DFS or OS observed.

Bottom Line: Recent studies in acute myeloid leukemia have associated PTK7 expression with resistance to anthracycline therapy.Association of PTK7 expression with clinicopathological features was seen only for age in PTT and nodal stage in LNT.High LN PTK7 was associated with poorer disease-free survival (DFS) in the total population (3-year DFS: low [81.7%] versus high [70.4%]; P=0.016) and in patients without adjuvant chemotherapy (3-year DFS: low [91.7%] versus high [22.3%]; P<0.001), but not in patients receiving adjuvant chemotherapy (P=0.552).

View Article: PubMed Central - PubMed

Affiliation: Department of Gynecology and Gynecologic Oncology, Kliniken Essen-Mitte, Essen, Germany ; Department of Gynecology and Obstetrics, Rotkreuzklinikum Munich, Munich, Germany.

ABSTRACT
Biomarkers predicting resistance to particular chemotherapy regimens could play a key role in optimally individualized treatment concepts. PTK7 (protein tyrosine kinase 7) belongs to the receptor tyrosine kinase family involved in several physiological, but also malignant, cell behaviors. Recent studies in acute myeloid leukemia have associated PTK7 expression with resistance to anthracycline therapy. PTK7 mRNA expression in primary tumor tissue (PTT) and corresponding lymph node tissue (LNT) were retrospectively measured in 117 patients with early breast cancer; PTK7 expression was available in 103 PTT and 108 LNT samples. Median age was 60 years (range, 27-87 years). At a median follow-up of 28.5 months, 6 deaths and 16 recurrences had occurred. PTK7 expression correlations with clinicopathological features were computed and PTK7 expression effects on patient outcome were analyzed in three cohorts defined by adjuvant treatment: anthracycline-based treatment, other chemotherapy regimens (including taxane or other substances), or no chemotherapy. Association of PTK7 expression with clinicopathological features was seen only for age in PTT and nodal stage in LNT. High LN PTK7 was associated with poorer disease-free survival (DFS) in the total population (3-year DFS: low [81.7%] versus high [70.4%]; P=0.016) and in patients without adjuvant chemotherapy (3-year DFS: low [91.7%] versus high [22.3%]; P<0.001), but not in patients receiving adjuvant chemotherapy (P=0.552). DFS stratified by PTK7 expression was compared in treatment cohorts: In patients with low LN PTK7 expression, neither chemotherapy cohort showed significantly better survival than the no-chemotherapy cohort. In patients with high LN PTK7 expression, those receiving chemotherapy, including substances other than anthracyclines, but not those receiving only anthracycline-based chemotherapy, showed significantly better DFS than those receiving no chemotherapy (P=0.001). Our results support earlier findings that PTK7 may be a prognostic and predictive marker associated with resistance to anthracycline-based chemotherapy. Further investigations are needed to validate these findings in breast cancer.

No MeSH data available.


Related in: MedlinePlus