Infection prevention in breast implant surgery - A review of the surgical evidence, guidelines and a checklist.

INTRODUCTION: As a result of increasing use of implant-based breast reconstruction, complications such as infection are being encountered more frequently. Surgical Site Infections (SSIs) cause morbidity for the patient, can lead to capsular contracture or implant loss and are costly to healthcare systems. National Guidelines suggesting methods to reduce SSI related complications have been produced, but are limited in the scope of interventions covered and underlying evidence presented. METHODS: We performed a literature review encompassing a wide variety of possible SSI prevention strategies. We aimed to present summaries of the available evidence and give pragmatic recommendations as to their validity to use as guidelines for infection prevention strategies for implant-based breast reconstruction. RESULTS: A lack of high quality data relating to the benefit of SSI prevention strategies in implant-based breast reconstruction exists. Many papers relate to orthopaedic implant surgery, or clean surgery in general. Following review of the evidence, sufficient data exists to support use of perioperative antibiotics at implant-based breast reconstruction, with continuation for an extended period in "high risk" patients. Alcohol containing skin preparations should be used over aqueous solutions. Laminar air flow use is suggested. Theatre traffic should be kept to a minimum, as should duration of operative procedure. The implant pocket should be washed prior to implantation. Double gloving and conductive warming are also endorsed. CONCLUSIONS: We have produced a perioperative "Theatre Implant Checklist" for SSI prevention in implant-based breast surgery, with a set of pragmatic up to date guidelines, which allows the reader to evaluate the evidence upon which our recommendations are based.

Molecular phenotypes of DCIS predict overall and invasive recurrence.

BACKGROUND: Molecular phenotypes of invasive breast cancer predict early recurrence. Ductal carcinoma in situ (DCIS) exhibits similar phenotypes, but their frequency and significance remain unclear. To determine whether DCIS molecular phenotypes predict recurrence, 314 women (median age 57.7 years) with primary DCIS who were screened or entered DCIS trials in a specialist breast unit from 1990 to 2010 were studied. PATIENTS AND METHODS: Expression of Ki67, estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) within primary DCIS was established using immunohistochemistry (IHC). Patients were subdivided into molecular phenotypes using IHC surrogates [Luminal A (ER/PR+HER2-), Luminal B (ER/PR+/HER2+), HER2 type (ER and PR-/HER2+) or triple negative (ER/PR/HER2)] and recurrence rates compared. RESULTS: Overall, there were 57 (18.2%) recurrences, 35 (11.2%) DCIS and 22 (7%) invasive cancer. A low rate of recurrence at 5 years was seen in Luminal A DCIS (7.6%), compared with 15.8%-36.1% in other phenotypes. Independent predictors of overall recurrence on multivariate analysis were involved (<1 mm) surgical margins (HR 4.31, P < 0.001), high-grade lesions (HR 2.28, P < 0.024) and molecular phenotype (HR 5.14, P = 0.001 for Luminal B; HR 6.46, P < 0.001 for HER2 type and HR 3.27, P = 0.028 for triple-negative disease compared with Luminal A DCIS). Independent predictors for invasive recurrence were high Ki67 expression (HR 1.04, P = 0.021) and molecular phenotype (HR 13.4, P = 0.014 for Luminal B; HR 11.4, P = 0.027 for HER2 type and HR 10.3, P = 0.031 for triple negative compared with Luminal A DCIS). CONCLUSIONS: DCIS molecular phenotype predicts for both overall and invasive recurrence. HER2 testing of DCIS could help clinicians individualise the treatment of patients with DCIS.

The frequency of presentation and clinico-pathological characteristics of symptomatic versus screen detected ductal carcinoma in situ of the breast.

INTRODUCTION: DCIS accounts for 20% of screen-detected breast cancers, but also presents symptomatically. Historically, approximately 5% of DCIS was thought to be symptomatic, but accurate evaluation of the presentation of symptomatic DCIS is needed to determine its incidence and tumour biology. METHODS: Clinico-pathological details of a consecutive series of patients presenting to a single breast-unit, with a pre-operative diagnosis of DCIS, were selected. Data included age, mode of presentation, pre-operative clinical and radiographical findings. The final tumour histology, operation, size, grade, ER status (and HER2 expression in invasive cases) were recorded. RESULTS: 375 patients had a pre-operative histological diagnosis of DCIS. 308 (82%) screen-detected (median age 59), 67 (18%) presented via symptomatic clinics (median age 50). At final histology 286 (74%) were pure DCIS, and 67 (23%) had an invasive focus. 43% (29/67) of symptomatic cases had an invasive focus at final histology versus 19% (60/308) screen-detected (p ≤ 0.001). 31% (9/29) of symptomatic, versus 10% (6/60) of screen-detected cases with invasion were node positive (p = 0.05). 45% (28/62) intermediate/high-grade symptomatic cases had an invasive focus at final histology, compared to 19% (57/297) intermediate/high-grade screen-detected cases. 86% (212/248) screen-detected pure DCIS was ER positive compared to 68% (26/38) symptomatically presenting pure DCIS (p ≤ 0.001). Overall, 13% (38/248) pure DCIS presented symptomatically (p = 0.001). CONCLUSIONS: Overall, thirteen percent of pure DCIS present symptomatically. Nearly half of symptomatically presenting DCIS at core biopsy has an occult invasive focus and is more frequently ER negative. Symptomatic DCIS with an invasive focus is more likely to have lymph node involvement.

