1. The Value of an Intermediate Recurrence Score® Result in the Oncotype DX® Assay
GHI10014_0511

2. Does an Oncotype DX® Recurrence Score® result in the intermediate range (18-30) provide value in treatment decision-making?
The objective of this slide module is to examine and review the value that the Oncotype DX® intermediate Recurrence Score® information provides in the treatment decision process for early-stage breast cancer patients.

3. The Intermediate Oncotype DX® Recurrence Score® Result
Factors in Medical Decision-making
The Prognostic Value of the Oncotype DX Assay Across All Risk Groups
The Predictive Value of the Oncotype DX Assay Across All Risk Groups
Case 1: Components of a Complex Treatment Decision
The Oncotype DX Recurrence Score Result
Reinforces the Treatment Decision
Case 2: Treatment Decision Based on Many Factors
TAILORx Study: Refining Estimations of Risk/Benefit of Adjuvant Treatment Options

4. Intermediate test results are part of the continuous nature of biology
Treatment Decision
Test Result Information
Type of Test Result
Evaluation of hypertension
Level of systolic and diastolic blood pressure
Continuous scale
Evaluation for prostate cancer
Level of serum PSA
Evaluation of cholesterol level
Level of serum LDL cholesterol
PSA, prostate-specific antigen; LDL, low-density lipoprotein
Main point: Treatment decisions in medicine are often based on test results that provide information on a continuous scale.
In oncology, treatment choices are rarely black-and-white. Thus, clinicians are required to make decisions by collecting different types of information to make more informed treatment decisions. Although some information is clearly positive or negative (eg, presence or absence of the Philadelphia chromosome in chronic myelogenous leukemia and acute lymphoblastic leukemia), more often information is provided on a continuous scale (eg, level of blood pressure in hypertension, level of serum prostate-specific antigen in prostate cancer, or level of serum low-density lipoprotein cholesterol). Often, when continuously measured variables fall into an “intermediate” zone, the information must be applied in context with other clinical and/or pathological information to make the best treatment decision for the patient.
Let’s look at an example of how physicians use “intermediate” zone information in context to make a treatment decision.

5. Other risk factors for cardiovascular event
Many factors contribute to treatment decisions for patients of “intermediate” risk
LDL cholesterol (measured on a continuous scale)
< 100 mg/dL mg/dL > 160 mg/dL
Risk of cardiovascular event (continuum of risk)
Low Intermediate High
Other risk factors for cardiovascular event
Main point: When information measured on a continuous scale falls into an “intermediate” zone, physicians must apply such information in context of other clinical and/or pathological information to make the best treatment decisions.
Decision-making about therapy for hypercholesterolemia is a complex process that uses information measured on a continuous scale. Although an LDL cholesterol of < 100 mg/dL is considered optimal in patients at risk of heart disease and > 160 mg/dL is considered high, there is a large “intermediate” zone. Other risk factors for heart disease include blood pressure, family, smoking history, and diabetes, and these factors are considered in all cases. While an LDL level in the intermediate zone cannot definitively identify patients who would benefit from statin therapy, when used with other risk factors, the information obtained from the intermediate zone values can be very important in making optimal decisions for patients. An LDL level on the high end of the intermediate zone may not be sufficient to justify therapy, but when combined with information about blood pressure, family history, smoking history, and diabetes, it can be very useful in decision-making regarding risk-reduction therapy. Similarly, an LDL level on the low end of the intermediate zone may be helpful in deciding how aggressively to pursue preventive therapy. The point is that there is a continuum of risk, and when patients are at intermediate risk for an event, the decision to treat them is based on many sources of information.
The Oncotype DX® Recurrence Score® value is also measured on a continuous scale. In the next several slides, we will explore what information we can glean from the Recurrence Score value about risk of distant recurrence and response to therapy. We will also see how the Recurrence Score value, along with the information we’ve gathered about our patient, helps us to tailor the most appropriate treatment plan for our patient and contributes to the final treatment decision.
• Blood pressure
• Family history
• Smoking history
• Diabetes
No statin therapy
Statin therapy

