Breast cancer (non-metastatic)

Overview

Abstract | Cite as | Substantive changes

Abstract

INTRODUCTION: Breast cancer affects at least 1 in 10 women in the UK, but most present with primary operable disease, which has an 80% 5-year survival rate overall. METHODS AND OUTCOMES: We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of interventions after breast-conserving surgery for ductal carcinoma in situ? What are the effects of treatments for primary operable breast cancer? What are the effects of interventions in locally advanced breast cancer (stage 3B)? We searched: Medline, Embase, The Cochrane Library, and other important databases up to April 2009 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS: We found 83 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. CONCLUSIONS: In this systematic review we present information relating to the effectiveness and safety of the following interventions: adding chemotherapy (cyclophosphamide/methotrexate/fluorouracil and/or anthracycline and/or taxane-based regimens), or hormonal treatment to radiotherapy; adjuvant treatments (aromatase inhibitors, adjuvant anthracycline regimens, tamoxifen); axillary clearance; axillary dissection plus sentinel node dissection; axillary radiotherapy; axillary sampling; combined chemotherapy plus tamoxifen; chemotherapy plus monoclonal antibody (trastuzumab); extensive surgery; high-dose chemotherapy; hormonal treatment; less extensive mastectomy; less than whole-breast radiotherapy plus breast-conserving surgery; multimodal treatment; ovarian ablation; primary chemotherapy; prolonged adjuvant combination chemotherapy; radiotherapy (after breast-conserving surgery, after mastectomy, plus tamoxifen after breast-conserving surgery, to the internal mammary chain, and to the ipsilateral supraclavicular fossa, and total nodal radiotherapy); sentinel node biopsy; and standard chemotherapy regimens.

Cite as

Stebbing J, Delaney G and Thompson A. Breast cancer (non-metastatic). Clinical Evidence 2011; 02:102.

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Substantive changes

Radiotherapy after breast-conserving surgery (for ductal carcinoma in situ) One systematic review added, which found that radiotherapy after breast-conserving surgery for ductal carcinoma in situ significantly reduced ipsilateral recurrence at up to 10.5 years of follow-up.[6] Categorisation changed from Likely to be beneficial to Beneficial because of confirmation given in systematic review and maintenance of benefit with long-term follow-up.

Tamoxifen plus radiotherapy after breast-conserving surgery (for ductal carcinoma in situ) Existing evidence re-evaluated. Tamoxifen plus radiotherapy (reduced recurrence in women with oestrogen receptor-positive tumours) recategorised from Likely to be beneficial to Unknown effectiveness because the two large RCTs identified present conflicting results.

Adjuvant aromatase inhibitors (for primary operable breast cancer) Two follow-up studies added comparing adjuvant aromatase inhibitors versus placebo, which found that letrozole remained beneficial when analysing results by HER2 status[15] and by age.[16] One follow-up study added comparing adjuvant aromatase inhibitors versus tamoxifen, which found that anastrozole improved disease-free survival, time to recurrence, and time to distant recurrence compared with tamoxifen at 8.5 years.[20] Categorisation unchanged (Beneficial).

Adjuvant combination chemotherapy (for primary operable breast cancer) One new systematic review added, which compared combination chemotherapy versus no chemotherapy in women with oestrogen-receptor-poor breast cancer.[27] The review found that chemotherapy reduced recurrence compared with no chemotherapy across all age groups.[27] Categorisation unchanged (Beneficial compared with no chemotherapy).

Enhanced-dose regimens of adjuvant combination chemotherapy (for primary operable breast cancer) One RCT added, which compared epirubicin plus cyclophosphamide versus higher-dose epirubicin plus cyclophosphamide.[31] At 15 years' follow-up, the RCT found that higher-dose epirubicin improved disease-free survival compared with standard-dose epirubicin, but found no significant difference in overall survival. Categorisation unchanged (Unlikely to be beneficial).

Anthracycline regimens as adjuvant chemotherapy (for primary operable breast cancer) One large RCT added, which found no significant difference between epirubicin-based regimens and standard CMF (cyclophosphamide, methotrexate, fluorouracil) regimens in disease-free survival and overall survival at 15 years.[31] Categorisation unchanged (Beneficial) as most anthracycline-based regimens are more effective than standard CMF chemotherapy.

