It is indeed paradoxical that the use postmastectomy radiation therapy (PMRT) continues to cause considerable debate and controversy despite having been the subject of over 20 randomized prospective trials spanning 5 decades of research activity. In fact, some of the first prospective randomized trials ever conducted attempted to define the role of PMRT.1 Nonetheless, several important questions still await definitive answers.

Historically, PMRT was offered to the majority of women with breast cancer in the early and mid-20th century.2 Many of these women had locally advanced breast cancer, and oncologists of the time intuitively understood that additional locoregional therapy was needed for these women with a high burden of locoregional disease. Clinicians became cognizant of the potential risks of PMRT at the same time that surgical techniques improved and systemic therapy was developed. Consequently, the role of PMRT in the nascent therapeutic strategy for women with breast cancer came under rigorous scrutiny.

This chapter will focus exclusively on the topic of PMRT and is divided into 4 themes. First, the rationale for PMRT will be considered, by reviewing data supporting the efficacy of PMRT. Because the rationale for any intervention is contingent on the risks of the intervention, the risks and sequelae of PMRT will also be reviewed in this section. Second, data that attempt to shed light on the often vexing problem of appropriate patient selection will be reviewed. Third, breast reconstruction after mastectomy and its relevance to PMRT will be reviewed. Finally, the technique for PMRT will be discussed as well as the related issues of treatment volume and dose.

Efficacy of PMRT

The efficacy of irradiating the chest wall and draining lymph nodes after mastectomy in improving locoregional control has been firmly established by multiple older trials comparing mastectomy alone to mastectomy with postoperative radiation.3-9 These trials typically used outdated radiation techniques and equipment that produced orthovoltage x-rays. Orthovoltage x-rays produce suboptimal dose distributions that would never be used for therapy in the modern context. Because of these reasons, the relevance of these older trials is limited in the context of modern radiation therapy, but they adequately demonstrated 2 important facts: (1) PMRT can effectively reduce the burden of residual locoregional disease; and (2) in terms of treatment volume, radiation therapy is more comprehensive and more “radical” than even the most radical surgery. Notably, these trials did not demonstrate improvements in survival end points.

The locoregional effects of adjuvant systemic therapy alone (without radiation) can be studied through those trials of systemic therapy versus nil that have reported patterns of failure.10-24 In summary, data demonstrating an improvement in locoregional control with systemic cytotoxic chemotherapy are somewhat inconsistent. However, the most recent Early Breast Cancer Trialists Colloborative Group (EBCTCG) meta-analysis of systemic therapy trials reported statistically fewer isolated local relapses in patients receiving polychemotherapy (recurrence rate ratio of 0.63 and 0.70 for women < 50 and 50-69, respectively).25 However, it appears that increasing the intensity or agents of chemotherapy does not improve locoregional control over standard chemotherapy.26-31 In contrast, adjuvant tamoxifen seems to improve locoregional control rather consistently, reducing the likelihood of recurrence on average by about one-half.10,12-14,23 This was also demonstrated in the most recent EBCTCG meta-analysis just mentioned, which showed an isolated local recurrence rate ratio of 0.47 with tamoxifen versus without.25 These observations, along with the demonstrable improvement in survival with systemic agents, call into question the relative benefit of PMRT in improving locoregional and survival end points in patients who have received or will receive systemic therapy.

Several trials have studied the efficacy and added benefit of PMRT in the presence of systemic therapy.32-44 The most definitive of these have come from the Danish Breast Cancer Cooperative Group40,41 and the British Columbia Cancer Agency.42 In addition to these, the updated findings of EBCTCG meta-analysis of postoperative radiation trials, which will be discussed later,45 have decisively altered practice and reaffirmed the role of PMRT in modern breast oncology.

The Danish Breast Cancer Cooperative Group’s protocol 82b randomized premenopausal women with high-risk breast cancer after modified radical mastectomy (total mastectomy and level 1 and 2 axillary dissection) to either 9 cycles of CMF chemotherapy or to 8 cycles of CMF chemotherapy and radiation therapy to the chest wall and regional nodes between the first and second cycles of chemotherapy.40 High-risk status was defined as positive lymph nodes, tumor size greater than 5 cm, or invasion of the skin or pectoralis fascia. Radiation therapy was delivered to a total dose of 50 Gy in 25 fractions or 48 Gy in 22 fractions using an anterior electron field to treat the chest wall and internal mammary nodes (IMNs) and a matched anterior photon field to treat the supraclavicular, infraclavicular and axilla lymph nodes. A posterior axillary photon field was used in patients with a large anterior-posterior separation. Over 92% of all patients were treated with megavoltage equipment. The study enrolled 1708 patients from 1982 to 1989. With a median follow-up of 114 months, the irradiated group demonstrated statistically significant improvements in locoregional recurrence (32% vs 9%), disease-free survival (35% vs 48% at 10 years), and overall survival (45% vs 54% at 10 years). Notably, over half of all locoregional recurrences were on the chest wall.

