Nav: Home

Updated testing guidelines make more women eligible for herceptin, yet benefit uncertain

July 27, 2016

ROCHESTER, Minn. -- Changes to HER2 testing guidelines for breast cancer in 2013 significantly increased the number of patients who test HER2-positive, according to a new study by Mayo Clinic researchers published in the Journal of Clinical Oncology. Cancers that have an excess of HER2 protein or extra copies of the HER2 gene are called HER2-positive and can be treated with drugs like Herceptin that target HER2. HER2 stands for human epidermal growth factor receptor 2.

Mayo Clinic researchers found that the number of HER2-positive breast cancers doubled after testing guidelines were changed by the American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) in 2013. "The new guidelines were established to reduce the number of equivocal cases, where HER2 status is uncertain, but we found that they did just the opposite," says senior study author Robert Jenkins, M.D., Ph.D., the Ting Tsung and Wei Fong Chao Professor of Individualized Medicine Research and Professor of Laboratory Medicine and Pathology at Mayo Clinic. "The number of equivocal cases went up, resulting in additional testing and a much larger number of women with cancers ultimately labeled as HER2-positive.

According to Breastcancer.org, more than 10 percent of women will develop breast cancer in their lifetime. In the U.S. alone, the American Cancer Society estimates there will be more than 246,000 new cases of invasive breast cancer diagnosed this year, along with 61,000 new cases of noninvasive breast cancer. All newly diagnosed breast cancers are tested for human epidermal growth factor receptor 2 (HER2), a molecule that promotes the growth of cancer cells. HER2-positive cancers tend to be more aggressive and spread more quickly than other breast cancers.

Dr. Jenkins says the development of drugs like trastuzumab (Herceptin) and lapatinib (Tykerb) that target HER2 have greatly improved the prognosis of patients with HER2-positive breast cancer, but it is not clear what level of HER2 is needed on cancer cells for these targeted therapies to be effective. Therefore, he says, it is critical that clinicians accurately determine the HER2 status of a particular cancer. HER2 testing is performed using two methods: immunohistochemistry, which detects how much of the HER2 protein is present on cancer cells, and fluorescence in-situ hybridization (FISH), which measures how many copies of the HER2 gene are inside each cell.

The U.S. Food and Drug Administration (FDA) approved the first HER2 testing guidelines for determining eligibility for HER2-directed therapy for breast cancer in 1998. The American Society of Clinical Oncology/College of American Pathologists published a new set of guidelines in 2007 (AC2007), which were updated in 2013 (AC2013). The latest guidelines changed the cut-off for equivocal and positive cases.

Dr. Jenkins and his colleagues hypothesized that the new criteria outlined in AC2013 would lead to an increase in the number of breast cancers that test HER2-positive. They analyzed FISH results for 2,851 breast cancer cases referred to the Mayo Clinic Cytogenetics Laboratory for FISH testing between November 2013 and October 2014, and then compared the prevalence of HER2 FISH amplification using the three guidelines.

In their analysis, the researchers found a near doubling in the proportion of HER2 FISH-positive cases interpreted using AC2013 (23.6 percent), compared to the FDA criteria (13.1 percent) or AC2007 (11 percent). The Mayo researchers previously reported a 13 percent HER2-positivity rate using the FDA criteria in their clinical practice in 2000, and that rate had remained constant until the implementation of AC2013. Since the implementation of AC2013, an additional 10-15 percent of women with breast cancer are considered eligible for HER2-directed therapies, even though it is unknown if they would benefit from addition of HER2-directed treatments.

"Women who receive false positive results are not only exposed to the risks of HER2-directed therapies, but they also miss out on the treatments that could be effective against their cancer. That is counter to the goal of personalized medicine, which is to give the right drug to the right patient at the right time," says Dr. Jenkins. "Given the medical, financial and psychosocial aspects of these targeted therapies, it is prudent that we prospectively identify the most optimal candidates for treatment."

Dr. Jenkins says that the recent National Surgical Adjuvant Breast and Bowel Project B-47 trial could provide insight into whether the additional patients labeled as HER2-positive by AC2013 actually will benefit from HER2-directed therapies. Ultimately, he says, the decision to use such targeted therapies should be taken only after carefully considering the risks and benefits by patients and their physicians, as well as any additional information that can be gleaned from other HER2 tests results, including immunohistochemistry.
-end-
Co-authors are:
  • Mithun Vinod Shah, M.D. Ph.D., Mayo Clinic
  • Anne Wiktor, Mayo Clinic
  • Reid Meyer, Mayo Clinic
  • Kathleen Tenner, Mayo Clinic
  • Karla Ballman, Ph.D.
  • Stefan Green, Mayo Clinic
  • William Sukov, M.D., Mayo Clinic
  • Rhett Ketterling, M.D., Mayo Clinic
  • Edith Perez, M.D., Mayo Clinic
The study was supported by grants from the National Cancer Institute of the National Institutes of Health.

