Mammatyper Seen to Ably Classify Invasive Breast Cancers, Key to Proper Treatment
July 21, 2016
BioNTech Diagnostics reports that data supporting the superiority of a device called the MammaTyper in classifying newly diagnosed invasive breast cancer has been confirmed by a recently published study.
The study, “Biological subtyping of early breast cancer: a study comparing RT-qPCR with immunohistochemistry,” published in the journal Breast Cancer Research and Treatment, compared the device, building on analyses of mRNA, with current practices allowing trained pathologists to analyze tumor tissue samples under the microscope.
Knowledge of how levels of various proteins expressed in breast cancer tissue correlate with such concerns as response to treatment and prognosis has allowed scientists to segregate breast cancer into several distinct subtypes, in what is known as the St. Gallen classification.
According to this system, tumors can be classified into five types referred to as luminal A-like, luminal B-like (HER2 negative), luminal B-like (HER2 positive), HER2 positive (non-luminal) and triple negative (ductal) tumors.
Traditionally, the work to detect and quantify the levels of the protein markers characterizing a tumor’s subtype has been the job of a trained pathologist, analyzing tissue samples under the microscope. But such analysis can often be imprecise, leading to suboptimal care for cancer patients.
The Mammatyper builds on an established technique to quantify the levels of messenger RNA, acting as an intermediate step between gene and protein. BioNTech has refined the method to specifically identify messenger RNA from the breast cancer proteins HER2, ER, PR, and MKI67.
The validation study, using breast cancer tissue samples from 769 women enrolled in the FinHer trial, comparing the drugs vinorelbine, docetaxel, and trastuzumab as add-on treatments in patients with a high risk of cancer recurrence, allowed both pathologists and the Mammatyper analyze tissues under different conditions — varying the laboratory site, content of tumor cells in the sample, and method of RNA isolation and preparation.
Results showed that the Mammatyper was more precise in classifying tumor types than protein detection by microscopy. The team discovered that patients treated with the combination of docetaxel and chemotherapy, in which the tumor had been classified as luminal B subtype based on RNA analysis, had better outcomes than patients treated with the drug vinorelbine and chemotherapy.
Such differences could not be detected when the tumors were classified using the older method, suggesting that the classification was more arbitrary. Also, other analyses confirmed that RNA analysis with Mammatyper produced more robust results.
“Once again the MammaTyper test kit has been proven as an unambiguous technical advance in breast cancer subtyping,” Dr. Sierk Poetting, managing director at BioNTech Diagnostics, said in a news release.
“This means that the results with the MammaTyper test kit are stable, even between different sites and under varying conditions. Thus, MammaTyper allows standardized, precise and reproducible breast cancer subtyping,” Dr. Poetting concluded.
First Patient Dosed in HA HER2-Negative Breast Cancer Trial
Tuesday, Jul 26, 2016
First Patient Dosed in HA HER2-Negative Breast Cancer Trial RDR Staff Published Online: Tuesday, Jul 26, 2016 3 24 3 0 The first patient was dosed in a collaborative phase 1b/2 clinical trial between Eisai Inc. and Halozyme Therapeutics to assess whether Esai’s eribulin mesylate (Eribulin) in combination with Haloyzym’s PEGylated recombinant human hyaluronidase (PEGPH20) is beneficial to overall response rate (ORR) in patients diagnosed with High-Hyaluronan (HA) human epidermal growth factor receptor 2 (HER2)-negative breast cancer.
The study is a randomized, Open-label, Multicenter, Phase 1b/2 trial estimating in 96 patients enrolled. The Phase 1b part of the trial will have dose limiting toxicity (DLT) assessed in the first cycle to determine the Recommended Phase 2 dose (RP2D) of eribulin mesylate in combination with PEGPH20. In the Phase 2 part, participants will be stratified by triple negative breast cancer (TNBC) status and randomized to receive eribulin mesylate and PEGPH20 at the established RP2D level or eribulin mesylate alone at 1.4 milligram per square meter (mg/m2). PEGPH20/Eribulin PEGPH20 is designed to target the degradation of HA, a glycosaminoglycan and increases blood flow to the tumor which may allow cancer therapies to be more efficiently delivered to their target. The drug accumulates around cancer cells, increasing tumor interstitial fluid pressure and constricting tumor vasculature, subsequently inhibiting anticancer agents from reaching cancer cells.
Eribulin is a microtubule dynamics inhibitor with a distinct binding profile that has been shown in in vitro studies to lead to apoptotic cell death after prolonged and irreversible mitotic blockage. Eribulin is currently approved for the treatment of advanced breast cancer in approximately 60 countries worldwide.
Both companies hope to see positive results from each phase of the trial in order to move forward with this collaboration of drugs.
For more information on the trial, click here. HER2 Negative Breast Cancer The HER2 gene makes HER2 proteins which are receptors on breast cells. Normally, HER2 receptors help control how a healthy breast cell grows, divides, and repairs itself. But in about 25% of breast cancers, the HER2 gene doesn't work correctly and makes too many copies of itself (known as HER2 gene amplification) or the breast cancers have little or no HER2 protein (HER2 Negative Breast Cancer).
Updated guidelines for breast cancer increase number of patients who test HER2-positive
July 28, 2016
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.
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