In the companion 82c protocol,41 postmenopausal women younger than 70 with high-risk breast cancer (defined as in 82b) were randomized after modified radical mastectomy to receive either 30 mg of tamoxifen daily for 1 year beginning 2 to 4 weeks after surgery alone or with concurrent radiation therapy delivered to the chest wall and draining lymph nodes. Radiotherapy details were identical to the 82b trial. Similar to the 82b trial, over 90% of women were treated with megavoltage equipment. Between 1982 and 1990, a total of 1375 patients were recruited and followed for a median time of 10 years. As in the 82b study, the irradiated group demonstrated statistically significant improvements in locoregional recurrence (35% vs 8%), disease-free survival (24% vs 36%), and overall survival (36% vs 45%). Again, the majority of locoregional recurrences were on the chest wall, but the proportion of recurrences at all locoregional subsites was lower with PMRT than without. The Danish investigators deserve much praise for these well-designed efforts, which although not without flaw (as will be discussed later), clearly demonstrated that in certain patient subsets, aggressive locoregional control could translate into improved survival—independent of systemic therapy.

The British Columbia trial enrolled 318 node-positive premenopausal breast cancer patients and randomized them after modified radical mastectomy to either radiation therapy or no additional locoregional therapy.42 Both groups received adjuvant CMF chemotherapy for 12 months (first 80 patients) or 6 months. Radiation therapy was delivered to the chest wall to a dose of 37.5 Gy in 16 daily fractions through opposed tangential photon fields. The supraclavicular and axilla nodes were treated with an AP field and a posterior axillary field, as is conventionally done, with a target midaxilla dose of 35 Gy. Bilateral IMNs were treated with an additional anterior field to a dose of 37.5 Gy in 16 fractions. All treatments were delivered with cobalt machines, between cycle 4 and 5 of chemotherapy. After a median follow-up of 20 years, the 20-year survival free of locoregional disease developing before systemic disease was 61% in the chemotherapy-alone arm and 87% in the irradiated group. The irradiated group had significantly higher 20-year event-free survival (25% vs 38%), systemic disease-free survival (31% vs 48%), breast-cancer-specific survival (38% vs 53%), and overall survival (37% vs 47%). There were slightly more non-breast-cancer deaths in the irradiated group (9% vs 4%, p = 0.11). There were 3 cardiac deaths (2%) in the irradiated group versus 1 (0.6%) in the control group (p = 0.62), and 9% of patients in the irradiated group developed arm edema compared with 3% in the control group (p = 0.035).

The EBCTCG has collected primary data from every randomized trial of adjuvant radiotherapy in breast cancer, and periodically reports the ongoing analyses on the benefits and risks of radiation therapy in these patients. The most recent report from 2005 reviewed data on 9933 patients enrolled on 25 trials of PMRT, all of which were unconfounded by the use of systemic therapy.45 Node-positive patients who had axillary clearance and received radiation therapy after mastectomy had a 5-year locoregional recurrence rate of 6%, compared to 23% for unirradiated controls (15-year rates were 8% vs 29%). In every large trial of PMRT in node-positive women, radiation therapy produced comparable proportional reductions in local recurrence in all women irrespective of age or tumor characteristics and regardless of time period—indeed a powerful demonstration of the efficacy of radiation therapy in reducing local recurrence.

