Cancer Screening and Genetic Services May Help Women Make Critical Decisions Based on Their Lifetime Risk for Breast Cancer
Some women live with a very palpable fear, often because a family member, maybe a mother or older sister, experienced breast cancer and succumbed to it. With the hopes of preventing breast cancer, these women are making extremely difficult and often emotionally charged decisions, such as undergoing bilateral prophylactic mastectomy. Studies have shown that this procedure reduces “the risk of breast cancer by at least 95% in women who have a deleterious (disease-causing) mutation in the BRCA1 gene or the BRCA2 gene and by up to 90% in women who have a strong family history of breast cancer.”1
In addition, women diagnosed with early-stage breast cancer are also electing to undergo bilateral mastectomy at alarming rates. Between 2002 and 2012, the proportion of young women (aged 20-44 years) across the United States who opted for contralateral mastectomy rose from about 11% to about 33%; over the same time frame the proportion of women aged 45 years and older who had both breasts removed rose from about 4% to about 10%. In addition, there are striking differences in rates of bilateral mastectomies by state.2
As with any invasive procedure, bilateral mastectomy can lead to a difficult road to recovery; complications can result, along with lifelong body image issues.
Sometimes, patients make these decisions based on fear because of their family history, having cared for or watched a loved one die of complications from cancer, without that family member having undergone genetic testing—thus not having genetic information to serve as a guide. One area that may help to offer more information to these patients and clinicians is risk assessment and/or genetic testing for hereditary cancer syndromes. The ability to identify deleterious mutations in the BRCA1 and BRCA2 genes relevant to hereditary breast and ovarian cancer syndrome has been available to providers since 1996. With time and dedicated clinical and laboratory research, the hunt for other cancer-related genes was on a fast track. By 2013, genetic testing included not only BRCA1 and BRCA2 but expanded to panels, including several to many cancer-related genes, and at decreasing cost and time to complete the sequencing.
Learning whether someone carries a deleterious or pathogenic mutation on a cancer-related gene may be a heavy burden for some patients and their families. This topic has always led to complex discussions. Increasing access to this powerful information can assist in the prevention of cancer. Individuals who fit into this predisposition category are now called “previvors.” These previvors can opt for increased screening and/or prophylactic surgeries. They can also explore the option of preimplantation genetic determination so as not to pass a mutation on to their offspring. This information can also bring relief to a family member who is negative for a known mutation in the family, which places their risk closer to that of the general population.
Family nurse practitioner Michelle Weaver Knowles’s path to becoming an advocate of genetic testing is one that begins as many powerful stories do—through personal experience. Michelle’s sister, Sherri, was diagnosed with breast cancer at age 30 years. Sherri had just finished breastfeeding her youngest son, and she felt a lump in one of her breasts. Sherri underwent treatment for 3 long years and passed away in 1994 at 33 years of age, leaving behind a husband and 3 young boys.
Four years later at age 38, Michelle was diagnosed with triple-negative breast cancer. She had 2 young girls, aged 10 and 14 years. She had heard of BRCA1 and BRCA2 testing and asked her OB/GYN about this test, motivated by her young daughters. Her family’s experience with breast cancer sparked her interest in becoming a nurse navigator focusing on breast cancer patients, patients at high risk, and those with hereditary cancer syndromes.
Michelle has more than 34 years of nursing experience. While filling the role of a nurse navigator at Community Medical Center in Missoula, MT, she developed a high-risk breast program using the National Comprehensive Cancer Network (NCCN) guidelines for identifying and testing patients.3 Patient risk information was collected when a patient checked in at the breast imaging center for a mammogram or other imaging. If the patient was “red flagged” or met NCCN criteria for genetic counseling, they received follow-up communication and were invited to undergo a cancer risk consultation with Michelle and her collaborating providers. Informed by the Tyrer-Cuzick computerized risk assessment model,4 women who did not meet criteria for testing or who tested negative for a hereditary cancer syndrome were still managed using high-risk guidelines. Michelle coordinated access to testing, follow-up, and resources in collaboration with the patient’s primary care physician or oncology care team. She realized she could do more for patients and families with an advanced degree and earned a master of science in nursing as a family nurse practitioner, graduating from Gonzaga University, Spokane, WA, in May 2018. She will be opening a private practice, Ava Health, LLC, in October 2018, focusing on these high-risk patients.
