What Does it Mean to be High Risk for Breast Cancer?

Each year, more than a quarter million women will be diagnosed with breast cancer, making it the second most common type of cancer in women behind only skin cancer. In fact, breast cancer diagnoses annually account for about 30 percent of new female cancers, according to the American Cancer Society.

Based on gender alone, women have a one in eight (13 percent) chance of developing breast cancer during their life. Due to various controllable factors, such as weight, activity level, diet, alcohol consumption and lack of screening, mammograms these percentages increase.

In certain cases, some women are categorized as being at high risk of developing breast cancer due to uncontrollable risk factors. To learn more about what high risk breast cancer means, we sought out information from Nicole Sharp Cottrell, M.D., a board-certified and fellowship-trained breast surgical oncologist at INTEGRIS Breast Surgery.

High risk breast cancer

Genetics and family history are the two main factors that place a woman in the high risk breast cancer category. These women have at least a 20 percent chance of developing breast cancer compared to 13 percent of all other women in the average risk category.

In addition to these factors, Dr. Sharp also noted how gender and age can increase your risk of breast cancer. There are additional factors that can also increase your risk of breast cancer, such as obesity, exposure to hormones and activity level. 

Genetics

Certain genetic mutations can increase your breast cancer risk by more than 80 percent.

Everyone has BRCA1 and BRCA2 genes that help with cellular repair and inhibit tumor growth. In some people, BRCA 1/2 genes, which encode tumor suppression proteins,  have mutations resulting in increased risk of cancer.  Only about 5-10% of breast cancers are from a known genetic mutation, with BRCA1/2 mutations being the most common mutation associated with breast and ovarian cancer syndromes. In addition, men with BRCA mutations are at increased risk for prostate cancer. Additional risks include pancreatic cancer, melanoma and potentially serious uterine cancers. 

While BRCA genes are the most common genetic risk factor for breast cancer, other genes can also lead to a diagnosis. These genes currently include:

• ATM
• BARD1
• CDH1
• CHEK2
• NF1
• PALB2
• PTEN
• RAD51C
• RAD51D
• STK11
• TP53

“It’s important to know the gene mutations you are being tested for, because there may be limited genetics testing done for just BRCA1/2 versus a broader genetics panel testing done,” Dr. Sharp says. “Genetics research is continuously evolving to identify additional mutations and their associated cancers. People with a known family history of a gene mutation or those with family histories suspicious of mutations, should seek evaluation for genetic testing for themselves.”

Family history

As with other types of cancers, your risk of developing breast cancer increases if an immediate family member, also called first-degree relative (mother, sister or daughter), previously had breast cancer. The risk is even higher if multiple family members had breast cancer, especially those who develop cancerous cells before menopause or if both breasts were affected.

Although family history is a strong indicator of potential future breast cancer, it is by no means a guarantee you’ll end up having breast cancer. For example, nearly 90 percent of breast cancer cases have no family history.

Additional factors

Aside from genetics and family history, the following factors may also put you at high risk:

Previous breast cancer diagnosis: Women who had a previous bout with breast cancer are three to four times more likely to have a recurrent diagnosis. This includes ductal carcinoma in situ (DCIS), which is a type of cancer that affects the milk ducts but has not spread outside of the ducts. DCIS is a stage 0 breast cancer.

History of breast lesions: Women can develop a condition called lobular carcinoma in situ (LCIS), which describes abnormal tissue growth in the lobules (the sacs responsible for producing breast milk). Although LCIS isn’t breast cancer, women with these lesions are seven to 11 times more likely to develop breast cancer.

Radiation exposure: Radiation therapy can treat many conditions, from cancer to tuberculosis. Women who are exposed to certain types of radiation are at a higher risk of developing breast cancer. Younger women with a history of radiation exposure are more at risk than older women.

Breast cancer risk assessment tool

For some women, a family or personal history of having breast cancer makes it easy to determine future risk. For others, it isn’t as obvious. 

To help estimate risk, there are several tools you can use to determine the likelihood of developing breast cancer in the future.

