Evidence
This page contains a snapshot of featured content which highlights evidence addressing key clinical questions including areas of uncertainty. Please see the main topic reference list for details of all sources underpinning this topic.
BMJ Best Practice evidence tables
Evidence tables provide easily navigated layers of evidence in the context of specific clinical questions, using GRADE and a BMJ Best Practice Effectiveness rating. Follow the links at the bottom of the table, which go to the related evidence score in the main topic text, providing additional context for the clinical question. Find out more about our evidence tables.
This table is a summary of the analysis reported in a guideline (underpinned by a systematic review) that focuses on the above important clinical question.
Confidence in the evidence is moderate or low to moderate where GRADE has been performed and the intervention may be more effective/beneficial than the comparison for key outcomes.
Population: Women with invasive breast cancer (M stage 0) who have undergone breast-conserving surgery
Intervention: Whole-breast radiotherapy
Comparison: No whole-breast radiotherapy
| Outcome | Effectiveness (BMJ rating)? | Confidence in evidence (GRADE)? |
|---|---|---|
Local recurrence at 10 years for women with T stage 1 | Favours intervention | Moderate |
Local recurrence at 5 years for women with N stage 0 | Favours intervention | Moderate |
Local recurrence at 5 years for women with negative surgical margins | Favours intervention | Moderate |
Local recurrence at 5 years for women ≥65 years | Favours intervention | Low |
Treatment-related morbidity: fractures ᵃ | No statistically significant difference | Low |
Treatment-related morbidity: congestive cardiac failure ᵃ | No statistically significant difference | Moderate |
Treatment-related morbidity: myocardial infarction ᵃ | No statistically significant difference | Low |
Treatment-related morbidity: secondary cancer ᵃ | No statistically significant difference | Low |
Treatment-related morbidity: score 10+ on Hospital Anxiety and Depression Scale ᵃ | No statistically significant difference ᵇ | Low |
Health-related quality of life (measured with EuroQol Research Foundation measure of general health status EQ5D scale) ᵃ | No statistically significant difference | Low |
Recommendations as stated in the source guideline The National Institute of Health and Care Excellence 2018 guideline on Early and locally advanced breast cancer: diagnosis and management makes the following recommendation: Offer whole‑breast radiotherapy to women with invasive breast cancer who have had breast‑conserving surgery with clear margins.
Note Only outcomes that NICE considered critical to decision-making are reported in this table. Please see the full guideline for information on overall survival which was considered an important outcome (NICE did not identify any evidence for the other important outcomes: disease-free survival or treatment-related mortality). The following subgroups of women were of interest to the guideline committee but no direct evidence was identified: women with positive surgical margins, oestrogen-receptor (ER) status, human epidermal growth factor receptor 2 (HER2) status, tumour grade, younger age, women who received adjuvant systemic therapy, T stage 2 and above, and N stage 1 and above. The committee noted that radiotherapy reduces recurrence rates for all women, but the benefits and risks must be discussed with individual patients. They made separate recommendations for women considered to be at low or very low risk of local recurrence (see guideline for more information). ᵃ Evidence only found for women aged 65 years and over with N stage 0 invasive breast cancer and negative surgical margins; 5-year follow-up. ᵇ The guideline committee felt the results were clinically significant; however, they were not statistically significant, event rates were low, and were only measured at a single point in time.
This evidence table is related to the following section/s:
This table is a summary of the analysis reported in a guideline (underpinned by a systematic review) that focuses on the above important clinical question.
Confidence in the evidence is moderate or low to moderate where GRADE has been performed and there is a trade off between benefits and harms of the intervention.
Population: Adults (≥18 years) with invasive breast cancer (M stage 0) who have undergone primary mastectomy.
