Women At Risk
Research Highlights
Established in 1991, this unique and comprehensive surveillance program, which started with less than 100 participants, has grown to monitor more than 1,700 women at high risk for developing breast cancer.
With more than ten years of follow-up data, the WAR Registry serves as a valuable resource for researchers in their ongoing efforts to understand the complex causes of breast cancer and develop new methods of risk assessment for prevention, surveillance, and effective treatment.
The following are some highlights of research conducted using the Registry:
2008
Risk Perception Study And Educational Intervention At Nyack Hospital
Michael Rader, MD, Jennifer Chun, MPH, Ana Abraido-Lanza, PhD, Jessica Ancker, MPH, Anna Komorowski, MD, Freya Schnabel, MD
Women's perceptions of breast cancer risk and how they assess the value of prevention strategies are likely to determine their interest in preventive interventions and trials. The objectives of this study were to assess the effectiveness of an educational intervention on women's perception of breast cancer risk, understand their perceptions on the effectiveness of risk reduction interventions and assess which level of risk reduction would justify their participation in chemoprevention trials.
An educational seminar on breast cancer risk was conducted in Rockland County. Questionnaires were administered before and after the educational intervention. These pre- and post-questionnaires provided data to calculate Gail risk scores and assess risk perception. This study was approved by the IRB of Nyack Hospital. Paired data analyses using Mantel-Haenszel odds ratios were conducted with statistical significance at p-value <0.05.
Although 65 women completed both questionnaires, the total study population was restricted to the 38 participants who had no prior history of breast cancer and who provided information to compute a Gail score. Median age was 56 years (range: 28-72); 12 out of 38 (32%) women had a strong family history of breast cancer. The mean Gail score was 2.2. Seventeen out of 38 (45%) women had Gail scores ≥1.7%. Thirty-four per cent of the participants overestimated the average woman's lifetime risk of developing breast cancer. This perception decreased significantly to 8% after the educational intervention. Most women rated diet as the "most effective" risk reduction intervention, followed by physical activity. A majority of the participants (53%) said they would be willing to consider participating in chemoprevention trials if they promised a risk reduction of at least 35%.
The results of this study demonstrate that educational efforts can reduce inaccuracies in women's perception of breast cancer risk. Participants expressed marked interest in participating in potential risk reduction interventions including vitamins, diet, and chemoprevention trials. However, participants seemed to indicate that a potential risk reduction of 35% would be required for them to consider a chemoprevention trial.
This study will be presented this month at the 44th American Society of Clinical Oncology Annual Meeting in Chicago, IL.
Assessing A Bayesian Risk Prediction Model In A High-Risk Breast Cancer Population
Jennifer Chun, MPH, Freya Schnabel, MD, Omolola Ogunyemi, PhD
There are a number of models that currently exist for predicting breast cancer risk in various populations. Of these, the Gail Model is the most widely utilized; however, there are significant limitations to this model. Bayesian networks are a novel technique for developing risk prediction models by incorporating expert opinion and empirical evidence along with established risk factors.
The aim of this study was to develop a computer-based individualized 5-year breast cancer risk prediction model. We evaluated the Bayesian model by assessing its predictive value in a select group of women known to be at high-risk for developing breast cancer and by comparing the results of our Bayesian model to the Gail model.
The WAR Registry, established in 1991, provided the study population of 210 women who were between the ages of 23-69 years at time of enrollment. Ten women had developed breast cancer (5%) during the study period. Women were defined as high-risk if they had one or more of the following: a strong family history of breast cancer (FHBC), a biopsy-proven history of atypical ductal hyperplasia (ADH), atypical lobular hyperplasia (ALH), or lobular carcinoma in situ (LCIS). Using features that included risk factors such as race, age, age at menarche, age at first live birth, and body mass index, a 10-fold cross-validation was performed using a Naïve Bayes classifier to evaluate the predictive ability of the model. To measure prediction accuracy, we measured the Receiver Operating Characteristic (ROC) and estimated the area under the ROC curve (AUC).
At present, there is no single model that accurately predicts the risk of developing breast cancer for an individual woman. Interestingly, in our study, the Bayesian model appeared to better predict breast cancer risk than the Gail model. Recent studies have demonstrated an improvement in predictive power of multivariate risk models when additional risk factors are incorporated, including BRCA status, body mass index (BMI), and mammographic density. Bayesian models represent an advance in risk prediction modeling by allowing continual modification of the model as new risk factors are identified. Further studies utilizing this model are underway.
This study was presented at the 2007 Breast Cancer Symposium and the American Medical Informatics Association 2007Annual Symposium.
