Prophylactic Nipple-Sparing Mastectomy and Direct-to-Implant Reconstruction of the Large and Ptotic Breast: Is Preshaping of the Challenging Breast a Key to Success?

BACKGROUND: Nipple-sparing mastectomy with simultaneous hammock technique direct-to-implant reconstruction is increasingly offered to patients opting for risk-reducing mastectomy. Despite this promising method, patients with macromastia and ptotic breasts remain a challenging group to treat satisfactorily and more often end up undergoing a difficult corrective procedure and experience an unacceptably high rate of failed reconstruction. The authors examined whether targeted preshaping mastopexy/reduction could prepare these patients for a successful nipple-sparing mastectomy/direct-to-implant reconstruction. METHODS: Patients seeking risk-reducing nipple-sparing mastectomy/direct-to-implant reconstruction at the authors' institutions deemed unfit for a one-stage procedure based on their previous experience were offered a targeted two-stage, risk-reducing mastopexy/reduction followed by a delayed secondary nipple-sparing mastectomy and direct-to-implant reconstruction. Patients were followed up at 3 weeks and 6 or 12 months. RESULTS: Forty-four reconstructions were performed in 22 patients aged 43 years (range, 26 to 57 years). All 44 procedures were completed successfully without any failure or nipple-areola complex losses. Patients' median body mass index was 30 kg/m (range, 22 to 44 kg/m). Six patients were smokers and one had hypertension. Two patients underwent reoperation because of hematoma and fat necrosis. CONCLUSIONS: The authors' results demonstrate that a targeted preshaping mastopexy/reduction followed by nipple-sparing mastectomy/direct-to-implant reconstruction can be safely planned in women who opt for a risk-reducing mastectomy and can be performed successfully with a 3- to 4-month time span between operations. On the basis of these results and the superior cosmetic outcome, the two-stage approach has become the authors' standard of care in all such settings. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

How to perform a NAC sparing mastectomy using an ADM and an implant.

BACKGROUND: Preservation of the nipple areolar complex (NAC) provides the optimal conditions for immediate breast reconstruction (IBR). Growing evidence suggests the oncological safety of nipple sparing mastectomy (NSM) when neither NAC nor skin is affected by tumor. This paper presents our initial experience performing NSM and IBR in a selected group of patients through the inframammary incision assisted by hydrodissection. MATERIAL AND METHODS: The study includes 20 healthy women, aged 23-53, and referred for bilateral risk-reducing mastectomy. NSM was carried out using inframammary crease incision assisted by hydrodissection followed by IBR with an acellular dermal matrix (ADM) and an implant as presented in the attached video. Exclusions criteria were hypertension, diabetes, active smoking and previous chest radiation therapy. Data was collected retrospectively. RESULTS: We achieved the reconstructive goal for all 40 breasts (100%). There were no cases of NAC necrosis. Minor complications were registered in two reconstructions (5%), including one case of small partial necrosis and one case of wound dehiscence. The median follow-up was 13 months (range, 1-32 months). CONCLUSIONS: Bilateral risk-reducing NSM and IBR can be successfully achieved through an inframammary crease incision assisted by hydrodissection. Patient selection is the key to a successful outcome.

Successful breast reconstruction using acellular dermal matrix can be recommended in healthy non-smoking patients.

INTRODUCTION: We present Scandinavia's first series of immediate alloplastic breast reconstructions with an acellular dermal matrix. MATERIAL AND METHODS: Data were collected retrospectively in 76 cases of immediate breast reconstruction using an acellular dermal matrix (ADM) and an implant. RESULTS: A total of 59 women were reconstructed between June 2011 and January 2013. Cases included 42 unilateral and 17 bilateral reconstructions. A large number of patients had adjuvant therapy, hormone therapy (34), radiation therapy (27) or chemotherapy (38). The median age was 51 years (30-70 years) and the median follow-up period was 326 days (68-624 days). The co-morbidity factors included hypertension (n = 11), diabetes (n = 2) and 19 patients were smokers. Unsuccessful reconstructions counted ten cases (13%), eight of these due to necrosis and/or wound dehiscence (10%) and two due to infection (3%). The failure rate in non-smokers was 2/52 (4%) compared with 8/24 (33%) in smokers, p = 0.001. In hypertensive patients, the failure rate was 6/12 (50%) compared with 4/64 (6%)in normotensive patients, p = 0.001. 70% of the failed reconstructions occurred in patients older than 65 years of age. CONCLUSION: Immediate alloplastic breast reconstruction using an ADM can be recommended to healthy non-smoking patients. FUNDING: not relevant. TRIAL REGISTRATION: not relevant.

Propeller TAP flap: is it usable for breast reconstruction?

The aim of this study was to examine if a propeller thoracodorsal artery perforator (TAP) flap can be used for breast reconstruction. Fifteen women were reconstructed using a propeller TAP flap, an implant, and an ADM. Preoperative colour Doppler ultrasonography was used for patient selection to identify the dominant perforator in all cases. A total of 16 TAP flaps were performed; 12 flaps were based on one perforator and four were based on two. A permanent silicone implant was used in 14 cases and an expander implant in two. Minor complications were registered in three patients. Two cases had major complications needing additional surgery. One flap was lost due to a vascular problem. Breast reconstruction can be performed by a propeller TAP flap without cutting the descending branch of the thoracodorsal vessels. However, the authors would recommend that a small cuff of muscle is left around the perforator to ensure a sufficient venous return.

