Clinical and imaging modality factors impacting radiological interpretation of breast screening in young women with neurofibromatosis type 1.

Young women with Neurofibromatosis type 1 (NF1) have a high risk of developing breast cancer and poorer survival following breast cancer diagnosis. International guidelines recommend commencing breast screening between 30 and 35 years; however, the optimal screening modality is unestablished, and previous reports suggest that breast imaging may be complicated by the presence of intramammary and cutaneous neurofibromas (cNFs). The aim of this study was to explore potential barriers to implementation of breast screening for young women with NF1.Twenty-seven women (30-47 years) with NF1 completed breast screening with breast MRI, mammogram and breast ultrasound. Nineteen probably benign/suspicious lesions were detected across 14 women. Despite the presence of breast cNFs, initial biopsy rate for participants with NF1 (37%), were comparable to a BRCA pathogenic variant (PV) cohort (25%) (P = 0.311). No cancers or intramammary neurofibromas were identified. Most participants (89%) returned for second round screening.The presence of cNF did not affect clinician confidence in 3D mammogram interpretation, although increasing breast density, frequently seen in young women, impeded confidence for 2D and 3D mammogram. Moderate or marked background parenchymal enhancement on MRI was higher in the NF1 cohort (70.4%) than BRCA PV carriers (47.3%), which is an independent risk factor for breast cancer.Breast MRI was the preferred mode of screening over mammogram, as the majority (85%) with NF1 demonstrated breast density (BI-RADS 3C/4D), which hinders mammogram interpretation. For those with high breast density and high cNF breast coverage, 3D rather than 2D mammogram is preferred, if MRI is unavailable.

The psychological impact and experience of breast cancer screening in young women with an increased risk of breast cancer due to neurofibromatosis type 1.

Women with neurofibromatosis type 1 (NF1) have an increased risk of developing early breast cancer with a poorer prognosis compared to the general population. Therefore, international management guidelines recommend regular screening in women with NF1 starting from 30 to 35 years. As the psychological impacts of breast cancer screening in other high-risk populations cannot be extended to women with NF1, due to increased incidence of cognitive and mental health issues, the psychological harms of breast screening in women with NF1 are unknown. Consequently, the aim of this study was to assess the psychological impact of breast cancer screening in women with NF1 attending an established risk management clinic. Twenty-eight women with NF1 (30-50 years) completed psychological well-being and patient experience questionnaires, administered across five time points, before and after their initial and second round annual breast screening visits. Preliminary findings demonstrated the screening regimen was well-tolerated, with most participants reporting high satisfaction with the screening process. Overall, no significant increase in psychological distress related to the breast screening process was identified, with mean cancer worry and anxiety scores decreasing over time. However, some women did experience negative aspects of screening and barriers to re-attendance at annual breast screening appointments. As some women with NF1 exhibited clinical levels of psychological distress prior to screening, efforts to identify those at risk and additional support to address concerns and expectations throughout the breast screening process may be beneficial.

Occult breast cancer: Where are we at?

Occult breast cancer (OBC) is described as an axillary metastatic carcinoma without detection of a primary breast lesion and is uncommon. Significant advances in breast imaging have occurred since its description, decreasing its incidence. However current management is based upon old studies, with variable clinical, radiological and pathological definitions of OBC. We suggest standardised definitions of OBC to facilitate more homogenous data representation in the literature. This review also discusses the conflicting heterogeneous data and its influence in determining the current management guidelines. We discuss whether the current significant surgical recommendations are necessary and postulate whether they could be safely substituted with less invasive management.

A novel truncated form of S100P predicts disease-free survival in patients with lymph node positive breast cancer.

The calcium-binding protein S100P is overexpressed in various cancers and may contribute to the oncogenic phenotype. This study used mass spectrometry to characterize a novel 9.2-kDa C-terminally truncated form of S100P (t-S100P), and to investigate its potential prognostic value in breast cancer. Univariate analysis demonstrated the association between breast tissue t-S100P levels (n = 148) and conventional pathological markers. Across all tumor samples, high t-S100P was strongly prognostic for poor disease-free survival (P = 0.005), its efficacy confined to lymph node-positive tumors (n = 74, P = 0.007). Matrix-assisted laser desorption/ionization imaging mass spectrometry confirmed differential t-S100P abundance between breast cancer and unaffected adjacent tissue. t-S100P was exclusively located in the cell nucleus of breast cancer tissue, and full-length S100P was essentially undetectable by mass spectrometry. We conclude that t-S100P is the predominant form of S100P in breast cancer tissue and is strongly prognostic for disease-free survival in women with lymph node-positive disease.

