NIHR: Breast cancer surgery is safer for older women than has been assumed

NIHR | October 2020 |Breast cancer surgery is safer for older women than has been assumed

Between 2013-2018 over 3000 women aged 70 or over with operable breast cancer were recruited to a NIHR- funded cohort study. The majority (83.4 %) of the women underwent surgery; with researchers tracking their progress for two years. One of the study’s key findings is that no deaths were attributable to surgery for breast cancer. According to the authors of the study, this suggests that surgery for breast cancer in women in this age group is perhaps safer than thought.

This study is part of a wider- Bridging the Age Gaps in Breast Cancer- project which aims to examine the characteristics and outcomes (survival, quality of life and adverse events) of women aged at least 70 years in the UK undergoing surgery for breast cancer.

Researchers found:

  • Fewer than one in five women (19.3%) had an adverse outcome, such as a dangerous blood clot (DVT) or wound pain.
  • a woman’s age predicted what surgery she would receive. The oldest women in the group were twice as likely to have a mastectomy than the youngest women (59.1% vs 29.9%). Younger women were more likely to have breast-conserving surgery, with less breast tissue removed. This may relate to the lack of screening in older women, so cancers tend to be found when they are bigger and women feel a lump.
  • older women were less likely to have lymph glands under the armpit removed (axillary surgery) than younger women (91.4% vs 98.6%). The aim of axillary surgery is to find out if the cancer has spread, and to remove any cancer in the axilla.
  • just 2.8% of the women in this study who had a mastectomy went on to have reconstructive sugery. This compares to one in five (20%) women overall in the UK.
  • quality of life was lower after surgery particularly for those who had more breast tissue removed as in mastectomy.
  • the risk of being unable to carry out some standard day to day tasks was higher after surgery.
Morgan, J. L., George, J., Holmes, G., Martin, C., Reed, M. W., Ward, S., … & Wyld, L. (2020). Breast cancer surgery in older women: outcomes of the Bridging Age Gap in Breast Cancer study. British Journal of Surgery.

Abstract

Background

Breast cancer surgery in older women is variable and sometimes non‐standard owing to concerns about morbidity. Bridging the Age Gap in Breast Cancer is a prospective multicentre cohort study aiming to determine factors influencing treatment selection and outcomes from surgery for older patients with breast cancer.

Methods

Women aged at least 70 years with operable breast cancer were recruited from 57 UK breast units between 2013 and 2018. Associations between patient and tumour characteristics and type of surgery in the breast and axilla were evaluated using univariable and multivariable analyses. Oncological outcomes, adverse events and quality‐of‐life (QoL) outcomes were monitored for 2 years.

Results

Among 3375 women recruited, surgery was performed in 2816 patients, of whom 24 with inadequate data were excluded. Sixty‐two women had bilateral tumours, giving a total of 2854 surgical events. Median age was 76 (range 70–95) years. Breast surgery comprised mastectomy in 1138 and breast‐conserving surgery in 1716 procedures. Axillary surgery comprised axillary lymph node dissection in 575 and sentinel node biopsy in 2203; 76 had no axillary surgery. Age, frailty, dementia and co‐morbidities were predictors of mastectomy. Age, frailty and co‐morbidity were significant predictors of no axillary surgery. The rate of adverse events was moderate, with no 30‐day mortality. Long‐term QoL and functional independence were adversely affected by surgery.

Conclusion

Breast cancer surgery is safe in women aged 70 years or more, with serious adverse events being rare and no mortality. Age, ill health and frailty all influence surgical decision‐making. Surgery has a negative impact on QoL and independence, which must be considered when counselling patients about choices.

Full paper BJS Breast cancer surgery in older women: outcomes of the Bridging Age Gap in Breast Cancer study

Further information on the project is available from the University of Sheffield’s Medical School Bridging the Age Gap in Breast Cancer

Breast Cancer UK: Almost one million women in UK miss vital breast screening due to COVID-19

Breast Cancer UK| September 2020| Almost one million women in UK miss vital breast screening due to COVID-19

Close to a million women in the UK have missed potentially lifesaving NHS breast screening due to COVID-19, the leading UK breast cancer charity has warned on the eve of Breast Cancer Awareness Month.

