Breast cancer

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

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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)

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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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Breast Screening Age Extension; High Cancer Pick up Rate of Small Breast Cancers Amenable to Breast and Axillary Conservation (2019)

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Type of publication:
Conference abstract

Author(s):
*Cielecki L. ; *Burley S.; *Lake B.; *Williams S.; *Appleton D.

Citation:
European Journal of Surgical Oncology; Nov 2019; vol. 45 (no. 11); p. 2212-2213

Abstract:
Background: In 2012, Public Health England (PHE) extended the age range for breast screening up to 73. For screening to be an effective tool, one of the Wilson criteria is to detect disease that could be treated at an early stage. This audit aimed to measure the effectiveness of the upper age screening extension in Shropshire by comparing the cancer diagnosis rate to general screening population, size of cancer, and the ability to perform breast conservation.
Method(s): Retrospective analysis of Breast Screening age extension of women invited to be screened aged 71 to 73 years old in Shropshire. Data included number of women invited, uptake rate, recall rate, cancer diagnosis and surgical treatment.
Result(s): 5517 older women were invited into Shropshire Breast Screening Programme as part of the AgeX trial by PHE since September 2014. 4801 women attended and were screened; 87% uptake rate, which exceeds BSP attendance rate of >80%. 104 women were recalled to assessment (2.1%) which is below BSP standard of <5% recall rate for incident screens. 46.1% (48) of women recalled to assessment were given a cancer diagnosis, this is compared to 30.5% in general screening population. 41.6% of the invasive cancer was <15mm. 95.8% of patients had surgery, with 70.8% of patients having breast and axillary conservation surgery.
Conclusion(s): BSP Standards uptake rate and recall rate have been exceeded by upper age extension. Our experience shows high cancer pick up rate of small cancers with the majority patients able to have breast conserving surgery.

Local experience at DGH shows combination Pertuzumab and Herceptin nearly doubles PCR rate of Neo-adjuvant Chemotherapy (NAC) in HER2 positive breast cancer (2018)

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Type of publication:
Poster presentation

Author(s):
*Blossom Lake, *Donna Appleton, *Abel Zachariah, *Habib Khan, *Kerry Flemming, *Jennifer Neill, *Laura Pettit

Citation:
Presented at BASO: The Association for Cancer Surgery

Link to poster [PDF]

Breast Reconstruction Affects Coping Mechanisms in Breast Cancer Survivors (2019)

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Type of publication:
Journal article

Author(s):
*Lake, Blossom; Fuller, Heidi R; *Rastall, Sarah; *Usman, Tamoor

Citation:
Indian Journal of Surgery; Feb 2019; vol. 81 (no. 1); p. 43-50

Abstract:
Coping strategies used by women with breast cancer are vital for adjustment to their disease. Whilst it is clear that factors such as age at diagnosis, social support and ethnicity can influence coping mechanisms, there is currently no information about whether breast reconstruction changes mechanisms of coping for such patients. The aims of this study, therefore, were to determine how women who have had immediate breast reconstruction and mastectomy cope, compared to those who have mastectomy alone, and whether there are differences in coping mechanisms due to breast reconstruction surgery. This was a retrospective cohort study, using a standardised questionnaire called the Brief Cope Scale. Inclusion criteria was the following: all women
who had immediate breast reconstruction and mastectomy in Shropshire from 2003 to 2014 for ductal carcinoma in situ or node-negative invasive breast cancer. Each patient was matched for year of diagnosis, adjuvant therapy and age to one woman who had mastectomy alone. Two hundred thirty-four questionnaires were sent with a 58% response rate. Significantly more patients from the reconstruction cohort coped by active coping (T value 1.66, P value 0.04) compared to those in the mastectomy alone cohort. In contrast, significantly more patients in the mastectomy alone cohort coped by active venting compared to the reconstruction cohort (T value 1.71, P value 0.04). This study indicates for the first time that breast reconstruction may alter coping mechanisms in breast cancer survivors. Awareness of these coping mechanisms will enable clinicians to provide appropriate, individualised support.

Over 70s breast cancer management: A single institute experience (2018)

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Type of publication:
Conference abstract

Author(s):
Dube M.; Talaat A.; *Rastall S.; *Przyczyna A.; *Usman T.

