Assessment of Risk ~ Algorithm 1

Breast Cancer Diagnostic Algorithms for Primary Care Providers
(Third Edition, June 2005)

A woman's risk of developing breast cancer should be assessed at each routine screening visit since her personal risk factors will change over time. The Assessment of Risk Algorithm provides a basic guide for primary care providers to follow and can help identify women at greater risk of breast cancer than the general population. A sample Breast Cancer History and Risk Assessment Form is also available for download and can be used as a tool to help collect relevant patient information at every breast cancer screening visit.

Assessment of Risk
	Learn more about this algorithm: Introduction Flowchart Notes References
View the flowchart online! (Flash 8 required) Open in a new window: 800X600 size or Full Screen size	Hints for online viewing

• Download the pdf version of this flowchart now! (Adobe Reader required)
• Download all seven 2005 algorithm flowcharts as a single pdf! (Adobe Reader required)
• Go to the Algorithm Booklet (2005) page to see the table of contents and to download the complete booklet (pdf)
• Prior to using an algorithm in your clinical practice, be sure to read the Information Applicable to All the Algorithms.

Introduction to Assessment of Risk ~ Algorithm 1

Risk assessment for breast cancer effectively engages the PCP and the patient in a discussion about breast cancer prevention, educates a woman about her specific risk factors, and helps guide a personalized plan for risk reduction and early detection. For the woman with high risk determined by a risk assessment algorithm, a referral to a risk assessment counselor can be helpful in further defining the risk, identifying possible genetic risks, and recommending appropriate risk reduction strategies.

Risk is the probability or likelihood that an event will occur. Risk can be expressed in several ways, the most common being relative risk and lifetime risk. Relative risk is the ratio of the risk of disease (in this case breast cancer) among those exposed to a risk factor to the risk of disease among those not exposed to the risk factor. For breast cancer, important risk factors include age, gender, family history, age at menarche, other reproductive factors, use of hormone replacement therapy, radiation exposure, alcohol use, and previous breast biopsies – especially those with abnormal findings. See Appendix A-2 for details on relative risk estimates associated with certain risk factors. Absolute risk describes the risk of disease in the context of time, such as the lifetime risk for a disease or risk by a certain age. The Gail Model estimates the absolute risk of breast cancer for a woman over the next five years and over her lifetime based on certain risk factors for the disease. It is an excellent breast cancer risk assessment tool for most women. However, it may underestimate risk for women with a family history of cancer. The Claus Tables provide a better estimate of absolute risk for women with a family history of cancer. These tables estimate breast cancer risk based on the family history of breast cancer and/or ovarian cancer taking into account the age of onset of the disease.

Algorithm #1 is intended to assist PCPs with the identification of women at increased risk for developing breast cancer. Breast cancer risk assessment should be performed as part of routine screening, and it should be repeated annually since risk factors for breast cancer change over time. Certain breast cancer risk factors are more significant than others, and generally, there are interactions between these major risk factors. The interactions make true risk assessment difficult to calculate. This algorithm attempts to incorporate the risk factors that have epidemiologic evidence of significant risk; it does not include all possible risk factors or assess absolute risk for combinations of risk factors. Rather, the algorithm provides a qualitative assessment of risk based on personal history, family history, medical/pathological/genetic factors, with the outcome of either normal or increased risk for breast cancer.

Pathological factors:
A personal history of breast cancer increases the general risk of a second primary breast cancer either in the contralateral breast or the ipsilateral breast if there is remaining tissue. For most women, this risk is estimated to be 0.7% to 1.0% per year for the first 10 years with a 20-year cumulative risk of 4%-20%. However, the personal risk of another primary breast cancer depends to a great extent on the presence of risk factors. For example, a BRCA1 or BRCA2 mutation is associated with a 10-year cumulative risk of 43% and 34% respectively (Metcalfe et al., 2004).

Ductal carcinoma in situ (DCIS) confers a risk similar to invasive breast cancer (Yen, 2003). Other pathological features that increase breast cancer risk include: lobular carcinoma in situ (LCIS), atypical ductal hyperplasia (ADH), atypical lobular hyperplasia (ALH), fibroadenoma with complex features, moderate or florid hyperplasia and solitary papillomas without coexistent hyperplasia.

Genetic and family history risk factors:
Inherited mutations in breast cancer susceptibility genes are associated with a very high risk of the occurrence of breast cancer. The breast cancer susceptibility genes identified to date include:

• BRCA1/BRCA2, associated with the diagnoses of hereditary breast-ovarian cancer and hereditary site-specific breast cancer.
• PTEN, associated with the diagnosis of Cowden syndrome.
• STK11, associated with the diagnosis of Peutz-Jeghers syndrome
• MLH1/MSH2/MSH6, associated with hereditary non-polyposis, colorectal carcinoma and breast cancer in certain families.
• ATM, associated with a 4-fold increase in risk among heterozygotes.
• CHK2, associated with a 2-fold increase in risk among heterozygotes.
• TP53, 50% risk of breast cancer by age 50.

