As one of the most significant predictors of hereditary breast and ovarian cancer, the BRCA1/2 genes have become the poster child for genetic testing. In the past 18 months, the floodgates for testing options have opened, as companies seek to enter the diagnostic market in the wake of the US Supreme Court’s June 2013 ruling that “naturally occurring” human genes are a “product of nature” and cannot be patented, breaking Myriad Genetics’ monopoly on BRCA1/2 gene testing.

Yet even as BRCA1/2 testing becomes more widely available in oncology practice, fresh questions about interpreting the results of these assays and a debate about which individuals should be screened for mutations have arisen. Genetic alterations are central to the development of cancer and, though most are acquired over a person’s lifetime, between 5% and 10% are inherited germline mutations that can increase the lifetime risk of particular cancer types. Mutations associated with more than 50 hereditary cancer syndromes have been identified to date, and testing for such mutations can help to assess an individual’s cancer risk.

Thousands of BRCA1/2 mutations have been identified to date throughout the coding regions of these genes. BRCA1/2 alterations are generally classed as pathogenic on the basis of observed frequencies in cases of cancer compared with healthy controls. Though sporadic BRCA1/2 mutations are thought to be relatively rare, inherited germline mutations are more common. Overall, the prevalence of pathogenic BRCA 1/2 mutation carriers in the general population is estimated to be between 1 out of every 400 persons and 1 out of 800 persons. There are a number of founder mutations, which are high-frequency mutations that are particular to a specific population such as the 185delAG, 5382insC, and 6174T mutations, that are found at a frequency of 1 out of 40 persons in the Ashkenazi Jewish population. BRCA1/2 mutations are autosomal dominant, meaning an individual only needs to inherit a single defective copy of the gene from a parent to have an increased cancer risk.

BRCA1/2 mutations are particularly significantly associated with increased risk of breast and ovarian cancer. A genetic link between chromosome 17 (where BRCA1 resides) and breast cancer risk was first uncovered in the 1990s, and no predictor of risk of developing these cancer types has proved to be as powerful.

Compared with the general population, in whom the currently estimated lifetime risk of breast and ovarian cancer are 12% and 1.4%, respectively, individuals with inherited BRCA1/2 mutations have a substantially increased risk; by age 70, the risk of breast cancer is estimated to be 55% to 65% for BRCA1 carriers and 45% for BRCA2 carriers, whereas the risk of ovarian cancer is 39% for BRCA1 carriers and 11% to 17% for BRCA2 carriers.

Studies have shown that BRCA1/2 mutations are associated with increased risk of several other cancer types as well, with pancreatic and prostate cancers being the best studied. Both cancer types display a lower frequency of familial BRCA1/2 mutations than breast or ovarian cancers, and appear to be more closely associated with BRCA2.

More recently, studies have implicated BRCA2 in the development of lung cancer. Using four genomewide association data sets of more than 11,000 individuals of European descent, researchers found that BRCA2 mutations significantly increased the risk of non—small cell lung cancer, specifically squamous cell carcinoma, particularly among smokers in whom the risk may be doubled.

The association between breast cancer risk and BRCA1/2 mutations fueled a race to develop a means to identify mutation carriers at increased risk of breast and ovarian cancer. The victor was Myriad Genetics, a Utah-based company that subsequently patented the genes and began to offer commercial sequencing tests. Its monopoly on BRCA1/2 gene testing lasted close to 15 years, but came to an end in 2013 with a landmark ruling from the US Supreme Court. Historically, patents have been granted on genes, with some estimates suggesting that as much as 20% of the human genome may be noted on patents.

However, many believed that patenting genes was unconstitutional and invalid. In 2009, the American Civil Liberties Union and Public Patent Foundation filed a lawsuit against Myriad Genetics on behalf of researchers, genetic counselors, patients, and others to argue that human genes were products of nature and should not be patented. The Supreme Court ruled unanimously in favor of this position, and the door was opened for other companies to begin offering BRCA1/2 testing.

The controversy hasn’t ended there, however. Myriad has since filed a number of lawsuits against companies for patent infringement, contending that the Supreme Court only removed five claims out of its patents and that it still has more than 500 remaining claims across 24 patents. While it remains to be seen whether any of these lawsuits hold water, some believe they have succeeded in scaring away smaller competitors. One example is Gene By Gene, which settled with Myriad and is only able to market its BRCA1/2 tests outside North America.

Regardless of the legal fracas surrounding BRCA1/2 testing, the development of newer sequencing technologies and the emergence of other BRCA1/2 testing companies have created a broader range of testing options.

Myriad’s original BRCA1/2 tests used Sanger sequencing, which is limited in its ability to detect all variants within a gene. They and other companies offering BRCA1/2 testing are now making use of next-generation sequencing and other state-of-the-art techniques that are able to deliver faster and more accurate results at a lower cost and have the potential to identify all BRCA1/2 variants.

Although the BRCA1/2 genes are the most strongly associated with breast and ovarian cancer risk, there are many other genes that convey increased susceptibility to these and other tumor types, which may also be present. As such, companies are now beginning to offer rationally designed screens that look for a range of different genetic variants.

In an effort to maintain its competitive edge, Myriad Genetics also has numerous novel testing platforms under development. Among them is myChoiceHRD, which will offer a DNA-based readout of the degree to which a tumor has lost the ability to repair damaged DNA—the HRD stands for homologous repair deficiency&mdash;which includes analysis of BRCA1/2 genes in addition to other genes involved in DNA repair.

Regardless of which test is performed, the principal application is the same: a prognostic tool for patients with family or personal history of breast and ovarian cancer.

Currently, it is recommended that women with family members who have had breast or ovarian cancer talk with their healthcare provider and undergo genetic risk assessment and counseling to identify those at increased risk of hereditary breast and ovarian cancers.