6. Recurrence Score® value 18-30
Many factors weigh into the adjuvant treatment decision in breast cancer
Recurrence Score® value 18-30
Small tumor size
Low tumor grade
Patient old age
Patient co-morbidities
Patient preference
Oncotype DX® Recurrence Score value
Degree of ER expression
Large tumor size
High tumor grade
Patient young age
Patient good health
Oncotype DX Recurrence Score value
Main point: As with all medical treatment decisions, many factors weigh into the treatment decision.
Whether the Oncotype DX® Recurrence Score® value is in the intermediate range or not, the decision to include chemotherapy in the adjuvant treatment regimen depends on many factors.
Some of these factors are disease -or tumor-related (eg, tumor size and grade), and some are patient-related (eg, age, overall health status, and preference).
The Oncotype DX Recurrence Score value plays an important role in the adjuvant treatment decision by providing additional biological insight not provided by traditional markers, which allows for an individualized assessment of recurrence risk and likely response to therapy.
Paik S, et al. ASCO. 2005; Abstract 510.
Chemotherapy + hormonal therapy
Hormonal therapy only
Paik S, et al. ASCO. 2005; Abstract 510.

7. The Intermediate Oncotype DX® Recurrence Score® Result
Factors in Medical Decision-making
The Prognostic Value of the Oncotype DX Assay Across All Risk Groups
The Predictive Value of the Oncotype DX Assay Across All Risk Groups
Case 1: Components of a Complex Treatment Decision
The Oncotype DX Recurrence Score Result
Reinforces the Treatment Decision
Case 2: Treatment Decision Based on Many Factors
TAILORx Study: Refining Estimations of Risk/Benefit of Adjuvant Treatment Options

8. Distribution of Recurrence Score® results in US clinical practice shows that 52% of patients are low-risk
Main point: As in clinical studies, the distribution of Recurrence Score® results in US clinical practice shows that about half of all patients are in the low-risk group.
In this study, the distribution of Recurrence Score results for patients in Europe and the Middle East was compared with that for patients in the United States.
The distribution of the Recurrence Score results in Europe and the Middle East is consistent with that in the US, despite regional variability in management of early-stage breast cancer.
Of the >100,000 tumor specimens successfully examined in the Genomic Health laboratory, Oncotype DX consistently identifies >50% of patients who have a RS <18, regardless of geography. This finding is consistent with the results from the validation and confirmatory studies, although the ECOG 2197 and SWOG 8814 studies had only 49% and 40%, respectively, of patients who had a RS <18.
Palmer GP, et al. ECCO-ESMO 2009; abstract 194.
Palmer G, et al. ECCO-ESMO 2009; abstract 194.
Data collected between January 2004 and April 2009.

9. Distant Recurrence at 10 Years
Oncotype DX® Recurrence Score® result has prognostic and predictive clinical value
Lower Risk Higher Risk
Distant Recurrence at 10 Years
Main point: The Oncotype DX® Recurrence Score® value is correlated with distant recurrence rate at 10 years, hormone therapy benefit, and chemotherapy benefit.
Distant recurrence rate at 10 years with 5 years of tamoxifen treatment: the higher the score, the higher the risk of distant recurrence.
Hormone therapy benefit: the lower the score, the greater the impact of tamoxifen given for 5 years on proportion of patients recurrence-free at 10 years.
Chemotherapy benefit: the higher the score, the greater the proportion of patients recurrence-free at 10 years.
Since a low Recurrence Score value is associated with low risk of recurrence and low benefit from adding chemotherapy to tamoxifen, many oncologists will choose to forego chemotherapy.
Conversely, a high Recurrence Score value is associated with a high risk of distant recurrence and significant benefit from adding chemotherapy to tamoxifen, prompting many oncologists to add chemotherapy.
Approximately 35% of patients will fall into the intermediate Recurrence Score range. Although the continuous nature of the assay results allows oncologists to ascertain distant recurrence risk for these patients, there are multiple ways to apply the information. Patients with a “high” intermediate Recurrence Score value may be considered differently from those with a “low” intermediate Recurrence Score value. Nonetheless, the information provided by the Recurrence Score result can be very helpful in making treatment decisions when viewed in the context of other patient-specific factors, including patient concern, age, and conditions that may increase the risk of chemotherapy-associated toxicity.
Paik S, et al. N Engl J Med. 2004;351:2817.
Habel LA, et al. Breast Cancer Res. 2006;8:R25.
Paik S, et al. J Clin Oncol. 2006;24:3726.
Recurrence Score
The lower the Recurrence Score value:
The lower the risk of distant recurrence
The lower the benefit of chemotherapy
The greater the benefit of tamoxifen
The higher the Recurrence Score value:
The greater the risk of distant recurrence
The greater the benefit of chemotherapy
Paik S, et al. N Engl J Med. 2004;351:2817. Paik S, et al. J Clin Oncol. 2006;24:3726. Habel LA, et al. Breast Cancer Res. 2006;8:R25.

