Invasive lobular carcinoma of the breast; clinicopathologic profile and response to neoadjuvant chemotherapy over a 15-year period.

INTRODUCTION: Invasive lobular carcinoma (ILC) accounts for 5-15% of invasive breast cancers. Typical ILC is oestrogen receptor (ER) positive and human epidermal growth factor receptor 2 (HER2) negative. Atypical biomarker profiles (ER- and HER2+, ER+ and HER2+ or triple negative) appear to differ from typical ILCs. This study compared subtypes of ILC in terms of clinical and pathological parameters, and response to neoadjuvant chemotherapy (NACT) according to biomarker profile. METHODS: All patients with ILC treated in a single centre from January 2005 to December 2020 were identified from a prospectively maintained database. Clinicopathologic and outcome data was collected and analysed according to tumour biomarker profile. RESULTS: A total of 582 patients with ILC were treated. Typical ILC was observed in 89.2% (n = 519) and atypical in 10.8% (n = 63). Atypical ILCs were of a higher grade (35% grade 3 vs 9.6% grade 3, p < 0.001). A larger proportion of atypical ILC received NACT (31.7% vs 6.9% p < 0.001). Atypical ILCs showed a greater response to NACT (mean RCB (Residual Cancer Burden Score) 2.46 vs mean RCB 3.41, p = 0.0365), and higher pathological complete response rates (15% vs 0% p = 0.017). Despite this, overall 5-year disease-free survival (DFS) was higher in patients with typical ILC (91% vs 83%, p = 0.001). CONCLUSIONS: Atypical ILCs have distinct characteristics. They are more frequently of a higher grade and demonstrate a superior response to NACT. Despite the latter, atypical ILCs have a worse 5-year DFS which should be taken into consideration in terms of prognostication and may assist patient selection for NACT.

The association between breast density and breast cancer pathological response to neoadjuvant chemotherapy.

PURPOSE: Mammographic Density (MD) refers to the amount of fibroglandular breast tissue present in the breast and is an established risk factor for developing breast cancer. The ability to evaluate treatment response dynamically renders neoadjuvant chemotherapy (NACT) the preferred treatment option in many clinical scenarios. Previous studies have suggested that MD can predict patients likely to achieve a pathological complete response (pCR) to NACT. We aimed to determine whether there is a causal relationship between BI-RADS breast composition categories for breast density at diagnosis and the pCR rate and residual cancer burden score (RCB) by performing a retrospective review on consecutive breast cancer patients who received NACT in a tertiary referral centre from 2015 to 2021. METHODS: The Mann-Whitney U Test was used to test for differences between two independent groups (i.e. those who achieved pCR and those who did not). A binary logistic regression model was used to estimate odds ratios (OR) and corresponding 95% confidence intervals (CI) for an association between the independent variables of molecular subtype, MD, histological grade and FNA positivity and the dependant variable of pCR. Statistical analysis was conducted with SPSS (IBM SPSS for Mac, Version 26.0; IBM Corp). RESULTS: 292 patients were included in the current study. There were 124, 155 and 13 patients in the BI-RADS MD category b, c and d, respectively. There were no patients in the BI-RADS MD category a. The patients with less dense breast composition (MD category b) were significantly older than patients with denser breast composition (MD category c, d) (p = 0.001) and patients who had a denser breast composition (MD category d) were more likely to have ER+ tumours. There was no significant difference in PgR status, HER2 status, pathological complete response (pCR), FNA positivity, or RCB class dependent upon the three MD categories. A binary logistic regression revealed that patients with HER2-enriched breast cancer and triple-negative breast cancer are more likely to achieve pCR with an OR of 3.630 (95% CI 1.360-9.691, p = 0.010) and 2.445 (95% CI 1.131-5.288, p = 0.023), respectively. CONCLUSION: Whilst dense MD was associated with ER positivity and these women were less likely to achieve a pCR, MD did not appear to independently predict pCR post-NACT.

