The second press conference held at the San Antonio Breast Cancer Symposium featured four studies that looked at emerging therapies in the treatment of breast cancer.
The first study, " Targeting Intrinsically-Resistant Breast Cancer Stem Cells with Gamma-Secretase Inhibitors," was presented in a general session by Jenny Chang, MD, professor of medicine at Baylor College of Medicine. In this study, researchers tested gamma-secretase inhibitors in stem cell models in the lab and in a complementary clinical trial of a gamma-secretase inhibitor in women with breast cancer.
Gamma-secretase (GS) is a protein that prompts activity in the Notch-signaling pathway, which regulates the way our bodies reproduce stem cells. In some cancers, Notch has a mutation, or mistake, which makes it produce too much of itself. By inhibiting, or lessening, the amount of GS that reaches Notch, gama-secretase inhibitor medicines may cause the death of cancer cells.
The study concluded that treating breast cancer with a Notch pathway inhibitor reduced the ability of cancer stem cells to replenish themselves and promote tumor growth. These findings suggest that ongoing clinical trials testing this class of agents could offer promising results, especially when combined with other anticancer treatments.
The second study in the press conference, " A Phase III, Randomized, Parallel-Group Trial Comparing Fulvestrant 250 mg vs Fulvestrant 500 mg in Postmenopausal Women with Estrogen Receptor-Positive Advanced Breast Cancer," was presented in a general session by Angelo Di Leo, MD, PhD, director of the department of oncology at the Hospital of Prato, Italy.
In this study researchers concluded that a higher dose (500 mg) of fulvestrant (brand name: Faslodex) prompts few side effects and works more actively than the standard, lower dose (250 mg) in postmenopausal women with metastatic breast cancer.
"We believe that, based on the results of this study, treatment and practice should change; patients should receive the 500 mg dose," said Dr. Di Leo.
The researchers are now conducting an additional study in an effort to understand whether the higher dose works similarily in all women, or only some.
The third study, "A Double-Blind, Randomized, Placebo-Controlled, Phase 2b Study Evaluating the Efficacy and Safety of Sorafenib in Combination with Paclitaxel as a First-line Therapy in Patients with Locally Recurrent or Metastatic Breast Cancer," was presented in a general session by William Gradishar, MD, professor of medicine at the Robert H. Laurie Comprehensive Cancer Center at Northwestern University.
This study concluded that combining paclitaxel (brand name: Taxol)—a chemotherapy agent commonly used to treat a number of different cancers, including both early and advanced breast cancer—with sorafenib (brand name: Nexavar) offers women with advanced, HER2 negative breast cancer significant improvement in overall response rate (shrinking of the cancer) and time to disease progression (length of time the cancer does not grow).
Although this study is still early, the combination of sorafenib and paclitaxel also trends toward longer progression-free survival (living longer without growth of the cancer. Data on overall survival are not yet available.
"These data indicate that sorafenib provides added benefit when combined with paclitaxel compared to single-agent paclitaxel in the first-line treatment of advanced breast cancer," said Dr. Gradishar. "There were no new [side effects] observed with the combination and [they] were manageable."
The final study featured in the press conference, " Targeting Aldose Reductase: A Novel Strategy in Treating Endocrine Resistance Using Combination Therapy," will be presented Saturday in a general session by Rajeshwar Rao Tekmal, PhD, professor in obstetrics and gynecology at the University of Texas Health Science Center at San Antonio.
This study concluded that treating estrogen receptor-positive breast cancers with a combination of fidarestat (an inhibitor of the aldose reductase enzyme, which is important in controlling nerve damage in diabetes) and letrozole (an aromatase inhibitor, brand name: Femara) could delay or stop tumor resistance to endocrine therapy.
About two-thirds of breast cancer tumors initially are hormone sensitive or estrogen receptor-positive and respond well to endocrine therapy. However, close to half of those tumors develop resistance to endocrine therapy, said Dr. Tekmal. In this study in the lab, researchers treated estrogen receptor-positive tumors already resistant to letrozole with letrozole and fidarestat. As an inhibitor of aldose reductase enzyme, fidarestat blocks the metabolism of glucose (sugar) in cancer cells. Together, the combination effectively re-sensitized the cells to letroloze, allowing for effective endocrine therapy and more cell death.
While this is a preclinical study, Dr. Tekmal believes it could lead to future medical treatments that will make endocrine therapy more effective for longer periods of time.
Stay tuned for more breaking news from the San Antonio Breast Cancer Symposium and dial in to our SABCS Annual Update teleconference scheduled for January 6 for a recap of the latest information presented at the Symposium.