Table 1.
GRADE evaluation of interventions for breast cancer (non-metastatic)
| Important outcomes | Treatment success, mortality, adverse effects | ||||||||
| Number of studies (participants) | Outcome | Comparison | Type of evidence | Quality | Consistency | Directness | Effect size | GRADE | Comment |
| What are the effects of interventions after breast-conserving surgery for ductal carcinoma in situ? | |||||||||
| 4 (3925) | Treatment success | Radiotherapy v no radiotherapy | 4 | 0 | 0 | 0 | 0 | High | |
| 2 (2327) | Treatment success | Tamoxifen plus radiotherapy v radiotherapy plus placebo | 4 | −1 | −1 | 0 | 0 | Low | Quality point deducted for incomplete reporting of result. Consistency point deducted for conflicting results |
| 1 (1804) | Mortality | Tamoxifen plus radiotherapy v radiotherapy plus placebo | 4 | −1 | 0 | 0 | 0 | Moderate | Quality point deducted for incomplete reporting of results |
| What are the effects of treatments for primary operable breast cancer? | |||||||||
| 1 (5187 | Mortality | Adjuvant aromatase inhibitors v placebo | 4 | −1 | 0 | 0 | 0 | Moderate | Quality point deducted for incomplete reporting of results |
| 2 (14,068) | Treatment success | Adjuvant aromatase inhibitors v tamoxifen | 4 | −1 | 0 | 0 | 0 | Moderate | Quality point deducted for incomplete reporting of results |
| 2 (14,068) | Mortality | Adjuvant aromatase inhibitors v tamoxifen | 4 | −1 | 0 | 0 | 0 | Moderate | Quality point deducted for incomplete reporting of results |
| 1 (9366) | Treatment success | Adjuvant aromatase inhibitors plus tamoxifen v tamoxifen alone | 4 | −1 | 0 | 0 | 0 | Moderate | Quality point deducted for incomplete reporting of results |
| 47 (18,000) | Treatment success | Adjuvant combination chemotherapy v no chemotherapy | 4 | −1 | 0 | 0 | 0 | Moderate | Quality point deducted for incomplete reporting of results |
| 47 (18,000) | Mortality | Adjuvant combination chemotherapy v no chemotherapy | 4 | −1 | 0 | 0 | 0 | Moderate | Quality point deducted for incomplete reporting of results |
| not reported (3454) | Treatment success | Different treatment durations compared with each other (prolonged adjuvant combination chemotherapy) | 4 | 0 | 0 | 0 | 0 | High | |
| not reported (3454) | Mortality | Different treatment durations compared with each other (prolonged adjuvant combination chemotherapy) | 4 | 0 | 0 | 0 | 0 | High | |
| 3 (4399) | Treatment success | Different doses compared with each other (enhanced-dose regimens of adjuvant combination chemotherapy) | 4 | −1 | 0 | 0 | 0 | Moderate | Quality point deducted for incomplete reporting of results |
| 3 (4399) | Mortality | Different doses compared with each other (enhanced-dose regimens of adjuvant combination chemotherapy) | 4 | −1 | 0 | 0 | 0 | Moderate | Quality point deducted for incomplete reporting of results |
| 12 (6719) | Treatment success | Anthracycline regimens v standard CMF (cyclophosphamide, methotrexate, fluorouracil) regimens | 4 | −1 | 0 | 0 | 0 | Moderate | Quality point deducted for incomplete reporting of results |
| 12 (6719) | Mortality | Anthracycline regimens v standard CMF regimens | 4 | −1 | 0 | 0 | 0 | Moderate | Quality point deducted for incomplete reporting of results |
| 55 (37,000, primarily with oestrogen) | Treatment success | Adjuvant tamoxifen v placebo | 4 | −1 | 0 | 0 | 0 | Moderate | Quality point deducted for incomplete reporting of results |
| 55 (37,000) | Mortality | Adjuvant tamoxifen v placebo | 4 | −1 | 0 | 0 | 0 | Moderate | Quality point deducted for incomplete reporting of results |
| 1 (3887) | Treatment success | Durations of treatment compared with each other (adjuvant tamoxifen) | 4 | −1 | 0 | 0 | 0 | Moderate | Quality point deducted for incomplete reporting of results |
| 1 (3887) | Mortality | Durations of treatment compared with each other (adjuvant tamoxifen) | 4 | −1 | 0 | 0 | 0 | Moderate | Quality point deducted for incomplete reporting of results |