10. 10-Year Rate of Recurrence
Clinical validation of the Oncotype DX® assay: Risk groups defined for distant recurrence
NSABP B-14
100%
90%
80%
P < 0.001
70%
60%
50%
Proportion Without Distant Recurrence
40%
Main point: The value of the Oncotype DX® Recurrence Score® result has been validated to predict the risk of distant recurrence in women with newly diagnosed ER+, node-negative, early-stage breast cancer.
The large multicenter NSABP Study B-14 was performed to clinically validate the Oncotype DX assay and Recurrence Score algorithm as a predictor of the risk of distant recurrence for patients who are treated with tamoxifen.
NSABP B-14 trial (original): 2828 node-negative, ER+ patients were randomized 1:1 to tamoxifen or placebo in double-blind fashion. An additional 1235 patients were registered to receive tamoxifen following closure of the trial, yielding a total of 2617 tamoxifen-treated patients eligible for the Oncotype DX validation study.
Of these, 668 tamoxifen-treated patients for whom tissue blocks were available were evaluated as part of the Oncotype DX study.
The Recurrence Score value was calculated for each patient: 51% of the patient population fell into the low-risk group (n = 338), 22% fell into the intermediate-risk group (n = 149), and 27% fell into the high- risk group (n = 181).
The Kaplan-Meier plot shows the proportion without Distant Recurrence over time for the different risk categories. The proportions without Distant Recurrence for the high- and low-risk groups were statistically significantly different.
The 10-year Kaplan-Meier estimated rates of distant recurrence for the low-, intermediate-, and high-risk groups were 6.8%, 14.3%, and 30.5%, respectively.
These results were also confirmed in multivariate analyses adjusted for the clinical variables. Thus, the Oncotype DX assay can predict the risk of distant recurrence, which provides important biological information beyond that provided by traditional markers. The assay allows an individualized assessment of the likelihood of distant recurrence, which helps inform adjuvant treatment decisions.
Paik S, et al. N Engl J Med. 2004;351:2817.
Risk Group
n (%)
10-Year Rate of Recurrence
95% CI
Low (RS < 18)
338 (51)
6.8%
4.0%, 9.6%
Intermediate (RS 18-30)
149 (22)
14.3%
8.3%, 20.3%
High (RS ≥ 31)
181 (27)
30.5%
23.6%, 37.4%
30%
20%
10% 0% 2 4 6 8 10 12 14 16
Years
RS, Recurrence Score® result
Paik S, et al. N Engl J Med. 2004;351:2817.

11. The Intermediate Oncotype DX® Recurrence Score® Result
Factors in Medical Decision-making
The Prognostic Value of the Oncotype DX Assay Across All Risk Groups
The Predictive Value of the Oncotype DX Assay Across All Risk Groups
Case 1: Components of a Complex Treatment Decision
The Oncotype DX Recurrence Score Result
Reinforces the Treatment Decision
Case 2: Treatment Decision Based on Many Factors
TAILORx Study: Refining Estimations of Risk/Benefit of Adjuvant Treatment Options

12. Myth vs Fact: The Intermediate Recurrence Score® Group
Intermediate Oncotype DX® Recurrence Score value doesn’t provide any information regarding a treatment recommendation.
Intermediate Oncotype DX Recurrence Score value does provide information about the likely response of patients to adjuvant hormonal therapy and adjuvant chemotherapy.
Main point: It is untrue that an intermediate Oncotype DX® Recurrence Score® value does not provide any information regarding a treatment recommendation.
One myth that should be dispelled is that of the Oncotype DX intermediate Recurrence Score value not providing any information regarding a treatment recommendation.
The fact is that the Oncotype DX Recurrence Score value, including values in the intermediate range, does provide information about the likely response of patients to adjuvant therapy.
In the following slides, we will examine the study data surrounding the Oncotype DX Recurrence Score value and its prognostic and predictive value in breast cancer.
In addition, we will discuss the TAILORx study, which aims to determine whether adjuvant hormonal therapy is not inferior to adjuvant chemotherapy followed by hormonal therapy in patients who have a mid-range Recurrence Score value of

