5. • ET should be used in all luminal-like cancers.
• Indications for ChT within this subtype depend on the individual’s risk
of relapse, the tumour burden and features suggestive of biological
aggressiveness (grade, proliferation, vascular invasion), presumed
responsiveness to ET and patient preferences.
• Features associated with lower endocrine responsiveness include low
steroid receptor expression, lack of PgR expression, high tumour
grade and high expression of proliferation markers.
6. • The majority of luminal A-like cancers do not require ChT, except those with high disease burden.
• Data from neoadjuvant studies have demonstrated that ChT sensitivity depends on the intrinsic
phenotype, the highest being for HER2-positive (when combined with anti-HER2 therapy) and
TNBC.
• However, even assuming the relative benefit would be similar, the absolute benefit derived from
adjuvant ChT depends on the individual risk of relapse, which is determined by both the biology
and the burden of the disease.
• For example, the absolute benefit of adjuvant ChT for a low-burden, luminal A-like breast
cancer is extremely small.
• When balanced against the known short- and long-term side-effects, ChT is not recommended in
this setting.
7. • Several decision-making tools such as PREDICT Plus, NPI and
Adjuvant! Online exist to help predict recurrence risk and potential benefit
from systemic treatments.
• In cases of uncertainty regarding indications for adjuvant ChT, urokinase
plasminogen activator–plasminogen activator inhibitor 1 (uPA-PAI1) or
gene expression assays, such as MammaPrint, Oncotype DX, Prosigna,
Endopredict or Breast Cancer Index, may be used.
• These assays can help determine the individual’s recurrence risk and
potentially predict the benefit of ChT
8. ADJUVANT ONLINE
Adjuvant! Online uses the parameters :
• Age and
• Selected tumour characteristics (tumour size and grade,
number of positive axillary nodes, and hormone receptor status)
This allowed for the prediction of the 10-year risk of
relapse-free and OS in EBC.
9. PREDICT
PREDICT uses
• Patient age,
• Tumour size,
• Tumour grade,
• Number of positive nodes,
• ER status, HER2 status, ki67 status and
• Mode of detection.
Predict gives overall and breast cancer-specific survival for women
treated for early breast cancer.
10. ONCOASSIST
The ONCOassist breast adjuvant tool is based on the PREDICT
algorithm and provides the same information as PREDICT.
PREDICT is recommended by the National Institute for Health and Care
Excellence (NICE) as a tool for supporting clinical decisions on adjuvant
treatment benefit and has been endorsed by the American Joint
Committee on Cancer
11. PREDICT, NPI AND ONCOTYPE DX
In a study on Correlation Between Oncotype DX, PREDICT and the
Nottingham Prognostic Index for the Management of Early Breast Cancer
Published on CUREUS Journal of Medical Science on 2020 Apr 6 concluded
that :
• The risk of recurrence estimated by ODX in patients deemed low risk by
PREDICT or NPI highly correlated,
• No such correlation existed in patients with an estimated intermediate-
or high-risk breast cancer.
In PREDICT- or NPI-estimated intermediate- and high-risk patients,
ODX provided valuable additional prognostic information to guide adjuvant
treatment, while the potential avoidance of ODX testing in low-risk patients
presents significant cost-savings.
12. Another study on “The concordance of treatment decision guided by OncotypeDX
and the PREDICT tool in real-world early-stage breast cancer” published on 06
May 2020 in OnlineLibrary Cancer Medicine Journals concluded that :
• Compared to PREDICT, use of OncotypeDX in node negative, ER positive, HER2
negative breast cancer, is expected to change treatment decisions in a 25% of the
patients.
• As the concordance between PREDICT and OncotypeDX is influenced by
pathological features and is much higher in clinically very low-risk disease, the
added value of OncotypeDX in these patients is questionable
• It is not clear whether the associated budget impact and the delay in treatment
decisions justify its use in such patients
13. • A study on “70-Gene Signature as an Aid to Treatment
Decisions in Early-Stage Breast Cancer” published in The
New England Journal Of Medicine on AUG 2016 used the 70-
gene signature to determine genomic risk and Adjuvant!
Online to determine clinical risk.
• Categorization in to Low and high risk groups was done.
• A low clinical risk was defined as the 10-year probability of
breast-cancer–specific survival without systemic therapy
• Patients with low-risk disease according to both clinical and
genomic results did not receive adjuvant chemotherapy,
whereas patients who were categorized as having high-risk
disease by both tests received chemotherapy.
14. • Patients with discordant results (i.e., either high clinical risk and
low genomic risk or low clinical risk and high genomic risk) were
randomly assigned to the chemotherapy group or the no-
chemotherapy group on the basis of either the clinical result or the
genomic result.
• The results for the 70-gene signature do not provide evidence
for making recommendations regarding chemotherapy for
patients at low clinical risk according to AO.
• The study concluded that, in a large group of patients at high clinical
risk(AO) for breast-cancer recurrence, the addition of the 70-gene
signature to the traditional clinical and pathological factors provided
valuable information for considering which patients might benefit
from adjuvant chemotherapy.
• Chemotherapy could be avoided in patients at high clinical risk
but low genomic risk at a cost of a risk of distant metastasis at 5
years that is 1.5 percentage points higher.