| 1 (3387) | Treatment success | Trastuzumab v observation (after chemotherapy) | 4 | −1 | 0 | 0 | 0 | Moderate | Quality point deducted for incomplete reporting of results |
| 1 (3387) | Mortality | Trastuzumab v observation (after chemotherapy) | 4 | −1 | 0 | 0 | 0 | Moderate | Quality point deducted for incomplete reporting of results |
| 2 (3351) | Treatment success | Trastuzumab v observation (during chemotherapy) | 4 | −1 | 0 | 0 | 0 | Moderate | Quality point deducted for incomplete reporting of results |
| 2 (3351) | Mortality | Trastuzumab v observation (during chemotherapy) | 4 | −1 | 0 | 0 | 0 | Moderate | Quality point deducted for incomplete reporting of results |
| 15 (26,277) | Treatment success | Adjuvant taxane-based regimens v anthracycline-based regimens | 4 | −1 | 0 | 0 | 0 | Moderate | Quality point deducted for incomplete reporting of results |
| 15 (26,277) | Mortality | Adjuvant taxane-based regimens v anthracycline-based regimens | 4 | −1 | 0 | 0 | 0 | Moderate | Quality point deducted for incomplete reporting of results |
| 1 (4950) | Treatment success | Different adjuvant taxane-based regimens v each other | 4 | −1 | 0 | 0 | 0 | Moderate | Quality point deducted for incomplete reporting of results |
| Mortality | Different adjuvant taxane-based regimens v each other | 4 | −1 | 0 | 0 | 0 | Moderate | Quality point deducted for incomplete reporting of results | |
| 4 (1296) | Mortality | Radical/total mastectomy v simple mastectomy plus radiotherapy | 4 | −1 | 0 | 0 | 0 | Moderate | Quality point deducted for incomplete reporting of results |
| 1 (666) | Treatment success | Radical or total mastectomy v simple mastectomy plus radiotherapy | 4 | −1 | 0 | 0 | 0 | Moderate | Quality point deducted for incomplete reporting of results |
| 5 (2090) | Mortality | Supraradical, radical, and total mastectomy v each other | 4 | −1 | 0 | 0 | 0 | Moderate | Quality point deducted for incomplete reporting of results |
| 9 (3107) | Treatment success | Mastectomy v breast conservation with or without radiotherapy | 4 | 0 | 0 | −1 | 0 | Moderate | Directness point deducted as unclear how many women in analysis received radiotherapy |
| 9 (at least 4891) | Mortality | Mastectomy v breast conservation with or without radiotherapy | 4 | 0 | 0 | −1 | 0 | Moderate | Directness point deducted as unclear how many women in analysis received radiotherapy |
| 1 (705) | Treatment success | Different extents of local excision compared with each other | 4 | −1 | 0 | 0 | 0 | Moderate | Quality point deducted for incomplete reporting of results |
| 12 (2102) | Treatment success | Ovarian ablation v no ablation | 4 | −1 | 0 | 0 | 0 | Moderate | Quality point deducted for incomplete reporting of results |
| 12 (2102) | Mortality | Ovarian ablation v no ablation | 4 | −1 | 0 | 0 | 0 | Moderate | Quality point deducted for incomplete reporting of results |
| 11 (7575) | Treatment success | Breast-conserving surgery plus radiotherapy v breast-conserving surgery alone | 4 | −1 | 0 | 0 | 0 | Moderate | Quality point deducted for incomplete reporting of results |
| 11 (7575) | Mortality | Breast-conserving surgery plus radiotherapy v breast-conserving surgery alone | 4 | −1 | 0 | 0 | 0 | Moderate | Quality point deducted for incomplete reporting of results |
| 7 (3294) | Mortality | Breast-conserving surgery plus radiotherapy v mastectomy | 4 | −1 | 0 | 0 | 0 | Moderate | Quality point deducted for incomplete reporting of results |
| 1 (666) | Treatment success | Breast-conserving surgery plus radiotherapy v breast-conserving surgery plus endocrine therapy | 4 | 0 | 0 | 0 | 0 | High | |
| 1 (666) | Mortality | Breast-conserving surgery plus radiotherapy v breast-conserving surgery plus endocrine therapy | 4 | −1 | 0 | 0 | 0 | Moderate | Quality point deducted for assessment of only among-group differences for this outcome (3-armed trial) |
