Many patients are treated with a mastectomy rather than a lumpectomy. In most cases, if the cancer was relatively small with little lymph node spread, then radiation is generally not necessary after surgery. For women with high risk features (as discussed below) postoperative radiation will not only decrease the risk of a local relapse but also decrease the risk of distant spread and improve the overall chances of survival (see section on local relapses and images here).

Read the NCCN guidelines for PostOp radiation, ASTRO consensus statement below and the ASCO Guidelines.

1. Postmastectomy irradiation will decrease local relapses by 2/3. Overall survival was not improved in most studies but in the more recent studies there was an improvement in survival (the greatest survival benefit was for those with only 1-3 N+ and tumors less than 5cm (not the more advanced cases.)
2. Patients with 4 or more N(+) should get XRT (and maybe even those with 1-3N+ because of survival advantage.)
3. The chest wall should be treated and the supraclav area if 4 or more N+. PAB should be treated if there are concerns about the completeness of the axillary dissection and the benefits of IMN radiation is uncertain

Locoregional Recurrence Patterns After Mastectomy and Doxorubicin-Based Chemotherapy: Implications for Postoperative Irradiation

By Angela Katz, Eric A. Strom, Thomas A. Buchholz, Howard D. Thames, Cynthia D. Smith, Anuja Jhingran, Gabriel Hortobagyi, Aman U. Buzdar, Richard Theriault, S. Eva Singletary, Marsha D. McNeese Journal of Clinical Oncology, Vol 18, Issue 15 (August), 2000: 2817-2827

From the Departments of Radiation Oncology, Biomathematics, Medical Oncology, and Surgical Oncology, University of Texas M.D. Anderson Cancer Center, Houston, TX.

PURPOSE: The objective of this study was to determine locoregional recurrence (LRR) patterns after mastectomy and doxorubicin-based chemotherapy to define subgroups of patients who might benefit from adjuvant irradiation. A total of 1,031 patients were treated with mastectomy and doxorubicin-based chemotherapy without irradiation on five prospective trials. Median follow-up time was 116 months. Rates of isolated and total LRR (± distant metastasis) were calculated by Kaplan-Meier analysis. The 10-year actuarial rates of isolated LRR were 4%, 10%, 21%, and 22% for patients with zero, one to three, four to nine, or  10 involved nodes, respectively. Chest wall (68%) and supraclavicular nodes (41%) were the most common sites of LRR. T stage, tumor size, and  2-mm extranodal extension were also predictive of LRR. Separate analysis was performed for patients with T1 or T2 primary disease and one to three involved nodes (n = 404). Those with fewer than 10 nodes examined were at increased risk of LRR compared with those with  10 nodes examined (24% v 11%;). Patients with tumor size greater than 4.0 cm or extranodal extension  2 mm experienced rates of isolated LRR in excess of 20%. Each of these factors continued to significantly predict for LRR in multivariate analysis by Cox logistic regression. CONCLUSION: Patients with tumors  4 cm or at least four involved nodes experience LRR rates in excess of 20% and should be offered adjuvant irradiation. Additionally, patients with one to three involved nodes and large tumors, extranodal extension  2 mm, or inadequate axillary dissections experience high rates of LRR and may benefit from postmastectomy irradiation.

RANDOMIZED TRIALS that date back to the early 1970s have established that adjuvant radiation therapy after mastectomy reduces the incidence of locoregional recurrence (LRR) of breast cancer by approximately two thirds. After the publication in 1987 of a meta-analysis by Cuzick et althat reported increased mortality in women who had received postmastectomy radiotherapy as a component of their treatment, its use was intensely challenged. An update published in 1994 reported no significant difference in overall mortality. A similar reduction in breast cancer mortality, as well as a two thirds reduction in LRR, was reported in a third meta-analysis, which was published by the Early Breast Cancer Trialists’ Collaborative Group.These authors also reported an increase in non–breast cancer deaths, which was most evident for women older than 60 years and which resulted in no difference in OS. More recently, two trials published in the New England Journal of Medicine have demonstrated superior locoregional control, DFS, and OS with the addition of postoperative radiotherapy to mastectomy and chemotherapy. The Danish 82b trial evaluated the use of postoperative radiotherapy in 1,708 high-risk premenopausal women treated with mastectomy and CMF.At 10 years, there was a decrease in LRR from 32% to 9% in the patients who received radiation to the chest wall and regional lymphatics. This translated into improvements in both DFS (48% v 34%) and OS (54% v 45%;). Most surprising was the observation that these significant improvements in DFS and OS were evident for all subgroups of patients, including patients with one to three involved nodes. A second trial from British Columbia also reported improvements in locoregional control (87% v 67%) and DFS (50% v 33%) in node-positive premenopausal women treated with adjuvant radiation after mastectomy and CMF.Similar benefits in postmenopausal women treated with mastectomy and tamoxifen were recently reported by the Danish Breast Cancer Cooperative Group.

