- Email: [email protected]
Barriers to genetic testing in newly diagnosed breast cancer patients: Do surgeons limit testing?
Accepted Manuscript Barriers to Genetic Testing in Newly Diagnosed Breast Cancer Patients: Do Surgeons Limit Testing? Laura Hafertepen, DO, Alyssa Pastorino, DO, Nichole Morman, MS, Jennifer Snow, DO, Deepa Halaharvi, DO, Lindsey Byrne, MS, LGC, Mark Cripe, DO PII:
S0002-9610(16)30509-8
DOI:
10.1016/j.amjsurg.2016.08.012
Reference:
AJS 12056
To appear in:
The American Journal of Surgery
Received Date: 5 July 2016 Revised Date:
18 August 2016
Accepted Date: 20 August 2016
Please cite this article as: Hafertepen L, Pastorino A, Morman N, Snow J, Halaharvi D, Byrne L, Cripe M, Barriers to Genetic Testing in Newly Diagnosed Breast Cancer Patients: Do Surgeons Limit Testing?, The American Journal of Surgery (2016), doi: 10.1016/j.amjsurg.2016.08.012. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT
ABSTRACT
patients. However, those at risk do not uniformly undergo testing.
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BACKGROUND: Genetic testing results influence treatment recommendations in breast cancer
METHODS: A prospective database of newly diagnosed breast cancer patients over an 18-
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month period was created and retrospectively reviewed in order to identify barriers to genetic
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testing.
RESULTS: 532 women were identified at risk for genetic mutation. 313(59%) completed a genetic counseling appointment. 292(55%) underwent genetic testing. 127(24%) were never referred to genetics. 89(17%) were referred but did not complete an appointment. Patients
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referred to genetics were younger than the non-referred patients (50.9 vs 60.6-years, p<0.001). Those referred to genetics but did not complete an appointment were surveyed; they had varied
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reasons for not completing the appointment.
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CONCLUSIONS: The largest barrier to genetic testing was lack of physician referral; therefore provider education must be improved. Appointments should be convenient and the significant implications of testing results should be discussed proactively.
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Barriers to Genetic Testing in Newly Diagnosed Breast Cancer Patients: Do Surgeons Limit Testing?
Laura Hafertepen,1 Alyssa Pastorino, Nichole Morman, Jennifer Snow,2 Deepa Halaharvi, Lindsey Byrne,3 Mark Cripe
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OhioHealth Breast and Cancer Surgeons Grant Medical Center 285 East State Street, Suite 300 Columbus, OH 43215 (614) 566-0774 Fax (614) 533-0438
Corresponding Author: Laura Hafertepen,1 [email protected], (909) 374-0019, Fax (303) 798-0916 1
Present Address: SurgOne, PC; 3333 South Bannock Street, #350; Englewood, CO 80110 Present Address: Texas Breast Specialists; 191 Walls Drive; Cleburne, TX 76033 3 Present Address: Mount Carmel Cancer Genetics Program; 5969 East Broad Street, Suite 102; Columbus, Ohio 43213 2
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INTRODUCTION Breast cancer is the most common cancer and the second leading cause of cancer death in women.1 The American Cancer Society (ACS) estimates that over 290,000 women were diagnosed
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with breast cancer in 2015 and that 40,000 women died as a result of the disease.2 Genetic
counseling and testing is useful for appropriate individuals, as up to 10% of new breast cancers are attributed to hereditary predisposition.3 Hereditary Breast and Ovarian Cancer (HBOC) is caused by
SC
mutations in the BRCA1 and BRCA2 genes. There are also several other genes that can lead to
hereditary breast cancer (e.g., PTEN, TP53, STK11, CHEK2). The risk of carrying a genetic mutation
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is higher among specific groups of women, such as those diagnosed with breast cancer at age 50 or younger, women with “triple negative” cancer at age 60 or younger, or those with a family history of breast or ovarian cancer.[4-5]
Results of genetic testing may influence surgical planning and modify screening recommendations, as well as guide risk reduction strategies for family members. For example, a
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newly diagnosed breast cancer patient found to be positive for a BRCA mutation should discuss the option of bilateral mastectomy as well as breast conservation, secondary to the risk of developing a second breast malignancy. Furthermore, after age 35 and upon completion of reproduction,
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patients with BRCA mutation are encouraged to undergo a prophylactic oophorectomy. Relatives of individuals with a genetic mutation may also undergo counseling and testing. Based on those test
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results, cancer screening and risk reduction decisions can be introduced.[3,6-7] The National Comprehensive Cancer Network (NCCN) Clinical Guidelines recommend that patients with breast cancer should have a referral to a cancer genetics professional if they meet specific predetermined criteria.8
Patients at risk for a genetic mutation are not uniformly seen by genetic counselors, even at nationally accredited breast centers. The objective of this study was to examine the utilization of genetic counseling and testing throughout our hospital system. We also set out to identify barriers
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to genetic counseling referral and appointment completion in newly diagnosed breast cancer patients that meet NCCN criteria for genetic counseling.
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MATERIALS AND METHODS We performed an analysis of our prospectively collected, multi-site database of newly
diagnosed breast cancer patients meeting NCCN guidelines for genetic counseling from January 1,
SC
2014 through June 30, 2015. All patients in our hospital system with breast cancer are presented at a weekly multi-disciplinary pre-treatment conference where genetic counselors are present.
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Patients that meet NCCN criteria are recommended for genetic counseling and are subsequently referred at the discretion of their physician. All patients presented at pre-treatment conference that met NCCN criteria for referral were included in our study cohort.
