Grading methodology
IMPLEMENTATION OF RECOMMENDATION
Will this recommendation result in changes in usual care?
Yes as women with a mutation may opt for bilateral mastectomy rather conservation, resulting in increased demand for bilateral mastectomy.
YE S
Are there any resource implications associated with implementing this recommendation?
There are no significant resource implications associated with implementing this recommendation.
NO
Will the implementation of this recommendation require changes in the way care is currently organised? This recommendation will not result in changes in the way care is currently organised.
NO
Is the guideline development group aware of any barriers to the implementation of this recommendation? Yes as may potentially be limited by availability of breast reconstructive surgery across Australia. Addition- ally uncertainty surrounding requesting genetic testing in those without a known genetic mutation.
YE S
Key question 1: What is the optimal surgical management, with or without radiotherapy, on the ipsilater- al side for women diagnosed with breast cancer with a BRCA 1/2 mutation?
Recommendation 2:
Recommend radiotherapy after breast conserving surgery in women diagnosed with breast cancer with a BRCA1/2 mutation to decrease the risk of ipsilateral breast cancer (as similarly recommended to other women with breast cancer that is not attributable to a BRCA1/2 mutation).
Metcalfe, Lynch 201120; Shanley 200621; Pierce 200022
Key question 1: What is the optimal surgical management, with or without radiotherapy, on the ipsilater- al side for women diagnosed with breast cancer with a BRCA 1/2 mutation?
1. Evidence base
Three Level III-2 retrospective cohort studies (A5 and A6 evidence statements) included in systematic review with generally a low risk of bias.
C
(One or two level III studies with a low risk of bias, or level I or II studies with a moderate risk of bias)
2. Consistency
Most studies consistent and any inconsistency may be explained.
B
(Most studies consistent and inconsis- tency may be explained)
3. Clinical impact
This course of treatment is already used in practice and therefore does not alter the recommended treatment of women post breast conserving surgery.
D
(Slight/Restricted)
4. Generalisability
Population/s studied in body of evidence are the same as the target population in the guideline.
A
(Population/s studied in body of evi- dence are the same as the target popu- lation in the guideline)
5. Applicability
Directly applicable to Australian healthcare context.
A
(Directly applicable to Australian health- care context)
Overall grade of recommendation: C
Body of evidence provides some support for recommendation(s) but care should be taken in its applica- tion
UNRESOLVED ISSUES None identified.
IMPLEMENTATION OF RECOMMENDATION
Will this recommendation result in changes in usual care?
There is no perceived change to standard clinical practice and care.
NO
Are there any resource implications associated with implementing this recommendation?
There are no significant resource implications associated with implementing this recommendation.
NO
Will the implementation of this recommendation require changes in the way care is currently organised? This recommendation will not result in changes in the way care is currently organised.
NO
Is the guideline development group aware of any barriers to the implementation of this recommendation? There are no barriers identified to the implementation of this recommendation.
NO
Key question 2: Are there particular neoadjuvant and adjuvant systemic therapies which are specifically effective for women diagnosed with breast cancer and a BRCA1/2 mutation?
Key question 2: Are there particular neoadjuvant and adjuvant systemic therapies which are specifically effective for women diagnosed with breast cancer and a BRCA1/2 mutation?
Base the use of neoadjuvant/adjuvant chemotherapy for women diagnosed with breast cancer with a BRCA1/2 mutation on similar considerations for women with breast cancer not attributable to a BRCA1/2 mutation. Goodwin 201234; Metcalfe, Lynch 201120; Metcalfe, Gershman 201135; Arun 201136; Pierce 201012; Reding
201037; Rennert 200738; Brekelmans 200639; Robson 200418
Component Grading
1. Evidence base
One Level II prospective cohort study, seven Level III-2 retrospective cohort studies and one Level III-3 case-control study (B1, B2, B3, B4, B8, B9 and B10 evidence statements) included in systematic review generally with low risk of bias.
B
(Several Level II/III studies with a low risk of bias)
2. Consistency
Rated as C due to inconsistencies in some study results comparing ad- juvant chemotherapy to no adjuvant chemotherapy. Also different varia- bles were compared and measured across the separate studies.
C
(Some inconsistency, reflecting genuine uncertainty around clinical question)
3. Clinical impact
No significant change to current clinical practice – this evidence reaf- firms the use of these clinical practices.
C
(Moderate)
4. Generalisability
Population/s studied in the body of evidence are similar to the target population for the guideline.
B
(Population/s studied in the body of evi- dence are similar to the target popula- tion for the guideline)
5. Applicability
Types of chemotherapy treatments readily available in Australia and currently widespread clinical practice. Therefore directly applicable to Australian healthcare context
A
(Directly applicable to Australian health- care context)
Overall grade of recommendation: C
Body of evidence provides some support for recommendation(s) but care should be taken in its applica- tion
UNRESOLVED ISSUES None identified.
