Serum DNA methylation for monitoring response to neoadjuvant chemotherapy in breast cancer patients

Ayelet Avraham, Ronit Uhlmann, Aino Shperber, Miriam Birnbaum, Judith Sandbank, Avishay Sella, Saraswati Sukumar, Ella Evron

Research output: Contribution to journalArticle

Abstract

Patients with large or nonoperable breast cancers often receive neoadjuvant chemotherapy to facilitate full resection of the tumor and enable conservation of the breast. However, currently available methods for evaluation of response during therapy are limited and the actual effect of the treatment is only recognized at surgery upon completion of chemotherapy. Timely assessment of response could allow individual tailoring of the treatment and save noneffective drugs and unnecessary toxicity. Here, we suggest that tumor derived DNA methylation in the serum may reflect changes in tumor burden and allow early recognition of responders versus nonresponders. In this pilot study, we collected 7 consecutive serum samples from 52 patients with locally advanced breast cancer during neoadjuvant chemotherapy. We selected RASSF1, which was methylated in more than 80% of the tumors, for serum analysis. Using the "methylation sensitive PCR and high resolution melting," we detected RASSF1 methylation in the serum of 21 patients prior to therapy. In four patients who achieved complete pathological response, RASSF1 methylation in the serum became undetectable early during therapy. In contrast, in 17 patients that had partial or minimal pathological response, serum RASSF1 methylation persisted longer or throughout the treatment (complete versus partial response p = 0.02). These findings support further development of this assay for monitoring response during neoadjuvant therapy.

Original languageEnglish (US)
JournalInternational Journal of Cancer
Volume131
Issue number7
DOIs
StatePublished - Oct 1 2012

Fingerprint

DNA Methylation
Breast Neoplasms
Drug Therapy
Methylation
Serum
Therapeutics
Neoplasms
Neoadjuvant Therapy
Secondary Prevention
Tumor Burden
Drug-Related Side Effects and Adverse Reactions
Freezing
Breast
Polymerase Chain Reaction

Keywords

  • locally advanced breast cancer
  • monitoring response
  • neoadjuvant therapy
  • serum DNA methylation

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Avraham, A., Uhlmann, R., Shperber, A., Birnbaum, M., Sandbank, J., Sella, A., ... Evron, E. (2012). Serum DNA methylation for monitoring response to neoadjuvant chemotherapy in breast cancer patients. International Journal of Cancer, 131(7). https://doi.org/10.1002/ijc.27526

Serum DNA methylation for monitoring response to neoadjuvant chemotherapy in breast cancer patients. / Avraham, Ayelet; Uhlmann, Ronit; Shperber, Aino; Birnbaum, Miriam; Sandbank, Judith; Sella, Avishay; Sukumar, Saraswati; Evron, Ella.

In: International Journal of Cancer, Vol. 131, No. 7, 01.10.2012.

Research output: Contribution to journalArticle

Avraham, Ayelet ; Uhlmann, Ronit ; Shperber, Aino ; Birnbaum, Miriam ; Sandbank, Judith ; Sella, Avishay ; Sukumar, Saraswati ; Evron, Ella. / Serum DNA methylation for monitoring response to neoadjuvant chemotherapy in breast cancer patients. In: International Journal of Cancer. 2012 ; Vol. 131, No. 7.
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