CE / CME
Pharmacists: 1.00 contact hour (0.1 CEUs)
Nurses: 1.00 Nursing contact hour
Physicians: Maximum of 1.00 AMA PRA Category 1 Credit™
Released: March 27, 2023
Expiration: March 26, 2024
Charles E. Geyer, Jr., MD:
When early breast cancer is discovered, the evaluation generally begins with the surgeon. Dr. Diego, we talked about BRCA testing in the setting of early breast cancer. Do we have enough genetic counselors to see all of our patients?
Emilia Diego, MD, FACS:
No, we do not. And genetic counseling is a double‑edged sword, particularly for patients who have early‑stage breast cancer, because the notion of testing suggests that they may be at increased risk for future cancers. For some patients, their surgical decision making will be influenced by the test results. Small studies and institutional reports have found that even just the concept of genetic testing will more likely result in a patient electing to have more extensive surgical intervention, even if the patient is not shown to have any pathogenic variants.24-30 Nevertheless, as a member of the American Society of Breast Surgeons, I recognize that our Society is advocating for every single person who has a diagnosis of breast cancer to be tested, regardless of family history or personal history. This is because there will be a very small fraction of women who will be found to have a pathogenic variant and some cases may be BRCA positive.23
Personally, I remain hesitant about whether everyone needs to be tested, if only because there are, first, a lot of conversations that need to be had with the patient when genetic testing is ordered because there will be very different mindsets regardless of whether the results are positive or negative or when you have the presence of a variant of uncertain significance. We need more HCPs to become well versed in genetic counseling to interpret these results and minimize stress in patients due to newly discovered variants of uncertain significance.
I think the most important reason to do genetic testing, in addition to identifying an individual’s future risk for breast cancer, is to help us better understand how to be more directed with their therapeutics. The medical oncologists play an important role here.
What Dr. Geyer was alluding to, however, is that when we are considering treatment for a newly diagnosed patient with early breast cancer, it is likely that they are going to meet a surgeon first. In a multidisciplinary setting, the surgeon can drive the decision-making or the referral for genetic testing, which is a difficult decision in the setting of HR-positive early breast cancer. I do not think anyone will argue about patients with TNBC receiving genetic testing, but which patients with HR-positive disease should be tested? Looking at the results of the OlympiA trial, even the patients who are candidates for olaparib tended to not have early‑stage, HR‑positive breast cancer because the study criteria required a heavy burden of nodal disease or a high CPS+EG score. I think that in this specific group of women who are HR positive and early stage, we would have to have a higher level of suspicion that there might be some benefits, but I don’t know that I have the answer just yet.
Banu Arun, MD:
Like you said, Dr. Diego, it’s a multidisciplinary group effort. A patient with metastatic breast cancer might come to a medical oncologist initially, but a patient with early-stage breast cancer might see a surgeon first and even undergo initial workup by a nurse practitioner. Not everybody needs testing, but there is a strong indication for treatment purposes, and any provider should be thinking about eligibility, whether they have an on‑site genetic counselor available or not.
Banu Arun, MD:
Dr. Diego, you mentioned the CPS+EG criteria. I am interested to hear Dr. Albarracin’s comments on that scoring system also because not everyone is familiar with it.
Constance Albarracin, MD, PhD:
The CPS+EG score is targeted toward patients treated in the neoadjuvant setting and takes into consideration the pretreatment clinical stage as well as the posttreatment pathologic stage.30 “E” represents the ER, in which ER negativity (ie, <1%) is given a score of 1. “G” represents the nuclear grade, in which high grade (grade 3) is considered 1 and any other grade is 0.
This scoring system has not gained much popularity outside of a trial setting. But what it has done is provided further stratification of the groups that is much better than the current American Joint Committee on Cancer breast cancer staging system.31 Its use may be enhanced by the availability of accessible, online tools which can make it easier to use. For now, it’s been useful primarily in the context of clinical trials, as seen here.
Charles E. Geyer, Jr., MD:
The CPS+EG score is used after neoadjuvant therapy and surgery to determine if eligibility criteria for the OlympiA trial have been met, which would provide support for germline BRCA testing. However, it is important to consider what we actually encounter in clinical practice. For example, a young patient with HR-positive breast cancer with a substantial clinical nodal burden and moderate‑sized disease will likely receive neoadjuvant chemotherapy. Depending on the genetic testing results and the surgical pathology findings, this patient may be a candidate for adjuvant olaparib. Important benefits of neoadjuvant chemotherapy are to inform complex decisions about locoregional management, contralateral breast surgery, and reconstruction and to provide time for patients to consider these important issues. A CPS+EG score of 3 or higher basically means clinical stage IIB or III disease did not respond well to chemotherapy. The question is: Do you really want to wait until you have that information after surgery to consider germline testing? I don’t think so, because with this approach, time and opportunity to help everyone make a better decision on surgery are lost.
The monarchE trial of adjuvant abemaciclib plus endocrine therapy in high-risk, HR-positive/HER2-negative early breast cancer included patients with positive lymph nodes before or after (neo)adjuvant chemotherapy.32 It is important to consider testing for pathogenic variants in BRCA1/2 in patients with HR-positive disease who do not respond well to neoadjuvant chemotherapy and otherwise meet eligibility criteria for OlympiA because of the potential benefit of olaparib. Hopefully, that’s already occurring in practice when we see younger patients and obtain the family history. It certainly emphasizes the importance of obtaining a family history to consider the whole picture in planning therapy.
