False negative results found in prognostic testing for breast cancer

June 18, 2014
False negative results found in prognostic testing for breast cancer
Peter A. Kaufman, MD

A recent study evaluating HER2 testing in a large cohort of women with breast cancer found important limitations in the conventional way HER2 testing is performed in the US and internationally.

Dartmouth-Hitchcock Norris Cotton Cancer Center physicians and researchers retested tumor samples from a large group of women and found that 22 out of 530 women had their tumor type incorrectly classified. They reported their findings in a publication titled "Assessing the Discordance Rate between Local and Central HER2 Testing in Women with Locally Determined HER2-Negative Breast Cancer," which was published in Cancer on June 13, 2014.

Breast cancer is categorized into several subtypes based on conventional laboratory, and newer molecular tests. This study looked at the accuracy in classifying breast cancers in one particular subtype, specifically those that are "human epidermal growth factor receptor 2" or HER2 positive. What is particularly important in accurately determining HER2 in breast cancer is that when a woman's cancer tests positive for HER2, there are specific treatments proven extremely effective in improving outcome and preventing recurrence of cancer. These HER2 directed, or targeted, therapies are critically important in treating women with HER2 positive breast cancer.

"We, and other groups, have previously shown that a certain percentage of cases found to be HER2 positive in local laboratories are in fact HER2 negative when tested in more experienced central labs. There has, however, been almost no research evaluating the accuracy of a negative HER2 result," said Peter A. Kaufman, MD. "This is the first large study to look at this. What is comforting is that we found that re-testing in experienced larger labs confirmed the original local lab results in the majority of cases."

Kaufman noted that they did find about four percent of cases that were originally determined to be HER2 negative were in fact HER2 positive on repeat testing. Many of these cases were detected as being positive by testing for HER2 using both of two different and complementary tests (IHC and FISH, as described below).

The repercussions of incorrectly identifying a cancer's subtype are considerable. "While it is comforting that only four percent of these women were misclassified initially, this is an enormous issue for those who fall into this group," said Kaufman. "This is because HER2 targeted therapies are critically important for women with HER2 positive breast cancer."

The variance in accuracy may be related to how tests are conducted in smaller versus larger pathology laboratories. Two different tests are approved for and widely used for HER2: immunohistochemistry (IHC) or florescence in situ hybridization (FISH). Either may be used to determine a woman's HER2 status. Frequently, based on recommendations by leading oncology groups, one or the other is used. In this case, using both tests allowed researchers to uncover errors resulting from reliance on a single test. Of the 22 samples incorrectly categorized, 18 had been processed by a local laboratory using only one testing method.

The analysis was based on the VIRGO study, a large, disease-based, observational cohort study of more than 1,200 with HER2-negative metastatic from June 2008 through January 2011. Out of the 1,267 patients enrolled in VIRGO, 776 submitted samples for this study from which 552 were suitable for centralized testing using IHC and FISH assays.

Explore further: Molecular imaging finds novel way to knock down breast cancer

Related Stories

Molecular imaging finds novel way to knock down breast cancer

June 9, 2014
For years researchers have been developing molecular imaging techniques that visualize hormonally active breast cancer cells—specifically those testing positive for human epidermal growth factor receptor 2 (HER2). A recent ...

Study finds risk of recurrence low in smallest HER2+ breast cancer tumors

June 2, 2014
Patients with specific HER2+ breast cancer tumors had a low risk of the cancer recurring five years after diagnosis, even without chemotherapy or treatment with a common antibody, according to a Kaiser Permanente study published ...

Advanced breast cancer: Benefits of Trastuzumab (Herceptin) outweigh the risk of harm

June 11, 2014
In women with advanced (or metastatic) breast cancer, treatment with the breast cancer drug Trastuzumab (Herceptin) is associated with prolonged survival but also increases the risk of developing heart problems, a new systematic ...

Breast cancer recurrence defined by hormone receptor status

October 1, 2012
Human epidermal growth factor (HER2) positive breast cancers are often treated with the same therapy regardless of hormone receptor status. New research published in BioMed Central's open access journal Breast Cancer Research ...

Scientists propose a breast cancer drug for bladder cancer patients

January 22, 2014
Researchers at Mayo Clinic have found amplification of HER2, a known driver of some breast cancers, in a type of bladder cancer called micropapillary urothelial carcinoma (MPUC) and have shown that the presence of HER2 amplification ...

New research could provide key to overcoming resistance to HER2 targeted cancer treatments

June 11, 2014
Scientists from the School of Pharmacy & Pharmaceutical Sciences, Trinity College Dublin have made a significant discovery of a new biomarker which may help overcome resistance to newer and more targeted anti-cancer drugs, ...

Recommended for you

Stem cell therapy attacks cancer by targeting unique tissue stiffness

July 26, 2017
A stem cell-based method created by University of California, Irvine scientists can selectively target and kill cancerous tissue while preventing some of the toxic side effects of chemotherapy by treating the disease in a ...

Understanding cell segregation mechanisms that help prevent cancer spread

July 26, 2017
Scientists have uncovered how cells are kept in the right place as the body develops, which may shed light on what causes invasive cancer cells to migrate.

Study uncovers potential 'silver bullet' for preventing and treating colon cancer

July 26, 2017
In preclinical experiments, researchers at VCU Massey Cancer Center have uncovered a new way in which colon cancer develops, as well as a potential "silver bullet" for preventing and treating it. The findings may extend to ...

Compound shows promise in treating melanoma

July 26, 2017
While past attempts to treat melanoma failed to meet expectations, an international team of researchers are hopeful that a compound they tested on both mice and on human cells in a petri dish takes a positive step toward ...

Study may explain failure of retinoic acid trials against breast cancer

July 25, 2017
Estrogen-positive breast cancers are often treated with anti-estrogen therapies. But about half of these cancers contain a subpopulation of cells marked by the protein cytokeratin 5 (CK5), which resists treatment—and breast ...

Breaking the genetic resistance of lung cancer and melanoma

July 25, 2017
Researchers from Monash University and the Memorial Sloan Kettering Cancer Center (MSKCC, New York) have discovered why some cancers – particularly lung cancer and melanoma – are able to quickly develop deadly resistance ...

0 comments

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.