Alice Chung, MD
Armando Giuliano, MD
As reviewed in this issue of The ASCO Post, Losk and colleagues from Dana-Farber/Brigham and Women’s Cancer Center report their institution’s implementation of a protocol of surgeon-initiated genomic profiling of estrogen receptor–positive tumors in women with early breast cancer that resulted in a significant reduction in the time interval between the day of the last definitive breast surgery and initiation of chemotherapy.1 This protocol was developed through a systematic multidisciplinary collaboration between surgeons and medical oncologists in which patients were evaluated in the clinic in a multidisciplinary setting. The protocol provided surgeons with specific criteria for Oncotype DX testing, which was ordered by the surgeon one day following release of surgical pathology results.
According to the protocol, the surgeon reported pathology results to the medical oncologist, who had already evaluated the patient in the multidisciplinary clinic. This communication provides the opportunity for the medical oncologist to order Oncotype DX testing if the patient’s tumor does not meet standard criteria for testing. The authors compared the days from the last definitive breast surgery to Oncotype DX ordering, Oncotype DX result reporting, and chemotherapy initiation in 472 patients treated prior to the protocol implementation vs 248 patients treated after protocol implementation. The time interval to Oncotype DX ordering, Oncotype DX result reporting, and chemotherapy initiation were shown to be reduced by 7.3, 6.3, and 6.4 days, respectively. The authors conclude that these reductions in wait times have the potential to improve quality of care for the patients to whom the testing criteria apply.
Commendable Protocol but Not Always Feasible
Timing of chemotherapy initiation is critical in maximizing the efficacy of therapy,2-4 and any tools that minimize delays in treatment should be utilized. Although some surgeons may be resistant to accepting the responsibility of ordering a test that was developed for systemic therapy recommendations, surgeon-initiated Oncotype DX testing likely already occurs in many centers, although not with a standard protocol. The advantage to the protocol is that it provides guidelines for ordering, which minimize struggling with insurance companies and relieve the surgeon from the potential burden of ordering the test inappropriately.
The protocol ultimately made a difference in the quality of care for only a limited number of patients. It would be valuable to assess whether [it] reduced the time to onset of radiation or hormonal therapy.— Alice Chung, MD and Armando Giuliano, MD
Tweet this quote
However, the procedure outlined by Losk and colleagues, while commendable, is not always feasible, depending on the practice setting. Many surgeons who treat breast cancer in the United States lack the amenity of working in a multidisciplinary setting. If standardized criteria for ordering Oncotype DX testing were applied among community surgeons, reduction in the time to chemotherapy initiation might not necessarily be observed. It is important to acknowledge that other factors may contribute to delays in chemotherapy initiation that were not addressed in the Losk et al study, such as patient demographics, surgical treatment, treatment setting, delays caused by insurance companies, timing of release of pathology results to the surgeon, and laboratory technical factors.5
With the advent of tumor genomic profiling, adjuvant chemotherapy recommendations have declined, especially in the estrogen receptor–positive population.6-10 In the Losk et al study, chemotherapy was utilized in only 17.8% (pre-protocol) and 16.1% (post-protocol) of patients who had Oncotype DX testing. Therefore, the protocol ultimately made a difference in the quality of care for only a limited number of patients. It would be valuable to assess whether implementation of this protocol reduced the time to onset of radiation or hormonal therapy. Other factors that would be interesting to assess include the psychological impact of delay in receiving an adjuvant treatment plan for patients and increase in work hours for providers that may result from protocol implementation.
Finally, as data from genomic profiling of breast tumors continue to evolve, use of additional genomic assays is increasing. A report from the MINDACT trial demonstrated the clinical utility of the 70-gene signature in the selection of adjuvant chemotherapy for patients with T1–3N0–1 breast cancer.11 It may be important to consider how additional types of genomic profiling might be incorporated into the Dana-Farber/Brigham and Women’s protocol.
Closing Thoughts
Surgeon-initiated testing of genomic assays can reduce the time interval to systemic therapy, as shown in this study, and may improve the quality of patient care. Implementation of protocols for surgeon-initiated genomic profiling of tumors is likely more feasible in clinics that function in a multidisciplinary setting. Development of criteria for utilization of multiple genomic assays may be required, as validation of additional genomic assays increases. ■
DISCLOSURE: Drs. Chung and Giuliano reported no conflicts of interest.
Drs. Chung and Giuliano are general surgeons at Cedars-Sinai Medical Center, Los Angeles.
REFERENCES
1. Losk K, Freedman RA, Lin NU, et al: Implementation of surgeon-initiated gene expression profile testing (Oncotype DX) among patients with early-stage breast cancer to reduce delays in chemotherapy initiation. J Oncol Pract 13:e815-e820, 2017.
2. Gagliato Dde M, Gonzalez-Angulo AM, Lei X, et al: Clinical impact of delaying initiation of adjuvant chemotherapy in patients with breast cancer. J Clin Oncol 32:735-744, 2014.
3. Lohrisch C, Paltiel C, Gelmon K, et al: Impact on survival of time from definitive surgery to initiation of adjuvant chemotherapy for early-stage breast cancer. J Clin Oncol 24:4888-4894, 2006.
4. Raphael MJ, Biagi JJ, Kong W, et al: The relationship between time to initiation of adjuvant chemotherapy and survival in breast cancer: A systematic review and meta-analysis. Breast Cancer Res Treat 160:17-28, 2016.
5. He X, Ye F, Zhao B, et al: Risk factors for delay of adjuvant chemotherapy in non-metastatic breast cancer patients: A systematic review and meta-analysis involving 186982 patients. PLoS One 12:e0173862, 2017.
6. Loncaster J, Armstrong A, Howell S, et al: Impact of Oncotype DX breast recurrence score testing on adjuvant chemotherapy use in early breast cancer: Real world experience in Greater Manchester, UK. Eur J Surg Oncol 43:931-937, 2017.
7. Geffen DB, Abu-Ghanem S, Sion-Vardy N, et al: The impact of the 21-gene recurrence score assay on decision making about adjuvant chemotherapy in early-stage estrogen-receptor-positive breast cancer in an oncology practice with a unified treatment policy. Ann Oncol 22:2381-2386, 2011.
8. Joh JE, Esposito NN, Kiluk JV, et al: The effect of Oncotype DX recurrence score on treatment recommendations for patients with estrogen receptor-positive early stage breast cancer and correlation with estimation of recurrence risk by breast cancer specialists. Oncologist 16:1520-1526, 2011.
9. Lo SS, Mumby PB, Norton J, et al: Prospective multicenter study of the impact of the 21-gene recurrence score assay on medical oncologist and patient adjuvant breast cancer treatment selection. J Clin Oncol 28:1671-1676, 2010.
10. Partin JF, Mamounas EP: Impact of the 21-gene recurrence score assay compared with standard clinicopathologic guidelines in adjuvant therapy selection for node-negative, estrogen receptor-positive breast cancer. Ann Surg Oncol 18:3399-3406, 2011.
11. Cardoso F, van’t Veer LJ, Bogaerts J, et al: 70-Gene signature as an aid to treatment decisions in early-stage breast cancer. N Engl J Med 375:717-729, 2016.