Breast Cancer Now estimates that around 986,000 women missed their mammograms due to breast screening programmes being paused in March 2020, in a bid to reduce the risk of COVID-19 spreading and to free up emergency resource for the NHS.

Although the charity says screening for breast cancer is now beginning again, it cautions that this varies across the UK, with availability of appointments being significantly reduced to enable social distancing, and the programme has recommenced at different paces across England.

 Breast Cancer Now  Almost one million women in UK miss vital breast screening due to COVID-19

NIHR: International trial shows single-dose radiotherapy as effective for treating breast cancer

National Institute Health Research |August 2020 | International trial shows single-dose radiotherapy as effective for treating breast cancer

A pioneering breast cancer therapy requiring just one shot of radiotherapy rather than conventional weeks-long treatment, has proven to be as effective for most women in treating the disease, finds research funded and supported by NIHR.

Results of the large international randomised trial, published in the BMJ, confirm the long-term effectiveness of Targeted Intraoperative Radiotherapy (TARGIT-IORT): a breast cancer treatment which is increasingly available throughout the world. 

TARGIT-IORT is delivered immediately after lumpectomy (tumour removal), via a small ball-shaped device placed inside the breast, directly where the cancer had been. The single-dose treatment lasts for around 20 to 30 minutes and replaces the need for extra hospital visits, benefiting both patient safety and well-being.

Researchers compared this technique to conventional external beam radiotherapy (EBRT), delivered from outside the body via a linear accelerator radiotherapy machine. This consists of daily treatment sessions, known as fractions, to the whole breast, over three to six weeks. EBRT is given over a few minutes, but requires 15 to 30 hospital visits, which could be a significant distance from where the patient lives.

At the five-year follow up, recurrence risk of localised breast cancer was 2.1% for TARGIT-IORT compared to 0.95% for EBRT showing TARGIT-IORT to be non-inferior to EBRT. There were 14 fewer deaths for the TARGIT-IORT group.

Significantly, at long-term follow up (average 8.6 years, maximum 18.9 years) there was no statistically significant difference found in any of the breast cancer outcomes, and a substantial reduction in deaths from causes other than breast cancer with TARGIT-IORT.

Researchers say they hope the treatment can be made more available to patients (Source: NIHR)

Full news release from NIHR

BMJ (2020)| Long term survival and local control outcomes from single dose targeted intraoperative radiotherapy during lumpectomy (TARGIT-IORT) for early breast cancer: TARGIT-A randomised clinical trial |370|m2836 |

Abstract

Objective To determine whether risk adapted intraoperative radiotherapy, delivered as a single dose during lumpectomy, can effectively replace postoperative whole breast external beam radiotherapy for early breast cancer.

Design Prospective, open label, randomised controlled clinical trial.

Setting 32 centres in 10 countries in the United Kingdom, Europe, Australia, the United States, and Canada.

Participants 2298 women aged 45 years and older with invasive ductal carcinoma up to 3.5 cm in size, cN0-N1, eligible for breast conservation and randomised before lumpectomy (1:1 ratio, blocks stratified by centre) to either risk adapted targeted intraoperative radiotherapy (TARGIT-IORT) or external beam radiotherapy (EBRT).

Interventions Random allocation was to the EBRT arm, which consisted of a standard daily fractionated course (three to six weeks) of whole breast radiotherapy, or the TARGIT-IORT arm. TARGIT-IORT was given immediately after lumpectomy under the same anaesthetic and was the only radiotherapy for most patients (around 80%). TARGIT-IORT was supplemented by EBRT when postoperative histopathology found unsuspected higher risk factors (around 20% of patients).

