The indications for different adjuvant radiotherapy options are discussed below. It is important to note that not all patients will be eligible for all radiotherapy techniques and dose and fractionation regimens. Radiotherapy treatment options will be presented and discussed with the patient by their radiation oncologist to determine the most effective, safe, and efficient treatment based on the individual patient and disease factors.
Radiation Therapy following Breast Conserving Surgery (pT1T2;N0)
Patients treated with breast conserving surgery (BCS; lumpectomy, partial or segmental mastectomy) for stage I or II breast cancer should have a consultation with a Radiation Oncologist regarding the role of radiation therapy (RT).
RT to the breast following BCS reduces the risk of breast recurrence and may lower the risk of systemic recurrence and breast cancer death.1,2,3,4,5 In a meta-analysis of 17 older breast cancer trials, at 10 years after diagnosis, a 20% absolute reduction in the risk of breast recurrence (from 30% to 10%) translated into a 4-5% reduction in the chance of dying from breast cancer.1 However, in newer breast cancer radiotherapy trials, in lower-risk patients, in-breast local recurrences were closer to 1-3% after radiotherapy with no difference in survival.6,7 RT should be considered following BCS but patients with multiple comorbidities, limited life expectancy, who desire to avoid RT, or who have a low risk of recurrence may be considered to omit RT (see below section). In addition to breast RT, regional nodal RT may be indicated in select node-negative patients, such as those with a number of high-risk features including large tumour, high grade, lymphovascular involvement, central/inner quadrant location, or those with triple-negative (i.e. ER/PR negative, her-2-neu negative) disease.5
Timing of Adjuvant Radiotherapy
- RT should optimally start once healing from the BCS is complete and generally within 10 weeks of BCS
- If post-operative problems occur, including hematoma, large seroma, infection, breast edema with erythema, or wound dehiscence occur, the start of RT may be delayed to allow resolution. In such cases or to accommodate patient convenience, there is no randomised trial evidence showing detriment to delay the start of RT until 20 weeks after BCS. Longer intervals may be associated with reduced RT efficacy and inferior local control.8
- If the patient receives adjuvant chemotherapy, then RT should follow the chemotherapy and start approximately 3-4 weeks after the last intravenous chemotherapy. Trastuzumab as a single agent may be delivered concurrently with radiation therapy. Adjuvant hormonal therapy may be commenced prior to or after RT.
Randomized trials have shown improved local control with a boost of RT to the surgical bed following tangential RT for selected patients. Boost RT can increase radiation induced breast fibrosis and decrease cosmetic outcome. 9,10,11
Indications for supplemental boost dose of RT:
- close or positive margins (less than or equal to 2 mm) post-breast conserving surgery, without possibility of further excision
- age 50 years or younger, even if the margins are greater than 2 mm
Patients who might be spared radiation therapy after breast conserving surgery
Radiation therapy consistently reduces the relative risk of local recurrence by 60-70%. Patients with a < 5% risk of local recurrence at 10 years are challenging to identify but might reasonably be considered for treatment with BCS alone. Women with the following factors likely have a 10 year risk of breast recurrence of 5% or less, if also prescribed adjuvant hormonal therapy: age >60 years, pN0, ER strongly positive, Grade 1 ductal carcinoma without lymphatic or vascular invasion and clear margins. Such women should be informed that RT will further decrease the risk of breast recurrence, but that the absolute benefit of RT on long-term survival is small.12,13,14,15
Partial breast radiotherapy following breast conserving surgery
Multiple randomized trials have tested the efficacy, safety and convenience of partial-breast irradiation (PBI) as an alternative to conventional whole-breast irradiation (WBI) for early-stage, favorable breast cancer. The rationale for this approach is that most recurrences occur at, or near, the primary tumor bed. PBI refers to the use of focused radiation to only the part of the breast where the tumor was removed. Accelerated partial breast irradiation (APBI) describes PBI treatment over a short period of time. There are three common modalities for PBI: 1) external beam radiotherapy (short tangents, 3D conformal radiotherapy and IMRT), 2) brachytherapy, and 3) intraoperative radiotherapy
Trials have shown similar outcomes with a low rate of ipsilateral-breast tumor recurrence (IBTR) for women who received WBI or PBI (accelerated and conventionally fractionated).6,7,16,17,18 Long-term data from two large randomized studies, the RAPID trial and the NSABP B-39/RTOG 0413, comparing WBI with APBI were recently published. In the RAPID trial, which used external-beam radiotherapy in both arms(6) there was no difference in the rate of IBTR between APBI and WBI (3.0% versus 2.8% respectively). Compared to the WBI arm, in which only 21% were treated with boost radiotherapy, the twice daily regimen was associated with an increase in moderate late toxicity and adverse cosmesis. In the NSABP B-39 trial Ref), the 10-year IBTR was 3.9% for WBI and 4.6%for APBI. The trial did not meet its goal of establishing equivalence, but the small absolute difference in recurrence-free interval (0.7%) is not likely to be clinically significant. In addition, the 10-year IBTR outcomes were nearly identical for patients treated with external beam radiotherapy: 3.8% for WBI and 3.7% for APBI. Compared to the WBI arm, in which 80% were treated with the addition of boost radiotherapy, the twice daily regimen was not associated with an increase in moderate late toxicity and adverse cosmesis. Other previously reported randomized trials evaluating different PBI methods have demonstrated equivalent early and late toxicity to that of whole-breast irradiation.