Michelle is a believer in essential elements of informed consent for her patients and their families.
She spoke with AONN+ about her cancer experience, considerations for patients undergoing genetic testing, and her approach to patient education on the topic.
AONN+ Can you tell us about your experience when you were diagnosed with breast cancer?
Weaver Knowles I was 38 years old, and I was having some breast pain. I had my OB/GYN do a breast exam, but neither of us could really feel anything. It had only been 9 or 10 months since my last mammogram; I had already been getting mammograms because of my sister. I watched and waited. The pain came back with a vengeance. They thought I had a breast abscess. The surgeon took me to surgery the next day, thinking he was going to be draining an abscess, but it turned out to be poorly differentiated triple-negative breast cancer.
I had to go back to surgery the next week for a lymph node dissection. I met with the surgeon, oncologist, and radiation oncologist. I had heard of BRCA testing. It was discovered back in 1994—the year my sister died. I had asked my OB/GYN to do the test on me. It came back with a variant of uncertain significance, most likely deleterious—basically positive. Subsequently, it was reclassified as positive. I was terrified. My sister had died. My 10-year-old was asking me, “Mom, are you going to die like Aunt Sherri did?”
And then I considered getting a bilateral mastectomy. My providers recommended doing a lumpectomy, chemo, and radiation.
The whole point of genetic testing is obtaining more information. I advocate for my patients, because it provides them with a more informed consent about what their choices are—this is shared decision-making. In my experience, I had a higher probability of having breast cancer again in my lifetime. My life would be different if I had made different decisions back then. The decisions patients make at the beginning of their treatment affect them for the rest of their life. This is why I’m passionate about my patients understanding what their choices are and helping them weigh the pros and cons.
In breast cancer, it’s also hard because some women come in to see us not knowing what to do. They want us to tell them what to do. Often, they have had personal experiences with cancer, or maybe they have had numerous breast biopsies, and it has been torment coming in for mammograms and biopsy after biopsy. You have to think about that as a provider helping patients make decisions. For example, is it a controversial thing to do bilateral mastectomy on a patient who has a hereditary cancer syndrome or has had numerous biopsies and lives with the fear of being diagnosed with breast cancer as well as the expense of frequent mammography, MRI, and provider visits? You also have to think about the emotional impact. How is this going to affect this woman and her family for the rest of her life?
About 3 years after my chemo, radiation, and lumpectomy, I was concerned about my daughters, so I called the genetics lab for my kids. And they were really great about providing information to educate me on my daughters’ risk. I realized when doing research for my kids that my own risk of having a second primary breast cancer was 64%, so I went back to my medical oncologist, and I said, “I think I want to have a bilateral mastectomy, because I don’t want to go through this again.” He wanted to do an MRI, and it showed a suspicious area. I said, “Let’s do the mastectomies.” Thankfully, I had already had my ovaries removed.
AONN+ Has anyone in your family had genetic testing, and what were their results?
Weaver Knowles I inherited the mutation from my mom. She has not had cancer and is a previvor. We can only speculate that Sherri was positive. The reason is that she had a couple of those red flags; she was diagnosed before the age of 50 years, and she was estrogen and progesterone negative. Back then, they did not have HER2 testing. I was triple negative, so regardless of family history, if you take my sister out of the picture, I was the perfect person who met the guidelines. I had a really aggressive cancer, which was triple negative, before the age of 50 years.
Both my daughters were tested, and they are both negative. When we do genetic testing, we like to test the person who has been affected. This is the one who is most likely to have a mutation and is most informative. So, if we test additional family members and they don’t have the known mutation, they are a true negative, and their risk goes back to that of the general population or risk based on factors other than genetic predisposition.
