DCIS Topic-Driven Round Table: Decision-Making and Treatment Choices
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Facilitator Deb Hackenberry is joined by Cecilia Hammond, Senior Medical Science Liaison at Genomic Health, to discuss better decision-making and your treatment choices with DCIS.
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DCIS Topic-Driven Round Table: Decision-Making and Treatment Choices
- 1. EXACT SCIENCES Embracing Genomics in Cancer Care: Oncotype DX® Assay for DCIS Cecilia Hammond MSN, RN Exact Sciences Medical Affairs 1 February 26, 2020
- 2. EXACT SCIENCES 2 • How do we define genetics and genomics and what is their importance in cancer care? • How does genomics help in treatment decisions for DCIS? • What is the Oncotype DX® Breast DCIS Score™? • Questions/Discussion - throughout, please! Cancer Care in 2020: What will we discuss today?
- 3. EXACT SCIENCES How do we define genetics and genomics? 3 How are they different? Does it matter?
- 4. EXACT SCIENCES 4 • GENETICS: The study of heredity • GENOMICS: The study of genes and their functions Genetics examines the function of a single gene (or chromosome) while genomics examines groups of genes and their relationships in order to identify their combined influence on an organism Flower / Garden World Health Organization Definitions: Genetics & Genomics
- 5. EXACT SCIENCES 5 • Can be used to predict risk of disease development ̶ BRCA1 & 2: Increased risk of breast, ovarian, and other tumors ̶ APC (Adenomatous polyposis coli): Increased risk of familial adenomatous polyposis/colon cancer • Can be used to locate “targets” for intervention • Generally involves mutations, variations Clinical Utility of Genetics in Oncology
- 6. EXACT SCIENCES 6 • Early and accurate diagnoses • Greater individualization of treatment decisions • Targeted therapy based on individual disease • Greater likelihood of clinical trial success • More rational drug discovery • Faster drug development – Patient selection – Trial design Normal gene expression and interaction - BIOLOGY Clinical Utility of Genomics in Oncology
- 7. EXACT SCIENCES Ductal Carcinoma In-Situ (DCIS) 7
- 8. EXACT SCIENCES 8 Ductal Carcinoma In Situ (DCIS)
- 9. 9 Approximately 20% of All New Breast Cancers in the US Are DCIS1 • Advances in technologies for screening and diagnosis have led to an increase in detection of DCIS – It is estimated that by 2020, over 1 million women in the US will be living with a diagnosis of DCIS compared to 500,000 in 20052 BUT… • Methods for assessing risk of local recurrence (LR) and making treatment decisions have not kept pace with diagnostic advances Alvarado et al. J Surg Oncol. 2015; Allegra et al. J Natl Cancer Inst. 2010.
- 10. 10 Mammography Screenings Link to Rise in DCIS Incidence Percent Change in the Age-Adjusted Incidence of DCIS, Invasive Breast Cancer, and Mammography After Introduction of Widespread Screening Mammography Virnig et al. AHRQ. 2009.
- 11. How Does Your Doctor Make a Treatment Recommendation for DCIS? 1. Ernster et al. J Natl Cancer Inst. 2002. 2. NCCN Guidelines in Breast Cancer. v3.2014. 3. Fisher et al. J Clin Oncol. 1998. 4. Wapnir et al. J Natl Cancer Inst. 2011. 5. Bijker et al. J Clin Oncol. 2006. 6. Emdin et al. Acta Oncol. 2006. 7. McCormick et al. ASCO 2012. • Local recurrence rates with surgery alone range from 15-60% (about 50% are invasive)2 Goals of DCIS therapy are varied Multiple factors influence treatment decisions Treatments include:1a • Radiation therapy reduces local recurrence by 50% but has not been shown to impact overall or disease-free survival3-7 Breast conserving surgery Partial or whole breast irradiation Mastectomy Preventive hormonal therapy
- 12. How Does Your Doctor Make a Treatment Recommendation for DCIS? 1. Ernster et al. J Natl Cancer Inst. 2002. 2. NCCN Guidelines in Breast Cancer. v3.2014. 3. Fisher et al. J Clin Oncol. 1998. 4. Wapnir et al. J Natl Cancer Inst. 2011. 5. Bijker et al. J Clin Oncol. 2006. 6. Emdin et al. Acta Oncol. 2006. 7. McCormick et al. ASCO 2012. Goals of DCIS therapy are varied •Prevention of any local recurrence and particularly an invasive local recurrence is a primary consideration •Cosmetic outcomes: mastectomy vs. breast conservation (also referred to as Breast Conserving Surgery (BCS) or lumpectomy) 1. Ernster et al. J Natl Cancer Inst. 2002. 2. NCCN Guidelines in Breast Cancer. v3.2014. 3. Fisher et al. J Clin Oncol. 1998. 4. Wapnir et al. J Natl Cancer Inst. 2011. 5. Bijker et al. J Clin Oncol. 2006. 6. Emdin et al. Acta Oncol. 2006. 7. McCormick et al. ASCO 2012.