Real-world analysis of clinical and economic impact of 21-gene recurrence score (RS) testing in early-stage breast cancer (ESBC) in Ireland.

PURPOSE: Results from TAILOR-X suggest that up to 70% of hormone receptor-positive (HR+) node-negative (N0) ESBC patients (pts) may avoid chemotherapy (CT) with RS ≤ 25. We assess clinical and economic impacts of RS testing on treatment using real-world data. METHODS: From October 2011 to February 2019, a retrospective, cross-sectional observational study was conducted of HR+ N0 ESBC pts who had RS testing in Ireland. Pts were classified low risk (RS ≤ 25) and high risk (RS > 25). Clinical risk was calculated. Data were collected via electronic patient records. Cost data were supplied by the National Healthcare Pricing Regulatory Authority. RESULTS: 963 pts. Mean age is 56 years. Mean tumour size is 1.7 cm. 114 (11.8%), 635 (66%), 211 (22%), 3 (0.2%) pts had G1, G2, G3 and unknown G, respectively. 796 pts (82.8%) low RS, 159 (16.5%) high RS and 8 pts (0.7%) unknown RS. 263 pts (26%) were aged ≤ 50 at diagnosis; 117 (45%) had RS 0-15, 63 (24.5%) 16-20, 39 (15.3%) 21-25 and 40 (15.2%) RS 26-100. 4 pts (1.5%) had unknown RS. Post-RS testing, 602 pts (62.5%) had a change in CT decision; 593 changed to hormone therapy (HT) alone. In total, 262 pts received CT. Of pts receiving CT; 138 (53%) had RS > 25, 124 (47%) had RS ≤ 25. Of pts aged ≤ 50, 153 (58%) had high clinical risk, of whom 28 had RS 16-20. Assay use achieved a 62.5% change in treatment with 73% of pts avoiding CT. This resulted in savings of €4 million in treatment costs. Deducting assay costs, savings of €1.9 million were achieved. CONCLUSION: Over the 8 years of the study, a 62.5% reduction in CT use was achieved with savings of over €1,900,000.

Value of a 21-gene expression assay on core biopsy to predict neoadjuvant chemotherapy response in breast cancer: systematic review and meta-analysis.

BACKGROUND: A recurrence score based on a 21-gene expression assay predicts the benefit of adjuvant chemotherapy in oestrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer. This systematic review aimed to determine whether the 21-gene expression assay performed on core biopsy at diagnosis predicted pathological complete response (pCR) to neoadjuvant chemotherapy. METHODS: The study was performed according to PRISMA guidelines. Relevant databases were searched to identify studies assessing the value of the 21-gene expression assay recurrence score in predicting response to neoadjuvant chemotherapy in patients with breast cancer. The Newcastle-Ottawa Scale was used to assess the quality of the studies. Results are reported as risk ratio (RR) with 95 per cent confidence interval using the Cochrane-Mantel-Haenszel method for meta-analysis. Sensitivity analyses were carried out where appropriate. RESULTS: Seven studies involving 1744 patients reported the correlation between pretreatment recurrence score and pCR. Of these, 777 patients (44.6 per cent) had a high recurrence score and 967 (55.4 per cent) a low-intermediate score. A pCR was achieved in 94 patients (5.4 per cent). The pCR rate was significantly higher in the group with a high recurrence score than in the group with a low-intermediate score (10.9 versus 1.1 per cent; RR 4.47, 95 per cent c.i. 2.76 to 7.21; P < 0.001). A significant risk difference was observed between the two groups (risk difference 0.10, 0.04 to 0.15; P = 0.001). CONCLUSION: A high recurrence score is associated with higher pCR rates and a low-intermediate recurrence score may indicate chemoresistance. Routine assessment of recurrence score by the 21-gene expression assay on core biopsy might be of value when considering neoadjuvant chemotherapy in patients with ER-positive, HER2-negative breast cancer.

