Impact of progesterone receptor status on response to neoadjuvant chemotherapy in estrogen receptor-positive breast cancer patients.

INTRODUCTION: Breast cancer patients respond differently to neoadjuvant chemotherapy(NAC) based on receptor subtype. The aim of this study was to assess the impact of progesterone receptor (PgR) status on response to neoadjuvant chemotherapy (NAC) in estrogen receptor (ER)+, human epidermal growth factor receptor (HER)- breast cancer patients. METHODS: ER+ and HER- patients receiving NAC over a 7-year period (2011-2017) were identified. The primary outcome was breast complete pathological response (pCR) rate. Secondary outcomes included axillary pCR, axillary/breast pCR and complete radiological response (cRR). RESULTS: A total of 203 patients were identified (149 in the ER+, PgR+, and HER- group and 54 in the ER+, PgR-, and HER- group). Compared with the PgR+ group, PgR- patients were significantly associated with breast pCR (31.5% vs 7.4%; χ² test; P < .01). In multivariable analysis, PgR- status (odds ratio [OR], 4.58; 95% confidence interval [CI]: 1.58,13.28; P = .005), radiological size >50 mm (OR, 5.38; 95% CI: 1.07,27.04; P = .04) and grade (OR, 3.52;95% CI: 1.21,10.23;P = .02) were significant predictors of breast pCR. Only PgR- status was a significant predictor of cRR (OR, 6.234; 95% CI: 2.531, 15.355; P < .001). In node positive patients, PgR negativity was associated with a trend towards breast/axillary nodal pCR (22% vs 12.7%; χ² test; P = .055). CONCLUSION: Over 30% of ER+, PgR-, and HER- patients will have a breast pCR after NAC. PgR- is the only significant predictor of breast pCR/cRR in this tumor subtype. ER+, PgR-, and HER- patients should be considered for NAC.

Decision aids for female BRCA mutation carriers: a scoping review.

OBJECTIVES: Women who inherit a pathogenic BRCA1 or BRCA2 mutation are at substantially higher risk of developing breast and ovarian cancer than average. Several cancer risk management strategies exist to address this increased risk. Decisions about which strategies to choose are complex, personal and multifactorial for these women. Decision aids (DAs) are tools that assist patients in making health-related decisions. The aim of this scoping review was to map evidence relating to the development and testing of patient DAs for cancer unaffected BRCA mutation carriers. DESIGN: Scoping review conducted according to the Joanna Briggs Institute's (JBI's) scoping review methodological framework. DATA SOURCES: MEDLINE, EMBASE, CINAHL, Web of Science. No restrictions applied for language or publication date. A manual search was also performed. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Studies on DAs for cancer risk management designed for or applicable to women with a pathogenic BRCA1 or BRCA2 mutation who are unaffected by breast or ovarian cancer. DATA EXTRACTION AND SYNTHESIS: Data were extracted using a form based on the JBI instrument for extracting details of studies' characteristics and results. Data extraction was performed independently by two reviewers. Extracted data were tabulated. RESULTS: 32 evidence sources relating to development or testing of 21 DAs were included. Four DAs were developed exclusively for cancer unaffected BRCA mutation carriers. Of these, two covered all guideline recommended risk management strategies for this population though only one of these was readily available publicly in its full version. All studies investigating DA effectiveness reported a positive effect of the DA under investigation on at least one of the outcomes evaluated, however only six DAs were tested in randomised controlled trials. CONCLUSION: This scoping review has mapped the landscape of the literature relating to developing and testing, DAs applicable to cancer unaffected BRCA mutation carriers.

A prospective investigation of predictive and modifiable risk factors for breast cancer in unaffected BRCA1 and BRCA2 gene carriers.

