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Osteopontin splice variants are differential predictors of breast cancer treatment responses.

Zduniak K, Agrawal A, Agrawal S, Hossain MM, Ziolkowski P, Weber GF - BMC Cancer (2016)

Bottom Line: It is not known which splice variants may mediate treatment resistance.We found from Cox hazard models, logrank test and Wilcoxon test that osteopontin exon 4 was associated with a favorable response to tamoxifen, but a poor response to chemotherapy with CMF (cyclophosphamide, methotrexate, fluorouracil).Osteopontin-c is prognostic, but falls short of being a significant predictor for sensitivity to treatment.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, Wroclaw Medical University, Wroclaw, Poland.

ABSTRACT

Background: Osteopontin is a marker for breast cancer progression, which in previous studies has also been associated with resistance to certain anti-cancer therapies. It is not known which splice variants may mediate treatment resistance.

Methods: Here we analyze the association of osteopontin variant expression before treatment, differentiated according to immunohistochemistry with antibodies to exon 4 and to the osteopontin-c splice junction respectively, with the ensuing therapy responses in 119 Polish breast cancer patients who presented between 1995 and 2008.

Results: We found from Cox hazard models, logrank test and Wilcoxon test that osteopontin exon 4 was associated with a favorable response to tamoxifen, but a poor response to chemotherapy with CMF (cyclophosphamide, methotrexate, fluorouracil). Osteopontin-c is prognostic, but falls short of being a significant predictor for sensitivity to treatment.

Conclusions: The addition of osteopontin splice variant immunohistochemistry to standard pathology work-ups has the potential to aid decision making in breast cancer treatment.

No MeSH data available.


Related in: MedlinePlus

Kaplan-Meier survival curves for patients undergoing hormone therapy. Survival of patients under hormone treatment, distinguished according to low (levels 0–1) versus high (levels 2–3) osteopontin-c staining (top left), low versus high osteopontin-exon 4 staining (top right), or low (1) versus high (2–3) tumor grade (bottom left). The overall survival of patients receiving hormone treatment versus not receiving hormone treatment is shown for comparison on the bottom right. Untreated subgroups are displayed in black, treated subgroups in gray, low marker levels are shown as circles, high marker levels as triangles. The x-axis indicates years since diagnosis, the y-axis reflects % surviving patients
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Fig1: Kaplan-Meier survival curves for patients undergoing hormone therapy. Survival of patients under hormone treatment, distinguished according to low (levels 0–1) versus high (levels 2–3) osteopontin-c staining (top left), low versus high osteopontin-exon 4 staining (top right), or low (1) versus high (2–3) tumor grade (bottom left). The overall survival of patients receiving hormone treatment versus not receiving hormone treatment is shown for comparison on the bottom right. Untreated subgroups are displayed in black, treated subgroups in gray, low marker levels are shown as circles, high marker levels as triangles. The x-axis indicates years since diagnosis, the y-axis reflects % surviving patients

Mentions: Tamoxifen is a selective estrogen receptor modulator that is used for the treatment of both early and advanced ER+ (estrogen receptor positive) breast cancers in pre- and post-menopausal women. Kaplan-Meier curves (Fig. 1) suggested a moderate survival benefit from treatment. When comparing hormone-treated to non-hormone-treated patients, low-grade cancers (grade 1) responded better to treatment than high-grade cancers (grade 2–3). In contrast, patients with high intensity staining (2–3) of exon 4 or osteopontin-c responded better to hormone therapy than those with low intensity staining (0–1) of these markers, as judged by a divergence with time between the hormone-treated and the non-hormone-treated patient groups at high marker intensity, but much less at low marker intensity.Fig. 1


Osteopontin splice variants are differential predictors of breast cancer treatment responses.

Zduniak K, Agrawal A, Agrawal S, Hossain MM, Ziolkowski P, Weber GF - BMC Cancer (2016)

Kaplan-Meier survival curves for patients undergoing hormone therapy. Survival of patients under hormone treatment, distinguished according to low (levels 0–1) versus high (levels 2–3) osteopontin-c staining (top left), low versus high osteopontin-exon 4 staining (top right), or low (1) versus high (2–3) tumor grade (bottom left). The overall survival of patients receiving hormone treatment versus not receiving hormone treatment is shown for comparison on the bottom right. Untreated subgroups are displayed in black, treated subgroups in gray, low marker levels are shown as circles, high marker levels as triangles. The x-axis indicates years since diagnosis, the y-axis reflects % surviving patients
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4940753&req=5

Fig1: Kaplan-Meier survival curves for patients undergoing hormone therapy. Survival of patients under hormone treatment, distinguished according to low (levels 0–1) versus high (levels 2–3) osteopontin-c staining (top left), low versus high osteopontin-exon 4 staining (top right), or low (1) versus high (2–3) tumor grade (bottom left). The overall survival of patients receiving hormone treatment versus not receiving hormone treatment is shown for comparison on the bottom right. Untreated subgroups are displayed in black, treated subgroups in gray, low marker levels are shown as circles, high marker levels as triangles. The x-axis indicates years since diagnosis, the y-axis reflects % surviving patients
Mentions: Tamoxifen is a selective estrogen receptor modulator that is used for the treatment of both early and advanced ER+ (estrogen receptor positive) breast cancers in pre- and post-menopausal women. Kaplan-Meier curves (Fig. 1) suggested a moderate survival benefit from treatment. When comparing hormone-treated to non-hormone-treated patients, low-grade cancers (grade 1) responded better to treatment than high-grade cancers (grade 2–3). In contrast, patients with high intensity staining (2–3) of exon 4 or osteopontin-c responded better to hormone therapy than those with low intensity staining (0–1) of these markers, as judged by a divergence with time between the hormone-treated and the non-hormone-treated patient groups at high marker intensity, but much less at low marker intensity.Fig. 1

Bottom Line: It is not known which splice variants may mediate treatment resistance.We found from Cox hazard models, logrank test and Wilcoxon test that osteopontin exon 4 was associated with a favorable response to tamoxifen, but a poor response to chemotherapy with CMF (cyclophosphamide, methotrexate, fluorouracil).Osteopontin-c is prognostic, but falls short of being a significant predictor for sensitivity to treatment.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, Wroclaw Medical University, Wroclaw, Poland.

ABSTRACT

Background: Osteopontin is a marker for breast cancer progression, which in previous studies has also been associated with resistance to certain anti-cancer therapies. It is not known which splice variants may mediate treatment resistance.

Methods: Here we analyze the association of osteopontin variant expression before treatment, differentiated according to immunohistochemistry with antibodies to exon 4 and to the osteopontin-c splice junction respectively, with the ensuing therapy responses in 119 Polish breast cancer patients who presented between 1995 and 2008.

Results: We found from Cox hazard models, logrank test and Wilcoxon test that osteopontin exon 4 was associated with a favorable response to tamoxifen, but a poor response to chemotherapy with CMF (cyclophosphamide, methotrexate, fluorouracil). Osteopontin-c is prognostic, but falls short of being a significant predictor for sensitivity to treatment.

Conclusions: The addition of osteopontin splice variant immunohistochemistry to standard pathology work-ups has the potential to aid decision making in breast cancer treatment.

No MeSH data available.


Related in: MedlinePlus