- 13. How Does Your Doctor Make a Treatment Recommendation for DCIS? 1. Ernster et al. J Natl Cancer Inst. 2002. 2. NCCN Guidelines in Breast Cancer. v3.2014. 3. Fisher et al. J Clin Oncol. 1998. 4. Wapnir et al. J Natl Cancer Inst. 2011. 5. Bijker et al. J Clin Oncol. 2006. 6. Emdin et al. Acta Oncol. 2006. 7. McCormick et al. ASCO 2012. Multiple factors influence treatment decisions • Estimated risk of local recurrence based on clinical and pathologic features - patient age, size of the tumor, tumor grade. • Estimated risk of invasive recurrence (approximately 50% of recurrences) • Balancing toxicity of therapy for a non-life threatening disease • Patient preference 1. Ernster et al. J Natl Cancer Inst. 2002. 2. NCCN Guidelines in Breast Cancer. v3.2014. 3. Fisher et al. J Clin Oncol. 1998. 4. Wapnir et al. J Natl Cancer Inst. 2011. 5. Bijker et al. J Clin Oncol. 2006. 6. Emdin et al. Acta Oncol. 2006. 7. McCormick et al. ASCO 2012.
- 14. Local Recurrence in DCIS – Recurrence in Same Breast •Non-invasive = cells that line the milk ducts of the breast have become cancer, but they have not spread into surrounding breast tissue. •Invasive Recurrence = cancer that has spread into surrounding breast tissue •Local recurrence rates with surgery alone range from 15-60% of which about 50% are invasive2 •Radiation therapy reduces local recurrence by 50% but has not been shown to impact overall or disease-free survival3-7
- 15. How Does Your Doctor Make a Treatment Recommendation for DCIS? 1. Ernster et al. J Natl Cancer Inst. 2002. 2. NCCN Guidelines in Breast Cancer. v3.2014. 3. Fisher et al. J Clin Oncol. 1998. 4. Wapnir et al. J Natl Cancer Inst. 2011. 5. Bijker et al. J Clin Oncol. 2006. 6. Emdin et al. Acta Oncol. 2006. 7. McCormick et al. ASCO 2012. NCCN Treatment Recommended Treatments Include: Breast conserving surgery Partial or whole breast irradiation Mastectomy Preventive hormonal therapy 1. Ernster et al. J Natl Cancer Inst. 2002. 2. NCCN Guidelines in Breast Cancer. v3.2014. 3. Fisher et al. J Clin Oncol. 1998. 4. Wapnir et al. J Natl Cancer Inst. 2011. 5. Bijker et al. J Clin Oncol. 2006. 6. Emdin et al. Acta Oncol. 2006. 7. McCormick et al. ASCO 2012.
- 16. How Does Your Doctor Make a Treatment Recommendation for DCIS? Surgery Mastectomy/BCS Benefits: reduces risk of local recurrence Risks: poor cosmetic outcome, surgical complications (i.e. bleeding, infection, scar tissue), loss of breast (mastectomy) Radiation Therapy (RT) Whole Breast/Partial Benefits: reduces risk of local recurrence Risks: breast pain, fatigue; long-term adverse effects – breast/skin changes (i.e. scar tissue), cardiac disease, secondary cancers Preventive Hormonal Therapy (HT) ER+ DCIS Benefits: reduces risk of local recurrence of ER+ DCIS & contralateral breast cancer Risks: Hot flashes, sexual dysfunction, mood changes, osteoporosis/bone fractures, joint arthralgia Rare but serious – endometrial cancer, deep vein thrombosis, stroke 16 Allegra et al. J Natl Cancer Inst. 2010. Standard treatment options for DCIS include: mastectomy, BCS alone, BCS + RT, mastectomy + HT, BCS + HT or BCS + RT + HT ER: estrogen receptor HR: hormonal therapy BCS: breast-conserving surgery HT: hormonal therapy RT: radiation therapy
- 17. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) DCIS Primary Treatment 17 DCIS Tis, N0,M0 Lumpectomy without lymph node surgery + whole breast radiation therapy (category 1) with or without boost to tumor bed* OR Total mastectomy with or without sentinel node biopsy + reconstruction (optional) OR Lumpectomy without lymph node surgery + accelerated partial breast irradiation (APBI)* *Whole-breast radiation therapy following lumpectomy reduces recurrence rates in DCIS by about 50%. Approximately half of the recurrences are invasive and half are DCIS. A number of factors determine local recurrence risk: palpable mass, larger size, higher grade, close or involved margins, and age <50 years. If the patient and physician view the individual risk as “low,” some patients may be treated by excision alone. Select patients with low-risk DCIS may be considered suitable for APBI if they meet all aspects of the definition of low-risk DCIS from the RTOG 9804 trial, including screen-detected DCIS, low to intermediate nuclear grade, tumor size ≤2.5 cm, and surgical resection with margins negative at >3 mm. Adapted with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Breast Cancer V.2.2019. © 2019. National Comprehensive Cancer Network, Inc. All rights reserved. The NCCN Guidelines® and illustrations herein may not be reproduced in any form for any purpose without the express written permission of NCCN. To view the most recent and complete version of the NCCN Guidelines, go online to NCCN.org. The NCCN Guidelines are a work in progress that may be refined as often as new significant data becomes available. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way. Lumpectomy without lymph node surgery without radiation therapy* (category 2B) OR