BACKGROUND: Breast cancer is the most common female cancer worldwide. The lifetime risk of a woman being diagnosed with breast cancer is approximately 12.5%. For women who carry the deleterious mutation in either of the BRCA genes, BRCA1 or BRCA2, the risk of developing breast or ovarian cancer is significantly increased. In recent years there has been increased penetrance of BRCA1 and BRCA2 associated breast cancer, prompting investigation into the role of modifiable risk factors in this group. Previous investigations into this topic have relied on participants recalling lifetime weight changes and subjective methods of recording physical activity. The influence of obesity-related biomarkers, which may explain the link between obesity, physical activity and breast cancer risk, has not been investigated prospectively in this group. This paper describes the design of a prospective cohort study investigating the role of predictive and modifiable risk factors for breast cancer in unaffected BRCA1 and BRCA2 gene mutation carriers. METHODS/DESIGN: Participants will be recruited from breast cancer family risk clinics and genetics clinics. Lifestyle risk factors that will be investigated will include body composition, metabolic syndrome and its components, physical activity and dietary intake. PBMC telomere length will be measured as a potential predictor of breast cancer occurrence. Measurements will be completed on entry to the study and repeated at two years and five years. Participants will also be followed annually by questionnaire to track changes in risk factor status and to record cancer occurrence. Data will be analysed using multiple regression models. The study has an accrual target of 352 participants. DISCUSSION: The results from this study will provide valuable information regarding the role of modifiable lifestyle risk factors for breast cancer in women with a deleterious mutation in the BRCA gene. Additionally, the study will attempt to identify potential blood biomarkers which may be predictive of breast cancer occurrence.

The presentation of metabolic dysfunction and the relationship with energy output in breast cancer survivors: a cross-sectional study.

BACKGROUND: Breast cancer prognosis can be adversely influenced by obesity, physical inactivity and metabolic dysfunction. Interventions aimed at improving surrogate markers of breast cancer risk such as insulin resistance may result in improved breast cancer outcomes. The design of such interventions may be improved through increased understanding of metabolic presentation in this cohort. This cross-sectional study aimed to characterise the metabolic profile of breast cancer survivors relative to abdominal obesity and insulin resistance. A secondary aim was to compare measures of energy output across these groups. METHODS: Sixty-nine women (mean (SD) age 53.43 (9.39) years) who had completed adjuvant chemotherapy and radiotherapy for breast cancer were recruited. All measures were completed during one assessment conducted 3.1 (1.0) years post diagnosis. Body composition was measured by bioimpedance analysis and waist circumference (WC). Fasting (12 hour) blood samples were drawn to measure lipid profile, glucose, insulin, glycosylated haemoglobin A1c (HBA1c) and C-reactive protein (CRP). Insulin resistance was estimated by the homeostatic model assessment index (HOMA-IR)). Energy output was evaluated by resting metabolic rate (RMR) measured by indirect calorimetry and physical activity measured by accelerometry. Characteristics were compared across four groups (1. WC <80 cm, not insulin resistant; 2. WC 80-87.9 cm, not insulin resistant; 3. WC >88 cm, not insulin resistant; 4. WC >80 cm, insulin resistant) using ANOVA (p < 0.05). RESULTS: Group 4 was characterised by significant disturbances in measures of glucose metabolism (glucose, insulin, HOMA-IR and HBA1c) and raised CRP compared to other groups. Group 4 also displayed evidence of dyslipidemia and higher body composition values compared to Groups 1 and 2. Both absolute and adjusted RMR were significantly higher in the Group 4 versus all other groups. Physical activity levels were similar for all groups. CONCLUSIONS: The results from this study suggest that participants who were both centrally obese and insulin resistant showed evidence of dyslipidemia, low-grade inflammation and glucose dysregulation. Metabolic profiles of participants who were centrally obese only were not significantly different from lean participants. Consideration of baseline metabolic presentation may be useful when considering the therapeutic targets for future interventions in this cohort.

A pilot study investigating feasibility of mainstreaming germline BRCA1 and BRCA2 testing in high-risk patients with breast and/or ovarian cancer in three tertiary Cancer Centres in Ireland.

