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
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
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.
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:
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.