Skin-Preserving Delayed-Immediate Breast Reconstruction

Steven J. Kronowitz

Geoffrey L. Robb

Introduction

The increasing use of postmastectomy radiation therapy (PXRT) in patients with early-stage breast cancer has increased the complexity of planning for immediate breast reconstruction. Two trials have demonstrated superior locoregional control, disease-free survival, and overall survival in node-positive breast cancer patients with the addition of PXRT to mastectomy and chemotherapy. Unfortunately, in patients with early-stage disease the need for XRT is often not known until after review of the permanent pathology, 1 week after surgery. It is not possible to predict or detect radiologically the presence or extent of axillary lymph node involvement—a major determinant of the need for PXRT—before mastectomy. With the increasing use of core biopsy techniques for breast cancer diagnosis, the extent of invasive disease within the breast parenchyma is also not often known until after review of the permanent pathology. So, if immediate breast reconstruction is performed and after review of the permanent pathology a need for XRT is found, there are two potential problems with performing PXRT. First, PXRT can adversely affect the aesthetic outcome of an immediate breast reconstruction. Second, an immediate breast reconstruction can interfere with the delivery of PXRT. However, if no reconstructive intervention is performed at the time of mastectomy because of a concern for the possible need for PXRT, this results in the loss of opportunity for the best possible aesthetic outcome because of the loss of the reconstructive benefits of skin-sparing mastectomy.

In this chapter, we discuss the issues that must be considered in determining whether PXRT is required and how best to sequence PXRT and breast reconstruction. We also discuss a two-stage approach, delayed-immediate reconstruction, that permits the best possible oncologic and aesthetic outcomes in patients at risk for requiring PXRT whose need for XRT is not known at the time of mastectomy.

The Increasing Use and Evolving Indications for Postmastectomy Radiation Therapy

PXRT improves the outcomes of breast cancer patients whose risk of local-regional recurrence (LRR) is greater than 25% to 30% (1,2,3). There is consensus that patients with T3 or T4 tumors or four or more positive axillary lymph nodes have this risk. The American Society for Therapeutic Radiology and Oncology (4), the American Society of Clinical Oncology (5), and Health Canada’s Canadian Breast Cancer Initiative (6) recommend PXRT for breast cancer patients with advanced disease (T3 or T4 tumors or at least four positive axillary nodes).

The role of PXRT is controversial in the treatment of patients with T1 or T2 tumors and one to three positive axillary nodes. Although the Danish and British Columbia prospective trials reported a risk of LRR from 20% to 30% (1,7), PXRT reduced this risk by two thirds (3). Most contemporary retrospective analyses of postmastectomy LRR in women with T1 or T2 breast cancer with one to three positive axillary lymph nodes treated with systemic chemotherapy but without PXRT report an approximate 10-year LRR risk of 15%. Woodward and colleagues reported a reduction in LRR rate from 13% without PXRT to 3% with PXRT in patients with one to three positive nodes (8). The heterogeneity of the reported risk for LRR in patients with T1 or T2 tumors and one to three positive nodes indicates that more prospective studies are needed to establish how much the addition of PXRT to mastectomy and systemic chemotherapy reduces LRR risk and improves survival.

A study at the University of Texas MD Anderson Cancer Center found that extranodal extension of at least 2 mm, fewer than ten nodes excised, and tumor size greater than 4 cm were independent predictors of LRR, even in patients with one to three positive nodes (9). Another study, of patients with T1 and T2 tumors with one to three positive nodes, showed that age less than 45 years, more than 25% of excised nodes positive, medial tumor location, and estrogen receptor–negative status were significantly associated with LRR risk greater than 20% (10), which may be a reasonable indication for PXRT.

Because of the downstaging that often occurs after neoadjuvant chemotherapy, both clinical and pathologic tumor stage must be considered in determining the need for PXRT (11). Studies indicate that patients with T3 or T4 tumors or clinical stage III disease at diagnosis clearly benefit from PXRT after neoadjuvant chemotherapy and definitive surgery, even if they have a complete response to the chemotherapy (12,13). It is unclear whether patients with T1 or T2 tumors at diagnosis, regardless of the response to neoadjuvant chemotherapy, should also receive PXRT. In the future, the need for radiation therapy may be determined solely on the basis of microarray gene analysis of core biopsy specimens obtained before surgery; permanent pathology results and downstaging due to neoadjuvant chemotherapy may no longer influence treatment.

Choosing Between Immediate and Delayed Breast Reconstruction

The status of the axillary lymph nodes is a major determinant of the need for PXRT and thus can significantly affect the decision of whether to perform immediate or delayed breast reconstruction. At present, breast cancer patients who have four or more positive lymph nodes are considered candidates for
PXRT (4,5). However, patients must be made aware that having one to three involved lymph nodes will make them eligible for PXRT if they have a large T2 tumor (8). The possibility that XRT will be required should be thoroughly investigated preoperatively before immediate breast reconstruction.