Because the proportional reductions in local failures were similar across heterogeneous patient groups, the absolute reductions in local recurrence were variable and dependent on the control risk, that is, larger reductions were seen in subsets with greater risk and smaller reductions were noted in women with lower risk. For patients with a control risk of local recurrence that exceeded 10%, the addition of RT improved local recurrence irrespective of systemic therapy (chemotherapy and/or hormonal therapy). Importantly, the overall 17% absolute improvement in 5-year local control translated into a 5.4% absolute improvement in 15-year breast cancer mortality (60.1% vs 54.7%, 2p = 0.0002).45 In terms of absolute effects, a 4:1 ratio of benefit was seen, whereby a 20% absolute reduction in 5-year local recurrence resulted in a 5% absolute reduction in 15-year breast cancer mortality. Furthermore, women with node-positive disease who were irradiated after mastectomy and axillary clearance experienced a 4.4% absolute improvement in all-cause mortality over controls (2p = 0.0009), a difference not detected in the prior EBCTCG report published in 2000.46

In their review of the EBCTCG data, Punglia and associates note that treatments that had little or no effect on decreasing the 5-year local recurrence rate produced no benefit in 15-year breast cancer mortality.47 They also draw attention to a subgroup analysis in the report that showed that the use of radiation therapy after mastectomy in node-positive patients improved 15-year survival only in patients who also received adjuvant systemic therapy and not in patients who were treated with mastectomy alone. This lends credence to the concept of an independent yet cooperative effect of adjuvant locoregional therapy and adjuvant systemic therapy.

Updated data from the EBCTCG was presented at the 2007 annual meeting of the American Society of Clinical Oncology.48 In contrast to prior reports, the subgroup of patients with 1 to 3 positive lymph nodes demonstrated statistically significant improvements in 15-year breast cancer mortality (50.9% vs 43.3%, 2p = 0.002) and all-cause mortality (56.1% vs 50.9%, 2p = 0.05) with PMRT. In addition, a study of prognostic factors for 5-year local recurrence risks identified tumor grade as a highly significant factor, even when controlling for other known risk factors. These findings will undoubtedly be expounded upon in the next full report from the EBCTCG trialists.

The value of the EBCTCG overview cannot be overstated. However, the relevance of its findings may be limited by the inclusion of trials that used fractionation schemes, treatment machines, and treatment volumes that are antiquated by today’s standards, as well as by the other limitations inherent to all meta-analyses. Attempts to correct for these limitations suggest that the EBCTCG results may actually underestimate the benefit of PMRT. For example, Van de Steene and coworkers conducted a similar meta-analysis and demonstrated improved odds ratios for survival with PMRT by excluding trials that began before 1970, trials with small sample sizes (< 600 patients), trials with poor survival rates (crude survival less than 80%), and trials that used outdated fractionation schemes.49 Similarly, Whelan and associates performed a meta-analysis of PMRT trials that specifically included systemic therapy in both the control and experimental groups.50 As with the EBCTCG study, the addition of RT led to reductions in the risk of any recurrence (odds ratio = 0.69) and death (odds ratio = 0.83). Finally, Gebski and colleagues performed a meta-analysis in which they carefully attempted to control for the quality of radiation delivery in PMRT trials. The authors defined optimal dose as 40 to 60 Gy delivered in 2-Gy fractions (nonconventional fractionation schemes were converted to 2-Gy equivalents using bioeffective dose calculations) and appropriate treatment volumes as both chest wall and regional lymphatics (but not necessarily inclusive of the IMNs).51 The data from the EBCTCG meta-analyses were then reanalyzed applying these criteria. Locoregional control was greater for trials with optimal dose and volume (80%), compared to those with suboptimal dose (70%) or volume (64%). An improvement in breast cancer mortality was limited to those trials that used appropriate doses and fields for irradiation (6.4% absolute increase in survival, p < 0.001).

It is worth noting that the survival improvements demonstrated in the collective Danish and British Columbia experiments are among the most remarkable improvements in survival ever reported for any adjuvant therapy in a randomized trial. Taken together, these studies show that certain patient cohorts have a high risk for locoregional recurrence that cannot be addressed by systemic therapy alone. Reducing the rates of locoregional failure can result in improved survival, perhaps because persistent or recurrent locoregional disease serves as a source of distant metastases and subsequent death. The collective PMRT data seems to indicate that adjuvant locoregional therapy and adjuvant systemic therapy independently benefit patients on the principle of spatial cooperation, with the former addressing microscopic locoregional residual disease and the latter addressing systemic micrometastases.