Cyclooxygenase-2 inhibition: effects on tumour growth, cell cycling and lymphangiogenesis in a xenograft model of breast cancer.

Cyclooxygenase-2 (COX-2) is associated with poor-prognosis breast cancer. We used a nude mouse xenograft model to determine the effects of COX-2 inhibition in breast cancer. Oestrogen receptor (ER)-positive MCF7/HER2-18 and ER-negative MDAMB231 breast cancer cell lines were injected into nude mice and allowed to form tumours. Mice then received either chow containing Celecoxib (a COX-2 inhibitor) or control and tumour growth measured. Tumour proliferation, apoptosis, COX-2, lymphangiogenesis and angiogenesis were assessed by immunohistochemistry (IHC), Western blotting or Q-PCR. Celecoxib inhibited median tumour growth in MCF7/HER2-18 (58.7%, P=0.029) and MDAMB231 (46.3%, P=0.0002) cell lines compared to control. Cyclooxygenase-2 expression decreased following Celecoxib treatment (MCF7/HER2-18 median control 65.3% vs treated 22.5%, P=0.0001). Celecoxib increased apoptosis in MCF7/HER2-18 tumours (TUNEL 0.52% control vs 0.73% treated, P=0.0004) via inactivation of AKT (median pAKT(ser473) 57.3% control vs 35.5% treated, P=0.0001--confirmed at Western blotting). Q-PCR demonstrated decreased podoplanin RNA (lymphangiogenesis marker) in the MCF7/HER2-18 - median 2.9 copies treated vs 66.6 control (P=0.05) and MDAMB231-treated groups--median 160.7 copies vs 0.05 control copies (P=0.015), confirmed at IHC. Cyclooxygenase-2 is associated with high levels of activated AKT(ser473) and lymphangiogenesis in breast cancer. Cyclooxygenase-2 inhibition decreases tumour growth, and may potentially decrease recurrence, by inactivating AKT and decreasing lymphangiogenesis.

Potential use of COX-2-aromatase inhibitor combinations in breast cancer.

Cyclooxygenase-2 (COX-2) is overexpressed in several epithelial tumours, including breast cancer. Cyclooxygenase-2-positive tumours tend to be larger, higher grade, node-positive and HER-2/neu-positive. High COX-2 expression is associated with poor prognosis. Cyclooxygenase-2 inhibition reduces the incidence of tumours in animal models, inhibits the development of invasive cancer in colorectal cancer and reduces the frequency of polyps in familial adenomatous polyposis (FAP). These effects may be as a result of increased apoptosis, reduced angiogenesis and/or proliferation. Studies of COX-2 inhibitors in breast cancer are underway both alone and in combination with other agents. There is evidence to suggest that combining COX-2 inhibitors with aromatase inhibitors, growth factor receptor blockers, or chemo- or radiotherapy may be particularly effective. Preliminary results from combination therapy with celecoxib and exemestane in postmenopausal women with advanced breast cancer showed that the combination increased the time to recurrence. Up to 80% of ductal carcinomas in situ (DCISs) express COX-2, therefore COX-2 inhibition may be of particular use in this situation. Cyclooxygenase-2 expression correlates strongly with expression of HER-2/neu. As aromatase inhibitors appear particularly effective in patients with HER-2/neu-positive tumours, the combination of aromatase inhibitors and COX-2 inhibitors may be particularly useful in both DCIS and invasive cancer.

Relationship between hormone receptor status and tumour size, grade and comedo necrosis in ductal carcinoma in situ.

BACKGROUND: Results of the National Surgical Adjuvant Breast Project B-24 trial indicate that adjuvant tamoxifen therapy is of benefit only in oestrogen receptor (ER)- positive ductal carcinoma in situ (DCIS). In the UK, ER status is not routinely determined in DCIS. The aim of this study was to assess the ER status in women with DCIS to determine whether any clinicopathological factors could predict positivity instead of immunohistochemical assessment. METHODS: The ER and progesterone receptor (PR) status of consecutive women diagnosed with DCIS during 2001 and 2002 was determined by immunohistochemistry. RESULTS: One hundred and nineteen tumours diagnosed between 2001 and 2002 were analysed; 73.0 per cent were ER positive and 61.1 per cent were PR positive. PR positivity was associated with ER positivity (P < 0.001). Increasing tumour grade correlated with a decrease in ER and PR positivity (both P = 0.002). Comedo necrosis was associated with ER negativity (P = 0.026), PR negativity (P = 0.033) and a lower percentage of ER expression in ER-positive tumours (mean(s.d.) 82(27) versus 93(10) per cent; P = 0.021). CONCLUSION: Tumour grade and comedo necrosis were not strong enough predictors to be used as surrogates for immunohistochemical assessment. ER status should be determined before commencing endocrine therapy.