There were four hospital sites included in the study, three of which are accredited by the National Accreditation Program for Breast Centers (NAPBC) and Commission on Cancer (CoC),
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named sites “A” through “C.” The fourth hospital site (named site “D”) is CoC accredited only. Data on demographics, pathology, imaging and genetic testing results was collected. A follow up phone call was placed to those patients that were referred, but did not complete a genetic
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counseling appointment in order to identify barriers to appointment completion. After three unsuccessful attempts, those that did not respond were deemed “unable to contact.”
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Comparisons were done using two-sample t-tests, Wilcoxon rank sum tests, and chi-square tests. Statistical significance was defined as p<0.05. This study was approved through the institutional review board.
RESULTS During the study time period, 532 patients met NCCN criteria for referral to genetics and 292 (55%) completed genetic testing. The largest group of patients who did not undergo testing
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was 127 patients (24%) that were never referred by their physician. The next largest group was 89 patients (17%) that were referred but did not complete an appointment. The vast majority of patients that saw a genetic counselor had genetic testing (292 of 316, 92%). Thirty two patients
in Figure 1 and the results of genetic testing are listed in Table 1.
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(11% of those tested) had pathogenic mutations. The outcomes of patients in our study are outlined
Age was the only statistically significant difference in patients who were referred to genetic
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counseling versus those that were not referred, with the average age being 10 years younger in a referred patient than a non-referred patient (50.9 years versus 60.6 years, p<0.001). There was no
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statistically significant difference between those referred and those not referred in regards to stage at diagnosis or phenotype of breast cancer (Table 2).
There were 316 patients that completed genetic counseling appointments, for a 78% appointment completion rate when referred. The patients that completed a genetic counseling appointment were about 10 years younger than those that were not referred (48.6 vs 59.1 years,
(Table 3).
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p<0.001) and the most common breast cancer was low grade Stage 1 Invasive Ductal Carcinoma
The rate of appointment completion was significantly higher at our highest volume hospital
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site (Site A, p=0.001). This site also had the highest number of patients who qualified for genetic counseling, and their referral rate was slightly higher but not statistically significantly different to
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that of other sites (Table 4). Our study was unfortunately not designed to objectively compare hospital sites.
The 89 women that were referred to genetics but did not complete a counseling
appointment were contacted via telephone to evaluate the reasons why a counseling session was not completed. We were able to contact the majority of patients (65 of 89, 73%) and 13 patients (13 of 89, 14%) had their care transferred to another health system. The results of the telephone survey of the patients who continued their care at our health system are listed in Table 5.
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DISCUSSION Results of genetic testing in newly diagnosed breast cancer patients may influence surgical
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recommendations and modify screening and risk reduction strategies for family members. [1-3] The NCCN Clinical Guidelines recommend that patients with breast cancer should have a referral to a cancer genetics professional if they meet specific predetermined criteria.8 This study demonstrates
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that even at high volume nationally accredited breast centers, a significant number of patients at risk for a genetic mutation are never seen by a genetics professional nor undergo testing. This is the
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only study to our knowledge that looks specifically at limitations in referral for genetic counseling and appointment completion in newly breast cancer patients identified pre-operatively.7 This study identified the main reason to not undergo genetic testing was a lack of referral in 24% of the patients identified. Unfortunately, this number does not account for the possibility that the physician may have discussed referral and the patient refused or preferred to delay until after
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active treatment. For example, if the patient already confidently decided upon bilateral mastectomy or breast conservation therapy, then the genetic testing outcomes would not change immediate surgical management and may understandably defer the genetics consultation to a later time.
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The data reported was collected 3-6 months following accrual of patients. At the time of chart evaluation, some patients would have completed their treatments while others were just
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beginning. We plan to re-evaluate the data in 1-2 years to get a better understanding of additional post-operative referrals. After this additional time, the patients identified during the study time frame will theoretically have had follow up appointments with providers and other opportunities for genetics referral. We expect the reason for lack of referrals is a combination of provider education deficiency, limited genetic counselor availability, and potentially delayed until after surgery.
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Once referred for genetic counseling, patients that did not complete an appointment were contacted via telephone to discern the reason for lacking completion of appointment. Patients had varied responses. Many (25%) of patients contacted expressed that they felt overwhelmed with the
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number of appointments they already had and decided that the genetic counseling could be delayed or that it was not important for their treatment. Others (21%) did not want to know the results of a genetic test.
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The standard practice in our genetics department is to identify appropriate patients for counseling at our weekly pretreatment conferences. Physicians are sent a note through electronic
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medical records stating that their patient is appropriate for counseling. Physicians must make the referral, and all referred patients are contacted and sent pre-appointment forms to complete. These forms inquire specifically about family history of malignancies and are available either online or in paper form. After the forms are completed, an appointment with a genetic counselor is scheduled. However, patients that are referred urgently as results may impact surgical decision making are
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scheduled in the absence of this paperwork. Testing is completed at the time of counseling appointment when appropriate. In the group of patients that described “bad timing” during the study phone follow up, about half (6 of 14) spoke with the genetics department at initial referral
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but never returned the pre-appointment paperwork nor scheduled an appointment. One of these patients decided to postpone counseling until after treatment. Five patients were not able to be
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contacted initially by the genetics department. One patient we contacted during the process of the study did follow up with a genetic counseling appointment after our conversation. She had genetic testing which revealed a variant of uncertain significance. A few patients commented specifically that there was too much preparation prior to the
genetic counseling appointment. This may reflect that our current genetic counseling appointment preparation involves reporting a significant amount of information which requires time, knowledge of family history, and patient literacy. An investigation into family history may be difficult if the
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patient has a large family, is estranged from family, or does not want to disclose their cancer diagnosis to other family members. However, family history is crucial to genetic counselors to make recommendations for testing. Patients that are interested in testing but have a significant barrier to
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reporting family history may benefit from assistance by helping to obtain and report this information.