- 18. EXACT SCIENCES Oncotype DX® Breast DCIS Score 18 Determining Risk of Recurrence
- 19. The Oncotype DX® Breast DCIS Score • WHAT: The Oncotype DX® Breast DCIS Score is a tissue based test for Patients diagnosed with Stage 0 breast cancer also called ductal carcinoma in situ (DCIS) • HOW: Identifies the expression of 7 cancer-related genes that are expressed in tissue biopsy. • WHY: Helps determine the risk of a DCIS recurrence based on the patient’s individual tumor biology. • RESULTS: • A score ranging from 1 - 100 • Reflects each individual patient’s tumor biology
- 20. Oncotype DX Breast DCIS Score® Test: Gene Selection • Seven breast cancer-related genes (proliferation gene group, PR, GSTM1) were predictive of local recurrence risk in development studies Solin et al. J Natl Cancer Inst. 2013. PR: progesterone receptor GSTM1: Glutathione S-transferase Mu 1 7 Breast Cancer- Related Genes Beta-actin GAPDH RPLPO GUS TFRC Hormone Receptor Group Proliferation Others GSTM1PRKi-67 STK15 Survivin Cyclin B1 MYBL2 5 Reference Genes 20
- 21. EXACT SCIENCES Oncotype DX DCIS Score Results DCIS Score Result What the Score Means Lower than 39 The breast cancer has a low risk of local recurrence. The benefit of radiation therapy is likely to be small. Between 39 and 54 The breast cancer has an intermediate risk of local recurrence. Greater than 54 The breast cancer has a high risk of local recurrence, and absolute benefit of radiation therapy is likely to be greater.
- 22. Oncotype DX® Breast DCIS Score™ Test Personalizes Each Patient’s Treatment Plan with a Refined Risk Assessment • Oncotype DX® Breast DCIS Score™ test: • Quantifies 10-year risk of any local recurrence or an invasive local recurrence • Confirmed in a meta-analysis involving 773 patients • Refined risk estimates with specified clinicopathologic features • Increases clarity and confidence in a patient’s personalized treatment plan A refined risk assessment reflects tumor biology, tumor size, and patient’s age: • Patients with a low-risk of recurrence may be candidates for Breast Conserving Surgery alone • Patients with a high-risk of recurrence may require additional local therapy
- 23. EXACT SCIENCES 23 • Patients diagnosed with Stage 0, or ductal carcinoma in situ (DCIS) • Tested on breast cancer tumor tissue (after surgery) to help determine risk that breast cancer will return in the same breast (local recurrence), either as DCIS or as invasive breast cancer ̶ Helps in the decision for additional therapy with radiation and hormone therapy • Covered by most insurance plans • Patient Assistance Program is also available for those underinsured or uninsured Appropriate Use of Oncotype DX® Assay for DCIS
- 24. Key Clinical Trials • Clinical Validation of the Oncotype DX® Breast DCIS Score™:The ECOG E5194 Analysis • Second Validation of the Oncotype DX® Breast DCIS Score™ : The Ontario Provincial DCIS Cohort Analysis (Breast-Conserving Surgery Alone) • Integrating the Oncotype DX® Breast DCIS Score™ with Prognostic Clinical and Pathological Factors: A Meta-Analysis • Impact of the DCIS Score™ Result on Physicians’ Treatment Recommendations, Alvarado et al. J Surg Oncol. 2015
- 25. First Validation Study: A Prospective Cohort Study • The ECOG E5194 parent study was a non-randomized, prospective, multicenter study that was designed to evaluate treatment using surgical excision without radiation for selected women with DCIS (conducted from 1997 to 2002) Primary Objective • To determine whether there is a significant association between the Breast DCIS Score™ result and local recurrence risk Secondary Objective • To determine whether the Breast DCIS Score result provides value beyond standard clinical and pathologic factors Hughes et al. J Clin Oncol. 2009.