Main outcome measures Non-inferiority with a margin of 2.5% for the absolute difference between the five year local recurrence rates of the two arms, and long term survival outcomes.

Results Between 24 March 2000 and 25 June 2012, 1140 patients were randomised to TARGIT-IORT and 1158 to EBRT. TARGIT-IORT was non-inferior to EBRT: the local recurrence risk at five year complete follow-up was 2.11% for TARGIT-IORT compared with 0.95% for EBRT (difference 1.16%, 90% confidence interval 0.32 to 1.99). In the first five years, 13 additional local recurrences were reported (24/1140 v 11/1158) but 14 fewer deaths (42/1140 v 56/1158) for TARGIT-IORT compared with EBRT. With long term follow-up (median 8.6 years, maximum 18.90 years, interquartile range 7.0-10.6) no statistically significant difference was found for local recurrence-free survival (hazard ratio 1.13, 95% confidence interval 0.91 to 1.41, P=0.28), mastectomy-free survival (0.96, 0.78 to 1.19, P=0.74), distant disease-free survival (0.88, 0.69 to 1.12, P=0.30), overall survival (0.82, 0.63 to 1.05, P=0.13), and breast cancer mortality (1.12, 0.78 to 1.60, P=0.54). Mortality from other causes was significantly lower (0.59, 0.40 to 0.86, P=0.005).

Conclusion For patients with early breast cancer who met our trial selection criteria, risk adapted immediate single dose TARGIT-IORT during lumpectomy was an effective alternative to EBRT, with comparable long term efficacy for cancer control and lower non-breast cancer mortality. TARGIT-IORT should be discussed with eligible patients when breast conserving surgery is planned.

The research findings are published in the BMJ, available here

Association of Menopausal Hormone Therapy With Breast Cancer Incidence and Mortality During Long-term Follow-up of the Women’s Health Initiative Randomized Clinical Trials

Chlebowski RT, Anderson GL, Aragaki AK, et al. |2020|Association of Menopausal Hormone Therapy With Breast Cancer Incidence and Mortality During Long-term Follow-up of the Women’s Health Initiative Randomized Clinical Trials |JAMA|324 |4| P. 369–380. doi:10.1001/jama.2020.9482

Key Points

Question  What is the association of estrogen plus progestin or estrogen alone with breast cancer incidence and breast cancer mortality?

Findings  In long-term follow up of 2 placebo-controlled randomized clinical trials involving 27 347 postmenopausal women, prior randomized use of conjugated equine estrogen (CEE), compared with placebo, among women with prior hysterectomy was significantly associated with lower risk of breast cancer (annualized incidence, 0.30% vs 0.37%; hazard ratio [HR], 0.78); and breast cancer mortality (annualized mortality, 0.031% vs 0.046%; HR, 0.60), whereas prior randomized use of CEE plus medroxyprogesterone acetate (MPA), compared with placebo, among women with an intact uterus, was significantly associated with higher risk of breast cancer (annualized incidence, 0.45% vs 0.36%; HR, 1.28) and no significant difference in breast cancer mortality (annualized mortality, 0.045% vs 0.035%; HR, 1.35).

Meaning  Among postmenopausal women, prior randomized use of CEE in women with prior hysterectomy was significantly associated with a lower risk of breast cancer incidence and mortality, whereas prior randomized use of CEE plus MPA in women with an intact uterus was significantly associated with a higher risk of breast cancer incidence and no significant difference in breast cancer mortality.

Association of Menopausal Hormone Therapy With Breast Cancer Incidence and Mortality During Long-term Follow-up of the Women’s Health Initiative Randomized Clinical Trials

Case 22-2020: A 62-Year-Old Woman with Early Breast Cancer during the Covid-19 Pandemic #covid19rftlks

Spring, L. M. et al. (2020) |A 62-Year-Old Woman with Early Breast Cancer during the Covid-19 Pandemic| NEJM |DOI: 10.1056/NEJMcpc2002422

Presentation of Case

Dr. Aditya Bardia: A 62-year-old woman was evaluated at this hospital after she had identified a mass in her left breast, confirmed by her physician on physical examination, during the pandemic of coronavirus disease 2019 (Covid-19), the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

The patient, who was of Ashkenazi Jewish ancestry, had no known family history of breast or ovarian cancer. Medical history included asthma and a fibroadenoma in the left breast, for which she had undergone excisional biopsy 30 years earlier. Menarche had occurred at 12 years of age and menopause at 54 years of age; she had not received hormone-replacement therapy.