13. 10-Year Absolute Risk BC Death (%) (95% CI)
The Oncotype DX® assay identifies patients for whom tamoxifen alone may be appropriate therapy (NSABP B-14)
Recurrence Score® value
< ≥ 31
NO SYSTEMIC TREATMENT
Tamoxifen
benefit
Tamoxifen benefit
Main point: The Kaplan-Meier estimates of the risk of death from breast cancer at 10 years indicate that systemic treatment with tamoxifen is more beneficial in low- and intermediate-risk patients than in high-risk patients.
Shown here are the Kaplan-Meier estimates of the risk of breast cancer death at 10 years for the NSABP B-14 study.
The results on top are for patients with no systemic therapy.
The results at the bottom are for patients treated with hormonal therapy.
The largest benefits of tamoxifen are observed in low- and intermediate-risk patients. One should not expect a large benefit of tamoxifen for patients in the high-risk group.
Paik S, et al. ASCO. 2005; Abstract 510.
Tamoxifen
10-Year Absolute Risk BC Death (%) (95% CI)
Paik S, et al. ASCO. 2005; Abstract 510.

14. 10-Year Absolute Risk BC Death (%) (95% CI)
The Oncotype DX® assay can predict benefit from chemotherapy and tamoxifen (NSABP B-20)
Recurrence Score® value
< ≥ 31
Tamoxifen
Chemotherapy benefit
Main point: The Kaplan-Meier estimates of the risk of death from breast cancer at 10 years indicate that the addition of chemotherapy to tamoxifen is more beneficial in high-risk patients than in low- or intermediate-risk patients.
Shown here are the Kaplan-Meier estimates of the risk of breast cancer death at 10 years for the NSABP B-20 study.
The results on top are for patients treated with hormonal therapy.
The results at the bottom are for patients treated with hormonal therapy plus chemotherapy.
The largest benefits of chemotherapy are observed in the high-risk patients. There was a 28% absolute benefit observed in patients with Recurrence Score values ≥ 31.
Patients in the low- or intermediate-risk group should not expect a large benefit from the addition of adjuvant chemotherapy to hormonal therapy.
These data demonstrate that not all patients benefit equally from adjuvant chemotherapy.
Adapted from Paik S, et al. J Clin Oncol. 2006;24:3726.
Tamoxifen + CHEMO
10-Year Absolute Risk BC Death (%) (95% CI)
Adapted from Paik S, et al. J Clin Oncol. 2006;24:3726.

15. The Intermediate Oncotype DX® Recurrence Score® Result
Factors in Medical Decision-making
The Prognostic Value of the Oncotype DX Assay Across All Risk Groups
The Predictive Value of the Oncotype DX Assay Across All Risk Groups
Case 1: Components of a Complex Treatment Decision
The Oncotype DX Recurrence Score Result Reinforces the Treatment Decision
Case 2: Treatment Decision Based on Many Factors
TAILORx Study: Refining Estimations of Risk/Benefit of Adjuvant Treatment Options