A number of mathematical and predictive models have been developed to assist; the most commonly used include BOADICEA, BRCAPRO, and Myriad I and II. Individuals who screen positive at this stage may then be recommended for BRCA1/2 testing. A BRCA1/2 test generally provides one of three results:

		Positive—The individual has a BRCA1/2 mutation with a known association with cancer

		Negative—The individual has no known BRCA1/2 mutation

		Variant of unknown significance (VUS)— An abnormality was found, but it has not been evaluated for its potential association with cancer risk

A positive BRCA1/2 test result has several potential therapeutic implications. Patients without cancer can choose to be closely monitored for early detection or to undergo bilateral prophylactic mastectomy or salpingo-oophorectomy. The latter has been shown to reduce the risk of breast and ovarian cancer and improve overall survival.

Meanwhile, in patients who already have cancer or eventually develop cancer, having a BRCA1/2 mutation can impact treatment efficacy. BRCA1/2 mutant cancers have been shown to be exquisitely sensitive to DNA-damaging therapeutic agents as a result of synthetic lethality—the concept derived from yeast genetics that a single mutation in either of two genes is insufficient to cause cell death, but a combination of both mutations is lethal. Under normal circumstances, backup DNA repair pathways can repair the damage induced by DNA-damaging chemotherapeutics (eg, platinum-based) and radiation therapy, but the double hit in cells that also have a defective BRCA1/2 pathway overwhelms the cancer cell. This concept has also driven the development of molecularly targeted therapies against the poly(ADP)ribose polymerase 1 (PARP1) enzyme, which repairs single-strand breaks in DNA, known as PARP inhibitors.

BRCA1/2 testing companies are now also creating tests that aid in the development of these therapeutic strategies. In a study presented at the 2014 ASCO meeting, MyChoiceHRD accurately predicted response to cisplatin and paclitaxel in triple-negative breast cancer (TNBC).

Ideally, BRCA1/2 testing produces a definitive “yes” or “no” result, but in reality the outcome is significantly more ambiguous.

The implications of a negative result, for example, depend upon the kind of test that is used and the family history available. For comprehensive analyses in which the whole genome is screened, a negative result means an individual has no known pathogenic mutation.

However, if single-site analysis is used, then although a specific heritable mutation can be ruled out, other mutations cannot. Furthermore, a result can really only be classed as a “true” negative if the individual being tested has relatives with known BRCA1/2 mutations. If no relatives have been tested or no mutations have been detected in tested relatives, then the result is seen as an “uninformative” negative.

BRCA1/2 testing is also clouded by a third type of result, the identification of VUS, which can complicate clinical management since it is unclear what the associated cancer risk may be. Reducing the VUS rate would vastly improve the utility of genetic testing, and large collaborative research efforts are under way to catalogue and evaluate unknown variants.

The ultimate goal is to determine the potential pathogenicity of these variants using a variety of different methods. The International Agency for Cancer Research convened a panel of experts who developed a five-tiered classification scheme for the probability of pathogenicity.

Reported VUS rates vary between BRCA1/2 testing companies; while newer companies have higher reported rates (4%-6%), many years of experience have allowed Myriad to accumulate a large proprietary repository of genetic information that, the company contends, affords its tests an extremely low rate (0.6% and 1.6% for BRCA1 and BRCA2, respectively).

Myriad stopped publicly sharing data in 2004 and has received much criticism for it. In response, numerous groups have organized public databases to expand the pool of publicly available genetic information.

The Free the Data movement, which is gaining significant popularity among patient groups, established the ClinVar database, whereas the National Institutes of Health has developed the Breast Cancer Information Core, among others.

In September, four prominent academic centers established the Prospective Registry of Multiplex Testing (PROMPT), an online registry for individuals and families who have undergone testing for inherited cancer-causing genetic mutations. The founding institutions are the Dana-Farber Cancer Institute, Mayo Clinic, Memorial Sloan Kettering Cancer Center, and Penn Medicine; commercial test providers, including Myriad Genetics, have agreed to offer information about the PROMPT registry to patients and providers.

A number of organizations have generated clinical guidelines for genetic testing, with the most widely followed being those generated by the National Comprehensive Cancer Network and the US Preventive Services Task Force.

Both organizations recommend that only individuals with a family history of breast or ovarian cancer undergo BRCA1/2 testing, while individuals without family history are not encouraged to undergo testing unless they have breast or ovarian cancer. Indeed, Medicare and many private medical insurers don’t cover testing outside this protocol.

Mary-Claire King, PhD, who discovered the genetic link between breast cancer and BRCA1/2 mutations, has become a vocal advocate for universal BRCA1/2 testing among all women over the age of 30 years. King is a professor of Medical Genetics and Genome Sciences at the University of Washington and recently was honored with the 2014 Lasker- Koshland Special Achievement Award in Medical Science.

She cites the growing number of studies showing that pathogenic BRCA1/2 mutations frequently occur in a significant proportion of women who do not have a strong family history of relevant cancers.

This includes a study in which more than 8000 healthy Ashkenazi Jewish men aged 30 years and older were screened for one of three BRCA1/2 mutations. The female relatives of the 175 men who were found to harbor one of these mutations were then tested, and 211 carriers were identified.

Almost half of these women reported little or no family history of relevant cancer. Other studies have shown that assessment of family history through the use of models such as BRCAPRO, as recommended by current guidelines, does not effectively target testing to high-risk patient populations. Not everyone supports this position, however. Other prominent researchers urge more caution, arguing that there are a plethora of other genes involved in breast and ovarian cancer risk and that there is still ambiguity surrounding testing results, which could lead to many women undergoing unnecessary testing and prophylactic procedures. They also argue that the study in question looked at individuals with a high prevalence of BRCA1/2 mutations and may not translate into the general population.

Articles

Cover Story

As one of the most significant predictors of hereditary breast and ovarian cancer, the BRCA1/2 genes have become the poster child for genetic testing. In the past 18 months, the floodgates for testing options have opened, as companies seek to enter the diagnostic market in the wake of the US Supreme Court's June 2013 ruling that "naturally occurring" human genes are a "product of nature" and cannot be patented, breaking Myriad Genetics' monopoly on BRCA1/2 gene testing.

