Journal of Surgical Oncology. 2015 Jun;111(8):935-40.

The Impact of Genomic Testing on the Recommendation for XRT Therapy in Patients with Ductal Carcinoma in Situ: A Prospective Clinical Utility Assessment of the 12-gene DCIS Score™ Result

 

Alvarado M1, Carter DL2, Guenther JM3, Hagans J4, Lei RY2, Leonard CE5, Manders J6, Sing AP7, Broder MS8, Cherepanov D8, Chang E8, Eagan M8, Hsiao W9, Schultz MJ10.

 

1University of California, San Francisco, California.
2Rocky Mountain Cancer Centers, Aurora, Colorado.
3St. Elizabeth Healthcare, Edgewood, Kentucky.
4The Surgical Center of Central Arkansas, Little Rock, Arkansas.
5Rocky Mountain Cancer Centers, Littleton, Colorado.
6The Christ Hospital, Cincinnati, Ohio.
7Genomic Health, Inc., Redwood City, California.
8Partnership for Health Analytic Research, LLC, Beverly Hills, California.
9University of Southern California, Los Angeles, California.
10University of Maryland St. Joseph Medical Center, Towson, Maryland.

 

Abstract

Background and Objectives: Twenty percent of breast cancers are ductal carcinoma in situ (DCIS), with 15-60% local recurrence (LR) after surgery. Radiotherapy reduces LR by 50% but has not impacted survival. The validated Oncotype DX® 12-gene assay (DCIS Score) provides individualized 10-year LR estimates. This is the first study to assess whether DCIS Score impacts physicians’ recommendations for radiation.

Methods: 10 sites enrolled women (9/2012-2/2014) with DCIS eligible for breast-conserving therapy, excluding patients with invasive carcinoma and planned mastectomy. Prospective data collected included clinicopathologic factors, DCIS Score assay, and treatment recommendation before and after the assay result was known.

Results: In 115 patients (median age: 61 years; 74.8% postmenopausal), median DCIS size was 8mm; 20% were nuclear grade 1, 46.1% grade 2; 64.4% reported necrosis. 86.1% were ER+, 79.1% PR+ (immunohistochemistry assay). Median DCIS Score: 29 (range: 0-85). Pre-assay, 73% (95%-CI: 64.0-80.9%) had radiotherapy recommendations vs. 59.1% (95%-CI: 49.6-68.2%) post-assay (p=0.008). Physicians rated DCIS Score as the most impactful factor in planning treatment.

Conclusions: The radiotherapy recommendation changed from pre-assay to post-assay 31.3% (95%-CI: 23.0-40.6%) of the time—a clinically significant change. This study supports the clinical utility of the DCIS Score and indicates that the test provides additional, individualized information on LR risk.

PMID: 26031501

 

SUPPLEMENT

The aim of treatment of ductal carcinoma in situ (DCIS), a stage 0 breast cancer that comprises 20% of all breast cancers diagnosed by mammography, is to prevent the occurrence of invasive disease and any local recurrence (LR) of DCIS.[1-3]. Although breast conserving therapy is an appropriate treatment option for most patients [1], addition of whole breast irradiation (XRT) after excision reduces the relative LR risk by about 50% but with no shown impact on survival [1,4]. Literature has not reported patient subgroups that do not receive some benefit from XRT [4], so many patients, even those with low likelihood of recurrence, may continue to be treated with XRT. LR risk has been historically based on clinicopathologic factors, such age and tumor grade, but such factors are only proxy for the biologic aggressiveness of the disease. The Oncotype DX® Breast Cancer assay for DCIS (DCIS Score) is the first multigene expression assay that is based on the biology of the tumor and is generated from an algorithm that includes 12 of the 21 genes in the Oncotype DX invasive assay, generating individualized estimates of 10-year risk of any LR (DCIS or invasive carcinoma) and invasive LR [5]. The clinical validity of the DCIS Score result and its independent association with LR for any or an invasive recurrence was previously shown in the Eastern Cooperative Oncology Group (ECOG) E5194 study [5]. The current study is the first to assess if the DCIS Score assay influences patient management or the “clinical utility” of the assay in clinical practice [6] by examining the impact of the DCIS Score result on the recommendation for XRT in patients after primary surgical excision of their tumors.

We analyzed data collected from medical charts of 115 DCIS patients, enrolled at 10 centers between September 2012 and February 2014. Mean age was 60.1 years (SD: 10.2); 74.8% of patients were postmenopausal; and median DCIS size was 8mm. 20% of patients had a nuclear grade 1, 46.1% had a grade 2. Necrosis was reported as present in 64.4%. Of these patients, 86.1% were ER+ and 79.1% PR+ (by immunohistochemistry assay). Mean DCIS Score was 30.7 (SD: 22.1), ranging from 0 (n=11) to 85 (n=1). Eighty-four patients were recommended XRT pre-assay (73%; 95%-CI: 64%-80.9%), 26 patients had a change to no XRT recommendation post-assay (22.6%) – a 31.0% change. Of 31 patients who were not recommended XRT pre-assay (27%), 10 patients were recommended XRT post-assay (8.7%), reflecting a change of 32.3%. Only 59.1% of patients were recommended XRT post-assay versus 73% pre-assay (p=0.008). The change in XRT recommendation was statistically significant in the DCIS Score low risk group and the high risk group. Overall, patients had a 31.3% (95%-CI: 23%-40.6%) change in recommendation for XRT from pre-assay to post-assay, which is both statistically significant and clinically meaningful. Considering a variety of factors, physicians rated the DCIS Score as most impactful on their treatment recommendations on a scale of 1 to 5.

Our study revealed the use of the DCIS Score leads to meaningful changes in XRT recommendation, indicating that the DCIS Score result adds value beyond traditional clinicopathologic factors. The use of this test by physicians in management of patients with DCIS may aid in making treatment recommendations that reduce both under- and overtreatment with XRT by incorporating information based on patients’ individual underlying tumor biology and making the treatment of DCIS truly personalized.

 

REFERENCES

  1. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®): Breast Cancer. Version 3.2015.
  2. Kerlikowske K. Epidemiology of ductal carcinoma in situ. J Natl Cancer Inst Monogr 2010;2010(41):139-141.
  3. American Cancer Society. Breast Cancer Facts & Figures 2013-2014. Atlanta: American Cancer Society, Inc. 2013.
  4. Hughes LL, Wang M, Page DL, et al.: Local excision alone without irXRT for ductal carcinoma in situ of the breast: a study of the Eastern Cooperative Oncology Group. J Clin Oncol 2009;27:5319-5324.
  5. Solin LJ, Gray R, Baehner FL, et al.: A multigene expression assay to predict local recurrence risk for ductal carcinoma in situ of the breast. J Natl Cancer Inst 2013;105(10):701-710.
  6. Febbo PG, Ladanyi M, Aldape KD, et al.: NCCN Task Force report: Evaluating the clinical utility of tumor markers in oncology. J Natl Compr Canc Netw 2011;9(Suppl 5):S1-32, quiz S33.

 

ACKNOWLEDGEMENTS

This research was funded by the Novartis Pharmaceuticals Corporation.

 

CONTACT

Michael S. Broder, MD, MSHS President Partnership for Health Analytic Research, LLC 280 S. Beverly Drive, Suite 404 Beverly Hills, CA 90212 mbroder@PHARLLC.com www.pharllc.com

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