Cisplatin plus Gemcitabine Improves Outcomes in Metastatic Triple-Negative Breast Cancer

“Cisplatin plus gemcitabine demonstrated superior PFS outcomes compared with paclitaxel plus gemcitabine for women with metastatic triple-negative breast cancer, according to results of a randomized phase 3 study.

“ ‘Despite general improvements in the management of breast cancer, triple-negative breast cancer represents a continuing challenge because, when compared with other subtypes, it is associated with a higher frequency of recurrence, shorter DFS and poor OS, despite similar therapeutic approaches to other breast cancers,’ Xi-Chun Hu, MD, of the department of medical oncology at the Fudan University Shanghai Medical College, and colleagues wrote. ‘The median distant disease-free interval for relapsed triple-negative breast cancer is about 1 to 2 years and the median survival for metastatic triple-negative breast cancer is about 1 year.’

“Hu and colleagues evaluated data from 236 patients (median age, 47 years) from 12 institutions or hospitals within the Chinese Breast Cancer Study Group. Patients had not undergone previous chemotherapy for metastatic disease and they had an ECOG performance status of 0 to 1.

“Researchers randomly assigned patients 1:1 to a chemotherapy regimen of 1,250 mg/m2 gemcitabine on days 1 and 8 plus 75 mg/m2 cisplatin or 175 mg/m2 paclitaxel on day 1 for eight 3-week cycles.”


Celldex Reports Positive Phase II EMERGE Trial of Glembatumumab Vedotin to Treat Breast Cancer

“Celldex Therapeutics has reported positive data from the Phase II EMERGE trial of glembatumumab vedotin, an antibody-drug conjugate, in patients with metastatic breast cancer.

“Data from this trial supported the initiation of the ongoing, pivotal Phase II METRIC trial in patients with triple negative breast cancers that over-express glycoprotein NMB (gpNMB).

“Glembatumumab vedotin targets and binds to gpNMB, a protein expressed by multiple tumor types, including breast cancer.

“A total of 124 patients with advanced, heavily pre-treated breast cancer were enrolled in the randomized, multi-center, controlled EMERGE trial and they were randomized (2:1) to receive glembatumumab vedotin or ‘Investigator’s Choice’ (IC) single agent, approved chemotherapy.”


New Data Helps Doctors Zero in on Breast Cancer Risks, Treatments

“At Ricki Fairley’s annual check-up in 2012, doctors found a tiny lump. She was diagnosed with triple negative breast cancer, a less common and more aggressive form of the disease that has very few treatment options. Approximately 15 percent of all breast cancer cases are categorized as triple negative.

“Triple negative breast cancer can be effectively treated if the disease is caught early, and Fairley, now 58 years old, is living proof. She underwent a long course of aggressive chemotherapy and radiation and is now doing well.

“Triple negative is one of four subtypes of breast cancer, and a new report emphasizes how important it is for doctors to identify the risks and treatments for each. For example, triple negative cancers do not respond to certain hormonal therapies that can help other women.

“The nationwide data — published in the Journal of the National Cancer Institute and co-authored by the American Association of Central Cancer Registries, the American Cancer Society, the Centers for Disease Control and Prevention, and the National Cancer Institute at the National Institutes of Health — may help doctors identify which patients are at most risk for each type of breast cancer and which treatments may be most effective.”


Is There a Future for Immunotherapy in Breast Cancer?


Lately, immunotherapy—treatment that helps the body’s own immune system fight cancer—has made frequent appearances in news headlines. Indeed, researchers have reported remarkable clinical trial results for a new class of drugs known as ‘immune checkpoint blockade drugs‘ in the treatment of metastatic melanoma, lung, and kidney cancers. Approvals from the U.S. Food and Drug Administration (FDA) for the drugs Keytruda and Opdivo for melanoma and lung cancer have quickly followed. However, it may be that immunotherapies won’t work for all cancers, but only for those considered to be ‘immunogenic’; that is, cancers that trigger activation of the immune system. Researchers are studying different types of breast cancer to determine whether they are immunogenic, and what that might mean for their prognosis and treatments. Continue reading…


The Switch That Might Tame the Most Aggressive of Breast Cancers

“Australian researchers have found that so-called ‘triple-negative breast cancers’ are two distinct diseases that likely originate from different cell types. This helps explain why survival prospects for women with the diagnosis tend to be either very good or very bad.

“The Sydney-based research team has found a gene that drives the aggressive disease, and hopes to find a way to ‘switch it off’.

“The aggressive form of triple-negative breast cancer appears to arise from stem cells, while the more benign form appears to arise from specialised cells.

“Stem cells have many of the same features as cancers. They are plastic and flexible, and have the ability to proliferate and spread into other tissues – deadly traits in cancers.”


A Breast Cancer Tumor's Immune Signature Could Predict Response to Neoadjuvant Therapy

“In a study reported in the Journal of Clinical Oncology, Denkert et al found that increased tumor-infiltrating lymphocytes and the presence of lymphocyte-predominant breast cancer were associated with increased rates of pathologic complete response in patients receiving neoadjuvant anthracycline-taxane treatment with or without carboplatin. Higher rates were observed with carboplatin, with treatment interactions being significant among all patients and among those with HER2-positive disease but not among those with triple-negative disease. mRNA profiles for immune-related genes also distinguished pathologic complete response rates.

