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1.
Psychooncology ; 33(1): e6294, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38282220

ABSTRACT

OBJECTIVE: There is variation in practice in the treatment of older women with breast cancer. International guidelines highlight the importance of patient autonomy in treatment decision-making. The aim of this study is to identify factors which influence decision-making in older women with operable breast cancer, which will enable us to further understand how to support these patients. METHODS: Systematic review in accordance with the PRISMA guidelines was performed to identify factors which influence treatment decision-making in older women with operable breast cancer. Medline, Web of Science and SCOPUS were searched. RESULTS: The search yielded 5840 results; 13 articles met the inclusion criteria and reported on a total of 1118 women. Thematic analysis identified three key themes in which decision-making factors could be categorised. These were healthcare-related factors, patient-related factors and impact of treatment. Healthcare-related factors included communication with clinicians and provision of information. Patient-related factors were age, pre-existing knowledge, preconceptions of breast cancer and treatment, decision-making style and co-morbidities. The impact of treatment considerations included body image and effect on quality of life. Decision-making style was frequently reported; older women did not demonstrate one preferred style. CONCLUSIONS: The findings have highlighted the complex interplay of factors which influence how older women make breast cancer treatment-decisions. Clinicians should have an awareness of the factors highlighted to maximise their ability to provide support and personalised care to older women with breast cancer whilst treatment decisions are made.


Subject(s)
Breast Neoplasms , Decision Making , Female , Humans , Aged , Quality of Life , Breast Neoplasms/surgery , Communication
2.
Br J Surg ; 111(1)2024 Jan 03.
Article in English | MEDLINE | ID: mdl-37930678

ABSTRACT

BACKGROUND: The aim of this multicentre prospective audit was to describe the current practice in the management of mastitis and breast abscesses in the UK and Ireland, with a specific focus on rates of surgical intervention. METHODS: This audit was conducted in two phases from August 2020 to August 2021; a phase 1 practice survey and a phase 2 prospective audit. Primary outcome measurements for phase 2 included patient management pathway characteristics and treatment type (medical/radiological/surgical). RESULTS: A total of 69 hospitals participated in phase 2 (1312 patients). The key findings were a high overall rate of incision and drainage (21.0 per cent) and a lower than anticipated proportion of ultrasound-guided aspiration of breast abscesses (61.0 per cent). Significant variations were observed regarding the rate of incision and drainage (range 0-100 per cent; P < 0.001) and the rate of needle aspiration (range 12.5-100 per cent; P < 0.001) between individual units. Overall, 22.5 per cent of patients were admitted for inpatient treatment, out of whom which 72.9 per cent were commenced on intravenous antibiotics. The odds of undergoing incision and drainage for a breast abscess or being admitted for inpatient treatment were significantly higher if patients presented at the weekend compared with a weekday (P ≤ 0.023). Breast specialists reviewed 40.9 per cent of all patients directly, despite the majority of patients (74.2 per cent) presenting within working hours on weekdays. CONCLUSIONS: Variation in practice exists in the management of mastitis and breast abscesses, with high rates of incision and drainage in certain regions of the UK. There is an urgent need for a national best-practice toolbox to minimize practice variation and standardize patient care.


Mastitis and breast abscess is a painful infection of the breast. It is an extremely common breast problem. One in three women can get this condition at some stage in their life. To treat a breast abscess, the pus inside should be drained out of the body. This can be done either by cutting into the breast using surgery or by inserting a fine needle using an ultrasonography scan (which uses ultrasound). Fine-needle drainage has the benefit that it does not require admission to hospital. Surgery can cause the breast to look misshapen. It is unknown which method is used more often in the UK and Ireland. The aim of this study was to describe how mastitis and breast abscesses are treated in the UK and Ireland. This study involved a survey of practice (phase 1) and collection of data, which are routinely recorded for these patients (phase 2). This study involved 69 hospitals and 1312 patient records. One in five women had an operation for a breast abscess. This was higher than expected. Six in 10 women had a pus drainage using a fine needle. The chance of having an operation depended on the hospital. Women that came to hospital at the weekend were almost twice as likely to have an operation. One in five women were admitted to hospital. The chances of that more than doubled if a woman came to hospital at the weekend. There are differences in treatment of mastitis and breast abscesses across the UK and Ireland. Changes need to be put in place to make access to treatment more equal.


