ACR Appropriateness Criteria®
Clinical Condition: Locally Advanced Breast Cancer
Variant 1: 45-year-old premenopausal female, 4.5 cm infiltrating ductal carcinoma (IDC) left breast, estrogen receptor/progesterone receptor (ER/PR) (-), Her2 amplified, positron emission tomography (PET) (+) in breast, axilla and medial infraclavicular fossa. Palpable nodes in high axilla. Metastatic workup negative. Patient desires breast conservation.
| Treatment |
Rating |
Comments |
| Principles of Treatment |
| Initial chemotherapy |
9 |
|
| Breast conservation therapy (BCT) if ≥PR to chemotherapy |
8 |
For some patients with less than PR, breast conservation may be appropriate if surgically feasible. |
| Initial mastectomy and axillary dissection |
1 |
N3 status contraindicates initial surgical approach. |
| Initial BCT and axillary dissection |
1 |
|
| Radiation Volumes (assume initial chemotherapy followed by BCT, clear margins, and axilla dissection level I-II, 8/16 LN+, highest node+) |
| Whole breast only ± boost (no nodal RT) |
1 |
|
| Partial breast irradiation (no nodal RT) |
1 |
|
| Whole breast and supraclavicular + apical axillary nodes |
9 |
|
| Whole breast and supraclavicular LNs and full axilla |
7 |
Probably not required after a standard axillary dissection. |
| Internal mammary nodes (assumes breast RT given concurrently) |
8 |
Provided caution is taken to minimize cardiac pulmonary volumes. |
| Boost infraclavicular region |
8 |
Boost determined by extent of surgical resection and clinical features. |
| Radiation Doses (1.8-2.0 Gy/day unless specified otherwise) (assume initial chemotherapy followed by BCT, clear margins, and axilla dissection level I-II, 8/16 LN+, highest node+) |
| Whole breast: 42.5 Gy (16 fractions) |
1 |
|
| Whole breast: 45-50 Gy |
9 |
|
| Total dose to breast tumor bed: 45-50 Gy |
1 |
|
| Total dose to breast tumor bed: 60-66 Gy |
9 |
|
| Total dose to supraclavicular fossa and axillary apex: 45-50 Gy |
9 |
|
| Total dose to supraclavicular fossa and axillary apex: 60 Gy |
1 |
|
| Total dose to medial infraclavicular nodes: ≥60Gy |
8 |
Gross tumor may require higher doses. Higher doses risk brachial plexus. CT planning recommended. |
| Full axilla: 45-50 Gy |
7 |
|
| IMN: 45-50 Gy |
7 |
|
| Rating Scale: 1=Least appropriate, 9=Most appropriate |
Note: Abbreviations used in the table are listed at the end of the "Major Recommendations" field.
Variant 2: 40-year-old woman, 4 cm primary with diffuse suspicious microcalcifications in breast, direct skin invasion, satellite skin nodule, matted axilla (N2), ER (+)/PR (–), Her2 (–). Metastatic workup negative.
| Treatment |
Rating |
Comments |
| Principles of Treatment |
| Initial chemotherapy |
9 |
|
| Mastectomy if response to initial chemotherapy |
9 |
|
| Initial endocrine therapy |
2 |
Only if cytotoxic therapy contraindicated or on a clinical trial. |
| Initial surgery |
1 |
|
| Initial breast and nodal RT |
1 |
|
| BCT if response to initial chemotherapy |
1 |
|
| Radiation Volumes (assume chemotherapy, mastectomy, axillary dissection level I-II, 3/16 LN+) |
| Chest wall only ± boost (no nodal RT) |
1 |
|
| Chest wall, supraclavicular and apical nodes |
9 |
|
| Chest wall, supraclavicular fossa + full axilla |
7 |
|
| Internal mammary nodes (assumes chest wall RT) |
8 |
|
| Boost to chest wall |
9 |
|
| Radiation Doses (1.8–2.0 Gy/day unless specified otherwise) (assume chemotherapy, mastectomy, clear margins, and axilla dissection level I-II, 3/16 LN+) |
| Chest wall: 45-50 Gy |
9 |
|
| Total dose to chest wall including boost: 60-66 Gy |
9 |
|
| Supraclavicular and axillary nodes: 45-50 Gy |
9 |
|
| Full axilla: 45-50 Gy |
7 |
|
| IMN: 45-50 Gy |
7 |
|
| Rating Scale: 1=Least appropriate, 9=Most appropriate |
Note: Abbreviations used in the table are listed at the end of the "Major Recommendations" field.
Variant 3: 80-year-old woman, 4 cm primary, direct skin invasion, satellite nodule, matted axilla (N2), strongly ER/PR (+), Her2 (–). Metastatic workup negative. Medically fit.
| Treatment |
Rating |
Comments |
| Treatment Modalities |
| Initial endocrine therapy |
9 |
Both are considered equally appropriate. |
| Initial chemotherapy |
9 |
Both are considered equally appropriate. |
| Initial surgery |
1 |
|
| Initial breast and nodal RT |
1 |
|
| Rating Scale: 1=Least appropriate, 9=Most appropriate |
Note: Abbreviations used in the table are listed at the end of the "Major Recommendations" field.
Variant 4: 50-year-old woman, T3N2M0 disease, with clinical CR post 4-cycle multidrug chemotherapy. ER/PR (–), Her2 (–). Does not desire BCT.
| Treatment |
Rating |
Comments |
| Treatment Modalities |
| Mastectomy and axillary dissection |
9 |
|
| Additional chemotherapy |
9 |
Would complete all chemotherapy up front. Depends on what drugs are used |
| Postmastectomy RT |
9 |
|
| No surgery: RT + chemotherapy |
1 |
|
| Rating Scale: 1=Least appropriate, 9=Most appropriate |
Note: Abbreviations used in the table are listed at the end of the "Major Recommendations" field.