- 26. ECOG E5194: 10-Year Local Recurrence by Risk Group for the Breast DCIS Score™ Solin et al. J Natl Cancer Inst. 2013.; Genomic Health, Data on File. The study validated the Breast DCIS Score result as a predictor of any local recurrence (LR) or an invasive LR • The Breast DCIS Score result provides greater visibility into the risk of LR based on the underlying tumor biology and separates patients with a lower risk from patients with a higher risk of LR Any Local Recurrence Invasive Local Recurrence
- 27. The ECOG E5194 Study Validated the Breast DCIS Score™ Result as a Predictor of Local Recurrence Solin et al. J Natl Cancer Inst. 2013. Any Local Recurrence Invasive Local Recurrence CI: confidence interval; HR: hazard ratio; LR: local recurrence
- 28. Consistent Spectrum of Risk Across Breast DCIS Score™ Validation Studies ECOG E5194 Ontario Cohort Solin et al. J Natl Cancer Inst. 2013. Rakovitch et al. Breast Cancer Res Treat. 2015. Breast DCIS Score Breast DCIS Score
- 29. 29 Integrating the Oncotype DX® Breast DCIS Score™ with Prognostic Clinical and Pathological Factors: A Meta-Analysis
- 30. 30 Refining Risk Estimates Combining Tumor Biology and Relevant Clinical/Pathologic Factors • Some clinical and pathologic features are independently prognostic with regards to local recurrence, but do not provide an individualized risk estimate 30 • Underlying tumor biology provides prognostic information beyond that of clinical and pathologic features Tumor SizePatient AgeTumor Grade Tumor Biology DCIS Score result The prognostic power of the DCIS Score® test could be enhanced by refining risk estimates with relevant clinical/pathologic factors
- 31. 31 Refining Risk Estimates for Individual Patients Integrating Genomic, Clinical, and Pathologic Information • A meta-analysis was conducted to identify the combination of prognostic factors that provide the most precise risk assessment for individual patients with DCIS Rakovitch et al. Breast Cancer Res Treat. 2018. BCS: breast-conserving surgery 31 ECOG-ACRIN E5194 Ontario Cohort Meta-analysis of patients treated with BCS alone (N=773) Tumor Size (≤1 cm, >1-2.5 cm, >2.5 cm) Patient Age (<50 years, ≥50 years) DCIS Score® result
- 32. 32 Combining Genomic, Clinical, and Pathologic Information Identifies More Patients with Recurrence Risk below 10% 0% 10% 20% 30% 40% 50% 60% 70% 0 20 40 60 80 100 10yRiskofLocalRecurrence DCIS Score Meta-analysis: Age ≥ 50 yo, Size ≤ 1 cm Estimate LCL UCL Now 70% of patients in this subgroup would receive risk estimates below 10% E5194 Data Ontario Data (BCS Alone) Solin et al. J Natl. Cancer Inst. 2013.; Rakovitch et al. Breast Cancer Res Treat. 2015.; Rakovitch et al. ASCO 2017. BCS: breast-conserving surgery LCL: lower confidence limit UCL: upper confidence limit
- 33. 33 EXACT SCIENCES PATIENT A 55-year-old patient with 1.4-cm tumor Menopausal Status: Postmenopausal Tumor Type: DCIS Tumor Size: 1.4 cm ER Status (IHC): Positive PR Status (IHC): Positive Histologic Grade: 2 PATIENT B 60-year-old patient with 1.6-cm tumor Menopausal Status: Postmenopausal Tumor Type: DCIS Tumor Size: 1.6 cm ER Status (IHC): 90% Positive PR Status (IHC): 98% Positive Histologic Grade: 3 Comparative Case Study 33
- 34. 3434 Case Study Results PATIENT A RESULTS Clinical Experience Patients with a DCIS Score of 56 had a 22% risk of any local recurrence and a 12% risk of an invasive local recurrence. PATIENT B RESULTS Clinical Experience Patients with a DCIS Score of 24 had a 13% risk of any local recurrence and a 6% risk of an invasive local recurrence.
