“Combination treatment with the poly(ADP-ribose) polymerase (PARP) inhibitor olaparib plus the phosphatidylinositol 3-kinase (PI3K) inhibitor BKM120 resulted in clinical activity in women with triple-negative breast cancer and those with high-grade serous ovarian cancer.
“Patients that had BRCA-mutant and BRCA wild-type tumors responded to the treatment.
“The results of this phase I trial were presented at a press briefing at the American Association for Cancer Research (AACR) Annual Meeting, held April 18 to 22 in Philadelphia.”
“Early data in a preliminary human study show that an experimental immune system drug is generally safe and well tolerated in women with metastatic, triple-negative breast cancer, a persistently difficult form of the disease to treat.
“Results of the early-phase clinical trial of the therapy, called MPDL3280A, which aims to restore the immune system’s ability to recognize and attack cancer cells, are expected to be presented at the American Association for Cancer Research’s 2015 Annual Meeting in Philadelphia from April 18-22. Triple-negative breast cancer cells lack expression of estrogen receptor, progesterone receptor and HER2 protein, the established targets for breast cancer therapies.
“The small study was conducted on 54 patients treated at the Johns Hopkins Kimmel Cancer Center and several other institutions.
” ‘Early data in this trial show that the drug is generally safe and well-tolerated, and it appears to be able to control disease in some of these patients,’ says Leisha Emens, M.D., Ph.D., an associate professor of oncology at the Johns Hopkins University School of Medicine. ‘Now we’ll need to test it further in more patients and compare it with standard therapies to establish its therapeutic value.’ “
“Roche Holding AG will skip a mid-stage study of an experimental immunotherapy for breast cancer and proceed directly to a phase 3 trial later this year.
“The Swiss company will study MPDL3280A for triple-negative breast cancer, which is currently treated mostly with chemotherapy, spokeswoman Holli Dickson said in a phone interview. The drug will be tested in combination with chemotherapy.
“The company will present results from an early-stage study of the drug at a cancer meeting in Philadelphia on April 20. Roche is competing with Merck & Co. to develop a drug for a segment of the breast cancer market that may reach as much as $5 billion in peak sales, according to Goldman Sachs Group Inc. analysts.”
“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 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.”
“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.”
“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’.
“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).”
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).”