My younger brother is positive, and he has not had cancer. My mother is positive, in her mid-70s, and has never had cancer. My younger sister, Bridget, is a true negative like my daughters. Think of the empowerment for her; she has had 2 sisters with breast cancer, so she must have been terrified. It wasn’t until 10 years later that she got tested. That result put her back at general screening guidelines, and none of her children have to worry about having inherited that mutation from their mom.
AONN+ You made a distinction between negative and true negative. Can you explain that?
Weaver Knowles A true negative person is a person who tested negative for a known family mutation. I’m positive and my daughters are true negative, because they were tested for the known mutation in the family and do not have it. You inherit 1 copy from each parent. Both my daughters inherited a good, not mutated, copy of my BRCA1 gene, located on chromosome 17. My sister Bridget is another true negative because she inherited my mom’s good copy.
If someone like Bridget showed up at her OB/GYN and they noticed that she had 2 sisters with breast cancer in their 30s, a savvy provider would recognize she is at risk and needed to be tested. If they test her, and the test comes back negative but no one else in the family has been tested, we don’t know if she is a true negative or just negative. If she had been tested first, one might think there must not be a mutation in the family. But, she is an unaffected person. That’s why I was the better person to initially test as a family member who has the highest risk (ie, the proband), with a diagnosis of cancer. If you think about it like a misspelled word, I got my mom’s misspelled word and my sister got her correctly spelled word. Until we find the misspelled word, we cannot call that person a true negative, but we can call them negative. My sister could still get a sporadic breast cancer, but her lifetime risk is approximately 8% (that of the general population) versus up to 87% if BRCA1 positive.
AONN+ When you assess a patient’s risk, what is one of the most difficult concepts you discuss with a patient and their family?
Weaver Knowles Oftentimes, we test patients, and we don’t find anything deleterious, or a mutation that can significantly increase cancer risk. I had a patient last week whose maternal grandmother, mom, and maternal aunt all had breast cancer. They all had hereditary cancer panel testing and were all negative for known mutations. My patient is now diagnosed with breast cancer. There were no cancers on her paternal side, and her hereditary cancer panel was also negative. Just because genetic testing is negative doesn’t mean the individual can’t still be at high risk. This is where nurse navigators can really be helpful. Running the Tyrer-Cuzick risk prediction model would have red-flagged this patient, and she would have been getting additional imaging that might have detected her cancer earlier, or she could have been offered prophylactic surgery or other risk-reduction modalities. This patient’s genetic testing might be negative, but she would have been at risk because she has so many relatives and generations of family members on her maternal side already with the disease. Maybe there is a genetic impact on a mutation that is not yet well understood? Maybe there are lifestyle or environmental factors at play? Nurse navigators need to be looking out for many patients to prevent cancers and make more previvors. Genetic testing companies have begun running the Tyrer-Cuzick risk prediction model on patients who test negative and incorporating what we call SNPs [single nucleotide polymorphisms, or variations in an individual’s makeup] in genetics to generate a score predicting a patient’s risk.
AONN+ Who are the types of families you believe should consider genetic testing?
Weaver Knowles Mary-Claire King, the pioneer researcher who discovered the BRCA1 gene, believes everyone should be tested regardless of family history. The statistics are that 1 in 400 people will get a hereditary cancer—unless you are Ashkenazi Jewish; they are 1 in 40.
It is surprising to me that people don’t know their family history, so I encourage them to call family members. Many families now are blended or may have few siblings in a generation, so the family structure has really changed over the past few decades. We need to know if a patient meets the criteria for testing, because if not, medical insurance may not cover it. I look at the person sitting in front of me and ask, does he or she have any red flags, like triple-negative breast cancer? In genetics, we do a 3-generation pedigree. There are many other cancers that can be hereditary (Lynch syndrome, Li-Fraumeni syndrome, etc). Endoscopy centers would also be great places for nurse navigators to screen patients for hereditary cancers. Basically, I feel if a patient is young, the cancer is an aggressive or specific subtype, the patient has had more than 1 type of cancer, and multiple generations on one side of the family have cancer, it should raise some red flags. It is our duty to our patients to identify them and get them to a genetics professional for risk assessment and informed consent. Currently, chemotherapy and treatments are being recommended based on hereditary cancer mutations.
