“While neratinib plus paclitaxel was not superior to trastuzumab plus paclitaxel as first-line treatment for ERBB2-positive metastatic breast cancer in terms of progression-free survival, the combination was associated with delayed onset and reduced frequency of central nervous system metastases, a finding that requires a larger study to confirm, according to an article published online by JAMA Oncology.
“Metastatic ERBB2-positive breast cancer has a characteristic spread with most patients developing liver metastases and about half having poor prognosis with central nervous system involvement.
“Ahmad Awada, M.D., of the Jules Bordet Institute, Brussels, and coauthors conducted a randomized clinical trial to examine progression-free survival in women with recurrent or metastatic ERBB2-positive breast cancer. They also examined secondary outcomes that included time to symptomatic or progressive central nervous system lesions and safety.”
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“Amsterdam, The Netherlands: Approximately a quarter of women with HER2 positive breast cancer, who were treated with a combination of the targeted drugs lapatinib and trastuzumab before surgery and chemotherapy, saw their tumours shrink significantly or even disappear, according to results from a clinical trial.
“Professor Nigel Bundred told the 10th European Breast Cancer Conference (EBCC-10) today (Thursday): ‘This has ground-breaking potential because it allows us to identify a group of patients who, within 11 days, have had their tumours disappear with anti-HER2 therapy alone and who potentially may not require subsequent chemotherapy. This offers the opportunity to tailor treatment for each individual woman.’
“Prof Bundred, who is Professor of Surgical Oncology at The University of Manchester and the University Hospital of South Manchester NHS Foundation Trust (UK), was presenting results from the UK EPHOS-B multi-centre, clinical trial, in which 257 women with newly-diagnosed, operable, HER2 positive disease were recruited between November 2010 and September 2015.”
“A tumor’s immune response to a single dose of the HER2 inhibitor trastuzumab predicted which patients with HER2-positive breast cancer would respond to the drug on a more long-term basis, according to the results of a study published recently in Clinical Cancer Research.
“In addition, Vinay Varadan, PhD, assistant professor at Case Western Reserve University School of Medicine and member of the Case Comprehensive Cancer Center, and his colleagues found that women with the HER2-enriched subtype of HER2-positive breast cancer—a subtype that is estrogen and progesterone receptor negative—had the highest rate of immune response to treatment with trastuzumab, with significant increases in immune response after a single dose of the drug.
“ ‘Our study showed, for the first time, that the immune-cell–activating properties of trastuzumab are likely related to the subtypes of breast cancer,’ Varadan said. ‘Knowing this can inform future trials studying the usefulness of adding immunotherapy drugs to trastuzumab.’ “
TNBC has long been considered to be more amenable to immune system-based treatments than other types of breast cancer because it is more immunogenic; that is, relatively high levels of immune cells accumulate within or adjacent to TNBC tumors. These immune cells could be triggered to attack tumors if properly activated. TNBC tumors are also likely to have a higher mutational burden (number of genetic mutations). This is one of the predictors of sensitivity to a type of treatment called immune checkpoint blockade. Drugs known as checkpoint inhibitors block the proteins PD-1 or PD-L1. In cancer, PD-L1 proteins on tumor cells bind to PD-1 proteins on immune T cells and inhibit their tumor-killing activity. Immune checkpoint drugs disable this interaction and enable activation of T cells. These drugs are actively being explored in TNBC in clinical trials.
“Heart medication taken in combination with chemotherapy reduces the risk of serious cardiovascular damage in patients with early-stage breast cancer, according to results from a new landmark clinical trial.
“Existing research has shown some cancer therapies such as Herceptin greatly improve survival rates for early-stage breast cancer, but come with a fivefold risk of heart failure—a devastating condition as life-threatening as the cancer itself.
“A new five-year study, led by researchers at the University of Alberta and Alberta Health Services and funded by the Canadian Institutes for Health Research (CIHR) and Alberta Cancer Foundation, shows that two kinds of heart medications, beta blockers and ACE inhibitors, effectively prevent a drop in heart function from cancer treatment.”
“Among patients with HER2-positive, metastatic breast cancer that had progressed despite treatment with two or more forms of HER2-targeted therapy (trastuzumab [Herceptin] and lapatinib [Tykerb]), median overall survival was increased for those treated with trastuzumab emtansine (T-DM1 [Kadcyla]) compared with those who received treatment of physician’s choice, according to results from the phase III TH3RESA clinical trial presented at the 2015 San Antonio Breast Cancer Symposium, held Dec. 8–12.
“The HER2-targeted antibody-drug conjugate T-DM1 was approved by the U.S. Food and Drug Administration in February 2013 for treating patients with HER2-positive, metastatic breast cancer that had progressed after treatment with trastuzumab and a taxane.”
Erika P. Hamilton, MD, associate director, Breast Cancer and Gynecologic Cancer Research Program, principal investigator, Sarah Cannon Research Institute, on ONT-380 for HER2-positive breast cancer and the treatment’s ability to cross the blood-brain barrier. Hamilton says the reason ONT-380’s ability to cross that barrier is important is because patients with HER2-positive breast cancer have a predilection to develop brain metastases.
She added that ONT-380 was proven to be effective when combined with capecitabine (Xeloda) and trastuzumab (Herceptin), though sometimes a combination of all three proved most useful. ONT-380 is a HER2-specific inhibitor and showed promising results when tested in patients with HER2-positive breast cancer who had previously received trastuzumab and T-DM1.
In 2013, Lyndsay Sung noticed something new on the edge of her right breast. “I felt something weird—an odd thickening along the rib,” she recalls. At the time, her son was only a year old, so she thought it might have been related to breastfeeding. But then she felt it again in September 2014. Lyndsay knew she was at risk for breast cancer because her grandmother had had it, and she also knew her breasts from years of self-exams. So she went to see her family doctor. Continue reading…
“Prognosis for human epidermal growth factor receptor 2 (HER2)-positive patients with lymphocyte-predominant breast cancer (LPBC) was significantly better following treatment with chemotherapy alone than it was for their counterparts receiving chemotherapy plus trastuzumab (Herceptin), an exploratory analysis of the North Central Cancer Treatment Group-N9831 trial has shown.
“Among 489 patients from the N9831 trial receiving chemotherapy alone, 10-year Kaplan-Meier estimates for recurrence-free survival (RFS) among participants with high-levels of stromal tumor-infiltrating lymphocytes (STILs) was 90.9% compared with 64.5% for patients with low-levels of STILs.
“In dramatic contrast, 10-year estimates for RFS among 456 patients who received the same chemotherapy regimen followed by weekly paclitaxel plus trastuzumab followed by trastuzumab alone were virtually identical in patients with high- and low-levels of STILs at 80% and 80.1%, respectively (HR 1.26; 95% CI 0.50-3.17; P=0.63).”