- 35. 35
- 36. 36
- 37. 37 Impact of the DCIS Score™ Result on Physicians’ Treatment Recommendations Alvarado et al. J Surg Oncol. 2015 A US Multicenter Study
- 38. 38 How Does Knowing the DCIS Score Impact Treatment Recommendations? Patient Characteristics • 10 US centers; 115 patients included in the analysis • Representative of a contemporary patient population – Majority of patients – postmenopausal, ER+, < 2 cm • Both physician groups represented: 5 radiation oncologists, 5 surgical oncologists Alvarado et al. J Surg Oncol. 2015. Primary objective: to estimate the proportion of patients for whom the DCIS Score™ result led to a change in the recommendation for radiation therapy (XRT) • Patient meeting study inclusion criteria is enrolled • Patient characteristics • Pathology; ERPR • Treatment recommendation • DCIS Score report results • Treatment recommendation • Factors affecting physician recommendations DCIS Score ReportProspective Enrollment Collected Pre-Assay Data Collected Post-Assay Data
- 39. 39 The DCIS Score™ Result Impacts Recommendation for Radiation Therapy (XRT) by Revealing Underlying Biology Alvarado et al. J Surg Oncol. 2015. • The DCIS Score result changed the recommendation for XRT 31% of the time (P = 0.008; McNemar’s test) • This degree of change reflects the impact of the additional information regarding the risk of LR and the individual underlying tumor biology that is not evident with the clinical and pathologic features 31 (27.0%) 47 (40.9%) 68 (59.1%) 84 (73.0%)
- 40. 40 Changes in Recommendation for Radiation Therapy Within DCIS Score™ Groups 0 10 20 30 40 50 60 70 80 Low Low Int Int High High No XRT XRT NumberofPatients Pre-Assay Pre-Assay Pre-AssayPost-Assay Post-Assay Post-Assay Low Intermediate High DCIS Score Group • The change in XRT recommendation by DCIS Score result had the greatest impact in the low-risk group • There was a change in the opposite direction for an XRT recommendation in the high-risk group towards XRT after the assay results were known • Overall, incorporation of the DCIS Score result changed XRT recommendations 31.3% of the time, but change was bidirectional, reflecting that the information is useful for identifying patients at lower risk as well as higher risk of LR Alvarado et al. J Surg Oncol. 2015. XRT Recommendation
- 41. EXACT SCIENCES 41 • Genetics and genomics play important roles in cancer care in 2020 and will continue to drive cancer treatment in the future • It is important to understand and treat underlying individual tumor biology • Sometimes personalized care doesn’t involve a “treatment” • Your interactions with clinicians are a KEY factor in receiving optimal care. Closing Thoughts
- 42. Harnessing the Power of Genomics for Personalized Management of DCIS The Oncotype DX® Breast Cancer Assay for DCIS is an important advancement in providing an individualized risk of local recurrence and personalizing treatment for patients with DCIS Proven to risk stratify patients with DCIS in a real-world patient population Enhances conversations between patients and physicians by providing an individualized risk assessment Increases patient and physician confidence in the personalized treatment plan
- 43. Oncotype DX Breast DCIS Score® Test • Integrates tumor biology, patient age, and tumor size to provide accurate risk assessments specific to individual patients • Quantifies individualized 10-year risk of developing any local recurrence and specifically an invasive local recurrence • Validated independently by two prospective studies and subsequent meta- analysis involving 773 patients • Increases clarity and confidence in your personalized treatment plan Solin et al. J Natl. Cancer Inst. 2013.; Rakovitch et al. Breast Cancer Res Treat. 2015.; Rakovitch et al. J Natl Cancer Inst. 2017. Individualized patient prognosis provided by the DCIS Score® test: • Enriches treatments discussions across multiple medical disciplines • Prevents under- and overtreatment that may occur by utilizing clinical and pathologic features alone 43
- 47. Company Confidential Second Validation of the Oncotype DX® Breast DCIS Score™ : The Ontario Provincial DCIS Cohort Analysis (Breast-Conserving Surgery Alone)
- 48. An Observational Patient Cohort • Registry of 5,752 patients with DCIS collected from the Canadian province of Ontario, between 1994 and 2003 Primary Objective • To evaluate if the Breast DCIS Score™ result is associated with the risk of local recurrence (DCIS or invasive) in patients treated with BCS alone with clear margins (no tumor on ink) and no XRT Main Secondary Objectives • To evaluate if the Breast DCIS Score result is independently associated with LR adjusting for other clinical and pathologic factors • To evaluate if the Breast DCIS Score result is associated separately with the risk of DCIS or invasive LR Rakovitch et al. Breast Cancer Res Treat. 2015. BCS: breast-conserving surgery
- 49. Invasive Local Recurrence Rakovitch et al. Breast Cancer Res Treat. 2015. Genomic Health, Data on File. Breast DCIS Score™ Result: 10-Year Invasive or DCIS Local Recurrence by Risk Group in the Ontario Cohort DCIS Local Recurrence • The study showed that the Breast DCIS Score result stratifies patients for risk of an invasive local recurrence • Further, the Breast DCIS Score result was able to stratify patients for risk of a DCIS local recurrence BCS: breast-conserving surgery
Editor's Notes
- Main points: Advances in diagnosis and screening have led to an increase in the number of patients with DCIS. In 2005, 500,000 women were estimated to be living in the US with a diagnosis of DCIS; this number is expected to reach 1 million in 2020. However, treatment decision making has not evolved to keep pace with the advances in detection of these tumors. The traditional measures for assessing risk of recurrence for DCIS are similar to the clinical and pathologic measures used to assess risk of recurrence in invasive breast cancer: age, residual tumor/margin width, grade, histology, size and menopausal status. None of these characteristics, however, provide a quantitative assessment of recurrence risk. Alvarado et al. J Surg Oncol. 2015. Allegra et al. J Natl Cancer Inst. 2010. Leonard et al. SABCS 2016.
