N Engl J Med 2015 Jul 23
Regional Nodal Irradiation in Early-Stage Breast Cancer.
Abstract
Background
Most women with breast cancer who undergo breast-conserving surgery receive whole-breast irradiation. We examined whether the addition of regional nodal irradiation to whole-breast irradiation improved outcomes.
Methods
We randomly assigned women with node-positive or high-risk node-negative breast cancer who were treated with breast-conserving surgery and adjuvant systemic therapy to undergo either whole-breast irradiation plus regional nodal irradiation (including internal mammary, supraclavicular, and axillary lymph nodes) (nodal-irradiation group) or whole-breast irradiation alone (control group). The primary outcome was overall survival. Secondary outcomes were disease-free survival, isolated locoregional disease-free survival, and distant disease-free survival.
Results
Between March 2000 and February 2007, a total of 1832 women were assigned to the nodal-irradiation group or the control group (916 women in each group). The median follow-up was 9.5 years. At the 10-year follow-up, there was no significant between-group difference in survival, with a rate of 82.8% in the nodal-irradiation group and 81.8% in the control group (hazard ratio, 0.91; 95% confidence interval [CI], 0.72 to 1.13; P=0.38). The rates of disease-free survival were 82.0% in the nodal-irradiation group and 77.0% in the control group (hazard ratio, 0.76; 95% CI, 0.61 to 0.94; P=0.01). Patients in the nodal-irradiation group had higher rates of grade 2 or greater acute pneumonitis (1.2% vs. 0.2%, P=0.01) and lymphedema (8.4% vs. 4.5%, P=0.001).
Conclusions
Among women with node-positive or high-risk node-negative breast cancer, the addition of regional nodal irradiation to whole-breast irradiation did not improve overall survival but reduced the rate of breast-cancer recurrence. (Funded by the Canadian Cancer Society Research Institute and others; MA.20 ClinicalTrials.gov number, NCT00005957.).
Related Questions
How does SUPREMO alter your recommendations for PMRT?
There has been a very long debate as to which, if any, patients having upfront mastectomy and axillary surgery who are found to have 1-3 positive axillary nodes (pN1) benefit from post-mastectomy radiation therapy (PMRT). I gave my thoughts in this forum on the implications of the "SUPREMO" trial fo...
Given the final publication of NSABP B-51, for which patients meeting trial eligibility would you still recommend regional nodal irradiation?
The very first thing that should occur before one makes a decision about what they are going to do is to understand how the trial was designed and who was actually accrued to it. The first point is that B51 was a superiority and not a non-inferiority trial. A very related point to that is that they ...
Given the new ASCO guidelines on SNB in early stage breast cancer, how does the omission of SNB in patients aged 50-70 impact your adjuvant radiation recommendations?
If the patient is otherwise a good candidate for APBI (age > 50, pT1 tumor, ER+, HER2 negative, Recurrence score low and intending to take endocrine therapy) that was clinically node negative and ultrasound axilla negative, I feel completely comfortable treating with APBI post lumpectomy with negati...
What dose of reirradiation would you consider for locally recurrent breast cancer after mastectomy, excised with positive margins?
These are complex cases and lots of factors to consider when planning adjuvant therapy (age and comorbidities, tumor biology, other pathologic features like LVI, reason for the positive margin, plans for systemic therapy, presence of reconstruction, the volume of prior radiation, extent of clinicall...
What evidence supports the use of high tangents for pN1mic breast cancer?
This is a great question. To add to the excellent answers from @Dr. First Last and @Dr. First Last, here are some of my thoughts on this topic:At the time of MA.20, the size of nodal metastasis was not routinely measured so it is unclear what percent of patients in MA.20, if any, had micrometastases...
What are your top takeaways from SABCS 2023?
The B51 trial surprised the radiation oncology community, showing that in patients with an exceptional response to systemic therapy, radiation to the regional nodes did not result in a significant improvement in the invasive breast cancer recurrence free interval nor the isolated loco-regional recu...
In light of the NSABP B-51 data presented at SABCS, will you defer RNI in all patients with negative nodes after chemotherapy?
Results of the NSABP B-51 trial were presented at the 2023 San Antonio Breast Cancer Symposium (Mamounas et al., abstract GS-02-07). This trial was designed to test the value of postoperative radiation therapy in patients who presented with clinical T1-3N1 tumors with biopsy-proven axillary node inv...
When treating breast cancer patients with RNI, how often do you include internal mammary nodes?
Treating the internal mammary nodes (IMNs) increases heart and lung exposure; hence, the value of prophylactic IMN RT has been controversial for decades. Randomized trials suggest there may be some benefit to such treatment but disagree on which patient subgroups benefit most or not at all.A trial c...