The American Society of Therapeutic Radiation and Oncology (ASTRO)19, the American Brachytherapy Society (ABS) 20, and the Groupe Européen de Curiethérapie- European Society for Therapeutic Radiation and Oncology (GEC-ESTRO)21 have all published evidence-based guidelines on the appropriate selection of patients for APBI following breast-conserving surgery and surgical lymph node evaluation. The BC Cancer Breast Tumor Group has reviewed the published guidelines and concluded that PBI is a reasonable alternative standard of care treatment in appropriately selected patients who meet the following criteria:
- Age ≥ 40 years
- Invasive ductal carcinoma or DCIS < 3 cm
- Pathologically node negative
- Margin negative for invasive carcinoma
- Margin ≥ 2 mm for pure DCIS
- Clinically unifocal (by physical examination and breast imaging)
- Clearly visible operative bed
Patients with minimal lymphovascular invasion may be suitable for PBI if their other breast cancer risk factors are favorable. Microscopic multifocality may be suitable for PBI, provided the total lesion size (including foci of multifocality and intervening normal breast parenchyma) is < 3 cm. Patients with (1) anterior (at skin) and/or posterior (at pectoralis fascia) positive margins that cannot be rendered negative with further surgery (2) mixed invasive and DCIS component with clear invasive margins but close DCIS margins (≤ 2 mm) and (3) pure DCIS and a single close non-anterior, non-posterior margin can have PBI with a boost. Patients over 70 with low-risk disease who are clinically node negative and did not have SLNB or ALND may have PBI as per the discretion of the treating oncologist.
Patients with lobular breast cancer and patients treated with neoadjuvant chemotherapy are not suitable for PBI.
PBI can be delivered using external beam radiation treatment (short tangents, 3D conformal radiotherapy or IMRT) or permanent seed brachytherapy.22,23 Due to concerns of adverse late cosmetic outcomes, the use of 38.5 Gy / 10 APBI twice daily fractionation over 5 days (ie accelerated partial breast RT) is not recommended.6,18 Based on the results of the FAST-Forward trial, comparing whole breast irradiation with 40 Gy / 15 versus 27 Gy / 5 and 26 Gy / 5, it is recommended to use 26 Gy / 5 PBI for patients whose dosimetry meets the planning constraints of the FAST-Forward trial and 40 Gy / 15 for patients whose breast separation is too large to meet the planning constraints of the FAST-Forward trial.24 If a boost is indicated when using 26Gy/ 5 PBI, the recommend boost dose is 10 Gy / 5 or 16 Gy / 8, as was used in the FAST-Forward trial.24
Short-course adjuvant radiotherapy
Five-fraction breast radiotherapy can be offered to patients undergoing tangent, breast-only, adjuvant treatment. It is a 5-fraction regimen delivered over 5 consecutive working days as used in the FAST-Forward Phase III trial.24 Five-year follow-up data demonstrated that local control with 26 Gy in 5 daily fractions was not inferior for local control with 40 Gy in 15 daily fractions. Cosmetic outcomes were also equivalent at 5 years. Greater than 5-year follow-up data has not yet been published. Although a wide range of patients were included in the trial, some patient, disease, and treatment characteristics were uncommon and therefore the overall conclusions may be less applicable to these sub-groups. Patients should only be treated with one-week breast radiotherapy if their plans meet the dosimetric constraints used in the trial. Patients with DCIS and with very low risk invasive breast cancer were not included in the FAST-Forward trial because they had a very low likelihood of outcome events occurring. The results of the FAST-Forward could be extrapolated to include these groups of patients. It is recommended that patients undergoing nodal radiotherapy and patients with breast reconstruction should not be treated with short-course at this time unless participating in a clinical trial.
Radiation therapy following mastectomy (pT1,T2;N0)
The majority of patients with pT1-T2 pN0 disease will not derive a benefit from adjuvant RT.25 Some patients may have a higher risk of locoregional recurrence and may benefit from adjuvant radiotherapy for local control but an overall survival benefit has not been demonstrated. This group would include: patients with close or positive margins with pT2 tumour plus other high risk features, such as grade 3 histology, high volume lymphatic or vascular invasion, age<50 years, and central or inner quadrant tumours26 and patients with clear margins post-mastectomy with central/inner quadrant tumours, or those with T2 tumour size with other high risk features, e.g. high grade, lymphovascular involvement, or triple-negative (i.e. ER/PR negative, her-2-neu negative) disease.27 Patients with these high-risk features should be referred after mastectomy for discussion of adjuvant RT with a radiation oncologist.
Radiation therapy following mastectomy or breast conserving surgery (pT1,T2;N1, and T3;N0)
Locoregional RT improves outcomes following mastectomy or breast conserving surgery for patients with node-positive breast cancer or node-negative T3 breast cancer. 25,27,28,29,30,31 A reduction in loco-regional recurrence and reduced breast cancer mortality is seen even for patients with only a moderate risk (e.g. 1-3 nodes positive) of loco-regional recurrence.25,28,29,32 The breast cancer specific-outcomes improvement may not translate to an overall survival benefit.5,32 Patients with lymph node positive disease and increased risk of internal mammary chain involvement may derive proportionally more benefit from adjuvant loco-regional radiotherapy. 33 Patients with pT1-T2 pN1 and T3N0 should be referred for discussion of adjuvant RT with a radiation oncologist.
Radiation therapy following mastectomy or breast conserving surgery (pT1-T3;N2-3, and T4;N0-3)
Locoregional RT is recommended for patients with locally advanced breast cancer following mastectomy or breast conserving surgery. Adjuvant RT has been shown to decrease locoregional recurrence and reduce breast cancer mortality even in patients treated with adjuvant chemotherapy.25,28,29,30
Timing of adjuvant radiotherapy following mastectomy or in lymph node positive patients: Timing is as described above in the post-BCS for node-negative patients.
**Details of radiotherapy planning and prescription in the post-breast conserving surgery and post-mastectomy setting are described separately (Section 6.10).