Update on BRCA1/2: Technical and Policy Questions Arise as Testing Options Expand

		Lisa Schulmeister, RN, MN, APRN-BC, OCN®, FAAN

Oncology Nursing Consultant, Adjunct Assistant Professor of Nursing

		Louisiana State Health Sciences Center in New Orleans, Louisiana

Brittany Maynard is now the face of the “right-to- die movement” after the news media began covering her controversial decision to end her life, on her own terms, on November 1, 2014. Her YouTube video about her decision, made for the advocacy group Compassion & Choices, has been viewed over 11 million times (

Her decision ignited a timely and much needed discussion about autonomy, decision-making, and options at the end of life.

In September 2014, the Institute of Medicine (IOM) issued the Dying in America: Improving Quality and Honoring Individual Preferences Near the End of Life report that concluded that end-of-life care in the United States is deficient at every level. The IOM noted that our current healthcare system is geared to doing more and more, which often does not improve outcomes, nor is it cost-effective or necessarily want patients want.

We can expect questions from our patients about Maynard’s decision, and in order to respond accurately and effectively, we need to be well informed about end-of-life choices and resources. No one would argue that advance planning should occur well before the very end of life. Plans should be documented and communicated in a living will, which lists end-of-life preferences, and a medical durable power of attorney, which identifies who will speak on behalf of the individual, should the individual become incapacitated to make decisions.

Each state has its own guidelines and forms for advance directives, and the Compassion & Choices website (www.compassionandchoices.org) lists each state’s requirements. Additional provisions (eg, dementia provision, hospital visitation authorization) may be considered, and contrary to popular belief that an attorney must be consulted to complete advance directives, the forms become legally valid as soon as they are signed in front of the required witnesses. It’s recommended that advance directives be reviewed periodically to ensure that the most current, state-approved format is used and that they continue to accurately reflect the individual’s wishes, which may change over time.

In a patient-centered model of care, unwanted treatment should not be delivered, and patients should always be the focus of care. Patients have the legal right to refuse medical treatment, and the 1990 Patient Self-Determination Act states that healthcare facilities that participate in Medicare and Medicaid must follow state laws, educate patients about their right to make their wishes known through advance directives, and document whether or not a patient has advance directives. By law, when healthcare providers do not want to uphold a patient’s wishes, they are required to facilitate a transfer to providers and/or facilities that will honor the patient’s wishes.

As our patients approach the end of life, they may be interested in an out-of-hospital do not resuscitate (DNR) order, which applies to death occurring at home or anywhere outside of a medical facility. This document, signed by a physician, must be accessible and in some states must be displayed (eg, a few states require that a specific colored paper copy of the DNR order is posted on a refrigerator). Patients also may be unaware of the Sectarian Health Care Directive, an optional addendum to advance directives that was implemented in 2011. The addendum clarifies that admission to a religiously affiliated facility does not imply consent to particular care mandated by the facility’s religious policies and directs a transfer to another facility when the facility declines to follow wishes outlined in an advance directive.

Five states (Oregon, Washington, Vermont, Montana, and New Mexico) have right-to-die laws (bills have been introduced in some other states). Maynard moved from California to Oregon, the first state to pass these laws.

Oncology nurses need to continue the conversation— and in some cases, start the conversation&mdash;about dying and honoring an individual’s preferences at the end of life. Patients want, and deserve, compassionate patient-focused care in their final days.

Nurse's Notes

Brittany Maynard is now the face of the "right-to- die movement" after the news media began covering her controversial decision to end her life, on her own terms, on November 1, 2014.

Death With Dignity

	Amy Hoffman is an assistant professor at Michigan State University College of Nursing in East Lansing.

“Let me show you my incision. It’s nearly 2 feet long! I never imagined I would be in this much pain. I was sent home with 30 Vicodin for pain to get me through the first week, but I’m worried I may need more pain medicine.”

This is the typical greeting I receive when I first meet my post-thoracotomy patients after they return home from the hospital. The incision is shockingly large, the pain is outrageously significant, and consequently, their longer term plan for pain control has them very apprehensive. Unfortunately, more often than not, the post-thoracotomy patients’ apprehension is proven correct, and their severe pain is continuing well past the first week of their home recovery.

However, many patients choose not to call their providers, stating their fear of being labeled “drug seeking” or a “wimp,” believing that since they were given no refills for their pain medication, the expectation must be that they should not need more when they run out.

 Instead, many patients choose to “tough it out” and try in vain to treat their pain by taking over-the-counter medications and limiting their mobility. Further, the continuous pain and lack of movement initiates and/ or exacerbates other symptoms like weakness, fatigue, dyspnea, difficulty remembering things, and distress, thus leaving the patient in a dangerous downward spiral during what should be their recovery process and decreasing functional status and quality of life.

 Unfortunately, it appears that an unintended consequence of addressing opioid abuse has been the reluctance of providers to prescribe and an unwillingness of patients to request needed and appropriate pain medication.

Healthcare policy and provider behaviors in response to anti-opioid reporting continue to cast a pall over access to effective pain management for those who suffer from acute and chronic pain. The crux of the problem lies in the National Institutes of Health, National Institute of Drug Abuse report that abuse of prescription medications is on the rise with more than 5.1 million people reported using prescription painkillers non-medically in 2010, that is, using them without a prescription.

Reports such as these have cast a black cloud over all providers and patients such that providers under prescribe so they cannot be accused of over-prescribing, while patients under report their pain so they cannot be accused of being an “addict.” This combination of under-prescribed pain medication, coupled with underreporting by patients, has created the perfect storm for post-thoracotomy patients. As a result, many post-thoracotomy patients act as good soldiers following orders without complaint, left to their own devices to fight their severe pain with over-the- counter medications.

Unfortunately, the deleterious effects of the pain often take a significant toll, ultimately leading to a call to their provider—not by the patient&mdash; by the emergency room, who is trying to piece together what to do to alleviate the multiple, significant issues the patient presents. Consequently, although healthcare policy has changed, some things have not changed since Margo McCaffery stated in 1968: “Pain is whatever the experiencing person says it is, existing whenever he says it does.”

 Pain after a thoracotomy is very severe, and more than likely the most severe pain ever experienced after surgery—just ask someone who has had this surgery.

