FORCE has a strong commitment to promoting research to benefit our community. We advocate for more research funding, educate people about available studies, and report findings back to our community.
by Julie Huynh, MS
In December 2015, we attended the San Antonio Breast Cancer Symposium. Below are highlights from presentations that impact the HBOC community. You can view accompanying abstracts for free by visiting the SABCS website and requesting guest access.
Dr. Benjamin Smith and colleagues from the University of Texas MD Anderson Cancer Center wanted to understand the relative value of early breast cancer treatment options by looking at these factors:
The women in this study had early stage breast cancer and were divided into two groups: those diagnosed under age 65 and those age 66 and older. Regardless of age, the researchers found that women who had a mastectomy and reconstruction had more complications than women who had a lumpectomy and whole breast irradiation. The increase in complications resulted in additional costs for the women who had mastectomy and reconstruction.
They also found that the women under 65 who had mastectomy alone (without reconstruction) had the lowest number of complications associated with the surgery and the lowest costs, while the women 66 and older who had lumpectomy alone had the lowest number of complications and the lowest cost.
Mary Pritzlaff and colleagues from Ambry Genetics looked at panel testing in men with breast cancer. They reviewed multi-gene panel test results for all male breast cancer patients at Ambry Genetics between March 2012-2015 and gathered information about 280 men. The mutation rate in this group was 14%. The researchers found that the age of men at diagnosis was significantly lower in those who carried CHEK2 mutations. Additionally, men who carried CHEK2 mutations were more likely to have a family history of male breast cancer than men with other mutations. Multi-gene testing in male breast cancer patients allowed for detection of mutations that would not have been detected via single gene testing. This work suggests that men with male breast cancer should undergo genetic testing regardless of age or family history, and highlights the role of CHEK2 mutations in male breast cancer.
Jeffrey Weitzel and colleagues from City of Hope and Myriad Genetic Laboratories wanted to study the different pathogenic gene variants and clinical characteristics for women with two breast cancers. The researchers used a 25-gene hereditary cancer panel from Myriad Genetic Laboratories. They found that:
Li-Fraumeni syndrome is caused by mutations in the TP53 gene. Individuals with TP53 mutations can develop leukemia, brain cancer, and breast cancer, among other cancers. Increased use of multi-gene panels is identifying individuals who carry TP53 mutations but would not have been expected to carry them given their personal or family history of cancer. Thereasa Rich and colleagues at Myriad Genetic Laboratories wanted to study the clinical characteristics of individuals with TP53 mutations identified using Myriad Genetic Laboratory’s 25-gene panel. The researchers found that a high number of TP53 mutation carriers would not have been identified as being at risk for Li-Fraumeni syndrome using NCCN guidelines. They also saw that approximately 30% of the TP53 mutations detected were likely not inherited mutations. Rather, only some of the individuals’ cells carried the TP53 mutation. Overall, the researchers suggest that each individual TP53 mutation carrier “should be evaluated cautiously in light of the patient’s clinical history and follow-up testing may be appropriate.”
Gregory Idos and his colleagues from the USC Norris Comprehensive Cancer Center, Keck School of Medicine, and Stanford Cancer Institute asked this question: How does panel testing affect patient care? They want to determine how often non-BRCA mutations are detected by panels, and whether the mutations uncovered changed patient’s medical management (such as qualifying them for new screening or risk-reducing surgery). The researchers have results from 500 people who have a greater than 2.5% chance of carrying a mutation (based on a personal or family cancer history), and found:
Of those who carry a mutation, 4% are in a gene other than BRCA. According to the study authors, “identification of non-BRCA deleterious mutations prompts appropriate risk-reduction recommendations and enhanced cancer surveillance.” The authors believe that multi-gene panel testing may identify patients with mutations even without an expected personal or family history. Ultimately, they want a study population of 2000 people who have a greater than 2.5% chance of carrying a mutation (based on a personal or family cancer history). The researchers continue to recruit individuals toward the goal of 2000 patients, and will follow-up on existing participants by tracking their clinical outcomes and medical interventions for risk reduction.
BRCA mutation status may be a predictor of how well a patient responds to a certain therapy. Using data from 471 patients who had triple negative breast cancer and testing for BRCA mutations, Dr. Peter Fasching and his colleagues looked to see if BRCA mutation status could predict how well patients responded to chemotherapy alone as compared to chemotherapy with Bevacizumab, an antibody that prevents angiogenesis (growth of blood vessels). The study group was divided into the TNBC patients who were BRCA mutation carriers (82 patients) and those who were not BRCA mutation carriers (389 patients).
When the patients who were BRCA negative were broken into two groups (chemotherapy versus chemotherapy and Bevacizumab), more patients that received both chemotherapy and Bevacizumab had what is known as a “pathologic complete response” (absence of cancer after treatment) than those treated with chemotherapy alone (about 36% versus 26%).
The researchers found an even larger difference in pathological complete response when the BRCA mutation carriers were separated into the two groups (chemotherapy versus chemotherapy and Bevacizumab). Patients who received both chemotherapy and Bevacizumab did better than those who received only chemotherapy (about 66% compared to 38%). This research suggests that BRCA mutation status may serve as a predictor for how well a patient will respond to certain therapies. However, as the number of BRCA mutation carriers in this study was small, more work needs to be done to fully understand this possibility.
Smith, BD, et. al. Complication and economic burden of local therapy options for early breast cancer. Abstract at San Antonio Breast Cancer Symposium. December, 2015.
Pritzlaff, et. al. Multi-gene testing in a male breast cancer cohort: Insights and unexpected results.Abstract at San Antonio Breast Cancer Symposium. December, 2015.
Rich, T. et. al. Characterization of Li-Fraumeni syndrome diagnosed using a 25-gene hereditary cancer panel. Abstract at San Antonio Breast Cancer Symposium. December, 2015.
Idos, GE, et. al. Interim analysis of multiplex gene panel testing for inherited susceptibility to breast cancer. Abstract at San Antonio Breast Cancer Symposium. December, 2015.
Fasching, PA, et. al. BRCA mutations, therapy response and prognosis in the neoadjuvant GeparQuinto study. Abstract at San Antonio Breast Cancer Symposium. December, 2015.