Identifying a Knowledge Deficit among Pediatric and General Practitioner Trainees in Pediatric and Adolescent Gynecology in an Irish Hospital: A Pilot Study.

STUDY OBJECTIVE: We aim to show that there is a knowledge deficit among pediatric and general practitioner (GP) trainees in pediatric and adolescent gynecology (PAG) and that this has implications for increased morbidity in girls. DESIGN, SETTING, PARTICIPANTS, INTERVENTIONS, AND MAIN OUTCOME MEASURES: In October 2019 in a tertiary Irish pediatric hospital 50 junior doctors were approached (of a possible 66) and were surveyed in their knowledge of PAG with a written 21-question questionnaire incorporating 10 topics. RESULTS: Forty candidates participated (n = 31 pediatric and 9 GP). Sixty percent (n = 24/40) incorrectly misdiagnosed vulvovaginitis as candida; 80% (n = 32/40) could not identify labial adhesions; 47.5% (n = 19/40) were unable to define heavy menstrual bleeding. All of the GP trainees (n = 9/9) said they would prescribe the oral contraceptive pill compared with 51.6% (n = 16/31) of pediatric trainees; 52.5% (n = 21/40) did not consider sexually transmitted infection screening; and 70% (n = 28/40) could not identify female genital mutilation. There was generally no statistically significant difference between GP and pediatric trainees. CONCLUSION: A knowledge deficit among trainees was evident in relation to PAG from common to rare, but serious PAG conditions. Misdiagnosis and delayed treatment could lead to increased morbidity for girls. We recommend the introduction of a standardized training program in PAG for trainees.

The approach to an isolated close anterior margin in breast conserving surgery.

INTRODUCTION: Although close radial margins after breast-conserving surgery routinely undergo re-excision, appropriate management of patients with close anterior margins remains a topic of controversy. An increasing body of literature suggests that re-excision of close anterior margins yields low rates of residual malignancy and may only be necessary in selected patients. The aim of this study was to examine the management of close anterior margins after breast conserving surgery in a single institution and to analyse the rate of residual disease in re-excised anterior margins. METHODS: All patients having breast conserving surgery at St Vincent's University Hospital from January 2008 to December 2012 were reviewed retrospectively. Data collected included patient demographics, tumour characteristics, margin positivity, re-excision rates and definitive histology of the re-excision specimens. A close margin was defined as les than 2 mm. RESULTS: A total of 930 patients were included with an average age of 65 years (range 29-94 years). Of these, 121 (13%) had a close anterior margin. Further re-excison of the anterior margin was carried out in 37 patients (30.6%) and a further 16 (13.2%) proceeded to mastectomy. Residual disease was found in 18.5% (7/36) of those who underwent re-excision and 7/16 (43.75%) of those who underwent mastectomy. Overall, 11.57% (14/121) of patients with close anterior margins were subsequently found to have residual disease. CONCLUSION: The low yield of residual disease in re-excised anterior margins specimens supports the concept that routine re-excision of close anterior margins is not necessary. Further research is required to definitively assess its influence on the risk of local recurrence.

Meta-analysis of sentinel lymph node biopsy after neoadjuvant chemotherapy in patients with initial biopsy-proven node-positive breast cancer.