One look at a post-thoracotomy patient’s incision would leave even the staunchest opponent to opioid prescriptions asking for their prescription pad to help alleviate pain for 1 more week of recovery. I know that if you had asked my grandfather who had a thoracotomy and later passed away from lung cancer in 1975, he would have told you that he can attest to the post-thoracotomy pain that he and many of his heroic buddies who stormed the beaches with him in Normandy experienced.

Moreover, although I was only 10 at the time, I clearly witnessed my grandfather suffer through the pain caused by his huge incision, retraction, resection, fracture of ribs, irritated pleura, injured nerves, and more normal responses of the human thoracotomy experience expressed as pain, including other comorbid diseases. I would have to agree that when he said he had severe pain, I had to believe what he said was true—it truly was pain.

While abuse of prescription drugs is a phenomenon that needs to be addressed, the phenomenon of under medicated pain for post-thoracotomy patients must also be addressed.

Judgment must be used, such that pain management no longer negatively stigmatizes patients and providers alike, especially in obvious areas of need such as for post-thoracotomy patients. To prescribe or not to prescribe is no longer the question for post-thoracotomy patients. To prescribe is the answer, and work is needed to remove the disincentives to prescribing and the stigmas attached to requesting help when obvious pain is out of control.

			Bayman EO, Brennan TJ. Incidence and severity of chronic pain at 3 and 6 months after thoracotomy: meta-analysis. J Pain. 2014;15(9):887-897.

			Yang P, Cheville AL, Wampfler JA, et al. Quality of life and symptom burden among long-term lung cancer survivors. J Thorac Oncol. 2012;7(1):64-70.

			Sarna L, Cooley ME, Brown JK, et al. Symptom severity 1 to 4 months after thoracotomy for lung cancer. Am J Crit Care. 2008;17(5):455-67.

			Brown JK, Cooley ME, Chernecky C, et al. A symptom cluster and sentinel symptom experienced by women with lung cancer. Oncol Nurs Forum. 2011;38(6):E425-E435.

			Handy JR, Asaph JW, Skokan L, et al. What happens to patients undergoing lung cancer surgery? Outcomes and quality of life before and after surgery. Chest. 2002;122(1):21-30.

			Borneman T, Koczywas M, Sun V, et al. Reducing patient barriers to pain and fatigue management. J Pain Symptom Manage. 2010;39(3):486-501.

			Simoff MJ, Lally B, Slade MG et al. Symptom management in patients with lung cancer: Diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2013;143(suppl 5):e455S-e497S.

			Paice J, Ferrell B. The management of cancer pain. CA Cancer J Clin. 2011;61(3):157-182.

			Beck S, Towsley G, Berry P, et al. Core aspects of satisfaction with pain management: cancer patients’ perspectives. J Pain Symptom Manage. 2010;39(1):100-115.

			National Institute on Drug Abuse, National Institutes of Health. Popping pills: Prescription drug abuse in America 2014. http://www. drugabuse.gov/related-topics/trends-statistics/infographics/popping- pills-prescription-drug-abuse-in-america. Accessed November 12, 2014.

			McCaffery M. Nursing Practice Theories Related to Cognition, Bodily Pain, and Man-environment Interactions. Los Angeles, CA: UCLA Students’ Store; 1968.

			Gerner P. Post-thoracotomy pain management problems. Anesthesiol Clin. 2008;26(2):355-367.

			Blades B, Dugan DJ. War wounds of the chest observed at Thoracic Center, Walter Reed General Hospital. J Thorac. Surg. 1944;13:294- 306.

Partner Perspectives

Many patients choose not to call their providers, stating their fear of being labeled "drug seeking" or a "wimp," believing that since they were given no refills for their pain medication, the expectation must be that they should not need more when they run out.

To Prescribe or Not to Prescribe?: Pain Management for Post-Thoracotomy Patients

		Alice Kerber, MN, APRN, ACNS-BC, AOCN, APNG

In a role that’s already multifaceted and growing ever more so, many oncology nurses and navigators are facing a new layer of complexity in their everyday practice: directing patients and their families to the right resources so that they can make informed decisions about their genetic risk, whether testing is warranted, and if so, what to do about the results.

The availability and breadth of genetic testing options have expanded exponentially since the US Supreme Court’s landmark decision last year to open up the testing market to competition. Awareness of genetic and familial risk factors has also soared in the wake of decisions by the actress Angelina Jolie and other high-profile figures to undergo prophylactic mastectomies because of their known genetic predispositions. Together, these trends have put cancer genetics center stage, posing one more challenge for today’s busy oncology practitioners who sometimes may feel like “they are expected to know everything, even though it’s impossible to know everything,” explained Alice Kerber, MN, APRN, ACNS-BC, AOCN, APNG. Many nurses feel pressure from “how quickly the information is coming, and how much of it is coming; it’s such a rapidly changing field, and it’s hard.”

Kerber is the oncology and genetics nurse specialist with Georgia CORE—the Center for Oncology Research and Education, a nonprofit organization working to improve the quality of cancer care in Georgia. She explained that multiple organizations have issued genetics guidelines for practitioners, including the NCCN, whose guidelines, she noted, “a lot of us use all the time”: “The beauty: these guidelines are updated all the time. The burden: they are updated all the time.”

“It’s a very complicated arena,” concurred Sue Friedman, DVM, who founded the organization FORCE (Facing Our Risk of Cancer Empowered) in 1999 following her own breast cancer diagnosis at the age of 33. Shocked that her healthcare team didn’t alert her to the possibility of being at high risk and disappointed at having to make critical treatment decisions while unaware of her mutation, she established FORCE so others could benefit from her experience.

The organization she leads works to fill the information void for individuals and families with hereditary breast and ovarian cancer (HBOC) and provides resources to help them to advocate for themselves.

Friedman described the explosion in genetic testing options following the Supreme Court’s decision as “astonishing,” noting that while costs of testing have come down, the number and variety of tests have gone up.