Should BED or EQD2 be used when deciding on a fractionation scheme for breast cancer radiation, and should tumor or normal tissue be prioritized in this consideration?
I feel, with many prospective randomized data, we are beyond looking at EQ2 dose for deciding fractionation. We follow the below rationale/pathway in our practice. Is biology suitable for PBI or not? (If suitable then plan for 30 Gy in 5 fractions like Italian data) Biology is suitable for PBI but ...
For a postmenopausal patient with a pT2N0 breast cancer s/p BCS+SNB who qualifies for MA20, how do you decide between RNI, high tangents, and standard whole breast RT?
TL;DR: "This patient would have fit Z11 criteria - if they had positive nodes. Patients did very well with tangents/high tangents. For N0 patients that would have been otherwise eligible for Z11, I would treat with standard whole breast RT." The absolute reduction in isolated LRR in MA.20 was 5% at ...
Would you offer PMRT to a pre-menopausal patient with early stage breast cancer, favorable biology, and an axillary dissection showing pN1a disease?
The role of PMRT in this situation remains controversial with factors considered including age/menopausal status, number of nodes, presence of ECE, receptor status, neoadjuvant chemo use, etc.If the patient received neoadjuvant therapy and ypN1, I would offer PMRT.If no neoadjuvant therapy, I often ...
Would you treat comprehensive nodes in an ER+/PR+/HER2+ breast cancer with an initial biopsied node showing atypia and then pCR (0/2 SLN) on lumpectomy?
These are challenging cases. I will ask the pathologist if there is any sign of treatment effect in the nodes. If there is, I will treat comprehensively.If no treatment effect, I will discuss the pros/cons with the patient. I do offer and consider given that MA20 showed modest increases in toxicity ...
Would you treat regional lymph nodes in an elderly patient with a triple negative pT2 IDC of the UOQ of the left breast s/p lumpectomy with N0 sentinel node biopsy, but was clinically node negative?
What was the reason SLNB was omitted? While pathological nodal assessment is sometimes omitted, that most commonly applies to patients who are older (age >70) with small (T1) tumors that are ER positive, paralleling the inclusion criteria of CALGB 9343 in which 2/3 of patients did not have pathologi...
Do you offer RNI to a T1N0 breast cancer patient who underwent inadequate axillary dissection?
I would not do RNI but include level 1 and 2 nodes for inadequate assessment of axilla with a tangential field for BCS.
What is the role for RNI in a postmenopausal female with clinically N+, hormone receptor positive breast cancer s/p lumpectomy and ALND with low volume nodal disease (e.g., 1/12 nodes positive)?
When thinking about low volume nodal disease in cN+ patients, I tend to think about MA20 which included patients undergoing an ALND and 85% had 1-3 LN involved. I will offer these patients adjuvant RT to the breast and RNI (SCV/axilla with consideration of IM nodes based on dosimetry) based on the i...
Would you consider treating the regional nodes in addition to the breast in a patient with skin involvement (pT4b) after a lumpectomy with negative margins/nodes who refuses chemotherapy?
I can't say that this is a commonly encountered scenario. It's tough to imagine the T4 patients that's a good upfront BCT candidate. In my opinion, it is very reasonable to consider RNI in a high risk node negative patient. High risk N0 patients were included in MA.20 and EORTC 22922 and derived sim...
Would you offer nodal RT for pT2N0 triple negative breast cancer s/p BCS?
I agree with above and generally haven't routinely offered RNI for such patients. However, I consider making an exception in the setting of a tumor with multiple risk factors, such as medial location, young age, large T2, poor response to neo-adjuvant chemotherapy (so cT2N0, ypT2N0) with LVI, etc.
Would you ever recommend PMRT to the chest wall alone without nodal radiation for invasive or in situ breast disease?
In patients who are node negative upfront, I do offer PMRT for adverse primary tumor factors which meets criteria for PMRT to CW only. Retrospective data suggest majority of local recurrence in CW in these pts and can skip RNI
Would you recommend RNI for a triple negative cancer s/p lumpectomy and ALND with low LN positivity rate?
My current practice is to offer patients with triple negative disease and positive nodes after ALND RNI with their whole breast irradiation. MA20 included such patients with roughly 85% having 1-3 LN+ and more than 65% had 10+ LN removed. The addition of RNI increased survival in ER- patients (81 vs...
Is pectoralis muscle invasion an indication for post-mastectomy radiation (PMRT) for an otherwise early stage, node negative breast cancer with clear margins?
In and of itself no. Given the inclusion of specific node negative patients in MA.20 and EORTC 22922 and small but significant DFS benefit in both, by extrapolation to mastectomy it behooves us to consider carefully the potential benefit of PMRT in node negative patients without over-treating. In re...