Subject(s)
Breast Diseases , Mastitis , Female , Humans , Abscess/surgery , Breast Diseases/surgery , Ireland/epidemiology , Mastitis/therapy , Drainage , United Kingdom/epidemiology
3.
Cancers (Basel) ; 15(19)2023 Sep 28.
Article in English | MEDLINE | ID: mdl-37835476

ABSTRACT

Cancer is a disease associated with ageing. Managing cancer in older adults may prove challenging owing to pre-existing frailty, comorbidity, and wider holistic needs, as well as the unclear benefits and harms of standard treatment options. With the ongoing advances in oncology and the increasing complexity of treating older adults with cancer, the geriatric oncology field must be a priority for healthcare systems in education, research, and clinical practice. However, geriatric oncology is currently not formally taught in undergraduate education or postgraduate training programmes in the United Kingdom (UK). In this commentary, we outline the landscape of geriatric oncology undergraduate education and postgraduate training for UK doctors. We highlight current challenges and opportunities and provide practical recommendations for better preparing the medical workforce to meet the needs of the growing population of older adults with cancer. This includes key outcomes to be considered for inclusion within undergraduate and postgraduate curricula.

4.
Curr Oncol ; 30(9): 8294-8309, 2023 09 07.
Article in English | MEDLINE | ID: mdl-37754517

ABSTRACT

BACKGROUND: A previous systematic review by our team (2012) undertook comprehensive geriatric assessment (CGA) in breast cancer and concluded there was not sufficient evidence to instate CGA as mandatory practice. SIOG/EUSOMA guidelines published in 2021 advocate the use of CGA in breast cancer patients. The aim is to perform an updated systematic review of the literature. METHODS: A systematic review of studies published between 2012 and 2022 that assessed the use of CGA in breast cancer was performed on Cochrane, PubMed and Embase. RESULTS: A total of 18 articles including 4734 patients with breast cancer were identified. The studies covered four themes for use of CGA in breast cancer: (1) to determine factors influencing survival (2) as an adjunct to treatment decision-making (3) to measure quality of life, and (4) to determine which tools should be included. There was evidence to support the use of CGA in themes 1-3; however, it is uncertain which assessment tools are best to use (theme 4). CONCLUSIONS: CGA can be used to determine factors affecting survival and quality of life in breast cancer patients and can therefore be used to aid treatment decision-making. Further work is required to determine gold standard CGA.


Subject(s)
Breast Neoplasms , Humans , Female , Aged , Breast Neoplasms/therapy , Geriatric Assessment , Quality of Life , Uncertainty
5.
Br J Surg ; 110(10): 1309-1315, 2023 09 06.
Article in English | MEDLINE | ID: mdl-37310128

ABSTRACT

BACKGROUND: Oncoplastic procedures allow excision of larger breast tumours, or unfavourable tumour/breast ratio lesions while achieving a good cosmetic outcome. This increases the pool of patients eligible for breast conservation over mastectomy, reducing the need for more extensive surgery in older women and potentially improving their quality of life. Nonetheless, studies to date suggest a poor uptake of oncoplastic breast surgery in the older group. This review aimed to establish whether a disparity in uptake of oncoplastic breast surgery exists between older and younger women, and to explore the underlying reasons for this. METHODS: A literature search was conducted on 17 January 2022 using MEDLINE and Embase. Eligible studies comprised full-text articles of patients who underwent oncoplastic breast surgery for primary invasive breast cancer, and included those aged at least 65 years. RESULTS: Ten published studies were identified. One study was ranked as providing level 2 evidence, and the remainder were level 3. A total of 567 women underwent oncoplastic breast surgery for primary breast cancer, of whom only 61 (10.8 per cent) were aged 65 years or older. None of the studies directly compared younger with older women, or explored the underlying factors contributing to this discrepancy in uptake. CONCLUSION: This review has demonstrated a lower uptake of oncoplastic breast surgery in older compared with younger women. Given the increasing number of older women living with breast cancer who may be eligible for breast-conserving surgery, further research into this area is required.