Patients also stated they did not follow up with a genetic counseling appointment because
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of financial concerns, or concerns over potential future health or life insurance discrimination. A brochure with basic genetic testing information is available, but is not always given to the patient at
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the time of referral. This brochure includes general financial information as well as information regarding health and life insurance discrimination. Genetic counselors are also available to discuss financial and insurance information with each patient individually prior to the patient being charged any fees. Based on the patient responses in this study, patients are either not receiving or not reading this pamphlet.
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A limitation to our study was not being able to contact almost a quarter (21 of 89, 23.5%) of the patients that were referred to genetic counseling but did not complete an appointment. The reason we were unable to contact them may be the same reason that they did not follow through
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with genetic counseling in the first place. Many of these patients are not following up as instructed, which could indicate that some may have chosen alternative therapy, transferred their care
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elsewhere, or elected not to undergo treatment. Some of the patients (13 of 89, 14%) that we did contact had transferred their care to another health system. They may have had genetic counseling and testing elsewhere, but we do not have access to these records. The rate of appointment completion was significantly higher at our highest volume hospital
site. Site “A” also had the highest number of patients who qualified for genetic counseling, and their referral rate was slightly higher but not statistically significantly different to that of other sites. We expect that there are characteristics of this site that create a better environment for genetic
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counseling appointment completion. Potentially these patients had a higher socioeconomic status, higher literacy rates, there may have been more available patient appointments, or providers at this
compare sites and we cannot confirm any of these statements.
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site may put more emphasis on genetic test results. However, our study was not designed to
As medical providers, we have the responsibility to educate ourselves and arm our patients with the knowledge to allow individuals to make an informed decision regarding treatment options.
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Genetic testing is a component of patient education that may have significant surgical implications. Our study is the first to evaluate barriers to physician referral and patient appointment completion.
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This study demonstrates that the most common barrier to genetic testing in newly diagnosed breast cancer patients is lack of physician referral. Many patients who were referred to genetics but did not complete an appointment had concerns regarding genetic testing and/or felt that it was not a priority in their treatment. Our study is unable to examine whether these concerns were shared with the referring physician or genetics staff.
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We have the duty to educate ourselves and encourage our patients to receive optimum cancer treatment, of which genetic testing is an important component. After a genetic counseling appointment, the patient should be able to make their own decision regarding testing. This means
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proactively discussing information, providing patients with adequate resources to answer their questions, and following up after a genetics referral. Genetic counselors should be readily
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available and provide prompt appointments for counseling and testing for this population of newly diagnosed breast cancer patients where testing results will influence treatment recommendations. This study demonstrates that we still have opportunities to improve patient care, provider and patient education, and expand access to genetic counseling and testing.”
CONCLUSIONS
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This study confirms that newly diagnosed breast cancer patients at risk for a genetic mutation are not uniformly seen by a genetics professionals, even at nationally accredited breast centers. The largest barrier to genetic testing in our cohort of newly diagnosed breast cancer patients is lack of
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physician referral. We must improve provider education on current guidelines and stress the importance and impact of genetic counseling. Once identified for referral, providers should
proactively discuss the importance of genetic testing and its implications. Physicians should also
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provide resources to answer frequently asked questions. We may be able to improve genetic
counseling appointments by decreasing the pre-appointment paperwork, assisting with paperwork,
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and making appointments convenient by coordinating them with other scheduled appointments.
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REFERENCES:
1. U.S. Cancer Statistics Working Group. United States Cancer Statistics: 1999–2012 Incidence and
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Mortality Web-based Report. Atlanta (GA): Department of Health and Human Services, Centers for Disease Control and Prevention, and National Cancer Institute; 2015.
2. American Cancer Society. Breast Cancer: Facts and Figures 2015-2016. Atlanta: American
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Cancer Society, Inc. 2015.
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3. Rebbeck TR, Friebel T, Lynch HT, et al. Bilateral prophylactic mastectomy reduces breast cancer risk in BRCA 1 and BRCA 2 mutation carriers: the PROSE study group. J Clin Oncol. 2004;22:1055-1062.
4. Frank TS, Deffenbaugh AM, Reid JE, et al. Clinical characteristics of individuals with germline mutations in BRCA 1 and BRCA 2: analysis of 10,000 individuals. J Clin Oncol. 2002;20:1480-
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1490.
5. Antoniou AC, Cunningham AP, Peto J, et al. The BOADICEA model of genetic susceptibility to
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breast and ovarian cancers: updates and extensions. Br J cancer. 2008;98: 1457-1466. 6. Rebbeck TR, Kauff ND, Domchek SM. Meta-analysis of risk reduction estimates associated with
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risk-reducing salpingo-oophorectomy in BRCA 1 or BRCA 2 mutation carriers. J Natl Cancer Inst. 2009; 101:80-87.