Unfortunately, preoperative (clinical) detection of micrometastases or small-volume metastases in the axillary lymph nodes of breast cancer patients is not always possible (14). Furthermore, intraoperative examination of sentinel lymph nodes with frozen section or imprint cytology techniques or both does not reveal all micrometastases (14,15,16,17). In addition, even if a positive sentinel node is identified intraoperatively and a complete level I and II axillary dissection is performed, the final number of positive axillary nodes and the extent of invasive carcinoma within the breast—and thus the need for PXRT—will not be known until the final pathology review several days after surgery.

Several recent studies (8,18) evaluated clinicopathologic factors that may help identify preoperatively which clinically node-negative patients are at risk for undetectable micrometastatic axillary disease. A recent report from our institution (18) demonstrated that patients who were 50 years of age or younger, patients who had tumors larger than 2 cm, and patients who had lymphovascular invasion detected in the initial biopsy specimen were at higher risk for harboring axillary metastases. Clinically, node-negative patients who were 50 years of age or younger with T2 tumors and evidence of lymphovascular invasion in their biopsy specimen had a 67% incidence of pathologic nodal involvement. However, although risk factors can help identify high-risk patients, the ability to consistently predict and quantify axillary involvement before surgery is limited.

Recently, consideration has been given to performing axillary sentinel node biopsy prior to mastectomy and breast reconstruction (19). Although premastectomy sentinel node biopsy may be useful to rule out lymph node involvement in high-risk patients, it probably will not benefit all patients with invasive breast cancer. At present, only patients with multiple positive nodes are advised to receive PXRT, so if the premastectomy sentinel node biopsy reveals one to two positive nodes, the need for PXRT may still not be known until after the final review of the complete level I and II axillary lymph nodes, several days after mastectomy and completion axillary nodal dissection. If a patient with a few positive nodes on premastectomy sentinel node biopsy undergoes immediate breast reconstruction before the final pathology report is complete and the final report indicates that PXRT is needed, the patient may be at risk for a poor aesthetic outcome, and radiation delivery may be compromised. Additional considerations include the increased cost, patient inconvenience, and potential complications associated with sentinel node biopsy. In the future, if the indications for PXRT are changed such that XRT is recommended for patients with any axillary disease, the use of premastectomy sentinel node biopsy probably could be further justified.

Two Potential Problems with Radiation Therapy After Immediate Breast Reconstruction

The increasing use of PXRT in patients with early-stage breast cancer and the inability to determine preoperatively or intraoperatively which patients will require PXRT has increased the complexity of planning for immediate breast reconstruction. Although immediate breast reconstruction is ideal for many patients, there are two potential problems with performing an immediate breast reconstruction in a patient who will require PXRT. First, PXRT can adversely affect the aesthetic outcome of an immediate breast reconstruction. Second, an immediate breast reconstruction can interfere with the delivery of PXRT.

Postmastectomy Radiation Therapy Can Adversely Affect the Aesthetic Outcome of Immediate Breast Reconstruction

Aesthetic Outcomes of Implant-Based Reconstruction with Modern Radiation Delivery Techniques

Studies evaluating the outcomes of two-stage breast reconstruction, with placement of a tissue expander followed by placement of a permanent breast implant after PXRT, consistently reveal high rates of acute and chronic complications and poor aesthetic outcomes (20). Capsular contracture that results from PXRT not only distorts the appearance of the breast, but it also causes chronic chest wall pain and tightness that can be crippling. Many surgeons attribute the poor outcomes with implant-based breast reconstruction to older, less precise techniques of radiation delivery. However, even with modern radiation delivery techniques, complication rates with implant-based reconstruction are high.

Ascherman and colleagues (21) recently evaluated the complications and aesthetic outcomes of 104 patients who underwent two-stage implant-based reconstruction. Twenty-seven patients also underwent radiation therapy, either before mastectomy (patients who were undergoing salvage mastectomy after lumpectomy and radiation therapy) or after mastectomy. In all 27 of these patients, radiation therapy was completed before the tissue expander was exchanged for a permanent breast implant or before the expander port was removed. Despite use of the latest prosthetic materials and modern radiation delivery techniques, the overall complication rates for the irradiated and nonirradiated breasts were 40.7% and 16.7%, respectively (p ≤ 0.01). Complications that resulted in removal or replacement of the prosthesis occurred in 18.5% of the irradiated and only 4.2% of the nonirradiated breasts (p ≤ 0.025). In addition, the extrusion rate was higher for implants in irradiated breasts (14.8% vs. 0%; p ≤ 0.001). Breast symmetry scores were significantly higher in the patients who did not receive radiation therapy (p < 0.01). Despite the retrospective study design, these findings are important because they represent the experience of a single surgeon who evaluated patients treated using the latest prosthetic devices with total submuscular coverage and modern radiation therapy techniques.

In another recent study, Benediktsson and Perbeck (22) used applanation tonometry to prospectively evaluate rates of capsular contracture around saline-filled, textured implants in 107 patients who underwent mastectomy with immediate breast reconstruction. Twenty-four of the patients received PXRT. Radiation was delivered using a modern, three-beam technique with a combination of photons and electrons, and reconstruction was accomplished using the latest prosthetic devices. The rate of capsular contracture was significantly higher for irradiated breasts than for nonirradiated breasts (41.7% vs. 14.5%;
p = 0.01). The difference in contracture rates was not evident during the first 6 months but was highly significant thereafter, even 5 years later.

