Elisabeth Elder

Alterations of the SDHD gene locus in midgut carcinoids, Merkel cell carcinomas, pheochromocytomas, and abdominal paragangliomas.

Several types of endocrine tumors show frequent somatic deletions of the distal part of chromosome arm 11q, where the tumor‐suppressor gene SDHD (succinate‐ubiquinone oxidoreductase subunit D), constitutionally mutated in paragangliomas of the head and neck, is located. In this study, we screened 18 midgut carcinoids, 7 Merkel cell carcinomas, 46 adrenal pheochromocytomas (37 sporadic and 9 familial), and 7 abdominal paragangliomas for loss of heterozygosity (LOH) and/or mutations at the SDHD gene locus. LOH was detected in 5 out of 8 (62%) informative midgut carcinoids, in 9 out of 30 (30%) sporadic pheochromocytomas, in none of the familial pheochromocytomas (0%), and in 1 out of 6 (17%) abdominal paragangliomas. No sequence variants were detected in the pheochromocytomas or paragangliomas. However, two constitutional putative missense mutations, H50R and G12S, were detected in two midgut carcinoids, which were both associated with LOH of the other allele. The same sequence variants were also detected in two Merkel cell carcinomas. In addition, the S68S polymorphism was found to coexist with the G12S sequence variant in both cases. In conclusion, we show that alterations of the SDHD gene seem to be involved in the tumorigenesis of both midgut carcinoids and Merkel cell carcinomas.

Loss of heterozygosity on the short arm of chromosome 1 in pheochromocytoma and abdominal paraganglioma

Pheochromocytomas and abdominal paragangliomas are catecholamine-producing tumors that arise from sympathetic paraganglia within and outside the adrenal medulla, respectively. Deletions of the short arm of chromosome 1 have been implicated as important genetic events in their tumorigenesis and suggest a common genetic etiology. The aim of this study was to define further the chromosomal regions on 1p that are involved in the development of these tumor types. We analyzed 46 pheochromocytomas (1 benign, 6 malignant, 9 hereditary) and 7 paragangliomas (3 benign, 4 malignant) from 50 patients for loss of heterozygosity (LOH) on 1p by genotyping 15 microsatellite markers spread over the chromosome arm. Overall, LOH was detected in 33 of 46 pheochromocytomas (72%) and in 6 of 7 (86%) paragangliomas. Three minimal regions of overlapping deletions were identified: one telomeric of D1S1612(1p36.2-pter), one centromeric of D1S429 (1cen-p13), and one in the 18 cM interval defined by D1S2134 andD1S1669 (1p32). The latter region harbors the leukocyte common antigen-related (LAR) gene, which shows altered expression in sporadic rat pheochromocytomas. In conclusion, chromosome 1p may be the site of at least three putative tumor-suppressor gene loci involved in the tumorigenesis of pheochromocytomas and abdominal paragangliomas. Further studies of these regions and of LARas a candidate gene would be valuable.

Tissue biomarkers of breast cancer and their association with conventional pathologic features.

Background:Tissue protein expression profiling has the potential to detect new biomarkers to improve breast cancer (BC) diagnosis, staging, and prognostication. This study aimed to identify tissue proteins that differentiate breast cancer tissue from healthy breast tissue using protein chip mass spectrometry and to examine associations with conventional pathological features.Methods:To develop a training model, 82 BC and 82 adjacent unaffected tissue (AT) samples were analysed on cation-exchange protein chips by time-of-flight mass spectrometry. For validation, 89 independent BC and AT sample pairs were analysed.Results:From the protein peaks that were differentially expressed between BC and AT by univariate analysis, binary logistic regression yielded two peaks that together classified BC and AT with a ROC area under the curve of 0.92. Two proteins, ubiquitin and S100P (in a novel truncated form), were identified by liquid chromatography/tandem mass spectrometry and validated by immunoblotting and reactive-surface protein chip immunocapture. The combined marker panel was positively associated with high histologic grade, larger tumour size, lymphovascular invasion, ER and PR positivity, and HER2 overexpression, suggesting that it may be associated with a HER2-enriched molecular subtype of breast cancer.Conclusion:This independently validated protein panel may be valuable in the classification and prognostication of breast cancer patients.

Reducing Decisional Conflict and Enhancing Satisfaction with Information among Women Considering Breast Reconstruction following Mastectomy: Results from the Breconda Randomized Controlled Trial

Background: Deciding whether or not to have breast reconstruction following breast cancer diagnosis is a complex decision process. This randomized controlled trial assessed the impact of an online decision aid [Breast RECONstruction Decision Aid (BRECONDA)] on breast reconstruction decision-making. Methods: Women (n = 222) diagnosed with breast cancer or ductal carcinoma in situ, and eligible for reconstruction following mastectomy, completed an online baseline questionnaire. They were then assigned randomly to receive either standard online information about breast reconstruction (control) or standard information plus access to BRECONDA (intervention). Participants then completed questionnaires at 1 and 6 months after randomization. The primary outcome was participants’ decisional conflict 1 month after exposure to the intervention. Secondary outcomes included decisional conflict at 6 months, satisfaction with information at 1 and 6 months, and 6-month decisional regret. Results: Linear mixed-model analyses revealed that 1-month decisional conflict was significantly lower in the intervention group (27.18) compared with the control group (35.5). This difference was also sustained at the 6-month follow-up. Intervention participants reported greater satisfaction with information at 1- and 6-month follow-up, and there was a nonsignificant trend for lower decisional regret in the intervention group at 6-month follow-up. Intervention participants’ ratings for BRECONDA demonstrated high user acceptability and overall satisfaction. Conclusions: Women who accessed BRECONDA benefited by experiencing significantly less decisional conflict and being more satisfied with information regarding the reconstruction decisional process than women receiving standard care alone. These findings support the efficacy of BRECONDA in helping women to arrive at their breast reconstruction decision.