Gail model

The most common breast cancer risk assessment tool uses the Gail Model, a statistical analysis model created in 1989 by Mitchell Gail, MD, pHd. The Gail Model calculates the likelihood of developing breast cancer within the next five years.

The tool uses the following factors to determine risk:

• Age
• Age of first menstrual cycle
• Age of first child birth 
• Family members (mother, sisters, daughters) with breast cancer
• Number of previous breast biopsies (whether positive or negative)
• Number of previous breast biopsies
• Race/ethnicity

Once calculated, women are considered high risk if their five-year risk is greater than 1.67 percent. It’s important to note the model is made for women who have no history of breast cancer, LCIS or known genetic mutation.

International Breast Cancer Intervention Study (IBIS)

This calculator uses the Tyrer-Cuzick model to project the risk of breast cancer within the next 10 years.

The tool uses the following factors to determine risk: 

• Age
• Age of first menstrual cycle
• BRCA gene mutation
• Childbirth history
• Family history
• Height
• History of breast biopsies
• Specific pathology of breast biopsies (e.g atypia and LCIS)
• History of ovarian cancer
• Menopausal status
• Use of hormonal therapy
• Weight
• Breast density
• Ashkenazi inheritance

The results fall under one of three categories: average risk (less than 15 percent), immediate risk (15 to 19 percent) and high risk (more than 20 percent).

Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm (BOADICEA)

The BOADICEA model, which was developed in 2002, is used primarily to assess future breast cancer risk in women who have a genetic mutation. While BRCA1 and BRCA2 are the most common mutations, the tool can also predict other genes such as PALB2, ATM, CHEK2, BARD1, RAD51C and RAD51D.

The tool uses the following factors to determine risk: 

• Family history
• Gene variants
• Hormonal factors
• Lifestyle factors
• Mammographic density
• Polygenic risk scores

What to do if you’re at a high risk for breast cancer

People identified as being high-risk for breast cancer, typically defined as a greater than 20 percent lifetime risk of breast cancer, should be offered counseling on risk-reducing options and offered high-risk breast cancer screening, Dr. Sharp says. While this may be done through a primary care provider or gynecologist, INTEGRIS offers high-risk breast counseling and surveillance through our INTEGRIS Breast Surgery Clinic. 

“Breast self-awareness is encouraged, including monthly self-exams,” Dr. Sharp says. “Any concerns should prompt a patient to reach out to their provider immediately even if they aren’t due for an exam or imaging for clinical evaluation.”

Depending on your specific risk factors, your doctor may recommend the following:

• Genetic counseling and testing
• Medications to lower estrogen levels
• Lifestyle changes
• Preventive (‘prophylactic’) surgery
• High risk breast cancer screening

As Dr. Sharp points out, there is no such thing as “preventative” treatment.

“Instead, we discuss options for risk-reduction treatment as there is always the chance that breast cancer can occur or even recur,” she says. “In addition to high-risk surveillance, we offer patients options for risk-reduction for breast cancer through lifestyle changes, medications, and consideration of surgery.”

Genetic counseling and testing

For women who have a family history of breast cancer or are at a high risk based on results from the assessment tool, your doctor may recommend meeting with a genetic counselor or a geneticist to determine if you have a mutation to the BRCA gene or another genetic mutation.

Genetic testing for breast cancer is done by analyzing saliva or blood samples for any genetic mutations. In general, you will either test positive or negative for a genetic mutation, although you may have a gene change that isn’t covered by the genetic test. In some cases, you may receive an inconclusive test or the test may discover a gene variant of uncertain significance, also known medically as a VUS. A VUS means there is a change in your genetic makeup, but it’s unclear what effect it will have.

Medicines to lower breast cancer risk

Two medications, tamoxifen and raloxifene, can help lower breast cancer risk by blocking estrogen in breast tissue. Raloxifene is typically only used for older women who have experienced menopause. Studies have shown raloxifene can lower your risk of future breast cancer by nearly 50 percent. 