7. Domchek SM, Friebel TM, Singer CF, et al. Association of risk-reducing surgery in BRCA 1 or BRCA 2 mutation carriers with cancer risk and mortality. JAMA. 2010; 304:967-975. 8. National Comprehensive Cancer Network (NCCN). www.nccn.org. Version 3.2014
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9. Anderson B, McLosky J, Wasilevich E, et al. Barriers and Facilitators for Utilization of Genetic Counseling and Risk Assessment Services in Young Breast Cancer Survivors. J Cancer Epidemiol.
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2012;298745, 1-11.
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Table 1: Results of Genetic Testing Genetic Testing Results
Number of Patients
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(Total Number Tested 292)* Pathogenic Mutation (BRCA1, BRCA2, 32 CHEK2, ATM, PALB2, MSH2, MUTYH**, NBN, RAD51C) Variant, Uncertain Significance 70 Variant, Likely Benign 23 Variant, Likely Pathogenic 2 Negative 284 * The total number of tests is greater than the number of patients as some individuals had testing completed in a reflexive manner (i.e. BRCA1/2 with reflex to panel) ** Heterozygous for MUTYH mutation
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Table 2: Demographic and Pathologic Comparison of Patients Referred vs. Not Referred to Genetic Counseling
290 (71.6) 70 (17.3) 31 (7.7) 14 (3.5)
83 (66.4) 25 (20.0) 9 (7.2) 8 (6.4)
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Patient Not Referred to Genetic Counseling (n=127) 60.6 (12.5)
p-value <0.001
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0.427
94 (23.8) 137 (34.7) 164 (41.5)
39 (32.5) 42 (35.0) 39 (32.5)
0.100
71 (17.7) 163 (40.7) 128 (31.9) 34 (8.5) 5 (1.3)
26 (21.9) 48 (40.3) 30 (25.2) 11 (9.2) 4 (3.4)
0.326
317 (81.1) 74 (18.9)
92 (76.7) 28 (23.3)
0.291
270 (69.1) 121 (31.0)
84 (70.0) 36 (30.0)
0.844
48 (14.3) 288 (85.7)
11 (11.2) 87 (88.8)
0.437
51 (15.2) 285 (84.8) 18.0 (0.0 – 96.0)
18 (18.4) 80 (81.6) 13.0 (1.0 – 92.0)
0.448
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Age in years, mean (SD) Type of carcinoma, n (%) Invasive Ductal DCIS Invasive Lobular Other Grade, n (%) 1 2 3 Stage, n (%) 0 1 2 3 4 Estrogen receptor status, n (%) Positive Negative Progesterone receptor status, n (%) Positive Negative Herceptin receptor status, n (%) Positive Negative Triple Negative Status, n (%) Triple Negative Not Triple Negative Ki67, percent, median (range)
Patient Referred to Genetic Counseling (n=405) 50.9 (11.6)
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0.394
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Table 3: Comparison of Patients that Completed vs. Did Not Complete Genetic Counseling Appointment
242 (76.6) 44 (13.9) 19 (6.0) 11 (3.5)
48 (53.9) 26 (29.2) 12 (13.5) 3 (3.4)
<0.001
67 (21.8) 96 (31.3) 144 (46.9)
27 (30.7) 41 (46.6) 20 (22.7)
<0.001
45 (14.4) 131 (42.0) 107 (34.3) 26 (8.3) 3 (1.0)
26 (29.2) 32 (36.0) 21 (23.6) 8 (9.0) 2 (2.3)
0.013
247 (80.5) 60 (19.5)
70 (83.3) 14 (16.7)
0.551
212 (69.1) 95 (30.9)
58 (69.0) 26 (31.0)
0.999
42 (15.7) 226 (84.3)
6 (8.8) 62 (91.2)
0.150
42 (15.7) 226 (84.3) 21.0 (0.0 – 96.0)
9 (13.2) 59 (86.8) 13.5 (1.0 – 93.0)
0.617
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Referred but Did Not Complete Genetic Counseling Appointment (n=89) 59.1 (11.5)
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Age in years, mean (SD) Type of carcinoma, n (%) Invasive Ductal DCIS Invasive Lobular Other Grade, n (%) 1 2 3 Stage, n (%) 0 1 2 3 4 Estrogen receptor status, n (%) Positive Negative Progesterone receptor status, n (%) Positive Negative Herceptin receptor status, n (%) Positive Negative Triple Negative Status, n (%) Triple Negative Not Triple Negative Ki67, percent, median (range)
Completed Genetic Counseling Appointment (n=316) 48.6 (10.6)
p-value <0.001
0.054
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Table 4: Genetics Appointment Completion Rate by Location Referred
Appointment
Percentage of Referred Patient
Completed
Appointment Completion
A
275
230
83.6%
B
92
62
67.4%
C
25
16
64.0%
D
13
8
61.5%
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Site
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Table 5: Patient Reasoning for Not Completing Genetic Counseling Reason
Number of Patients 14 (25%)
Did not want to know results
12 (21%)
Financial Concerns
8 (14.5%)
Didn’t know about referral
4 (7.2%)
Too much pre-‐appointment preparation
3 (5.5%)
Actual family history changed
3 (5.5%)
Unclear about reason for referral
2 (3.6%)
Deceased
2 (3.6%)
Insurance Concerns
1 (1.8%)
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Bad timing / too much stress
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N=55 (%)
Other
8 (14.5%)
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Figure 1: Genetic Testing Outcomes of Breast Cancer Patients Meeting NCCN Criteria for Genetic Counseling
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Newly diagnosed breast cancer patients with NCCN criteria for genetics referral (n=532)
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NOT referred to genetics (n=127)
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Referred to genetics (n=405)
Did NOT complete genetic counseling appointment (n=89)
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Completed genetic counseling appointment (n=316)
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Did not meet testing criteria (n=13)
Declined testing (n=11)
Completed genetic testing (n=292)
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S0002-9610(16)30509-8
DOI:
10.1016/j.amjsurg.2016.08.012
Reference:
AJS 12056
To appear in:
The American Journal of Surgery
Received Date: 5 July 2016 Revised Date:
18 August 2016
Accepted Date: 20 August 2016
Please cite this article as: Hafertepen L, Pastorino A, Morman N, Snow J, Halaharvi D, Byrne L, Cripe M, Barriers to Genetic Testing in Newly Diagnosed Breast Cancer Patients: Do Surgeons Limit Testing?, The American Journal of Surgery (2016), doi: 10.1016/j.amjsurg.2016.08.012. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT
ABSTRACT
patients. However, those at risk do not uniformly undergo testing.