About the Mayo Clinic Cancer Center

As a leading institution funded by the National Cancer Institute, the Mayo Clinic Cancer Center conducts basic, clinical and population science research, translating discoveries into improved methods for prevention, diagnosis, prognosis and therapy. For information on cancer clinical trials, call the clinical trials referral office at 1-855-776-0015 (toll-free).

About Mayo Clinic

Mayo Clinic is a nonprofit organization committed to clinical practice, education and research, providing expert, whole-person care to everyone who needs healing. For more information, visit http://www.mayoclinic.org/about-mayo-clinic or http://newsnetwork.mayoclinic.org/.

Mayo Clinic

Related Breast Cancer Articles:

Breast cancer: AI predicts which pre-malignant breast lesions will progress to advanced cancer
New research at Case Western Reserve University in Cleveland, Ohio, could help better determine which patients diagnosed with the pre-malignant breast cancer commonly as stage 0 are likely to progress to invasive breast cancer and therefore might benefit from additional therapy over and above surgery alone.
Partial breast irradiation effective treatment option for low-risk breast cancer
Partial breast irradiation produces similar long-term survival rates and risk for recurrence compared with whole breast irradiation for many women with low-risk, early stage breast cancer, according to new clinical data from a national clinical trial involving researchers from The Ohio State University Comprehensive Cancer Center - Arthur G.
Breast screening linked to 60 per cent lower risk of breast cancer death in first 10 years
Women who take part in breast screening have a significantly greater benefit from treatments than those who are not screened, according to a study of more than 50,000 women.
More clues revealed in link between normal breast changes and invasive breast cancer
A research team, led by investigators from Georgetown Lombardi Comprehensive Cancer Center, details how a natural and dramatic process -- changes in mammary glands to accommodate breastfeeding -- uses a molecular process believed to contribute to survival of pre-malignant breast cells.
Breast tissue tumor suppressor PTEN: A potential Achilles heel for breast cancer cells
A highly collaborative team of researchers at the Medical University of South Carolina and Ohio State University report in Nature Communications that they have identified a novel pathway for connective tissue PTEN in breast cancer cell response to radiotherapy.
Computers equal radiologists in assessing breast density and associated breast cancer risk
Automated breast-density evaluation was just as accurate in predicting women's risk of breast cancer, found and not found by mammography, as subjective evaluation done by radiologists, in a study led by researchers at UC San Francisco and Mayo Clinic.
Blood test can effectively rule out breast cancer, regardless of breast density
A new study published in PLOS ONE demonstrates that Videssa® Breast, a multi-protein biomarker blood test for breast cancer, is unaffected by breast density and can reliably rule out breast cancer in women with both dense and non-dense breast tissue.
Study shows influence of surgeons on likelihood of removal of healthy breast after breast cancer dia
Attending surgeons can have a strong influence on whether a patient undergoes contralateral prophylactic mastectomy after a diagnosis of breast cancer, according to a study published by JAMA Surgery.
Young breast cancer patients undergoing breast conserving surgery see improved prognosis
A new analysis indicates that breast cancer prognoses have improved over time in young women treated with breast conserving surgery.
Does MRI plus mammography improve detection of new breast cancer after breast conservation therapy?
A new article published by JAMA Oncology compares outcomes for combined mammography and MRI or ultrasonography screenings for new breast cancers in women who have previously undergone breast conservation surgery and radiotherapy for breast cancer initially diagnosed at 50 or younger.
More Breast Cancer News and Breast Cancer Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Listen Again: Reinvention
Change is hard, but it's also an opportunity to discover and reimagine what you thought you knew. From our economy, to music, to even ourselves–this hour TED speakers explore the power of reinvention. Guests include OK Go lead singer Damian Kulash Jr., former college gymnastics coach Valorie Kondos Field, Stockton Mayor Michael Tubbs, and entrepreneur Nick Hanauer.
Now Playing: Science for the People

#562 Superbug to Bedside
By now we're all good and scared about antibiotic resistance, one of the many things coming to get us all. But there's good news, sort of. News antibiotics are coming out! How do they get tested? What does that kind of a trial look like and how does it happen? Host Bethany Brookeshire talks with Matt McCarthy, author of "Superbugs: The Race to Stop an Epidemic", about the ins and outs of testing a new antibiotic in the hospital.
Now Playing: Radiolab

Dispatch 6: Strange Times
Covid has disrupted the most basic routines of our days and nights. But in the middle of a conversation about how to fight the virus, we find a place impervious to the stalled plans and frenetic demands of the outside world. It's a very different kind of front line, where urgent work means moving slow, and time is marked out in tiny pre-planned steps. Then, on a walk through the woods, we consider how the tempo of our lives affects our minds and discover how the beats of biology shape our bodies. This episode was produced with help from Molly Webster and Tracie Hunte. Support Radiolab today at Radiolab.org/donate.