With regard to implant-based reconstruction, most researchers have found that adjuvant chemotherapy typically does not increase implant infection or complication rates or affect cosmetic outcomes.^2,²⁰^–²² In addition, no significant delays in receiving chemotherapy or changes in dose intensity have been observed.³^,²⁰ Based on these studies and our experience with implant-based reconstruction and tissue expansion during chemotherapy, we recommend that patients undergo tissue expansion and implant placement before starting chemotherapy. If tissue expansion is not complete before a patient starts chemotherapy, absolute neutrophil counts should be assessed to make certain that the patient’s immune system can fight the bacteria that are introduced during the expansion process.

Although whether delaying adjuvant chemotherapy affects cancer-related outcomes is not yet definitively known, most oncologists prefer to initiate therapy 4–6 weeks after mastectomy or breast-conservation surgery given concerns that longer periods may increase recurrence or diminish survival.²³ Immediate breast reconstruction may increase the risk of complications as a result of the additional surgical procedures performed, but it does not seem to delay adjuvant chemotherapy or affect overall survival and recurrence rates.

Hormone therapy

Selective estrogen receptor modulators

Tamoxifen has been shown to reduce the risk of recurrence and death in women with early-stage, hormone receptor-positive invasive breast cancer; reduce the risk of invasive and non-invasive recurrences in women who undergo breast-conserving surgery for ductal carcinoma in situ; and reduce the risk of breast cancer in women who have a high risk for the disease because of personal characteristics or family history.¹⁶^,²⁴ Despite tamoxifen’s benefits, 1–2% of patients may experience thromboembolic events such as deep vein thromboses, pulmonary embolisms, and cerebrovascular thrombi. Although the mechanisms by which tamoxifen causes thromboembolic events are not totally understood, the events are thought to be related to tamoxifen’s reduction of levels of antithrombin III, and factor V, and protein C.²⁵^–²⁷

Because tamoxifen presents a theoretical risk of thrombosis, it may be appropriate to have the patient stop tamoxifen therapy 10–14 days prior to undergoing free-flap reconstruction and restart the therapy after breast reconstruction. (This time frame is based on the pharmacokinetics and the 9–14-day terminal half-life of tamoxifen’s major metabolite.²⁸) However, we recommend consulting with the patient’s medical and surgical oncologists to confirm that tamoxifen therapy can be stopped safely without negatively affecting the patient’s cancer treatment.

Aromatase inhibitors

The most common aromatase inhibitors studied in breast cancer patients are anastrozole and letrozole. In comparison trials, anastrozole was associated with higher disease-free survival rates, lower breast cancer event rates, and fewer incidences of contralateral breast cancer than tamoxifen. Also, significantly fewer venous thrombolic events occurred in the anastrozole group than in the tamoxifen group.²⁹ We currently do not routinely stop aromatase inhibitor therapy prior to breast reconstruction.

Biological therapy

Trastuzumab, a humanized monoclonal antibody directed against the HER-2 receptor, has been shown to significantly improve survival rates in metastatic breast cancer patients when used alone or in combination with chemotherapy. Trastuzumab also has been shown to reduce recurrence rates and improve survival in early-stage breast cancer patients.³⁰

Patients who receive trastuzumab alone or in combination with other chemotherapy may experience neutropenia and an increased incidence of infections. An increase in the incidence of thrombotic events has also been reported.³¹ Because of these potential complications, we recommend that patients complete trastuzumab therapy and undergo immune status evaluation before undergoing breast reconstruction. And as always, we recommend consulting with the patient’s medical and surgical oncologists.

Radiotherapy

Giving adjuvant radiotherapy following mastectomy has been shown to significantly reduce the risk of locoregional recurrence in early-stage breast cancer patients with positive lymph nodes.³²^,³³ Furthermore, recent prospective trials have demonstrated improved locoregional control, disease-free survival, and overall survival rates in node-positive breast cancer patients who receive adjuvant radiotherapy in addition to mastectomy and chemotherapy.³⁴^,³⁵ Currently, post-mastectomy adjuvant radiotherapy is recommended for patients with locally advanced tumors or four or more involved lymph nodes.³⁶^,³⁷ However, many institutions are evaluating the efficacy of radiotherapy in patients who have T1 or T2 disease and one to three involved nodes.³³