Citation:
European Journal of Surgical Oncology; Jun 2018; vol. 44 (no. 6); p. 898

Abstract:
Introduction: With increasing life expectancy, awareness and improved referral system more women over the age of 70 (70+) are diagnosed with breast cancer. NICE guidelines recommended standard treatment of breast cancer irrespective of age and decision rather based on co-morbidities and frailty. To review our compliance with NICE guidelines we audited management of breast cancer of 70+ women over a period of five years. Methods: Retrospective case note analysis of 833 70+ women with breast cancer diagnosed from April 2010 to March 2015. Breast MDT recommendations, reason for choice of treatment, co-morbidities and performance status recorded. Results: Out of 2729 breast cancer diagnosis 30% (833) were 70+. The median age was 78. Surgery was the treatment of choice in all five years and is represented by 60% in year one, four and five; 55% in year two; 45% in year three. Primary endocrine treatment was the next treatment of choice among 28% in year one, 23% in year two, 30% in year three, 20% in year four, and 25% in year five. Offer and acceptance adjuvant treatments have increased in year wise analysis. Conclusions: We have noticed a shift towards surgery from primary endocrine therapy in year wise analysis. There has been an increase of number of 70+ patients diagnosed with breast cancer. Inclusion of performance status had improved offer of adjuvant treatment in the last year of the study. More individualised and evidence based management recommended to offer appropriate treatment in this age group.

Breast reconstruction affects coping mechanisms in breast cancer survivors (2017)

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Type of publication:
Journal article

Author(s):
*Lake, B., Fuller, H.R., *Rastall, S, *Usman, T

Citation:
Indian Journal of Surgery, December 2017

Abstract:
Coping strategies used by women with breast cancer are vital for adjustment to their disease. Whilst it is clear that factors such as age at diagnosis, social support and ethnicity can influence coping mechanisms, there is currently no information about whether breast reconstruction changes mechanisms of coping for such patients. The aims of this study, therefore, were to determine how women who have had immediate breast reconstruction and mastectomy cope, compared to those who have mastectomy alone, and whether there are differences in coping mechanisms due to breast reconstruction surgery. This was a retrospective cohort study, using a standardised questionnaire called the Brief Cope Scale. Inclusion criteria was the following: all women who had immediate breast reconstruction and mastectomy in Shropshire from 2003 to 2014 for ductal carcinoma in situ or node-negative invasive breast cancer. Each patient was matched for year of diagnosis, adjuvant therapy and age to one woman who had mastectomy alone. Two hundred thirty-four questionnaires were sent with a 58% response rate. Significantly more patients from the reconstruction cohort coped by active coping (T value 1.66, P value 0.04) compared to those in the mastectomy alone cohort. In contrast, significantly more patients in the mastectomy alone cohort coped by active venting compared to the reconstruction cohort (T value 1.71, P value 0.04). This study indicates for the first time that breast reconstruction may alter coping mechanisms in breast cancer survivors. Awareness of these coping mechanisms will enable clinicians to provide appropriate, individualised support.

The impact of age on the art of mammography and how to adapt accordingly (2017)

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Type of publication:
Journal article

Author(s):
*Lake, B.; *Cielecki, L. ; *Williams, S.; *Worrall, C.; *Metelko, M.

Citation:
Radiography; Nov 2017; vol. 23 (no. 4) e120–e121

Abstract:
Introduction Breast cancer is increasingly a disease of the elderly, and combined with the NHS Breast Screening Extension means that more elderly patients are having mammography. Increasing age can make mammography more technically difficult. This is a technical note detailing the results of a local audit which may be of interest due to potential service implications. Method A retrospective audit of the first year of screening extension of The Shropshire Breast Screening Programme. Aims to collect data on patient demographics and describe the technical adaptations developed in Shropshire. Results Breast screening extension has increased by 2.5 times the number of women aged 70–74 screened, and doubled the overall numbers of women over 70 screened. Significantly more older patients are being screened to present technical challenges to a screening programme. Data was obtained from a month of screening showed that 29% of patients over 70 needed extra time for positioning. Reasons included 22% difficulty in obtaining adequate positioning and 15% needed a relative to aid with consent. Discussion In the Shropshire screening programme different technical adaptations have been developed and are key to ensuring adequate images. These include double appointments, two radiographers, thorough assessment, steeper angles, seated examinations, from-below imaging and pre-planning for subsequent screen. Conclusion Significantly more older women are having breast screening due to the increasing incidence of breast cancer and the Breast Screening Programme extension. Increasing age can significantly increase time taken for adequate imaging and present technical challenges. Development of technical adaptations to art of mammography is key to achieve adequate images.

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