Here is a highlight of recent publications that utilize data collected at the New York site of the Breast Cancer Family Registry. For a full listing of all BCFR publications, please visit the BCFR site at http://www.bcfamilyregistry.org/publications.
Dependence of cancer risk from environmental exposures on underlying genetic susceptibility: an illustration with polycyclic aromatic hydrocarbons and breast cancer.
Shen J, Liao Y, Hopper JL, Goldberg M, Santella RM, Terry MB.
Br J Cancer. 2017 Apr 25;116(9):1229-1233.
Polycyclic aromatic hydrocarbons (PAH) are a group of environmental pollutants comprised of hundreds of different chemicals. They occur naturally in petroleum and coal products such as crude oil, gasoline and coal and are released in the atmosphere when coal, oil, gas, wood, garbage, or tobacco are burned. As a class, PAH represent the most prevalent of environmental pollutants. People are exposed to PAH through motor vehicle exhaust, cigarette smoke, wood smoke, fumes from asphalt roads, or by eating grilled or charred meats or foods contaminated by PAH during the food manufacturing process. Previous studies have found that high exposure to PAH is associated with increased risk of breast cancer. It is not clear if women with a high risk of breast cancer due to their family history also experience an increase in breast cancer risk if exposed to PAH.
In this study, we measured markers of PAH exposure in the blood of 80 women that were later diagnosed with breast cancer and 156 women that have not been diagnosed with breast cancer, all of whom are enrolled in the Metropolitan New York Registry. We estimated the 10-year risk of breast cancer for the women based on family history and genes where relevant using the BOADICEA risk model. High breast cancer risk in clinical terms is usually defined as a 10-year risk of 3.4% or more. PAH exposure above the mean was associated with a twofold increase in breast cancer risk in all women. Very high PAH exposure was associated with a 3-7 fold increased risk of breast cancer for women with a 10-year breast cancer risk above 4%.
This is the first study to prospectively examine whether exposure to PAH, as measured through blood biomarkers, increases risk in women at high risk of breast cancer and demonstrates that environmental exposures may modify breast cancer risk even in those at highest risk of breast cancer.
The impact of cancer prevention guideline adherence on overall mortality in a high-risk cohort of women from the New York site of the Breast Cancer Family Registry.
Cloud AJ, Thai A, Liao Y, Terry MB.
Breast Cancer Res Treat. 2015 Jan;149(2):537-46.
Adherence to the threefold breast cancer prevention guidelines established by the American Cancer Society (ACS) (maintain a BMI of <25 kg/m2, spend ≥150 minutes doing moderate intensity physical activity per week, and limiting alcohol intake to ≤1 drink per day) has been shown to lower overall rates of mortality, as well as reduce the risk of chronic diseases such as diabetes, myocardial infarction, stroke, and cancer. Women who adhere to all three guidelines have a 33% lower risk of death from breast cancer, and adherence to the three guidelines has been found to lead to a 22% decrease in incidence of breast cancer in postmenopausal women. This study looked into whether or not this trend also applies to women at high risk, given a family history of breast cancer.
This study followed 2,905 women with breast cancer or at increased risk for breast cancer due to family history or genetic predisposition, from a Breast Cancer Family Registry in New York (77% non-Hispanic white and 23% Hispanic). Although women with and without breast cancer at the start of the study generally did not follow all three guidelines, those that followed three guidelines compared to those that followed one guideline demonstrated a 44–53 % reduction in rate of overall mortality. Furthermore, the study found that adherence to the three guidelines was associated with a 27 % reduced mortality in cancer-free women <50 years and a 32 % reduced mortality in women >50 years that had cancer. The disparity between the rate of adherence to the three guidelines and the rate of reduction in mortality illustrates room for improvement in lifestyle-based cancer prevention.
Breast cancer risk assessment across the risk continuum: genetic and nongenetic risk factors contributing to differential model performance.
Quante AS, Whittemore AS, Shriver T, Strauch K, Terry MB.