2007
Breast Cancer Risk Factors in Young Women
Ben Pocock, MD, Jennifer Chun, MPH, Kathie-Ann Joseph, MD, MPH, Laura Klein, MD, Mahmoud El-Tamer, MD, Freya Schnabel, MD, Department of Surgery, Columbia University Comprehensive Breast Center, Women At Risk, NewYork-Presbyterian Hospital/Columbia University Medical Center
This study queried the Registry for women ≤35 years to determine the significance of established risk factors over time in a population of high-risk younger women. High-risk was defined as having one or more of the following: a strong family history of breast cancer (FHBC), a biopsy-proven history of atypical ductal hyperplasia (ADH), atypical lobular hyperplasia (ALH), or lobular carcinoma in situ (LCIS). Descriptive analyses were used to look at these factors over time and to compare women with and without breast cancer. Out of 1412 high-risk women, 199 were identified as ≤35 years of age with a median follow-up of 4 years. The median age was 32 years (range 15-35 years). 178 (89%) women had a strong FHBC, 21 (11%) had ADH, 5 (3%) had ALH and 12 (6%) had LCIS. Only 3 (1.5%) developed breast cancer during the study period; all of these 3 cases had a strong FHBC and none had a prior high-risk lesion. Patients who had high-risk lesions but no FHBC did not develop breast cancer during this follow-up period. In conclusion, being ≤35 years of age and having a strong family history of breast cancer appeared to be associated with the development of breast cancer, while other well-established histologic risk factors were not. Therefore, ADH, ALH, and LCIS may have different prognostic significance in young women. These findings help us to better understand risk factors in this group of younger women and may aid in the evolution of defining age-appropriate risk management and strategies. Results of the study were presented at the 24th Annual Miami Breast Cancer Conference in Miami, FL.
2007
The Interaction of Increasing Age and Breast Cancer Risk Factors
Jennifer Chun, MPH, Ben Pocock, MD, Kathie-Ann Joseph, MD, MPH, Laura Klein, MD, Mahmoud El-Tamer, MD, Freya Schnabel, MD, Department of Surgery, Columbia University Comprehensive Breast Center, Women At Risk, NewYork-Presbyterian Hospital/Columbia University Medical Center
Currently, there is no information on how risk factors predict breast cancer incidence in women who are ≥70 years of age. This study explored the impact of known risk factors on high-risk women 70 years of age or older. Out of 1412 women in the WAR Registry, 82 women were ≥70 years of age (range 70-91). Twenty had a history of ADH (24%), 5 had ALH (6%), 27 had LCIS (33%), and 52 women had FHBC (63%). With a mean follow-up of 4 years, 6 of these women developed breast cancer (7.3%). The mean Gail score for the ≥70 age group was 4.3, as compared to 4.7 in the subset with cancer. Of the 6 breast cancer cases, two patients presented with DCIS. The remaining four were stage I at diagnosis. All tumors were low-grade with positive estrogen receptors. The Fisher's exact tests demonstrated that ADH (p=0.15), ALH (p=1.0), LCIS (p=0.66), and FHBC (p=0.62) were not statistically significant predictors of breast cancer within this age group of high-risk women. Preliminary data on high-risk women who are ≥70 years indicate that having a history of ADH, ALH, LCIS and FHBC were not strong predictors of breast cancer in this population. These findings contribute to a better understanding of the interaction of established risk factors and age. This study also emphasizes the importance of defining age-appropriate recommendations for breast cancer risk management, including surveillance and chemoprevention, for women who are 70 years of age or older. Results of the study were presented at the 31st Annual Symposium of the American Society of Breast Disease in San Francisco, CA.Other Highlights
- Women with a history of lobular carcinoma in situ (LCIS) were enrolled in a study that investigated the effects of chemical carcinogens in charcoal-broiled, barbequed and fried meat. The study found that women with LCIS who ate the charred meat may have been more susceptible to DNA damage compared to women with LCIS who didn't eat it, raising awareness of dietary interventions for breast cancer prevention.
- Women with Gross Cystic Disease (GCD) were compared to women without GCD with respect to breast cancer outcome. The results indicated that there were no differences in overall survival between the two groups. These results suggest that GCD is not a significant risk factor for women at high risk for breast cancer.
- Another study found that having a strong family history of breast cancer, a biopsy-proven history of atypical ductal hyperplasia (ADH) or lobular carcinoma in situ (LCIS), and obesity (BMI ≥ 30) were all significantly associated with the development of breast cancer. These findings helped to further identify women who might benefit most from various risk reduction strategies.
- To help fill the gap in data about breast cancer risk in women aged 35 and younger, researchers looked at young women over time and found that a strong family history of breast cancer appeared to be associated with the development of breast cancer, while other established risk factors were not. Therefore, atypical ductal hyperplasia (ADH), atypical lobular hyperplasia (ALH), and lobular carcinoma in situ (LCIS) may have different prognostic significance in young women, and further studies are needed.
Contact
- Research and High-Risk Program Coordinator
- Amy Whiffen
Phone: 212-305-3238
Email: awhiffen@womenatrisknyc.org