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BACKGROUND: Genetic testing results influence treatment recommendations in breast cancer
METHODS: A prospective database of newly diagnosed breast cancer patients over an 18-
SC
month period was created and retrospectively reviewed in order to identify barriers to genetic
M AN U
testing.
RESULTS: 532 women were identified at risk for genetic mutation. 313(59%) completed a genetic counseling appointment. 292(55%) underwent genetic testing. 127(24%) were never referred to genetics. 89(17%) were referred but did not complete an appointment. Patients
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referred to genetics were younger than the non-referred patients (50.9 vs 60.6-years, p<0.001). Those referred to genetics but did not complete an appointment were surveyed; they had varied
EP
reasons for not completing the appointment.
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CONCLUSIONS: The largest barrier to genetic testing was lack of physician referral; therefore provider education must be improved. Appointments should be convenient and the significant implications of testing results should be discussed proactively.
2
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Barriers to Genetic Testing in Newly Diagnosed Breast Cancer Patients: Do Surgeons Limit Testing?
Laura Hafertepen,1 Alyssa Pastorino, Nichole Morman, Jennifer Snow,2 Deepa Halaharvi, Lindsey Byrne,3 Mark Cripe
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OhioHealth Breast and Cancer Surgeons Grant Medical Center 285 East State Street, Suite 300 Columbus, OH 43215 (614) 566-0774 Fax (614) 533-0438
Corresponding Author: Laura Hafertepen,1 [email protected], (909) 374-0019, Fax (303) 798-0916 1
Present Address: SurgOne, PC; 3333 South Bannock Street, #350; Englewood, CO 80110 Present Address: Texas Breast Specialists; 191 Walls Drive; Cleburne, TX 76033 3 Present Address: Mount Carmel Cancer Genetics Program; 5969 East Broad Street, Suite 102; Columbus, Ohio 43213 2
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INTRODUCTION Breast cancer is the most common cancer and the second leading cause of cancer death in women.1 The American Cancer Society (ACS) estimates that over 290,000 women were diagnosed
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with breast cancer in 2015 and that 40,000 women died as a result of the disease.2 Genetic
counseling and testing is useful for appropriate individuals, as up to 10% of new breast cancers are attributed to hereditary predisposition.3 Hereditary Breast and Ovarian Cancer (HBOC) is caused by
SC
mutations in the BRCA1 and BRCA2 genes. There are also several other genes that can lead to
hereditary breast cancer (e.g., PTEN, TP53, STK11, CHEK2). The risk of carrying a genetic mutation
M AN U
is higher among specific groups of women, such as those diagnosed with breast cancer at age 50 or younger, women with “triple negative” cancer at age 60 or younger, or those with a family history of breast or ovarian cancer.[4-5]
Results of genetic testing may influence surgical planning and modify screening recommendations, as well as guide risk reduction strategies for family members. For example, a
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newly diagnosed breast cancer patient found to be positive for a BRCA mutation should discuss the option of bilateral mastectomy as well as breast conservation, secondary to the risk of developing a second breast malignancy. Furthermore, after age 35 and upon completion of reproduction,
EP
patients with BRCA mutation are encouraged to undergo a prophylactic oophorectomy. Relatives of individuals with a genetic mutation may also undergo counseling and testing. Based on those test
AC C
results, cancer screening and risk reduction decisions can be introduced.[3,6-7] The National Comprehensive Cancer Network (NCCN) Clinical Guidelines recommend that patients with breast cancer should have a referral to a cancer genetics professional if they meet specific predetermined criteria.8
Patients at risk for a genetic mutation are not uniformly seen by genetic counselors, even at nationally accredited breast centers. The objective of this study was to examine the utilization of genetic counseling and testing throughout our hospital system. We also set out to identify barriers
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to genetic counseling referral and appointment completion in newly diagnosed breast cancer patients that meet NCCN criteria for genetic counseling.
RI PT
MATERIALS AND METHODS We performed an analysis of our prospectively collected, multi-site database of newly
diagnosed breast cancer patients meeting NCCN guidelines for genetic counseling from January 1,
SC
2014 through June 30, 2015. All patients in our hospital system with breast cancer are presented at a weekly multi-disciplinary pre-treatment conference where genetic counselors are present.
M AN U
Patients that meet NCCN criteria are recommended for genetic counseling and are subsequently referred at the discretion of their physician. All patients presented at pre-treatment conference that met NCCN criteria for referral were included in our study cohort.