Physical examination revealed a mass, measuring 3 cm in greatest dimension, in the left breast. No other masses or axillary lymph nodes were palpable. The patient underwent imaging studies in accordance with the American College of Radiology guidelines.1 Both breasts were imaged, since the patient’s last mammogram had been obtained 7 years earlier.



Dr. Gary X. Wang:
 Mammography revealed an irregular mass with spiculated margins underlying the skin marker in the left breast, with imaging characteristics highly suggestive of cancer. Subsequent ultrasound examination revealed a solid, irregular mass in the left breast that measured 3.1 cm by 1.5 cm by 1.2 cm and normal left axillary lymph nodes. Tissue sampling with core-needle biopsy under ultrasonographic guidance was performed.

NICE recommends atezolizumab for treating people with triple negative breast cancer

Improved deal means new treatment for a type of advanced breast cancer can be recommended by NICE

Draft guidance published by NICE recommends atezolizumab for treating people with a type of breast cancer, called triple negative breast cancer, that has spread to other parts of the body.

The positive recommendation follows consultation on NICE’s previous draft guidance which did not recommend atezolizumab. The company has agreed to provide a larger discount to the list price of the drug following a deal with NHS England & NHS Improvement.

Around 2000 people in England have triple negative breast cancer, of whom around 600 people would be eligible for treatment with atezolizumab and nab-paclitaxel.

Full detail at National Institute for Health & Care Excellence

NICE draft guidance recommends new treatment option for people with early breast cancer

NICE  |  May 2020  | NICE draft guidance recommends new treatment option for people with early breast cancer

NICE published draft guidance which recommends trastuzumab emtansine (also called Kadcyla and made by Roche) as an option for some people with HER2-positive early breast cancer.

Around 7000 people diagnosed each year in England with early breast cancer have HER2-positive disease. HER2, which stands for human epidermal growth factor receptor 2, is a protein on the surface of cancer cells which makes them grow and divide.

Trastuzumab emtansine is a type of targeted cancer drug. Trastuzumab attaches to the HER2 receptor allowing the emtansine to go into the cancer cell where it becomes active and kills the cancer cell.

Clinical trial evidence shows that in people who still have some cancer cells remaining after chemotherapy to shrink their tumour and HER2-targeted treatment, trastuzumab emtansine increases the time people remain free of disease compared with trastuzumab alone. It is not known if trastuzumab emtansine increases the length of time people live because the final trial results are not yet available.

NICE NICE draft guidance recommends new treatment option for people with early breast cancer

Breast screening programme

Breast Screening Programme, England 2018-19 | NHS Digital |  30 January 2020

Women between the ages of 50 and 70 are invited for regular breast screening (every three years) under a national programme. Screening is intended to reduce mortality by detecting breast cancer at an early stage when there is a better chance of successful treatment.

This report presents information about the NHS Breast Screening Programme in England in 2018-19 and includes data on women invited for breast screening, coverage, uptake of invitations, outcomes of screening and cancers detected.

The publication also features an online interactive dashboard to complement the existing publication resources.

Full report: Breast Screening Programme England, 2018-19 | NHS Digital

Further detail at NHS Digital

International evaluation of an AI system for breast cancer screening

McKinney, S. M., et al. |2020| International evaluation of an AI system for breast cancer screening| Nature| 577|(7788)| P. 89-94.