“The study involved 580 tumors from patients in the GeparSixto trial, which assessed the effects on pathologic complete response rates of adding carboplatin to neoadjuvant anthracycline plus taxane treatment. The current analysis assessed the effects on pathologic complete response of tumor-infiltrating lymphocyte levels, the presence of lymphocyte–predominant disease, and levels of immune-activating (CXCL9, CCL5, CD8A, CD80, CXCL13, IGKC, CD21) and immunosuppressive genes (IDO1, PD-1, PD-L1, CTLA4, FOXP3).”


New Research Points to Potential for Measuring Aggressiveness of Triple-Negative Breast Cancer

The gist: New research shows that it may soon be possible to measure how aggressive a patient’s triple-negative breast cancer might be. Patients with aggressive cancer might benefit from different treatment approaches from those prescribed for patients with less aggressive cancer. The new technique looks at patterns of “DNA methylation” in a tumor. In DNA methylation, molecules called methyl groups become attached to DNA molecules in distinctive patterns. The new research shows that certain DNA methylation patterns can indicate whether a tumor is likely to be aggressive.

“Australian researchers have identified epigenetic ‘signatures’ that could help clinicians tell the difference between highly aggressive and more benign forms of triple-negative breast cancer.

“The new study, published in Nature Communications, compares the breast cancer DNA ‘methylome’ with that of healthy individuals. The methylome provides a new picture of the genome and shows how it is epigenetically ‘decorated’ with methyl groups, a process known as DNA ‘methylation’.

“The study reveals ‘distinct methylation patterns’ in the primary biopsy breast cancer cells indicating better or worse prognosis.

“Triple-negative breast cancers, which make up 15-20% of all breast cancers, lack any of the three receptors (oestrogen, progesterone or HER2) that would make them responsive to targeted drugs. Overall, patients have a higher risk of disease recurrence and shorter survival than those with other breast cancers.

“Triple-negative breast cancer patients tend to fall into two categories: those that succumb to their disease within 3-5 years, regardless of treatment; and those that remain disease free for longer than the average non-triple-negative breast cancer patient (at least 8 years post-diagnosis).”


BRCA Mutation Testing in Triple Negative Breast Cancer Useful Even When There Is No Family History

The gist: Recent research shows that testing for BRCA1 and BRCA2 mutations might be useful for patients with triple-negative breast cancer, even if they have no family history of breast cancer.

“The high prevalence of deleterious mutations in predisposition genes in patients with triple-negative breast cancer unselected for family history suggests germline genetic testing for BRCA1 and BRCA2 mutations may be appropriate in this population, according to study results.

“However, further analyses of non-BRCA genes are needed to assess their utility in this setting, researchers wrote.

“Fergus J. Couch, PhD, of the department of laboratory medicine and pathology at Mayo Clinic in Rochester, Minn., and colleagues evaluated data from 1,824 women with triple-negative breast cancer who were enrolled on one of 12 studies. All women were unselected for family history of breast or ovarian cancer, and most were non-Hispanic white (97%). The median age of the population at diagnosis was 51 years (range, 22-93).”


Immune System-Boosting ImmunoPulse to Be Tested in Triple-Negative Breast Cancer Patients in Pilot Study

The gist: A new treatment that has shown promise in other types of cancer will soon be tested in triple negative breast cancer (TNBC) patients. The treatment, called IL-12 ImmunoPulse, delivers instructions for making a protein called IL-12 into a patient’s tumor. The patient’s cells then make IL-12, which boosts the immune system. A small pilot study will take place at Stanford University in California. It will test whether ImmunoPulse has promising effects on the immune system. If it is successful, researchers might try combining the treatment with drugs that are known to be more effective when the immune system is stimulated.

“OncoSec Medical Inc. (OTCQB: ONCS), a company developing DNA-based intratumoral cancer immunotherapies, plans to initiate a pilot study to assess IL-12 ImmunoPulse in patients with Triple Negative Breast Cancer (TNBC). The study will be conducted at Stanford University with Melinda L. Telli, MD, serving as lead investigator.

“This pilot study is designed to assess whether IL-12 ImmunoPulse increases TNBC tumor immunogenicity by driving a pro-inflammatory cascade of events that leads to increases in cytotoxic tumor-infiltrating lymphocytes (TILs). The presence and number of TILs is thought to be a key requirement for promoting the anti-tumor activity of antibodies like anti-PD-1/PD-L1. By driving cytotoxic immune cells into the tumor, IL-12 ImmunoPulse may be an ideal candidate to combine with checkpoint blockade therapies which reported some activity in TNBC.

“Worldwide, TNBC amounts to approximately 200,000 cases each year and accounts for approximately 20 percent of all breast cancer. It is most commonly diagnosed in younger women (less than 40 years) and is characterized by higher relapse rates when compared with estrogen receptor (ER)-positive breast cancers. TNBC is also associated with an increased risk of recurrence, both locally and in distant sites, including the lung and brain. Advanced TNBC remains a significant area of unmet medical need and there is no established standard-of-care. Treatment generally includes chemotherapy, with or without radiation and/or surgery. However, no treatment regimen has clearly demonstrated superiority.”