In the Republic of Ireland (ROI), BRCA1/BRCA2 genetic testing has been traditionally undertaken in eligible individuals, after pre-test counselling by a Clinical Geneticist/Genetic Counsellor. Clinical Genetics services in ROI are poorly resourced, with routine waiting times for appointments at the time of this pilot often extending beyond a year. The consequent prolonged waiting times are unacceptable where therapeutic decision-making depends on the patient's BRCA status. "Mainstreaming" BRCA1/BRCA2 testing through routine oncology/surgical clinics has been implemented successfully in other centres in the UK and internationally. We aimed to pilot this pathway in three Irish tertiary centres. A service evaluation project was undertaken over a 6-month period between January and July 2017. Eligible patients, fulfilling pathology and age-based inclusion criteria defined by TGL clinical, were identified, and offered constitutional BRCA1/BRCA2 testing after pre-test counselling by treating clinicians. Tests were undertaken by TGL Clinical. Results were returned to clinicians by secure email. Onward referrals of patients with uncertain/pathogenic results, or suspicious family histories, to Clinical Genetics were made by the treating team. Surveys assessing patient and clinician satisfaction were sent to participating clinicians and a sample of participating patients. Data was collected with respect to diagnostic yield, turnaround time, onward referral rates, and patient and clinician feedback. A total of 101  patients underwent diagnostic germline BRCA1/BRCA2 tests through this pathway. Pathogenic variants were identified in 12 patients (12%). All patients in whom variants were identified were appropriately referred to Clinical Genetics. At least 12 additional patients with uninformative BRCA1/BRCA2 tests were also referred for formal assessment by Clinical Geneticist or Genetic Counsellor. Issues were noted in terms of time pressures and communication of results to patients. Results from a representative sample of participants completing the satisfaction survey indicated that the pathway was acceptable to patients and clinicians. Mainstreaming of constitutional BRCA1/BRCA2 testing guided by age- and pathology-based criteria is potentially feasible for patients with breast cancer as well as patients with ovarian cancer in Ireland.

Influence of the metabolic syndrome on leptin and leptin receptor in breast cancer.

Obesity and its associated metabolic syndrome (MetS) are recognized risk factors for breast cancer. The molecular basis for this association remains largely unknown. Adipokines, in particular leptin and adiponectin, are thought to form part of the mechanism linking obesity with cancer through their altered expression/production either systemically (endocrine pathway) or locally (paracrine/autocrine pathway). Using quantitative PCR, mRNA expression of adiponectin (AdipoQ) and leptin (Ob) in mammary adipose tissue (MAT), intratumoral leptin and associated ligand receptors (ObR, AdipoR1, and AdipoR2) was examined in 77 patients with complete anthropomorphic and serological data. Expression of Ob in MAT, and ObR in matched tumor tissue was significantly higher in patients with MetS compared to obese only or normal weight cancer patients (P < 0.005). There was no difference in intratumoral leptin adiponectin or its ligand receptors in the same groups. Individual features of MetS correlated with Ob and ObR expression, but not obesity markers (BMI, waist circumference). mRNA expression of leptin (Ob) and ObR, in adipose tissue and matched tumor samples, respectively, appear to be associated with obesity status in breast cancer. Increasing insulin resistance is a predominant feature of this higher Ob/ObR expression observed. These novel data indicate that the MetS may be an amenable risk factor for breast cancer.

Decision aids for female BRCA mutation carriers: a scoping review protocol.

INTRODUCTION: Women who inherit a pathogenic mutation in Breast Cancer Susceptibility Genes 1 or 2 (BRCA1 or BRCA2) are at substantially higher risk of developing breast and ovarian cancer than the average woman. Several cancer risk management strategies exist to address this increased risk. Decisions about which risk management strategies to choose are complex, personal and multifactorial for these women. This scoping review will map evidence relevant to cancer risk management decision making in BRCA mutation carriers without a personal history of cancer. The objective is to identify and describe the features of patient decision aids that have been developed for BRCA mutation carriers. This information may be beneficial for designing new decision aids or adapting existing decision aids to support decision making in this population. METHODS AND ANALYSIS: This scoping review will be conducted according to the Joanna Briggs Institute's scoping review methodological framework. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews checklist will be used for guidance. Studies on decision aids for women with a BRCA mutation who are unaffected by breast or ovarian cancer will be considered for inclusion. Five electronic databases will be searched (MEDLINE, EMBASE, Cochrane Library, CINAHL, Web of Science) with no restrictions applied for language or publication date. Studies for inclusion will be selected independently by two review authors. Data will be extracted using a predefined data extraction form. Findings will be presented in tabular form. A narrative description of the evidence will complement the tabulated results. ETHICS AND DISSEMINATION: Ethical approval for conducting this scoping review is not required as this study will involve secondary analysis of existing literature. Findings will be published in a peer-reviewed journal and presented at relevant conferences.

Fibromatosis of the breast: a 10-year multi-institutional experience and review of the literature.