Subject(s)
Breast Neoplasms , Mammaplasty , Female , Humans , Aged , Mastectomy , Breast Neoplasms/surgery , Quality of Life , Treatment Outcome , Mastectomy, Segmental/methods , Mammaplasty/methods
6.
Adv Ther ; 40(6): 2820-2835, 2023 06.
Article in English | MEDLINE | ID: mdl-37118159

ABSTRACT

INTRODUCTION: Breast cancer in older women tends to have more favourable biology, compared to younger women. Androgen receptor (AR) is significant for breast tumour carcinogenesis; however, the role of AR in older women has not been fully explored. METHODS: Surgical specimens were obtained from an existing series of 1758 older women (≥ 70 years) with primary breast cancer, treated in a single institution with long-term (≥ 37 years) follow-up. As part of previous work, it was possible to construct good quality tissue microarrays (TMAs) in 575 surgical specimens and a panel of 24 biomarkers was measured by immunohistochemistry (IHC) in these TMAs. AR positivity was assessed by IHC and defined as H-score ≥ 40. The relationship between AR in this cohort was compared to an equivalent group of younger women (< 70 years, n = 1708); the panel of 24 biomarkers and breast cancer specific survival (BCSS) in the older cohort. RESULTS: AR was assessed in 509 samples. Overall, 59% of the older women cohort had positive expression of AR, compared to 63% in the younger cohort. AR positivity (regardless of age) was associated with smaller size of tumour, lower grade of tumour, lower tubule formation, lower nuclear polymorphism and lower mitotic frequency. AR positivity was associated with positive expression of oestrogen receptor (ER), progesterone receptor (PR), breast cancer gene 1 (BRCA1), cytokeratin (CK) 7/8, CK18, CK19, B cell lymphoma (Bcl)2 and Mucin 1 (Muc1) expression. Conversely, AR-positive expression was associated with negative expression of human epidermal growth factor receptor 2 (HER2), Ki-67, CK5, CK17, epidermal growth factor receptor (EGFR), and CD44 expression. Older women with AR-positive tumours had better BCSS compared to AR-negative tumours (p = 0.009). CONCLUSIONS: There was no difference in AR expression between older and younger women with breast cancer. AR has prognostic potential in terms of BCSS. Further work is needed to investigate AR as a therapeutic target.


Subject(s)
Breast Neoplasms , Aged , Female , Humans , Biomarkers, Tumor/genetics , Breast Neoplasms/pathology , Prognosis , Receptor, ErbB-2/metabolism , Receptors, Androgen , Receptors, Estrogen , Receptors, Progesterone/metabolism , Middle Aged
7.
Int J Radiat Oncol Biol Phys ; 115(4): 1011-1012, 2023 Mar 15.
Article in English | MEDLINE | ID: mdl-36822777
8.
Oncologist ; 28(3): e128-e135, 2023 03 17.
Article in English | MEDLINE | ID: mdl-36718086

ABSTRACT

BACKGROUND: Polypharmacy is one factor contributing to increased mortality, hospitalization, and adverse drug reactions in older adults. The aim of this study was to measure the prevalence of polypharmacy in a cohort of older women with early-stage operable primary breast cancer and the relationship of polypharmacy to primary treatment decision and functional status. METHODS: A total of 139 patients with a new diagnosis of early-stage operable primary breast cancer proven histologically were recruited as part of a prospective study. The average age was 77 years. Assessment using a cancer-specific Comprehensive Geriatric Assessment (CGA) tool was conducted within 6 weeks of diagnosis of breast cancer. Association was determined between number of medications and treatment decision and physical status as measured by the CGA outcomes. Additional analysis was performed to determine the associations above with polypharmacy defined by ≥5 daily medications, and if cardiovascular-related diseases have a role in the treatment decision. RESULTS: Polypharmacy was present in 48% of patients (n = 139). CGA determined that polypharmacy was associated with greater comorbidity (P < .001), reduced physical status rated by physicians (P = .009) and patients (P = .019), and reduced ability to perform activities of instrumental ADLs (P = .008). Similar findings were present in the analysis of cardiovascular-related diseases. CONCLUSIONS: This work suggests that patients with polypharmacy are more likely to be frail. The number of medications could help us screen patients who should go on to receive full CGA.


Subject(s)
Breast Neoplasms , Drug-Related Side Effects and Adverse Reactions , Humans , Female , Aged , Breast Neoplasms/drug therapy , Breast Neoplasms/surgery , Prospective Studies , Comorbidity , Hospitalization , Polypharmacy , Geriatric Assessment
9.
Cancers (Basel) ; 14(20)2022 Oct 14.
Article in English | MEDLINE | ID: mdl-36291809

