Our non-traditional framework

In this paper, we eschew a formal analysis of cost-effectiveness in terms of life years gained or quality of life promoted that populates much of the health economics literature on the value of genetic testing as a screening tool (Myundra et al., Reference Myundra, Grosse, Hampel and Palomaki2010; Grosse et al., Reference Grosse, Palomaki, Myundura and Hampel2015; Grosse, Reference Grosse2015). Such analyses, of course, are influential when making comparative decisions about how best to allocate scarce resources, or for drug pricing and coverage decisions. While of significant import, we will instead turn our attention to the more fundamental issue of cost itself. In this, we will be asking a simpler question: can we afford to realize the potential benefits of genetic testing as a screening tool for adoptees, however great those benefits might be? We rely on the moral imperative to address a health disparity to motivate positive action where this can be done at minimal or no cost. Within this context, our aim is not to provide a definitive economic analysis of the price per life year gained or relative worth of genetic testing for adoptees; but rather is meant to explore whether addressing the health disparity experienced by adoptees in regard to access to FHx information can be done in a cost-neutral, or nearly cost-neutral, manner.

We do this with no intended judgment on traditional methods of health economics, whose focus is undoubtedly best for policy setting purposes. However, a focus on cost per life year saved will inevitably lead to the comparative aspects of funding this intervention over another. This calculation is valuable for setting policy within a context of costly interventions but is less valuable where the intervention poses little to no cost, as we argue is the case here. In fact, such a comparative analysis can be counterproductive in contexts like ours, where the relatively small population in question (adoptees constitute approximately 2.5% of the U.S. population) can distract from the disparity experienced by these individuals. We believe that where effective intervention to address a disparity is available at little or no cost, the value of undertaking this intervention should be recognized regardless of the relative size of the population.

Eschewing the traditional analysis of cost per life year saved, however, requires we in essence start from scratch in terms of establishing costs over a given population. Here, we hope to initiate this discussion through our best efforts to assemble costs – a project that is challenging for myriad reasons, including regional differences in cost for common interventions and limited economic analysis outside of the traditional context of cost per life year saved. Nonetheless, we believe that by relying on a mixture of academic and non-academic consumer studies and pricing estimate mechanisms, we can arrive at fairly reliable estimations of reasonable ranges for expected costs over a national population; albeit estimates that, because of the necessary mixture of academic and consumer sources, will to some extent reflect a feel of ‘back-of-the-envelope’ calculations. Recognizing this, we take great pains below to explain our rationale for relying on each number assumed, and err on the side of conservative estimates leading to higher costs and lower savings where conflicting numbers exist.

We also deviate from standard health economics in our focus on savings in the abstract, rather than savings to a particular entity. We do this because we do not wish to take up the very complex issue of the myriad ways in which cost for care is distributed (that is at least a paper of its own). For example, these savings would be realized by an insurance provider if that provider covers all costs in an old-style ‘fee for service’ model, but if the insurance contracts with a hospital or hospitals on a ‘capitated’ basis this savings would be distributed in a more complex way. And the billing codes for Medicaid/Medicare might themselves warrant a paper or more! Our point in this paper is more simple: that the costs associated with the delivery of care for the conditions examined would be reduced. We leave the issue of exactly who would realize these cost savings under different scenarios to future discussion.

Our method, then, is to provide reasonable healthcare delivery cost and savings estimates for a cohort of adoptees that might be offered testing at age 20 (an age that would optimally capture risks for adult-onset, medically actionable conditions identifiable through genetic testing, as we see below). We estimate this cohort to be no greater than 100,000 per year. based on the numbers above. We focus on savings from Lynch syndrome and BRCA because these are widely recognized as well-understood and reliable genetic tests that identify highly penetrant and highly pathological gene-disease associations; tests likely to be included in any genetic screening panel.

Costs

The costs associated with potential testing are best estimated using existing hereditary cancer screening panels currently offered by genetic testing companies. For example, Color Genomics offers a physician-ordered genetic cancer screening panel, with some genetic counseling, for $249; and Kailos Genetics offers a hereditary cancer screening panel of 30+ genes, including those associated with Lynch syndrome and BRCA (as well as others) for only $225. It should be noted that these prices are offered on each company’s website respectively to individuals, and do not reflect lower ‘volume testing’ prices that could be offered due to more efficient batching, that might be expected from the type of screening we propose. Moreover, the more limited panel of disease-associated genes we envision will likely be smaller than the existing 30 gene panel, which would mitigate costs a bit further. Using these costs as baseline estimates, then, should be more than reasonable.

