British Society for Echocardiography and British Cardio-Oncology Society guideline for transthoracic echocardiographic assessment of adult cancer patients receiving anthracyclines and/or trastuzumab (2021)

Type of publication:
Journal article

Author(s):
Dobson R.; Ghosh A.K.; Stanway S.; Manisty C.; Ky B.; Marwick T.; Stout M.; Pearce K.; Harkness A.; Steeds R.; Robinson S.; Oxborough D.; Adlam D.; Rana B.; *Ingram T.; Ring L.; Rosen S.; Plummer C.; Harbinson M.; Sharma V.; Lyon A.R.; Augustine D.X.

Citation:
Echo Research and Practice; Mar 2021; vol. 8 (no. 1)

Abstract:
The subspecialty of cardio-oncology aims to reduce cardiovascular morbidity and mortality in patients with cancer or following cancer treatment. Cancer therapy can lead to a variety of cardiovascular complications, including left ventricular systolic dysfunction, pericardial disease, and valvular heart disease. Echocardiography is a key diagnostic imaging tool in the diagnosis and surveillance for many of these complications. The baseline assessment and subsequent surveillance of patients undergoing treatment with anthracyclines and/or human epidermal growth factor (EGF) receptor (HER) 2-positive targeted treatment (e.g. trastuzumab and pertuzumab) form a significant proportion of cardio-oncology patients undergoing echocardiography. This guideline from the British Society of Echocardiography and British Cardio-Oncology Society outlines a protocol for baseline and surveillance echocardiography of patients undergoing treatment with anthracyclines and/or trastuzumab. The methodology for acquisition of images and the advantages and disadvantages of techniques are discussed. Echocardiographic definitions for considering cancer therapeutics-related cardiac dysfunction are also presented.

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Impact of COVID-19 pandemic on the 2WW breast referrals to a district general hospital (2021)

Type of publication:
Conference abstract

Author(s):
*Tokode O.; *Rastall S.; *Wilson M.

Citation:
European Journal of Surgical Oncology; May 2021; vol. 47 (no. 5)

Abstract:
Introduction: Recommendations were issued to the hospital Trusts to configure service delivery to balance cancer care with the safety of the patient and the hospital staff during the COVID-19 pandemic. The public felt the service restrictions might lead to delays in diagnosis and treatment of cancer patients. We compared the management of 2ww breast referrals in our centre between May to July 2019 and 2020. Method(s): We triaged all referrals to face-face consultation or initial telephone consultation during the pandemic. Patients with suspicious symptoms were offered face-face consultation after the telephone triage. Result(s): Overall, breast patients’ referrals fell by 28.3% during the pandemic. 10.2% reduction was noted in May (95% CI 6.73 – 13.59, p<0.001) but a non-significant increase was recorded in June and July. Waiting time reduced by 8.43 days (95% CI -8.88 to -7.98, p< 0.0001). Breast cancer suspicion increased across all age groups in 2020 (+10.4% to + 16.2%). Breast cancer diagnosis rose by 2.0% in 2020 (95% CI 0.19 – 3.92, p=0.030). No cancer was diagnosed among under 29 years. 29.1% of the 522 patients triaged to telephone consultation were discharged, and 70.9% needed face-to-face follow-up. One patient discharged after telephone consultation was later diagnosed with breast cancer. Conclusion(s): COVID-19 pandemic did not lead to a prolonged waiting time or reduced breast cancer diagnosis, but there was an overall reduction in referrals to our breast service.

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Systematic review and metanalyses of prognostic value of circulating tumour cells in early breast cancer (2021)

Type of publication:
Conference abstract

Author(s):
*Mahmood N.

Citation:
European Journal of Surgical Oncology; May 2021; vol. 47 (no. 5)

Abstract:
Background: Prognostic value of circulating tumour cells (CTC) in breast cancer is currently under investigation. This systematic review with Meta-analysis measures the evidence on prognostic relevance of CTC in early breast cancer presented in recent published studies. Method(s): A detailed search was made for published primary studies, those assessed prognostic value of CTC in early breast cancer. Review and quality assessment of 22 included studies were performed and data on CTC status and disease recurrence and death were extracted. Primary outcomes analysed were hazard ratios for disease-free survival (DFS) and overall survival (OS) between the patient groups with positive and negative detection of CTC. Meta-analysis calculated the pooled hazard ratio (HR) with 95% confidence intervals (CIs) as the overall effect measure on DFS and OS using the fixed and random effects models. Result(s): 22 studies enrolling total of 5724 patients were eligible for the systematic review and meta-analysis. Pooled HR for DFS: 2.81 (CI: 2.20-3, 61) and for OS: 2.74 (CI: 2.20-3.41) was found with CTC positive status. Conclusion(s): This systematic review and meta-analysis finds that positive detection of CTC in early breast cancer is a poor prognostic index for disease recurrence and mortality by nearly 3 times.