In 2006, Behranwala and colleagues (23) published results from a series of 136 breast reconstructions with a median follow-up of 4 years: 62 reconstructions were performed with submuscular implants alone and 74 with a latissimus dorsi flap plus an implant. Forty-four reconstructed breasts received PXRT. Capsule formation was detected in 14.1% of the nonirradiated reconstructed breasts and 38.6% of the irradiated reconstructed breasts. On univariate analysis, PXRT was the only variable related to capsule formation (p < 0.001). Significant differences in geometric measurements of the breasts and worse photographic assessments were seen in the group that received PXRT. Pain that persisted for 2 years or more after surgery was present in 27% of breasts with capsular contracture and less than 1% of breasts without capsular contracture.

Autologous Tissue Breast Reconstruction in Patients Receiving Postmastectomy Radiation Therapy

Although the consensus in the literature is that autologous tissue is preferable to breast implants within an irradiated operative field, even autologous tissue reconstructions can be adversely affected by PXRT (24,25,26,27). Some studies, mainly those conducted by radiation oncologists, have found acceptable outcomes with transverse rectus abdominis myocutaneous (TRAM) flap reconstruction and PXRT even when the flap is transferred before radiation delivery (28). However, until less destructive methods of radiation delivery can be implemented and proven effective, delayed transfer of the autologous tissue flap may be the best option in patients known at the time of mastectomy to require PXRT.

Unfortunately, the evaluation of complication rates and aesthetic outcomes in patients undergoing autologous tissue reconstruction before or after PXRT is extremely difficult because of significant variations in the administration of systemic therapy, the duration of follow-up, and the techniques of radiation delivery and breast reconstruction. Furthermore, few new studies evaluating this issue have emerged in recent years, probably because of decreased use of immediate reconstruction in patients who may require PXRT.

In 2001, investigators at the MD Anderson Cancer Center published a retrospective study (25) comparing complication rates in 32 patients who underwent immediate TRAM flap reconstruction before PXRT and 70 patients who underwent PXRT before TRAM flap reconstruction. The mean follow-up times after the end of treatment for the immediate and delayed reconstruction groups were 3 and 5 years, respectively. The incidence of early flap complications (vessel thrombosis and partial or total flap loss) did not differ significantly between the two groups. However, the incidence of late complications (fat necrosis, flap volume loss, and flap contracture) was significantly higher in the immediate reconstruction group (87.5% vs. 8.6%; p < 0.001). Furthermore, 28% of the patients with immediate reconstruction required an additional flap to correct a distorted contour resulting from flap shrinkage and severe flap contracture after PXRT.

In a study published in 2002, Rogers and Allen (26) evaluated the effects of PXRT on breasts reconstructed with a deep inferior epigastric perforator (DIEP) flap. A matched-pairs analysis was performed of 30 patients who underwent PXRT after reconstruction and 30 patients who did not. Patients who underwent PXRT had higher incidences of fat necrosis in the DIEP flap (23.3% vs. 0%; p = 0.006), fibrosis and shrinkage (56.7% vs. 0%; p < 0.001), and flap contracture (16.7% vs. 0%; p = 0.023).

In a study published in 2005, Spear and colleagues (27) evaluated the effects of PXRT before or after pedicled TRAM flap breast reconstruction. They found that patients who had PXRT after reconstruction had worse aesthetic outcomes, symmetry, and contractures. They recommended that pedicled TRAM flap reconstruction be postponed until after PXRT.

Immediate Breast Reconstruction Can Interfere with the Delivery of Postmastectomy Radiation Therapy

Immediate Implant-Based Breast Reconstruction Can Compromise the Design of the Radiation Treatment Fields

Not only can PXRT adversely affect the aesthetic outcome of immediate implant-based breast reconstruction, but also there is increasing evidence that such reconstructions can interfere with the delivery of PXRT (Fig. 37.1) (8,29,30,31,32,33,34). This interference can occur with a breast implant, a fully inflated tissue expander in situ on the chest wall, or even a partially deflated expander. The sloping contour of a reconstructed breast results in an imprecise geometric match of the medial electron and lateral photon radiation fields, which can lead to underdosing of the chest wall, especially centrally underneath the breast prosthesis and near the internal mammary nodes (33). The sloping contour also leads to nonuniform thickness of the chest wall across the width of the electron beam field, which can lead to a nonhomogeneous dose within the treatment field because the electron beam dose falls off as a function of tissue thickness (33). Chest wall treatment in patients who have undergone reconstruction must be accomplished using traditional, two-beam tangential fields alone rather than modern three-beam techniques (33,34,35). Unfortunately, it is not feasible to flatten the medial and apical aspects of the reconstructed breast to result in more favorable geometry for radiation treatment because of the higher density of flap tissues from the abdomen and gluteal regions.

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