Breast Cancer Risk Assessment

Having one gynecologic cancer does not increase your risk of having other types of gynecologic cancer. However, women with a hereditary cancer syndrome are at increased risk of developing a gynecologic cancer. These syndromes include Hereditary Breast and Ovarian Cancer (HBOC) caused by a BRCA mutation as well as Lynch syndrome, also called hereditary nonpolyposis colorectal cancer (HNPCC). Women with HBOC syndrome have markedly elevated risks of breast cancer and ovarian cancer, with a lifetime risk of breast cancer of 50 to 85 percent and a 15 to 40 percent chance of developing ovarian cancer. There is also an increased risk of a second breast cancer diagnosis.

Lynch syndrome is associated with cancer diagnosis at an early age and the development of multiple cancer types, particularly colon and endometrial cancer. Until recently, the majority of attention and research related to Lynch syndrome has focused on colorectal cancer. However, women with Lynch syndrome have a 27 to 71% risk of endometrial cancer, which equals or exceeds their risk of colorectal cancer. This is significantly higher than the 3% risk of endometrial cancer in the general population. In addition, women with Lynch syndrome have a 8-11% risk of ovarian cancer, compared with 1.5% in the general population. The management of endometrial and ovarian cancer risks in women with HBOC or Lynch syndrome includes surveillance, chemoprevention and risk-reducing surgery.

The role of hormonal therapy for risk reduction should be carefully considered and discussed with experts in breast cancer risk assessment and management in a shared decision-making environment. Guidelines from expert groups recommend that the risks and benefits of breast cancer prevention be discussed with premenopausal and postmenopausal women who are at high risk for the disease.

Women at high risk may include some women over the age of 60; women with certain high-risk conditions found on breast biopsy, such as lobular carcinoma in situ (LCIS) or atypical ductal or lobular hyperplasia; women between the ages of 35 and 59 years who have a calculated five-year risk of developing breast cancer of 1.7 percent or higher, according to a system called the Gail model. The Gail model uses a woman's current age, age at first menstrual period, age at first live birth, the number of first-degree relatives with breast cancer, and the number and pathologic findings of any breast biopsies to estimate the probability of breast cancer over time. This model, and others, is used by health professionals to calculate an individual’s risk and the results should be interpreted with an expert in breast cancer risk assessment. It is also important to remember that the presence of breast cancer risk factors does not mean that cancer is inevitable as many women with risk factors never develop breast cancer.

Another very important issue is that the Gail model does not consider the risk of cancer associated with inherited breast cancer-predisposing genes such as BRCA1 and BRCA2. If an individual has a strong family history that suggests the possibility of an inherited predisposition to breast cancer, then that individual should be referred for genetic counseling. Other components of a risk/benefit assessment and counseling include a careful discussion of the side effects of hormonal therapy, options for participation in clinical research and healthy lifestyle changes.

Americans get risk screening all the time but we generally don't think of these tests in those terms. Assessment of cholesterol levels in the blood and blood pressure are risk assessments for heart disease and stroke. These are offered to essentially everyone and help to direct additional testing (advanced cardiac/vascular examinations) and treatment (cholesterol and blood pressure lowering medicines). There is no downside to risk assessment in all women and can help direct advanced breast imaging and closer follow ups as well as alleviating fear in some women who overestimate their risk of developing breast cancer. The risk assessment requires no blood draws and can be done in less than 5 minutes by a trained medical assistant.

Tyrer-Cusick breast cancer risk assessment was developed in the UK by PhD's and is the most comprehensive risk assessment tool currently available. The model takes into account the person's history (age, extended family history of breast and ovarian cancer, child birth history, history of breast biopsy and it's pathology, age of menarche and menopause, exposure to post menopausal hormones, Ashkenazi Jewish heritage) as well as their height/weight (higher BMI-body mass index=increased risk). After taking all the various factors into consideration a curve is generated representing the person's lifetime risk compared to 'standard risk' and also the chance of having both a BRCA 1 and BRCA 2 genetic mutation.

The Gail model was developed in the 1980's by a US physician and combines some history (first generation relatives with breast cancer, age of menarche and menopause, number of breast biopsies, atypia in a biopsy) and age to calculate 5 year and lifetime risks of developing breast cancer. A Gail Model risk of 1.7% at 5 years was used as entry criteria for both of the NSABP breast cancer prevention trials.

The Mammaprint test, developed by Agendia (http://www.agendia.com/pages/mammaprint/21.php), is used to predict whether early breast cancer is likely to spread (metastasize) to other parts of the body. This is accomplished by looking (at the molecular level) at the activity of 70 different genes known to be involved in the progression of cancer. The results group the cancers into 'low' or 'high' risk for spread of cancer and can be used to guide treatment decisions. The test was initially approved in 2007 (http://www.fda.gov/ForConsumers/ConsumerUpdates/ucm048477.htm).

The development of accurate molecular tests for drug sensitivity and prediction of disease progression is critical. These tests have the potential to spare patients treatments that are unlikely to work for their cancer and let them begin more effective treatments immediately. Essentially, the tests allow clinicians to treat each cancer case individually. These types of test will (and already have had) have a great impact on cancer survival and quality of life for patients.

The HALO test is meant to be used as a risk assessment tool, not a cancer detection test - it primarily meant for women under the age of about 40 (in whom routine mammography is not performed). The idea is that if there are abnormal cells lining the milk ducts, they may be detected in the fluid obtained from the test. If there are abnormal cells, that generally signifies an increased risk of developing cancer, and additional testing (perhaps MRI) may be indicated.

When properly performed, as many as 50% of women will not produce fluid with the HALO test, and in young women, this is considered a "negative" result (no abnormality). However with the normal aging process, there can be atrophy of the milk ducts, so that in women over the age of 40-50, no fluid might be due to changes related to age, and not necessarily a negative result. In addition, the HALO test will probably not pick up abnormal cells even if a cancer is present if the tumor is in the outer aspects of the breast. Lobular cancer (as it is not growing initially in the milk ducts) also will not likely be picked up with the HALO test.

The HALO test is not for everyone and again it is important to stress that this test is not meant to be a screening test for breast cancer, and is not a substitute for clinical and self-examination as well as routine imaging such as mammogram (and ultrasound / MRI if indicated). However when used appropriately it can be helpful to provide some counseling to young women regarding their risk.