Extended Radical Mastectomy

The guiding premise in Halsted’s 1894 report of his technique for radical mastectomy (RM) was that local control and survival were related and that an operation that minimized local recurrence would maximize survival. This concept was extended to its limit by Wangensteen’s “super-radical mastectomy” (a staged operation, which included resection of the breast, IM, mediastinal, and supraclavicular nodes), first described in 1949 and eventually abandoned because of high operative mortality (12.5%) and few survivors. In 1951, Urban observed a high rate of parasternal chest wall recurrence (18%–28%) after RM in patients with inner-quadrant breast cancers. He logically hypothesized that extended RM (ERM), an operation that combined RM with a full-thickness resection of the parasternal chest wall and IM nodes, might offer a survival advantage for a subset of patients at increased risk for IM node involvement, specifically those with central or inner quadrant tumors. In his initial series of ERM, done for patients with stage I-II disease, he reported good results and no operative mortality.

The goal of improved survival with more radical versions of mastectomy was never met: Veronesi and Valagussa’s randomized trial comparing ERM with RM demonstrates a 1.1% to 3.5% reduction in the 10-year rate of parasternal chest wall recurrence but no difference in any other outcomes or in survival at 30 years’ follow-up. These studies clearly establish the prognostic significance of IM node metastases: Veronesi and colleagues trial, the final 10-year report from Cody and Urban, and the overall literature on ERM collectively show that the prognostic significance of axillary and IM node metastases is comparable. The prognosis of patients with disease limited to axillary or IM nodes is intermediate between that of patients with negative nodes and those with IM and axillary metastases. These results would seem to confirm the Fisher hypothesis that lymph node metastases have prognostic value but that occult systemic disease governs survival and that variations in local control are therefore unlikely to affect survival. More recently, the 2005 Early Breast Cancer Trialists’ Collaborative Group meta-analysis has made the historic observation that local control and survival are related but that survival is improved only when local relapse is reduced by more than 10%.

IM Nodes: Implications for the SLN Era

Three studies have reviewed the collective literature on IM nodes and are relevant and instructive for the SLN era. Klauber-DeMore and colleagues examined the results of ERM, comprising 4172 patients in 7 studies. IM node metastases were present in 19% to 33% of all cases, were more frequent in axillary node–positive (29%–52%) than node–negative (4%–18%) patients, were equally frequent for central/medial versus lateral tumors if the axillary nodes were negative (8%–10% vs 3%–13%), and were more frequent for medial/central tumors if the axillary nodes were positive (36%–49% vs 22%–26%). An exhaustive overview by Bevilacqua and colleagues (summarized in Table 1 and comprising 9 series of unselected patients and 16 series of patients selected for an increased risk of IM node involvement) and a more recent review by Chen and colleagues are substantially similar.

Current treatment protocols for stage I-II breast cancer do not include any IMN treatment, yet local recurrence in the IMN or parasternal area is rare, occurring in less than 1% of patients treated by mastectomy or breast conservation. If local recurrence must be reduced by more than 10% to improve survival and is already rare in untreated IM nodes, then it is inconceivable that any further reduction in local recurrence could improve survival. The identification of IM node metastases would, therefore, seem to be of importance mainly for the identification of increased systemic risk in patients who would not otherwise be candidates for systemic adjuvant chemo- or hormonal therapy by current National Comprehensive Cancer Network guidelines (ie, those with negative axillary nodes, negative hormone receptors, and tumors less than 0.5 cm). Within this small subset, perhaps 5% of all patients, only 10% would have positive IM nodes, changing their treatment, and only a minority of these would experience a survival benefit.

IM-SLN Biopsy

Lymphoscintigraphy (LSG) done routinely as part of lymphatic mapping identifies IM-SLN in a minority of all patients; high-resolution LSG done by a dedicated team has found IM-SLN in as many as 34% of cases, but most investigators have reported a lower yield. It is worth noting that intradermal isotope injection maximizes the success of SLN identification in the axilla but rarely drains to the IM nodes; intratumoral, peritumoral, or intraparenchymal injections are required to access the deeper lymphatics leading to the IM nodes. In a remarkable series of 700 SLN biopsy procedures (done with meticulous lymphatic mapping by intratumoral injection), Estourgie and colleagues report results that largely recapitulate those from the era of ERM: by preoperative LSG, 95% of patients drained to the axilla and 22% to the IM nodes. IM nodes were seen most frequently in the third (36%), second (27%), and fourth (24%) interspaces.