Breast Cancer Res. 2012 Nov 5;14(6):R144.
To evaluate a patient’s risk for breast cancer, a doctor chooses a prediction model based on the patient’s health information, including family history and genetic factors. The Breast Cancer Risk Assessment Tool (BRCAT, or the Gail model), which does not incorporate extended family history of breast cancer or BRCA1/2 mutation status, is typically used for patients at average risk, while the more advanced International Breast Cancer Intervention Study (IBIS, or the Tyrer Cuzick) model is used for patients with above-average risk.
This study followed 1,857 women over an average period of 8.1 years and compared predictions from the BRCAT and the IBIS models to their observed breast cancer outcomes. The women in the study, all non-cancer participants in the Breast Cancer Family Registry, ranged from low breast cancer risk to very high risk.
The results of the study found that the 10-year breast cancer risks as predicted by the BRCAT model were consistently lower than the actual breast cancer levels found in the participants. On the other hand, the predictions from the IBIS model were generally close to the actual findings, even for the women who were considered at average risk (e.g., those with no family history and no BRCA1/2 genetic mutations). These findings suggest that extending the use of the IBIS model to women with average risk of breast cancer may yield more accurate risk predictions and may thereby lead to more informed health decisions by doctors and their patients.
Risk factors for uncommon histologic subtypes of breast cancer using centralized pathology review in the Breast Cancer Family Registry.
Work ME, Andrulis IL, John EM, Hopper JL, Liao Y, Zhang FF, Knight JA, West DW, Milne RL, Giles GG, Longacre TA, O’Malley F, Mulligan AM, Southey MC, Hibshoosh H, Terry MB.
Breast Cancer Res Treat. 2012 Aug;134(3):1209-20. Epub 2012 Apr 25.
Breast cancer is a diverse grouping of diseases with varying affects on breast tissue. To distinguish between types of breast cancer, disease pathologists generally use codes from the International Classification of Diseases-Oncology (ICD-O). Alternatively, some researchers, doctors, and institutions adopt more involved, centralized review processes to classify tumor types.
This study reviewed 3,260 breast cancer cases from the Breast Cancer Family Registry (BCFR) and compared ICD-O classifications with classifications obtained from the centralized BCFR pathology review. While the classification methods demonstrated excellent agreement for the commonly occurring ductal tumors, the agreement was lower for the less common tumor types. For instance, only 26% of the cases classified as medullary carcinomas in the BCFR review received an identical ICD-O classification. Further, statistical relationships between tumor status and tumor-specific risk factors (e.g., body mass index and oral contraceptive use) were more precise when using the BCRF classifications as compared to the ICD-O classifications.
The findings from this study highlight inconsistencies between current classification methods and demonstrate the particular value of centralized pathology review when classifying rare tumor types.
Total energy intake and breast cancer risk in sisters: the Breast Cancer Family Registry.
Zhang FF, John EM, Knight JA, Kaur M, Daly M, Buys S, Andrulis IL, Stearman B, West D, Terry MB.
Breast Cancer Res Treat. 2013 Jan;137(2):541-51. Epub 2012 Dec 6.
Studies in animals have shown that consuming fewer calories reduces mammary tumor development, but among humans the connection between diet and breast cancer risk has not been so clearly established. Some research indicates that diet may work together with body size and physical activity to affect breast cancer risk.
This study examined breast cancer risk among 1,775 women diagnosed with breast cancer between 1995 and 2006 and among 2,596 of their unaffected sisters from the Breast Cancer Family Registry in relation to calorie consumption, physical activity, and body mass index (BMI). When comparing women with the highest levels of calorie consumption to those with the lowest levels, women with high calorie consumption were 60-70% more likely to develop breast cancer. This relationship persisted even after accounting for physical activity and BMI in the analyses. While further exploration is needed, these findings suggest that reducing calorie intake alone (without influencing physical activity or body size) may reduce breast cancer risk in some individuals.