- Main Points: Goal of screening mammography is to detect small malignant tumors before they grow large enough to cause symptoms Widespread implementation of screening mammography occurred in the 1980s Incidence of DCIS increased sharply as a result of widespread screening while incidence of invasive breast cancer remain constant Virnig et al. AHRQ 2009.
- This presentation is focused upon harnessing the power of genomics for DCIS management. Foremost in the clinician’s mind is the question of how to make a treatment decision for the patient. These decisions vary according to patient preference, and goals of treatment must be aligned with the patient’s own goals. The decision around recommending XRT is dependent on an assessment of LR risk with an assumption that around half of those recurrences will be invasive disease. While reduction of LR is important, particularly invasive LR, other goals of therapy are taken into consideration such as the cosmetic outcomes and the side effects from XRT. Currently LR risk is estimated based on clinicopathologic factors and provides an average risk derived from population studies. No studies have been able to identify a patient group that did not derive benefit (i.e. risk reduction) with XRT.
- This presentation is focused upon harnessing the power of genomics for DCIS management. Foremost in the clinician’s mind is the question of how to make a treatment decision for the patient. These decisions vary according to patient preference, and goals of treatment must be aligned with the patient’s own goals. The decision around recommending XRT is dependent on an assessment of LR risk with an assumption that around half of those recurrences will be invasive disease. While reduction of LR is important, particularly invasive LR, other goals of therapy are taken into consideration such as the cosmetic outcomes and the side effects from XRT. Currently LR risk is estimated based on clinicopathologic factors and provides an average risk derived from population studies. No studies have been able to identify a patient group that did not derive benefit (i.e. risk reduction) with XRT.
- This presentation is focused upon harnessing the power of genomics for DCIS management. Foremost in the clinician’s mind is the question of how to make a treatment decision for the patient. These decisions vary according to patient preference, and goals of treatment must be aligned with the patient’s own goals. The decision around recommending XRT is dependent on an assessment of LR risk with an assumption that around half of those recurrences will be invasive disease. While reduction of LR is important, particularly invasive LR, other goals of therapy are taken into consideration such as the cosmetic outcomes and the side effects from XRT. Currently LR risk is estimated based on clinicopathologic factors and provides an average risk derived from population studies. No studies have been able to identify a patient group that did not derive benefit (i.e. risk reduction) with XRT.
- This presentation is focused upon harnessing the power of genomics for DCIS management. Foremost in the clinician’s mind is the question of how to make a treatment decision for the patient. These decisions vary according to patient preference, and goals of treatment must be aligned with the patient’s own goals. The decision around recommending XRT is dependent on an assessment of LR risk with an assumption that around half of those recurrences will be invasive disease. While reduction of LR is important, particularly invasive LR, other goals of therapy are taken into consideration such as the cosmetic outcomes and the side effects from XRT. Currently LR risk is estimated based on clinicopathologic factors and provides an average risk derived from population studies. No studies have been able to identify a patient group that did not derive benefit (i.e. risk reduction) with XRT.
- Main Points: A clinician's treatment decision varies according to a patient’s perceived risk of recurrence in addition to patient preference Multiple factors influence treatment decisions Estimated risk of local recurrence local recurrence based on clinical and pathologic features Estimated risk of invasive LR (approximately 50% of recurrences) Balancing toxicity of therapy for a non-life-threatening disease Patient preference Although DCIS is not a lethal disease, the same treatments (or combination of treatments) are offered as patients with invasive breast cancer All standard treatments are given to reduce risk of local recurrence, however, side-effects with each treatment option must be considered on an individual basis Additional considerations regarding standard treatment options for DCIS: If a patient receives BCS + RT for DCIS and has an invasive recurrence, mastectomy is the only remaining surgical option. However, patients with an invasive recurrence that received BCS alone for DCIS may have the option of receiving BCS to remove the invasive recurrence Radiation therapy reduces LR by 50% but has not been shown to impact overall or disease-free survival Additional considerations for patients receiving radiation therapy include cost, distance patient needs to travel for RT Compliance is a large barrier with regards to hormonal therapy treatment for ER+ DCIS patients Allegra et al. J Natl Cancer Inst. 2010.