BACKGROUND: Breast fibromatosis is a rare clinical entity, but poses significant diagnostic and therapeutic challenges. In light of recent changes in management practices, the aim was to review our institutional experience of breast fibromatosis and provide a review of current available literature on such management. METHODS: A search of pathological databases within two tertiary institutions for all patients diagnosed with fibromatosis of the breast over a 10-year period (2007-2016) was performed. Clinicopathological characteristics and modes of treatment were recorded for each patient. Concurrently a comprehensive literature search was performed and studies relating to breast fibromatosis and its management were identified and reviewed. RESULTS: Sixteen patients were identified. Median age at diagnosis was 42 (range 21-70) and all patients were diagnosed with core biopsy. The most useful imaging modality in diagnosis was ultrasonography and magnetic resonance imaging. 13/16 were treated surgically whilst 3/16 were treated using a watch-and-wait approach. 6/13 (46%) required re-excision of margins and 2/13 (15%) had recurrence after surgery. On review of the literature, there is no dedicated guideline in place for the management of breast fibromatosis. Currently a 'watch and wait' approach is favoured over surgical intervention due to high levels of recurrence and associated surgical morbidity. All cases should be discussed at a sarcoma multidisciplinary team meeting and tyrosine kinase inhibitors should be considered in advanced cases. CONCLUSIONS: Breast fibromatosis is rare but affects young patients. Active surveillance is now favoured over surgical resection due to high recurrence rates and extensive morbidity. Dedicated guidelines are required to ensure best outcomes.

Mammary ductoscopy in the evaluation and treatment of pathologic nipple discharge: a Canadian experience.

BACKGROUND: Mammary ductoscopy allows direct visualization of ductal epithelium using a fibreoptic microendoscope. As the first centre in Canada to apply ductoscopy to surgical practice, we report our experience with this technology. METHODS: Between 2004 and 2008, 65 women with pathologic nipple discharge underwent ductoscopy before surgical duct excision under general anesthetic. Prospective data collection included cannulation and complication rates, procedure length and lesion visualization rate compared with preoperative ductography, if performed. In addition, we classified the endoscopic appearance according to Makita and colleagues and correlated it with surgical pathology. RESULTS: It took longer than 6 months to overcome technical problems before the routine use of ductoscopy in the operating room. The ductoscope was easy to use: we achieved cannulation in 63 of 66 breast ducts (95%) and we visualized a lesion in 52 of 63 breast ducts (83%). The mean procedure length was 5.1 minutes, with no complications. Lesions seen on ductography were seen endoscopically 30 of 33 (91%) times. All 3 malignancies were seen: invasive carcinoma in 1 of 62 (1.6%) and in situ disease in 2 of 62 (3.2%) patients. Surgeons found ductoscopy helpful in defining the extent of duct excision. Except for the "polypoid solitary" class, which accurately predicted a papilloma (23/23), we found poor correlation between Makita and colleague's endoscopic classification and final pathology. CONCLUSION: Ductoscopy is feasible, safe and practical. Our surgeons routinely use it to identify the location and extent of duct excision without ordering preoperative ductography. Identifying pathology based on the endoscopic appearance is unreliable unless the lesion is solitary and polypoid.

Breast reconstruction post mastectomy- Let's Google it. Accessibility, readability and quality of online information.

INTRODUCTION: This study evaluated the readability, accessibility and quality of information pertaining to breast reconstruction post mastectomy on the Internet in the English language. METHODS: Using the Google© search engine the keywords "Breast reconstruction post mastectomy" were searched for. We analyzed the top 75 sites. The Flesch Reading Ease Score and Gunning Fog Index were calculated to assess readability. Web site quality was assessed objectively using the University of Michigan Consumer Health Web site Evaluation Checklist. Accessibility was determined using an automated accessibility tool. In addition, the country of origin, type of organisation producing the site and presence of Health on the Net (HoN) Certification status was recorded. RESULTS: The Web sites were difficult to read and comprehend. The mean Flesch Reading Ease scores were 55.5. The mean Gunning Fog Index scores was 8.6. The mean Michigan score was 34.8 indicating weak quality of websites. Websites with HoN certification ranked higher in the search results (p = 0.007). Website quality was influenced by organisation type (p < 0.0001) with academic/healthcare, not for profit and government sites having higher Michigan scores. 20% of sites met the minimum accessibility criteria. CONCLUSIONS: Internet information on breast reconstruction post mastectomy and procedures is poorly written and we suggest that Webpages providing information must be made more readable and accessible. We suggest that health professionals should recommend Web sites that are easy to read and contain high-quality surgical information. Medical information on the Internet should be readable, accessible, reliable and of a consistent quality.

