Development of a Novel Patient-Reported Outcome Measure to Assess Symptoms and Impacts of Androgen Deprivation Therapy for Advanced Prostate Cancer.

INTRODUCTION: This qualitative research study was conducted to develop a novel, comprehensive, patient-reported outcome measure (PRO), the "Symptoms and Impacts of Androgen Deprivation Therapy (ADT) for Prostate Cancer" (SIADT-PC), assessing hormonal therapy-related symptoms and their impacts on men with advanced prostate cancer. METHODS: Concept elicitation (CE) interviews were conducted among adult men with prostate cancer to evaluate their experiences with ADT. Based on key symptom and impact concepts mentioned, an initial PRO measure was developed. The draft measure was further assessed in cognitive debriefing (CD) interviews with men with prostate cancer, in which participants reviewed items, response options, and recall periods. Initial item-based psychometric analyses were conducted using interview data. The draft questionnaire was revised on the basis of participant feedback, quantitative psychometric results, and consultation with clinical experts. RESULTS: A total of 21 participants were interviewed (CE concept elicitation, n = 12; CD cognitive debriefing, n = 17; n = 8 completed both). Mean participant age (SD) was 59.7 (8.7) years and 76.2% were white. The de novo SIADT-PC measure consists of 27 items: 11 symptoms (e.g., fatigue, hot flashes, and erectile dysfunction), 2 long-term symptoms (e.g., weight gain), 10 impacts (e.g., impacts on physical activities and relationships), and 4 related to mode of administration (i.e., injection-site reactions). Items were assessed with a 5-point verbal rating scale, with answer choices that capture frequency or severity. CONCLUSIONS: Once fully validated, this de novo measure may be used in clinical studies and clinical practice to assess hormone therapy-related symptoms and impacts, enabling physicians to identify timely and appropriate interventions.

A UK prospective multicentre decision impact, decision conflict and economic evaluation of the 21-gene assay in women with node+ve, hormone receptor+ve, HER2-ve breast cancer.

BACKGROUND: For a tumour profiling test to be of value, it needs to demonstrate that it is changing clinical decisions, improving clinical confidence, and of economic benefit. This trial evaluated the use of the Oncotype DX Breast Recurrence Score® assay against these criteria in 680 women with hormone receptor-positive (HR+), HER2-negative early breast cancer with 1-3 lymph nodes positive (LN+) in the UK National Health Service (NHS). METHODS: Prior to receipt of the Recurrence Score (RS) result, both the physician and the patient were asked to state their preference for or against chemotherapy and their level of confidence on a scale of 1-5. Following receipt of the RS result, the physician and patient were asked to make a final decision regarding chemotherapy and record their post-test level of confidence. RESULTS: Receipt of the RS result led to a 51.5% (95% CI, 47.2-55.8%) reduction in chemotherapy, significantly increased the relative and absolute confidence for both physicians and patients and led to an estimated saving to the NHS of £787 per patient. CONCLUSION: The use of the Oncotype DX assay fulfils the criteria of changing clinical decisions, improving confidence and saving money.

A 10 year service evaluation of the survival of 439 patients with early oestrogen receptor positive breast cancer who underwent initial OncotypeDX ® testing to guide adjuvant chemotherapy decisions.

OBJECTIVE: To explore the long-term outcome of patients who underwent Oncotype DX® testing. The relationship between the RS, adjuvant treatments received, and clinical outcomes across the entire range of RS results are reported. METHODS: 10-year Kaplan-Meier estimates for distant recurrence/BC-specific survival (BCSS) in this cohort. The analysis included 439 patients. The follow-up time ranged from 14 to 142 months. All analyses were performed using the SPSS v20. RESULTS: More than half of patients had low RS (<18) (55.6%) and 15.3% had RS ≥ 31. Chemotherapy use was consistent with the RS with 4.4%, 7.1%, 28.0%, 71.4% and 91.0% receiving adjuvant chemotherapy in patients with RS < 11, 11-17, 18-25, 26-30, and ≥31, respectively. The overall chemotherapy rate was 27.6%. Distant metastasis free survival (DMFS) differed significantly (P < 0.001) between the RS groups with 10 year DMFS rates of 99% (SE +/- 0.01) in the RS<11, 97% (SE +/- 0.03) in the RS 11-17, 97% (SE +/- 0.02) in the RS 18-25, 85% (SE +/- 0.1) in the RS 26-30 and 74% (SE +/- 0.08) in the RS ≥ 31 group. Ten year breast cancer specific survival also differed significantly (P < 0.001) between the RS groups; this risk was 100% (no deaths from breast cancer reported in the first 10 years) in RS < 11, 95% (SE +/- 0.03) in RS 11-17, 94% (SE +/- 0.04) in RS 18-25, 93% (SE +/- 0.07) in RS 26-30, and 79% (SE +/- 0.07) in the RS ≥ 31 group. CONCLUSIONS: Use of Oncotype DX RS does guide the treatment decisions and correlates with the BCSS and disease-free survival for ER positive, Her2 negative, early-stage, node negative breast cancer patients.

