Approximately 10% to 20% of patients with stage I–IIIA breast cancer will have a chest wall recurrence alone or as a component of failure within 10 years of undergoing mastectomy.[1,3,8,15-19] The median time to local recurrence after mastectomy is 2 to 3 years,[1,17,18,21,102-106] although a delay in recurrence has been observed in ER-positive patients and with the use of adjuvant tamoxifen(Drug information on tamoxifen).[16,107]
The location of a chest wall recurrence is not specified in most series, but involvement of the mastectomy scar has been reported to vary from a low of 23% of cases to a high of 70% of cases.[21,102,105] More than half of patients with chest-wall-only recurrences present with solitary nodules, and the remainder have more than one nodule or diffuse chest wall disease.[50,102,105,108] The majority of these locoregional recurrences involve the chest wall alone or occur simultaneously with regional nodal failure.[3,17,18,27,102-105,108-110] There is wide variability—from 10% to 60%—in the reported incidence of simultaneous locoregional and distant recurrence.[1,8,16,17,19,26,29]
A multidisciplinary approach is required for the management of a chest wall recurrence after mastectomy. Overall, local control is achieved after salvage of chest wall failures in 43% to 86% of patients.[15,102,104,108,109] There is a high risk (> 50%) of subsequent distant metastases following a clinically isolated chest wall recurrence after initial mastectomy.[1,17,18,21,103,105,109-111]
• Surgery—Wide local excision of all gross disease is recommended whenever possible for solitary or multiple nodules amenable to resection.[21,103,104,106,109,112] Wide excision alone has been associated with a second local recurrence in over 60% to 70% of patients, despite its use in a more favorable group of patients with smaller tumor sizes and solitary nodules, compared to patients typically managed with surgery and radiation or radiation alone.[15,21,106]
The excision of gross disease serves the purpose of both maximizing subsequent local control and moderating the required dose of chest wall irradiation. A negative resection margin is preferable, although there are no data on the risk of subsequent second chest wall relapse with a close or positive margin, as compared with a negative margin.
• Radiation—Chest wall irradiation is recommended for patients after wide local excision if there is no history of previous postmastectomy radiation as part of their initial breast cancer treatment.[21,103,104,106,107,109,112] Halverson et al reported that all of their chest wall recurrences < 3 cm that were excised prior to irradiation were controlled locally with doses of 45 to 59 Gy.
Schwaibold et al reported that 48% of patients had locoregional control after wide excision and radiation. In that series, no dose-response effect was observed above 50 Gy when irradiating after a gross total excision.
Even for small isolated recurrences that are completely excised, the whole chest wall and area of recurrence should be treated rather than just small limited-sized fields. Some have reported boosting the dose to the mastectomy scar or site of local recurrence,[103,104] but it is unclear if this contributes to an improvement in local control.
For isolated chest wall recurrences, the supraclavicular nodes should be electively treated concurrently with the entire chest wall because of the increased risk of subsequent relapse without radiation. Elective irradiation of a clinically uninvolved axillary or internal mammary node region is not necessary. The response rate to salvage chest wall irradiation after less than an excisional biopsy is high (73% to 96%), but approximately 60% to 70% will subsequently experience a second local failure.[21,102,104,106,110]
Schwaibold et al reported a dose-response effect with doses of 60 Gy or higher for local control of tumors £ 4 cm, but only 30% of larger or diffuse unresectable disease was controlled even with doses as high as 70 Gy. There is no benefit to hyperfractionated chest wall radiation, with or without complete excision of gross disease.
• Systemic Therapy—Systemic therapy should be considered for most patients following treatment of a clinically isolated chest wall recurrence.[103,104,106,112] As previously noted, the majority of patients are at risk for a subsequent second local recurrence and/or distant metastasis.
Schwaibold et al reported improved locoregional control after excision and radiation of isolated locoregional recurrence with the addition of systemic chemotherapy (78% vs 38%, P = .15). These investigators also found a nonsignificant trend to improvement in relapse-free and overall survival with the use of chemotherapy, but only in the subgroup of patients treated with wide excision and radiation.
In another retrospective series, Halverson et al found that the addition of hormonal therapy after local recurrence significantly improved disease-free and overall survival. Nevertheless, chemotherapy but not hormonal therapy was associated with a trend toward improved locoregional control.
