12. Towards the treatment of invasive breast cancer
12.1 Should a threshold of 10% or more vs. 1% or more of cells showing oestrogen receptor positivity be used for providing endocrine therapy in women with invasive breast cancer?
Recommendation
In women with invasive breast cancer, the ECIBC's Guidelines Development Group (GDG) suggests administration of adjuvant endocrine therapy if 1% or greater of tumour cells show oestrogen receptor positivity rather than applying a threshold of 10% tumour cell oestrogen receptor positivity.
Issued in September 2017.
Justification
The GDG agreed by consensus that the limited very low quality evidence reviewed favours the current practice, using an oestrogen receptor (ER) threshold of 1% positivity.
Monitoring and evaluation
The GDG suggested monitoring low (1-9%) and high (10% and above) ER positivity in relation to patient outcomes to better assess ER thresholds for treatment.
Research priorities
- New research using ideally modern oestrogen receptor (ER) immunohistochemical techniques on tumour tissue primarily fixed in 10% neutral buffered formalin.
- The GDG suggested additional observational studies to provide evidence on the current threshold used in practice, ideally using modern immunohistochemical techniques.
Supporting material
12.2 Should a threshold of 10% or more vs. 1% or more of cells showing progesterone receptor positivity be used for providing endocrine therapy in women with invasive breast cancer?
Recommendation
In women with invasive breast cancer, the ECIBC's Guidelines Development Group (GDG) suggests administration of adjuvant endocrine therapy if 1% or greater of tumour cells show progesterone receptor positivity rather than applying a threshold of 10% tumour cell progesterone receptor positivity.
Issued in September 2017.
Justification
The GDG agreed by consensus that the limited, very low quality evidence reviewed, favours the current practice, of using a progesterone (PR) threshold of 1% positivity.
Monitoring and evaluation
The GDG suggested monitoring low (1-9%) and high (10% and above) PR positivity in relation to patient outcomes to better assess PR thresholds for treatment.
Research priorities
- New research using ideally modern progesterone receptor (PR) immunohistochemical techniques on tumour tissue primarily fixed in 10% neutral buffered formalin.
- The GDG suggested additional observational studies to provide evidence on the current threshold used in practice, ideally using modern immunohistochemical techniques.
Supporting material
12.3 Should 70 gene signature test vs. no testing be used for patients who have hormone receptor positive, HER2-negative, lymph node negative or up to 3 lymph nodes positive invasive breast cancer to guide the use of chemotherapy (subgroup: low clinical risk)?
Recommendation
For women with hormone receptor positive, HER2-negative, lymph node negative or up to 3 lymph nodes positive invasive breast cancer at low clinical risk, the ECIBC's Guidelines Development Group (GDG) recommends not using the 70 gene signature test to guide the use of chemotherapy.
Issued in November 2018.
Justification
In the low clinical risk group the recommendation is strong against using the 70 gene signature testing to guide the use of chemotherapy as there were no benefits to using the test and a very large cost.
Subgroup considerations
The proportion of women with 2 or 3 node positive breast cancer were small, so the results may be less clear in this subgroup.
Definition
Low clinical risk refers to those patients with HR-positive and HER2-negative invasive breast cancer with either:
- G1 and node negative and tumour size </= 3cm
- G1 and 1-3 positive nodes and tumour size </= 2cm
- G2 and node negative and tumour size </= 2cm
- G3 and node negative and tumour size </= 1cm.
According to Adjuvant! Online (version 8.0 with HER2 Status) described in detail in the MINDACT trial (Cardoso F., van't Veer L.J., Bogaerts J., Slaets L., Viale G., Delaloge S.et al., 70-Gene Signature as an Aid to Treatment Decisions in Early-Stage Breast Cancer, 2016).
Considerations for implementation and policy making
Decreasing cost for the test would support widespread use - price negotiations may be appropriate.
Research priorities
Longer follow up studies would be needed, as currently there is only a follow-up of five years.
Supporting material
12.4 Should 70 gene signature test vs. no testing be used for patients who have hormone receptor positive, HER2-negative, lymph node negative or up to 3 lymph nodes positive invasive breast cancer to guide the use of chemotherapy (subgroup: high clinical risk)?