Thus, if we assume targeted testing costs of between $225 and $250 per person based on the current pricing described above, the costs of screening one cohort of 100,000 20-year-old healthy, symptom-free adoptees (see above) would be between $22.5 M and $25 M.

The greatest promise for affordability of genetic testing as a screening tool lies in its ability to reduce costs through the early detection of preventable conditions. The few studies that have looked at the effectiveness of genetic testing as a screening tool to date have (rightly) couched this effectiveness in a context of genetic testing vs alternative available means to access risk information, such as family history (Heald et al., Reference Heald, Endelman and Eng2012; Agalliu et al., Reference Agalliu and Wang2013). For example, a study of genetic testing to assess inherited colon cancer risk compares the effectiveness of genetic testing vs traditional family history for identifying risk (Agalliu et al., Reference Agalliu and Wang2013). The study found little-added benefit from genetic testing: unsurprisingly, as inherited colon cancer risks reliably identifiable through genetic testing typically have high rates of disease manifestation among those with a causative mutation (in the case of Lynch syndrome, as high as 80%). Such high rates of early onset, life-threatening conditions (e.g., colon cancer prior to the age of recommended screening) are precisely those characteristics that make such a condition relatively detectable through family history alone (Moyer and the U.S. Preventive Services Task Force, Reference Moyer2014). Traditional FHx, then, will be a reasonably effective mechanism for identifying the higher risk of such an inherited condition.

However, for those who lack FHx, a very different evaluative framework will apply (May et al., Reference May, Strong, Khoury and Evans2015). For these individuals, we must consider the likelihood that early identification of disease could be arrived at in another way, absent the use of traditional FHx. This will require an assessment of the adequacy of general population guidelines for routine screening for populations lacking FHx as an indicator of need to deviate from these guidelines (i.e., early or enhanced screening). That is, if general population screening guidelines exist, how likely are certain inherited diseases to manifest before screening would otherwise commence or be missed because of general recommendations for frequency of screening (e.g., 10-year colonoscopy) that are insufficient in someone at elevated risk? Are there effective interventions that could prevent or significantly mitigate the negative outcomes of disease manifestation if high risk is identified early? Is an increased risk identifiable through genetic testing sufficient to warrant intervention?

Lynch syndrome savings

Lynch syndrome is an excellent illustrative case (May et al., Reference May and Evans2016b), as it is a relatively common ‘rare’ disease with a very high rate of early onset cancer manifestation; has available a highly reliable genetic test; and is a condition for which there exist well-established, highly effective preventive interventions that are cost-effective and involve relatively minor burdens (e.g., compared to prophylactic intervention for breast cancer, as we will discuss below).

Lynch syndrome affects approximately 0.25% of the U.S. population, (American Gastroenterological Association, ND) and results in early onset colon cancer in up to 80% of cases. (American Cancer Society, NDa) Of our cohort of 100,000 tested adoptees, we would expect ~250 individuals to be identified as positive for Lynch syndrome (0.25%). Consistent with American Cancer Society and American Gastroenterological Association recommendations, for these individuals, colonoscopies would begin at age 20–25 (rather than at age 50 as is recommended for the general population), and be done every other year. (American Cancer Society, NDb) Costing an average of $1200 each (Rosenthal, Reference Rosenthal2013), these additional (i.e., in addition to standard population guidelines) ~15 colonoscopies between ages 20 and 50 would cost approximately $18,000 per person, or a total of ~$4.5 M for the 250 individuals who tested positive for Lynch syndrome. Thus, the costs of screening for the entire cohort of 100,000 adopted individuals, plus the costs of early interventions to prevent colon cancer for those who test positive, would total ~$27 M–$29.5 M.

By comparison, the cost of treatment for colon cancer is undoubtedly very high, particularly for late-stage cancer as would be expected for cases where onset occurs well before recommended screening and there is no alternative indicator of higher risk available, as is the case for our cohort. One review article concluded that cost estimates are confounded by so many variables – including stage of disease, regional variations in approach, a constantly changing array of available chemotherapies, specific characteristics of particular delivery systems (including billing code practices), a variety of (usually neglected) caregiver costs in different settings, etc., – that consistent, accepted cost numbers are difficult to establish (Yarbroff et al., Reference Yarbroff, Borowski and Lipsomb2013). Nonetheless, some attempts to examine comprehensive costs do exist. In 2007, a study based on the VA system estimated costs for late-stage colon cancer treatment to be ~$120,000 (Hynes, Reference Hynes2012) and estimates cited by The Lewin Group cite costs as high as $310,000 per year per case (National Colorectal Cancer Roundtable, ND). For the sake of being conservative, we will assume the lower 2007 estimate of ~$120,000. Note, however, that the estimates cited by the Lewin Group may well prove more accurate, meaning far greater cost savings. In fact, we believe this is likely, given the higher, more established costs of breast and ovarian cancer we discuss below, along with the knowledge that pharmaceutical (especially chemotherapy) costs are much higher for colon cancer (Drugwatch, 2015).