Breast reconstruction in a previously irradiated breast

The negative effects of radiation on implant-based breast reconstruction have been particularly well documented; studies of implant-based reconstruction of previously irradiated breasts have reported complications including infection, extrusion, capsular contracture, and failed reconstruction in 20–60% of cases. Thus, most prefer to use autologous tissue only for breast reconstruction in a previously irradiated breast. However, recent reports may support that when autologous tissue flap and implant are used together in a previously irradiated breast for breast reconstruction, an autologous tissue flap may protect the implant from the negative effects of radiotherapy. Spear et al evaluated 28 patients with previously irradiated breasts who underwent latissimus dorsi (LD) flap/implant breast reconstruction and found a 14% implant-related complication rate with a mean cosmetic satisfaction rating of 8.5 of 10 and mean overall satisfaction rating of 8.8 of 10. The authors concluded that although breast reconstruction with autologous tissue alone may be the best choice following radiotherapy, LD flap/implant reconstructions provide cosmetically acceptable results and acceptable complication rates.³⁸ In a study from our institution, of patients who received radiotherapy prior to mastectomy and reconstruction, significantly fewer reconstructions failed in patients with LD flap/implant reconstructions (15%) or transverse rectus abdominis myocutaneous (TRAM) flap/implant reconstructions (10%) than in patients with expander/implant-only reconstructions (42%; p < 0.03).³⁹

In our experience, an autologous tissue flap combined with an implant for breast reconstruction appears to reduce the incidence of implant-related complications in previously irradiated breasts. A well-vascularized flap may improve wound healing and thus reduce the risk of wound breakdown and infection. The flap also provides a well-vascularized pocket for the implant, which minimizes the implant’s direct contact with the surrounding irradiated tissue. Although the implant sits on the chest wall, covering the implant with well-vascularized tissue may reduce the risk of capsular contracture associated with radiotherapy. Because free TRAM flaps and deep inferior epigastric artery perforator (DIEP) flaps typically provide more well-vascularized tissue than LD flaps, covering the implant with a free TRAM or DIEP flap may provide better protection.

Immediate breast reconstruction followed by radiotherapy

There are conflicting results in the literature regarding almost all aspects of immediate reconstruction and radiotherapy. This conflict has clinical ramifications, since the first step after diagnosing breast cancer is offering a patient the best possible treatment in accordance with her and the tumor’s characteristics. Such treatment may include immediate breast reconstruction in cases in which mastectomy is indicated.

The mechanisms and clinical effects of radiation on the reconstructed breast depend on the radiation dose, the use of compensating filters and wedges, the use of bolus dosing to the skin, and the boost to the radiation bed.⁴⁰ The variability among radiation oncologists and centers makes it difficult to predict the effects radiotherapy will have on a reconstructed breast. Incompletely understood intrinsic patient factors can also alter the effects of radiotherapy. Immediate breast reconstruction can create technical challenges in administering adjuvant radiotherapy and may increase radiation exposure in the mediastinum. A flat chest – that is, one without a reconstructed breast – allows for beam angulations that minimize radiation doses to the heart and lungs while treating the internal mammary lymph nodes; however, the sloped contour of a reconstructed breast contributes to less precise geometric matching of the lateral and medial radiation fields, resulting in greater radiation doses in the mediastinum.^33,⁴¹^–⁴³

Autologous tissue-based reconstruction followed by radiotherapy

Most authors agree that autologous tissue-based reconstruction tolerates radiation better with more pleasing aesthetic outcomes and fewer complications than implant-based reconstruction.⁴⁴^,⁴⁵ Jhaveri et al performed a retrospective analysis of the long-term complication rates and cosmetic results in 69 patients who underwent immediate tissue expander/implant-based reconstruction with adjuvant radiotherapy and 23 patients who underwent autologous tissue-based reconstruction with adjuvant radiotherapy. The authors found that the tissue expander/implant group had a significantly higher rate of severe complications – those that required surgical intervention or removal and/or replacement of the implants (33.3%) – than the group who underwent autologous tissue-based reconstruction (0%). The autologous tissue group also had a higher rate of acceptable cosmesis (83%) than the tissue expander/implant group (51%).⁴⁶