Emilia Diego, MD, FACS:
Dr. Geyer, you make good points and I think that you have hit the nail on the head. When we’re thinking about testing, most women who would most likely benefit from the findings of the OlympiA trial are already being tested—these are the young patients with TNBC or those with locally advanced, HR‑positive breast cancers. We still need to better understand which older patients who have locally advanced disease may ultimately also benefit from olaparib at some point. One of the issues we currently encounter is whose genetic testing will be reimbursed by their insurance. At times, one insurance carrier will allow for it and another will not, despite the fact that genetic testing is guideline recommended.
Kristen Shannon, MS, CGC:
Yes, it varies widely by health insurance carrier. Medicare has stringent criteria that outline which patients they will reimburse for testing. For the most part, they seem to align with the NCCN guidelines but not always. The private insurance payers are vastly different and most of them are covering genetic testing for the classic cases, the ones that would benefit from adjuvant olaparib per the OlympiA trial, the early‑onset breast cancer cases. However, to Dr. Diego’s point, an older woman who has a very small breast cancer and no family history may not have coverage for BRCA1/2 testing by her private insurance company, even if she is going to benefit from a PARP inhibitor. Genetic testing is coming down in price, which is helpful. Most laboratories will do it for $250 out of pocket, but for many people, that often is not feasible.
One other hurdle is that there are a handful of private insurance companies that mandate genetic counseling by a genetic counselor to get the test covered. This is difficult because if you reside in an area of the country that doesn’t have access to genetic counselors, you are out of luck in terms of getting coverage. There’s a lot of difficulty navigating this space and it can make it a huge barrier for many patients.
Kristen Shannon, MS, CGC:
Getting the genetic testing done is one thing; getting it done well is another. Traditionally, genetic counseling performed by a certified genetic counselor has been the gold standard for genetic testing. Unfortunately, some smaller community hospitals and private practices don’t have access to genetic counselors. We need to start considering how best to get genetic testing done in a responsible way. There’s ongoing research looking at different service delivery models that increase access to quality genetic testing. This includes training more physicians and more “genetic counselor extenders,” such as nurse practitioners and physician associates/physician assistants, to provide a more tailored genetic pretest counseling session, testing, and follow-up. It’s definitely not a one‑size‑fits‑all approach, and although large academic medical centers may have more resources and more access to genetic counselors, the smaller community hospitals really need to think about developing relationships with either genetic counselors in their community or educating HCPs to identify the people who need the genetic testing, get it done responsibly, and make sure that the test results are given in an appropriate way so that, as Dr. Diego said, you don’t have patients with variants of uncertain significance thinking that they’re pathogenic variant carriers and taking inappropriate actions.
Charles E. Geyer, Jr., MD:
I have been in practice settings where we had more referrals than the single genetic counselor, who was available only 2 days a week, could handle. However, some of the diagnostic companies were able to do the testing and were willing to help address this issue. Is that occurring in practice? Is that a viable option when access to genetic counselors is limited?
Kristen Shannon, MS, CGC:
Some of the testing labs do have their own genetic counseling services that are being offered. Although it is important to recognize that these genetic counselors obviously have a conflict of interest, I do think they can be helpful.
Other options include using electronic tools and training other nongenetic counselors to help with the process. At our institution, we developed a decision aid to help with the pretest education and decision‑making process about genetic testing. This electronic tool helps the patients decide whether or not they want to pursue genetic testing and then what kind of multigene panel they want. This streamlines the pretest education and consent process for providers and improves efficiency in genetic testing.
Another option is to contract with genetic counseling companies that provide telehealth services to patients. Many insurance companies cover the virtual platform for patients and this provides access to genetic counselors that are available at a moment’s notice.
Kristen Shannon, MS, CGC:
It is very important to provide patients with their results in a way that is comprehensive and also meaningful to them. HCPs should always provide the exact results (PV found, no PV found, or variant of uncertain significance found) to patients. HCPs should discuss the associated medical risks and recommended medical management options including a discussion of therapeutic implications for the patient. The results should be interpreted in the context of the patient’s personal and family history of cancer. Patients should be informed of the importance of notifying their family members of their results, especially when they are identified as a PV carrier.
HCPs should remember that the genetic testing process can sometimes raise difficult emotions that typically lessen over time. For some, consultation with a psychologist, social worker, or psychiatrist may be helpful. Some people find it helpful to talk with others who have undergone genetic testing. The HCP should provide referrals for these issues as appropriate.
Banu Arun, MD:
Based on NCCN criteria, eligible patients for germline BRCA testing can be referred by any HCP. In some clinics, the patient presents to surgery first and, in other cases, to medical oncology first. Any HCP can refer to genetics (or order the test). Some practices also see patients in their multidisciplinary clinic, That would be the easiest platform to refer to genetics (or order the test)—while working up the patient as a multidisciplinary team.
Marissa Marti-Smith, MSN, APRN, AGNP-C, AOCNP:
If patients have positive BRCA tests and a family history of pancreatic cancer, we refer them to the high-risk pancreatic clinic for surveillance. Similarly, for patients with BRCA2 mutations, there is a slightly increased risk of melanoma, so we recommend follow-up with dermatology.33 It is important for any patients with positive genetic testing to be aware of any other coordinated follow-up that may be required, such as specialist visits and annual breast MRI scan.
Kristen Shannon, MS, CGC:
A referral to a genetics specialist is recommended when a patient has a PV identified; when a patient has negative test results but tumor profiling, personal history, or family history remain suggestive of an inherited condition; when a patient has a mosaic or possibly mosaic result; and whenever an HCP feels that the patient would benefit from further discussion of the test results.
It is important to note that patients with a PV can benefit from reconsultation with an HCP who is familiar with inherited risk for cancer. This follow-up can help increase compliance with screening guidelines, which is known to decrease over time, allow for re-evaluating personal choices about risk-reducing surgeries, based on changing life stage and circumstances, and of importance ensure patients are following up-to-date guidelines.
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