BACKGROUND: Neoadjuvant chemotherapy for breast cancer has the potential to achieve a pathological complete response in up to 40 per cent of patients, converting disease that was initially node-positive to node-negative. This has raised the question of whether sentinel lymph node biopsy could be an alternative to axillary lymph node dissection in these patients. The aim was to undertake a systematic review and meta-analysis of the accuracy and reliability of sentinel lymph node biopsy after neoadjuvant chemotherapy in patients with initial biopsy-proven node-positive breast cancer. METHODS: A literature search was conducted using PubMed, Ovid MEDLINE, Embase and Web of Science databases up to 30 April 2017. Inclusion criteria for studies were pathological confirmation of initial node-positive disease, and sentinel lymph node biopsy performed after neoadjuvant chemotherapy followed by axillary lymph node dissection. RESULTS: A total of 13 studies met the inclusion criteria and were included in the analysis (1921 patients in total). The pooled estimate of identification rate was 90 (95 per cent c.i. 87 to 93) per cent and the false-negative rate was 14 (11 to 17) per cent. In subgroup analysis, the false-negative rate with use of dual mapping was 11 (6 to 15) per cent, compared with 19 (11 to 27) per cent with single mapping. The false-negative rate was 20 (13 to 27) per cent when one node was removed, 12 (5 to 19) per cent with two nodes removed and 4 (0 to 9) per cent with removal of three or more nodes. CONCLUSION: Sentinel lymph node biopsy after neoadjuvant chemotherapy in patients with biopsy-proven node-positive breast cancer is accurate and reliable, but requires careful patient selection and optimal surgical techniques.

Reduced risk of emergency admission for colorectal cancer associated with the introduction of bowel cancer screening across England: a retrospective national cohort study.

AIM: We wanted to find out if roll-out of the bowel cancer screening programme (BCSP) across England was associated with a reduced risk of emergency hospital admission for people presenting with colorectal cancer (CRC) during this period. METHOD: This is a retrospective cohort study of 27 763 incident cases of CRC over a 1-year period during the roll-out of screening across parts of England. The primary outcome was the number of emergency (unplanned) hospital admissions during the diagnostic pathway. The primary exposure was to those living in an area where the BCSP was active at the time of diagnosis. Patients were categorized into three exposure groups: BCSP not active (reference group), BCSP active < 6 months or BCSP active ≥ 6 months. RESULTS: The risk of emergency admission for CRC in England was associated with increasing age, female gender, comorbidity and social deprivation. After adjusting for these factors in logistic regression, the odds ratio (OR) for emergency admission in patients diagnosed ≥ 6 months after the start-up of local screening was 0.83 (CI 0.76-0.90). The magnitude of risk reduction was greatest for cases of screening age (OR 0.75; CI 0.63-0.90) but this effect was apparent also for cases outside the 60-69-year age group (OR 0.85; CI 0.77-0.94). Living in an area with active BCSP conferred no reduction in risk of emergency admission for people diagnosed with oesophagogastric cancer during the same period. CONCLUSION: The start-up of bowel cancer screening in England was associated with a substantial reduction in the risk of emergency admission for CRC in people of all ages. This suggests that the roll-out of the programme had indirect benefits beyond those related directly to participation in screening.

A Positive Node on Ultrasound-Guided Fine Needle Aspiration Predicts Higher Nodal Burden Than a Positive Sentinel Lymph Node Biopsy in Breast Carcinoma.

INTRODUCTION: Axillary status remains an important prognostic indicator in breast cancer. Certain patients with a positive sentinel node (SLNB) may not benefit from axillary clearance (AC). Uncertainty remains if this approach could be applied to patients diagnosed with axillary metastases on ultrasound-guided fine needle aspiration cytology (USFNAC). The aim of this study was to compare nodal burden in patients with positive USFNAC and a positive SLNB. METHODS: A retrospective study was performed involving all BC patients between 2007 and 2014 who had either pre-operative USFNAC or a SLNB. Patient/tumour characteristics and nodal burden were examined in all patients proceeding to AC. RESULTS: 974 patients were eligible for analysis. 439 patients (45 %) had positive USFNAC and 535 (55 %) had a positive SLNB. USFNAC-positive patients were more likely to undergo mastectomy (Chi-square test; p < 0.001), have extra-nodal extension (p < 0.001), be oestrogen receptor negative (p < 0.001) and be HER2 positive (p < 0.001). The median total number of lymph nodes (LNs) excised during AC was higher in the USFNAC group (Mann-Whitney test; 23 vs. 21; p < 0.001). The median total number of involved LNs was 3 (range 1-47) in FNAC-positive patients versus 1 (range 1-37) in SLNB-positive patients (p < 0.001). The median number of involved LNs in level 1 was 3 in FNAC-positive patients versus 1 in SLNB-positive patients (p < 0.001). Within the SLN-positive group, 49 % of the patients had only one involved LN, 28 % had two nodes involved and 23 % had ≥3. In comparison, within the FNAC-positive group only 13 % of the patients had one involved LN, 12 % had two nodes involved and 74 % had ≥3. CONCLUSION: Patients with positive USFNAC have more aggressive clinico-pathological characteristics and higher nodal burden compared to SLNB-positive patients. Currently, the authors advocate that patients not receiving neoadjuvant chemotherapy, with a positive USFNAC, should proceed directly to an axillary ALND.