16. Case 1: Should this patient receive adjuvant chemotherapy?
Patient MP (65 years old)
Medical History
Compensated congestive heart failure
“Silent” myocardial infarction 4 years ago
Type 2 diabetes well controlled with oral therapy
Physical Exam
No symptoms climbing 1 flight of stairs
Healing well from recent lumpectomy and sentinel node biopsy
Patient anxious and fearful of breast cancer, wants “strongest chemotherapy”
Characteristic
Result
Tumor size
1.8 cm
Tumor grade 1
Lymph nodes
2 sentinel nodes negative
ER/PR status
ER+/PR+
HER2 status
Negative
Oncotype DX®
Recurrence Score® 25
Patient MP wants to have adjuvant chemotherapy, but her co-morbidities could make chemotherapy a difficult course.
Could the potential risks of chemotherapy outweigh the benefits?
Can the Oncotype DX Recurrence Score result be used to inform adjuvant treatment decisions?
Main point: A patient case is presented. Based on this patient’s presentation, medical history, brief interview, pathology results, and Oncotype DX® Recurrence Score® result, how would you treat this patient?
Patient MP is a 65-year-old retired elementary school principal who volunteers in the cancer center at your hospital. She is referred to your office by her surgeon, who has recently performed a lumpectomy and sentinel node biopsy for breast cancer discovered on routine mammogram.
The patient is quite anxious and opens up the conversation by telling you about her sister who died of breast cancer 3 years ago at age 57, a sister-in-law who died at 52, and a close friend who died at 59. She believes that she needs the “strongest chemotherapy you have.” She is recovering well from her surgery.
Past medical history is remarkable for compensated congestive heart failure following a “silent” myocardial infarction 4 years ago, as well as type 2 diabetes that is well controlled on oral therapy. The patient has no symptoms climbing 1 flight of stairs.
Clinicians must consider many pieces of information when tailoring a treatment plan for a patient.
In addition to a physical exam and medical history of the patient, the clinician may order laboratory tests and assays to be done to better characterize the disease.
Some of these test results may be reported as positive/negative (eg, HER2 status), but others may be reported on a continuous scale (eg, Recurrence Score result).
Regardless of how they are measured, test results can provide important information that can guide treatment decisions.
In the case study presented here, how does each piece of information contribute to the treatment plan decision for this patient?
What is the most appropriate treatment plan for this patient?
What did each piece of information tell you about the patient, her disease, her prognosis, or likely response to therapy?
In what way did each piece of information contribute to the treatment decision?
Did any one piece of information weigh more than any other in the treatment decision? 16

17. Case 1: What does the Oncotype DX® Recurrence Score® tell us about this patient?
CLINICAL EXPERIENCE
RESULTS 25
Recurrence Score =
Patients with a Recurrence Score of 25 in clinical validation study had an Average Rate of
Distant Recurrence at 10 years of 16.2% (95% CI: 12.6%, 19.8%)
Main point: The Oncotype DX® intermediate Recurrence Score® value can provide information that can influence treatment decisions.
This patient’s Recurrence Score result is 25, which means she has approximately 16% chance of distant recurrence of breast cancer in 10 years. Although the Recurrence Score value is in the intermediate risk group, the Recurrence Score result can still be helpful to you and this patient. A discussion of her risk may help alleviate fear, and balancing the risk of breast cancer recurrence against the risk of chemotherapy toxicity may help her make a more “data-based” and less “fear-based” decision about adjuvant therapy. Helping to control the fear may significantly improve the patient’s quality of life.
Because she is ER+ and node-negative, she is likely to experience a clinical benefit from hormonal therapy (eg, tamoxifen) but may not gain significant benefit from the addition of chemotherapy to hormonal therapy. 17

18. Case 1: Single-gene results suggest high likelihood of benefit from tamoxifen
QUANTITATIVE HORMONE RECEPTOR ANALYSIS
The Oncotype DX assay uses RT-PCR to determine the RNA expression of the hormone receptor genes below. These results may differ from ER
or PR results reported using other methods or reported by other laboratories.1
The ER Score and the PR Score are also included in the calculation of the Recurrence Score.
The ER Score positive/negative cut-off of 6.5 units was validated from a study of 761 samples using the 1D5 antibody (immunohistochemistry)
and 607 samples using the SP1 antibody (immunohistochemistry). The standard deviation for the ER Score is less than 0.5 units.2
Clinical Experience:
For ER positive breast cancer, the magnitude of tamoxifen benefit increases as the ER Score increases from 6.5 to ≥
Please note: The Average Rate of Distant Recurrence reported on Page 1 based on the Recurrence Score was determined in patients who
received 5 years of tamoxifen treatment and takes into account the magnitude of tamoxifen benefit indicated by the ER Score.
11.0
9.1
The PR Score positive/negative cut-off of 5.5 units was validated from a study of 761 samples using the PR636 antibody (immunohistochemistry)
and another study of 607 samples using the PR636 antibody (immunohistochemistry). The standard deviation for the PR Score is less than 0.5 units.2
References:
1. ER Score based on quantitative ESR1 expression (estrogen receptor); PR Score based on quantitative PGR expression (progesterone receptor).
2. ASCO Breast Cancer Symposium 2007 Abstracts #87 by S.S. Badve et al., and #88 by F.L. Baehner et al.
3. ASCO Annual Meeting 2005 Abstract #510 by S. Paik et al.
PR Score =
Positive
ER Score =
PATIENT REPORT
Patient: MP
Sex: Female
DOB: 06/17/1944
Requisition: A0000B
Order Received: 02/01/2009
Date Reported: 02/13/2008
Main point: This patient’s single-gene results from the Oncotype DX® assay indicate high ER expression.
Because this patient’s ER expression is high, she has a higher likelihood of response to hormone therapy alone.
Even in cases of intermediate Recurrence Score® results, other elements of the Oncotype DX report can provide additional information that can be used to guide adjuvant treatment decisions.