Variant 5: 38-year-old woman, T4 inflammatory, N1 disease, no response post 3-cycle multidrug chemotherapy. ER/PR (–), Her2 (–). Metastatic workup negative.
| Treatment |
Rating |
Comments |
| Principles of Treatment |
| Change chemotherapy; if no response, proceed to RT |
9 |
|
| Change chemotherapy; if response, mastectomy |
9 |
|
| Change chemotherapy; if no response, pre-op chemoradiation (radiosensitizing chemotherapy) |
7 |
|
| Immediate mastectomy/axillary dissection |
1 |
|
| Radiotherapy (assume sufficient response to be operable with clear margins) |
| Standard fractionation (1.8-2.0 Gy) |
9 |
|
| Accelerated fractionation (1.5 Gy BID) |
7 |
|
| Dose to central chest wall: 45-50 Gy |
9 |
|
| Total dose to chest wall including boost: 60-66 Gy |
9 |
|
| Rating Scale: 1=Least appropriate, 9=Most appropriate |
Note: Abbreviations used in the table are listed at the end of the "Major Recommendations" field.
Variant 6: 42-year-old woman, T2N1 (clin), M0 left breast cancer, Her2 amplified. Status post mastectomy with 11/12 (+) nodes and reconstruction plus chemotherapy, no evidence of disease. Will receive trastuzumab for one year.
| Treatment |
Rating |
Comments |
| Principles of Treatment |
| Chest wall RT |
9 |
|
| Supraclavicular RT |
9 |
|
| Attempt to exclude all heart from RT volume |
9 |
|
| Full axilla RT |
7 |
|
| IMN RT |
7 |
|
| RT dose adjustment (decrease) due to reconstruction |
5 |
|
| Discontinue trastuzumab during radiotherapy |
1 |
|
| Rating Scale: 1=Least appropriate, 9=Most appropriate |
Note: Abbreviations used in the table are listed at the end of the "Major Recommendations" field.
Variant 7: 57-year-old woman, triple negative IDC, status post-mastectomy: 3.5 cm inner quadrant primary, 7/12 LN (+). Focally positive deep margin. PET (+) IMC and S/C nodes. Adjuvant anthracycline and taxane, with normalization of PET findings. Metastatic workup negative.
| Treatment |
Rating |
Comments |
| Radiation Volumes |
| Chest wall only ± boost |
1 |
|
| Supraclavicular + apical nodes (assumes chest wall RT also) |
9 |
|
| Full axilla (assumes chest wall RT also) |
7 |
|
| Internal mammary nodes (assumes chest wall RT) |
9 |
|
| Boost to IMC |
8 |
|
| Boost supraclavicular nodes |
8 |
|
| Radiation Doses |
| Total dose to chest wall including boost: 45-50 Gy |
1 |
|
| Total dose to chest wall including boost: 60 Gy |
2 |
|
| Total dose to chest wall including boost: 64-66 Gy |
9 |
Clinical circumstance may require higher dose. |
| Total dose to supraclavicular fossa including boost: 45-50 Gy |
9 |
|
| Total dose to supraclavicular fossa including boost: 60-66 Gy |
9 |
|
| Total dose to entire IMN chain: 45-50 Gy |
9 |
|
| Total dose to entire IMN chain: 60-66 Gy |
9 |
|
| Rating Scale: 1=Least appropriate, 9=Most appropriate |
Note: Abbreviations used in the table are listed at the end of the "Major Recommendations" field.
Variant 8: 55-year-old woman with neglected primary. Large, fungating lesion and matted axilla. ER (–) /PR (+), Her2 (–). Metastatic workup negative. Not operable after three chemo regimens, including anthracyclines and taxanes.
| Treatment |
Rating |
Comments |
| Principles of Treatment |
| Switch to endocrine therapy |
9 |
|
| Switch to 4th line chemotherapy |
3 |
Appropriate in phase I clinical trial. |
| Debulking surgery with anticipated + margins |
3 |
|
| Palliative radiation (30-45 Gy) |
No consensus |
May be appropriate in selected clinical circumstances. |
| Concurrent chemoradiation |
No consensus |
May be appropriate in selected clinical circumstances. |
| Preoperative RT (50-54 Gy) |
No consensus |
May be appropriate in selected clinical circumstances. |
| Definitive RT to ≥70 Gy |
No consensus |
May be appropriate in selected clinical circumstances. |
| Rating Scale: 1=Least appropriate, 9=Most appropriate |
Note: Abbreviations used in the table are listed at the end of the "Major Recommendations" field.
Summary
Patients with locally advanced breast cancer (LABC) have a high risk for both local-regional recurrence (LRR) and distant metastasis (DM). Proper initial imaging of the breast and nodal beds is essential for both staging and RT planning. There are only a few randomized trials that specifically examined the role of radiation in LABC patients. Preferred techniques and clinical target volumes and the optimum doses to these regions have not been prospectively studied for advanced breast cancer. However, trimodality therapy with chemotherapy, surgery, and radiation seems to accomplish the best outcome. In fact, breast conservation can be achieved in a select population of patients who have a good response to neoadjuvant chemotherapy.
Abbreviations
- BCT, breast conservation therapy
- BID, twice a day
- CT, computed tomography
- ER, estrogen receptor
- IDC, infiltrating ductal carcinoma
- IMC, internal mammary chain
- IMN, internal mammary (lymph) node
- LN, lymph node
- PET, positron emission tomography
- PR, progesterone receptor
- RT, radiation therapy
- S/C, supraclavicular