Novel serum protein biomarker panel revealed by mass spectrometry and its prognostic value in breast cancer.

INTRODUCTION: Serum profiling using proteomic techniques has great potential to detect biomarkers that might improve diagnosis and predict outcome for breast cancer patients (BC). This study used surface-enhanced laser desorption/ionization time-of-flight (SELDI-TOF) mass spectrometry (MS) to identify differentially expressed proteins in sera from BC and healthy volunteers (HV), with the goal of developing a new prognostic biomarker panel. METHODS: Training set serum samples from 99 BC and 51 HV subjects were applied to four adsorptive chip surfaces (anion-exchange, cation-exchange, hydrophobic, and metal affinity) and analyzed by time-of-flight MS. For validation, 100 independent BC serum samples and 70 HV samples were analyzed similarly. Cluster analysis of protein spectra was performed to identify protein patterns related to BC and HV groups. Univariate and multivariate statistical analyses were used to develop a protein panel to distinguish breast cancer sera from healthy sera, and its prognostic potential was evaluated. RESULTS: From 51 protein peaks that were significantly up- or downregulated in BC patients by univariate analysis, binary logistic regression yielded five protein peaks that together classified BC and HV with a receiver operating characteristic (ROC) area-under-the-curve value of 0.961. Validation on an independent patient cohort confirmed the five-protein parameter (ROC value 0.939). The five-protein parameter showed positive association with large tumor size (P = 0.018) and lymph node involvement (P = 0.016). By matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) MS, immunoprecipitation and western blotting the proteins were identified as a fragment of apolipoprotein H (ApoH), ApoCI, complement C3a, transthyretin, and ApoAI. Kaplan-Meier analysis on 181 subjects after median follow-up of >5 years demonstrated that the panel significantly predicted disease-free survival (P = 0.005), its efficacy apparently greater in women with estrogen receptor (ER)-negative tumors (n = 50, P = 0.003) compared to ER-positive (n = 131, P = 0.161), although the influence of ER status needs to be confirmed after longer follow-up. CONCLUSIONS: Protein mass profiling by MS has revealed five serum proteins which, in combination, can distinguish between serum from women with breast cancer and healthy control subjects with high sensitivity and specificity. The five-protein panel significantly predicts recurrence-free survival in women with ER-negative tumors and may have value in the management of these patients.

Breast cancer-associated fibroblasts induce epithelial-to-mesenchymal transition in breast cancer cells.

Cancer-associated fibroblasts (CAFs) play a role in tumour initiation and progression, possibly by inducing epithelial-to-mesenchymal transition (EMT), a series of cellular changes that is known to underlie the process of metastasis. The aim of this study was to determine whether CAFs and surrounding normal breast fibroblasts (NBFs) are able to induce EMT markers and functional changes in breast epithelial cancer cells. Matched pairs of CAFs and NBFs were established from fresh human breast cancer specimens and characterised by assessment of CXCL12 levels, α-smooth muscle actin (α-SMA) levels and response to doxorubicin. The fibroblasts were then co-cultured with MCF7 cells. Vimentin and E-cadherin expressions were determined in co-cultured MCF7 cells by immunofluorescence and confocal microscopy as well as by western blotting and quantitative PCR. Co-cultured MCF7 cells were also assessed functionally by invasion assay. CAFs secreted higher levels of CXCL12 and expressed higher levels of α-SMA compared with NBFs. CAFs were also less sensitive to doxorubicin as evidenced by less H2AX phosphorylation and reduced apoptosis on flow cytometric analysis of Annexin V compared with NBFs. When co-cultured with MCF7 cells, there was greater vimentin and less E-cadherin expression as well as greater invasiveness in MCF7 cells co-cultured with CAFs compared with those co-cultured with NBFs. CAFs have the ability to induce a greater degree of EMT in MCF7 cell lines, indicating that CAFs contribute to a more malignant breast cancer phenotype and their role in influencing therapy resistance should therefore be considered when treating breast cancer.

Breast clinic triage tool: telephone assessment of new referrals.