Presentation of bone tumours: clinical findings and initial management of patients (2021)

Type of publication:
Journal article

Author(s):
*Green N.M.; Abas S.; Sajid S.; Cribb G.L.

Citation:
Orthopaedics & Trauma; Jun 2021; vol. 35 (no. 3); p. 108-114

Abstract:
Bone tumours are uncommon diagnoses and there is often a delay from first presentation to a healthcare professional (HCP) to definitive diagnosis and management. Patients may present to secondary care in a number of ways. Patients may present acutely with pathological (or impending) fractures, patients may present as urgent 2-week referral from primary care or patients may present with incidental findings on radiological investigations. A thorough history and examination is essential, followed by radiological investigations. Common clinical findings include pain, which is usually the main reason for patient presentation to an HCP. Other reasons include limp or loss of function of limb, swelling or lump, or pathological fracture. As part of the work-up, it is important to ask about constitutional symptoms, past history of malignancy and family history of known syndromes. Plain radiographs are vital for diagnosis. The patient’s age is important for the differential diagnosis. The location, morphology and how the tumour is affecting the bone, periosteum and soft tissues are key to the diagnosis. For patients presenting with bone lesions, it is essential to follow the bone sarcoma referral guidelines so that patients are promptly diagnosed and treated.

COVID-19 and the multidisciplinary care of patients with lung cancer: an evidence-based review and commentary (2021)

Type of publication:
Journal article

Author(s):
Round, Thomas; L’Esperance, Veline; Bayly, Joanne; Brain, Kate; Dallas, Lorraine; Edwards, John G; Haswell, Thomas; Hiley, Crispin; Lovell, Natasha; *McAdam, Julia; McCutchan, Grace; Nair, Arjun; Newsom-Davis, Thomas; Sage, Elizabeth K; Navani, Neal

Citation:
British Journal of Cancer; May 2021 [epub ahead of print]

Abstract:
Delivering lung cancer care during the COVID-19 pandemic has posed significant and ongoing challenges. There is a lack of published COVID-19 and lung cancer evidence-based reviews, including for the whole patient pathway. We searched for COVID-19 and lung cancer publications and brought together a multidisciplinary group of stakeholders to review and comment on the evidence and challenges. A rapid review of the literature was undertaken up to 28 October 2020, producing 144 papers, with 113 full texts screened. We focused on new primary data collection (qualitative or quantitative evidence) and excluded case reports, editorials and commentaries. Following exclusions, 15 published papers were included in the review and are summarised. They included one qualitative paper and 14 quantitative studies (surveys or cohort studies), with a total of 2295 lung cancer patients data included (mean study size 153 patients; range 7-803). Review of current evidence and commentary included awareness and help-seeking; lung cancer screening; primary care assessment and referral; diagnosis and treatment in secondary care, including oncology and surgery; patient experience and palliative care. Cross-cutting themes and challenges were identified using qualitative methods for patients, healthcare professionals and service delivery, with a clear need for continued studies to guide evidence-based decision-making.

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Efficacy of Reduced-Intensity Chemotherapy With Oxaliplatin and Capecitabine on Quality of Life and Cancer Control Among Older and Frail Patients With Advanced Gastroesophageal Cancer: The GO2 Phase 3 Randomized Clinical Trial (2021)

Type of publication:
Randomised controlled trial

Author(s):
Hall, Peter S; Swinson, Daniel; Cairns, David A; Waters, Justin S; Petty, Russell; Allmark, Christine; Ruddock, Sharon; Falk, Stephen; Wadsley, Jonathan; Roy, Rajarshi; Tillett, Tania; Nicoll, Jonathan; Cummins, Sebastian; Mano, Joseph; Grumett, Simon; Stokes, Zuzana; Konstantinos-Velios, Kamposioras; *Chatterjee, Anirban; Garcia, Angel; Waddell, Tom; Guptal, Kamalnayan; Maisey, Nick; Khan, Mohammed; Dent, Jo; Lord, Simon; Crossley, Ann; Katona, Eszter; Marshall, Helen; Grabsch, Heike I; Velikova, Galina; Ow, Pei Loo; Handforth, Catherine; Howard, Helen; Seymour, Matthew T; GO2 Trial Investigators