ABSTRACT

Window of opportunity (WoO) trials create the opportunity to demonstrate pharmacodynamic parameters of a drug in vivo and have increasing use in breast cancer research. Most breast cancer tumours are oestrogen receptor-positive (ER+), leading to the development of multiple treatment options tailored towards this particular tumour subtype. The aim of this literature review is to review WoO trials pertaining to the pharmacodynamic activity of drugs available for use in ER+ breast cancer in order to help guide treatment for patients receiving neoadjuvant and primary endocrine therapy. Five databases (EMBASE, Cochrane, MEDLINE, PubMed, Web of Science) were searched for eligible studies. Studies performed in treatment-naïve patients with histologically confirmed ER+ breast cancer were included if they acquired pre- and post-treatment biopsies, compared measurement of a proteomic biomarker between these two biopsies and delivered treatment for a maximum mean duration of 31 days. Fifteen studies were eligible for inclusion and covered six different drug classes: three endocrine therapies (ETs) including aromatase inhibitors (AIs), selective oestrogen receptor modulators (SERMs), selective oestrogen receptor degraders (SERDs) and three non-ETs including mTOR inhibitors, AKT inhibitors and synthetic oestrogens. Ki67 was the most frequently measured marker, appearing in all studies. Progesterone receptor (PR) and ER were the next most frequently measured markers, appearing five and four studies, respectively. All three of these markers were significantly downregulated in both AIs and SERDs; Ki67 alone was downregulated in SERMs. Less commonly assessed markers including pS6, pGSH3B, FSH and IGF1 were downregulated while CD34, pAKT and SHBG were significantly upregulated. There were no significant changes in the other biomarkers measured such as phosphate and tensin homolog (PTEN), Bax and Bcl-2.WoO studies have been widely utilised within the ER+ breast cancer subtype, demonstrating their worth in pharmacodynamic research. However, research remains focused upon routinely measured biomarkers such ER PR and Ki67, with an array of less common markers sporadically used.

10.
Br J Surg ; 109(11): 1063-1072, 2022 10 14.
Article in English | MEDLINE | ID: mdl-35909248

ABSTRACT

BACKGROUND: Postmastectomy immediate breast reconstruction (PMIBR) may improve the quality of life of patients with breast cancer, of whom older women (aged 65 years or more) are a growing proportion. This study aimed to assess PMIBR in older women with regard to underlying impediments (if any). METHODS: MEDLINE, Embase, and PubMed were searched by two independent researchers up to June 2022. Eligible studies compared PMIBR rates between younger and older women with invasive primary breast cancer. RESULTS: A total of 10 studies (2012-2020) including 466 134 women were appraised, of whom two-thirds (313 298) were younger and one-third (152 836) older. Only 10.0 per cent of older women underwent PMIBR in contrast to 45.0 per cent of younger women. Two studies explored factors affecting uptake of PMIBR in older women; surgeon-associated (usual practice), patient-associated (socioeconomic status, ethnicity, and co-morbidities), and system-associated (insurance status and hospital location) factors were identified. CONCLUSION: Uptake of PMIBR in older women is low with definable (and some correctable) barriers.


Subject(s)
Breast Neoplasms , Mammaplasty , Age Factors , Aged , Breast Neoplasms/surgery , Female , Humans , Mastectomy , Quality of Life
11.
Curr Oncol ; 29(2): 659-674, 2022 01 29.
Article in English | MEDLINE | ID: mdl-35200558

ABSTRACT

As our global population ages, we will see more cancer diagnoses in older adults. Surgery is an important treatment modality for solid tumours, forming the majority of all cancers. However, the management of older adults with cancer can be more complex compared to their younger counterparts. This narrative review will outline the current challenges facing older adults with cancer and potential solutions. The challenges facing older adults with cancer are complex and include lack of high-level clinical trials targeting older adults and selection of the right patient for surgery. This may be standard surgical treatment, minimally invasive surgery or alternative therapies (no surgery) which can be local or systemic. The next challenge is to identify the individual patient's vulnerabilities to allow them to be maximally optimised for treatment. Prehabilitation has been shown to be of benefit in some cancer settings but uniform guidance across all surgical specialties is required. Greater awareness of geriatric conditions amongst surgical oncologists and integration of geriatric assessment into a surgical clinic are potential solutions. Enhanced recovery programmes tailored to older adults could reduce postoperative functional decline. Ultimately, the greatest challenge an older adult with cancer may face is the mindset of their treating clinicians-a shared care approach between surgical oncologists and geriatricians is required.