19. Hormonal therapy plus chemotherapy
Case 1: Multiple factors to consider in the adjuvant treatment decision
Oncotype DX® Recurrence Score® value (measured on a continuous scale)
< ≥ 31
18-30
Distant recurrence (continuum of risk)
Low High
Intermediate
Favor no chemotherapy
Favor chemotherapy
Smaller tumor/lower grade
Larger tumor/higher grade
Diabetes
Extreme anxiety of cancer recurrence
Congestive heart failure
Coronary artery disease
Degree of ER expression
Main point: How can the Oncotype DX® intermediate Recurrence Score® result help us and this patient to decide on a course of treatment?
In this case study, patient factors exist that both favor chemotherapy (tumor size 1.8 cm) and favor endocrine therapy alone (tumor grade 1) with no chemotherapy. Based on the tumor size, tumor grade, ER/PR status, and HER2 status, Patient MP could have anywhere from a low risk to a high risk of recurrence, if treated with endocrine therapy alone. Therefore, adding chemotherapy to endocrine therapy might be beneficial.
On the other hand, her co-morbidities place her at high risk for a difficult course with chemotherapy.
Her history of congestive heart failure makes the use of anthracyclines very risky.
Her diabetes makes premedication for taxane therapy an important issue.
How can the Oncotype DX Recurrence Score result help us and this patient to decide on a course of treatment?
Hormonal therapy plus chemotherapy
Hormonal therapy only

20. Case 1: Low risk of recurrence reduces patient fears
Upon hearing the results of the Oncotype DX® assay and the predicted 10-year risk of distant recurrence of 16%, Patient MP is reassured and feels more comfortable with hormonal therapy without chemotherapy.
After discussing the risks and benefits of chemotherapy, she opts for adjuvant hormonal therapy alone.
Main point: The Oncotype DX® Recurrence Score® result provided information that the clinician and patient used to make a treatment decision.

21. The Intermediate Oncotype DX® Recurrence Score® Result
Factors in Medical Decision-making
The Prognostic Value of the Oncotype DX Assay Across All Risk Groups
The Predictive Value of the Oncotype DX Assay Across All Risk Groups
Case 1: Components of a Complex Treatment Decision
The Oncotype DX Recurrence Score Result Reinforces the Treatment Decision
Case 2: Treatment Decision Based on Many Factors
TAILORx Study: Refining Estimations of Risk/Benefit of Adjuvant Treatment Options

22. Both clinicians and patients find the Oncotype DX® assay helped with adjuvant treatment decisions
Parameter
% of Respondents
Medical oncologists (N = 16) who:
Reported increased confidence in treatment recommendation
Felt the Recurrence Score® result provided additional information
Felt the Recurrence Score result influenced treatment recommendation
93.8
87.6
Patients (N = 67) who:
Were glad (at 12 months) that they used the Oncotype DX assay
Found assay results easy to understand
Felt the assay influenced treatment decision
Were satisfied with their adjuvant treatment decision
92.5
89.6
80.6
95.5
Main point: The majority of medical oncologists and patients who chose the Oncotype DX® assay reported that the assay results (the Recurrence Score® value) influenced treatment decision.
Medical oncologists (N = 16) and patients (N = 67) answered questionnaires before the assay, immediately after the assay results were known, and 12 months later.
These findings show that the Oncotype DX assay has enduring impact on the adjuvant treatment decision-making process of medical oncologists and patients. Medical oncologists and patients reported continued confidence and satisfaction with the assay. Patients had a decrease in decisional conflict right after the test. Patient anxiety declined over the next 12 months after using the assay.
The vast majority of medical oncologists reported that the Recurrence Score result increased their confidence with the treatment decision, provided additional information, and influenced treatment.
Thus, the Oncotype DX assay provides an objective way to assess individual risk and likelihood of response to therapy, increases confidence in treatment decisions, and informs personalized adjuvant treatment decisions.
Lo SS, Mumby PB, Norton J, et al. J Clin Oncol. 2010;28:
Lo SS et al. SABCS 2008: Abstract 3113.
Lo SS, et al. J Clin Oncol. 2010; 28: Lo SS et al. SABCS 2008: Abstract 3113. 22