IMPLEMENTATION OF RECOMMENDATION
Will this recommendation result in changes in usual care?
There is no perceived change to standard clinical practice and care.
NO
Are there any resource implications associated with implementing this recommendation?
There are no significant resource implications associated with implementing this recommendation.
NO
Will the implementation of this recommendation require changes in the way care is currently organised? This recommendation will not result in changes in the way care is currently organised.
NO
UNRESOLVED ISSUES None identified.
There are no barriers identified to the implementation of this recommendation.
Key question 2: Are there particular neoadjuvant and adjuvant systemic therapies which are specifically effective for women diagnosed with breast cancer and a BRCA1/2 mutation?
Recommendation 4:
Base the type of neoadjuvant/adjuvant chemotherapy for women diagnosed with breast cancer with a BRCA1/2 mutation on similar considerations for women with breast cancer not attributable to a BRCA1/2 mutation.
Arun 201136; Byrski 201040; Fourquet 200941; Byrski 200842
Component Grading
1. Evidence base
Four small Level III-2 retrospective cohort studies (B5, B6 and B7 evi- dence statements) with a low risk of bias included in the systematic re- view.
C
(One or two level III studies with a low risk of bias)
2. Consistency
Inconsistent results and findings across three small studies, suggesting an unclear conclusion from these studies.
C
(Some inconsistency, reflecting genuine uncertainty around clinical question)
3. Clinical impact
Results demonstrate largely unconvincing findings, therefore a slight/ restricted clinical impact and insufficient evidence to prefer one type of chemotherapy over another.
D
(Slight/Restricted)
4. Generalisability
Population/s studied in the body of evidence are similar to the target population for the guideline.
B
(Population/s studied in the body of evi- dence are similar to the target popula- tion for the guideline)
5. Applicability
Directly applicable to Australian healthcare context.
A
(Directly applicable to Australian health- care context)
Overall grade of recommendation: C
Body of evidence provides some support for recommendation(s) but care should be taken in its applica- tion
UNRESOLVED ISSUES None identified.
IMPLEMENTATION OF RECOMMENDATION
Will this recommendation result in changes in usual care?
There is no perceived change to standard clinical practice and care.
NO
Are there any resource implications associated with implementing this recommendation?
There are no significant resource implications associated with implementing this recommendation.
UNRESOLVED ISSUES None identified.
Will the implementation of this recommendation require changes in the way care is currently organised? This recommendation will not result in changes in the way care is currently organised.
NO
Is the guideline development group aware of any barriers to the implementation of this recommendation? There are no barriers identified to the implementation of this recommendation.
NO
Key question 2: Are there particular neoadjuvant and adjuvant systemic therapies which are specifically effective for women diagnosed with breast cancer and a BRCA1/2 mutation?
Recommendation 5:
Base the use and type of Selective Estrogen Receptor Modulators (SERMs) in women diagnosed with ER posi- tive breast cancer with a BRCA1/2 mutation on similar considerations for women with breast cancer not attribut- able to a BRCA1/2 mutation.
Phillips 201343; Goodwin 201234; Metcalfe, Gershman 201135; Metcalfe, Lynch 201120; Reding 201037; Pierce
201012; Pierce 200616; Gronwald 200644; Robson 200418; Foulkes 200245
Component Grading
1. Evidence base
One Level II prospective cohort study, five Level III-2 retrospective co- hort studies and one Level III-3 case-control study (B13, B14, B15, and B16 evidence statements) included in systematic review.
B
(Several Level II/III studies with a low risk of bias)
2. Consistency
Studies have a degree of inconsistency due to mixed populations and older cohorts.
C
(Some inconsistency, reflecting genuine uncertainty around clinical question)
3. Clinical impact
No change to current practice so minimal clinical impact.
D
(Slight/Restricted)
4. Generalisability
Population/s studied in body of evidence are the same as the target population for the guideline.
A
(Population/s studied in body of evi- dence are the same as the target popu- lation for the guideline)
5. Applicability
Directly applicable to Australian healthcare context.
A
(Directly applicable to Australian health- care context)
Overall grade of recommendation: C
Body of evidence provides some support for recommendation(s) but care should be taken in its applica- tion
UNRESOLVED ISSUES None identified.
IMPLEMENTATION OF RECOMMENDATION
UNRESOLVED ISSUES None identified.
There is no perceived change to standard clinical practice and care.
Are there any resource implications associated with implementing this recommendation?
There are no significant resource implications associated with implementing this recommendation.
NO
Will the implementation of this recommendation require changes in the way care is currently organised? This recommendation will not result in changes in the way care is currently organised.
NO
Is the guideline development group aware of any barriers to the implementation of this recommendation? There are no barriers identified to the implementation of this recommendation.