“It’s hard even for the experts to keep track of who is offering which test, how they’re reporting it, what panels, what genes, which ones are clinically actionable and which ones really are more, ‘Yes, this is interesting,’ but it doesn’t guide treatment any more than family history,” Friedman said. “It has made it more challenging for providers who don’t have specific training in cancer genetics to really figure out what is the best path for the patient.”

“We want to make sure that people are not making healthcare decisions based on incomplete information,” Friedman stressed.

Providing Guidance, Identifying Resources

To further that goal, experts agree that nurses need to acquire knowledge and foster relationships with genetic counselors and other local and digital resources, an approach that aligns with the American College of Surgeons Commission on Cancer 2012 Standard 2.3 which states that “cancer risk assessment, genetic counseling, and testing services be provided to patients either on site or by referral, by a qualified genetics professional.”

Abundant resources are available online and through professional societies (Box) for nurses to improve their knowledge base and to support their patients who may be at high risk.

Emily Beard, RN, OCN, CBCN, is coordinator for the Women’s Oncology Program at Northside Hospital Cancer Center in Atlanta, where she specializes in breast and gynecologic cancer services, a role that includes facilitating referrals to the hospital’s Hereditary Cancer Program. The program currently employs three full-time genetic counselors and will be expanding, she said. “When treatment decisions are pending, we work to get patients into the program as quickly as possible.”

American Nurses Credentialing Center (ANCC): 

www.nursecredentialing.org/AdvancedGenetics. Credential awarded: AGN-BC. Eligible applicants submit an online portfolio of evidence to document their knowledge and skills.

Breast Cancer Genetics Referral Screening Tool (B-RST):

City of Hope—Cancer Genetics Education Program: 

http://www.cityofhope.org/cancer-genetics-education-program.

Facing Our Risk of Cancer Empowered (FORCE): 

www.facingourrisk.org. Provides support, education, and programs to help those facing hereditary breast and ovarian cancer know their healthcare options and make informed decisions.

International Society of Nurses in Genetics (ISONG): 

: www.lynchcancers.com. Offers quick guides for professionals to acquaint them with basic knowledge of Lynch syndrome.

 www.hhs.gov/familyhistory. A web-based tool from the US Surgeon General whereby users can organize their family history information and print it out for their healthcare provider.

National Coalition for Health Professional Education in Genetics (NCHPEG):

National Comprehensive Cancer Network (NCCN): 

www.nccn.org. Guidelines for detection, prevention, and risk reduction.

National Society of Genetic Counselors (NSGC):

 www.nsgc.org/. Among its resources is a Find a Genetic Counselor directory searchable by state and city.

Most practices, especially those not affiliated with larger hospitals, will not have a genetic program on site, however. “As much as possible, reach out to the genetics experts in your area, to enable your patients to get the best information, and this may mean reaching out to someone at a different institution,” advised Friedman. The National Society of Genetic Counselors (NSGC), for example, maintains a searchable directory to help locate certified genetics counselors based on location.

Kerber, a member of NSGC, said she works very collaboratively with the genetic counselors in Georgia to help keep up with the demand for counseling fueled by greater awareness as well as regulations from major health insurers that require counseling before authorizing reimbursement for testing: “We just have to work together, because there are not enough of us.” And when access to counseling is a challenge, both Kerber and Friedman agreed that telephone counseling is a viable option. Kerber said that although “face-to-face is always better,” when that option is not available, organizations such as InformedDNA, which provides the advice of independent, certified genetic counselors via telephone and internet technology, can help to meet the demand and offer the added advantage of not being affiliated with one particular testing laboratory.

“Not everyone is going to want to have the counseling by telephone, but there is now some good emerging evidence that it is equivalent,” Friedman noted. “Why not at least offer it to patients?” She added that some specialties like ophthalmology are not amenable to a “telemedicine” approach, but taking a pedigree, getting a good history, looking at the insurance issues, can be done remotely and improve access to the services. “We have to be careful that we don't let access issues keep patients from having the opportunity to speak with a genetics professional, especially as more and more insurers are covering the cost for telephone counseling.”

Another important role for nurses and navigators is to stress with patients and families that to pursue testing does not mean prophylactic surgery will necessarily be the next step. Friedman said that she has seen a misperception by some that “the only reason to have testing is if one is considering prophylactic surgery, and that is simply not true,” she emphasized. “There are other healthcare decisions or services that someone will want to consider, armed with the knowledge that they are high risk.”

Some of the problem is media-driven, she acknowledged.

“It is a lot more headline-grabbing to report on a celebrity having a prophylactic mastectomy than the fact that they’re getting increased MRI screening. That’s what people see, so someone who might benefit from increased surveillance may decide not to undergo testing because they don’t want to remove their breasts.

I think that with our messaging, we need to be clear that there are other options available,” Friedman stressed. Misinformation is a problem, concurred Beard. “I think a lot of people don’t understand what we mean when we talk about genetics.” She recalled a patient who was very well educated who insisted, “No, I’ve had genetic testing,” but it turned out that what she thought was genetic testing was actually a genomic profile. “There are issues with the nomenclature.”

“And now in genetics, we have all this new information, such as panel testing, large rearrangement testing, that wasn’t available even 5, 6 years ago. Women who were tested then who had a family history but didn’t come up with the BRCA mutation in that initial testing may have a false sense of security: ‘I’ve taken care of that, I’ve been tested, I don’t need to think about this again,’ when in reality, they may need to think about new testing that’s available. Obviously, our priority is to get the word out to those who have never been tested, but even among those who have been tested, there are still opportunities for more follow-up and surveillance.”

One idea Beard said that she is interested in developing at her institution is a high-risk clinic model to follow patients over time. “We know that if they’re at risk of developing cancer because of a hereditary mutation, they need to be followed closely, and there’s also so much that we don’t know. There are these families that we all have seen where nothing showed up on the genetic test, but clearly there is something going on because there are multiple generations of cancer in young adults or multiple incidences of the same type of cancer.”

Following patients over time to inform future research is the goal of a new initiative FORCE is spearheading under the auspices of PCORnet, the National Patient-Centered Outcomes Clinical Research Network with funding under the Affordable Care Act. The goal of PCORnet, Friedman explained, "is to be able to link electronic health records and patient-reported outcomes together for about 70 million Americans, which will allow us to conduct research with numbers that has never before been possible.”