An international team of researchers including experts from Imperial College London trained and tested an artificial intelligence (AI) system screening using a simulation of the double-reading process that is used in the UK.  29000 mammography images were used to demonstrate that the AI system was able to correctly identify cancers from the images with a similar degree of accuracy to expert radiologists, and holds the potential to assist clinical staff in practice. 

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The authors of the paper found that the computer algorithm (AI system) maintained non-inferior performance and reduced the workload of the second reader by 88%. This robust assessment of the AI system paves the way for clinical trials to improve the accuracy and efficiency of breast cancer screening (Source: Imperial College London). 

Full press release from Imperial College London Artificial intelligence could help to spot breast cancer

Screening mammography aims to identify breast cancer at earlier stages of the disease, when treatment can be more successful1. Despite the existence of screening programmes worldwide, the interpretation of mammograms is affected by high rates of false positives and false negatives2. Here we present an artificial intelligence (AI) system that is capable of surpassing human experts in breast cancer prediction. To assess its performance in the clinical setting, we curated a large representative dataset from the UK and a large enriched dataset from the USA. We show an absolute reduction of 5.7%and 1.2% (USA and UK) in false positives and 9.4% and 2.7% in false negatives. We provide evidence of the ability of the system to generalize from the UK to the USA. In an independent study of six radiologists, the AI system outperformed all of the human readers: the area under the receiver operating characteristic curve (AUC-ROC) for the AI system was greater than the AUC-ROC for the average radiologist by an absolute margin of 11.5%. We ran a simulation in which the AI system participated in the double-reading process that is used in the UK, and found that the AI system maintained non-inferior performance and reduced the workload of the second reader by 88%. This robust assessment of the AI system paves the way for clinical trials to improve the accuracy and efficiency of breast cancer screening.

Paper: International evaluation of an AI system for breast cancer screening

In the news:

BBC |  AI ‘outperforms’ doctors diagnosing breast cancer

BMJ |  AI system outperforms radiologists in first reading of breast cancer screening, study claims

 

Blood test for breast cancer may be a step closer

NCRI Cancer Research Institute |nd | Clinical Utility of Autoantibodies in Early Detection of Breast Cancer

A team of researchers including experts from the University of Nottingham have developed a blood test which could detect breast cancer up to five years earlier before its clinical presentation. white-plastic-syringe-1164531.jpg

Abstract

Background

Autoantibodies against numbers of tumour-associated antigens (TAAs) were shown to be relevant tumor biomarkers and can be detected up to 5 years before the tumour is overt clinically. Early diagnosis of cancer is paramount to improved survival by enabling treatment prior to cancer spreading, when tumours should be both surgically removable and curable. The NHS in Scotland is currently carrying out a RCT (ECLS) involving 12,000 individuals at high risk of developing lung cancer being randomised to having (or not) an autoantibody ELISA blood test (EarlyCDT-Lung®) – followed by CT scans over 2 years follow-up in those individuals with a positive test – for early lung cancer detection.

We are aiming to develop a blood test enabling the early detection of breast cancer to significantly improve clinical outcome.

Method

In this pilot study, 180 breast cancer matched control samples were screened for the presence of autoantibodies against 67 TAAs which have already been shown to involve in breast cancer pathology. Optimised Protein microarray technology was applied for this study.

Results

The results confirmed our hypothesis that BC induce autoantibodies (AAbs) against different panels of specific tumour associated antigens (TAAs) used in the pilot study. The assay provided cancer/control discrimination through detection of AAbs against TAAs.

Conclusion

We identified antigen panels of sufficient sensitivity and specificity for early detection of BC based upon serum profiling of autoantibody response. This opens the possibility of a blood test for screening and detection of breast cancer.

The research has been recently presented at NCRI Cancer Conference, in Glasgow, Scotland on Sunday 3 November.

Read the story at Science Daily 

OnMedica Blood test for breast cancer may be a step closer

See also:

Nottingham Post Nottingham researchers develop blood test which could detect breast cancer much earlier

The Telegraph Simple blood test could spot breast cancer five years before any symptom