Six series using comparable methods have reported strikingly similar results for IM-SLN biopsy and are summarized in Table 2 . The routine pursuit of IM-SLN biopsy in these series identified metastasis limited to the IM nodes in only 1% of all patients, a small incremental benefit. Beyond a potential change in systemic therapy, the investigators argue other benefits for this approach, including the addition or avoidance of IM RT and the avoidance of axillary dissection in patients draining only to the IM nodes. Nevertheless, in an era when virtually all patients receive some form of systemic therapy and in which local recurrence in untreated IM nodes is rare, the rationale for routine IM-SLN biopsy remains unclear.

IM-SLN Biopsy: Is It Ever Indicated?

• 
  

  These data suggest that the benefit of routine IM-SLN biopsy accrue to few patients. Nevertheless, there are several clear indications for the procedure.

  
  
• •
  

  A preoperative LSG showing drainage only to the IM nodes. IM node drainage on LSG is almost always accompanied by axillary drainage and isolated IM drainage is infrequent; in a recent series, LSG showed drainage only to the IMN in 4% of patients but in 75% of these axillary SLNs were found at surgery. For those few patients with exclusive IM drainage and with axillary SLNs, negative or absent, IM-SLN biopsy makes sense and allows the surgeon to avoid unnecessary axillary dissection.

  
  
• •
  

  A preoperative LSG showing drainage to IM and axillary nodes and when (1) the axillary SLN is benign on intraoperative examination and (2) the patient is not already a candidate for adjuvant chemotherapy based on other criteria. Although IM-SLN biopsy makes sense for any patient in whom a positive result would alter the plan for systemic therapy, this decision is increasingly based on factors other than lymph node status, among them estrogen receptor/progesterone receptor/her2 status, lymphovascular invasion, and (increasingly) gene expression profiles.

  
  
• •
  

  Evidence of IM node involvement on preoperative imaging (CT, MRI, positron emission tomography). Grossly enlarged IMN are usually amenable to CT-guided core biopsy and are thus a debatable indication for IM-SLN biopsy. As discussed previously, most patients with visible IMN metastases are candidates for chemotherapy on the basis of other criteria and there are no data to suggest that surgical excision of grossly involved IM nodes (and specifically IM-SLN) will improve local control beyond that achieved by chemotherapy and radiotherapy (RT).

  
  
• •
  

  Reoperative SLN biopsy with drainage to IM nodes. SLN biopsy is feasible in patients who have had prior axillary surgery (SLN biopsy or axillary dissection) for breast cancer and present with local recurrence. LSG in the reoperative setting is particularly useful because the prior surgery may have altered the lymphatic drainage of the breast unpredictably. The author has observed nonaxillary drainage (most often to the IM nodes) in 30% of reoperative SLN biopsies versus 6% of first-time procedures. Ipsilateral recurrence in the conserved breast occurs in approximately 5% to 10% of all patients, and these are the patients for whom LSG and IM-SLN biopsy may ultimately prove most useful.

IM-SLN Biopsy: Technical Considerations

The author’s technique of axillary SLN biopsy has previously been described in detail. Preoperative LSG, which the author does routinely, is of limited benefit if the goal at surgery is to identify axillary SLNs (a handheld gamma probe is more sensitive that a full field-of-view gamma camera) but is essential to identify nonaxillary patterns of lymphatic drainage, in particular IM-SLN. All of the isotope injections are given intradermally, because this maximizes identification of axillary SLNs, a result confirmed in a randomized trial by Povoski and colleagues. When the author has a specific aim to identify IM-SLN, then the isotope is injected peritumorally.

In the operating room, a subdermal injection is given next (1 to 5 mL of isosulfan blue dye) in 1 of 3 ways: directly over the tumor, just cephalad to the prior excision scar, or in the subareolar location. As the dye fills the dermal lymphatics, particularly in reoperative SLN biopsy, lymphatic flow as a blush extending laterally toward the axilla or medially toward the IM nodes if often seen. Using a handheld gamma probe, the breast is scanned, identifying and marking the site of isotope injection, any hot spots in the axillary or parasternal areas, and any hot spots in between (suggesting the presence of intramammary SLN).