Of the ~250 individuals expected to test positive for Lynch syndrome in the cohort of 100,000 adult adoptees who undergo targeted testing, ~200 (80%) would be expected to develop colon cancer prior to general population screening. As discussed above, because no alternative indicator of high risk is available, most of these individuals would likely need late-stage treatment absent testing, which would not be required if they were identified as high risk and received preventive intervention. While the percentage of these cases that are ‘late stage’ will not be 100% (some cases will be identified early through blood in stool, etc.), none will be caught as pre-cancerous polyps and thus actually prevented, as the vast majority would with colonoscopy. Thus, we will assume late-stage as the model, and allow our reliance on the lower cost estimate of $120,000 per case (see above) to account for outlier ‘early stage’ detection absent screening. This would mean a cost savings of ~$24 M for late-stage colon cancer treatment in 200 avoided cases among the 250 individuals positive for Lynch syndrome. In sum, testing of the entire cohort of 100,000 20-year-old adoptees, along with biennial colonoscopies that would prevent manifestation of the disease, should result in a net cost of ~$3 M–$5.5 M using conservative estimates at each cost point.

But testing for Lynch syndrome would surely not be the only FHx-like genetic test that would be included in the testing panel. Other potential candidates for the testing panel – for example, BRCA1/2 – also offer the promise of cost savings by using the same sequencing platform. As with Lynch syndrome, cost estimates are in most cases estimates of probabilities that themselves are only able to be characterized in ranges. Nonetheless, even a ‘fuzzy’ analysis can provide significant reason to believe that adding BRCA1/2 to a testing panel would add to the cost savings that Lynch syndrome anchors. As with Lynch syndrome, this is because most adoptees lack access to FHx information through which ‘high risk’ (indicating the need for early preventive action) would normally be identified.

BRCA-related breast cancer savings

Identifying individuals who carry pathogenic variants in BRCA1 and BRCA2 offers another attractive target for genomic screening. Indeed, the efficacy of prevention and surveillance is significant enough that there are calls for screening all women in the general population (King, et al., Reference King, Levy-Lahad and Lahad2014). Individuals testing positive for pathogenic BRCA variants are at high risk of developing breast and ovarian cancer; yet general screening modalities for breast cancer (such as annual mammograms) are ineffective for those at such increased risk (Warner et al., Reference Warner, Plewes and Hill2004) – and no effective modalities for ovarian cancer exist. Thus, identification of those at high risk by virtue of carrying a BRCA1/2 pathogenic variant affords the opportunity for such individuals to benefit from well-established, preventive modalities such as annual breast MRI, risk-reducing bilateral mastectomy and risk-reducing bilateral salpingoopherectomy (NCCN Guidelines, ND).

Estimates for risk of manifesting breast cancer among BRCA-positive women are a moving target, ranging from 65% to 85% lifetime risk. For our purposes here, we will assume the mid-point between these estimates (75%), which is a number very close to lifetime risk (72%) identified in a 2017 study published in JAMA (Kuchenbaecker et al., 2017).

For BRCA, an estimate of costs savings must take into account the preventive action taken by those testing positive; the likelihood that cancer would manifest prior to routine screening (so that reduced costs of early identification could be attributed to early screening); and any changes in screening approach that would result from a positive test that identified the individual as high risk (e.g., The American Cancer Society recommends that MRIs be used as adjuncts to mammography for women with at least 20–25% increased risk) (American Cancer Society, NDc).

