Oncotype DX is a prognostic test that uses gene expression profiles in tumors to predict the risk of breast cancer recurrence. It has been recommended in the UK to help guide chemotherapy decisions for women with early-stage, hormone receptor-positive breast cancer who are assessed to have intermediate risk. The test results categorize a patient's risk as low (score <18), intermediate (score 18-30), or high (score >30) to help determine if the benefits of chemotherapy outweigh the risks. Adjuvant! Online is a similar web-based tool that uses factors like age, tumor size, and hormone receptor status to calculate survival probabilities and expected benefit of adjuvant therapy. Treatment decisions for early-stage breast cancer consider

1. Oncotype DX
Oncotype DX™ is a prognostic model (breast cancer recurrence) based on a test of gene expression
profiles in tumours. It has recently been recommended by NICE (DG10) for use in women with
oestrogen receptor positive (ER+), lymph node negative (LN−) and human epidermal growth factor
receptor 2 negative (HER2−) early breast cancer to guide chemotherapy decisions if the person is
assessed as being at intermediate risk, and where the information on the biological features of the
cancer provided by oncotype DX™ is likely to help in predicting the course of the disease.
Sometimes the test may be considered for post-menopausal women recently diagnosed with lymph
node positive and ER+ primary breast cancer.
If you’ve been given primary endocrine (hormone) therapy it may not be possible to do this test.
Talk to your specialist team.
Lower than
18
The breast cancer has a low risk of recurrence with hormonal therapy. The benefit of
chemotherapy is likely to be small and will not outweigh the risks of side effects.
Between 18
and 30
The breast cancer has an intermediate risk of recurrence with hormonal therapy. It is
unclear whether the benefits of chemotherapy outweigh the risks of side effects.
Greater than
30
The breast cancer has a high risk of recurrence with hormonal therapy, and the
benefits of chemotherapy are likely to be greater than the risks of side effects.
Adjuvant! online
Adjuvant! Online (AO) is a web-based actuarial tool that incorporates such criteria in order to predict
patient outcome at 10 years on the basis of data from the Surveillance, Epidemiology, and End
Results (SEER) registry and therapeutic benefit on the basis of the Oxford overviews of randomized
clinical trials [2]. The AO model was developed in the US and validated with a Canadian cohort [2]
but is subject to a number of limitations. For example, individualized AO estimates of recurrence risk
are sensitive to variability in comorbidity assessment [3], and its (Adjuvant! Online) estimates of
recurrence are not truly individualized, because they are based on data incorporated into 'binned'
categories (tumor size, nodal status, and so on) The software uses similar factors to the NPI but also
includes; patient age, hormone receptor status and comorbidity level.15 These variables are used to
calculate the patients estimated 10-year survival probabilities, risk of relapse and the expected
benefit of adjuvant therapy. A large population-based study of Canadian women of all ages with
early breast cancer has validated the Adjuvant! model.
Web based tool to estimate the (absolute) net benefit of
Adjuvant treatment for an individual patient
By estimating a patient`s risk of a negative outcome (death, relapse) and then multiplying that by the
proportion of negative events that a given adjuvant Therapy is known to prevent.
Treatment decisions in the adjuvant therapy of early breast cancer
Small tumors, negative lymph nodes
Older patients> 70 years

2. Tumors ER/PgR+ andN0-3+
Treatment decisions in the adjuvant therapy of early breast cancer
Individual risk of relapse–without therapy → Prognosis
Individual risk of relapse-with therapy → benefit of treatment
Toxicities of treatment
Comorbidities and life expectancy
Source: SEER databank
(Surveillance Epidemiology and End Results) -big population-based data bank (comprises10% of all
breast cancer cases in the US)
Limitations:
•Only overall mortality is documented
•Relapse rate is not documented
•cause of death not reliably reported
•adjuvant treamtment is not known
•Grading, ER und PgR are frequently not available
Assessment of treatment effect is mainly based on:
EBCCTG Overview Meta anlyses
Limitations
•many old trials included (frequently not according to current quality standards)
•ER und PgR is only documented as positive or negative
•only few patients above70 years included
•HER2 Status is not considered
NPI
The Nottingham prognostic index (NPI) is used to determine prognosis following surgery for breast
cancer. Its value is calculated using three pathological criteria: the size of the lesion; the number of
involved lymph nodes; and the grade of the tumour.
The index is calculated using the formula:
NPI = [0.2 x S] + N + G
Where:
• 6.5 is the size of the index lesion in centimetres

3. • 1 is the node status: 0 nodes = 1, 1-4 nodes = 2, >4 nodes = 3
• '3 is the grade of tumour: Grade I =1, Grade II =2, Grade III =3
Score 5-year survival
>/=2.0 to </=2.4 93%
>2.4 to </=3.4 85%
>3.4 to </=5.4 70%
>5.4 50%
Nottingham Prognostic Index Plus
The Nottingham Prognostic Index Plus test (NPI+) is a biomarker-based test developed by the
University of Nottingham to support individualised clinical decision making in breast cancer
treatment. The immunohistochemistry test, which measures protein levels in the tumour tissue, is
intended to be used in women aged 18-70 years with primary operative breast cancer at either core
needle biopsy stage or post-surgery, pre-adjuvant therapy.
The ten biomarkers used for classification were ER, progesterone receptor (PgR), cytokeratin (CK)
5/6, CK7/8, epidermal growth factor receptor (EGFR; HER1), c-erbB2 (HER2), c-erbB3 (HER3), c-erbB4
(HER4), p53 and Mucin 1.