Dataset Information

Influence of secreted frizzled receptor protein 1 (SFRP1) on neoadjuvant chemotherapy in triple negative breast cancer does not rely on WNT signaling.

ABSTRACT:

Background

Triple negative breast cancer (TNBC) is characterized by lack of expression of both estrogen and progesterone receptor as well as lack of overexpression or amplification of HER2. Despite an increased probability of response to chemotherapy, many patients resistant to current chemotherapy regimens suffer from a worse prognosis compared to other breast cancer subtypes. However, molecular determinants of response to chemotherapy specific to TNBC remain largely unknown. Thus, there is a high demand for biomarkers potentially stratifying triple negative breast cancer patients for neoadjuvant chemotherapies or alternative therapies.

Methods

In order to identify genes correlating with both the triple negative breast cancer subtype as well as response to neoadjuvant chemotherapy we employed publicly available gene expression profiles of patients, which had received neoadjuvant chemotherapy. Analysis of tissue microarrays as well as breast cancer cell lines revealed correlation to the triple negative breast cancer subtype. Subsequently, effects of siRNA-mediated knockdown on response to standard chemotherapeutic agents as well as radiation therapy were analyzed. Additionally, we evaluated the molecular mechanisms by which SFRP1 alters the carcinogenic properties of breast cancer cells.

Results

SFRP1 was identified as being significantly overexpressed in TNBC compared to other breast cancer subtypes. Additionally, SFRP1 expression is significantly correlated with an increased probability of positive response to neoadjuvant chemotherapy. Knockdown of SFRP1 in triple negative breast cancer cells renders the cells more resistant to standard chemotherapy. Moreover, tumorigenic properties of the cells are modified by knockdown, as shown by both migration or invasion capacity as well reduced apoptotic events. Surprisingly, we found that these effects do not rely on Wnt signaling. Furthermore, we show that pro-apoptotic as well as migratory pathways are differentially regulated after SFRP1 knockdown.

Conclusion

We could firstly show that SFRP1 strongly correlates with the triple negative breast cancer subtype and secondly, that SFRP1 might be used as a marker stratifying patients to positively respond to neoadjuvant chemotherapy. The mechanisms by which tumor suppressor SFRP1 influences carcinogenic properties of cancer cells do not rely on Wnt signaling, thereby demonstrating the complexity of tumor associated signaling pathways.

SUBMITTER: Bernemann C

PROVIDER: S-EPMC4110378 | biostudies-literature | 2014 Jul

REPOSITORIES: biostudies-literature

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Publications

Influence of secreted frizzled receptor protein 1 (SFRP1) on neoadjuvant chemotherapy in triple negative breast cancer does not rely on WNT signaling.

Bernemann Christof C Hülsewig Carolin C Ruckert Christian C Schäfer Sarah S Blümel Lena L Hempel Georg G Götte Martin M Greve Burkhard B Barth Peter J PJ Kiesel Ludwig L Liedtke Cornelia C

Molecular cancer 20140717

<h4>Background</h4>Triple negative breast cancer (TNBC) is characterized by lack of expression of both estrogen and progesterone receptor as well as lack of overexpression or amplification of HER2. Despite an increased probability of response to chemotherapy, many patients resistant to current chemotherapy regimens suffer from a worse prognosis compared to other breast cancer subtypes. However, molecular determinants of response to chemotherapy specific to TNBC remain largely unknown. Thus, ther ...[more]

PMID: 25033833

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Project description:PurposeThis study aims to explore whether neoadjuvant chemotherapy with immunotherapy (NACI) leads to different tumor shrinkage patterns, based on magnetic resonance imaging (MRI), compared to neoadjuvant chemotherapy (NAC) alone in patients with triple-negative breast cancer (TNBC). Additionally, the study investigates the relationship between tumor shrinkage patterns and treatment efficacy was investigated.MethodsThis retrospective study included patients with TNBC patients receiving NAC or NACI from January 2019 until July 2021 at our center. Pre- and post-treatment MRI results were obtained for each patient, and tumor shrinkage patterns were classified into three categories as follows: 1) concentric shrinkage (CS); 2) diffuse decrease; and 3) no change. Tumor shrinkage patterns were compared between the NAC and NACI groups, and the relevance of the patterns to treatment efficacy was assessed.ResultsOf the 99 patients, 65 received NAC and 34 received NACI. The CS pattern was observed in 53% and 20% of patients in the NAC and NACI groups, respectively. Diffuse decrease pattern was observed in 36% and 68% of patients in the NAC and NACI groups. The association between the treatment regimens (NAC and NACI) and tumor shrinkage patterns was statistically significant (p = 0.004). The postoperative pathological complete response (pCR) rate was 45% and 82% in the NAC and NACI groups (p < 0.001), respectively. In the NACI group, 17% of patients with the CS pattern and 56% of those with the diffuse decrease pattern achieved pCR (p = 0.903). All tumor shrinkage patterns were associated with achieved a high pCR rate in the NACI group.ConclusionOur study demonstrates that the diffuse decrease pattern of tumor shrinkage is more common following NACI than that following NAC. Furthermore, our findings suggest that all tumor shrinkage patterns are associated with a high pCR rate in patients with TNBC treated with NACI.Trial registrationClinicalTrials.gov Identifier: NCT04909554.

Dataset Information

Influence of secreted frizzled receptor protein 1 (SFRP1) on neoadjuvant chemotherapy in triple negative breast cancer does not rely on WNT signaling.

Background

Methods

Results

Conclusion

Publications

Influence of secreted frizzled receptor protein 1 (SFRP1) on neoadjuvant chemotherapy in triple negative breast cancer does not rely on WNT signaling.

Similar Datasets

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