Citation:
JAMA oncology; May 2021; 7(6):869-877

Abstract:
Importance Older and/or frail patients are underrepresented in landmark cancer trials. Tailored research is needed to address this evidence gap. ObjectiveThe GO2 randomized clinical trial sought to optimize chemotherapy dosing in older and/or frail patients with advanced gastroesophageal cancer, and explored baseline geriatric assessment (GA) as a tool for treatment decision-making.Design, Setting, and Participants This multicenter, noninferiority, open-label randomized trial took place at oncology clinics in the United Kingdom with nurse-led geriatric health assessment. Patients were recruited for whom full-dose combination chemotherapy was considered unsuitable because of advanced age and/or frailty.InterventionsThere were 2 randomizations that were performed: CHEMO-INTENSITY compared oxaliplatin/capecitabine at Level A (oxaliplatin 130 mg/m2 on day 1, capecitabine 625 mg/m2 twice daily on days 1-21, on a 21-day cycle), Level B (doses 0.8 times A), or Level C (doses 0.6 times A). Alternatively, if the patient and clinician agreed the indication for chemotherapy was uncertain, the patient could instead enter CHEMO-BSC, comparing Level C vs best supportive care.Main Outcomes and MeasuresFirst, broad noninferiority of the lower doses vs reference (Level A) was assessed using a permissive boundary of 34 days reduction in progression-free survival (PFS) (hazard ratio, HR = 1.34), selected as acceptable by a forum of patients and clinicians. Then, the patient experience was compared using Overall Treatment Utility (OTU), which combines efficacy, toxic effects, quality of life, and patient value/acceptability. For CHEMO-BSC, the main outcome measure was overall survival. Results A total of 514 patients entered CHEMO-INTENSITY, of whom 385 (75%) were men and 299 (58%) were severely frail, with median age 76 years. Noninferior PFS was confirmed for Levels B vs A (HR = 1.09 [95% CI, 0.89-1.32]) and C vs A (HR = 1.10 [95% CI, 0.90-1.33]). Level C produced less toxic effects and better OTU than A or B. No subgroup benefited from higher doses: Level C produced better OTU even in younger or less frail patients. A total of 45 patients entered the CHEMO-BSC randomization: overall survival was nonsignificantly longer with chemotherapy: median 6.1 vs 3.0 months (HR = 0.69 [95% CI, 0.32-1.48], P = .34). In multivariate analysis in 522 patients with all variables available, baseline frailty, quality of life, and neutrophil to lymphocyte ratio were independently associated with OTU, and can be combined in a model to estimate the probability of different outcomes. Conclusions and Relevance This phase 3 randomized clinical trial found that reduced-intensity chemotherapy provided a better patient experience without significantly compromising cancer control and should be considered for older and/or frail patients. Baseline geriatric assessment can help predict the utility of chemotherapy but did not identify a group benefiting from higher-dose treatment. Trial Registrationisrctn.org Identifier: ISRCTN44687907.

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BSE and BCOS Guideline for Transthoracic Echocardiographic Assessment of Adult Cancer Patients Receiving Anthracyclines and/or Trastuzumab (2021)

Type of publication:
Journal article

Author(s):
Dobson R.; Ghosh A.K.; Manisty C.; Ky B.; Marwick T.; Stout M.; Pearce K.; Harkness A.; Steeds R.; Robinson S.; Oxborough D.; Adlam D.; Stanway S.; Rana B.; *Ingram T.; Ring L.; Rosen S.; Lyon A.R.; Plummer C.; Harbinson M.; Sharma V.; Augustine D.X.