Geriatric assessment tool application in treatment recommendations for older women with breast cancer.

INTRODUCTION: Treatment of early breast cancer in older women is usually not guideline concordant owing to lack of routine evaluation of their potential frailty. We assessed the feasibility and impact of a self-administered geriatric assessment on the decision-making process in women aged 65 and above treated in a UK District General Hospital. METHODS: One hundred and one patients, aged 65 and above, with early stage, non-metastatic breast cancer were prospectively recruited between Dec-2018 and March-2021. Patients with metastatic breast cancer, a previous history of cancer and dementia were excluded. All patients had a geriatric assessment with a self-administered questionnaire (mycarg.org). All cases were discussed in the multidisciplinary meeting (MDT) and a pre geriatric assessment recommendations was made, based on the tumour grade, size, node status and receptor status. The findings of the assessment were later discussed in a second meeting and a further recommendation was made based on the geriatric assessment. Any change in the proposed treatment was recorded. Potential factors (age, Body Mass Index, co-morbidities, medications, instrumental activities of daily living, and basic activities of daily living, social support and psychological status) associated with a change in the treatment recommendation were compared using Pearson's Chi square tests for categorized data, and Mann Whitney U test for continuous data. A multivariate logistic regression was performed to test the association between geriatric assessment domains and change in treatment decision. The multivariate model was built using variables which were associated in the bivariate analysis with a p-value< 0.20. RESULTS: Patients aged less than 70 years were more likely to be diagnosed through screening programme as compared to older women (64.4% vs. 35.6%, p = 0.001). Self-administered geriatric assessment identified patients who were requiring assistance in their daily routine activities, and hence, were assessed to have higher morbidity status. A third of patients required assistance in their routine activities, with 18/101 patients requiring significant help during self-care. 90% patients were independent for Activity of Daily Living (ADL) at baseline and 34.76% for Instrumental Activity of Daily Living (IADL). Among the 101 patients evaluated, proposed change in the initial cancer treatment plan was made in 21.8% of patients after the second MDT. Omission of chemotherapy was recommended in 4 patients, omission of radiotherapy in 15 patients and omission of both chemo and radiotherapy in 2 patients. One patient was advised to omit Zolidronic acid, as she was noted to have renal impairment. No patient in this cohort had suggestion for omission of surgery or endocrine therapy. In the bivariate analysis, need for assistance for activities of daily living (ADLs), low physical performance (KPS), polypharmacy (3 or more medications), lack of social support as assessed using the Social Support: Medical Outcomes Study (MOS) Social Support Survey and high BMI (30 or more) all showed significance but on multivariate analysis only polypharmacy was significantly associated with change in the initial cancer treatment plan. CONCLUSIONS: The results of this study of breast cancer patients aged 65 and above suggest that a self-administered geriatric assessment may influence treatment recommendations in a subset of patients. Recommendations that were influenced by the geriatric assessment mainly included those related to the significant morbidity that may have impacted the use of chemotherapy and/or radiotherapy.

Automated Breast Volume Assessment Derived From Digital Breast Tomosynthesis Images Compared to Mastectomy Specimen Weight and Its Applications in Cosmetic Optimisation.

BACKGROUND: Estimating the size and volume of the breast preoperatively is an important step in surgical planning for many breast procedures such as immediate implant-based breast reconstructions and reduction mammoplasties. Breast volume estimation helps in appropriate implant selection preoperatively. OBJECTIVES: The aim of this study was to objectively evaluate the estimation of breast weight by automatic volumetric breast assessment in digital breast tomosynthesis (DBT) using Quantra™ 2.2 Breast Density Assessment Software (Hologic Inc., Marlborough, Massachusetts, United States). METHODS: Breast specimen weight after mastectomy and volume estimated by Quantra software were recorded. RESULTS: Volume assessment obtained from Quantra software showed a high correlation with actual mastectomy specimen weight, with Pearson's correlation coefficients of 0.952. CONCLUSIONS: The automated DBT-derived breast volume using the Quantra software is a simple and practical method to assess breast size and weight preoperatively.

Pooled analysis of prospective European studies assessing the impact of using the 21-gene Recurrence Score assay on clinical decision making in women with oestrogen receptor-positive, human epidermal growth factor receptor 2-negative early-stage breast cancer.