A family history of breast cancer significantly increases the risk of breast cancer for the individual if the cancer occurs in first- and/or second-degree biological relative(s) – parents, siblings, children, grandparents, aunts, uncles, nieces and nephews. Red flags suggestive of genetic susceptibility to breast cancer include:

• One or more first- or second-degree relatives with breast cancer at an early age (less than 40-50 years of age).
• Breast cancer and a second primary cancer in a close relative, especially ovarian cancer. (Other cancers that may be associated with an increased genetic risk include: thyroid, colorectal, prostate, endometrial, pancreatic, adrenocortical carcinoma, melanoma, childhood sarcoma, leukemia/lymphoma, and brain tumors.)
• Male breast cancer in a close relative.
• Two or more relatives with breast cancer at any age.
• If of Ashkenazi Jewish descent, a biological relative with breast cancer diagnosed before age 50 or ovarian cancer at any age.

Personal risk factors:

• Gender is the most obvious and important risk factor for breast cancer. Females have a 100-fold increase in risk as compared to males. However, the ACS estimates that in 2005 there will be 1,690 new cases of invasive breast cancer diagnosed among men in the United States. (Male breast cancer is a red flag for a possible genetic susceptibility.)
• Age – breast cancer risk increases with age; 96% of breast cancers occur in women age 40 and older (ACS, 2003-2004). Most women face a lifetime risk of 12-13%.
• Race – Caucasian women have a greater risk of breast cancer than other racial groups.
• Prolonged exposure to endogenous estrogen and progestins (U.S. Preventive Services Task Force, 2005).
• Exposure to exogenous combined estrogen and progestin therapy in hormone replacement therapy for postmenopausal women has been shown to slightly increase the risk for breast cancer. It is controversial whether or not exogenous estrogen alone in estrogen replacement therapy for postmenopausal women affects the risk for breast cancer. ( U.S. Preventive Services Task Force, 2005.)
• Alcohol use – greater than 27 drinks per week. (Gronbaek, 2004.)
• Obesity – obese women with BMI >30 had estrogen concentrations between 60% and 219% higher then thin women and the risk of Brest cancer increased as BMI increased at an average rate of about 18% per 5-point increase in BMI. (Journal of National Cancer Institute, 2003.)
• Radiation exposure to the upper torso (e.g. treatment of Hodgkin’s lymphoma). ( Preston, 2002.)

The table below reveals changes in breast cancer risk across a woman's lifetime.

* Among those free of cancer at the beginning of the age interval. Based on breast cancer cases diagnosed 1988-2000. Percentages and "1 in" numbers may not be numerically equivalent due to rounding.
** Probability derived using NCE DEVCAN software.

Flowchart Notes and Footers

NOTE 1A: After ruling out the presence of Personal Risk Factors and Family History Risk Factors listed in Algorithm #1, assessment of Age and Other Risk Factors will identify most women at increased risk for breast cancer, but may over-estimate risk for some women. For a more accurate risk-estimate, calculate breast cancer risk using the National Cancer Institute (NCI) Risk Assessment Tool (Gail Model) instead of using the Algorithm’s Age and Other Risk Factors criteria. A five-year risk of >1.7 % should be considered Increased Risk. NCI's online risk assessment tool is available at http://bcra.nci.nih.gov/brc/

NOTE 1B: A Caucasian woman aged 65 with average risk factors has a 2% risk of developing breast cancer within the next 5 years according to the Gail Model . Therefore, women 65yrs or older should have their personal risk evaluated on an individual basis using the Gail Model if possible. Women with a 5-year risk of >1.7% meet FDA criteria for receipt of approved chemoprevention (e.g., Tamoxifen). However, the potential benefit of treatment must be weighed against the associated risk of serious side effects for the individual woman.

*Further Follow-up could include consideration and/or implementation of the following as appropriate: life style counseling; increased surveillance; referral to a breast specialist; genetic risk assessment; chemoprevention (e.g. tamoxifen); prophylactic surgery

**Associated cancers: ovarian; thyroid; colorectal; prostate; endometrial; pancreatic; adrenocortical; melanoma; childhood sarcoma; leukemia/lymphoma; brain tumor

References

Metcalfe, K., Lynch, H. T., Ghadirian, P., Tung, N., Olivotto, I., Warner, E., et al. (2004). Contralateral breast cancer in BRCA1 and BRCA2 mutation carriers. Journal of Clinical Oncology, 22(12), 2328-2335.

Preston , D.L., Mattsson, A., Holmberg, E., Shore, R., Hildreth, N. G., Boice, J. D., Jr. (2002). Radiation effects on breast cancer risk: a pooled analysis of eight cohorts. Radiation Research, 158(2), 220-235.

U.S. Preventive Services Task Force (2005). Hormone therapy for the prevention of chronic conditions in postmenopausal women: recommendations from the U.S. Preventive Services Task Force. Annals of Internal Medicine, 142(10), 855-860.

Yen, M. F., Tabar, L., Vitak, B., Smith, R. A., Chen, H. H., Duffy, S. W. (2003). Quantifying the potential problem of over diagnosis of ductal carcinoma in situ in breast cancer screening. European Journal of Cancer, 39(12), 1746-1754.

Updated: May, 2008.

Top of page