Model Might Help Predict How TNBC Spreads

Cancer tumors contain a variety of traits that affect their response to treatment and their risk of metastasis.  A team of researchers has used this fact to suggest a model that can predicts how a tumor might evolve.  Their research, published in Cell Reports, emphasizes the importance of mapping the genetic traits of specific tumors.

That is, while we all might be diagnosed with triple-negative breast cancer, our tumors are unique to us.

Led by Kornelia Polyak, at Dana-­Farber Cancer Institute and Harvard Medical School, the researchers analyzed the heterogeneity of tumors from 47 patients   before and after treatment for breast cancer.  After treatment, they found:

• an increase in the number of CD44^-CD24-positive cells in luminal A, luminal B, and TNBC tumors.

• lower levels of CD44^-CD24-negative  cells.

• the cell subpopulations in Her2-positive tumors changed very little.

• the fraction of Ki67-positive cells declined in all cell types in all tumors.

The significance of this research?  In an interview in Genomeweb, Polyak explained: "Based on this knowledge, we could predict which tumor cells will likely be eliminated or slowed down by treatment and how this may change the tumor overall.This knowledge could aid the design of subsequent therapies for those who do not respond to the first line of treatment."

It's one more step toward understanding what TNBC is, rather than just what it isn't, and that is a step toward targeted treatment.  And, maybe, eventually, prevention.

Read more about TNBC in my book, Surviving Triple-Negative Breast Cancer.

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Genes Related to the Metabolism of Fats Linked to Triple-Negative Breast Cancer

News Release from the American Association for Cancer Research

PHILADELPHIA — The overexpression or underexpression of a newly identified set of genes related to lipid metabolism may help physicians identify whether or not a woman is at risk for hormone receptor-positive or hormone receptor-negative breast cancer and to subsequently tailor prevention strategies appropriately, according to data published in Cancer Prevention Research, a journal of the American Association for Cancer Research.

Researchers sought to find a way to identify women at risk for estrogen receptor-negative breast cancer by examining gene expression in the unaffected breasts of women who had a primary breast cancer of known estrogen-receptor status.

They used this approach because prior research has indicated that if women who have had cancer in one breast subsequently develop a cancer in their second breast, the second cancer is likely to have hormone-receptor status that resembles the first cancer.

Using this logic, Khan and colleagues performed fine-needle aspiration on the unaffected breasts of 15 women with estrogen receptor-positive breast cancer and 15 women with estrogen receptor-negative breast cancer. They validated their results in a second group of women: 12 with estrogen receptor-positive disease, 12 with estrogen receptor-negative disease and 12 healthy controls. The cases in each set were matched by age, race and menopausal status.

The researchers identified 13 genes with significantly higher expression levels in samples from estrogen receptor-negative women. Eight of these genes were associated with lipid metabolism.

“This was interesting because obesity is a breast cancer risk factor for postmenopausal women, but obese women are generally thought to be at increased risk for hormone-sensitive cancer,” said Seema A. Khan, M.D., co-leader of the Breast Cancer Program at the Robert H. Lurie Comprehensive Cancer Center of Northwestern University in Chicago.  “We were surprised to see that some of these genes that are associated with lipid metabolism, or the metabolism of fats, are actually more highly expressed in the unaffected breasts of women with estrogen receptor-negative breast cancer.”

The researchers also found significant overexpression of four of the genes associated with lipid metabolism — DHRS2, HMGCS2, HPGD and ACSL3 — in estrogen receptor-negative samples when compared with healthy women. In estrogen receptor-positive samples, two different lipid metabolism-associated genes — UGT2B11 and APOD — were underexpressed.

“It will be a few more steps before this information is practically useful, but we are hoping that it can take us to a place where we can obtain a breast sample from healthy women, see that they are at risk for a certain type of breast cancer and tailor the prevention strategy accordingly,” Khan said.

Please consider a donation to Positives About Negative to keep this site going.  This work is entirely supported by readers.  Just click on the Donate button in the right of the page.  Thank you!

Read more about metabolism and TNBC in my book, Surviving Triple-Negative Breast Cancer.

SOX11 and p53 May Spell Unique Development of Triple-Negative Breast Cancer

Could you create a breast cancer tumor in mature mice by reactivating how embryonic breast cancer cells develop?  And, if you could, what would you learn?

In a study published in the journal Breast Cancer Research, scientists discovered that basal-like  breast cancers with the BRCA1 mutation—many of them triple-negative breast cancers—grow differently than other cancers.  In fact, the way they grow predicts the prognosis of the tumor.

The protein p53 was found to be active in development of these cancers, which supports much previous research.  The also determined that a progenitor cell,  SOX11,  may play a significant role.  A progenitor cel is active in cell development and regulation. In this research, SOX11 was also

• highly expressed in some mammary tumors with the BRCA1 mutation.

• found to regulate breast cancer cell proliferation and cell survival.

This is an initial study, but it gets us closer to understanding the genetic profile of triple-negative breast cancer.

Please consider a donation to Positives About Negative to keep this site going.  This work is entirely supported by readers.  Just click on the Donate button in the right of the page.  Thank you!

Read more about diet and TNBC in my book, Surviving Triple-Negative Breast Cancer.

Most, but not all, TNBC tumors are basal-like

A News Release from University of North Carolina Health Care 

[PAT"S NOTE:  This isn't really all that new, but it does shows that researchers are fine-tuning their definitions of TNBC, which will lead to new treatment.]

CHAPEL HILL, N.C. – Triple-negative breast cancers are more biologically diverse than previously believed and classification should be expanded to reflect this heterogeneity, according to University of North Carolina researchers.

In a study published in the February issue of The Oncologist conducted by UNC and the Vall d'Hebron Institute of Oncology in Barcelona, Spain, a team lead by Charles Perou, PhD, of UNC Lineberger Comprehensive Cancer Center, examined more than 1,700 breast tumors, including 412 triple negative (TN) breast cancers, and concluded that triple-negative cancers, and basal-like breast cancers should not be considered as a single type, since more than 30 percent of triple-negative cancers lack biological markers associated with basal-like tumors.

Breast cancers are sometimes classified into four main subtypes – basal-like (often called TN), luminal A, luminal B and HER2-enriched. While targeted therapies have been developed to exploit the weaknesses of some types of breast cancers, the lack of these drug markers on TN cancers means patients with these tumors must undergo broader, more aggressive therapies.

The researchers found at least four disease subtypes within TN tumors, with more than 75 percent of the tumors falling into the basal-like subtype. [PAT'S NOTE:  This contradicts the previous statement earlier in the release that says more than 30 percent are NOT basal-like.] Further research is needed to identify the distinct biomarkers shared by the expanded subtypes of TN cancers. The ultimate goal will be to target the individual biomarkers of these subtypes and create therapies that target their individual biology, according to Dr. Perou.

"Today, given that the basal-like subtype is the majority of TN patients, I believe that if we are to make therapeutic progress against TN disease, we are going to need to target the unique biology of the Basal-like subtype" said Dr. Perou.

Please consider a donation to Positives About Negative to keep this site going.  This work is entirely supported by readers.  Just click on the Donate button in the right of the page.  Thank you!

Read more about TNBC in my book, Surviving Triple-Negative Breast Cancer.