However, many feel that irradiating a reconstructed breast may diminish the aesthetic outcome and thus advocate delay reconstruction in patients who require adjuvant radiotherapy. Tran et al reported on a series of 41 patients undergoing immediate TRAM flap reconstruction (9 pedicled and 32 free) followed by radiation. No flap loss was reported; however, 10 patients (24%) required an additional flap to correct contracture, and only 9 patients (22%) maintained normal breast volumes. Hyperpigmentation occurred in 15 patients (37%), palpable fat necrosis in 14 patients (34%), and a loss of symmetry in 32 patients (78%).⁴⁷ In a later study, Tran et al evaluated 32 patients who underwent immediate reconstruction followed by radiotherapy and 70 patients who underwent reconstruction after radiotherapy. No significant difference was found in early flap complications between the two groups but significantly higher (87.5% versus 8.6%) rates of late complications (fat necrosis, flap volume loss, and flap contracture) were noted in patients who received immediate reconstruction prior to radiotherapy, with 28% requiring an additional flap to correct deformities (Fig. 3.2A–E).⁴⁸ Other studies have found similar results with higher rates of fat necrosis and necessary additional surgeries or flaps due to volume loss in patients who undergo autologous tissue-based reconstructions before adjuvant radiotherapy.⁴⁹^–⁵²

Fig. 3.2 A The patient is a 53-year-old woman with left breast invasive mixed ductal lobular carcinoma and ductal carcinoma in situ. B The patient underwent left modified radical mastectomy and right prophylactic mastectomy with immediate reconstruction with free TRAM flaps. C Pathology review revealed close surgical margin and patient was treated with 50 Gy in 25 fractions to the left chest wall and reconstructed breast followed by a 14 Gy electron boost to the skin overlying the TRAM flap. D At 12 months following completion of the radiation therapy. E At 4 years after mastectomy and free TRAM breast reconstruction, and 45 months following completion of the radiation therapy.

Meanwhile, for some surgeons, immediate reconstruction with autologous tissue remains the preferred approach in patients who require adjuvant radiotherapy. In a series of 25 patients, Soong et al found that radiotherapy did not increase the rate of complications after immediate reconstruction with TRAM flaps. The authors concluded that radiotherapy after reconstruction with TRAM flaps is well tolerated and that cosmetic outcome and local control of the breast cancer are satisfactory.⁵³ Other authors have reported similar results with good to excellent cosmetic outcomes and minimal flap loss and complications.⁵⁴^–⁵⁷

Implant-based breast reconstruction followed by radiotherapy

Among patients who had immediate implant-based breast reconstruction followed by radiotherapy, Cordeiro et al found that 68% experienced capsular contracture after radiotherapy, a rate significantly higher than in patients who did not receive radiotherapy. Also, the patients who did not receive radiotherapy had a higher percentage of very good to excellent outcomes of the reconstructed breast than patients who did receive radiotherapy. Nevertheless, the authors concluded that immediate reconstruction with expanders and implants is an acceptable option when adjuvant radiotherapy is necessary.⁵⁸ Hazard et al reached the same conclusion in a retrospective study in which 85% of patients had good or excellent cosmetic outcomes, with an acceptable rate of capsular contracture.⁵⁹

Other authors have reported higher complication, reoperation, and capsular contracture rates in patients with implant-based reconstructions followed by adjuvant radiotherapy, resulting in poor cosmetic outcome. Spear et al evaluated outcomes in 40 patients undergoing two-stage reconstruction with saline implants and adjuvant radiotherapy with 40 patients undergoing two-stage reconstruction without radiation and found that the group who received radiation had significantly more complications (52.5% versus 10.0%), capsular contractures (32% versus 0%), and additional procedures (47% versus 10%).⁴⁰ Other authors have come to the same conclusion and even consider the need for radiotherapy to be a relative contraindication to immediate breast reconstruction with tissue expanders and implants.⁶⁰^–⁶⁶

Delayed-immediate breast reconstruction

It remains unclear whether radiation will be required after mastectomy in many patients. The inability to consistently identify patients who require adjuvant radiotherapy complicates the decision about whether to perform immediate reconstruction in many early-stage breast cancer patients.

Because of this dilemma, Kronowitz et al described the ‘delayed immediate’ technique, in which a completely filled textured saline tissue expander is placed during mastectomy to preserve the skin envelope.⁴² Once the final pathology results are received, patients can undergo delayed reconstruction after they complete radiotherapy or immediate reconstruction if radiotherapy is unnecessary. The advantage of this technique is that it preserves the skin to achieve superior aesthetic outcomes in immediate reconstruction and it enables delay of final reconstruction in patients who are found to need postmastectomy radiation, thereby avoiding most effects of irradiating a reconstructed breast.