- Main Points based on NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) Version 2.2019: The NCCN Guidelines® for DCIS treatment include breast conserving surgery with or without radiation or mastectomy/reconstruction The treatment algorithm is accompanied by the following footnote: “…If the patient and physician view the individual’s risk as ‘low,’ some patients may be treated by excision alone.” Physician and patient perceptions of low risk will vary greatly, therefore the need to accurately asses a patient’s individual risk of local recurrence is critical to how the patient is clinically managed Use of the clinical/pathologic features alone have not been shown to accurately identify a group of patients whose risk of local recurrence is low enough to safely omit adjuvant radiation from the patient’s treatment plan Adapted with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Breast Cancer V.2.2019. © 2019. National Comprehensive Cancer Network, Inc. All rights reserved. The NCCN Guidelines® and illustrations herein may not be reproduced in any form for any purpose without the express written permission of NCCN. To view the most recent and complete version of the NCCN Guidelines, go online to NCCN.org. The NCCN Guidelines are a work in progress that may be refined as often as new significant data becomes available.
- Main Points: The Oncotype Breast DCIS Score® test is the only genomic assay that can assess an individual DCIS patient’s local recurrence risk The activity of 7 genes in critical molecular pathways is quantitatively measured to determine the DCIS Score® result that reflects the underlying biology of the tumor 7 cancer related genes (proliferation group, progesterone receptor (PR) and GSTM1) are included in the assay and are purely prognostic. The combined expression of these genes within a proprietary algorithm generates a DCIS Score result that provides an individual’s risk of any ipsilateral local recurrence and specifically risk of an invasive local recurrence ER gene is not included in the DCIS Score result as ER expression is predictive of endocrine therapy benefit and is not prognostic Solin et al. J Natl Cancer Inst. 2013.
- Main Point: Only the Oncotype DX® Breast DCIS Score™ report combines clinicopathologic features and tumor biology for an individualized determination of 10-year risk of local or invasive local recurrence Solin et al. J Natl. Cancer Inst. 2013. Rakovitch et al. Breast Cancer Res Treat. 2015. Rakovitch et al. ASCO 2017.
- Main Points: The first validation study was carried out in a prospective cohort study of patients Based on clinicopathological covariates (tumor grade and size) these patients were believed to have had a low-risk of local recurrence Hughes et al. J Clin Oncol. 2009.
- Main Points: In the high-risk group (red), the estimated 10-year percentage of patients free of any LR was 74%, with the low Breast DCIS Score™ risk group (green) having an estimated 89% of patients free of LR. The log rank P-value of 0.006 means that there was a significant trend in LR risk across the three Breast DCIS Score risk groups For invasive local recurrence, the high Breast DCIS Score risk group (red) had an estimated 81% of patients LR-free at 10 years, while in the low Breast DCIS Score risk group (green), 96% of patients were estimated to be LR-free at 10 years. The log rank P-value of 0.003 means that there was a significant trend in invasive LR risk across the three Breast DCIS Score risk groups While the E5194 population was generally believed to be at low-risk, it is important to note that 70% of the patients were in the low Breast DCIS Score risk group and 30% were in the intermediate or high-risk groups Solin et al. J Natl. Cancer Inst. 2013. Genomic Health, Data on File.
- Main Point: The estimation of 10-year risk of local recurrence risk evaluated as a continuous function shows that increasing Breast DCIS Score™ result is associated with increasing risk of local recurrence (any recurrence or invasive recurrence) in the E5194 study using a Cox proportional hazards model Solin et al. J Natl. Cancer Inst. 2013.
- Main Points: The risk curves generated across these two different studies were highly similar We see a similar distribution in risk group across both studies as well Solin et al. J Natl Cancer Inst. 2013. Rakovitch et al. Breast Cancer Res Treat. 2015.
- Main Points: Clinical and pathologic features such as tumor size, patient age, and tumor grade have been shown to be independently prognostic, proving an estimated risk of local recurrence for the average patient with similar features The DCIS Score® result provides insight into the patient’s underlying tumor biology, providing an individualized risk estimate beyond just clinical and pathologic features alone The DCIS Score result can identify patients whose risk of local recurrence is higher or lower than the relevant clinical and pathologic factors would suggest, allowing physicians to tailor treatment discussions and recommendations based on an individualized risk estimate Combining clinical and pathologic features with the DCIS Score result may improve the precision with which the test can provide an individual’s risk of local recurrence (DCIS or invasive cancer) after breast-conserving surgery alone
- Main Points: A patient-specific meta-analysis including data from patients from both E5194 and the Ontario cohort study was performed to determine how the DCIS Score® result could be combined with clinical and pathologic factors to provide the most precise risk assessment for each individual patient Pre-specified prognostic factors studied were: DCIS Score result Age at diagnosis (<50 years, ≥50 years) Tumor size (≤1 cm, >1-2.5 cm, >2.5 cm) An additional covariate was analyzed: year of diagnosis (before year 2000, year 2000 or later to more accurately reflect modern clinical practice) The meta-analysis integrating DCIS Score result, age, and tumor size: Risk estimates were produced for individual patients (from each cohort) based on patient covariate values Risk information was combined across cohorts using patient-specific meta-analysis Precision-weighted estimates of 10-year risk of local recurrence and invasive local recurrence were calculated Did not include patients with positive margins or multifocal disease Tumor grade was not found to be a significant prognostic factor in this patient-specific meta-analysis, nor was it significant in the independent validation studies Rakovitch et al. J Natl Cancer Inst. 2017.