Role of bone scan in addition to CT in patients with breast cancer selected for systemic staging.

BACKGROUND: The majority of women with breast cancer present with localized disease. The optimal strategy for identifying patients with metastatic disease at diagnosis remains unclear. The aim of this study was to evaluate the additional diagnostic yield from isotope bone scanning when added to CT staging of the thorax, abdomen and pelvis (CT-TAP) in patients with newly diagnosed breast cancer. METHODS: All patients diagnosed with breast cancer who underwent staging CT-TAP and bone scan between 2011 and 2013 were identified from a prospective database of a tertiary referral breast cancer centre that provides a symptomatic and population-based screening breast service. Criteria for staging included: biopsy-proven axillary nodal metastases; planned neoadjuvant chemotherapy or mastectomy; locally advanced or inflammatory breast cancer and symptoms suggestive of metastases. RESULTS: A total of 631 patients underwent staging by CT-TAP and bone scan. Of these, 69 patients (10·9 per cent) had distant metastasis at presentation, with disease confined to a single organ in 49 patients (71 per cent) and 20 (29 per cent) having metastatic deposits in multiple organs. Bone metastasis was the most common site; 39 of 49 patients had bone metastasis alone and 12 had a single isolated metastatic deposit. All but two of these were to the axial skeleton. No preoperative histological factors identified a cohort of patients at risk of metastatic disease. Omission of the bone scan in systemic staging would have resulted in a false-negative rate of 0·8 per cent. CONCLUSION: For patients diagnosed with breast cancer, CT-TAP is a satisfactory stand-alone investigation for systemic staging.

A Rare Case of BRCA2-Associated Breast Cancer in Pregnancy.

A 30-year old woman was referred to our department with symptomatic breast cancer at 35 weeks gestation. Genetic testing revealed a pathogenic BRCA2 mutation. Labour was induced at 38 weeks. Mastectomy and axillary clearance were performed with a view to adjuvant chemotherapy, radiation and hormonal therapy. Multidisciplinary involvement is crucial for management of BRCA-associated breast cancer, especially in the context of pregnancy. Bilateral mastectomy may be indicated given the increased risk of ipsilateral and contralateral breast cancers. Tamoxifen may lower contralateral breast cancer risk in those in whom risk-reducing surgery is not performed.

Phenotypic analysis of familial breast cancer: comparison of BRCAx tumors with BRCA1-, BRCA2-carriers and non-familial breast cancer.

