Breast Cancer
Figure 5: Distribution of Recurrence Score and Standard Prognostic Factors
A 100
60 80
20 40
0
n=63 <40
B 100
60 80
40 20 0
64% 20% 16%
n=110 ≤1
25% 19% 56%
n=318 1.1–2
30% 23% 46%
n=196 2.1–4
Clinical tumour size (cm) C 100
60 80
20 40
0
n=77 Well
Tumour grade (site) n=339
Moderate
n=163 Poor
A: Recurrence Score (RS) versus age; B: RS versus clinical tumour size; C: RS by tumour grade (National Surgical Adjuvant Breast and Bowel Project [NSABP] site pathologist).17 Reprinted with permission. © 2008 American Society of Clinical Oncology. All rights reserved. Paik S, et al., Gene Expression and Benefit of Chemotherapy in Women With Node- Negative, Estrogen Receptor-Positive Breast Cancer, J Clin Oncol, Vol. 24, No 23 (August 10), 2006: 3726–3734.
Of these, 872 women had node-negative and 306 node-positive disease, and in 53 cases nodal status was unknown. In a prospectively defined multivariate analysis, tumour size, grade and RS were each separately statistically significant in predicting time to distant recurrence in node-negative patients (p<0.01, 0.003 and <0.001). Similar results were seen in node-positive patients. For node-negative patients, distribution into the three risk categories was 59% for low,
40
73% 16% 12%
22% 22% 56%
42% 22% 36%
p<0.001
33% 21% 46%
n=24 >4
• In 2007, the American Society of Clinical Oncology (ASCO) updated its recommendations for the use of tumour markers in breast cancer. Oncotype DX is the only multigene assay recommended for use in newly diagnosed ER-positive, node-negative breast cancer patients to predict risk of recurrence. It is also recommended to identify patients who may be spared adjuvant chemotherapy.18
Among the plethora of potential new prognostic
factors, the only other prognostic factor recommended by ASCO for breast cancer decision-making was the urokinase plasminogen activator (uPA/plasminogen activator inhibitor 1 (PAI-1) assay.19
• The updated National Comprehensive Cancer Network guidelines include the option of using Oncotype DX to help guide chemotherapy treatment decisions within the systemic adjuvant treatment decision pathway for patients with node-negative or pN1mi HR-positive, HER-2-negative tumours that are 0.6–1cm in diameter and moderately/poorly differentiated, or with unfavourable features or >1cm in diameter.20
• In 2009 the St Gallen international expert consensus conference on the primary therapy of early breast cancer acknowledged the added value of validated multigene assays in the decision process for adjuvant chemotherapy of patients with ER-positive, HER-2- negative disease.21
• The 2010 guidelines of the German Arbeitsgruppe Gynaekologische Onkologie (AGO) consider Oncotype DX a prognostic marker for node-negative breast cancer (AGO±). To further clarify its prognostic and predictive value regarding adjuvant chemotherapy decision-making, the AGO recommends participation in clinical studies and using the assay as a predictive marker for decision- making for adjuvant chemotherapy only in individual cases outside clinical studies.22
Impact of Recurrence Score on Clinical Decision-making
Oncotype DX has been used in more than 120.000 patients in over 50 countries.23
An analysis of all ER-positive tumour specimens successfully examined in the Genomic Health Laboratory from June 2004 to December 2008 was performed.24
There were 347 male and
82,434 female breast cancer patients included in the analysis. The distribution of female breast cancer patients showed 53.4, 36.3 and 10.3% in the low, intermediate and high RS groups, respectively. While the proportion of low-risk tumours was similar to those found in the
EUROPEAN ONCOLOGY
n=226 40–49
n=166 50–59
Patient age (years) p=0.001
n=196 ≥60
Adoption of Oncotype DX in International Treatment Guidelines
Several international scientific societies and study groups have evaluated multigene assays in their guidelines:
44% 14% 41%
24% 21% 55%
28% 22% 50%
19% 21% 60%
p=0.018
26% for intermediate and 15% for high RS, and the nine-year rates of distant recurrence were 4, 12 and 25%, respectively. Both distribution of patients into the three RS categories and proportions of rates of distant recurrence were very similar to the patient distribution and rates of distant recurrence at 10 years reported by Paik in the NSABP B-14 validation set. For the node-positive subset, distribution into the low, intermediate and high RS groups were 52, 31 and 17%, respectively, with rates of distant recurrence at nine years of 17, 28 and 49%, respectively. RS showed statistically significant prognostic value beyond that provided in Adjuvant! Online in both node-negative (p<0.001) and node-positive patients (p=0.003). The data could not depict a differential benefit between anastrozole and tamoxifen, i.e. RS does not seem to be predictive for type of endocrine therapy.
Recurrence Score
Recurrence Score
Recurrence Score
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