Genetic testing of all women newly diagnosed with a common type of breast cancer could save money in the short term by cutting down on the use of chemotherapy; however, the long-term outlook is unclear, according to a study published April 24 in the Journal of the National Cancer Institute.
About 60% of newly diagnosed breast cancers in the U.S. are positive for hormone receptors (HR) and negative for human epidermal growth factor receptor 2 (HER2), with no involvement of lymph nodes. Along with hormonal therapy, these women may get adjuvant chemotherapy to help prevent cancer recurrence. But the value of chemotherapy has been debated for women at lower risk.
A research team led by Angela Mariotto, PhD, from the U.S. National Cancer Institute (NCI) examined the potential economic impact if all women with these kinds of cancers were tested with the Oncotype DX 21-gene assay (Genomic Health). The assay helps predict cancer recurrence based on a score of 1 to 100.
The study was based on deidentified population-based data from the NCI's Surveillance, Epidemiology, and End Results (SEER) program and Medicare costs, including reimbursement and out-of-pocket costs. The researchers modeled a cost of $3,400 per patient for testing with the Oncotype assay, which they noted was similar to another product that is used less commonly, called MammaPrint (Agendia).
Mariotto and colleagues concluded that across-the-board testing of women with HR-positive, HER2-negative, node-negative breast cancer could save the U.S. health system $50 million in the first year after the initial diagnosis by skipping chemotherapy in women at lower risk. This equates to 1.8% of total treatment costs for the first year, which the authors described as a small amount of savings.
"Our results suggest that personalizing care by selecting chemotherapy based on [risk score] has the potential to lower short-term costs, even after considering the added costs of expanded Oncotype DX testing," they wrote. "The results are intended to inform policy and payor discussions about the costs of personalized cancer care in the U.S."
Aside from costs, this strategy would also spare patients the harms of chemotherapy, including long-term morbidity, fatigue, hair loss, neurotoxicity, and early menopause, the researchers noted.
Putting genetic testing to the economic test
The Oncotype DX assay assesses risk based on the expression of 21 genes -- 16 are cancer-related and five are reference genes -- in a tumor sample from a biopsy or after surgery.
The test has been incorporated into a range of professional treatment guidelines, including those from the National Comprehensive Cancer Network, the American Society of Clinical Oncology, and the European Society for Medical Oncology.
The analysis by Mariotto et al in JNCI examined the impact in the U.S. of the Trial Assigning Individualized Options for Treatment (TAILORx), which was published by Dr. Joseph Sparano and colleagues in the New England Journal of Medicine (July 12, 2018, Vol. 379:2, pp. 111-121). This prospective study evaluated the role of Oncotype DX testing in almost 10,000 women with HR-positive, HER2-negative cancer and no lymph node involvement.
Those with an Oncotype DX risk score between 11 and 25 (intermediate risk of recurrence) after surgery were randomized to endocrine therapy alone or to endocrine therapy with chemotherapy. The researchers reported a similar rate of recurrence (5%) for these women, regardless of whether their regimen included chemotherapy.
Investigators on TAILORx concluded that the 21-gene assay may help identify women who do not need adjuvant chemotherapy, "especially those who are older than 50 years of age and have a recurrence score of 25 or lower, as well as women 50 years of age or younger with a recurrence score of 15 or lower."
However, they also reported some women who were 50 years or younger with a recurrence score between 16 and 25 in an exploratory analysis of the trial, leaving some uncertainty for this subset of patients.
Potential cost savings for most scenarios studied
In their JNCI paper, Mariotto and colleagues noted that prior to the TAILORx release, about 50% of women overall with HR-positive, HER2-negative early breast cancer were undergoing Oncotype testing. Use varied depending on age, ranging from 34.8% to 57.2%.
"The evidence provided by the TAILORx trial is likely to increase use of gene expression profile testing, leading to potential cost savings (and harm reduction) by omitting chemotherapy among women who will not benefit from it," the authors wrote.
If all women with the type of cancer examined in TAILORx were tested, then the annual cost in the first year of diagnosis for the assay would rise from $115 million to $231 million. If all women with a score of 0 to 25 did not get adjuvant chemotherapy and those with a score above 25 had chemotherapy, then the estimated costs for chemotherapy would drop by 8%, or $338 million, resulting in the net savings estimate of $50 million.
The researchers also looked at a range of other scenarios, including the potential impact if women younger than 50 with a score of 16 to 25 (the area of uncertainty in TAILORx) all wound up getting chemotherapy, or if chemotherapy use for those with a score over 26 did not increase.
"The predicted small savings in total initial care costs if care followed the TAILORx trial results was robust across most assumptions and ranged from savings of $32 million to $102 million," the authors wrote. "However, if 100% of women < 50 years who had tumors with [risk score] 16-25 received chemotherapy, total initial care costs would increase by $105 million from costs in the pretrial period (a 4% increase in total costs)."
However, "the absolute reduction in risk of recurrence with chemotherapy seen in TAILORx was small for this subgroup, so it is not clear what the actual chemotherapy patterns will be for this subgroup moving forward," the researchers added.
Addressing financial incentives for test use
Mariotto and colleagues acknowledged a number of other limitations of the study; for example, the Oncotype DX scores "have imperfect sensitivity and specificity."
"Hence, some women with scores from 11-25 could forego chemotherapy but may actually be destined to have a recurrence," they wrote.
Misclassifications and recurrences that occur in women who had chemotherapy would add to the lifetime costs of cancer care.
A range of practical factors also affect the use of testing, including patient and physician preferences and competing financial incentives for stakeholders. Payors have incentives to promote Oncotype DX testing due to small short-term savings from the lower use of chemotherapy, but oncologists and infusion centers have fewer incentives to decrease rates of chemotherapy administration, Mariotto and colleagues wrote.
"It will be important to evaluate how incentive and value-based reimbursement models that consider de-escalation of treatment will affect actual patterns of care and costs," the authors concluded.