15. • A study on “Evaluation and comparison of different breast cancer
prognosis scores based on gene expression data” published in
BioMedCentral Journals on Feb 2023,
• Evaluated the impact of adding Genetic Risk Scores (EndoPredict,
MammaPrint and Prosigna) to current standards of care for breast cancer
predictive modelling (PREDICT)
• These GRSs (EndoPredict, MammaPrint and Prosigna) demonstrated power
to predict BCSS(Breast CA Specific Survival) independent of PREDICT.
• However, incorporating these models into PREDICT had only a modest
impact on the calibration, discrimination and reclassification (with 4–10%
of patients reclassified into different clinical categories)
16. Genomic tests are not recommended for patients with:
• Clinicopathological low-risk tumours (pt1a, pt1b, g1, er high, pn0); and/or
• Special types of luminal-like breast cancer such as low-grade encapsulated papillary carcinoma
and solid papillary carcinoma (which should be considered as dcis for the sake of treatment
decisions),
• Invasive tubular carcinoma may be treated with locoregional treatment only, as the prognosis is
excellent; or
• 1–3 involved nodes coexisting with many other high-risk factors,
• Or with 4 positive nodes for whom adjuvant cht is indicated.
17. ESMO RECOMMENDATIONS
• All luminal-like cancers should be treated with ET.
• Most luminal A-like tumours do not require ChT, except those with high
disease burden.
• ChT use in luminal B-like HER2-negative patients depends on individual risk
of recurrence, presumed responsiveness to ET and patient preferences.
• In cases of uncertainty regarding indications for adjuvant ChT (after
consideration of all clinical and pathological factors), expression of uPA-
PAI1 or gene expression assays, such as MammaPrint, Oncotype DX ,
Prosigna, Endopredict or Breast Cancer Index, can be used.
18. • Luminal B-like HER2-positive tumours should be treated with ChT, ET and
anti-HER2 therapy.
• In selected low risk patients (T1abN0), the combination of anti-HER2
therapy and ET alone may be used .
• Patients with TNBC should receive ChT, with the possible exception of
low-risk ‘special histological subtypes’ such as secretory or adenoid cystic
carcinomas or very early (T1aN0) tumours .
• HER2-positive cancers should be treated with ChT plus anti-HER2
therapy, with the possible exception of selected cases with very low risk,
such as T1aN0 tumors.
20. • Hormone receptor status is an important predictor of beneft from chemotherapy.
• Although chemotherapy often leads to statistically signifcant risk reduction, the
differences in the absolute risk of recurrence for patients, especially patients with
small cancers or ER-positive cancers who also receive adjuvant endocrine therapy,
tend to be very small (single percentage points).
• Nearly all triple-negative tumors with nodal involvement and/or size greater than
0.5 cm carry sufficient risk to warrant adjuvant chemotherapy.
21. • Tumors with low or no expression of ER derive substantial
benefit from the addition of chemotherapy to endocrine therapy.
• By contrast, tumors with high quantitative levels of ER do not
appear to gain substantially from adding chemotherapy to
endocrine therapy.
• In current practice, most ER-positive cancers with tumor size 1
cm or greater, or involvement of 1 to 3 axillary lymph nodes,
should have genomic signature profiling.
22. NCCN
Estimating Risk of Relapse or Death and Benefits of Systemic
Treatment:
• The strongest prognostic factors are patient age, comorbidity, tumor
size, tumor grade, number of involved ALNs, and possibly HER2 tumor
status.
• A validated, computer-based model (Adjuvant! Online;
www.adjuvantonline.com) is available to estimate 10-year DFS and
OS that incorporates all of the above prognostic factors except for
HER2 tumor status.
23. • These tools aid the clinician in objectively estimating outcome with
local treatment only, and also assist in estimating the absolute
benefits expected from systemic adjuvant endocrine therapy and
chemotherapy.
• These estimates may be utilized by the clinician and patient in their
shared decision-making regarding the toxicities and benefits of
systemic adjuvant therapy
24. USE OF MULTIGENE ANALYSIS
• Small tumors (up to 0.5 cm in greatest diameter) that do not involve
the lymph nodes have a favorable prognosis so adjuvant
chemotherapy is not recommended.
• According to the NCCN Panel, adjuvant endocrine therapy may be
considered in this group of patients to reduce the risk for a second
contralateral breast cancer, as well as the small benefit in reducing
the risk of local/regional and distant recurrence.(Category 2B).
25. • For patients with invasive ductal or lobular tumors greater than 0.5
cm in diameter and N0, the NCCN panel recommends strongly
considering the 21-gene RT-PCR assay to help estimate likelihood of
recurrence and benefit from chemotherapy (category 1).
• The panel has noted that on an exploratory analysis from the TAILORx
study, adjuvant chemotherapy may be considered in patients <50
years with a 21-gene RS of 16-25.
• Also, patients with T1b tumors with low grade histology should be
considered for endocrine monotherapy, as the TAILORx study did
not include patients with such tumors.
(Neo)-adjuvant systemic treatment choice by marker expression and intrinsic phenotype. aWith possible exception of selected cases with very low risk T1abN0. bAnti-HER2: trastuzumab ± pertuzumab. cAdenoid cystic or apocrine, secretory carcinoma, low-grade metaplastic carcinoma. dDepending on level of ER and PgR expression, proliferation, genomically assessed risk, tumour burden and/or patient preference. eExcept for very low-risk patients T1abN0 for whom ET/anti-HER2 therapy alone can be considered. ChT, chemotherapy; ER, oestrogen receptor; ET, endocrine therapy; HER2, human epidermal growth factor receptor 2; N0, node-negative; PgR, progesterone receptor; TNBC, triple-negative breast cancer.