AIMS: Women with inherited pathogenic mutations in the BRCA1 or BRCA2 genes have up to an 85% risk of developing breast cancer in their lifetime. However, only about 20% of familial breast cancer is attributed to mutations in BRCA1 and BRCA2, while a further 5-10% are attributed to mutations in other rare susceptibility genes such as TP53, STK11, PTEN, ATM and CHEK2. Despite extensive efforts to explain the missing heritability of this disease, the majority of familial clustering in breast cancer remains largely unexplained. We aim to analyze the pathology of familial cases of which no pathogenic mutation is yet identified. METHODS: We compared the pathological phenotype of BRCA1/BRCA2 negative familial breast cancer (BRCAx) to BRCA1-positive, BRCA2-positive and sporadic cases without a family history. Age-adjusted analysis is summarized in odd's ratios and confidence intervals for tumor type, grade, lymph node, ER and HER2 status. RESULTS: We found non-familial cases to be more likely to be ER positive (P = 0.041) as compared with BRCAx tumors. More cases of lobular carcinoma were found with BRCAx as compared to BRCA1 tumors (P = 0.05). After multivariate logistic regression analysis, BRCAx tumors are more likely ER positive (P = 0.001) and HER2 positive (P = 0.047) in comparison to BRCA1. Conversely, BRCAx cases are less likely to be ER positive (P = 0.02) but more likely to be HER2 positive (P = 0.021) as compared with BRCA2 tumors. CONCLUSION: Our findings suggest that BRCA1, BRCA2 and BRCAx tumors differ in phenotype from non-familial and familial BRCA1-positive and BRCA2-positive tumors. Further studies will need to be performed in this important population in order to develop strategies for early detection and prevention.

A comparison of clinical-pathological characteristics between symptomatic and interval breast cancer.

BACKGROUND: An association between interval breast cancers (cancer detected after a normal mammogram and before the next scheduled mammogram) and tumour aggressiveness has been postulated which may reflect their relatively poor overall prognosis. The aim of this study was to evaluate known prognostic features of screen detected breast cancers compared to interval breast cancers. METHODS: Patients diagnosed with breast cancer between January 2010 and 2013 at a single unit of the National Breast Screening Program (NBSP) in Ireland and those between the ages of 50 and 65 diagnosed at a symptomatic breast clinic were included in the study. Patients who had not had a screening mammogram within the proceeding two years or had a previous history of breast cancer were excluded. Data were retrospectively collected on patient demographics, tumour type, grade, hormone receptor status and stage of disease at presentation. RESULTS: There were 915 patients included in the study, with 92% (n = 844) diagnosed through the NBSP. Ductal carcinoma in-situ accounted for 19% (n = 160) of screen-detected breast cancers but only 2.8% of interval cancers (p < 0.05). The most common type of invasive cancer was invasive ductal carcinoma. Tumour grade was significantly higher in interval breast cancers (p < 0.05). Interval cancers were identified at a significantly higher stage (Stage 1 versus 2; p < 0.001) than screen-detected cancers. Interval breast cancers were less likely to be ER positive (76% versus 81%; p < 0.05) and significantly more likely to over-express HER2 (20% vs 10%, p < 0.05) than screen-detected cancers. CONCLUSION: This study highlights the fact that interval cancers appear to have a number of adverse prognostic markers for overall breast cancer survival when compared to women with screen-detected breast cancers. Interval cancers were more likely to be invasive, of a higher grade and stage and with a greater predominance of HER2 and triple negative molecular subtypes. Therefore this heterogeneous group of tumours may be biologically more aggressive and account disproportionately to overall breast cancer mortality.

Axillary nodal burden in primary breast cancer patients with positive pre-operative ultrasound guided fine needle aspiration cytology: management in the era of ACOSOG Z011.

INTRODUCTION: Recent years have seen a dramatic shift to more conservative management of the axilla in patients with a positive sentinel lymph node biopsy (SLNB). Identification of nodal disease with positive pre-operative ultrasound guided axillary fine needle aspiration cytology (AUS/FNAC) may represent a higher axillary disease burden mandating an axillary clearance and thus an upfront SLNB may be avoided. The aims of this study were to quantify nodal burden in patients with positive pre-operative AUS/FNAC and identify patients who may have been able to avoid an axillary clearance (ALND) based on ACOSOG Z011 criteria. METHODS: A retrospective review of a prospectively maintained database identified patients with positive pre-operative AUS/FNAC between 2007 and 2012. Core biopsies were excluded. Demographic and tumour characteristics were analysed. Eligibility for ACOSOG Z011 criteria was assessed and patients who may have avoided ALND were identified. RESULTS: 432 patients were identified with positive AUS/FNAC. 85 patients were excluded leaving 347 for analysis. Median age was 56 years (22-87), median tumour size was 25 mm (1.5 mm-150 mm) and median tumour pathology was grade 3 (50%) and invasive ductal carcinoma (82%). Median number of nodes removed at ALND was 23 (1-55) with a median number of positive nodes being 4 (1-47). 134 (39%) patients had ≤2 positive nodes identified on ALND making them eligible for the ACOSOG Z011 study. When other ACOSOG Z011 exclusion factors were applied only 27 (7.8%) patients may have avoided ALND. CONCLUSIONS: Nodal positivity on AUS/FNAC is associated with higher axillary disease burden. Few patients would satisfy ACOSOG/Z011 criteria and avoid ALND making an upfront SLNB unnecessary.