The first two of the above variables we can estimate to some degree: a 2009 study of treatment choices made by asymptomatic women in the United States newly informed that they tested positive for BRCA1 or 2 found that ~13% chose to have prophylactic surgery such as a bilateral mastectomy (Lerman et al., Reference Lerman, Hughes, Croyle, Main, Durham, Snyder, Bonney, Lynch, Narod and Lynch2000). Because this reduces the lifetime risk of breast cancer in BRCA-positive women by more than 95% (Watson, Reference Watson2013), this is the most effective preventive choice that can be made. A similarly timed Dutch study found 51% of such women opted for prophylactic surgery (Meijers-Heijboer et al., Reference Meijers-Heijboer, Verhoog, Brekelmans, Seynaeve, Tilanus-Linthorst, Wagner, Dukel, Devilee, van den Ouweland, van Geel and Klijn2000), so it is possible that the numbers choosing this option would be higher; but we have, to date, no definitive empirical evidence that the cultural or individual values that might account for these dramatic differences (Klitzman and Chung, Reference Klitzman and Chung2010) can be effectively addressed. Thus, we will (again, conservatively) assume only the 13% rate identified in the study of U.S. women. For the remaining 87% of women who test positive, 24–35% will manifest breast cancer prior to the age of routine screening, which USPSTF (Siu and the U.S. Preventive Services Task Force, Reference Siu2016) recently revised to begin at age 50. All but 1–2% of these early cases will manifest between the ages of 30 and 50, thus benefitting from early surveillance beginning at age 30 based on high risk identified through genetic testing (in the absence of FHx).

The last of the above variables we can estimate in a straightforward manner. Data cited in American Cancer Society recommendations for MRI as an adjunct to mammography show MRI sensitivity to be ~100% in the United States (American Cancer Society, NDc), four times more sensitive than mammography (25%); while both MRIs and mammography enjoy specificity of greater than 95% in the U.S. The cost of MRIs as an adjunct to mammography is ~$1121 (Rosenthal, Reference Rosenthal2013). Multiplied by 109 women (see below) who test positive for BRCA but do not choose prophylactic surgery (which would eliminate need for MRI adjunct under ACS guidelines), and estimating 35 preventive MRIs per woman between ages 30 and 65, the estimated cost is ~$4.2 M (we will subtract this cost from cost-of-treatment savings at the end of this analysis).

With these background contexts in mind, lets begin our analysis with a few basic facts: Most early intervention aimed at prevention or early detection of breast cancer incorporate risk categories based on FHx (US Preventive Services Task Force, ND; American Cancer Society, NDd). For those lacking FHx, genetic testing is a viable (though still imperfect) alternative for identifying some inherited disease risk. BRCA testing will identify genetic variables associated with increased risk for inherited breast cancer in approximately 0.25% of the population. (Anglian Breast Cancer Study Group, 2000; Cancer.gov, NDa) Identification of risk can indicate early intervention that significantly reduces negative outcomes associated with breast cancer, either through prophylactic surgery or earlier detection (see above). Most importantly for our purposes here, breast cancer treatment costs are significantly lower if diagnosed at an earlier stage (Blumen et al., Reference Blumen, Fitch and Polkus2016). Exactly how much less expensive will depend on a number of variables.

A 2016 retrospective analysis of insurance claims for commercially insured women with newly diagnosed breast cancer compared costs of treatment for breast cancer categorized by different ‘stages at diagnosis’ after 1 and 2 years (Blumen et al., Reference Blumen, Fitch and Polkus2016). Since we are concerned with total costs, we will focus on the 2-year time-point as the most comprehensive analyzed in the study. For cancers diagnosed at stage 0 or I/II, average costs were ~$84,500; for stages III or IV, costs averaged ~$171,000. Sixty-one percent of breast cancer cases are diagnosed in stages 0, I or II (Cancer.net, ND) (although it should be noted that this percentage is skewed toward early detection as it reflects populations that generally have access to FHx as an indicator of risk, which adoptees do not), so we will assume a weighted average ‘breast cancer treatment cost savings’ from prophylactic surgery to be ~$118,235, reflecting the idea that 61% of the cases avoided would be early stage. Average cost of prophylactic bilateral mastectomy, according to a spokesman for the Susan G. Komen Foundation, is ~$15,000 (Watson, Reference Watson2013); thus, the potential net lifetime cost savings per case is ~$103,000, which can be applied to ~75% (lifetime breast cancer risk for BRCA) of the 13% of these BRCA-positive women who choose this preventive action.

