“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.’ “
The gist: The U.S. Food and Drug Administration (FDA) has granted a “Fast-Track” designation to a new treatment for people with metastatic, triple-negative breast cancer who haven’t had success with their previous treatments. The treatment is called sacituzumab govitecan (aka IMMU-132). The Fast-Track designation means that the FDA will facilitate a faster approval process so that the treatment can soon be prescribed by oncologists in the U.S.
“The FDA today granted fast track status to sacituzumab govitecan, an antibody–drug conjugate in development for treatment of patients with triple-negative breast cancer who failed prior therapies for metastatic disease, according to the drug’s manufacturer.
“Sacituzumab govitecan (IMMU-132, Immunomedics) is formed by using the moderately-toxic SN-38 — the active metabolite of irinotecan (Camptosar; Pfizer), used to treat certain solid tumors — conjugated to an anti–TROP-2 antibody.
“The FDA’s Fast Track program is intended to facilitate the development and expedite the review of new drugs intended to treat serious conditions, as well as agents that would fill unmet medical needs.
“The FDA based its decision on the efficacy sacituzumab govitecan has shown in patients with advanced triple-negative breast cancer.
“Reducing dietary fat intake for at least 5 years after diagnosis could help improve survival rates for early-stage breast cancer patients with hormone-unrelated breast cancer, according to a new study.
“The findings of the study were presented at the 2014 San Antonio Breast Cancer Symposium – a 5-day conference aiming to provide state-of-the-art information on breast cancer research to an audience of researchers and physicians from over 90 countries.
” ‘The current findings with respect to long-term influence of dietary lifestyle intervention on overall survival are mixed, but of potential importance,’ reports Dr. Rowan Chlebowski, a medical oncologist from the Harbor-UCLA Medical Center in Torrance, CA.
“The study utilized data taken from the Women’s Intervention Nutrition Study (WINS), a randomized trial that had previously been used to test whether dietary intervention can improve the clinical outcome of women with breast cancer, and assessed death rates after 15 years of follow-up.”
The gist: Researchers are hoping a treatment approach called ‘PI3K inhibition’ might improve outcomes for people with hormone receptor-positive breast cancer. But it’s unclear whether the approach will be successful, and a recent attempt did not give stellar results. In a clinical trial, researchers gave patients the PI3K inhibitor drug pictilisib along with the drug fulvestrant (Faslodex). It did not significantly lengthen the amount of time patients went without their cancer worsening. But later analysis showed that it did stave off cancer getting worse in certain patients: women whose breast cancer is both estrogen receptor-positive (ER+) and progesterone receptor–positive (PR+). Further research is needed to see if any PI3K drugs are particularly effective. For more information, click through to the full article and see this other article from Cancer Network.
“Interest is high in studying the PI3K pathway in hormone receptor–positive breast cancer, but it is not clear which of the PI3K inhibitors under development—if any—will be a ‘home run.’
“Adding the pan-class I selective PI3K inhibitor pictilisib to fulvestrant (Faslodex) did not significantly improve progression-free survival in women with estrogen receptor–positive breast cancer, but in an exploratory analysis of the trial, progression-free survival was significantly extended in women with both estrogen receptor–positive and progesterone receptor–positive breast cancer. The findings were presented at the 2014 San Antonio Breast Cancer Symposium (Abstract S2-02).
“ ‘When we considered only women with breast cancer positive for both estrogen receptor and progesterone receptor, adding pictilisib resulted in a significant doubling of progression-free survival in an exploratory analysis. We plan to investigate whether the benefit of pictilisib for women with estrogen receptor-/progesterone receptor–positive breast cancer holds true in an additional cohort of patients within this study,’ stated lead author Ian Krop, MD, Director of Clinical Research for the Breast Oncology Program at the Dana-Farber Cancer Institute, Boston.”
The gist: A new treatment that combines the drugs bortezomib and fulvestrant has shown promise in treating post-menopausal women with metastatic hormone receptor-positive breast cancer whose disease worsened after being treated with drugs called aromatase inhibitors. The combo treatment was tested in 118 patients in a clinical trial. It doubled the number of patients still alive after 12 months, and it lowered the chance of patients’ cancer worsening. Further studies will continue to measure the effectiveness of the treatment.
“A new combination of cancer drugs delayed disease progression for patients with hormone-receptor-positive metastatic breast cancer, according to a multi-center phase II trial. The findings of the randomized study (S6-03) were presented at the 2014 San Antonio Breast Cancer Symposium, held Dec. 6-9, by Kerin Adelson, M.D., assistant professor of medical oncology at Yale Cancer Center and chief quality officer at Smilow Cancer Hospital at Yale-New Haven.
“The trial enrolled 118 post-menopausal women with metastatic hormone-receptor-positive breast cancer whose cancer continued to progress after being treated with an aromatase inhibitor. The study, based on work done by Doris Germain of Mt. Sinai Hospital, found that the combination of the drugs bortezomib and fulvestrant—versus fulvestrant alone—doubled the rate of survival at 12 months and reduced the chance of cancer progression overall.
“Bortezomib, used most commonly in treating multiple myeloma, is a proteasome inhibitor that prevents cancer cells from clearing toxic material. Fulvestrant causes clumping of the estrogen-receptor protein. When bortezomib blocks the ability of the cell to clear these protein clumps, they grow larger and become toxic to the cancer cells. This, in turn, amplifies the effectiveness of fulvestrant, a drug commonly used in this subset of patients.