The 5-year outcome of patients having incomplete colonoscopy.

AIM: Incomplete colonoscopy indicated for the detection of neoplasia occurs in 2-23% of patients, but there is little information on the long-term outcome of such patients. METHOD: All patients who underwent colonoscopy over 5 years at the Royal Liverpool University Hospital with a follow-up of up to 5 years were identified. RESULTS: The risk of colorectal cancer (CRC) was 2.9% (312/10 580) for all patients undergoing colonoscopy. For a failed colonoscopy, the risk was five-fold higher [14.3% (99/693)]. The mean age of the patients was 61 years and 58% were female. Following incomplete colonoscopy the risk of finding additional CRC, advanced colonic neoplasia and extracolonic neoplasia on subsequent investigation was 6.2%, 3.2% and 1.9%. The diagnostic yield on subsequent investigation for CRC or colonic polyps was 7% for repeat colonoscopy, 13.4% for computed tomography colonography, 10.3% for standard computed tomography and 1.8% for barium enema. In the 363 patients who were not offered a subsequent investigation, there was no further instance of CRC or CRC-related mortality over a 36-month period. CONCLUSION: Although the risk of CRC is higher in patients who have had a failed colonoscopy, a protocol approach of subsequent investigation should not replace clinical assessment on whether another test is necessary in the light of the good outcome of patients who were not subsequently investigated.

Optimising faecal occult blood screening:retrospective analysis of NHS Bowel Cancer Screening data to improve the screening algorithm.

BACKGROUND: Colorectal neoplasia causes bleeding, enabling detection using Faecal Occult Blood tests (FOBt). The National Health Service (NHS) Bowel Cancer Screening Programme (BCSP) guaiac-based FOBt (gFOBt) kits contain six sample windows (or 'spots') and each kit returns either a positive, unclear or negative result. Test kits with five or six positive windows are termed 'abnormal' and the subject is referred for further investigation, usually colonoscopy. If 1-4 windows are positive, the result is initially 'unclear' and up to two further kits are submitted, further positivity leads to colonoscopy ('weak positive'). If no further blood is detected, the test is deemed 'normal' and subjects are tested again in 2 years' time. We studied the association between spot positivity % (SP%) and neoplasia. METHODS: Subjects in the Southern Hub completing the first of two consecutive episodes between April 2009 and March 2011 were studied. Each episode included up to three kits and a maximum of 18 windows (spots). For each positivity combination, the percentage of positive spots out of the total number of spots completed by an individual in a single-screening episode was derived and named 'SP%'. Fifty-five combinations of SP can occur if the position of positive/negative spots on the same test card is ignored.The proportion of individuals for whom neoplasia was identified in Episode 2 was derived for each of the 55 spot combinations. In addition, the Episode 1 spot pattern was analysed for subjects with cancer detected in Episode 2. RESULTS: During Episode 2, 284,261 subjects completed gFOBT screening and colonoscopies were performed on 3891 (1.4%) subjects. At colonoscopy, cancer was detected in 7.4% (n=286) and a further 39.8% (n=1550) had adenomas. Cancer was detected in 21.3% of subjects with an abnormal first kit (five or six positive spots) and in 5.9% of those with a weak positive test result.The proportion of cancers detected was positively correlated with SP%, with an R(2) correlation (linear) of 0.89. As the SP% increased from 11 to 100%, so the colorectal cancer (CRC) detection rate increased from 4 to 25%. At the lower SP%s, from 11to 25%, the CRC risk was relatively static at ~4%. Above an SP% of 25%, every 10-percentage points increase in the SP%, was associated with an increase in cancer detection of 2.5%. CONCLUSIONS: This study demonstrated a strong correlation between SP% and cancer detection within the NHS BCSP. At the population level, subjects' cancer risk ranged from 4 to 25% and correlated with the gFOBt spot pattern.Some subjects with an SP% of 11% proceed to colonoscopy, whereas others with an SP% of 22% do not. Colonoscopy on patients with four positive spots in kit 1 (SP% 22%) would, we estimate, detect cancer in ~4% of cases and increase overall colonoscopy volume by 6%. This study also demonstrated how screening programme data could be used to guide its ongoing implementation and inform other programmes.