Subject(s)
Neoplasms , Oncologists , Surgeons , Aged , Geriatric Assessment , Humans , Medical Oncology , Neoplasms/epidemiology , Neoplasms/surgery
12.
Histopathology ; 80(3): 468-484, 2022 Feb.
Article in English | MEDLINE | ID: mdl-34473381

ABSTRACT

AIMS: The biomarkers oestrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) are routinely measured in patients with breast cancer with international consensus on how they should be interpreted. There is evidence to support use of other biomarkers to give more detailed predictive and prognostic information. Ki-67 is one example, and measures the proliferative activity of cancer cells. It is important that this can be performed at diagnosis of breast cancer for patients who do not have initial surgical treatment (mainly older women) and those receiving neoadjuvant therapies. METHODS AND RESULTS: A systematic review was performed to assess concordance of measurement of Ki-67 between core needle biopsy (CNB) samples and surgical excision (SE) samples in patients with invasive breast cancer. MEDLINE and Embase databases were searched. Studies were eligible if performed within the last 10 years; included quantitative measurement of Ki-67 in both CNB and SE samples with no prior breast cancer treatment; measured concordance between two samples; and had full text available. A total of 22 studies, including 5982 paired CNB and SE samples on which Ki-67 was measured, were appraised. Overall, there appeared to be concordance; however, reliability was unclear. Where given, the Cohen's kappa coefficient (κ) of correlation between samples ranged from 0.261 to 0.712. The concordance rate between CNB and SE where measured as a percentage had a range from 70.3 to 92.7% CONCLUSIONS: Assessment of level of concordance of Ki-67 between CNB and SE samples is hampered by different methodologies. International consensus on Ki-67 measurement is urgently needed.


Subject(s)
Biopsy, Large-Core Needle , Breast Neoplasms , Ki-67 Antigen/metabolism , Breast Neoplasms/pathology , Breast Neoplasms/surgery , Female , Humans , Prognosis
13.
Oncol Ther ; 9(2): 373-383, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34529259

ABSTRACT

Surgery is the recommended treatment modality for primary breast cancer. Breast cancer surgery is non-visceral; therefore, it is often assumed that the subsequent impact on functional status in older women is less significant compared to other cancer types such as colorectal cancer. Evidence for this however, is lacking. The definition of functional status varies amongst healthcare professionals and patients, making comparisons between studies difficult. From the literature, the two most common themes in relation to functional status following breast cancer surgery are activities of daily living and quality of life. Both of these elements of functional status are adversely impacted in patients following breast cancer surgery. A more significant decline is seen in patients with pre-existing comorbidities and with greater intensity of surgery, which includes more invasive breast and/or axillary surgery as well as additional reconstructive procedures. Identifying and optimising pre-existing factors which may predict post-operative decline in functional status, such as cognitive impairment and deteriorating functional decline over the preceding year, may help in reducing deterioration in functional status after breast cancer surgery. Methods which may be employed to detect and optimise these factors include geriatric assessment and exercise intervention.

14.
Oncol Ther ; 9(1): 55-67, 2021 Jun.
Article in English | MEDLINE | ID: mdl-33481206

ABSTRACT

The number of older adults living with cancer is increasing. There is a clear lack of representation of older adults in clinical trials, including cancer trials. Reasons for this are multifactorial and complex and include protocol, patient and sponsor factors. Potential solutions to overcome issues with trial design include varied methods of recruitment with flexible inclusion criteria. Possible alternatives to randomised trials include prospective cohort studies, pragmatic trials and the use of national population-based data sets. Patient factors may be addressed by integration of geriatric assessment, so patients can be randomised or treated based on their individual needs. Additionally, standard protocols for including older adults with cognitive impairment should be developed, rather than automatic exclusion. Increased effort is needed from sponsors and governing health care bodies to make recruitment of older adults to clinical trials standard.

15.
Saudi J Kidney Dis Transpl ; 32(2): 415-417, 2021.
Article in English | MEDLINE | ID: mdl-35017335

ABSTRACT

There is no consensus regarding timing of peritoneal dialysis (PD) catheter removal following kidney transplant. We hypothesize that early removal of PD catheter reduces the risk of peritonitis. We conducted a prospective closed-loop audit to review existing practice in our department and determine whether a better strategy could be implemented. Simple descriptive and inferential statistics were used to generate results. Categorical data were described using frequency and percentage. Continuous values were reported as mean ± standard deviation. Between November 2016 and April 2017, forty patients had renal transplant with PD in situ. On average time to removal of PD catheter, posttransplant was 84 days. Four patients (10%) developed exit-site infection. Following departmental consultation, practice was changed to remove all PD catheters at the time of transplant. Between May 2017 and January 2018, twenty patients had renal transplant and 19 had PD catheter removed at the time of transplant. Of these, one required re-insertion. In the patient where PD catheter was left in situ, peritonitis was a complication. We continue to recommend PD catheter removal at the time of transplant.


