Molecular marker in healthy tissue can predict a woman's risk of getting the disease, research says

April 7, 2016 by Hannah L. Robbins, Harvard University
In healthy breast tissue, the percentage of cells expressing molecular marker Ki67 (green) and p27 (red) was low. Credit: Sung Jin Huh

Harvard Stem Cell Institute (HSCI) researchers at Dana-Farber Cancer Institute (DFCI) and collaborators at Brigham and Women's Hospital (BWH) have identified a molecular marker in normal breast tissue that can predict a woman's risk for developing breast cancer, the leading cause of death in women with cancer worldwide.

The work, led by HSCI principal faculty member Kornelia Polyak and Rulla Tamimi of BWH, was published in an early online release and in the April 1 issue of Cancer Research.

The study builds on Polyak's earlier research finding that already identified as having a high risk of developing cancer—namely those with a mutation called BRCA1 or BRCA2—or women who did not give birth before their 30s had a higher number of mammary gland progenitor cells.

In the latest study, Polyak, Tamimi, and their colleagues examined biopsies, some taken as many as four decades ago, from 302 participants in the Nurses' Health Study and the Nurses' Health Study II who had been diagnosed with benign breast disease. The researchers compared tissue from the 69 women who later developed cancer to the tissue from the 233 women who did not. They found that women were five times as likely to develop cancer if they had a higher percentage of Ki67, a that identifies proliferating cells, in the cells that line the mammary ducts and milk-producing lobules. These cells, called the mammary epithelium, undergo drastic changes throughout a woman's life, and the majority of breast cancers originate in these tissues.

Doctors already test breast tumors for Ki67 levels, which can inform decisions about treatment, but this is the first time scientists have been able to link Ki67 to precancerous tissue and use it as a predictive tool.

"Instead of only telling women that they don't have cancer, we could test the biopsies and tell women if they were at high risk or low risk for developing in the future," said Polyak, a breast cancer researcher at Dana-Farber and co-senior author of the paper.

"Currently, we are not able to do a very good job at distinguishing women at high and low risk of breast cancer," added co-senior author Tamimi, an associate professor at the Harvard T.H. Chan School of Public Health and Harvard Medical School. "By identifying women at of breast cancer, we can better develop individualized screening and also target risk reducing strategies."

To date, mammograms are the best tool for the early detection, but there are risks associated with screening. False positive and negative results and over-diagnosis could cause psychological distress, delay treatment, or lead to overtreatment, according to the National Cancer Institute (NCI).

Mammography machines also use low doses of radiation. While a single mammogram is unlikely to cause harm, repeated screening can potentially cause cancer, though the NCI writes that the benefits "nearly always outweigh the risks."

"If we can minimize unnecessary radiation for women at low risk, that would be good," said Tamimi.

Screening for Ki67 levels would "be easy to apply in the current setting," said Polyak, though the researchers first want to reproduce the results in an independent cohort of women.

Explore further: Predicting individual breast cancer risk may be possible

More information: S. J. Huh et al. The Proliferative Activity of Mammary Epithelial Cells in Normal Tissue Predicts Breast Cancer Risk in Premenopausal Women, Cancer Research (2016). DOI: 10.1158/0008-5472.CAN-15-1927

Related Stories

Predicting individual breast cancer risk may be possible

August 12, 2013
An international scientific collaborative led by the Harvard Stem Cell Institute's Kornelia Polyak, MD, PhD, has discovered why women who give birth in their early twenties are less likely to eventually develop breast cancer ...

Early MRI screening reduces risk of breast cancer death for survivors of childhood HL

March 1, 2016
Researchers at Princess Margaret Cancer Centre have confirmed in a screening effectiveness study that early screening with MRIs can reduce breast cancer mortality for female survivors of childhood Hodgkin's lymphoma (HL) ...

Study suggests breast density alone not a risk factor for cancer

December 2, 2015
Breast density may not be a strong independent factor for breast cancer risk, according to a new study presented today at the annual meeting of the Radiological Society of North America (RSNA).

What to know if breast cancer runs in your family

October 7, 2014
Breast cancer is the second leading cause of death from cancer in women. A woman's lifetime risk of developing breast cancer is 12 percent (1 of every 8 women). Breast cancer risk is higher among women whose close blood relatives ...

Targeted radiation shows promise in early breast cancer

March 10, 2016
(HealthDay)—For women with early-stage breast cancer, targeted doses of radiation therapy may be as effective as standard radiation treatment of the entire breast, according to research presented at the European Breast ...

False-positive mammograms may indicate increased risk of breast cancer later

December 2, 2015
Main Finding(s): Women with a history of a false-positive mammogram result may be at increased risk of developing breast cancer for up to 10 years after the false-positive result.

Recommended for you

A small, daily dose of Viagra may reduce colorectal cancer risk

March 19, 2018
A small, daily dose of Viagra significantly reduces colorectal cancer risk in an animal model that is genetically predetermined to have the third leading cause of cancer death, scientists report.

Cancer comes back all jacked up on stem cells

March 19, 2018
After a biopsy or surgery, doctors often get a molecular snapshot of a patient's tumor. This snapshot is important - knowing the genetics that cause a cancer can help match a patient with a genetically-targeted treatment. ...

Researchers create a drug to extend the lives of men with prostate cancer

March 16, 2018
Fifteen years ago, Michael Jung was already an eminent scientist when his wife asked him a question that would change his career, and extend the lives of many men with a particularly lethal form of prostate cancer.

Machine-learning algorithm used to identify specific types of brain tumors

March 15, 2018
An international team of researchers has used methylation fingerprinting data as input to a machine-learning algorithm to identify different types of brain tumors. In their paper published in the journal Nature, the team ...

Higher doses of radiation don't improve survival in prostate cancer

March 15, 2018
A new study shows that higher doses of radiation do not improve survival for many patients with prostate cancer, compared with the standard radiation treatment. The analysis, which included 104 radiation therapy oncology ...

Joint supplement speeds melanoma cell growth

March 15, 2018
Chondroitin sulfate, a dietary supplement taken to strengthen joints, can speed the growth of a type of melanoma, according to experiments conducted in cell culture and mouse models.


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.