2014 SABCS, Part Three: Clinical Trials in Breast Cancer
By BCRF | January 23, 2015
By BCRF | January 23, 2015
The 37th annual San Antonio Breast Cancer Symposium (SABCS) took place on December 9-13. The annual five-day program provides a forum for communication and education in breast cancer research.
Read on for part three of our four-part series of the most compelling research presented at the conference. Read parts one and two here.
In his closing remarks on the final day of the San Antonio Breast Cancer Symposium, Dr. Harold Burstein of the Dana Farber Cancer Institute highlighted the significant progress that has been made in breast cancer.
Patients are living much longer, due in large part to the practice of multi-disciplinary care and the widespread use of adjuvant therapy — systemic therapy after surgery to prevent recurrence. The incidence of local recurrences has dramatically decreased and there have been tremendous successes for some patients receiving targeted therapies.
Many challenges remain, however, particularly in triple negative and metastatic breast cancer.
Early results from clinical trials in triple negative breast cancer (TNBC) suggest that two treatments — platinum-based drugs and the drug Avastin™, neither of which has traditionally been very successful in the treatment of breast cancer — may be effective therapies against this aggressive type of cancer.
In a clinical trial supported in part by BCRF, investigators reported that the platinum drug carboplatin significantly reduced TNBC tumor size when added to traditional chemotherapy, but also increased side effects.
Avastin™, which blocks the production of new blood vessel formation in tumors, also significantly shrank TNBC tumors when combined with the chemotherapy, but only in triple negative cancers that were the basal subtype. According to study investigators, the results suggest these treatments may only be effective in certain tumors. Efforts are ongoing to identify biomarkers to help identify which patients are most likely to benefit.
As noted by Dr. Nancy Davidson in a plenary lecture, adjuvant endocrine therapy (anti-hormone therapy after surgery for ER+ breast cancer) has had a significant impact how breast cancer is treated. Resistance to endocrine therapy continues to be a challenge, especially in metastatic hormone receptor-positive disease.
Some encouraging results from the FIRST trial suggest that the anti-estrogen drug fulvestrant may be an effective first line therapy for metastatic ER+ breast cancer. In a study of 205 women with advanced ER+ breast cancer, fulvestrant was more effective than anastrozole, which is currently considered the most potent drug for ER+ metastatic breast cancer.
The study showed that the patients who took fulvestrant were 30 percent less likely to die of their disease than those who took anastrozole. While the difference in overall survival was encouraging, the study’s researchers cautioned that these results will not change clinical practice and have initiated a phase III follow-up study to gain FDA approval of fulvestrant as a first-line therapy.
Predicting which patients will most likely respond to hormonal therapies will be a key factor in successful treatments. Correlative studies from multiple groups are using gene expression in tumors and normal tissue to identify biomarkers that can be used to predict how patients will respond to specific therapies. Here are few examples:
Results from the TransCONFIRM study identified a potential 37-gene signature that predicted response to fulvestrant,
Another study in patients treated with tamoxifen for five years identified several gene mutations, some that predicted a worse outcome and others that predicted better outcome.
In a small study of post-menopausal women receiving letrozole as a neoadjuvant (pre-surgery) therapy, investigators used genomic analysis to develop a gene prediction model that could be used to select women most likely to respond to this therapy.
While all of these results need to be validated in additional studies, they collectively demonstrate the power of genomics in translational research.
Tamoxifen is an anti-estrogen treatment and standard therapy for young women with ER+ breast cancer. Several trials have looked at whether adding ovarian suppression to anti-estrogen therapy could improve the effects of the therapy. Results from the SOFT trial showed that young women under age 35 who received the drug triptorelin (for ovarian suppression) with tamoxifen had a 22 percent decreased risk of recurrence compared to women receiving tamoxifen alone.
The study also compared the effects of ovarian suppression with the aromatase inhibitor exemestane. Women in this group had a reduced risk of recurrence of 35 percent compared to women receiving tamoxifen alone. Older women in the study, who were closer to natural menopause, did not receive any added benefit from the ovarian suppression.
And while we've learned a great deal about breast cancer in women, we still know very little about breast cancer in men. This is partially because male breast cancer is a rare disease, affecting about one in every 100,000 men in the U.S. It is often diagnosed at an advanced stage and currently is treated the same way as female breast cancer, because there’s been little research done on how male and female breast cancers differ.
To better understand these differences, BCRF is supporting the largest international effort to characterize male breast cancer to date. The Male Breast Cancer Study is led by an international team coordinated by Dr. Fatima Cardoso of the Breast International Group under the auspices of the European Organisation for Research and Treatment of Cancer in collaboration with the North American Breast Cancer Group and Translational Breast Cancer Research Consortium.
Dr. Cardoso reported the initial results from a retrospective analysis of 1,700 breast tumors from men. The researchers found that the majority of tumors were grade 2 invasive ductal carcinomas and that the male breast cancers were typically positive for estrogen and progesterone receptors, as well as the androgen receptor. Very few expressed the HER2 protein and less than one percent were triple negative.
The study investigators are currently conducting additional analyses and have initiated a prospective study in the U.S. with TBCRC investigators and BCRF grantees Drs. Sharon Giordano and Peggy Porter.
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