23. The Intermediate Oncotype DX® Recurrence Score® Result
Factors in Medical Decision-making
The Prognostic Value of the Oncotype DX Assay Across All Risk Groups
The Predictive Value of the Oncotype DX Assay Across All Risk Groups
Case 1: Components of a Complex Treatment Decision
The Oncotype DX Recurrence Score Result Reinforces the Treatment Decision
Case 2: Treatment Decision Based on Many Factors
TAILORx Study: Refining Estimations of Risk/Benefit of Adjuvant Treatment Options

24. Case 2: Is adjuvant chemotherapy the right treatment option for this patient?
Patient JD (54 years old)
Referred to you for adjuvant treatment
Medical History
Unremarkable
Menopause 4 years ago
Physical Exam
Underwent a lumpectomy for adenocarcinoma and sentinel node sampling 2 weeks prior
Healing left breast and axillary wounds
Otherwise unremarkable
Patient JD is concerned about recurrence risk but is also fearful of the potentially disruptive effect chemotherapy may have on her life.
Characteristic
Result
Tumor size
1.1 cm
Tumor grade 2
Lymph nodes
3 sentinel nodes negative
ER/PR status
ER+/PR+
HER2 status
Negative
Oncotype DX®
Ordered, but results not yet returned
Main point: A second case study is presented here.
Patient JD is a 54-year-old real estate attorney who was found to have a small nodule in her left breast on annual exam by her gynecologist.
Mammogram showed a suspicious nodule, so the patient underwent a needle aspiration, which showed adenocarcinoma.
Two weeks ago, she underwent a lumpectomy and sentinel node sampling.
Patient JD’s past medical history and physical exam are unremarkable, other than healing left breast and axillary wounds. She went through menopause 4 years ago.
She is very physically active, playing on a neighborhood tennis team. She works part- time as a real estate attorney. She is the primary caregiver for her 3-year-old granddaughter. She is married to an airline pilot. She lives approximately 40 minutes from your office.
Prior to this visit, she researched breast cancer and concluded that many women with ER+, node-negative breast cancer don’t need chemotherapy. Nonetheless, she is conflicted: although she wants to avoid the side effects of chemotherapy and its potentially disruptive effect on her life, she wants to do everything reasonable to prevent the cancer from coming back, especially given her familial obligations.
Does Patient JD need chemotherapy?
What can the Oncotype DX Recurrence Score® result reveal about her recurrence risk?

25. Case 2: A Recurrence Score® result of 30 is on the high end of the intermediate range
RESULTS 30
Recurrence Score =
CLINICAL EXPERIENCE
Patients with a Recurrence Score of 30 in clinical validation study had an Average Rate of
Distant Recurrence at 10 years of 20.0% (95% CI: 15.4%, 24.4%)
Main point: This patient’s Recurrence Score® result is 30, which is on the high end of the intermediate risk range.
From this information, Patient JD has approximately 20% probability of distant recurrence of breast cancer in 10 years. Although the Recurrence Score value is in the intermediate risk range, it is on the high end of that range. Combined with the other factors of her case, including her age, tumor size and grade, medical and social histories, and the insight into the patient’s likely benefit from treatment that the Recurrence Score value provides, you and the patient can come to an agreement about the most appropriate adjuvant treatment.