Risks of PMRT

Perhaps the most concerning risk of PMRT for treating physicians is the risk of radiation-induced cardiac morbidity. As described earlier, the EBCTCG meta-analysis as well as other registry data have detected increased risks of cardiac mortality in irradiated patients.45,46,52 An older meta-analysis by Cuzick and colleagues contributed significantly to the PMRT discourse.53,54 First published in 1987 and then updated in 1994, the meta-analysis pooled data from 10 early trials (all initiated before 1975 and all without chemotherapy) of mastectomy with or without PMRT, and, in the second report, attempted to define cause-specific mortality in over 4000 patients who died at least 10 years after enrolling on study.53,54 The time period during which these trial were conducted saw an important shift of surgical technique away from radical mastectomy to less radical surgery. In women who had a radical mastectomy, an 18% deficit in all-cause mortality was found in women who received radiation therapy compared to controls who were observed. However, there was no difference in the group that had either simple or modified radical mastectomy followed by RT versus those who were observed. There was a nonsignificant 7% decrement in survival reported for all patients who received radiation therapy (p = 0.21). Older, node-negative women treated on the earlier trials with radical mastectomy contributed most to this observed decrement. Cause-specific mortality analysis revealed an excess of cardiac mortality in patients who received radiation therapy, and was greatest in the 3 trials in which the largest doses were given. The standardized mortality ratio (SMR) for cardiac mortality for left- versus right-sided irradiation was 1.34 (p = 0.09). Breast-cancer mortality was improved with PMRT and tended to balance cardiac-related mortality at 10 years. Nonetheless, the meta-analysis by Cuzick and associates raised significant concerns in the oncology community about the safety of PMRT, although it was clearly burdened by all the usual limitations of a meta-analysis of older trials.

There was excess mortality from heart disease and lung cancer in women studied on the updated EBCTCG report (including women treated with an intact breast), as well as and excess cancer incidence mainly in the contralateral breast and lung. The averaged detrimental effects of irradiation were minor, with 15-year absolute loss of 1.8% for contralateral breast cancer and 1.3% for non-breast-cancer mortality. Importantly, the proportional excess of non-breast-cancer deaths was greatest 5 to 14 years and >15 years after randomization, and the mean dates of randomization for these 2 groups were 1975 and 1970, respectively. The authors of the EBCTCG correctly note that the late hazards evident in their report could well be substantially lower for modern radiation therapy technique and regimens.

An analysis of the Danish postmastectomy trial patients by Hojris and associates found equal rates of ischemic heart disease and acute myocardial infarction (MI) in the irradiated and unirradiated group.55 Approximately 3% of patients in both groups had ischemia-related morbidity at a median follow-up of 117 months, and less than 1% of patients in both arms had death due to cardiac causes, with no notable differences when comparing left- versus right-sided irradiation. It should be mentioned that the Danish investigators deserve praise for their careful technique aimed at minimizing cardiac irradiation; the authors used customized blocks and all patients had a chest wall ultrasound to measure chest wall thickness so the correct electron energy could be selected for the IM field. On the one hand, these numbers can be interpreted to mean that, with good technique, the cardiac risks are minimal; on the other, these numbers may underestimate the true burden of radiation-related cardiac morbidity due to the competing risk of breast-cancer death in this high-risk population, and also because this study was an unplanned retrospective report on a prospectively studied patient cohort.

In their review of 960 patients treated on the first Stockholm Breast Cancer Trial (modified radical mastectomy alone vs preoperative vs postoperative RT accrued 1971-1976), Gyenes and associates reported 58 acute MI in the study population for a crude rate of 6%.56 There were no differences in acute MI or death due to cardiovascular disease (n = 63/960) between irradiated and unirradiated patients. In addition, only patients in the high-dose-volume group had an excess hazard of cardiovascular death (HR 2, 95% CI 1.0-3.9, p = 0.04). A retrospective study by Harris and coworkers examined cardiac events in a series of 961 women irradiated to the intact breast and reported no interaction between left- versus right-sided RT on cardiac mortality or congestive heart disease.57 However, a significant association was noted between left-sided irradiation and the subsequent development of coronary artery disease (20-year actuarial risk 25% vs 10% for right-sided, p < 0.001) and MI (15% vs 5%, p < 0.002). In their experience, coexistent hypertension was an independent hazard for the development of coronary artery disease.

