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.

Ten-Year Results of FAST: A Randomized Controlled Trial of 5-Fraction Whole-Breast Radiotherapy for Early Breast Cancer (2020)

Type of publication:
Randomised controlled trial

Author(s):
Brunt A.M.; Haviland J.S.; Sydenham M.; Bliss J.M.; *Agrawal R.K.; Algurafi H.; Alhasso A.; Barrett-Lee P.; Passant H.; Bliss P.; Bloomfield D.; Tremlett J.; Bowen J.; Donovan E.; Goodman A.; Harnett A.; Hogg M.; Kumar S.; Quigley M.; Sherwin L.; Stewart A.; Syndikus I.; Tsang Y.; Venables K.; Wheatley D.; Yarnold J.R.

Citation:
Journal of Clinical Oncology; Jul 2020 [epub ahead of print]

Abstract:
PURPOSE: Previous studies of hypofractionated adjuvant whole-breast radiotherapy for early breast cancer established a 15- or 16-fraction (fr) regimen as standard. The FAST Trial (CRUKE/04/015) evaluated normal tissue effects (NTE) and disease outcomes after 5-fr regimens. Ten-year results are presented. METHOD(S): Women >= 50 years of age with low-risk invasive breast carcinoma (pT1-2 pN0) were randomly assigned to 50 Gy/25 fr (5 weeks) or 30 or 28.5 Gy in 5 fr of 6.0 or 5.7 Gy (1 week). The primary end point was change in photographic breast appearance at 2 and 5 years; secondary end points were physician assessments of NTE and local tumor control. Odds ratios (ORs) from longitudinal analyses compared regimens. RESULT(S): A total of 915 women were recruited from 18 UK centers (2004-2007). Five-year photographs were available for 615/862 (71%) eligible patients. ORs for change in photographic breast appearance were 1.64 (95% CI, 1.08 to 2.49; P = .019) for 30 Gy and 1.10 (95% CI, 0.70 to 1.71; P = .686) for 28.5 Gy versus 50 Gy. alpha/beta estimate for photographic end point was 2.7 Gy (95% CI, 1.5 to 3.9 Gy), giving a 5-fr schedule of 28 Gy (95% CI, 26 to 30 Gy) estimated to be isoeffective with 50 Gy/25 fr. ORs for any moderate/marked physician-assessed breast NTE (shrinkage, induration, telangiectasia, edema) were 2.12 (95% CI, 1.55 to 2.89; P < .001) for 30 Gy and 1.22 (95% CI, 0.87 to 1.72; P = .248) for 28.5 Gy versus 50 Gy. With 9.9 years median follow-up, 11 ipsilateral breast cancer events (50 Gy: 3; 30 Gy: 4; 28.5 Gy: 4) and 96 deaths (50 Gy: 30; 30 Gy: 33; 28.5 Gy: 33) have occurred. CONCLUSION(S): At 10 years, there was no significant difference in NTE rates after 28.5 Gy/5 fr compared with 50 Gy/25 fr, but NTE were higher after 30 Gy/5 fr. Results confirm the published 3-year findings that a once-weekly 5-fr schedule of whole-breast radiotherapy can be identified that appears to be radiobiologically comparable for NTE to a conventionally fractionated regimen.

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The triple effect of the magseed for localisation of impalpable breast cancer: Significant reduction in re-excision rate, cost saving by reducing further surgery and high patient satisfaction (2020)

Type of publication:
Conference abstract

Author(s):
*Lake B.; *Wilson M.; *Thomas G.; *Williams S.; *Usman T.

Citation:
European Journal of Surgical Oncology; Jun 2020; vol. 46 (no. 6); e12

Abstract:
Introduction: Traditionally impalpable breast cancers have been localised with image guided techniques of wire guidance or ultrasound marking. Magseed is a small magnetic seed which is changing practice of localisation of these cancers. The aim of this study was to see if the change of practice of localisation to Magseed affected patient outcome evaluated by re-excision rate, specimen weight and patient satisfaction. Method(s): A change of practice service evaluation was conducted at the Shrewsbury and Telford Hospital of all patients who had imaged guided wide local excision for impalpable breast cancer from July 2017 to August 2019. Data recorded included tumour demographics, localisation method, size of tumour and specimen weight. Evaluation of localisation methods included re-excision rates, type of further surgery, cost saving in reduction in re-excision, and patient satisfaction. Result(s): 2017/2018 226 Traditional guided WLE were performed. 2018/2019 90 traditional guided WLE, and 106 Magseed WLE were performed. Tumour demographics, size of tumour were similar for localisation methods. The introduction of Magseed in our practice has resulted in a significant reduction in overall re-excision rates from 22.4 to 12%, (z =2.6616 p.00782), and average specimen weight from 40 to 27g (t= -3.2364, P.000716). Cost saving analysis of further surgery showed a saving of 34,457 with 48% less further operations following change of practice. 98% of patients had a very good/excellent experience of Magseed. Conclusion(s): Magseed demonstrates a triple effect on patient outcome with significant reduction in re-excision rate, cost saving by reducing further surgery and high patient satisfaction.