Recommendation
For women with hormone receptor positive, HER2-negative, lymph node negative or up to 3 lymph nodes positive invasive breast cancer at high clinical risk, the ECIBC's Guidelines Development Group (GDG) suggests using the 70 gene signature test to guide the use of chemotherapy.
Issued in November 2018.
Justification
In the high clinical risk group, the recommendation is conditional in favour of using the 70 gene signature testing to guide the use of chemotherapy mainly because of the low certainty of the evidence.
Subgroup considerations
The proportion of women with 2 or 3 node positive breast cancer were small, so the results may be less clear in this subgroup.
Definition
High clinical risk refers to those patients with HR-positive and HER2-negative invasive breast cancer with either:
- G1 and node negative and tumour size 3.1-5 cm
- G1 and 1-3 positive nodes and tumour size 2.1-5 cm
- G2 and node negative and tumour size 2.1-5 cm
- G2 and 1-3 positive nodes and any tumour size
- G3 and node negative and tumour size 2.1-5 cm
- G3 and 1-3 positive nodes and any tumour size.
According to Adjuvant! Online (version 8.0 with HER2 Status) described in detail in the MINDACT trial (Cardoso F., van't Veer L.J., Bogaerts J., Slaets L., Viale G., Delaloge S.et al., 70-Gene Signature as an Aid to Treatment Decisions in Early-Stage Breast Cancer, 2016).
Considerations for implementation and policy making
Decreasing cost for the test would support widespread use - price negotiations may be appropriate.
Research priorities
Longer follow up studies would be needed, as currently there is only a follow-up of five years.
Supporting material
12.5 Should 21 gene recurrence score vs. no testing be used for patients who have hormone receptor positive, HER2-negative, lymph node negative or up to 3 lymph nodes positive invasive breast cancer to guide the use of chemotherapy?
Recommendation
For women with hormone receptor positive, HER2-negative, lymph node negative invasive breast cancer, the ECIBC's Guidelines Development Group (GDG) suggests using the 21 gene recurrence score to guide the use of chemotherapy.
Issued in November 2018.
Justification
The recommendation is conditional because there was uncertainty about the evidence and the corresponding exact effects, thus making the balance of benefits and harms not completely clear, together with large costs.
Please also see the subgroup considerations that provide additional information and rationale.
Subgroup considerations
The GDG did not consider women with node positive invasive breast cancer to be included in this recommendation.
Women with high clinical risk and low genomic risk (larger tumour diameter and higher grade) may experience larger net desirable consequences and provide a better cost-benefit profile.
Women with low clinical risk and high genomic risk may experience smaller or no net desirable consequences. Indirect evidence from other gene based testing (e.g. 70 gene signature) supports that former conclusion.
Definitions
High clinical risk refers to those patients with HR-positive and HER-2 negative invasive breast cancer with either:
- G1 and node negative and tumour size 3.1-5 cm
- G1 and 1-3 positive nodes and tumour size 2.1-5 cm
- G2 and node negative and tumour size 2.1-5 cm
- G2 and 1-3 positive nodes and any tumour size
- G3 and node negative and tumour size 2.1-5 cm
- G3 and 1-3 positive nodes and any tumour size.
Low clinical risk refers to those patients with HR-positive and HER2-negative invasive breast cancer with either:
- G1 and node negative and tumour size </= 3cm
- G1 and 1-3 positive nodes and tumour size </= 2cm
- G2 and node negative and tumour size </= 2cm
- G3 and node negative and tumour size </= 1cm.
According to Adjuvant! Online (version 8.0 with HER2 Status) described in detail in the MINDACT trial (Cardoso F., van't Veer L.J., Bogaerts J., Slaets L., Viale G., Delaloge S.et al., 70-Gene Signature as an Aid to Treatment Decisions in Early-Stage Breast Cancer, 2016).
Considerations for implementation and policy making
Decreasing cost for the test would support widespread use - price negotiations may be appropriate. Data protection issues may be relevant because the samples are sent out (currently conducted only in the US).
Research priorities
Exploration of subgroups with anticipated larger benefits (risk stratification) or those that will not benefit from using the test for stratification to guide chemotherapy use e.g. women under 50.
Supporting material