There were four hospital sites included in the study, three of which are accredited by the National Accreditation Program for Breast Centers (NAPBC) and Commission on Cancer (CoC),
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named sites “A” through “C.” The fourth hospital site (named site “D”) is CoC accredited only. Data on demographics, pathology, imaging and genetic testing results was collected. A follow up phone call was placed to those patients that were referred, but did not complete a genetic
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counseling appointment in order to identify barriers to appointment completion. After three unsuccessful attempts, those that did not respond were deemed “unable to contact.”
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Comparisons were done using two-sample t-tests, Wilcoxon rank sum tests, and chi-square tests. Statistical significance was defined as p<0.05. This study was approved through the institutional review board.
RESULTS During the study time period, 532 patients met NCCN criteria for referral to genetics and 292 (55%) completed genetic testing. The largest group of patients who did not undergo testing
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was 127 patients (24%) that were never referred by their physician. The next largest group was 89 patients (17%) that were referred but did not complete an appointment. The vast majority of patients that saw a genetic counselor had genetic testing (292 of 316, 92%). Thirty two patients
in Figure 1 and the results of genetic testing are listed in Table 1.
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(11% of those tested) had pathogenic mutations. The outcomes of patients in our study are outlined
Age was the only statistically significant difference in patients who were referred to genetic
SC
counseling versus those that were not referred, with the average age being 10 years younger in a referred patient than a non-referred patient (50.9 years versus 60.6 years, p<0.001). There was no
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statistically significant difference between those referred and those not referred in regards to stage at diagnosis or phenotype of breast cancer (Table 2).
There were 316 patients that completed genetic counseling appointments, for a 78% appointment completion rate when referred. The patients that completed a genetic counseling appointment were about 10 years younger than those that were not referred (48.6 vs 59.1 years,
(Table 3).
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p<0.001) and the most common breast cancer was low grade Stage 1 Invasive Ductal Carcinoma
The rate of appointment completion was significantly higher at our highest volume hospital
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site (Site A, p=0.001). This site also had the highest number of patients who qualified for genetic counseling, and their referral rate was slightly higher but not statistically significantly different to
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that of other sites (Table 4). Our study was unfortunately not designed to objectively compare hospital sites.
The 89 women that were referred to genetics but did not complete a counseling
appointment were contacted via telephone to evaluate the reasons why a counseling session was not completed. We were able to contact the majority of patients (65 of 89, 73%) and 13 patients (13 of 89, 14%) had their care transferred to another health system. The results of the telephone survey of the patients who continued their care at our health system are listed in Table 5.
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DISCUSSION Results of genetic testing in newly diagnosed breast cancer patients may influence surgical
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recommendations and modify screening and risk reduction strategies for family members. [1-3] The NCCN Clinical Guidelines recommend that patients with breast cancer should have a referral to a cancer genetics professional if they meet specific predetermined criteria.8 This study demonstrates
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that even at high volume nationally accredited breast centers, a significant number of patients at risk for a genetic mutation are never seen by a genetics professional nor undergo testing. This is the
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only study to our knowledge that looks specifically at limitations in referral for genetic counseling and appointment completion in newly breast cancer patients identified pre-operatively.7 This study identified the main reason to not undergo genetic testing was a lack of referral in 24% of the patients identified. Unfortunately, this number does not account for the possibility that the physician may have discussed referral and the patient refused or preferred to delay until after
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active treatment. For example, if the patient already confidently decided upon bilateral mastectomy or breast conservation therapy, then the genetic testing outcomes would not change immediate surgical management and may understandably defer the genetics consultation to a later time.
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The data reported was collected 3-6 months following accrual of patients. At the time of chart evaluation, some patients would have completed their treatments while others were just
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beginning. We plan to re-evaluate the data in 1-2 years to get a better understanding of additional post-operative referrals. After this additional time, the patients identified during the study time frame will theoretically have had follow up appointments with providers and other opportunities for genetics referral. We expect the reason for lack of referrals is a combination of provider education deficiency, limited genetic counselor availability, and potentially delayed until after surgery.
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Once referred for genetic counseling, patients that did not complete an appointment were contacted via telephone to discern the reason for lacking completion of appointment. Patients had varied responses. Many (25%) of patients contacted expressed that they felt overwhelmed with the
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number of appointments they already had and decided that the genetic counseling could be delayed or that it was not important for their treatment. Others (21%) did not want to know the results of a genetic test.
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The standard practice in our genetics department is to identify appropriate patients for counseling at our weekly pretreatment conferences. Physicians are sent a note through electronic
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medical records stating that their patient is appropriate for counseling. Physicians must make the referral, and all referred patients are contacted and sent pre-appointment forms to complete. These forms inquire specifically about family history of malignancies and are available either online or in paper form. After the forms are completed, an appointment with a genetic counselor is scheduled. However, patients that are referred urgently as results may impact surgical decision making are
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scheduled in the absence of this paperwork. Testing is completed at the time of counseling appointment when appropriate. In the group of patients that described “bad timing” during the study phone follow up, about half (6 of 14) spoke with the genetics department at initial referral
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but never returned the pre-appointment paperwork nor scheduled an appointment. One of these patients decided to postpone counseling until after treatment. Five patients were not able to be
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contacted initially by the genetics department. One patient we contacted during the process of the study did follow up with a genetic counseling appointment after our conversation. She had genetic testing which revealed a variant of uncertain significance. A few patients commented specifically that there was too much preparation prior to the
genetic counseling appointment. This may reflect that our current genetic counseling appointment preparation involves reporting a significant amount of information which requires time, knowledge of family history, and patient literacy. An investigation into family history may be difficult if the
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patient has a large family, is estranged from family, or does not want to disclose their cancer diagnosis to other family members. However, family history is crucial to genetic counselors to make recommendations for testing. Patients that are interested in testing but have a significant barrier to
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reporting family history may benefit from assistance by helping to obtain and report this information.