—identify patients with increased genetic risk

—provide basic genetic information to patients and families

—refer to credentialed genetics professionals for counselling

—tailor surveillance and management with genetic information

—recognize psychosocial aspects of genetic testing and diagnosis and offer support

—through continuing education in genetics and genomics

The ABOUT Network (www.AboutNetwork. Org) is focused on HBOC and is part of PCORnet’s network of research networks. “Our goal is to get at least 10,000 to 15,000 people enrolled in this registry,” said Friedman, “so that we can start looking at the long-term patient-reported outcomes of people who are affected by hereditary cancer to find out things like what happens when people choose surgery, what happens when people choose surveillance, what is the quality of life like,” and use that information to guide future research that will underpin the development of new cancer genetic guidelines in those areas where currently none exist. For example, said Friedman, is there a benefit to removing your uterus and what impact does this have on quality of life? Do women who choose mastectomy have better outcomes than those who choose surveillance?

“We don’t really have answers to these questions for the high-risk population, and we hope to provide guidance for healthcare decision-making,” Friedman continued. Many individuals receive their care in the community or rural setting and thus may not have access to a registry.

Healthcare providers are encouraged to spread the word to their patients about the advantages of joining ABOUT, including receiving information about clinical trials for which they are qualified. FORCE has downloadable materials on its website which practitioners can share with patients who want to learn more about the program.

In an arena as rapidly changing as genetics, continuing education is essential. Kerber serves as one of the co-chairs for professional practice for the International Society of Nurses in Genetics (ISONG) which has been working with the American Nurses Association to develop scope and standards of practice for nurses in this field. She is also one of just 40 nurses worldwide and two in Georgia who hold the current advanced practice nurse-genetics (APNG) credential.

The credentialing function of the Genetic Nursing Credentialing Commission, under whose auspices she received her certification, will now be carried out by the American Nurses Credentialing Center (ANCC). ANCC will be awarding the advanced genetics nurse, board-certified credential (AGN-BC), and began accepting portfolios for the AGN-BC December 5.

Kerber added that nurses who already have their GCN credential should contact the ANCC and advocate that it be part of their new genetic credentialing process for nurses. She explained that ANCC has credentialing for many levels of practitioners, from generalist to advanced practice. “We need both. Nurses need to have knowledge about this, and they need support.”

Beard, who counts Kerber as one of her mentors, has a longstanding interest in cancer genetics and is considering pursuing formal certification in the future. In her prior work as a breast health navigator, she participated in educational workshops on genetics, worked closely with a medical oncologist who had a special interest in genetics, and she is a member of the ONS Genetics Special Interest Group. ONS offers online courses in genetics to assist nurses wanting to improve their knowledge.

Whether they are pursuing a specialty genetics credential or simply want to keep up with the ever-changing arena of cancer genetics, Friedman suggested that nurses tap into the expertise of the professional societies. “I would encourage oncology nursing professionals to educate themselves as much as possible, and to get that education from professional societies, rather than just taking information provided by the labs.” One of the benefits of a professional society, she continued, is the knowledge that professionals have met competency requirements and obtained the required continuing education.

In a role that's already multifaceted and growing ever more so, many oncology nurses and navigators are facing a new layer of complexity in their everyday practice.

Navigating the New Landscape of Cancer Genetics

In September of this year, the National Institute of Occupational Safety and Health (NIOSH) announced a $2.3 million research grant involving 11 of the nation’s leading cancer centers. The 4-year initiative will examine exposure risks during the administration of chemotherapy and other hazardous drugs and identify effective strategies to combat these risks.

What’s notable about this award is that the focus is squarely on oncology nurses, “the single largest group of oncology care providers,” noted Christopher R. Friese, PhD, RN, AOCN, FAAN, assistant professor at the University of Michigan School of Nursing, who will be leading the new Drug Exposure Feedback and Education for Nurses’ Safety (DEFENS) study.

 interviewed Friese to discuss the NIOSH award and the findings from research he led examining antineoplastic exposure in a high-volume ambulatory infusion center. For that study, oncology nursing personnel were asked to complete a survey after a drug spill event and also to provide urine samples over an 8-hour period. The researchers found detectable levels of drugs in the samples of nurses both with and without a reported spill.

We wanted to follow up on findings from a paper-based survey asking nurses if they had been exposed to chemotherapy in the last year.

There is always this problem in research of self-reporting. To obtain a more direct measure of the problem, we decided to collect biologic specimens that would confirm and quantify the degree to which nurses had been exposed.

We found that nurses are exposed to hazardous drugs and that we can measure hazardous drug levels after an acute exposure or spill, but also in the environment, including surfaces that are contaminated with drugs from old spills or faulty handling practices. Thus, there are two threats to oncology nurses: the first is during an acute spill if they’re not wearing their personal protective equipment (PPE), and the second is the sort of day-to-day faulty handling practices that can lead to an accumulation of surface contamination. A lot of these drugs have chemical properties that lead them to stick to floors, chairs, and countertops.

Second, though not a statistically significant finding, we saw a trend that spills are more common among more experienced nurses, which suggests that their level of vigilance may be lower because they have been practicing for so long. They may feel that nothing bad has happened to them yet, so nothing bad is going to happen now; their perceived threat of the problem is likely lower, and their safeguards may be lower. For managers and educators, it’s important to realize that training and reinforcement of safe practice is important, not just for new nurses entering the profession, but for those experienced nurses on whom we may not be focusing our attention.

Third, we also saw a trend, also not statistically significant due to the small sample size, that the work environment for nurses matters; when nurses reported higher workloads and lower performance on safety behaviors, spills were also higher.

Your study reported that 60% of the participants had either no or a low level of concern about spills. Did that surprise you?