Efficient systems to triage increasing numbers of new referrals to breast clinics are needed, to optimise the management of patients with cancer and benign disease. A tool was developed to triage the urgency of referrals and allocate the most appropriate clinician consultation (surgeon or breast physician (BP)). 259 consecutive new referrals were triaged using the tool. 100% new cancers and 256 (98.8%) referrals overall were triaged to both appropriate category of urgency and the appropriate clinician. This triage tool provides a simple method for assessing new referrals to a breast clinic and can be easily delivered by trained administrative staff by telephone.

Peer-led prenatal breast-feeding education: a viable alternative to nurse-led education.

OBJECTIVE: To evaluate a prenatal breast-feeding class developed and facilitated by peer Breast-feeding Buddies. DESIGN AND INTERVENTIONS: Non-equivalent control group quasi-experimental study comparing participants of the peer-led class (PLC) to those attending an established hospital-based breast-feeding nurse-led class (NLC). A brief questionnaire was completed immediately prior to the class, and telephone interviews were conducted approximately one week following the class, and one and six months post partum. SETTING AND PARTICIPANTS: 54 expectant mothers who registered for the community PLC and 55 expectant mothers who registered for the NLC. MEASUREMENTS AND FINDINGS: Breast-feeding intentions were measured at all time-points. Class evaluations, breast-feeding experiences, and breast-feeding support were measured at all post-class interviews. Both classes were considered worthwhile, but the PLC class was rated as more helpful and participants appreciated learning from the peers' personal experiences. Mothers taught by peers were more likely to access peer breast-feeding support. PLC participants initially decreased their prenatal breast-feeding duration intentions but had significantly stronger intentions to continue breast feeding at six months than did NLC mothers. KEY CONCLUSIONS: A peer-led prenatal breast-feeding class is as effective as a traditional model of breast-feeding education and is a valuable tool to promote and support successful breast feeding. RECOMMENDATIONS FOR PRACTICE: Peer-led breast-feeding classes should be provided to enhance the accessibility of breast-feeding education and support for expectant mothers.

Factors influencing treatment recommendations in node-negative breast cancer.

PURPOSE: To assess factors influencing recommendations for adjuvant chemotherapy (CT) in relation to perceived benefits in women with stage 1 breast cancer and to determine the degree to which recommendations were followed. METHODS: Recommendations from multidisciplinary team meetings at Royal North Shore Hospital (Sydney, Australia) during 2007 and 2008 for postoperative patients with invasive, primary breast cancer were reviewed. Treatment data were collected from patients' medical records. Estimated benefits of adjuvant CT on 10-year survival for node-negative patients were calculated using Adjuvant! Online. Univariate and multivariate analyses were performed using SPSS. RESULTS: Of 345 patients (mean age, 59 years), 51 were unsuitable for CT as a result of comorbidity and/or age > 80 years. All 93 patients with nodal macrometastases who were suitable for CT and 20 (80%) of 25 with micrometastases were recommended for CT, compared with 92 (53%) of 175 node-negative patients. Tumor size > 2 cm, grade 3, estrogen receptor negativity, and age less than 45 years were independent factors influencing CT recommendation. The mean estimated benefit of CT in node-negative patients who received this recommendation was 5.7% versus 1.3% in patients not recommended for CT. Twenty-one (23%) node-negative patients declined CT after discussion with a medical oncologist. A higher proportion of node-negative patients were recommended for CT in 2008 versus 2007 (60% v 44%, P = .04). CONCLUSIONS: Grade, tumor size, estrogen receptor status, and younger age are the most significant factors influencing CT recommendation in node-negative patients. The minimum level of benefit to recommend CT is approximately 2%. A significant proportion of patients do not proceed with CT after individualized review.

Outcomes for women with ductal carcinoma-in-situ and a positive sentinel node: a multi-institutional audit.