Patients also stated they did not follow up with a genetic counseling appointment because
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of financial concerns, or concerns over potential future health or life insurance discrimination. A brochure with basic genetic testing information is available, but is not always given to the patient at
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the time of referral. This brochure includes general financial information as well as information regarding health and life insurance discrimination. Genetic counselors are also available to discuss financial and insurance information with each patient individually prior to the patient being charged any fees. Based on the patient responses in this study, patients are either not receiving or not reading this pamphlet.
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A limitation to our study was not being able to contact almost a quarter (21 of 89, 23.5%) of the patients that were referred to genetic counseling but did not complete an appointment. The reason we were unable to contact them may be the same reason that they did not follow through
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with genetic counseling in the first place. Many of these patients are not following up as instructed, which could indicate that some may have chosen alternative therapy, transferred their care
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elsewhere, or elected not to undergo treatment. Some of the patients (13 of 89, 14%) that we did contact had transferred their care to another health system. They may have had genetic counseling and testing elsewhere, but we do not have access to these records. The rate of appointment completion was significantly higher at our highest volume hospital
site. Site “A” also had the highest number of patients who qualified for genetic counseling, and their referral rate was slightly higher but not statistically significantly different to that of other sites. We expect that there are characteristics of this site that create a better environment for genetic
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counseling appointment completion. Potentially these patients had a higher socioeconomic status, higher literacy rates, there may have been more available patient appointments, or providers at this
compare sites and we cannot confirm any of these statements.
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site may put more emphasis on genetic test results. However, our study was not designed to
As medical providers, we have the responsibility to educate ourselves and arm our patients with the knowledge to allow individuals to make an informed decision regarding treatment options.
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Genetic testing is a component of patient education that may have significant surgical implications. Our study is the first to evaluate barriers to physician referral and patient appointment completion.
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This study demonstrates that the most common barrier to genetic testing in newly diagnosed breast cancer patients is lack of physician referral. Many patients who were referred to genetics but did not complete an appointment had concerns regarding genetic testing and/or felt that it was not a priority in their treatment. Our study is unable to examine whether these concerns were shared with the referring physician or genetics staff.
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We have the duty to educate ourselves and encourage our patients to receive optimum cancer treatment, of which genetic testing is an important component. After a genetic counseling appointment, the patient should be able to make their own decision regarding testing. This means
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proactively discussing information, providing patients with adequate resources to answer their questions, and following up after a genetics referral. Genetic counselors should be readily
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available and provide prompt appointments for counseling and testing for this population of newly diagnosed breast cancer patients where testing results will influence treatment recommendations. This study demonstrates that we still have opportunities to improve patient care, provider and patient education, and expand access to genetic counseling and testing.”
CONCLUSIONS
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This study confirms that newly diagnosed breast cancer patients at risk for a genetic mutation are not uniformly seen by a genetics professionals, even at nationally accredited breast centers. The largest barrier to genetic testing in our cohort of newly diagnosed breast cancer patients is lack of
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physician referral. We must improve provider education on current guidelines and stress the importance and impact of genetic counseling. Once identified for referral, providers should
proactively discuss the importance of genetic testing and its implications. Physicians should also
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provide resources to answer frequently asked questions. We may be able to improve genetic
counseling appointments by decreasing the pre-appointment paperwork, assisting with paperwork,
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and making appointments convenient by coordinating them with other scheduled appointments.
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REFERENCES:
1. U.S. Cancer Statistics Working Group. United States Cancer Statistics: 1999–2012 Incidence and
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Mortality Web-based Report. Atlanta (GA): Department of Health and Human Services, Centers for Disease Control and Prevention, and National Cancer Institute; 2015.
2. American Cancer Society. Breast Cancer: Facts and Figures 2015-2016. Atlanta: American
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Cancer Society, Inc. 2015.
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3. Rebbeck TR, Friebel T, Lynch HT, et al. Bilateral prophylactic mastectomy reduces breast cancer risk in BRCA 1 and BRCA 2 mutation carriers: the PROSE study group. J Clin Oncol. 2004;22:1055-1062.
4. Frank TS, Deffenbaugh AM, Reid JE, et al. Clinical characteristics of individuals with germline mutations in BRCA 1 and BRCA 2: analysis of 10,000 individuals. J Clin Oncol. 2002;20:1480-
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1490.
5. Antoniou AC, Cunningham AP, Peto J, et al. The BOADICEA model of genetic susceptibility to
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breast and ovarian cancers: updates and extensions. Br J cancer. 2008;98: 1457-1466. 6. Rebbeck TR, Kauff ND, Domchek SM. Meta-analysis of risk reduction estimates associated with
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risk-reducing salpingo-oophorectomy in BRCA 1 or BRCA 2 mutation carriers. J Natl Cancer Inst. 2009; 101:80-87.
7. Domchek SM, Friebel TM, Singer CF, et al. Association of risk-reducing surgery in BRCA 1 or BRCA 2 mutation carriers with cancer risk and mortality. JAMA. 2010; 304:967-975. 8. National Comprehensive Cancer Network (NCCN). www.nccn.org. Version 3.2014
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9. Anderson B, McLosky J, Wasilevich E, et al. Barriers and Facilitators for Utilization of Genetic Counseling and Risk Assessment Services in Young Breast Cancer Survivors. J Cancer Epidemiol.