Citation:
JACC: CardioOncology; Mar 2021; vol. 3 (no. 1); p. 1-16

Abstract:
The subspecialty of cardio-oncology aims to reduce cardiovascular morbidity and mortality in patients with cancer or following cancer treatment. Cancer therapy can lead to a variety of cardiovascular complications, including left ventricular systolic dysfunction, pericardial disease, and valvular heart disease. Echocardiography is a key diagnostic imaging tool in the diagnosis and surveillance for many of these complications. The baseline assessment and subsequent surveillance of patients undergoing treatment with anthracyclines and/or human epidermal growth factor receptor (HER) 2-positive targeted treatment (e.g., trastuzumab and pertuzumab) form a significant proportion of cardio-oncology patients undergoing echocardiography. This guideline from the British Society of Echocardiography and British Cardio-Oncology Society outlines a protocol for baseline and surveillance echocardiography of patients undergoing treatment with anthracyclines and/or trastuzumab. The methodology for acquisition of images and the advantages and disadvantages of techniques are discussed. Echocardiographic definitions for considering cancer therapeutics-related cardiac dysfunction are also presented.

Link to full-text [open access – no password required]

Objective responses to first-line neoadjuvant carboplatin-paclitaxel regimens for ovarian, fallopian tube, or primary peritoneal carcinoma (ICON8): post-hoc exploratory analysis of a randomised, phase 3 trial (2021)

Type of publication:
Journal article

Author(s):
Morgan R.D.; Jayson G.C.; Clamp A.R.; McNeish I.A.; Krell J.; Cook A.D.; James E.C.; Lord R.; Dark G.; Glasspool R.M.; Parkinson C.; Poole C.J.; Hall M.; Gallardo-Rincon D.; Lockley M.; Essapen S.; Summers J.; Anand A.; *Zachariah A.; Williams S.; Jones R.; Scatchard K.; Walther A.; Kim J.-W.; Sundar S.; Ledermann J.A.

Citation:
The Lancet Oncology; Feb 2021; vol. 22 (no. 2); p. 277-288

Abstract:
Background: Platinum-based neoadjuvant chemotherapy followed by delayed primary surgery (DPS) is an established strategy for women with newly diagnosed, advanced-stage epithelial ovarian cancer. Although this therapeutic approach has been validated in randomised, phase 3 trials, evaluation of response to neoadjuvant chemotherapy using Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST), and cancer antigen 125 (CA125) has not been reported. We describe RECIST and Gynecologic Cancer InterGroup (GCIG) CA125 responses in patients receiving platinum-based neoadjuvant chemotherapy followed by DPS in the ICON8 trial. Method(s): ICON8 was an international, multicentre, randomised, phase 3 trial done across 117 hospitals in the UK, Australia, New Zealand, Mexico, South Korea, and Ireland. The trial included women aged 18 years or older with an Eastern Cooperative Oncology Group performance status of 0-2, life expectancy of more than 12 weeks, and newly diagnosed International Federation of Gynecology and Obstetrics (FIGO; 1988) stage IC-IIA high-grade serous, clear cell, or any poorly differentiated or grade 3 histological subtype, or any FIGO (1988) stage IIB-IV epithelial cancer of the ovary, fallopian tube, or primary peritoneum. Patients were randomly assigned (1:1:1) to receive intravenous carboplatin (area under the curve [AUC]5 or AUC6) and intravenous paclitaxel (175 mg/m2 by body surface area) on day 1 of every 21-day cycle (control group; group 1); intravenous carboplatin (AUC5 or AUC6) on day 1 and intravenous dose-fractionated paclitaxel (80 mg/m2 by body surface area) on days 1, 8, and 15 of every 21-day cycle (group 2); or intravenous dose-fractionated carboplatin (AUC2) and intravenous dose-fractionated paclitaxel (80 mg/m2 by body surface area) on days 1, 8, and 15 of every 21-day cycle (group 3). The maximum number of cycles of chemotherapy permitted was six. Randomisation was done with a minimisation method, and patients were stratified according to GCIG group, disease stage, and timing and outcome of cytoreductive surgery. Patients and clinicians were not masked to group allocation. The scheduling of surgery and use of neoadjuvant chemotherapy were determined by local multidisciplinary case review. In this post-hoc exploratory analysis of ICON8, progression-free survival was analysed using the landmark method and defined as the time interval between the date of pre-surgical planning radiological tumour assessment to the date of investigator-assessed clinical or radiological progression or death, whichever occurred first. This definition is different from the intention-to-treat primary progression-free survival analysis of ICON8, which defined progression-free survival as the time from randomisation to the date of first clinical or radiological progression or death, whichever occurred first. We also compared the extent of surgical cytoreduction with RECIST and GCIG CA125 responses. This post-hoc exploratory analysis includes only women recruited to ICON8 who were planned for neoadjuvant chemotherapy followed by DPS and had RECIST and/or GCIG CA125-evaluable disease. ICON8 is closed for enrolment and follow-up, and registered with ClinicalTrials.gov, NCT01654146. Finding(s): Between June 6, 2011, and Nov 28, 2014, 1566 women were enrolled in ICON8, of whom 779 (50%) were planned for neoadjuvant chemotherapy followed by DPS. Median follow-up was 29.5 months (IQR 15.6-54.3) for the neoadjuvant chemotherapy followed by DPS population. Of 564 women who had RECIST-evaluable disease at trial entry, 348 (62%) had a complete or partial response. Of 727 women who were evaluable by GCIG CA125 criteria at the time of diagnosis, 610 (84%) had a CA125 response. Median progression-free survival was 14.4 months (95% CI 9.2-28.0; 297 events) for patients with a RECIST complete or partial response and 13.3 months (8.1-20.1; 171 events) for those with RECIST stable disease. Median progression-free survival for women with a GCIG CA125 response was 13.8 months (95% CI 8.8-23.4; 544 events) and 9.7 months (5.8-14.5; 111 events) for those without a GCIG CA125 response. Complete cytoreduction (R0) was achieved in 187 (56%) of 335 women with a RECIST complete or partial response and 73 (42%) of 172 women with RECIST stable disease. Complete cytoreduction was achieved in 290 (50%) of 576 women with a GCIG CA125 response and 30 (30%) of 101 women without a GCIG CA125 response. Interpretation(s): The RECIST-defined radiological response rate was lower than that frequently quoted to patients in the clinic. RECIST and GCIG CA125 responses to neoadjuvant chemotherapy for epithelial ovarian cancer should not be used as individual predictive markers to stratify patients who are likely to benefit from DPS, but instead used in conjunction with the patient’s clinical capacity to undergo cytoreductive surgery. A patient should not be denied surgery based solely on the lack of a RECIST or GCIG CA125 response. Funding(s): Cancer Research UK, UK Medical Research Council, Health Research Board in Ireland, Irish Cancer Society, and Cancer Australia.