Is satisfaction with surgeon a determining factor in patient reported outcomes in breast reconstruction?

BACKGROUND: Patient reported outcomes are increasingly being taken into account in planning health service provision. Few studies have examined how the process of care influences patients' perception of outcome. The aim of the current study was to quantify patient satisfaction with breast reconstruction and to examine the demographic, disease and process-of-care variables that contributed to satisfaction with breasts and overall outcome. METHODS: A cross-sectional study was designed and the BREAST-Q outcomes assessment instrument was used to evaluate patient-reported psychosocial, physical and sexual well-being, as well as satisfaction with breasts, overall outcome and process of care. To identify factors predictive of satisfaction with breasts and overall outcome, the relation between covariates and each of these scales was assessed using linear regression models. RESULTS: Sixty one patients, with a mean age of 50 years, completed the survey. Mean satisfaction with breasts was 59.6% and satisfaction with overall outcome was 73.2%. Satisfaction across health-related quality of life scales ranged from 44.6% for sexual well-being to 74.6% for physical well-being. The mean rating for psychosocial well-being was 67.9%. Satisfaction ratings for surgeon, medical staff and office staff were all over 90%. Satisfaction with plastic surgeon was predictive of satisfaction with outcome and satisfaction with breasts (P = 0.001 and 0.021 respectively). DISCUSSION: The surgeon-patient relationship significantly influences patient reported outcomes in breast reconstruction. Further service development must recognize the need for additional time and personnel to deliver high standard, patient-centered care.

Osteopoikilosis masquerading as osseous metastases in breast cancer.

Osteopoikilosis (OPK) is a rare, congenital bone disorder characterised by multiple round or ovoid radio densities appearing throughout the axial and appendicular skeleton. It is usually an asymptomatic condition diagnosed incidentally on radiological imaging, and may mimic other bone disorders, including osseous metastases. In this case report, we present a patient with lobular breast cancer whose computed tomography findings were thought to be consistent with osseous cancer metastases. Radionuclide bone scintigraphy plays a key role in distinguishing OPK from osteoblastic bone metastases. This case demonstrates the importance of a clinical awareness of OPK to ensure that patients with potentially curable disease are properly diagnosed.

The development of the metabolic syndrome and insulin resistance after adjuvant treatment for breast cancer.

BACKGROUND: Adjuvant breast cancer treatment is associated with a number of adverse physical changes, including weight gain, and therefore may represent a critical period for the development of metabolic disturbance. OBJECTIVE: The aim of this study was to evaluate changes in the presentation of the metabolic syndrome (MetSyn) and insulin resistance from breast cancer surgery to postcompletion of adjuvant treatment. METHODS: Sixty-one participants who had completed metabolic screening, including fasting blood samples and anthropometric measurements, on the morning of breast cancer surgery were recruited. Measures were repeated after completion of adjuvant treatment. Change in the proportion of participants presenting with the MetSyn was evaluated using the related-samples McNemar test, and changes in measures of glucose metabolism (fasting insulin, insulin resistance [homeostatic model assessment index], and glycosylated hemoglobin [HbA1c]) were analyzed using paired t tests. The Kruskal-Wallis test was used to compare differences in changes in metabolic parameters across clinical and lifestyle characteristics. RESULTS: There was a significant (P < .001) increase in fasting insulin (mean [SE] change, 2.73 [0.57] mU/L), homeostatic model assessment index (0.58 [0.14]), and HbA1c level (4.49 [5.63] mmol/mol) from baseline to follow-up along with an increase in the proportion diagnosed with the MetSyn (P = .03). Those with the MetSyn at diagnosis experienced a greater increase in insulin resistance. Premenopausal women experienced greatest increases in HbA1c level. CONCLUSIONS: Results demonstrate the development of significant metabolic dysfunction, characterized by glucose dysmetabolism and MetSyn, after adjuvant treatment for breast cancer. IMPLICATIONS FOR PRACTICE: Interventions to improve the metabolic profile of breast cancer survivors are warranted.