26. Case 2: Single-gene results suggest low likelihood of benefit from tamoxifen
QUANTITATIVE HORMONE RECEPTOR ANALYSIS
The Oncotype DX assay uses RT-PCR to determine the RNA expression of the hormone receptor genes below. These results may differ from ER
or PR results reported using other methods or reported by other laboratories.1
The ER Score and the PR Score are also included in the calculation of the Recurrence Score.
The ER Score positive/negative cut-off of 6.5 units was validated from a study of 761 samples using the 1D5 antibody (immunohistochemistry)
and 607 samples using the SP1 antibody (immunohistochemistry). The standard deviation for the ER Score is less than 0.5 units.2
Clinical Experience:
For ER positive breast cancer, the magnitude of tamoxifen benefit increases as the ER Score increases from 6.5 to ≥
Please note: The Average Rate of Distant Recurrence reported on Page 1 based on the Recurrence Score was determined in patients who
received 5 years of tamoxifen treatment and takes into account the magnitude of tamoxifen benefit indicated by the ER Score.
7.0
6.0
The PR Score positive/negative cut-off of 5.5 units was validated from a study of 761 samples using the PR636 antibody (immunohistochemistry)
and another study of 607 samples using the PR636 antibody (immunohistochemistry). The standard deviation for the PR Score is less than 0.5 units.2
References:
1. ER Score based on quantitative ESR1 expression (estrogen receptor); PR Score based on quantitative PGR expression (progesterone receptor).
2. ASCO Breast Cancer Symposium 2007 Abstracts #87 by S.S. Badve et al., and #88 by F.L. Baehner et al.
3. ASCO Annual Meeting 2005 Abstract #510 by S. Paik et al.
PR Score =
Positive
ER Score =
PATIENT REPORT
Patient: JD
Sex: Female
DOB: 05/17/1955
Requisition: A1111B
Order Received: 03/01/2009
Date Reported: 03/13/2008
Main point: This patient’s single-gene results show low ER expression.
Because this patient’s tumor shows low ER expression, she is less likely to respond to hormonal therapy alone than someone with higher ER expression.
This information regarding her ER expression levels provides additional insight into the tumor biology beyond “ER-positive” or “ER-negative,” which may help guide adjuvant treatment decisions.

27. Hormonal therapy plus chemotherapy
Case 2: Multiple factors to consider in the adjuvant treatment decision
Oncotype DX® Recurrence Score® value (measured on a continuous scale)
< ≥ 31
Distant recurrence (continuum of risk)
Low Intermediate High
Favor no chemotherapy
Favor chemotherapy
Smaller tumor/lower grade
Larger tumor/higher grade
Patient fear of life disruption by chemo
Patient age
Patient good health
Degree of ER expression
Main point: How can the Oncotype DX® intermediate Recurrence Score® result help us and this patient to decide on a course of treatment?
In this case study, patient factors exist that both favor chemotherapy and favor endocrine therapy alone with no chemotherapy.
Patient JD expresses anxiety over the use of chemotherapy and how it might disrupt her life.
Based on the tumor size and grade, however, Patient JD could have a reasonable risk of recurrence, if treated with hormonal therapy alone. Therefore, adding chemotherapy to hormonal therapy might be beneficial. She is also of relatively young age and in good overall health.
Hormonal therapy plus chemotherapy
Hormonal therapy only

28. Case 2: Recurrence risk and patient characteristics factor into adjuvant chemotherapy decision
Patient JD understands her Recurrence Score® result of 30 means she has a substantial chance of recurrence of breast cancer in 10 years.
Because of the tumor grade, her relatively young age, and her good health, Patient JD decides to have adjuvant chemotherapy followed by hormonal therapy.
Main point: The Oncotype DX® Recurrence Score® result helped to make an adjuvant treatment decision for Patient JD.
Before receiving the Oncotype DX test results, what was the adjuvant treatment plan you would have recommended for Patient JD?
After receiving the Oncotype DX test results, what adjuvant treatment plan would you recommend?
Did the Recurrence Score result influence your treatment recommendation in any way? If not, did the Recurrence Score result confirm your recommendation?

29. The full range of Oncotype DX® results provides useful information to guide treatment decisions
The Oncotype DX Recurrence Score® value provides a scientifically validated continuous measure of risk of distant recurrence and magnitude of chemotherapy benefit.
Even when the Oncotype DX Recurrence Score® value is in the intermediate zone, the assay results provide information that, together with other clinical information, can help guide treatment decisions.
The Oncotype DX Recurrence Score result allows an individualized assessment of risk and response to therapy, which contributes to making more informed treatment decisions for individual patients.
Main point: Oncotype DX® Recurrence Score® result can provide useful information to guide treatment decisions
Oncotype DX Recurrence Score value is measured on a continuous scale.
Oncotype DX Recurrence Score value has been validated to predict.
Risk of distant recurrence at 10 years
Benefit of adjuvant chemotherapy added to hormonal therapy
In one study, the majority of medical oncologists and patients who have used the Oncotype DX assay report confidence in the results.
The Oncotype DX Recurrence Score value provides clinicians with information that influences treatment decision.