Intervention: Radiotherapy to the chest wall +/- nodes
Comparison: No radiotherapy
| Outcome | Effectiveness (BMJ rating)? | Confidence in evidence (GRADE)? |
|---|---|---|
Radiotherapy to the chest wall plus nodes versus no radiotherapy | ||
Treatment-related morbidity at 9 years: lymphoedema | No statistically significant difference | Very Low |
Treatment-related morbidity at 9 years: myocardial infarction | No statistically significant difference | Very Low |
Treatment-related morbidity at 9 years: irreversible clinical heart failure or lung morbidity | See notes ᵃ | Moderate |
Radiotherapy to the chest wall plus nodes versus no radiotherapy following mastectomy without axillary surgery | ||
First locoregional recurrence during years 0-9 | Favours intervention | Moderate to Low ᵇ |
20-year all-cause mortality | No statistically significant difference | Moderate |
Treatment-related morbidity: women with arm oedema on final measurement at 2 to 5 years' follow-up | Favours intervention | Low |
Radiotherapy to the chest wall plus nodes versus no radiotherapy following mastectomy with axillary surgery (women with invasive breast cancer and node-negative disease) | ||
First locoregional recurrence during years 0-9 (mastectomy plus axillary dissection) | No statistically significant difference | Low |
First locoregional recurrence during years 0-9 (mastectomy plus axillary sampling) | Favours intervention | Low |
20-year all-cause mortality (mastectomy plus axillary dissection) | Favours comparison | Moderate |
20-year all-cause mortality (mastectomy plus axillary sampling) | No statistically significant difference | Moderate |
Radiotherapy to the chest wall plus nodes versus no radiotherapy following mastectomy with axillary surgery (women with invasive breast cancer and node-positive disease) | ||
First locoregional recurrence during years 0-9 | Favours intervention | Low |
20-year all-cause mortality (mastectomy plus axillary dissection) | No statistically significant difference | Moderate to Low ᶜ |
20-year all-cause mortality (mastectomy plus axillary sampling) | Favours intervention | Moderate to Low ᶜ |
Treatment-related cardiac morbidity (ischaemic heart disease at 10 years; congestive heart failure at 15 years; or acute myocardial infarction at 10 or 20 years) | No statistically significant difference | Low |
Treatment-related morbidity: arm oedema requiring intervention at 15 years | No statistically significant difference | Low |
Treatment-related morbidity: pneumonitis at 15 years | No statistically significant difference | Low |
Recommendations as stated in the source guideline The National Institute of Health and Care Excellence 2018 guideline on Early and locally advanced breast cancer: diagnosis and management makes the following recommendations: Offer adjuvant post-mastectomy radiotherapy to people with node‑positive (macrometastases) invasive breast cancer or involved resection margins. Consider adjuvant post-mastectomy radiotherapy for people with node‑negative T3 or T4 invasive breast cancer. Do not offer radiotherapy following mastectomy to people with invasive breast cancer who are at low risk of local recurrence (for example, most people who have lymph node‑negative breast cancer).
Note Only outcomes that NICE considered critical to decision making are reported in this table. Please see the full guideline for more information. The guideline committee concluded that post-mastectomy radiotherapy should be offered to women at high risk of local recurrence as the benefits are likely to outweigh the risk. They also agreed that radiotherapy should not be offered to women at low risk of local recurrence (for example, women with node-negative disease and small tumours), as the potential for harm outweighed possible benefit. They made a weak ‘consider’ recommendation for women at intermediate risk as they felt the decision needed to be made on an individual basis, and warned that there was still a risk of overtreatment in women with intermediate risk disease. ᵃ Not estimable due to no events in either group. ᵇ GRADE was low for women with clinically node-negative disease and moderate for women with node-positive disease. ᶜ GRADE was low for women with 4+ pathologically positive nodes and moderate for women with 1-3 pathologically positive nodes.
This evidence table is related to the following section/s:
This table is a summary of the analysis reported in a guideline (underpinned by a systematic review) that focuses on the above important clinical question.
Confidence in the evidence is high or moderate to high where GRADE has been performed and there is a trade-off between benefits and harms of the intervention.
Population: Adults (≥18 years) with invasive breast cancer (M stage 0) who are planned to have surgery
Intervention: Anthracycline-containing neoadjuvant chemotherapy regimens ± biological therapy
Comparison: No neoadjuvant chemotherapy ± biological therapy
| Outcome | Effectiveness (BMJ rating)? | Confidence in evidence (GRADE)? |
|---|---|---|
Local recurrence (follow-up: 8-16 years) | See note ᵃ | High |
Locoregional recurrence-free survival (follow-up: 5-16 years) | No statistically significant difference | High |
Disease-free survival (follow-up: 2-16 years) | No statistically significant difference | High |
Breast-conservation therapy rate (follow-up: post-op) | Favours intervention | Low |
Overall survival (follow-up: 2-16 years) | No statistically significant difference | High |
Response rates | See note ᵇ | Low |
Any post-operative complications (follow-up: post-op) | No statistically significant difference | Low |
Cardiotoxicity (follow-up: during or post-chemotherapy) | No statistically significant difference | Low |
Leucopaenia, neutropaenia, or infection (follow-up: during or post-chemotherapy) | Favours intervention | High |
Nausea or vomiting (follow-up: during or post-chemotherapy) | No statistically significant difference | Low |
Alopecia (follow-up: during or post-chemotherapy) | No statistically significant difference | High |
Recommendations as stated in the source guideline The National Institute of Health and Care Excellence (NICE) 2018 guideline on Early and locally advanced breast cancer: diagnosis and management makes the following recommendations: Offer neoadjuvant chemotherapy to people with oestrogen receptor (ER)‑negative invasive breast cancer as an option to reduce tumour size. Consider neoadjuvant chemotherapy for people with ER‑positive invasive breast cancer as an option to reduce tumour size if chemotherapy is indicated.