Haylock et al reported a nonsignificant trend towards improvement in overall survival (62% vs 51% at 10 years, P = .24) in one cohort treated with immediate chemotherapy, compared to another control cohort treated without initial chemotherapy. Based on this trial, chemotherapy should be sequenced following radiation, with or without wide excision, in order to permit full delivery of the chest wall irradiation.
Hsi et al studied a series of 18 patients selected for favorable prognostic factors following initial mastectomy and isolated locoregional recurrence. The rates of subsequent disease-free survival were 83% with tamoxifen, compared to 33% without.
The only randomized trial in this setting has been reported by Borner et al.[114,115] Patients with ER-positive isolated locoregional recurrence, or with a disease-free interval > 1 year and less than four tumor nodules (none greater than £ 3 cm), were randomized to tamoxifen or placebo after complete local excision and radiation. The incidence of second local failure at 5 years was significantly reduced—from approximately 30% to 10%—in patients randomized to receive tamoxifen (P < .001). There was no significant overall survival benefit demonstrated with the use of tamoxifen.
However, a later subset analysis of the trial showed an improvement in the 5-year disease-free survival (29% vs 60%) and overall survival (71% vs 78%) of postmenopausal women treated with tamoxifen. In this subgroup, there was a reduction in subsequent local failure (27% vs 9%, P < .001) and distant metastases (30% vs 24%, P = .16) as first events. However, in premenopausal women, there was no improvement in disease-free survival (55% vs 57%), and there was an unexpected decrease in 5-year survival (90% vs 60%) for tamoxifen vs observation.
The prognosis for distant metastases and survival depends most upon interval to recurrence.[1,15,17,19,102,105,106, 108,110,111,114] The critical interval to recurrence that is associated with the highest risk of subsequent distant metastases and death is within 2 years from the time of initial mastectomy. In a recent update of the EORTC 10801 trial, van Dongen et al observed that 73% of patients with clinically isolated locoregional recurrence < 2 years after mastectomy had subsequent distant metastases, compared to 35% for an interval ³ 2 years.
Other favorable prognostic factors for survival are an isolated chest wall relapse (as opposed to one with an associated regional failure),[15,105,109,110] a smaller initial tumor size, and/or less extensive initial nodal disease.[15,17,19,105, 108,109,111] Estrogen-receptor positivity has been associated with improved distant disease-free survival[15,103] or overall survival[19,105] in some series. The ability to achieve local control after salvage of an isolated chest wall recurrence has also been prognostic for survival in some series.[102,105]
Many studies have looked at combinations of factors that together may be more predictive of subsequent outcome compared to individual factors. Schmoor et al reported that 114 patients (24% of all locoregional recurrences) with both initial node-negative disease and disease-free interval greater than 2 years had a 5-year survival rate of 66%, compared to 27% for those with initial node-positive disease and a disease-free interval less than 2 years. Schwaibold et al found three factors independently prognostic for survival on multivariate analysis: a disease-free interval of 24 months or more, use of excisional biopsy, and locoregional control. In their most favorable patient subgroup with all three factors (18% of all patients with isolated locoregional recurrence), the 5-year relapse-free and overall survival rates after recurrence were 59% and 61%, respectively.
Hsi et al reported on a favorable subgroup of 18 patients (25% of isolated locoregional recurrences) with a disease-free interval of more than 2 years, isolated chest wall disease, and tumor size < 3 cm or complete resection prior to radiation. In this subgroup, overall survival with salvage treatment was 81% at 5 years and 72% at 10 years. Willner et al reported a 5-year survival of 90% and a 10-year survival of 67% for a subgroup of 30 patients (26% of isolated locoregional recurrences) with a disease-free interval of at least 1 year, solitary recurrence, initial T1-2 disease, and absence of necrosis. Magno et al found that 43 patients (26% of their series) with three of five favorable prognostic factors—ie, T1 tumor, node negative, interval to recurrence more than 2 years, solitary recurrence, or recurrence £ 1 cm—had a 5-year survival of 75% vs 15% for those with no more than two of these factors.
In summary, these favorable subgroups of patients represent only 20% to 25% of all isolated locoregional recurrences after mastectomy, and a smaller percentage of all locoregional recurrences, but may be associated with a survival of 60% to 90% at 5 years and up to 70% at 10 years.[19,102,105,107,111]