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2012;298745, 1-11.
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Table 1: Results of Genetic Testing Genetic Testing Results
Number of Patients
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(Total Number Tested 292)* Pathogenic Mutation (BRCA1, BRCA2, 32 CHEK2, ATM, PALB2, MSH2, MUTYH**, NBN, RAD51C) Variant, Uncertain Significance 70 Variant, Likely Benign 23 Variant, Likely Pathogenic 2 Negative 284 * The total number of tests is greater than the number of patients as some individuals had testing completed in a reflexive manner (i.e. BRCA1/2 with reflex to panel) ** Heterozygous for MUTYH mutation
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Table 2: Demographic and Pathologic Comparison of Patients Referred vs. Not Referred to Genetic Counseling
290 (71.6) 70 (17.3) 31 (7.7) 14 (3.5)
83 (66.4) 25 (20.0) 9 (7.2) 8 (6.4)
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Patient Not Referred to Genetic Counseling (n=127) 60.6 (12.5)
p-value <0.001
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0.427
94 (23.8) 137 (34.7) 164 (41.5)
39 (32.5) 42 (35.0) 39 (32.5)
0.100
71 (17.7) 163 (40.7) 128 (31.9) 34 (8.5) 5 (1.3)
26 (21.9) 48 (40.3) 30 (25.2) 11 (9.2) 4 (3.4)
0.326
317 (81.1) 74 (18.9)
92 (76.7) 28 (23.3)
0.291
270 (69.1) 121 (31.0)
84 (70.0) 36 (30.0)
0.844
48 (14.3) 288 (85.7)
11 (11.2) 87 (88.8)
0.437
51 (15.2) 285 (84.8) 18.0 (0.0 – 96.0)
18 (18.4) 80 (81.6) 13.0 (1.0 – 92.0)
0.448
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Age in years, mean (SD) Type of carcinoma, n (%) Invasive Ductal DCIS Invasive Lobular Other Grade, n (%) 1 2 3 Stage, n (%) 0 1 2 3 4 Estrogen receptor status, n (%) Positive Negative Progesterone receptor status, n (%) Positive Negative Herceptin receptor status, n (%) Positive Negative Triple Negative Status, n (%) Triple Negative Not Triple Negative Ki67, percent, median (range)
Patient Referred to Genetic Counseling (n=405) 50.9 (11.6)
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0.394
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Table 3: Comparison of Patients that Completed vs. Did Not Complete Genetic Counseling Appointment
242 (76.6) 44 (13.9) 19 (6.0) 11 (3.5)
48 (53.9) 26 (29.2) 12 (13.5) 3 (3.4)
<0.001
67 (21.8) 96 (31.3) 144 (46.9)
27 (30.7) 41 (46.6) 20 (22.7)
<0.001
45 (14.4) 131 (42.0) 107 (34.3) 26 (8.3) 3 (1.0)
26 (29.2) 32 (36.0) 21 (23.6) 8 (9.0) 2 (2.3)
0.013
247 (80.5) 60 (19.5)
70 (83.3) 14 (16.7)
0.551
212 (69.1) 95 (30.9)
58 (69.0) 26 (31.0)
0.999
42 (15.7) 226 (84.3)
6 (8.8) 62 (91.2)
0.150
42 (15.7) 226 (84.3) 21.0 (0.0 – 96.0)
9 (13.2) 59 (86.8) 13.5 (1.0 – 93.0)
0.617
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Referred but Did Not Complete Genetic Counseling Appointment (n=89) 59.1 (11.5)
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Age in years, mean (SD) Type of carcinoma, n (%) Invasive Ductal DCIS Invasive Lobular Other Grade, n (%) 1 2 3 Stage, n (%) 0 1 2 3 4 Estrogen receptor status, n (%) Positive Negative Progesterone receptor status, n (%) Positive Negative Herceptin receptor status, n (%) Positive Negative Triple Negative Status, n (%) Triple Negative Not Triple Negative Ki67, percent, median (range)
Completed Genetic Counseling Appointment (n=316) 48.6 (10.6)
p-value <0.001
0.054
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Table 4: Genetics Appointment Completion Rate by Location Referred
Appointment
Percentage of Referred Patient
Completed
Appointment Completion
A
275
230
83.6%
B
92
62
67.4%
C
25
16
64.0%
D
13
8
61.5%
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Site
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Table 5: Patient Reasoning for Not Completing Genetic Counseling Reason
Number of Patients 14 (25%)
Did not want to know results
12 (21%)
Financial Concerns
8 (14.5%)
Didn’t know about referral
4 (7.2%)
Too much pre-‐appointment preparation
3 (5.5%)
Actual family history changed
3 (5.5%)
Unclear about reason for referral
2 (3.6%)
Deceased
2 (3.6%)
Insurance Concerns
1 (1.8%)
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Bad timing / too much stress
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N=55 (%)
Other
8 (14.5%)
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Figure 1: Genetic Testing Outcomes of Breast Cancer Patients Meeting NCCN Criteria for Genetic Counseling
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Newly diagnosed breast cancer patients with NCCN criteria for genetics referral (n=532)
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NOT referred to genetics (n=127)
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Referred to genetics (n=405)
Did NOT complete genetic counseling appointment (n=89)
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Completed genetic counseling appointment (n=316)
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Did not meet testing criteria (n=13)
Declined testing (n=11)
Completed genetic testing (n=292)
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