Adjuvant tamoxifen (for primary operable breast cancer) One systematic review added, which found no significant difference in mortality and recurrence between tamoxifen and no tamoxifen in women with oestrogen-receptor-poor breast cancer.[27] Categorisation unchanged (Beneficial in women with oestrogen receptor-positive tumours).

Chemotherapy plus monoclonal antibody (trastuzumab) in women with primary operable breast cancer who have overexpressed HER2/neu oncogene One subgroup analysis of an included RCT added, which found that trastuzumab after chemotherapy reduced relapse similarly across subpopulations defined by nodal status and steroid hormone receptor status.[40] Categorisation unchanged (Beneficial).

Adjuvant taxanes (for primary operable breast cancer) One systematic review[43] and three subsequent RCTs[44][45][46] added, which found that taxane-based therapies improved disease-free survival and overall survival compared with anthracycline-based regimens. Categorisation changed from Likely to be beneficial to Beneficial.

Less extensive mastectomy (for primary operable breast cancer) One RCT added, which found no significant difference in 25-year disease-free survival and 50-year overall survival between simple mastectomy plus radiotherapy and extended radical mastectomy.[50] One subgroup analysis providing 20-year follow-up of an already included RCT added, which found no significant difference between breast-conserving surgery and mastectomy in disease-free survival and overall survival.[54] Categorisation unchanged (Beneficial).

Radiotherapy after breast-conserving surgery (for primary operable breast cancer) One RCT added, which found that at a median follow-up of 12.1 years, lumpectomy plus radiotherapy significantly reduced local recurrence compared with surgery alone in women with good prognostic features.[68] One systematic review added to the harms section, which found that lymphoedema and shoulder restriction were significantly more common with radiotherapy compared with no radiotherapy, but that quality of life and upper limb symptoms were generally favourable in women with breast-conserving surgery plus radiotherapy.[71] Categorisation unchanged (Beneficial).

Radiotherapy with or without endocrine therapy after breast-conserving surgery (for primary operable breast cancer) One RCT added, which found that after breast-conserving surgery, radiotherapy plus adjuvant hormone therapy reduced recurrence and improved disease-free survival compared with adjuvant hormone therapy alone.[79] One RCT reporting no significant difference in quality of life between radiotherapy and no radiotherapy added to the harms section.[80] Categorisation changed from Likely to be beneficial to Beneficial.

Radiotherapy after mastectomy (for primary operable breast cancer) Two further reports of an included RCT added. The first report found that post-mastectomy radiotherapy significantly reduced locoregional recurrence and distant recurrence compared with no radiotherapy.[88] The second report found that locoregional recurrence rates were significantly reduced with radiotherapy compared with no radiotherapy irrespective of receptor status. Radiotherapy increased survival in people with good prognostic features, such as hormone receptor-positive and HER2-negative cancer.[89] Condition restructured to remove distinction between high-risk and low-risk people. Categorisation unchanged (Beneficial).

Different primary chemotherapy regimens versus each other (for primary operable breast cancer) One systematic review added, which found no significant difference between the various methods of sequencing adjuvant chemotherapy and radiotherapy in survival, distant metastases, or local recurrence.[114] Categorisation unchanged (Unknown effectiveness) as there is still insufficient evidence regarding which regimen is most effective.

Less than whole-breast radiotherapy plus breast-conserving surgery (for primary operable breast cancer) One systematic review added, which identified one RCT and reported no significant difference in recurrence rates between partial-breast radiotherapy and whole-breast radiotherapy.[116] Follow-up data from one already included RCT added, which found no significant difference between partial-breast radiotherapy and whole-breast radiotherapy in recurrence, disease-free survival, and overall survival at 5 years.[117] Categorisation unchanged (Unknown effectiveness) as late recurrence rates and long-term effects are not yet known.

Sentinel node biopsy (for primary operable breast cancer) One RCT assessing operative complications added, which found that sentinel node biopsy plus axillary dissection was associated with more surgical adverse effects, including wound infections, seromas, and paraesthesia, compared with sentinel node biopsy alone.[131] Categorisation changed from Unknown effectiveness to Likely to be beneficial.

High-dose chemotherapy plus autologous stem cell transplantation (for primary operable breast cancer) Two RCTs added, which both found that high-dose chemotherapy plus autologous stem cell transplantation did not improve disease-free survival or overall survival compared with chemotherapy alone.[141][142] Categorisation unchanged (Likely to be ineffective or harmful).