PURPOSE: The 21-gene Recurrence Score assay (Oncotype DX) provides prognostic/predictive information in oestrogen receptor positive (ER+) early breast cancer, but access/reimbursement has been limited in most European countries in the absence of prospective outcome data. Recently, two large prospective studies and a real-life 5-year outcome study have been reported. We performed a pooled analysis of prospective European impact studies to generate robust data on impact of use in different clinical subgroups. METHODS: The analysis included four studies (French, German, Spanish, and British) in ER+ human epidermal growth factor receptor 2-negative breast cancer patients (n = 527). Node-positive patients were excluded. RESULTS: The analysis demonstrated that treatment recommendations changed in 32% of patients post-testing; chemotherapy recommendation rate decreased from 55% to 34%. Change rates in the individual studies ranged from 30% to 37%. The highest change rates were in patients originally recommended chemotherapy and in grade II tumours; there was no subgroup without a treatment recommendation change. Notably, 31% of patients with an intermediate Recurrence Score result had a treatment recommendation change suggesting that testing provides actionable information in this group. With the exception of the German study (where chemotherapy rates remained high [41%] post-testing), between-study variability in treatment recommendations decreased post-testing (chemotherapy: from 36-52% to 26-29%; hormonal therapy: from 48-64% to 71-74%). Physicians' confidence regarding treatment recommendations improved in all the studies after testing. CONCLUSION: Recurrence Score testing led to changes in adjuvant chemotherapy use in approximately a third of patients, to an overall reduced chemotherapy use, and to more homogeneous decision making.

A multicentre validation of Metasin: a molecular assay for the intraoperative assessment of sentinel lymph nodes from breast cancer patients.

AIMS: Treatment strategies for breast cancer continue to evolve. No uniformity exists in the UK for the management of node-positive breast cancer patients. Most centres continue to use conventional histopathology of sampled sentinel lymph nodes (SLNs), which requires delayed axillary clearance in up to 25% of patients. Some use touch imprint cytology or frozen section for intraoperative testing, although both have inherent sensitivity issues. An intraoperative molecular diagnostic approach helps to overcome some of these limitations. The aim of this study was to assess the clinical effectiveness of Metasin, a molecular method for the intraoperative evaluation of SLNs. METHODS AND RESULTS: RNA from 3296 lymph nodes from 1836 patients undergoing SLN assessment was analysed with Metasin. Alternate slices of tissue were examined in parallel by histology. Cases deemed to be discordant were analysed by protein gel electrophoresis. There was concordance between Metasin and histology in 94.1% of cases, with a sensitivity of 92% [95% confidence interval (CI) 88-94%] and a specificity of 97% (95% CI 95-97%). Positive and negative predictive values were 88% and 98%, respectively. Over half of the discordant cases (4.4%) were ascribed to tissue allocation bias (TAB). CONCLUSIONS: Clinical validation of the Metasin assay suggests that it is sufficiently sensitive and specific to make it fit for purpose in the intraoperative setting.

Breast implant extrusion related to Herpesviridae.

INTRODUCTION: We present a case of wound dehiscence in a patient with clinical features of herpes zoster. PRESENTATION OF CASE: A 44 year old woman, with a history of recurrent herpes zoster infection, presented to the accident and emergency department with the extrusion of a left sided tear-drop shaped euro-silicone breast implant from an old surgical scar. A month prior to admission, this patient had developed unilateral crops of vesicles along the surgical scar which was apposing her left infra-mammary fold. This was preceded by fatigue and neuralgia. Histology revealed acute inflammation related to a probable Herpesviridae infection. DISCUSSION: In this report we discuss the first case of a viral infection predisposing to a wound dehiscence occurring in an old surgical scar. CONCLUSION: This case report illustrates the real but rare possibility of recurrent herpes zoster causing gradual thinning of an old surgical scar. This resulted in an extrusion of the underlying breast implant.

Core biopsy as a tool in planning the management of invasive breast cancer.

BACKGROUND: Core biopsy is a method of choice for the triple assessment of breast disease as it can reliably distinguish between benign and malignant tumours, between in-situ and invasive cancers and can be useful to assess oestrogen receptor status. This study was carried out to assess the reliability of core biopsy in predicting the grade and type of cancer accurately as obtaining this information can influence initial therapeutic decisions. PATIENTS AND METHODS: A total of 105 patients who had invasive breast carcinoma diagnosed by core biopsy in year 2001 and who subsequently underwent surgical management were included. The core biopsy results were compared with final histology with the help of kappa statastics. RESULTS: A moderate level of agreement between the predicted grades and final grades was noted (kappa = 0.585). The agreement was good between predicted and final type of tumour (kappa = 0.639). CONCLUSIONS: Core biopsy as a predictor of grade and type has limited use at present. We suggest that initial clinical decisions should not be based on the results of core biopsy.