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Triple Negative Male Breast Cancer (2021)

Type of publication:
Conference abstract

Author(s):
Qavi Q.; Alkistawi F.; Lesi O.; Asaad A.; Abdalla Al-Zawi A.S.; Abraham B.; Kumar S.; Ahmed R.; Barron M.; Arooj *Khan K.; Syed A.; Deniz E.; Abduljawad N.H.; Idaewor P.; Aladili Z.; Rasheed N.; Eldruki S.; Uddin A.

Citation:
European Journal of Surgical Oncology; Feb 2021; vol. 47 (no. 2)

Abstract:
Background: Male breast cancer (MBC) is a rare malignancy, may present at advanced disease stage. Triple negative breast cancer (TNBC) known to have the poorest prognosis of all other histological types of breast cancer. This paper presents a case of 71 years old gentleman diagnosed with TNBC. Material(s) and Method(s): A 71 years old male patient, presented with a right breast lump of a recent history also has chronic kidney disease, gastroesophageal reflux,, and excision of basal cell carcinoma of abdominal wall. Clinically he had a skin dent and apalpable 3cm lump underneath in the right breast axillary tail. Mammogramand breast US showed suspicious lesion in right breast axillary tail in additionto a suspicious lymph node in right axilla. Imaging guided core biopsies weretaken from the breast and axillary abnormalities. The histology revealed grade1 invasive ductal carcinoma NST, ER 0 and PR 0 and HER 2 negative. The Breast Multidisciplinary Team meeting advised for mastectomy and axillary clearance, this has been performed. The postoperative Pathomorphology report revealed 23 mm triple negative invasive ductal carcinoma NST, grade 1with Ki67 10%, T2N1M0. The postoperative MDT recommended annual surveillance with mammogram for 5 years. Result(s): MBC is very rare, it is the cause of 1% of all malignant diseases in men, andcauses < 1% of all breast cancers in both males and females.MBC is diagnosed at an average of 10 years later than the age at which breast cancer is diagnosed in females at 65 years of age.There are some reported risk factors associated with MBC as, cryptorchidism, family history, Klinefelter’s syndrome, infertility and smoking. Also it has been reported that Only 1/3 of male patients who have BRCA1/2 mutation maydevelop malignancy of breast, pancreas and prostate. Similar to female breast cancer, the most histological type of male breast cancer is invasive ductalcarcinoma NST, and the oestrogen hormone receptors expression is greaterthan in females (up to 95%).Male triple negative breast cancer (MTNBC) is associated with aggressivedisease course, late stage of diagnosis, large size of the tumour size, hightumor histological grade, and high rate nodal disease, also is reported more in a younger patients.Mastectomy is the mainstay of surgical treatment and the triple-negative breast cancer generally has a better to chemotherapy than tumours with oestrogen hormone-receptor positive expression. Adjuvant radiotherapy is recommended, however it doesn’t effect the cause-specific survival rate. Conclusion(s): MBC is uncommon entity, accounting for < 1% of all breast cancer diagnosed in both genders and the MTNBC still is rarer, and mastectomy is the mainstay of surgical treatment. in addition to chemotherapy and radiotherapy, however the later doesn’t effect the cause-specific survival rate.