Surgical management of an Irish cohort of BRCA-mutation carriers.

Little information is available regarding the management of BRCA-related breast cancer in Ireland. A cancer genetics programme was initiated in 1992 at our institution to provide counselling and expert management for those with cancers resulting from inherited predisposition. We examined a cohort of BRCA mutation-carriers treated at a single institution over 16 years. A total of 107 women from 57 families were found to be carriers of mutations in BRCA1/2. Bilateral salpingo-oophorectomy was the most common prophylactic surgery performed. Overall survival between BRCA-related and sporadic breast cancer was equivalent. This is the first publication on surgical management of BRCA-mutation carriers in Ireland. It is imperative that those considered likely to harbour a mutation are referred early to a dedicated clinic so that appropriate counselling, testing and subsequent management to reduce the risk of dying from cancer can be undertaken.

The effects of low-frequency endo-anal electrical stimulation on faecal incontinence: a prospective study.

BACKGROUND AND AIMS: Faecal incontinence is a distressing problem that is often not amenable to surgical correction. Chronic low-frequency electrical stimulation of damaged axons is thought to reduce synaptic resistance, increase the size of motor units by axonal sprouting and increase the rate of conduction of the pudendal nerve. The aim of this study was to prospectively evaluate the effect of chronic low-frequency endo-anal electrical stimulation on faecal incontinence using a home-based unit and hospital-supervised therapy. MATERIALS AND METHODS: Forty-eight patients with faecal incontinence completed a prospective randomised trial. Patients were allocated randomly to one of two groups; group 1 was exposed to endo-anal pudendal nerve stimulation daily at home with a portable home unit, group 2 attended the physiotherapy department for endo-anal electrical stimulation under supervision. RESULTS: Continence scores improved significantly after treatment in both groups (p<0.001). Both groups showed improved manometric scores, although only group 1 showed significant improvement in both resting and squeeze pressures (mean total resting pressure 184-224 mmHg, p<0.001; mean total squeeze pressure 253-337 mmHg, p<0.001). This was also reflected by an improvement in quality of life in both groups. CONCLUSIONS: Low-frequency endo-anal electrical stimulation significantly improves continence scores and quality of life in patients with faecal incontinence not amenable to surgical correction. It leads to improved manometric values when carried out on a daily basis with a portable home unit.

Prospective observational cohort study of time saved by prehospital thrombolysis for ST elevation myocardial infarction delivered by paramedics.

OBJECTIVES: To evaluate a system of prehospital thrombolysis, delivered by paramedics, in meeting the national service framework's targets for the management of acute myocardial infarction. DESIGN: Prospective observational cohort study comparing patients with suspected acute myocardial infarction considered for thrombolysis in the prehospital environment with patients treated in hospital. SETTING: The catchment area of a large teaching hospital, including urban and rural areas. PARTICIPANTS: 201 patients presenting concurrently over a 12 month period who had changes to the electrocardiogram that were diagnostic of acute myocardial infarction or who received thrombolysis for suspected acute myocardial infarction. MAIN OUTCOME MEASURES: Time from first medical contact to initiation of thrombolysis (call to needle time), number of patients given thrombolysis appropriately, and all cause mortality in hospital. RESULTS: The median call to needle time for patients treated before arriving in hospital (n=28) was 52 (95% confidence interval 41 to 62) minutes. Patients from similar rural areas who were treated in hospital (n=43) had a median time of 125 (104 to 140) minutes. This represents a median time saved of 73 minutes (P < 0.001). Sixty minutes after medical contact 64% of patients (18/28) treated before arrival in hospital had received thrombolysis; this compares with 4% of patients (2/43) in a cohort from similar areas. Median call to needle time for patients from urban areas (n=107) was 80 (78 to 93) minutes. Myocardial infarction was confirmed in 89% of patients (25/28) who had received prehospital thrombolysis; this compares with 92% (138/150) in the two groups of patients receiving thrombolysis in hospital. CONCLUSIONS: Thrombolysis delivered by paramedics with support from the base hospital can meet the national targets for early thrombolysis. The system has been shown to work well and can be introduced without delay.