For the remaining 87% of women who test positive for BRCA (those who do not choose prophylactic surgery), we will estimate cost savings in two categories: those manifesting breast cancer prior to the age of routine screening with mammography and, in our cases, MRIs as an adjunct; and those manifesting breast cancer after this age. In the first of these categories, 24–35% would be expected to manifest cancer prior to the age of 50. (Anglian Breast Cancer Study Group, 2000; Chen and Parmigiani, Reference Chen and Parmigiani2007; Bellcross, ND) It is unlikely that – for these women in our cohort of adoptees – BRCA-related breast cancer would be found at a particularly early stage absent genetic testing because no indicator of high risk (namely, FHx) would motivate early screening of any type, and BRCA-related cancers are especially difficult to detect. In these cases, by subtracting the average treatment cost of stage 0, I/II from the average treatment costs for stages III and IV, the average ‘breast cancer cost savings’ from diagnosis prior to stage III (due to undertaking early screening interventions because of their identification as high risk through genetic testing) would be ~$86,500. At an average cost of $102 per mammography, (Health Costhelper, NDa) costs of annual mammography beginning at age 30 (again, all but 1–2% will manifest between age 30–50) until the age of routine screening would be $2040. Thus, the net saving for delivery of healthcare for this category of BRCA-positive women who manifest breast cancer prior to age 50, would be ~$84,500. We will assume these savings for all of these pre-age-50 cases, given the near 100% sensitivity of MRIs for BRCA cancer cases, and the lack of screening recommendations prior to this age absent FHx indicators (which our cohort lacks). Again, we will subtract the cost of MRIs at the end of our overall breast cancer ‘cost-of-treatment’ savings.

If we now apply the above numbers to our cohort of 100,000 adoptees, we can see significant potential cost savings in terms of delivery of healthcare for breast cancer: ½ of our cohort would be expected to be women. About 0.25% of this sub-cohort of 50,000 would be expected to test positive for BRCA (Anglian Breast Cancer Study Group, 2000), or 125 women. Thirteen percent of those 125 women who test positive would choose prophylactic surgery (~16 women), and ~75% of these BRCA positive women would otherwise likely manifest breast cancer during their lifetime (~12 women). Thus, the net lifetime cost savings of delivery of healthcare for these cases would be ~$1,250,000 ($103,000 × 12 cases avoided).

For the remaining 109 women in our cohort who test positive, 24–35% (26–38 women) would be expected to realize saving through earlier identification of the disease than would happen under routine screening guidelines where no higher risk is identified, since these women would manifest breast cancer prior to the age of current routine screening.. The net saving for delivery of healthcare here would be somewhere between $2,197,000 ($84,500 × 26 women – 24%) and $3,211,000 ($84,500 × 38 women – 35%).

Assuming an overall lifetime 75% manifestation of breast cancer for women who test positive but do not choose prophylactic surgery, there should be ~82 expected cases of breast cancer within this sub-group of 109 women in our cohort in total. Subtracting 26–38 cases of breast cancer that manifest prior to age 50 (discussed above), there should remain ~44–56 cases of breast cancer expected to manifest after age 50. Since the sensitivity of MRI is near 100% in the U.S. (ACS guidelines identify MRI as particularly effective in BRCA-related detection), and MRI adjuncts are only recommended for women who can be identified as at least 20–25% increased risk, and since this higher risk is unlikely to be known without genetic testing in adopted women who lack FHx, we can also project a savings from earlier detection in this group.

Here, we will again (conservatively) presume that breast cancer is identified early (prior to stage III), by all ‘routine’ means of detection, in 61% of all breast cancer cases (again, the significant majority of women in the general population have access to FHx to indicate when early screening or supplemental screening is needed, skewing these data toward earlier detection than might be expected in adoptees who lack FHx). This means that adding MRI as adjuncts to mammography, offers the potential for earlier detection in 39% of these 44–56 women – representing ~18–22 cases of earlier detection. None of these cases post-age 50 would represent additional mammograms (as these are recommended for everyone at this age), so the subtraction of mammogram costs is not warranted for this group (although added MRI costs would remain – again, we will subtract these costs at the end of this analysis). This results in an average savings of $86,500 per case of early detection that would not otherwise have occurred. Total savings here would represent $1.5 M–$2 M.

Given that the lower pre-50 cost savings should correlate to the higher post-50 cost savings (as lower number of cases pre-50 means higher number of cases post-50), adding the cost savings from post-age 50 early detection due to MRIs as adjunct screening ($1.5 M–$2 M), to the savings from pre-age-50 early detection ($2.2 M–$3.2 M) and savings from prophylactic bilateral mastectomy (~1.25 M) would total ~$5.5 M–$6 M.

Subtracting the cost of MRIs (discussed above) over 35 years for all but the 13% of BRCA-positive women identified who chose prophylactic surgery (~$4 M), the net cost savings in delivery of healthcare should be ~$1.5 M–$2 M from breast cancer treatment costs.