The histopathological correlation of magnetic resonance imaging-identified additional lesions detected in 2nd read breast MRIS (2020)

Type of publication:
Conference abstract

Author(s):
*Aksoy U.; *Barlow E.; *Williams S.; *Lake B.; *Metelko M

Citation:
European Journal of Surgical Oncology; Jun 2020; vol. 46 (no. 6), p. e19

Abstract:
Introduction: Magnetic resonance imaging-identified additional lesions (MRALs) in breast cancer have always been a diagnostic dilemma as they may result in significant delay in management plans and sometimes cause overtreatment. Clinical guidelines for the management of breast cancer in the UK recommend second read MRIs in at least 50% of patients. In this audit project, our aim is to correlate the MRALs reported in 2nd read breast MRIs (2bMRI) with the histopathological outcomes.
Method(s): The patients who were referred to 2bMRIs between July 2018 and August 2019 were retrieved from the archives. 86 consecutive patients (mean age: 54) were included in the audit. First read MRIs were correlated with 2bMRI results and noted as; agreed, a larger lesion (>1cm) or additional foci reported, a smaller lesion or fewer number of additional foci reported. According to histopathology reports MRALs were classified as; proved malignant, benign or not applicable.
Result(s): In 80% (69/86) of the patients the 2bMRI reports agreed with the first and the management did not change. In 20% there was disagreement. Five true positive cases benefited from more extensive surgery. Eight false positive cases ended up with more extensive surgery.
Conclusion(s): Referral indications were in accordance with the guidelines and 5.8% of the patients benefited from the 2bMRIs. However, a significant number of the patients did not benefit from the 2bMRIs. Larger studies are needed to see the true benefit of 2bMRIs as they have the potential to delay the patient pathway and increase anxiety levels of breast cancer patients.

Magseed for Localisation of Impalpable Breast Cancer is associated with High Patient Satisfaction and Lower Re-excision Rates (2019)

Type of publication:
Poster presentation

Author(s):
*L.Deane, *B.Lake, *M.Wilson, *S.Williams, *M.Metelko, *G.Thomas, *S.Lewis, *L.Norwood, *T.Usman

Citation:
Poster presented at the International Cambridge Conference on Breast Cancer Imaging, July 2019

Link to poster [PDF]

Elevated BMI Significantly increases recurrence rate of Breast Cancer; a district general hospital experience (2019)

Type of publication:
Poster presentation

Author(s):
*Blossom Lake, *Albert Mansoor, *Donna Appleton

Citation:
British Journal Surgery; September 2019; Vol 106(S5), p.20 (Poster presentation at Association of Surgeons of Great Britain May 2019)

Abstract:
Aims: Excess body weight has been shown to be a risk factor for breast cancer recurrence. The aim of this study was to evaluate the effect of BMI on recurrence rate of Breast cancer in Shropshire.
Methods: Retrospective analysis of Somerset Database of all new breast cancers diagnosed from January 2012 to December 2012 at the Shrewsbury & Telford NHS Trust. Clinical portal and pre-op database were used to obtain patient demographics including BMI and recurrence rate. Excluded patients from analysis: no surgery performed, or operated at another hospital. Overall recurrence rate, local recurrence, distant metastasis rate and 5 year disease free survival (DFS) were compared for 3 groups: BMI< 25, overweight; 25.1-29.9,and obese; >30.
Results: 498 new breast cancers were diagnosed in 2012, of these 132 were excluded as per criteria. 366 records were analysed; 40 patients had recurrent breast cancer 10.9%. 97.5% of recurrent patients had one or more prognostic factor, size> 3cm, node positive or Grade 3, with no significant difference between BMI groups for adverse prognostic factors. Overall Recurrence rate for BMI <25 was 5.9%, this was significantly higher in BMI> 25, 13.3% p<0.05.BMI Overall Recurrence rate Local recurrence Distant Metastasis rate 5 year DFS<25 5.9% 0.8% 5.9% 94.1% Overweight 14.4% 4.2% 10.2% 85.6% Obese 12.3% 2.3% 11.5% 87.7%
Conclusion: Our experience suggests a significant increase in Breast Cancer recurrence with increasing BMI. Further studies are needed to clarify this and whether methods of reducing BMI may improve disease free survival