AONN+ What is the process for getting a genetic test?
Weaver Knowles There are different ways. A person can just go to his/her primary care provider or OB/GYN and request a test. There are great providers out there who do informed consent, but when a test result comes back, they don’t always know what to do with it, and that can pose a problem.
I think it is great that breast centers are recognizing high-risk people who are coming into the clinics, and they can get referred to a genetics team.
In some areas, it can take 3 to 6 months to get an appointment with a genetic counselor. I think it is important for nurses, genetic counselors, and providers to be working together with patients, because there are chemo drugs coming out for people who have hereditary mutations. There are genetics courses offered at Cincinnati Children’s Hospital, City of Hope, and Stanford.
Cancer care teams can play an integral role in identification and testing of patients based on age, specific subtypes of breast cancer (like triple-negative breast cancer <60 or hormone receptor–positive/HER2-negative metastatic breast cancer); family history of breast, ovarian, melanoma, prostate, or pancreatic cancer; and other factors associated with NCCN and other professional organizations’ guidelines.
AONN+ Is there an ideal person who should be delivering the results?
Weaver Knowles I think it should be a provider who knows and understands the topic and can present unbiased, evidence-based information so the patient and provider can engage in shared decision-making. A provider should also know what resources are available for the patient. Just as with anything in medicine, having colleagues to refer those difficult cases to is a bonus.
AONN+ How do you have conversations with families who are candidates for genetic testing?
Weaver Knowles I started a high-risk screening program in Montana. Women would get asked questions when they came in for their breast imaging, including questions like, “Are you Ashkenazi Jewish or do you have any unusual cancers in your family, like male breast cancer? Have you had breast cancer, and if yes, at what age were you diagnosed?” Sometimes we touch patients who had breast cancer more than 10 years ago. They never had genetic testing, but they got cancer when they were in their 40s. Genetic testing is an ongoing survivorship need, and we don’t want to miss the opportunity to test patients, regardless of where they are in their cancer journey.
Personal and family risk factors would be collected by me and a nurse colleague, who would follow up with “red-flag” patients and let them know they met the criteria for our high-risk breast cancer screening program and were invited to come in for a consultation. Patients were scheduled for a session that would include genetics education, discussion of risk factors, and whether they met eligibility criteria for genetic testing. If they didn’t meet criteria, then we would run the Tyrer-Cuzick risk assessment model on them. If the Tyrer-Cuzick was 20% or higher, they were scheduled with a breast surgeon for a breast exam. The breast surgeon would determine their screening schedule, which is generally yearly breast MRI and mammogram.
AONN+ What advice would you give to other families about genetic testing and the value it offers?
Weaver Knowles Many of these families have had multiple loved ones pass away because of cancer or its complications. This is a disease of the family, and most have questions. Having access to genetic testing, whether it is for cancer, cardiac disease, or any hereditary condition, provides information that can empower patients and their families with the tools to understand their risk, make choices to prevent cancer (previvors), or now, make treatment choices based on specific genetic mutations.
1. National Cancer Institute. Surgery to reduce the risk of cancer. www.cancer.gov/types/breast/risk-reducing-surgery-fact-sheet#q3. Accessed August 14, 2018.
2. Nash R, Goodman M, Lin CC, et al. State variation in the receipt of a contralateral prophylactic mastectomy among women who received a diagnosis of invasive unilateral early-stage breast cancer in the United States, 2004-2012. JAMA Surg. 2017;152:648-657.
3. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines). Genetic/Familial High-Risk Assessment: Breast and Ovarian. www.nccn.org/professionals/physician_gls/default.aspx#detection.
4. Himes DO, Root AE, Gammon A, Luthy KE. Breast cancer risk assessment: calculating lifetime risk using the Tyrer-Cuzick model. J Nurse Practitioners. 2016;12:581-592.