For patients having mastectomy, the skin incisions are marked out appropriately for conventional, skin-sparing, or skin and nipple–sparing mastectomy. If immediate reconstruction is planned, the incision is designed in collaboration with a plastic surgeon. For patients having breast conservation therapy (BCT), a circumareolar or transverse skin-line incision is made close to the tumor site but placed in such a way that if a completion mastectomy is required, the excision scar could be encompassed with minimal skin sacrifice.

The breast incision should be of adequate length to allow good exposure for the tumor excision and the IM-SLN biopsy. For mastectomy, the IM-SLN biopsy is easily done through the mastectomy incision after removal of the breast. For breast conservation therapy, the IM-SLN biopsy is done through the breast incision by dissecting in the retromammary fascial plane and retracting the breast medially as needed to expose the parasternal area. This is easily done even through lateral excision cavities. Some report using a separate parasternal breast incision for IM-SLN biopsy but the author has never found this necessary.

After identification of one or more a hot spots parasternally (most commonly in the second, third or fourth interspaces), the pectoralis major is split in the direction of its fibers, exposing the intercostal muscles. These are carefully divided from the sternal border laterally for approximately 3 to 4 cm. Lateral to this, the parietal pleural forms a single layer. Medially the pleura splits into an anterior and posterior portion, with the IM nodes, IM artery, and IM veins lying between the anterior and posterior pleural leaflets.

After division of the intercostal muscles parasternally, the fatty tissue containing the IM nodes and IM vessels is seen directly beneath the thin anterior layer of the pleura. The lung may be seen moving beneath the pleura more laterally where the anterior and posterior pleural layers have fused. The anterior layer of pleura is carefully divided proceeding from the sternal border laterally. The goal is to expose the IM nodes and vessels but not to divide the pleura so far laterally that the pleural cavity is entered.

The IM area is carefully inspected and scanned to identify any blue or hot nodes, which in general are much smaller than axillary nodes and can be found medial or lateral to the IM artery and (usually) paired IM veins. The IM nodes are dissected free with gentle sharp and blunt dissection, taking care not to injure the vessels, removing if necessary the adjacent fatty tissue, and submitting each node as a separate specimen labeled by interspace of origin and position relative to the vessels (medial or lateral). The IM nodes are submitted for permanent pathology, not frozen section. Processing, as for axillary SLN, includes serial sections and staining with hematoxylin-eosin and anticytokeratins.

IM-SLN biopsy is usually simple and straightforward, taking 5 to 10 minutes, but this is not always the case and surgeons must carefully weigh the small benefit of IM-SLN biopsy against the added morbidity of a more extended procedure. IM-SLNs that are inaccessible beneath the sternum or manubrium should be left in place. IM-SLNs that are inaccessible within a tight interspace (usually the fourth or fifth) or behind the costal cartilages should in general also be left, although the removal of a small segment of costal cartilage for exposure is usually safe. IM-SLNs, which are adherent to deeper structures or part of a large underlying tumor mass, should be biopsied but not excised; more radical chest wall resections are reserved for patients who have failed chemotherapy and RT and should not in general be done de novo.

Bleeding from small vessels is easily controlled with cautery, but significant bleeding from inadvertent injury to the IM artery or veins may require ligation/clipping of the vessels (through the adjacent interspaces or by resection of a costal cartilage for exposure). Inadvertent entry into the pleural cavity is easily recognized and treated. Some recommend suturing the pleural defect, but because the pleura is stretched tightly between the ribs this is easier said than done. For patients under positive pressure ventilation, the author prefers to hyperinflate the lungs and cover the pleural defect with a plug of moistened Surgicel, held in place by the overlying muscle layers. For patients breathing on their own under sedation, the pneumothorax is simply evacuated with a red rubber catheter, the pleural defect plugged, and the catheter pulled.

The intercostal muscles cannot be closed, but the pectoralis major is reapproximated over the IM-SLN biopsy site and the operative incisions are closed conventionally, with drains as needed. After IM-SLN biopsy, all patients have a chest radiograph in the recovery room; stable patients with pneumothorax are monitored with serial chest radiographs, and chest tubes are almost never required.

IM-SLN biopsy has little morbidity. In the 6 comparable series of IM-SLN biopsy (see Table 2 ), entry into the pleural cavity occurred in approximately 1% of patients, most of whom did not develop pneumothorax, and significant hemorrhage from the IM artery or veins occurred in less than 1%. The author and colleagues have previously reported a similar rate of complications in 142 IM-SLN biopsy procedures done at their institution and the European Institute of Oncology, which recently updated its own experience in 663 patients, with similar results.