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Will Weekly Win for Taxol in the UK: Comparison of Outcomes in Metastatic and locally advanced breast cancer with weekly vs. 3 weekly administration of paclitaxel: A randomised two-arm, prospective, multi-centre, open-label phase III trial comparing the activity and safety of a weekly versus a three-weekly paclitaxel treatment schedule in patients with advanced or metastatic breast cancer (2019)

Type of publication:
Randomised controlled trial

Author(s):
Cameron, D. and Verrill, M.

35 patients from Shrewsbury and Telford Hospital NHS Trust were involved in this trial.

Citation:
Unpublished final report

Abstract:
Background: Paclitaxel has significant anti-tumour activity in patients with metastatic breast cancer who either relapse after, or are resistant, to anthracycline based treatment. In this setting, paclitaxel was routinely given as a 3-hour IV infusion at a dose of 175 mg/m2 every 3 weeks. With the aim of optimising dose and schedule of paclitaxel for patients with metastatic breast cancer, a weekly, dose-dense regimen was developed and used in various settings.
Patients and Methods: A total of 569 patients were recruited into the trial – the first and last patients were randomised on 16 September 2002 and 31 July 2006 respectively. The 2 arms were well balanced for sites of metastases, extent of prior radiotherapy and chemotherapy. The median follow up at May 2012 (when the final analysis was performed) was 94 months = 7 years, 10 months.
Results: Response rates for the weekly regimen were significantly higher than the 3-weekly arm (chi-squared test of association: p = 0.002; responses were weekly CR 3.2%, PR 18.3% vs. 3-weekly CR 1.7% and PR 11.3%). There was no significant difference in either time to progression (log rank test: p = 0.127) or overall survival (log rank test: p = 0.193) between the 2 arms.
Conclusions: In this randomised controlled trial of best scheduling, weekly paclitaxel showed a statistically higher objective response activity compared to 3-weekly schedule but no survival benefit was seen.

Synchronous versus sequential chemo-radiotherapy in patients with early stage breast cancer (SECRAB): A randomised, phase III, trial (2020)

Type of publication:
Randomised controlled trial

Author(s):
Fernando I.N.; Spooner D.; Latief T.N.; Stevens A.; Bowden S.J.; Herring K.; Ahmed I.; Rea D.W.; Brookes C.L.; Marshall A.; Dunn J.; Grieve R.; Poole C.J.; Churn M.; *Agrawal R.K.; Brunt A.M.; Goodman A.; Canney P.; Ritchie D.; Bishop J.

Citation:
Radiotherapy and Oncology; 2020; Vol 24; p. 52-61

Abstract:
Background: The optimal sequence of adjuvant chemotherapy and radiotherapy for breast cancer is unknown. SECRAB assesses whether local control can be improved without increased toxicity.
Method(s): SECRAB was a prospective, open-label, multi-centre, phase III trial comparing synchronous to
sequential chemo-radiotherapy, conducted in 48 UK centres. Patients with invasive, early stage breast cancer were eligible. Randomisation (performed using random permuted block assignment) was stratified by centre, axillary surgery, chemotherapy, and radiotherapy boost. Permitted chemotherapy regimens included CMF and anthracycline-CMF. Synchronous radiotherapy was administered between cycles two and three for CMF or five and six for anthracycline-CMF. Sequential radiotherapy was delivered on chemotherapy completion. Radiotherapy schedules included 40 Gy/15F over three weeks, and 50 Gy/25F over five weeks. The primary outcome was local recurrence at five and ten years, defined as time to local recurrence, and analysed by intention to treat. ClinicalTrials.gov NCT00003893.
Finding(s): Between 02-July-1998 and 25-March-2004, 2297 patients were recruited (1150 synchronous and 1146 sequential). Baseline characteristics were balanced. With 10.2 years median follow-up, the ten-year local recurrence rates were 4.6% and 7.1% in the synchronous and sequential arms respectively (hazard ratio (HR) 0.62; 95% confidence interval (CI): 0.43-0.90; p = 0.012). In a planned sub-group analysis of anthracycline-CMF, the ten-year local recurrence rates difference were 3.5% versus 6.7% respectively (HR 0.48 95% CI: 0.26-0.88; p = 0.018). There was no significant difference in overall or disease-free survival. 24% of patients on the synchronous arm suffered moderate/severe acute skin reactions compared to 15% on the sequential arm (p < 0.0001). There were no significant differences in late adverse effects apart from telangiectasia (p = 0.03). Interpretation(s): Synchronous chemo-radiotherapy significantly improved local recurrence rates. This was delivered with an acceptable increase in acute toxicity. The greatest benefit of synchronous chemo-radiation was in patients treated with anthracycline-CMF.