| 4 (2907) | Treatment success | Breast-conserving surgery plus radiotherapy plus endocrine therapy v breast-conserving surgery plus endocrine therapy only | 4 | −1 | −1 | 0 | 0 | Low | Quality point deducted for incomplete reporting. Directness point deducted for different results with measures of treatment success |
| 3 (2268) | Mortality | Breast-conserving surgery plus radiotherapy plus endocrine therapy v breast-conserving surgery plus endocrine therapy only | 4 | −1 | 0 | 0 | 0 | Moderate | Quality point deducted for incomplete reporting |
| 36 (8505 node positive) | Treatment success | Radiotherapy after mastectomy v mastectomy | 4 | −1 | 0 | 0 | 0 | Moderate | Quality point deducted for incomplete reporting of results |
| 36 (8505 node positive) | Mortality | Radiotherapy after mastectomy v mastectomy | 4 | −1 | 0 | 0 | 0 | Moderate | Quality point deducted for incomplete reporting of results |
| 4 (2802) | Treatment success | Primary chemotherapy v adjuvant chemotherapy | 4 | −1 | 0 | 0 | 0 | Moderate | Quality point deducted for incomplete reporting of results |
| 5 (3216) | Mortality | Primary chemotherapy v adjuvant chemotherapy | 4 | −1 | 0 | 0 | 0 | Moderate | Quality point deducted for incomplete reporting of results |
| 1 (466) | Mortality | Axillary clearance v axillary sampling | 4 | −1 | 0 | 0 | 0 | Moderate | Quality point deducted for incomplete reporting of results |
| 8 (4370) | Treatment success | Axillary clearance v axillary radiotherapy | 4 | −1 | 0 | 0 | 0 | Moderate | Quality point deducted for incomplete reporting of results |
| 8 (4370) | Mortality | Axillary clearance v axillary radiotherapy | 4 | −1 | 0 | 0 | 0 | Moderate | Quality point deducted for incomplete reporting of results |
| 1 (448) | Treatment success | Standard v dose-intensified anthracycline based regimens | 4 | −1 | 0 | 0 | 0 | Moderate | Quality point deducted for incomplete reporting of results |
| 1 (448) | Mortality | Standard v dose-intensified anthracycline based regimens | 4 | −1 | 0 | 0 | 0 | Moderate | Quality point deducted for incomplete reporting of results |
| 1 (174) | Treatment success | FAC regimen (fluorouracil, doxorubicin [adriamycin], and cyclophosphamide) v single-agent paclitaxel | 4 | −2 | 0 | 0 | 0 | Low | Quality points deducted for sparse data and incomplete reporting of results |
| 1 (174) | Mortality | FAC regimen (fluorouracil, doxorubicin [adriamycin], and cyclophosphamide) v single-agent paclitaxel | 4 | −2 | 0 | 0 | 0 | Low | Quality points deducted for sparse data and incomplete reporting of results |
| 1 (101) | Treatment success | MPEMi (methotrexate, cisplatin, etoposide, mitomycin C), MPEpiE (methotrexate, cisplatin, epirubicin, etoposide), and MPEpiV (methotrexate, cisplatin, epirubicin, vincristine) regimens v each other | 4 | −2 | 0 | 0 | 0 | Low | Quality points deducted for sparse data and incomplete reporting of results |
| 2 (2515) | Treatment success | Sequencing of anthracycline-based chemotherapy and docetaxel | 4 | −2 | 0 | 0 | 0 | Low | Quality points deducted for incomplete reporting of results and for no long-term results |
| 1 (73) | Treatment success | Intra-arterial v intravenous administration | 4 | −2 | 0 | 0 | 0 | Low | Quality points deducted for sparse data and incomplete reporting of results |
| 3 (1134) | Treatment success | Less than whole-breast radiotherapy v whole breast radiotherapy | 4 | −1 | −1 | 0 | 0 | Low | Quality point deducted for incomplete reporting of results. Consistency point deducted for conflicting results |
| 2 (426) | Mortality | Less than whole-breast radiotherapy v whole breast radiotherapy | 4 | −1 | −1 | 0 | 0 | Low | Quality point deducted for incomplete reporting of results. Consistency point deducted for conflicting results |
| 1 (270) | Treatment success | Radiotherapy to the internal mammary chain v no internal mammary chain irradiation | 4 | −1 | 0 | 0 | 0 | Moderate | Quality point deducted for incomplete reporting of results |