- Main Points: The DCIS meta-analysis, presented at ASCO 2017, uses the ECOG E5194 and Ontario cohorts and identified year of surgery, patient age at time of diagnosis, and tumor size as consistently informative prognostic clinicopathologic factors By integrating the Breast DCIS Score™ with year of surgery, patient age at time of diagnosis, and tumor size a more refined risk estimate can be generated for patients It should be noted, the Breast DCIS Score remains the same, however, the associated percent risk of recurrence will change after integrating the patient’s age at time of diagnosis, tumor size, and surgery after the year 2000 Approximately 53% of patients in the Ontario cohort were ≥50 y.o. and had ≤1 cm tumors Solin et al. J Natl. Cancer Inst. 2013. Rakovitch et al. Breast Cancer Res Treat. 2015. Rakovitch et al. ASCO 2017.
- Main Points: The first page of the DCIS report clearly displays the patient’s Breast DCIS Score™ result as well as a written description explaining the assay result was combined with the patient’s age and tumor size to determine a patient’s 10-year percent risk of recurrence estimate The rest of the report clearly identifies the patient’s age category [≥ 50 or <50] and tumor size category (> 1 cm or ≤ 1 cm), summarizes the meta-analysis study, and provides risk estimates for any local recurrence (invasive or DCIS) and invasive only local recurrence The second page of the DCIS report provides quantitative single gene results for ER and PR
- Main Points: The first page of the DCIS report clearly displays the patient’s Breast DCIS Score™ result as well as a written description explaining the assay result was combined with the patient’s age and tumor size to determine a patient’s 10-year percent risk of recurrence estimate The rest of the report clearly identifies the patient’s age category [≥ 50 or <50] and tumor size category (> 1 cm or ≤ 1 cm), summarizes the meta-analysis study, and provides risk estimates for any local recurrence (invasive or DCIS) and invasive only local recurrence The second page of the DCIS report provides quantitative single gene results for ER and PR
- This was a prospectively enrolled observational study of newly diagnosed patients with histologically proven pure DCIS; 115 patients were evaluated. 122 patients were enrolled at 10 centers throughout the US from September 2012 to February 2014 115 patients were evaluable for the primary analysis The 122 patients were enrolled by 5 radiation oncologists (48 pts; 41.7%) and 5 surgeons (67 pts; 58.3%) Sites: RMCC, Denver CO- 48 pts; SCCA, Little Rock, AR- 28 pts; CH, Cincinnati, OH- 15 pts; UCSF, San Francisco, CA- 9 pts; SJMC, Baltimore, MD- 9 pts; SEH, Cincinnati, OH- 6 pts Physicians filled out standardized questionnaires prior to and after the DCIS Score results were known; patient and tumor characteristics were extracted from the medical record Inclusion Criteria: ≥18 years old, female Histologically proven DCIS Eligible for breast conserving therapy Surgical excision pathology report available Oncotype DX® Breast Cancer Assay for DCIS ordered but result not yet available Exclusion Criteria: LCIS without DCIS Invasive carcinoma Mastectomy planned
- Prior to receiving the DCIS Score result, physicians recommended XRT for 73% of patients. After receiving the assay results, XRT was recommended only for 59.1% of patients. This resulted in a net change of 31.3% in treatment recommendations.
- The change in XRT recommendation by DCIS Score result had the greatest impact in the low risk group; overall, treatment recommendations changed 31.3% of the time.
- The DCIS Score™ result facilitates treatment decisions by increasing clarity, comfort and confidence in your patient’s treatment plan.
- Main Point: Only the Oncotype DX Breast DCIS Score® report combines clinicopathologic features and tumor biology for an individualized determination of 10-year risk of local or invasive local recurrence Solin et al. J Natl. Cancer Inst. 2013. Rakovitch et al. Breast Cancer Res Treat. 2015. Rakovitch et al. J Natl Cancer Inst. 2017.
- Main Points: The second validation study was carried out in a real-world patient cohort that was not restricted as to margins, tumor grade, or size Therefore, this is a more stringent test of the performance of the assay Rakovitch et al. Breast Cancer Res Treat. 2015.
- Main Points: In the analysis, patients had breast-conserving surgery alone with clear margins For the invasive local recurrence alone graph, the intermediate group demonstrates a higher risk of recurrence than the high-risk group. This unexpected result is likely due to the relatively small numbers within each group Rakovitch et al. Breast Cancer Res Treat. 2015.