Increased concentrations of growth factors and activation of the EGFR system in breast cancer.

BACKGROUND: In this study the total and phosphorylated amount of epidermal growth factor receptor 1 (EGFR) and 2 (HER2) were measured together with EGFR ligands in tissue samples of breast cancer patients in order to investigate interrelations and possible prognostic values. METHODS: Samples of malignant and non-cancer autologous reference tissue were collected from 415 breast cancer patients. The tissue samples were cut and either paraffin-embedded or homogenized in a lysis buffer to extract the proteins. HER2 was measured using both immunohistochemistry (IHC)/fluorescence in situ hybridization (FISH) and ADVIA Centaur. Phosphorylated HER2 and EGFR (pHER2, pEGFR), total EGFR and the ligands: epidermal growth factor (EGF), transforming growth factor-α (TGFα), amphiregulin (AREG), heparin-binding EGF-like growth factor (HB-EGF), betacellulin (BTC) and epiregulin (EREG) were measured using the Luminex. RESULTS: The HER2 positivity rate was determined to be 25.2% by the Centaur method vs. 15.8% by IHC and FISH. HER2, HB-EGF, TGFα and AREG were upregulated in cancer tissue as compared with autologous reference tissue while EGFR, pEGFR and EGF were downregulated (p<10-6). pEGFR in autologous reference tissue was negatively correlated to the number of positive lymph nodes and to the tumor size (p=0.0007 and p=0.001, respectively) and furthermore, decreased in the group of mastectomy operated patients as compared with the lumpectomy group (p<10-6). HB-EGF in cancer tissue was positively associated with high grade tumors (p<10-6) and pHER2, HB-EGF and BTC were associated with poor disease free survival (p=0.017, p=0.012 and p=0.0026, respectively). CONCLUSIONS: Our study demonstrated a profound activation of the EGFR system. HB-EGF was increased by factor 10 in cancer tissue and related to the biological aggressiveness of the tumors, and pHER2, HB-EGF and BTC were associated with poor clinical outcome.

HER1-4 protein concentrations in normal breast tissue from breast cancer patients are expressed by the same profile as in the malignant tissue.

BACKGROUND: The epidermal growth factor receptor HER2 is overexpressed or amplified in 25%-30% of patients with breast cancer. The mechanism behind HER2 amplification is unknown, but may be a patho-physiological phenomenon caused by continuous stimulation and activation of the HER1-4 system. We have mapped the protein concentrations of HER1-4 in breast cancer tissue, autologous reference tissue, normal breast tissue and serum samples, to see whether non-cancer cells from these patients express a protein profile indicating general activation. METHODS: Tissue samples from malignant and adjacent normal breast tissue (autologous reference tissue) were collected from 118 women consecutively admitted for surgical treatment of breast cancer. In addition, 26 samples of normal breast tissue were collected from healthy women having breast reduction surgery. The tissue samples were homogenized and the proteins extracted. The tissue and serum concentrations of HER1-4 were determined quantitatively using a commercially available enzyme linked immunosorbent assay (ELISA) method. RESULTS: HER1 was down regulated in cancer tissue when compared to autologous reference tissue (p=8 x 10(-6)), while HER2 (p<10(-7)) and HER3 (p=3 x 10(-5)) were up regulated. Comparing autologous reference tissue with normal tissue showed down regulation of HER1 (p=0.122) and up regulation of HER2 (p=10(-6)), HER3 (p<10(-7)) and HER4 (p<10(-7)). Furthermore, we observed that correlations between the receptor combinations HER1-2, HER1-3 and HER1-4 were maintained from normal breast tissue to autologous reference breast tissue, but were lost in cancer tissue. CONCLUSIONS: We suggest that these findings indicate that breast cancer is a systemic disease where the HER1-4 system in autologous reference tissue is continuously activated, thus favoring the subsequent development of cancer.

HER-2 protein concentrations in breast cancer cells increase before immunohistochemical and fluorescence in situ hybridization analysis turn positive.

BACKGROUND: The level of HER-2/neu in breast cancer cells is normally measured by immunohistochemistry (IHC) and/or fluorescence in situ hybridization (FISH). It determines whether patients should be treated with trastuzumab (Herceptin). In this study, HER-2 protein in breast cancer tissue was measured using a quantitative method. METHODS: Tissue samples of malignant and adjacent benign breast tissue were collected from 118 consecutive women admitted for surgical treatment of breast cancer. The HER-2 protein concentration was determined by 2 HER-2 assays: ELISA and the Bayer ADVIA Centaur assay. Paraffin-embedded tissue sections of the corresponding tumors were analyzed by IHC and FISH. RESULTS: Increased HER-2 concentrations in cancer tissue were found compared to autologous reference tissue (p<0.0001, Wilcoxon test) and normal breast tissue (p<0.0001, Mann-Whitney test). Good concordance rates were observed between the methods: 95.8% for IHC and FISH; 86.4% for IHC and ELISA; and 87.3% for FISH and ELISA. The HER-2 positivity rate was determined to 26.3% by ELISA, 12.7% by IHC and 16.9% by FISH. No correlation was found with tumor grade, axillary node status or serum HER-2 levels. CONCLUSIONS: Detection of HER-2 overexpression by measuring HER-2 in tissue extracts by ELISA seems to be more sensitive than IHC and FISH. This suggests that some patients deprived of Herceptin treatment may benefit from this treatment and may also explain the conversion phenomenon from HER-2-negative to HER-2-positive observed in relapse and metastatic disease.