NO
Key question 3: What is the effectiveness of the use of surgical risk-reducing strategies for women with a BRCA1/2 mutation subsequent to diagnosis of breast cancer?
Recommendation 6:
Discuss contralateral risk-reducing mastectomy with women diagnosed with breast cancer with a BRCA1/2 mu- tation, particularly in younger women (less than 50 years), to substantially decrease the risk of contralateral
breast cancer.
Domchek 201046; Brekelmans 200639; Van Sprundel 200547; Metcalfe 200448
Component Grading
1. Evidence base
One Level II prospective cohort study and three Level III-2 retrospec- tive cohort studies (C1 and C2 evidence statements) included in sys- tematic review, generally with a low risk of bias.
B
(One level II study with low risk of bias, and several level III studies mostly with low risk of bias)
2. Consistency
All studies consistent with one another.
A
(All studies consistent)
3. Clinical impact
Recommending surgical risk-reducing strategies so substantial clinical impact.
B
(Substantial)
4. Generalisability
Population/s studied in body of evidence are the same as the target population for the guideline.
A
(Population/s studied in body of evi- dence are the same as the target popu- lation for the guideline)
5. Applicability
Directly applicable to Australian healthcare context.
A
(Directly applicable to Australian health- care context)
Overall grade of recommendation: B
Body of evidence can be trusted to guide practice in most situations
UNRESOLVED ISSUES None identified.
UNRESOLVED ISSUES None identified.
Will this recommendation result in changes in usual care?
This recommendation involves consideration of both ipsilateral and contralateral breast surgery.
YE S
Are there any resource implications associated with implementing this recommendation?
Yes, issue of cost of operating on both breasts (compared to one breast); accessibility to genetic counsel-
ling and testing; and accessibility to breast reconstructive options, particularly in rural areas.
YE S
Will the implementation of this recommendation require changes in the way care is currently organised? This recommendation will not result in changes in the way care is currently organised.
Level of organisation care depends on capacity of organisation providing care to patients. Need for access to plastic surgery but this need is the same for women requiring single mastectomy, regardless.
NO
Is the guideline development group aware of any barriers to the implementation of this recommendation? Yes, accessibility to genetic counselling and testing and accessibility to breast reconstructive options, which may be limited particularly in rural areas.
YE S
Key question 3: What is the effectiveness of the use of surgical risk-reducing strategies for women with a BRCA1/2 mutation subsequent to diagnosis of breast cancer?
Recommendation 7:
Discuss risk-reducing salpingo-oophorectomy with women diagnosed with breast cancer with a BRCA1/2 muta- tion around the age of 40 years or when child-bearing is complete to improve overall survival and substantially decrease the risk of ovarian/fallopian tube cancer.
Metcalfe, Lynch 201120; Metcalfe, Gershman 201135; Pierce 201012; Domchek 201046; Pierce 200616; Brekel- mans, 200639; Van Sprundel 200547
Component Grading
1. Evidence base
One Level II prospective cohort study and six Level III-2 retrospective cohort studies (C3, C4, C5 and C6 evidence statements) included in systematic review generally with a low risk of bias.
B
(One level II study with low risk of bias, and several level III studies mostly with low risk of bias)
2. Consistency
The evidence measures different outcomes: Two studies measure sur- vival outcomes, one study measures ipsilateral breast cancer, one study measures contralateral breast cancer and one study measures
ovarian cancer.
B
(Some caveats)
3. Clinical impact
Implementing a recommendation for risk-reducing salpingo-oophorec- tomy will have a very large clinical impact for these women.
A
(Very large)
4. Generalisability
Population/s studied in body of evidence are the same as the target population for the guideline.
A
(Population/s studied in body of evi- dence are the same as the target popu- lation for the guideline)
5. Applicability
Directly applicable to Australian healthcare context.
A
(Directly applicable to Australian health- care context)
Key question 3: What is the effectiveness of the use of surgical risk-reducing strategies for women with a BRCA1/2 mutation subsequent to diagnosis of breast cancer?
Overall grade of recommendation: B
Body of evidence can be trusted to guide practice in most situations UNRESOLVED ISSUES
None identified.
IMPLEMENTATION OF RECOMMENDATION
Will this recommendation result in changes in usual care?
Yes as involves consideration of salpingo-oophorectomy by women with a BRCA1/2 mutation, at around 40 years or when child-bearing decisions are complete, which is not considered usual care. Also dependent on where the patient is located.
YE S
Are there any resource implications associated with implementing this recommendation?
Yes as requirement for surgical and pathology evaluations and additionally referral to gynaecological spe- cialists (limited availability of speciality oncologists in rural areas).
YE S
Will the implementation of this recommendation require changes in the way care is currently organised? This recommendation will not result in changes in the way care is currently organised.
NO
Is the guideline development group aware of any barriers to the implementation of this recommendation? Yes as requires referral to gynaecological oncologists (limited availability of specialty oncologists).
YE S