There is a perception in the field that while this is a known hazard, the health hazards are minimal. What needs to be understood is that it’s the cumulative exposure that’s so difficult. We have a radiation badge for people who work with x-rays. When they turn the badge in, it’s monitored, and workers with high levels are reassigned. We don’t have a similar mechanism to measure cumulative exposure to chemotherapy in the oncology nurse. It’s the daily low exposure that poses the greatest threat to nurses. The low level of concern is not surprising, but it is still alarming. It means we have a long way to go to educate nurses on the health hazards of exposure.

Also worth noting is that increasingly, nurses are handling these drugs who are not oncology nurses and have far less training and understanding about these agents. We’re working with the American Nurses Association and others on developing a comprehensive policy that would help these nurses as well.

The study also found that use of PPE was not optimal. What accounts for this?

One explanation is that the policies in place were not quite clear to nurses as to when, where, and how they should be wearing PPE in the outpatient setting where the volume is high, and nurses are dealing with multiple patients, often at the same time. These data helped us to have a really clear conversation with nurses about what they should be doing.

Based on these findings and other research to date, what is necessary to improve safe handling practice?

Ideally, we want a multilayered strategy where we’re using the best technology and building on nurses’ knowledge of the potential hazards, so that we’re doing whatever we can to minimize the risks. This includes making sure the environment is uncluttered, that the pumps work, that the patient understands what’s going on and they’re being monitored so they’re not dislodging the tubing, and then making sure the PPE is in place so that in case all else fails, the nurse is still adequately protected.

Finally, it is important for nurses to report events to their superiors. This study found that spills were not reported to risk management, so the traditional approach of learning from our mistakes would not have happened if this study were not taking place. There may be some “blame and shame” going on, with nurses reluctant to report spills, seeing it as a reflection on their personal practice. We know, however, that this is a multifactorial problem: the ergonomics of the suite, the volume, being pressed for time, equipment, patient variables—all of this comes together, and unless we report these events and learn from them, we’re not going to improve on the problem.

			Friese CR, McArdle C, Zhao T, et al. Antineoplastic drug exposure in an ambulatory setting: a pilot study [published online ahead of print May 14, 2014] Cancer Nurs.

			Friese CR, Himes-Ferris L, Frasier MN, et al. Structures and processes of care in ambulatory oncology settings and nurse-reported exposure to chemotherapy. BMJ Qual Saf. 2012;21(9):753-759.

Feature Story

In September of this year, the National Institute of Occupational Safety and Health (NIOSH) announced a $2.3 million research grant involving 11 of the nation's leading cancer centers. 

Talking With Christopher Friese About Chemotherapy Safety

	Colleen Castelein is an advanced practice nurse with the GI and sickle cell disease teams at Seidman Cancer Center, University Hospitals Case Medical Center, and a member of the clinical faculty at the Frances Payne Bolton School of Nursing, Case Western University in Cleveland, Ohio.

Here is a quiz for hematology/oncology nurses: What group of our patients is diagnosed with a devastating illness in early childhood which gets increasingly worse with age and leads to debilitating pain which is both chronic and acute in nature? Every organ system is affected. These patients lose their spleens at an early age and are at risk for infections which may prove fatal. The disease has far-reaching effects for both the patient’s ability to hold down a job and lead a full life. While lifespan for these patients has increased from a mere 20 years 2 decades ago to well into their 50’s and 60’s today, most patients live with the knowledge that they are at risk of sudden death from infection and acute chest syndrome at any time.

You likely guessed it: sickle cell patients. They have the most common inherited blood disorder, but their suffering is often under-recognized and under-treated by health professionals. Sickle cell disease is not rare. The disease itself affects one out of every 500 African Americans, and one out of 12 is a carrier of the gene and has the sickle cell trait.

 Approximately 100,000 Americans have the disease.

Some advances have been made to improve the care of sickle cell patients, improve quality of life, and increase lifespan. Comprehensive vaccination programs have prevented infections with devastating consequences, and hydroxyurea therapy has contributed to some decrease in both painful crises and acute chest syndrome episodes. Increasingly, patients are getting appropriate pain management interventions, but still pain crises are woefully underappreciated and undertreated. More research and concentrated clinical care programs are needed to help these patients throughout their lives.

At the Seidman Cancer Center we are trying to address this need. We established a formal program for caring for sickle cell patients. Under the leadership of a dedicated hematologist, Jane Little, MD, and two nurse practitioners, Tara Alin NP, and myself, we coordinate the care of all the adult sickle cell patients in our system. In the 5 years that we have been working together, we have learned a lot. Here are some of the lessons learned:

Comprehensive, interprofessional and multidisciplinary outpatient care with specialists under one roof improves care.

		Not only do we work together as a team, meeting once a week to discuss all patients seen that week, and twice a week with the inpatient team, we invite specialists from cardiology, nephrology, and pulmonary to join us in our clinic. They see our patients where we do, and we can collaborate in real time.

It takes a village—our patients deserve a wide range of services.

		We found that our young adult patients were missing appointments and having problems navigating our complex healthcare system and the social system they live in. Now a lay navigator works with them to help them find their way, and a full-time social worker is a permanent part of our team. Music therapists are available at crucial points of care offering our young patients a special form of therapy they can readily relate to.

The emergency room is not the best place to treat painful crises. An alternative to the emergency room manages patients more effectively when they have a painful crisis, increases patient satisfaction, and keeps our patients out of the hospital.

		Ten years ago we established a fast-track clinic in our infusion center. We see 6-8 patients per day there. We can treat pain for a longer period of time, see patients for multiple days, and get pain medicine to them more quickly. Today patients who go to our emergency room for a painful crisis are admitted approximately 50% of the time. We admit patients about 20% of the time. A dedicated group of nurse practitioners and clinical nurse specialists run the clinic and know the patients well.

Transition from pediatric clinic to the adult clinic is an important time and needs special attention.

		This is a time when our patients are seeking independence from parents and learning to make their way in the world. We need to manage this transition and treat our young adult patients with respect and kindness. It is also a time when their disease symptoms increase in severity. We are still experimenting with ways to help in this transition. Music therapy has played a big role in our patients’ care.

More research is needed to treat both the symptoms of the disease and the disease itself.