Ovarian cancer savings

Significantly, breast cancer is not the only condition with which BRCA is associated. According to NCI and American Cancer Society estimates, 35% (Cancer.gov, NDb) up to 70% (American Cancer Society, 2016) of BRCA-positive women will develop ovarian cancer by age 70. These percentages of our sub-cohort of 125 BRCA-positive female adoptees equals ~44–88 women. Risk-reducing salpingoopherectomy (RRSPO) after child-bearing is completed is highly effective and decreases all-cause mortality. As RRSPO is the only effective available intervention, we will limit our analysis of cost savings for ovarian cancer to prophylactic surgical intervention. Again, we will (conservatively) assume ~13% of these women will choose prophylactic surgery (bilateral prophylactic salpingo-oophorectomy), reducing their risk of ovarian cancer by 90% (Cancer.gov, NDc). This represents ~6–12 avoided cases among the 16 women who choose prophylactic surgery, depending on which rate of estimated cancer manifestation proves more accurate (35% or 70%). The cost of prophylactic salpingo-oophorectomy is ~$10,000–$15,000 (Health Costhelper, NDb). provided to 16 (13% of 125 BRCA-positive) women who choose prophylactic surgery, this represents a cost of ~$250,000.

Treatment for ovarian cancer is both notoriously poor and very costly: >$210,000 per case based on a 2017 Kentucky study. (Louis et al., Reference Louis, Christophe and Cooper2017) (and, as one analysis of the economics literature on cancer costs noted, Kentucky is generally less expensive than other states when it comes to cancer treatments and other healthcare costs) (HerWarOnCancer, ND). Using these (again conservative) numbers, our expected cost savings from avoided ovarian cancer cases due to BRCA testing is ~$1.25 M (6 cases) to $2.5 M (12 cases), for a net savings of $1 M–$2.25 M

When these savings from ovarian cancer is added to the combined savings from breast cancer through BRCA testing, total savings from adding BRCA to the genetic testing panel is ~$2.5 M–$4.5 M.

While this savings from BRCA testing alone would not offset the estimated ~$22.5 M–$25 M cost of testing a cohort of 100,000 adoptees, it is significant when added to the net ~$19.5 M treatment savings from testing for Lynch syndrome as part of the same panel (~$24 M in late-stage treatment savings minus ~$4.5 M for preventive colonoscopies). Indeed, it makes testing at worst cost-neutral (or nearly cost-neutral). Furthermore, ‘this cost-neutrality is based upon only a couple of potentially several disease-associated gene variants, and the most common of the several actionable conditions with which each of these particular variants are associated (and which we have not fully enumerated here). Most important, these estimated savings do not account for many other inherited disease conditions that might also be included in the panel while remaining within the cost parameters we estimated ($225–$250 per panel test)’.

Additional potential for savings (not included)

Were higher estimates of late-stage treatment costs to prove more accurate (e.g., the estimate of $310,000 for late stage colon cancer rather than the $120,000 we assumed), or if higher rates of prophylactic surgery were realized (closer to the 51% realized in the Dutch study, as opposed to the 13% we assumed based on the U.S. study), very significant savings might be realized from Lynch syndrome and BRCA testing alone. These savings are likely to be compounded by additional conditions tested in the panel. In addition, many other additional savings are likely to be realized by identification of increased risk through phenomena known to occur with current genetic testing. For example, if risk identification motivated better compliance with screening recommendations, since ~30% of commercially insured women do not follow USPSTF guidelines for screening (Smith et al., Reference Smith and Hochhalter2011; Blumen et al., Reference Blumen, Fitch and Polkus2016). Moreover, a distinct advantage of genetic testing is that other biological family members are identified at risk once one individual has been so identified. This can lead to ‘cascade testing’ that extends potential benefits to other individuals. For example, biological children of adoptees would now be able to take advantage of early intervention based on risks that would otherwise not be identified.

For reasons we describe in our analysis of savings for each condition above, we suspect that the higher estimates of savings will indeed prove more accurate; that the price of testing will decrease due to both advancing technologies and savings from more efficient ‘batching’ through greater volume; that choices to undertake more effective (and cost-saving) prophylactic options for BRCA risks will increase; and that substantial additional cost savings will be realized from other candidate tests included in the panel, as well as from cascade testing of adoptee offspring. Even in the absence of these increased benefits, however, the potential for cost neutrality itself should be sufficient to explore targeted screening for a population who without this will suffer an avoidable disparity in access to inherited disease information.