A study of the SEER database conducted by Giordano and colleagues compared 15-year cardiac mortality rates in left- versus right-sided breast cancer as a function of the year of diagnosis in patients who received RT.58 As in other studies, the presumption was that patients with left-sided lesions received more heart irradiation than those with right-sided lesions. Although the authors demonstrated excess cardiac mortality in left-sided breast cancer patients diagnosed from 1973 to 1979 (13% vs 10%, p = 0.02), they found no significant difference in patients irradiated in the most recent time periods (approximately 9% for both groups in the 1980-1984 cohort, and 5-6% in the 1985-1989 cohort). Beginning in 1979, the hazard of death from ischemic heart disease in left-sided breast cancer patients (vs right-sided) declined by an average of 6% per year. Taken together, these data are certainly reassuring and imply that improvements in image-based treatment delivery should further reduce cardiac morbidity associated with radiation therapy.

Additional non-life-threatening late risks of postmastectomy radiation can include arm edema, fibrosis, shoulder stiffness, and brachial plexopathy. In a valuable report from the Danish postmastectomy trialists, patients irradiated at Aarhus University Hospital who were alive and without evidence of disease were invited to participate in a study of the late effects of PMRT.59 Eighty-four patients accepted the invitation and were eligible for analysis, and these patients were carefully assessed for late toxicity based primarily on LENT-SOMA criteria. More women in the irradiated group had lymphedema (17% vs 9%) and impaired shoulder movement (16% vs 2%) that interfered with work or daily activities. Irradiated patients also had more arm paresthesias (21% vs 7%) and more arm weakness (14% vs 2%). Perhaps because this analysis was limited by small numbers, only the decline in shoulder function reached statistical significance. Symptomatic pulmonary complications and cardiac events were equal in irradiated and unirradiated patients. In a separate report of 161 patients with neurologic follow-up who were irradiated on the Danish 82 protocols, 5% of patients had disabling and 8% had mild radiation-induced brachial plexopathies.60 Finally, Kunht and associates reported acute and chronic reactions in 194 patients receiving PMRT. Twenty-two percent of patients had any incidence of chronic effects, mostly from arm edema (28/43).61 Five patients had telangiectasia and 1 patient had plexopathy.

In summary, randomized trials as well as data from meta-analyses provide a strong rationale for PMRT in patients at high risk for residual locoregional disease, regardless of the use of systemic therapy in these patients. Additional locoregional therapy in the form of RT reduces LR recurrence rates by a factor of approximately two-thirds, and 1 breast-cancer death is averted for every 4 LR recurrences prevented by RT. The risks of PMRT are modest but demonstrable, and cardiac effects may largely be attributable to radiotherapy techniques and schedules no longer in use. The cardiac detriment of modern-day PMRT is unknown.

Node-Positive Patients

Axillary node-positivity is the most significant predictor of locoregional recurrence after mastectomy. It should be remembered, however, that approximately two-thirds of locoregional recurrences occur on the chest wall, and that axillary failures are far less common.62-65 Therefore the degree of node positivity should be viewed as a nonspecific surrogate for locoregional recurrence risk (ie, risk not limited to axillary failure).

The Danish and Canadian PMRT trials demonstrated stable relative risk reductions for all events in all groups of node-positive patients. However, there are 2 general criticisms of these studies that limit the translation of these findings to all node-positive patients: (1) the adequacy of the systemic therapy in the control arms of these studies and (2) the issue of the “background risk” in the study populations.

The EBCTCG meta-analysis of systemic therapy revealed a modest but statistically significant improvement for anthracycline-containing polychemotherapy regimens over CMF-based regimens.25 How this small incremental benefit affects locoregional control is unknown, but a significant benefit in patients with high risk for locoregional microscopic residual seems unlikely. For example, we do know that neither the addition of taxanes nor increases in the intensity or density of chemotherapy demonstrably improve locoregional control in node-positive patients, although they do improve survival end points, presumably by addressing micrometases.26-31 Given these data it is probably safe to conclude that present-day chemotherapy regimens would not significantly alter the findings of the postmastectomy trials. However, the Danish 82c trial treated the postmenopausal patients (untested for ER/PR status) with only 1 year of tamoxifen,41 and it is unknown how a longer duration of hormonal therapy in an exclusively hormone-receptor-positive population would modulate the risk of locoregional recurrence and, in turn, the benefit of PMRT.