| 1 (270) | Mortality | Radiotherapy to the internal mammary chain v no internal mammary chain irradiation | 4 | −1 | 0 | 0 | 0 | Moderate | Quality point deducted for incomplete reporting of results |
| 1 (1375) | Treatment success | Radiotherapy v no radiotherapy to the ipsilateral supraclavicular fossa | 4 | −1 | 0 | 0 | 0 | Moderate | Quality point deducted for incomplete reporting of results |
| 3 (1389) | Treatment success | Sentinel node biopsy plus total axillary dissection v with sentinel node biopsy alone | 4 | −2 | 0 | 0 | 0 | Low | Quality points deducted for incomplete reporting of results and for uncertainty about follow-up |
| 1 (200) | Mortality | Sentinel node biopsy plus total axillary dissection v with sentinel node biopsy alone | 4 | −2 | 0 | 0 | 0 | Low | Quality points deducted for incomplete reporting of results and for uncertainty about follow-up |
| at least 8 RCTs (at least 3858 women) | Mortality | High-dose chemotherapy plus autologous stem cell transplantation v conventional chemotherapy | 4 | −1 | 0 | 0 | 0 | Moderate | Quality point deducted for incomplete reporting of results |
| at least 8 RCTs (at least 3858 women) | Treatment success | High-dose chemotherapy plus autologous stem cell transplantation v conventional chemotherapy | 4 | −1 | 0 | 0 | 0 | Moderate | Quality point deducted for incomplete reporting of results |
| 13 (5064) | Adverse effects | High-dose chemotherapy plus autologous stem cell transplantation v conventional chemotherapy | 4 | 0 | 0 | 0 | +2 | High | Effect size points added for RR >5 |
| What are the effects of interventions in locally advanced breast cancer (stage 3B)? | |||||||||
| 4 (3599) | Treatment success | Postoperative radiotherapy (in women also receiving postoperative systemic treatment) v no radiotherapy | 4 | −2 | 0 | −1 | 0 | Very low | Quality points deducted for incomplete reporting of results and for weak methods. Directness point deducted for inclusion of women with different disease severities |
| 4 (3599) | Mortality | Postoperative radiotherapy (in women also receiving postoperative systemic treatment) v no radiotherapy | 4 | −2 | 0 | −1 | 0 | Very low | Quality points deducted for incomplete reporting of results and for weak methods. Directness point deducted for inclusion of women with different disease severities |
| 2 (219) | Treatment success | Surgery alone v radiotherapy alone | 4 | −1 | 0 | 0 | 0 | Moderate | Quality point deducted for incomplete reporting of results |
| 2 (219) | Mortality | Surgery alone v radiotherapy alone | 4 | −1 | 0 | 0 | 0 | Moderate | Quality point deducted for incomplete reporting of results |
| 1 (143) | Mortality | Low-dose radiotherapy v tamoxifen | 4 | −2 | 0 | 0 | 0 | Low | Quality points deducted for sparse data and incomplete reporting of results |
| 3 (580) | Treatment success | Systemic treatment plus radiotherapy v radiotherapy | 4 | −1 | −1 | −1 | 0 | Very low | Quality point deducted for incomplete reporting of results. Consistency point deducted for conflicting results. Directness point deducted for inclusion of women with less severe disease |
| 3 (580) | Mortality | Systemic treatment plus radiotherapy v radiotherapy | 4 | −1 | −1 | −1 | 0 | Very low | Quality point deducted for incomplete reporting of results. Consistency point deducted for conflicting results. Directness point deducted for inclusion of women with less severe disease |
| 1, 2 publications (107) | Treatment success | Multimodal treatment v hormone treatment | 4 | −1 | −1 | 0 | +1 | Moderate | Quality point deducted for sparse data. Consistency point deducted for different results at different end points. Effect size point added for OR 2 to 5 |
| 1 (101) | Mortality | Adjuvant chemotherapy v primary plus adjuvant chemotherapy | 4 | −1 | 0 | 0 | 0 | Moderate | Quality point deducted for sparse data |
Type of evidence: 4 = RCT; 2 = Observational Consistency: similarity of results across studies.Directness: generalisability of population or outcomes.Effect size: based on relative risk or odds ratio.