New Breast Cancer Classification Based on Epigenetics

The gist: Breast cancer can be broken down into different subtypes that behave differently and might be treated differently. New research has shown that characteristics of DNA known as epigenetic marks can be used to categorize different subtypes of breast cancer. Tumors with different epigenetic marks might need different treatment. In the future, doctors might use epigenetic marks to identify which patients need more aggressive treatments.

“Breast cancer is the most common in women. One in nine will suffer breast cancer over their lifetime. Progress in prevention and early detection, and the use of chemotherapy after surgery (adjuvant chemotherapy), have achieved significantly increase survival in this disease in the last ten years, but much remains to be done.

“The identification of patients with high-risk breast cancer is key to knowing whether a patient will require only the removal of the tumor by surgery or whether if she will need additional chemotherapy to make sure the removal of breast cancer cells. Currently, known genetic mutations and expression patterns are determined, but the puzzle of the genetics of the disease remains a large unfinished part.

“The director of the Program Epigenetics and Cancer Biology (PEBC) at Bellvitge Biomedical Research Instiute (IDIBELL), Professor of Genetics at the University of Barcelona and ICREA researcher, Manel Esteller, has established the epigenetic patterns of breast cancer and also its clinical consequences. The finding is published in the journal Molecular Oncology.

” ‘We’ve analyzed epigenetic alterations, namely the chemical signal called DNA methylation in 500 breast tumors and have compared the patterns obtained with the clinical behavior of these cancers,’ says Esteller.”


Drug Shows Promise for Subset of Stage III Colon Cancer Patients

This article describes the results of a clinical trial—a research study with volunteer patients. The trial tested adding a third drug to a standard two-drug chemotherapy treatment for colorectal cancer. The standard treatment consists of the drugs fluorouracil and leucovorin. It is given to patients after tumor-removal surgery to keep the cancer from coming back (recurrence). In the trial, a third drug called irinotecan was added. The researchers found that stage III patients whose tumors tested positive for a genetic change called CIMP benefitted from the irinotecan addition. Stage III CIMP-negative patients did not.

“When added to the standard chemotherapy treatment — fluorouracil and leucovorin — adjuvant irinotecan therapy improved overall survival rates for patients with the CpG island methylator phenotype (CIMP). CIMP is seen in about 10 to 20 percent of colorectal cancers. Patients with CIMP-negative tumors, however, exhibited significant harm from the addition of irinotecan — overall survival was 68 percent compared with 78 percent for those receiving the standard treatment alone.

“Our results serve as an example that the molecular characterization of individual tumors may help to determine the most appropriate treatment for patients with colon cancer,” said lead study author Stacey Shiovitz, MD, from the department of medicine, University of Washington, Seattle, WA, and the clinical research division of Fred Hutchinson Cancer Research Center, also in Seattle. “Based on our findings, identification of a tumor’s CIMP status should play a greater role in the clinical setting.”


Value of Epigenetic Test for Markers of Prostate Cancer Affirmed in Study

“A commercial test designed to rule out the presence of genetic biomarkers of prostate cancer may be accurate enough to exclude the need for repeat prostate biopsies in many — if not most — men, a new article reports. ‘Often, one biopsy is not enough to definitively rule out prostate cancer, says a study researcher. ‘Our research finds that by looking for the presence or absence of cancer in a different way, we may be able to offer many men peace of mind without putting them through the pain, bleeding and risk of infection that can come with a repeat biopsy.’ “


Depleting Tumor-Specific Tregs at a Single Site Eradicates Disseminated Tumors

“Activation of TLR9 by direct injection of unmethylated CpG nucleotides into a tumor can induce a therapeutic immune response; however, Tregs eventually inhibit the antitumor immune response and thereby limit the power of cancer immunotherapies. In tumor-bearing mice, we found that Tregs within the tumor preferentially express the cell surface markers CTLA-4 and OX40.”


Depleting Tumor-Specific Tregs at a Single Site Eradicates Disseminated Tumors

“Activation of TLR9 by direct injection of unmethylated CpG nucleotides into a tumor can induce a therapeutic immune response; however, Tregs eventually inhibit the antitumor immune response and thereby limit the power of cancer immunotherapies. In tumor-bearing mice, we found that Tregs within the tumor preferentially express the cell surface markers CTLA-4 and OX40.”


Depleting Tumor-Specific Tregs at a Single Site Eradicates Disseminated Tumors

“Activation of TLR9 by direct injection of unmethylated CpG nucleotides into a tumor can induce a therapeutic immune response; however, Tregs eventually inhibit the antitumor immune response and thereby limit the power of cancer immunotherapies. In tumor-bearing mice, we found that Tregs within the tumor preferentially express the cell surface markers CTLA-4 and OX40.”


Methylated Tissue Factor Pathway Inhibitor 2 (TFPI2) DNA in Serum Is a Biomarker of Metastatic Melanoma

Transcriptional silencing of tissue factor pathway inhibitor 2 (TFPI2) occurs in several human tumors including melanoma. We investigated methylated TFPI2 as a biomarker of metastatic melanoma using qRT-PCR to assess TFPI2 expression and pyrosequencing to analyze CpG island methylation in malignant melanoma cell lines, in benign nevi, in 112 primary and metastatic melanomas, and in serum from 6 healthy individuals and 35 patients: 20 patients with primary and 15 patients with metastatic melanoma…”