Relevance of the American College of Surgeons Oncology Group Z0011 Trial to breast cancer in the Australian setting.

Conventional wisdom suggests that a patient with a positive sentinel node requires a completion axillary clearance to obtain full staging and durable regional control. However, this dictum has been challenged by the recent American College of Surgeons Oncology Group Z0011 Trial demonstrating that women with node‐positive breast cancer who underwent sentinel node biopsy only, and were treated with breast conserving surgery and radiation, had equivalent locoregional recurrence and survival rates to those who had a completion axillary clearance. The aim of our study was to determine what the clinical impact of the Z0011 findings might be if patients were managed according to the Z0011 criteria in an Australian teaching hospital setting.

Nipple-sparing mastectomy with implant reconstruction: the Westmead experience.

Nipple‐sparing mastectomy (NSM) involves the removal of all breast tissue with preservation of the breast skin envelope and nipple‐areola complex (NAC). The objective of this study was to report the outcomes from our initial experience with NSM.

Body image and psychological distress in nipple-sparing mastectomy: the roles of self-compassion and appearance investment

Women with breast cancer face threats to body image following surgery. Nipple‐sparing mastectomy with immediate breast reconstruction (NSM + IBR) may minimise body image disturbance as this preserves the womans skin and areola complex. We assessed levels of body image disturbance and psychological distress in women undergoing NSM + IBR. To further understand the body image–distress relationship, we investigated the potential moderating effect of self‐compassion and appearance investment on this relationship.

Implant salvage in breast reconstruction with severe peri-prosthetic infection.

Although treatment of mild peri‐prosthetic infection in implant‐based breast reconstruction results in high rates of resolution, successful management of severe peri‐prosthetic infection remains a significant challenge.

Nonsurgical Management Should be First-Line Therapy for Breast Abscess

Dear Editor, We read with great interest the study by Bharat and colleagues describing risk factors for the development of breast abscess and recurrent abscess [1]. However, we were intrigued by their statement that surgical incision and drainage is the ‘‘gold standard’’ for treatment of benign breast abscesses. In our experience, the majority of both lactational and nonlactational breast abscesses can be managed successfully with serial percutaneous aspiration under ultrasound guidance, in combination with appropriate antibiotic therapy. The advantages of this strategy, which has been described in the literature since at least the early 1990s and is the mainstay of treatment in many specialist breast units around the world [2–7], include reduced incidence of scarring and fistula formation, feasibility of outpatient treatment and continued breast feeding in lactating women, reduced costs, and a superior cosmetic result. This approach has been shown to have a very high success rate in women with both lactational and nonlactational breast abscesses [3, 4, 8]. There are a number of issues to consider when treating breast abscesses nonsurgically. Early and repeated ultrasound assessment of a breast infection provides a reliable way of differentiating between cellulitis, mastitis, and abscess formation [3]. Aspiration under ultrasound guidance rather than blindly has significant advantages in assessing the adequacy of pus aspiration and allows complete drainage of multiloculated collections with minimal tissue damage [9]. It has been shown that a significant amount of pus may remain after attempted drainage using a needle and syringe without ultrasound guidance [10]. Multiple aspirations often are required to achieve complete healing [2, 3]. The frequency is dependent on the volume and aggressiveness of the abscess, but initially patients often need to be reviewed every 2–3 days. Although repeated visits for serial aspiration may pose a resource issue for the outpatient clinic, this approach is justified by the reduced inconvenience, pain, and cost to the patient and reduced overall utilization of hospital services. Adequate antibiotic cover is essential and, if possible, choices should be guided by microbiological culture and sensitivity. In nonlactational, periareolar abscesses, the need for additional anaerobic cover is well established [3, 7]. Furthermore, it is important to try to establish the underlying etiology of a breast abscess, because this will direct subsequent management. In conclusion, serial aspiration under ultrasound guidance, in combination with appropriate antibiotic therapy, can be safely employed as the first-line approach to breast abscess management. Incision and drainage under general anaesthesia should be reserved for abscesses that do not respond to repeated aspiration.

Factors associated with romantic relationship formation difficulties in women with breast cancer

Many un‐partnered women report difficulty in forming romantic relationships after breast cancer, characterized by high dating‐related anxiety and low perceived interpersonal competence. This study examined the relationship between poor body image (appearance investment and body dissatisfaction) and self‐compassion, and womens ability to form romantic relationships post‐breast cancer.