Note The BMJ evidence rating and corresponding rating text in this table have been chosen as the guideline committee debated the balance of benefits (increase in breast conservation therapy and reduced risk of leucopaenia or neutropaenia) and harms (risk of local recurrence) of treatment, and only made a strong guideline recommendation for people with ER-negative invasive breast cancer. Overall, in the absence of any evidence of a difference in overall or disease-free survival, the guideline committee felt the benefits of neoadjuvant chemotherapy (increase in breast conservation therapy and reduced risk of leucopaenia or neutropaenia) outweighed the small risk of local recurrence. The guideline also considered evidence looking at predictive factors for response to anthracycline-containing neoadjuvant chemotherapy. They found low-quality evidence that people with ER-negative invasive breast cancer might respond better to neoadjuvant chemotherapy (see guideline for more information). The guideline committee also acknowledged existing NICE technology appraisal guidance (TA424) which recommends neoadjuvant pertuzumab in patients with HER2-positive breast cancer, and therefore made a separate recommendation for this group (see guideline for more information). ᵃ Although not statistically significant, the guideline committee decided that the results (HR 1.16, 95% CI 0.98 to 1.38) could represent a small potential increased risk of local recurrence with anthracycline-containing neoadjuvant chemotherapy compared with no neoadjuvant chemotherapy. ᵇ There was low-quality observational evidence from the neoadjuvant chemotherapy arms of 7 RCTs (N=2173) that the objective response rate ranged from 11% to 83%, and the pathological complete response rate from 4% to 23% (data not pooled).
This evidence table is related to the following section/s:
This table is a summary of the analysis reported in a guideline (underpinned by a systematic review) that focuses on the above important clinical question.
Confidence in the evidence is very low or low where GRADE has been performed and there may be no difference in effectiveness between the intervention and comparison for key outcomes. However, this is uncertain and new evidence could change this in the future.
Population: Post-menopausal women with oestrogen receptor (ER)-positive/HER2 unknown or HER2-negative invasive breast cancer (M stage 0) who have not yet undergone surgery
Intervention: Neoadjuvant endocrine therapy
Comparison: No neoadjuvant endocrine therapy or neoadjuvant chemotherapy
| Outcome | Effectiveness (BMJ rating)? | Confidence in evidence (GRADE)? |
|---|---|---|
Neoadjuvant endocrine therapy versus no neoadjuvant endocrine therapy | ||
Overall survival (6.7 year follow-up) | No statistically significant difference | Low |
Neoadjuvant endocrine therapy versus neoadjuvant chemotherapy | ||
Breast conservation rates | No statistically significant difference | Very Low |
Changes in tumour size: clinical response | No statistically significant difference | Low |
Changes in tumour size: complete or partial radiological response on ultrasound | No statistically significant difference | Very Low |
Changes in tumour size: complete or partial radiological response on mammography | No statistically significant difference | Very Low |
Overall survival (4-year follow-up) | No statistically significant difference | Very Low |
Recommendations as stated in the source guideline The National Institute of Health and Care Excellence 2018 guideline on Early and locally advanced breast cancer: diagnosis and management makes the following recommendations: Consider neoadjuvant endocrine therapy for post-menopausal women with ER‑positive invasive breast cancer as an option to reduce tumour size if there is no definite indication for chemotherapy. Discuss with women the benefits and risks of neoadjuvant endocrine therapy compared with neoadjuvant chemotherapy.
Note For neoadjuvant endocrine therapy compared with no neoadjuvant endocrine therapy, the guideline did not identify any evidence for any of the critical outcomes (disease-free survival, breast conservation rates, or changes in tumour size). Due to the uncertainty in the evidence, the guideline committee discussed their clinical experience and knowledge of the balance of benefits with side-effect profiles and patient acceptability of endocrine therapy compared with chemotherapy. They concluded that individual discussions of benefit and harms were very important to allow patients to make an informed decision. The committee agreed that in post-menopausal women, neoadjuvant endocrine therapy and neoadjuvant chemotherapy were equally effective, but from their expert knowledge and clinical experience the treatment-related comorbidity was much less with the endocrine therapy.
This evidence table is related to the following section/s:
Cochrane Clinical Answers
Cochrane Clinical Answers (CCAs) provide a readable, digestible, clinically focused entry point to rigorous research from Cochrane systematic reviews. They are designed to be actionable and to inform decision making at the point of care and have been added to relevant sections of the main Best Practice text.
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- In women with early breast cancer, how do different types of follow-up strategy compare with each other for improving outcomes?
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