There are also drugs called aromatase inhibitors to reduce the risk of breast cancer. These drugs, sold as generic anastrozole or exemestane don’t stop estrogen production, rather they lower levels by inhibiting the production of aromatase, an enzyme found in fat tissue. As a result, aromatase can’t change other hormones, such as androgen, into estrogen.

“While these medications are sometimes called ‘chemoprevention,’ they are not considered chemotherapy and do not have traditional chemotherapy-associated side effects,” Dr. Sharp says. “The patient’s menopausal status and the side effect profile of each drug impact recommendations for which drug is best for specific patients. These medications are a single oral pill that are taken for 5 years for risk-reduction.”

“In those patients with dense breasts, we often have improved breast exams and breast imaging studies while they take risk-reducing medications, as the density of the breasts is often decreased. There can be significant side effects associated with these medications, so they are only prescribed to patients at substantial increased risk of breast cancer where the benefits outweigh the risks.”

Preventive (prophylactic) surgery

Some women may be interested in risk-reducing surgery with removal of both breasts (bilateral mastectomy). Dr. Sharp says there is evidence to support this in patients at the very highest risk of breast cancer, like those with BRCA 1/2 mutations. However, for most patients, there is no improvement in overall survival after bilateral mastectomy.

“Bilateral mastectomy is considered risk-reducing and not risk-eliminating, as breast cancer can still reoccur on the chest wall, in the lymph nodes or distantly,” she notes.

“Patients may be interested in breast reconstruction. Breast reconstruction may be considered in a delayed fashion at a later operation or in an immediate fashion at the time of their mastectomy, if they are an appropriate candidate after meeting with a plastics and reconstruction team.”

It’s important to note that even after bilateral mastectomy, ongoing screening with clinical exams is recommended but surveillance breast imaging is no longer indicated. If women are at increased risk of breast and ovarian cancer syndromes, like BRCA 1/2, then a referral to gynecology for surveillance and discussion of risk-reduction with bilateral salpingo-oophorectomy is recommended. 

High risk breast cancer screening

Because medications and surgery come with side effects, a less invasive option includes an annual mammograms consideration of the addition of supplemental breast screening with breast MRI.

Women who fall in the high-risk category should receive a comprehensive clinical breast exam, including both breasts and lymph node basins, every six to 12 months, according to Dr. Sharp. The exact age of when to begin screenings may be determined by the presence of a gene mutation or considered as early as 10 years before the earliest affected family member. For instance, patients with a known high-risk BRCA 1/2 mutation typically begin annual MRI as early as age 25, followed by alternating mammogram with tomosynthesis and MRI every 6 months at age 30. 

“Annual mammograms should be performed with tomosynthesis (3D mammography),” she says. “Patients should also be offered options for supplemental breast screening imaging like breast MRIs annually. We typically space out our annual mammograms and MRIs so that you receive an imaging study every six months.”

Breast cancer screening doesn’t prevent breast cancer, but it allows doctors to find and treat the cancer at an early stage – earlier treatment leads to more effective results.

To schedule your mammogram, call 1-855-MY-MAMMO (1-855-696-2666) or talk with your doctor about how often you should receive a mammogram.

When should someone see a genetic counselor for breast cancer?

Dr. Sharp encourages cancer genetic testing in patients with a family history suspicious for breast and ovarian cancer syndromes. Any patients with a family history of ovarian cancer should be considered for genetic testing. Patients with multiple generations of breast cancer, early onset breast cancer or triple negative breast cancer should also be considered for genetic testing. Additionally, patients with family history of pancreatic cancer or metastatic or advanced stage prostate cancer are also often offered genetic testing.  

“The American Society of Breast Surgeons (ASBrS) recommends consideration of genetics testing in all breast cancer patients,” she says. “We work with insurance to obtain coverage whenever possible. If genetics testing is desired and not covered by insurance, we do have options for significantly discounted testing.”

For women who are at a high risk for breast cancer, INTEGRIS Breast Health Services has a High Risk and Genetics Clinic to determine the best course of treatment to reduce your risk of developing breast cancer in the future.