Postmastectomy radiotherapy: indications and implications.

BACKGROUND: Although breast conservation surgery, when combined with radiotherapy, has been shown to provide excellent locoregional control for breast cancer, approximately one third of women with breast cancer require mastectomy. Many of these women are offered immediate reconstruction. Postmastectomy radiotherapy (PMRT) is indicated in some cases, but is associated with side-effects, including its impact on the reconstructed breast. OBJECTIVE: To review the pertinent issues surrounding PMRT, including patient selection for radiotherapy and the effect of radiotherapy on reconstructive decisions. METHODS: A literature review was performed using the Medline database. CONCLUSIONS: PMRT is indicated in patients who are deemed to have a high risk of loco-regional recurrence. Although PMRT is strongly recommended for patients with four or more positive lymphnodes, other indications for PMRT remain controversial. Immediate reconstruction post mastectomy has been shown to have favorable outcomes. However, PMRT may increase the need for revision surgery post immediate reconstruction. There are few randomized trials looking at these key issues, and the evidence is largely derived from observational retrospective studies. Patients should be carefully counseled before a decision is made to proceed with immediate reconstruction, where there is a high chance that PMRT may be indicated.

Management of large bowel obstruction with self-expanding metal stents. A multicentre retrospective study of factors determining outcome.

AIM: UK cancer guidelines recommend patients with colonic obstruction due to suspected malignancy be considered for stenting with a self-expanding metal stent (SEMS). Considerable variation in practice exists due to a lack of expertise, technical difficulties and other, as yet ill-defined features. This retrospective multi-centre study aims to determine the outcome following colonic stenting for large bowel obstruction and identify factors associated with successful intervention. METHOD: A regional programme of colonic stenting for large bowel obstruction, in five UK centres from 2005 to 2010 was evaluated for outcome including technical and clinical success, survival, complications and reoperation. RESULTS: A SEMS was inserted in 334 patients, including 264 (79.0%) for palliation and 52 (15.6%) as a bridge to surgery. Technical success was achieved in 292 (87.4%) patients, with 46 (13.8%) experiencing a complication or technical failure. Reoperation was required in 39 (14.8%) patients stented for palliation of colorectal cancer of whom 16 (6.1%) subsequently required a colostomy. A one-stage primary anastomosis was achieved in 35 (67.3%) of the 52 patients undergoing stenting as a bridge to resection. Technical success did not vary by indication or site of obstruction (P = 0.60) but was higher for operators who had performed more than 10 procedures (OR 3.34, P = 0.001). ASA grade ≥3 predicted a worse clinical outcome (OR 0.43, P = 0.04). The through-the-scope (TTS) endoscopy technique was more successful than radiological placement alone (90.3% vs 74.8%, P < 0.001). CONCLUSION: Experienced operators using a TTS technique achieved a better outcome for the emergency management of large bowel obstruction. Older, sicker patients and those with extracolonic and benign strictures fared less well.