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Several developments emphasize the increasing clinical relevance of germline testing within the oncology arena and the need for associated genetic counseling.
Although early discussions of personal genetic history became entwined with the since-discredited eugenics movement of the 1920s and 1930s, genetic counseling in clinical medicine has developed a long and scientifically meritorious history. The concept of counseling for medical conditions became an important component of health care with the discovery in 1959 that chromosomal analysis could diagnose Down syndrome.1
This led to formal prenatal testing for the presence of the characteristic defect (an extra partial or full chromosome 21). Prospective parents are counseled before the test regarding the potential implication of results and afterward for interpretation of the findings. Prenatal testing and counseling for several clinically relevant germline variations remain a critical component of routine obstetrical care.
In oncology, the relationship between a family history of cancer and the risk of subsequent development of a malignancy in other family members was known for decades. But it was the discovery of the genetic basis for these malignancies that dramatically heightened interest in germline testing and the critical need to provide meaningful counseling before and after testing.
The clinical arena of genetic counseling for cancer risk assessment is uniquely complex. Where else in clinical medicine can one find an area where basic molecular knowledge accumulates so rapidly, where what is standard-of-care medical practice today is literally modified tomorrow based on biological and clinical data, where each individual US state has its own regulations and laws regarding how germline information must be discussed with patients, and where such information may potentially be linked to both insurability and employability not only for the individual requesting the test but also for other family members?
If this complexity were not enough, consider that in the not-so-distant past discussions with individuals concerning their family or personal cancer histories were related to questions of family planning, prognosis of an existing cancer, and perhaps surveillance for the presence of a malignancy. Today, however, there is solid evidence to support the favorable impact of rather aggressive and life-changing prophylactic surgical interventions (eg, bilateral prophylactic oophorectomy to prevent ovarian cancer) on both cancer-specific and overall survival.2,3 Thus, discussions with individuals and their families about the implications of germline testing findings are potentially far more meaningful, complex, and stressful.
Finally, we must add to this evolving cancer counseling landscape the need that patients may have for information related to rapidly expanding settings where the administration of effective antineoplastic drugs is based on the presence of germline and possibly somatic genetic abnormalities.4 It is important to highlight the fact that, although the genetic test may have been obtained for the purpose of defining optimal cancer care, this does not alter the potential implications to the individual’s family related to germline findings.
The importance of identifying BRCA mutations illustrates the evolving role of genetic testing in oncology. In the relatively recent past, obtaining germline testing for BRCA mutations was strongly recommended by multiple organizations for women diagnosed with ovarian cancer. The results were principally to inform family members that they might also carry this abnormality and need to consider their own testing and potentially prophylactic strategies if a mutation were discovered.2,3 However, today, knowledge of the presence of a BRCA mutation has major therapeutic implications for an individual patient associated with the administration of a PARP inhibitor as a maintenance or therapeutic antineoplastic management strategy.
During the past year, this therapeutic strategy has been extended to both men and women with pancreatic cancer and men with prostate cancer who are found to have a germline BRCA mutation, dramatically expanding the patient population where genetic counseling has become essential and standard-of-care in cancer management. These developments emphasize the increasing clinical relevance of germline testing within the oncology arena and the need for associated genetic counseling.
Unfortunately, although the clinical utility of BRCA testing in patients with ovarian cancer has been established, reports about the uptake of germline testing are sobering. For example, in a recent report examining the American Society of Clinical Oncology’s CancerLinQ “real world” database of 2654 individuals who met well-established criteria for obtaining BRCA mutation testing, only 22.6% (fewer than 1 in 4) of those with ovarian cancer had documentation in their electronic health record of having such testing performed.5 These data are consistent with previous reports regarding BRCA testing.6
Although there are a number of possible reasons, one explanation is the lack of availability to many oncology practices—and, therefore, patients—of genetic counselors to provide essential discussions of the meaning and implications of germline genetic testing results. With the requirements for both pre- and posttest counseling and the number of critical items that must be discussed, the time commitment for a patient can be extensive.
However, a number of provocative proposals have been advanced to utilize online strategies to provide well-designed educational content. The content satisfies regulatory requirements for pretest counseling and, most importantly, helps the individual undertand the full range of personal and family implications of obtaining information related to the germline.7-9 It is hoped that future widespread availability of such approaches and their acceptance by state agencies will substantially improve the number of individuals and families whose health and welfare will be enhanced through this knowledge.
1. Löwy I. How diseases become “genetic.” Cien Saude Colet. 2019;24(10):3607-3617. doi:10.1590/1413-812320182410.19102019
2. Rebbeck TR, Lynch HT, Neuhausen SL, et al; Prevention and Observation of Surgical End Points Study Group. Prophylactic oophorectomy in carriers of BRCA1 or BRCA21 mutations. N Engl J Med. 2002;346(21):1616-1622. doi:10.1056/NEJMoa012158
3. Finch APM, Lubinski J, Møller P, et al. Impact of oophorectomy on cancer incidence and mortality in women with a BRCA1 or BRCA2 mutation. J Clin Oncol. 2014;32(15):1547-1553. doi: 10.1200/JCO.2013.53.2820
4. Markman M. Poly (ADP-ribose) polymerase inhibitors in the management of ovarian cancer. Women’s Health (Lond). 2018;14:1745505717750694. doi:10.1177/1745505717750694
5. Dewdney S, Potter D, Haidle JL, et al. Low rates of BRCA1 and BRCA2 testing for patients with ovarian cancer in ASCO’s CancerLinQ, a real-world database. J Clin Oncol. 2020;38:2020(suppl 15):6041. doi:10.1200/JCO.2020.38.15_suppl.6041
6. Childers CP, Childers KK, Maggard-Gibbons M, Macinko J. National estimates of genetic testing in women with a history of breast or ovarian cancer. J Clin Oncol. 2017;35(34):3800-3806. doi: 10.1200/JCO.2017.73.6314. Published correction appears in J Clin Oncol. 2018;36(4):432.
7. Swisher EM, Rayes N, Bowen D, et al. Results from MAGENTA: a national randomized four-arm noninferiority trial evaluating pre- and post-test genetic counseling during online testing for breast and ovarian cancer genetic risk. J Clin Oncol. 38:2020(suppl 15):1506. doi:10.1200/JCO.2020.38.15_suppl.1506
8. McCuaig JM, Tone AA, Maganti M, et al. Modified panel-based genetic counseling for ovarian cancer susceptibility: a randomized non-inferiority study. Gynecol Oncol. 2019;153(1):108-115. doi:10.1016/j.ygyno.2018.12.027
9. Cragun D, Weidner A, Tezak A, Zuniga B, Wiesner GL, Pal T. A web-based tool to automate portions of pretest genetic counseling for inherited cancer. J Natl Compr Canc Netw. 2020;18(7):841-847. doi:10.6004/jnccn.2020.7546