The second and more significant issue that limits interpretation of the Danish and British Columbia trials is that node-positive patients on the control arms of these trials had higher locoregional recurrence rates than commonly reported for patients treated in the United States and elsewhere.40-42,62 This difference is even more apparent in the subgroup of patients with 1 to 3 positive lymph nodes, who comprised about 60% of patients on these studies. The 18-year probability of locoregional recurrence (as first site of failure) was 59% for patients with 4 or more positive nodes, and 37% for those with 1 to 3 positive nodes in the control arms of the Danish trials.66 Similarly, the 20-year isolated locoregional recurrence rate was 41% for patients with 4 or more positive nodes, and 21% for patients with 1 to 3 positive nodes on the control arm of the Canadian trial.42 Locoregional recurrence developing any time before distant failure (ie, cumulative LRR as first failure) was 39% for the entire unirradiated group, but was not reported by number of positive nodes.

In contrast to this, several large series of patients treated in the United States and elsewhere have reported locoregional recurrence rates in the range of 6% to 13% for patients with 1 to 3 positive nodes (Table 96-1).63,64,67,68 For example, Recht and associates reviewed the ECOG experience of over 2000 node-positive patients treated with adjuvant systemic therapy but without RT. The 10-year rate of LRR (with or without distant failure) was 13% for patients with 1 to 3 positive nodes, and 29% for patients with 4 or more involved nodes.64 The MD Anderson Cancer Center (MDACC) reviewed recurrence data for postmastectomy patients treated on studies of doxorubicin-based chemotherapy without RT. The 10-year actuarial total LRR was 13% for patients with 1 to 3 positive nodes and 26% for patients with more than 3 positive nodes.63 This seems to indicate that the background risk for locoregional recurrence in the Danish and BC trials was higher than average, and this may have exaggerated the benefit of PMRT in this population.

Differences in axillary surgical evaluation may account for these differences; a median of 7 lymph nodes were removed in the Danish studies and a median of 11 lymph nodes were examined in patients on the Canadian trial.40-42 These differences in axillary evaluation may have shifted the entire spectrum of risk; patients scored as having 1 to 3 positive lymph nodes may actually have had 4 or more positive nodes on full dissection. This in turn could have magnified the benefits of PMRT. Tellingly, failure in the axilla either alone or as a component of LRR represented 43% of all LRR in the Danish studies,62 compared to 14% in the MDACC study cited in the preceding paragraph.63

Although the differences in the extent of axillary evaluation may account for the differences in the control risk observed between the PMRT trial population and the other reported populations, it should be noted that the studies in Table 96-1 have reported results typically at a median of 10 years of follow-up. In contrast, the Danish studies report 18-year recurrence rates, and also document a consistent LRR of about 1% per year between follow-up years 10 and 25.62 Similarly, in the BC trial, which has reported 20-year recurrence rates, approximately 20% of LRRs occurred after follow-up year 10.42 Other identified and unidentified risk factors, such as T4 tumors and/or pectoral fascia invasion, may have been over-represented in the postmastectomy trials,62 increasing the background risk for locoregional failure. For example, in a combined report of patients with 1 to 3 positive axillary nodes treated on the control arm of the British Columbia postmastectomy trial (n = 82) and similar patients treated on prospective systemic therapy trials at the MDACC (n = 462), statistically significant differences were detected in patients on the BC trial who were younger (median age 43 vs 48) and had more lympovascular invasion (52% vs 33%), in addition to fewer examined nodes (median 10 vs 16).69 The resultant 10-year Kaplan–Meier estimates of LRR were 21.5% and 12.6% for the BC and MDACC patients, respectively.

Still, several reports have demonstrated the prognostic impact of total dissected nodes, nodal ratio (number of involved to uninvolved nodes), and number of total uninvolved nodes on LRR and even overall survival.63,64,67-72 Indeed, in the combined BC/MDACC study described above, nodal ratio greater than 0.20 was reliably associated with a 10-year LRR > 20% across both groups of patients.69 Attempts by Danish investigators to reanalyze their patients to include only those with adequate dissections are limited by the fact that these patients were not stratified by this important risk factor at randomization.73 This issue remains unclear and contested and will perhaps be settled by ongoing randomized trials (see “Future Directions” later in the chapter). The American Society of Therapeutic Radiology and Oncology (ASTRO), the American Society of Clinical Oncology (ASCO), and other advisory organizations have endorsed the routine use of PMRT in women with 4 or more involved nodes and node-positive women with tumors greater than 5 cm; these groups have a high (> 20-25%) risk of locoregional recurrence without RT.74-77 Both societies recognize the uncertain benefit of PMRT in patients with T1/T2 primaries with 1 to 3 positive nodes (stage II) in whom the risk of LRR is intermediate (around 10-20%).75,76