Epidemiology, Incidence and Outcomes from Male breast cancer in Mid and South Essex (2021)

Type of publication:
Conference abstract

Author(s):
Alkistawi F.E.; Qavi Q.; Omotara L.; Asaad A.; Salih A.; Chicken W.; Elamass M.; Cathcart P.; Venkat S.E.; Syed A.; Barron M.; *Khan K.; Deniz E.; Abduljawad N.; Aladili Z.; Ozua P.; Idaewor P.; Uddin A.; Rasheed N.; Abdalla Al-Zawi A.S.

Citation:
European Journal of Surgical Oncology; Feb 2021; vol. 47 (no. 2)

Abstract:
Background: Breast Cancer is the most common cancer in the United Kingdom and the second most common cancer in the world. Male breast cancer (MBC) is rare, but reported to account for <1 % of all breast cancer cases and 1% of all male malignancies. The management protocols for male breast cancer are largely derived from the evidence in female breast cancer management.In this study we analysed all MBC within our region presenting over a 6 year period. We are reporting the incidence, clinico-pathological features, management and outcomes of MBC patient treated in 3 breast centres serving the Mid and South Essex region of England. Material(s) and Method(s): Retrospective multicentre review of all the male breast cancer patients presented between 2014 and 2019, in Basildon Hospital, Broomfield Hospital & Southend Hospital. We identified 44 patients and collected data from their clinical records. Data related to patients’ age, risk factors, histopathology,surgical treatment, adjuvant treatment and survival were analysed. Result(s): Out of 6952 cases of breast cancer diagnosed between 2014 and 2019, 44 cases of male breast cancer were identified which represents 0.63% of all cases. This lies within the international figures of incidence of male breast cancer. The age group ranged between 43 &96 years with higher incidence on the 9th decade of life. Family history was significantly linked to MBC,in our study and it was observed in 31% of cases.Smoking association with male breast cancer needs to be further assessed in a larger study as in our study group only 3 patients were actively smoking, though another 9 were ex-smokers, this gives a total of 25% of cases associated with smoking history.As for female breast cancer, Invasive ductal carcinoma (IDC) is the most common encountered histological subtype (77%), though other histopathologic subtypes were recorded including invasive lobular carcinoma (4.5%), tubular (4.5%), papillary carcinoma (4.5%) Combined IDC & ILC (2.5%) and DCIS (7%).The receptor status is comparable to the reported figures except for the triple negative cancers which showed a higher rate 6.5% compared to less than 1% rate in documented literature. Mastectomy and sentinel node biopsy remains the main line of treatment, though management with hormonal manipulation only was undertaken in 20% of patients due to frailty or metastatic disease. At a median follow-up of 3 years, 11 patients had died, but only 3 deaths were caused by breast cancer, the mortality rate in our cohort was 25%; however the MBC specific mortality in the cohort was only 6.8%. Conclusion(s): Male breast cancer is rare. It maybe associated with late presentation and less favorable outcomes. Public and health professional education is recommended to enable early disease detection. Multi-centre collaboration is suggested to allow access to a larger database for research to determine the risk factors, optimum treatment and outcomes.