Neoadjuvant chemotherapy

Although it has not been shown to provide survival benefit compared with postoperative adjuvant chemotherapy, neoadjuvant chemotherapy has become a widely accepted treatment option for breast cancer patients. Neoadjuvant chemotherapy has been shown to reduce tumor size in some patients with large tumors, thereby facilitating breast-conservation surgery and enabling in vivo assessment of the tumor’s response to chemotherapy.^4–6 Many studies have shown that neoadjuvant chemotherapy followed by mastectomy and immediate breast reconstruction is safe and viable, does not delay other adjuvant treatment, and can be used to identify patients who do not respond to chemotherapy, which enables oncologists to modify post-surgical treatment.^7–9 In addition, studies have shown that the complication rate after implant- or autologous tissue-based reconstruction is not significantly higher in patients who have undergone neoadjuvant chemotherapy, nor are the local recurrence and disease-free survival rates affected.^7,9–13

Generally, neoadjuvant chemotherapy is not a contraindication to immediate breast reconstruction and does not increase the complication rate or significantly delay further adjuvant therapy. At our institution, we recommend delaying reconstruction for 3–4 weeks following neoadjuvant chemotherapy to allow the immunosuppressive effects of the chemotherapy to resolve (Fig. 3.1A, B).

Fig. 3.1 A This is a 54-year-old woman with left breast multicentric invasive ductal carcinoma. The patient’s clinical stage at presentation is stage II-A with T2, N0, M0. She received neoadjuvant chemotherapy consisting of 12 weekly cycles of Taxol followed by four cycles of FAC. Four weeks after the completion of her chemotherapy, the patient underwent left mastectomy and immediate reconstruction with free DIEP flap. Her postoperative course was uneventful. B At 8 weeks following mastectomy and reconstruction.

Adjuvant chemotherapy

Postoperative chemotherapy is a common adjuvant treatment for breast cancer because it reduces the risk of local and systemic recurrence due to occult micrometastatic disease. Randomized trials and meta-analyses have shown that post-mastectomy adjuvant chemotherapy reduces recurrence and death rates in breast cancer patients.^14–16

Many researchers have studied whether immediate breast reconstruction affects the timely delivery of adjuvant chemotherapy and whether adjuvant chemotherapy after reconstruction affects wound healing. Allweiss et al compared 49 patients who underwent mastectomy, immediate breast reconstruction with various autologous tissue techniques, chemotherapy with 308 patients who underwent mastectomy alone followed by chemotherapy and found that the type of reconstruction did not significantly delay chemotherapy and that the time to chemotherapy was in fact significantly longer in patients who did not undergo immediate reconstruction.¹⁷ In addition, Wilson et al compared patients who had undergone mastectomy with immediate reconstruction, mastectomy with no reconstruction, or breast-conservation surgery, all followed by adjuvant chemotherapy, and found no significant differences in the time to chemotherapy among the three cohorts.¹⁸ At our institution, Mortenson et al found that patients who underwent immediate breast reconstruction followed by adjuvant chemotherapy had a higher incidence of wound complications (22.3%) than patients who did not undergo immediate reconstruction (8.3%) but did not find that immediate breast reconstruction delayed postoperative chemotherapy.¹⁹

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.

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.