“The drug combination doubled the number of patients whose cancer had not progressed after one year from 14% to 28%, according to Adelson.”
The gist: New research shows that triple-negative breast cancer (TNBC) patients who have a particular molecule called miR-21 near their tumor, but not actually in the tumor cells, have worse clinical outcomes. This opens up the future possibility that doctors could check for miR-21 in order to better understand a patient’s disease and make treatment decisions.
” ‘Triple-negative’ breast cancer (TNBC) occurs in patients whose cells do not express receptors for estrogen, progesterone, and/or human epidermal growth factor receptor 2 (ER-/PR-/HER2-). Because of the absence of these predictive biomarkers, treatment assignment can be difficult. Now, researchers report that high levels of the microRNA miR-21 in the tumor microenvironment, but not in the tumor epithelia (cancer cells), are associated with worse clinical outcomes for patients with TNBC, thus identifying a possible TNBC prognostic biomarker, according to a study in The American Journal of Pathology.
“TNBC accounts for 15% to 20% of breast cancer cases, and patients have shorter recurrence-free survival (RFS) and breast cancer-specific survival (CSS) relative to other major subgroups. It is likely that different subtypes of TNBCs exist, and the heterogeneity may be responsible for a wide variation in response to treatment. ‘Predictive biomarkers for therapeutic response prediction and novel therapeutic targets that address distinct biological features of TNBC subgroups are needed for these patients,’ says Lorenzo F. Sempere, PhD, head of the Laboratory of microRNA Diagnostics and Therapeutics at Van Andel Research Institute in Grand Rapids, MI. ‘These findings add support to the growing importance of miRNA-based diagnostics.’ “
“The cancer drug eribulin, originally developed from sea sponges, could give women with advanced triple negative breast cancer an average of five extra months of life, according to research presented at the National Cancer Research Institute (NCRI) Cancer Conference in Liverpool.
“Researchers led by Professor Chris Twelves, based at the University of Leeds and Leeds Teaching Hospitals NHS Trust, looked at two major clinical trials of more than 1,800 women with breast cancer that had started to spread to other parts of the body. The phase III trials – the final stage of testing before deciding whether a drug can be prescribed to patients – compared the survival of women treated with eribulin* to those given standard treatment.
“The two studies showed an overall improvement in survival of more than two months for women treated with eribulin**. The most significant improvement was seen in women with the advanced triple negative form of breast cancer, where there are limited treatment options; these women’s survival improved by nearly five months. There was also a survival boost of more than two months for women with the HER2 negative form of breast cancer***.
“Cancer spreading to other organs – called metastasis – is responsible for around 90 per cent of all cancer deaths. And, when patients with breast cancer are diagnosed after the disease has started to spread, 10-year survival is around one in 10, compared to nearly nine in 10 for those diagnosed at the earliest stage.
“Study author, Professor Chris Twelves, said: ‘Our results show a substantial improvement in survival for women with metastatic triple negative breast cancer, and a more modest, but significant, benefit for those with HER2 negative breast cancers.’
“ ‘Eribulin has previously been offered to women who’ve already been through several lines of chemotherapy. But the European Union has recently approved eribulin for patients who have received less treatment for their breast cancer, which means we hope to give more patients another treatment option in the not-too-distant future.’ “
“A federal prescription-subsidy program for low-income women on Medicare significantly improved their adherence to hormone therapy to prevent the recurrence of breast cancer after surgery.
” ‘Our findings suggest that out-of-pocket costs are a significant barrier’ to women complying with hormone therapy, said Dr. Alana Biggers, assistant professor of clinical medicine at the University of Illinois at Chicago College of Medicine, and lead investigator on the study. Programs that lower these costs can ‘improve adherence—and, hopefully, breast cancer outcomes—for low-income women,’ she said. Biggers presented the results of the study at an Oct. 14 press conference in advance of the American Society for Clinical Oncology Quality Care Symposium in Boston.
“Breast cancer is a leading cause of cancer-related deaths for women of all races, but survival rates differ by race and socioeconomic status, with African American women and women of low income having higher rates of death.”
Editor’s note: Women with early-stage breast cancer have surgery to remove their tumors. They can choose between a mastectomy to remove the entire breast or a lumpectomy to remove the diseased part of the breast (breast conserving therapy, or BCT). Until now, it was thought that a mastectomy and BCT had similar results in terms of long-term survival for a patient. But a new study shows that BCT offers better survival for women who are PR-positive or ER-positive. Further studies are needed to figure out why. The researchers speculate it may have to do with the radiation treatment usually given just after BCT to keep the cancer from returning. Unfortunately, there appear to be socioeconomic barriers to receiving BCT instead of a mastectomy.
“When factoring in what is now known about breast cancer biology and heterogeneity, breast conserving therapy (BCT) may offer a greater survival benefit over mastectomy to women with early stage, hormone-receptor positive disease, according to research from The University of Texas MD Anderson Cancer Center.
“The study findings defy the conventional belief that the two treatment interventions offer equal survival, and show the need to revisit some standards of breast cancer practice in the modern era.
“The research was presented at the 2014 Breast Cancer Symposium by Catherine Parker, MD, formerly a fellow at MD Anderson, now at the University of Alabama Birmingham.”