		Other centers, particularly Johns Hopkins, have led the way in bone marrow transplantation, the only known way to cure this disease. While we are planning to initiate this therapy for some of our patients, many will not be candidates. We are participating in a variety of research projects to improve care for our patients. Research is needed in all aspects of care, including quality of life strategies.

The National Heart, Lung and Blood Institute has recently published new evidenced-based guidelines for the care of the patient with sickle cell.

 Review them when you can. Reach out to your hospital administrator or head nurse to take steps to improve care for this underserved population. Help us address the suffering. Join us in treating these patients with the compassion and attention they deserve.

			US Department of Health and Human Services. National Institutes of Heath. National Heart, Lung and Blood Institute Disease and Conditions Index: What Is Sickle Cell Anemia? http://www.nhlbi.nih.gov/health/ dci/Diseases/Sca/SCA WholsAtRisk.html. Accessed November 17, 2014.

			US Department of Health and Human Services. National Institutes of Heath. National Heart, Lung and Blood Institute. Evidence-Based Management of Sickle Cell Disease: Expert Panel Report 2014. https:// www.nhlbi.nih.gov/health-pro/guidelines/sickle-cell-disease-guidelines/. Accessed November 17, 2014.

What group of our patients is diagnosed with a devastating illness in early childhood which gets increasingly worse with age and leads to debilitating pain which is both chronic and acute in nature? 

Managing Sickle Cell Disease: Lessons From Our Comprehensive Cancer Center

An increasing focus in oncology care is on survivorship and quality-of-life issues that arise once patients are living beyond treatment. For female breast cancer patients, important survivorship issues include sexual and reproductive health.

Breast cancer is the most common cancer in women, with 232,676 new cases expected in 2014; approximately 7% of these cases are diagnosed in women of reproductive age (<40 years).

 Despite the growing incidence of breast cancer, mortality has declined due to increased awareness, improved screening, and better treatment. However, the increase in the number of women who delay childbirth beyond age 35, as well as the increased use of cytotoxic adjuvant chemotherapy, have resulted in significant rates of infertility.

Fertility can be impaired in breast cancer patients for the following reasons: age at diagnosis, gonadotoxic chemotherapy, duration of endocrine treatment, or a combination of factors. As a woman ages, the number of oocytes diminishes over time. By the age of 37 years, only 10,000 out of 300,000 oocytes remain and by 40 years, fertility is halved and the chance of a spontaneous abortion is tripled.

 Therefore, age >35 at diagnosis is an obstacle to optimal fertility and should be discussed as a first step of counseling.

Beyond surgical management, axillary dissection, and radiotherapy, level I evidence has demonstrated that adjuvant use of chemotherapy and endocrine therapy has been shown to increase relapse-free and overall survival in young early-stage breast cancer patients.

 Many of these adjuvant therapies are both cytotoxic and gonadotoxic, significantly affecting fertility. The most common adjuvant chemotherapy regimens use an anthracycline-based combination therapy with an alkylating agent (ie, cyclophosphamide, cisplatin, and carboplatin). Gonadal toxicity occurs by two mechanisms: the direct induction of follicle and oocyte apoptosis and the vascular damage to the ovary. Both mechanisms are more pronounced in patients receiving alkylating agents.

The fertility effects of endocrine therapy are less clear. The use of tamoxifen sequentially with adjuvant chemotherapy has been shown to increase the risk for infertility. When used alone, it is associated with a low risk of premature menopause.

 The effects of tamoxifen is dependent on the length of treatment; the longer the treatment duration, the more reduced reproductive chances for a woman diagnosed after 35 years of age.

There is sufficient evidence to show that any breast cancer treatment option will have an inevitable effect on a woman’s fertility. Given the number of young women newly diagnosed with breast cancer and the rapid decline in fertility with age, provider discussions should be initiated as early as possible at diagnosis. Multiple studies have shown that early fertility counseling was associated with decreased psychosocial distress, less regret, and greater quality of life for survivors.

 Research on treatment-related infertility as well as qualitative studies on patient concerns and preferences, demonstrate a need for practice standards regarding fertility care of breast cancer patients.

In 2006, the American Society of Clinical Oncology (ASCO) issued recommendations on fertility preservation in cancer patients. The main purpose of the 2006 recommendations was to establish a standard of practice regarding counseling and fertility preservation methods.

 The following questions were addressed: What is the quality of evidence supporting current and forthcoming options for preservation of fertility in females? Are cancer patients interested in interventions to preserve fertility? What is the role of the oncologist in advising patients about fertility preservation options? In its 2013 guideline update, ASCO replaced “oncologist” with “healthcare provider,” emphasizing the interdisciplinary nature of fertility care and expanding its scope.

Current fertility preservation options for female breast cancer patients include embryo and oocyte cryopreservation.8 Other treatments, such as ovarian suppression with gonadotropin-releasing hormone (GnRH) agonists, are in development, but have insufficient evidence regarding effectiveness and safety. Options depend on age, diagnosis, treatment type, presence or participation of a male partner and/or patient preferences regarding use of banked donor sperm, time available, and likelihood that the cancer has metastasized to her ovaries.

It is unsurprising that the literature review revealed that fertility is of great importance to patients. Patients may fail to mention their concerns due to feeling overwhelmed, being more focused on the cancer diagnosis itself, being unaware of treatment effects on fertility, or fearing that pursuing fertility care would delay the actual cancer treatment. Key recommendations include discussing fertility preservation with all patients of reproductive age if infertility is a potential risk of therapy. Furthermore, all healthcare providers are responsible for fully informing patients about the risks that their cancer treatment may impair their fertility.

Oncology advanced practice providers (APPs) are in a key position to communicate with and educate young breast cancer patients regarding fertility issues at diagnosis. Discussions should start as early as possible in order to preserve the full range of options, reduce distress, and improve quality of life. With the growing incidence of both breast cancer and survivorship of breast cancer, fertility remains important for young women and should be an essential focus of their healthcare.

		American Cancer Society. What are the key statistics about breast cancer? http://www.cancer.org/cancer/breastcancer/detailedguide/breast-cancer-key-statistics. Accessed November 13, 2014.

December 2014