Together, these trials have demonstrated that the improvement in locoregional control observed with adjuvant irradiation translates into an improvement in OS. It is, therefore, imperative to identify those patients at significant risk of LRR who are most likely to realize the benefit of adjuvant irradiation. Our analysis of recurrence patterns in 1,031 patients found that doxorubicin-based adjuvant systemic therapy does not obviate the need for postmastectomy irradiation for subsets of breast cancer patients at substantial risk of LRR. Patients with tumors larger than 4 cm or involvement of four or more axillary lymph nodes experienced rates of isolated LRR in excess of 20%. The results of the Danish trial demonstrated that the reduction in LRR observed with the addition of radiotherapy in patients with comparable LRR rates translated into an absolute benefit in DFS of 10% and an absolute benefit in OS of approximately 6%. This survival benefit is similar in magnitude to that achievable with adjuvant systemic therapy. Together, these data suggest that all patients with tumors larger than 4 cm or with four or more involved axillary lymph nodes should be offered postoperative radiotherapy.

The risk of LRR and, thus, the value of postmastectomy radiotherapy in patients with one to three involved nodes remain controversial. Although the Danish group observed an improvement in OS for this subset of patients, the reported LRR rate of 30% was much greater than that reported in other studies, in which it ranged from 5% to 20%.As a group, patients with stage II breast cancer and one to three involved nodes experienced a low risk of LRR (10% isolated LRR and 14% total LRR). However, there were subsets of these patients who were observed to have a much higher risk of LRR. These include patients with tumors larger than 4.0 cm (26% isolated LRR risk) or with lymph node disease displaying extranodal extension > 2 mm (33% isolated LRR risk). Because patients without these risk factors who have undergone an adequate axillary dissection have a low risk of LRR, any survival benefit from adjuvant radiotherapy is likely to be small. Although the proportional reduction in breast cancer deaths in these low-risk patients is likely to be similar to that of those at greater risk of LRR, the absolute benefit would be expected to be modest. Assuming the same proportional risk reductions observed in the British Columbia and Danish Cooperative Group trials, a reduction in LRR rates from 10% to 3% with comprehensive postmastectomy irradiation would be predicted to result in a 3% survival advantage for these low-risk patients. The specific threshold of LRR risk that warrants the addition of adjuvant irradiation is debatable and requires the clinical judgment of the physician in consultation with individual patients. In fact, the threshold for the recommendation of adjuvant systemic therapy has gradually been lowered over the years, and for many patients, absolute survival benefits of less than 10% are considered acceptable indications for adjuvant therapy.

Consistent with most previous reports,our study found that the chest wall and supraclavicular fossa are the most common sites of LRR. The low overall rates of axillary recurrence do not support the routine supplementation of axillary dose beyond that delivered by the supraclavicular/axillary apex field and the chest wall tangents. Although the rate of documented IMC failures in our cohort was quite low, CT scans and ultrasound were not routinely performed as screening procedures in these patients, many of whom were treated before the routine use of CT scans. It is, therefore, possible that many IMC recurrences went undetected. Indeed, despite the observation that these clinical recurrences are rare, autopsy and surgical reports have documented microscopic involvement of the IMC nodes in up to 25% of node-positive patients with outer quadrant tumors and 50% of those with central/inner quadrant tumors.Whether subclinical involvement of these nodes is a source of seeding for distant metastasis is also unknown. The indications for treatment to the regional lymphatics, particularly the use of a posterior axillary supplemental field and targeting of the IMC nodes, remain questions worthy of further study.

The results of this analysis demonstrate that doxorubicin-based chemotherapy does not obviate the need for postmastectomy irradiation. Patients with zero, one to three, four to nine, and 10 or more involved nodes experience isolated LRR rates of 4%, 10%, 21%, and 22%, respectively. The corresponding rates of total LRR are 7%, 14%, 25%, and 34%, respectively. Because of the longer duration of follow-up and precise definition of isolated and total LRR in the current series, these rates are consistent with previous reports from our institution. Our results also support the recently published recommendations of the American Society for Therapeutic Radiology and Oncology (ASTRO) consensus statement regarding the indications for postmastectomy irradiation.We conclude that patients with stage II disease and four or more involved nodes or stage III disease are at the greatest risk of isolated LRR and are most likely to derive a benefit from the addition of postmastectomy irradiation. Taken as a whole, patients with stage II breast cancer and one to three involved lymph nodes are at low risk of LRR, and the corresponding absolute benefit in survival derived from postmastectomy irradiation is likely to be small. However, there may be a subset of these patients who are also at a significant risk of LRR and for whom adjuvant irradiation should be considered. These include patients with large tumors, those with extranodal extension > 2 mm, and those who have not undergone an adequate axillary dissection.

The question of whether radiation benefits subgroups of stage II patients with one to three involved nodes takes on increased importance with the growing evidence that modern radiotherapy has the potential to improve survival in properly selected patients. Because our experience does not reproduce the findings of the recent prospective trials, it is difficult to justify the routine use of postmastectomy irradiation in patients with one to three involved nodes unless other risk factors are present. The results of this study support the need for a prospective, randomized trial to specifically assess the role of postmastectomy irradiation in this patient group.