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6 versus 12 months of adjuvant trastuzumab for HER2-positive early breast cancer (PERSEPHONE): 4-year disease-free survival results of a randomised phase 3 non-inferiority trial (2019)

Type of publication:
Randomised controlled trial

Author(s):
Helena M Earl, Louise Hiller, Anne-Laure Vallier, Shrushma Loi, Karen McAdam, Luke Hughes-Davies, Adrian N Harnett, Mei-Lin Ah-See, Richard Simcock, Daniel Rea, Sanjay Raj, Pamela Woodings, Mark Harries, Donna Howe, Kerry Raynes, Helen B Higgins, Maggie Wilcox, Chris Plummer, Janine Mansi, Ioannis Gounaris, Betania Mahler–Araujo, Elena Provenzano, Anita Chhabra, Jean E Abraham, Carlos Caldas, Peter S Hall, Christopher McCabe, Claire Hulme, David Miles, Andrew M Wardley, David A Cameron, Janet A Dunn on behalf of PERSEPHONE Steering Committee and Trial Investigators.

Randomising consultants at the Royal Shrewsbury Hospital were: *Huzeifa Gadir, *Laura Pettit, *Rajiv Agrawal, and *Sheena Khanduri. Principal investigator at the Royal Shrewsbury Hospital was: *Laura Pettit.

Citation:
Lancet 2019; 393: p. 2599–612

Abstract:
Background: Adjuvant trastuzumab significantly improves outcomes for patients with HER2-positive early breast cancer. The standard treatment duration is 12 months but shorter treatment could provide similar efficacy while reducing toxicities and cost. We aimed to investigate whether 6-month adjuvant trastuzumab treatment is noninferior to the standard 12-month treatment regarding disease-free survival.
Methods: This study is an open-label, randomised phase 3 non-inferiority trial. Patients were recruited from 152 centres in the UK. We randomly assigned patients with HER2-positive early breast cancer, aged 18 years or older, and with a clear indication for chemotherapy, by a computerised minimisation process (1:1), to receive either 6-month or 12-month trastuzumab delivered every 3 weeks intravenously (loading dose of 8 mg/kg followed by maintenance doses of 6 mg/kg) or subcutaneously (600 mg), given in combination with chemotherapy (concurrently or sequentially). The primary endpoint was disease-free survival, analysed by intention to treat, with a non-inferiority margin of 3% for 4-year disease-free survival. Safety was analysed in all patients who received trastuzumab. This trial is registered with EudraCT (number 2006–007018–39), ISRCTN (number 52968807), and ClinicalTrials.gov (number NCT00712140).
Findings: Between Oct 4, 2007, and July 31, 2015, 2045 patients were assigned to 12-month trastuzumab treatment and 2044 to 6-month treatment (one patient was excluded because they were double randomised). Median follow-up was 5·4 years (IQR 3·6–6·7) for both treatment groups, during which a disease-free survival event occurred in 265 (13%) of 2043 patients in the 6-month group and 247 (12%) of 2045 patients in the 12-month group. 4-year disease-free survival was 89·4% (95% CI 87·9–90·7) in the 6-month group and 89·8% (88·3–91·1) in the 12-month group (hazard ratio 1·07 [90% CI 0·93–1·24], non-inferiority p=0·011), showing non-inferiority of the 6-month treatment. 6-month trastuzumab treatment resulted in fewer patients reporting severe adverse events (373 [19%] of 1939 patients vs 459 [24%] of 1894 patients, p=0·0002) or stopping early because of cardiotoxicity (61 [3%] of 1939 patients vs 146 [8%] of 1894 patients, p<0·0001).
Interpretation: We have shown that 6-month trastuzumab treatment is non-inferior to 12-month treatment in patients with HER2-positive early breast cancer, with less cardiotoxicity and fewer severe adverse events. These results support consideration of reduced duration trastuzumab for women at similar risk of recurrence as to those included in the trial.

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