Expression Patterns of Biomarkers in Primary Tumors and Corresponding Metastases in Breast Cancer

Tumor heterogeneity has been shown for several cancers including breast cancer (BC). Despite the fact that expression of tumor markers may change throughout the metastatic process, rebiopsies at the time of recurrence are still not performed routinely at all institutions. The aims of the study were to evaluate changes in biomarker profiles during the metastatic process and to investigate whether previous anthracycline or endocrine therapy given in the adjuvant setting could affect the biomarker profile in metastatic lesions. We investigated the expression pattern of ER, HER2, TOP2a, TOP1, p53, Bcl-2, and Ki-67 in 110 paired samples of primary BC and corresponding asynchronous metastases. We found discordant expressions in primary tumor and metastasis for all biomarkers, although only significant for Ki-67. Changes in the expression profile of the metastatic lesions would have altered treatment decisions in 14% of patients. We found no effect of previous anthracycline or endocrine therapy on the expression profiles. Our data confirm that discordant expressions of biomarkers are common in BC and often carry therapeutic consequences. This emphasizes the need for biopsies from metastatic lesions, even in cases where the localization of the metastatic process is not easily accessible.
Source: Applied Immunohistochemistry and Molecular Morphology - Category: Chemistry Tags: Review Article Source Type: research

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ConclusionsPalbociclib in combination with endocrine therapy shows an unexpectedly high CBR and favorable safety profile in heavily pretreated endocrine-resistant estrogen receptor-positive, HER2-negative MBC patients.
Source: Breast Cancer Research and Treatment - Category: Cancer & Oncology Source Type: research
ERα-mediated cell cycle progression is an important requisite for CDK4/6 inhibitor response in HR+ breast cancer. Oncotarget. 2018 Jun 12;9(45):27736-27751 Authors: Petrossian K, Kanaya N, Lo C, Hsu PY, Nguyen D, Yang L, Yang L, Warden C, Wu X, Pillai R, Bernal L, Huang CS, Kruper L, Yuan Y, Somlo G, Mortimer J, Chen S Abstract While ER has multiple biological effects, ER-cyclin D1-CDK4/6-RB is a critical pathway for the action of estrogen on the cell cycle, especially for breast cancers that rely on estrogen for growth. The latest and most efficient CDK4/6 inhibitors target the phosphorylation o...
Source: Oncotarget - Category: Cancer & Oncology Tags: Oncotarget Source Type: research
ConclusionPost-menopausal women with HR+/HER2 − mBC receiving first-line therapy with CDK4/6, ET, or chemotherapy were regularly monitored regardless of the first-line regimen received.FundingNovartis Pharmaceuticals Corporation.
Source: Advances in Therapy - Category: Drugs & Pharmacology Source Type: research
Authors: AlFakeeh A, Brezden-Masley C Abstract Endocrine therapy, a major modality in the treatment of hormone receptor (hr)-positive breast cancer (bca), has improved outcomes in metastatic and nonmetastatic disease. However, a limiting factor to the use of endocrine therapy in bca is resistance resulting from the development of escape pathways that promote the survival of cancer cells despite estrogen receptor (er)-targeted therapy. The resistance pathways involve extensive cross-talk between er and receptor tyrosine kinase growth factors [epidermal growth factor receptor, human epidermal growth factor receptor 2...
Source: Current Oncology - Category: Cancer & Oncology Tags: Curr Oncol Source Type: research
Cancers, Vol. 10, Pages 209: Crosstalk between ERα and Receptor Tyrosine Kinase Signalling and Implications for the Development of Anti-Endocrine Resistance Cancers doi: 10.3390/cancers10060209 Authors: Rugaia Z. Montaser Helen M. Coley Although anti-endocrine therapies have significantly advanced the treatment of breast cancer, they pose the problem of acquired drug resistance. The oestrogen receptor (ER)-expressing breast cancer cell lines MCF-7 and T47D alongside their in vitro derived resistant counterparts MCF-7-TR (tamoxifen-resistant) and T47D-FR (fulvestrant-resistant) showed dual resistance to fulv...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
Conditions:   Anatomic Stage III Breast Cancer AJCC v8;   Anatomic Stage IIIA Breast Cancer AJCC v8;   Anatomic Stage IIIB Breast Cancer AJCC v8;   Anatomic Stage IIIC Breast Cancer AJCC v8;   Anatomic Stage IV Breast Cancer AJCC v8;   Estrogen Receptor Positive;   HER2/N eu Negative;   Invasive Breast Carcinoma;   Prognostic Stage III Breast Cancer AJCC v8;   Prognostic&n...
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
Conclusion: Palbociclib has clinical activity as a single agent in women with moderately pre-treated, oestrogen receptor-positive, HER2-negative advanced breast cancer. Palbociclib may have potential to reverse endocrine resistance in patients with a history of previous durable response to ET. Clinical trial information: NCT02549430. PMID: 29893790 [PubMed - as supplied by publisher]
Source: Ann Oncol - Category: Cancer & Oncology Authors: Tags: Ann Oncol Source Type: research
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