BACKGROUND: A positive sentinel lymph node (SLN) has been reported in 6% to 13% of patients with ductal carcinoma in situ (DCIS). Although it is well established that nodal status for invasive disease is prognostically important, the clinical relevance of a positive SLN in patients with DCIS remains undetermined. METHODS: SLN biopsy was performed on 470 high-risk patients with DCIS (22% of all patients with DCIS) at 3 institutions. Of these, 43 (9%) had SLN metastases. Pathology findings of positive cases were reviewed, and follow-up was obtained. At 2 of the 3 institutions, data were also collected on DCIS patients who had negative findings on SLN biopsy. For these 414 patients, univariate analyses of tumor characteristics were performed to identify factors associated with node positivity. RESULTS: Extensive disease requiring mastectomy (p = 0.02) and the presence of necrosis (p = 0.04) were associated with an increased risk of nodal positivity. Three (7%) of the 43 SLN-positive patients had macrometastases (pN1), 4 (9%) had micrometastases (pN1mi), and 36 (84%) had single tumor cells or small clusters (pN0(i+)). Of the 25 women that underwent completion axillary dissection, one was found to have a macrometastasis. On pathological review of the primary lesion, 2 (5%) of 43 patints were found to have microinvasion, and 2 (5%) lymphovascular invasion. Nine of 43 (21%) high-risk DCIS patients with a positive SLN and 9/470 (2%) of all high-risk DCIS patients were upstaged to AJCC stage I or II as a result of the SLN biopsy. At a median (range) follow-up of 27 (3-88) months, 1 patient had developed hepatic metastases. This patient had immunohistochemistry detected isolated tumor cells in her SLN (N0(i+)), and upon pathologic review, was found to have high-grade DCIS with microinvasion. CONCLUSION: SLN biopsy for high-risk DCIS patients is a mean of detecting those who may have unrecognized invasive disease and therefore are at risk for distant disease.

Immunohistochemically detected tumor cells in the sentinel lymph nodes of patients with breast carcinoma: biologic metastasis or procedural artifact?

BACKGROUND: Sentinel lymph node (SLN) biopsy is a new standard of care for patients with breast carcinoma, and allows enhanced pathologic analysis with serial sections and immunohistochemical (IHC) staining for cytokeratins to be performed on a routine basis. However, the significance of SLN micrometastases detected only by IHC is uncertain. Are these tumor cells truly markers of metastatic potential, or simply evidence of passive displacement by preoperative instrumentation of the tumor site? Here we evaluate whether the pattern of SLN metastasis in breast carcinoma is related to the degree of manipulation at biopsy before surgery, independently of other known predictors. METHODS: Among 4016 consecutive eligible patients with breast carcinoma registered in a prospective SLN database at Memorial Sloan Kettering Cancer Center, we noted patient/tumor characteristics, pathologic status of the SLN (negative, positive by hematoxylin and eosin [H&E], or positive only on IHC), and method of previous biopsy (none, fine-needle aspiration biopsy [FNAB], core needle biopsy, or surgical biopsy). RESULTS: Multivariate analysis showed that the likelihood of an H&E-positive SLN was significantly associated with lymphovascular invasion, tumor size, tumor type, and tumor location, but not with the method of biopsy. In contrast, the likelihood of finding an SLN positive only on IHC was unassociated with any of the four variables above, but was significantly associated with the method of biopsy. After no previous biopsy, FNAB, core needle biopsy, or surgical biopsy, IHC-positive SLN were present in 1.2%, 3.0%, 3.8%, and 4.6% of patients, respectively (P = 0.002). CONCLUSIONS: These data suggest that the frequency of IHC-positive SLN in patients with breast carcinoma 1) is unrelated to conventional predictors of lymph node positivity, 2) is increased after instrumentation of the tumor site, and 3) is increased approximately proportionate to the degree of manipulation. A proportion of IHC-positive SLN were present before biopsy and therefore less likely to be artifactual.

How are we treating patients with hepatic colorectal metastases in Sydney?

INTRODUCTION: Colorectal cancer is common. At presentation 25% of patients have established hepatic metastases and overall at least half will develop hepatic metastases. Many different therapeutic options have been proposed. This study evaluates the current resources available and patterns of care for patients with hepatic colorectal metastases in the Sydney metropolitan area. METHODS: Prospective data were collated describing all patients presenting to any one of nine hospitals within the Sydney metropolitan area in a 12-month period, diagnosed with hepatic metastases. The data included patient demographics and background, treatment of the primary tumour, diagnosis and treatment of the hepatic metastases and histopathology both of the primary and of the hepatic metastases. RESULTS: There were 194 patients in the study. Most when diagnosed with hepatic colorectal metastases were independent, active, retired and usually had existing social supports. The majority had had their primary colorectal cancer resected and were later treated with systemic chemotherapy. CONCLUSIONS: This study highlights the need for a comprehensive multicentre, prospective data collection of patients with hepatic metastatic disease. This would clarify the effectiveness or otherwise of the health system caring for such patients and provide additional information for the development and implementation of guidelines.