Subject(s)
Catheters, Indwelling , Device Removal , Kidney Transplantation , Peritoneal Dialysis/instrumentation , Peritonitis/microbiology , Catheters, Indwelling/adverse effects , Humans , Kidney Transplantation/adverse effects , Peritoneal Dialysis/adverse effects , Peritoneal Dialysis, Continuous Ambulatory , Peritonitis/diagnosis , Peritonitis/etiology , Prospective Studies
16.
Ecancermedicalscience ; 14: 1101, 2020.
Article in English | MEDLINE | ID: mdl-33082851

ABSTRACT

The ageing population poses new challenges globally. Cancer care for older patients is one of these challenges, and it has a significant impact on societies. In the United Kingdom (UK), as the number of older cancer patients increases, the management of this group has become part of daily practice for most oncology teams in every geographical area. Older cancer patients are at a higher risk of both under- and over-treatment. Therefore, the assessment of a patient's biological age and effective organ functional reserve becomes paramount. This may then guide treatment decisions by better estimating a prognosis and the risk-to-benefit ratio of a given therapy to anticipate and mitigate against potential toxicities/difficulties. Moreover, older cancer patients are often affected by geriatric syndromes and other issues that impact their overall health, function and quality of life. Comprehensive geriatric assessments offer an opportunity to identify and address health problems which may then optimise one's fitness and well-being. Whilst it is widely accepted that older cancer patients may benefit from such an approach, resources are often scarce, and access to dedicated services and research remains limited to specific centres across the UK. The aim of this project is to map the current services and projects in the UK to learn from each other and shape the future direction of care of older patients with cancer.

17.
Cancers (Basel) ; 12(8)2020 Jul 27.
Article in English | MEDLINE | ID: mdl-32726924

ABSTRACT

The majority of biological profiling studies use surgical excision (SE) samples, excluding patients receiving nonsurgical and neoadjuvant therapy. We propose using core needle biopsy (CNB) for biological profiling in older women. Over 37 years (1973-2010), 1 758 older (≥70 years) women with operable primary breast cancer attended a dedicated clinic. Of these, 693 had sufficient quality CNB to construct tissue microarray (TMA). The pattern of biomarkers was analysed in oestrogen receptor (ER)-positive cases, using immunohistochemistry and partitional clustering analysis. The biomarkers measured were: progesterone receptor (PgR), Ki67, Epidermal Growth Factor Receptor (EGFR), Human Epidermal Growth Factor Receptor (HER)-2, HER3, HER4, p53, cytokeratins CK5/6 and CK7/8, Mucin (MUC)1, liver kinase B1 (LKB1), Breast Cancer Associated gene (BRCA) 1, B-Cell Lymphoma (BCL)-2, phosphate and tensin homolog (PTEN), vascular endothelial growth factor (VEGF), and Amplified in breast cancer 1 (AIB1). CNB TMA construction was possible in 536 ER-positive cases. Multivariate analysis showed progesterone receptor (PgR) (p = 0.015), Ki67 (p = 0.001), and mucin (MUC)1 (p = 0.033) as independent predictors for breast-cancer-specific survival (BCSS). Cluster analysis revealed three biological clusters, which were consistent with luminal A, luminal B, and low-ER luminal. The low-ER luminal cluster had lower BCSS compared to luminal A and B. The presence of the low-ER luminal cluster unique to older women, identified in a previous study in SE TMAs in the same cohort, is confirmed. This present study is novel in its use of core needle biopsy tissue microarrays to profile the biology of breast cancer in older women.

18.
Oncol Ther ; 8(2): 231-250, 2020 Dec.
Article in English | MEDLINE | ID: mdl-32700048

ABSTRACT

A move is under way towards personalised cancer treatment, where tumour biology of an individual patient is examined to give unique predictive and prognostic information. This is extremely important in the setting of older women, who have treatment-specific goals which may differ from their younger counterparts, and may include conservation of quality of life rather than curative intent of treatment. One method employed to assist with this is the use of tumour-based prognostic and predictive tools. This article explores six of the most common tumour-based tools currently available on the market: MammaPrint, Oncotype DX, Mammostrat, Prosigna, EndoPredict, IHC4. The article discusses the creation and validation of these tools, their use and validation in older women, and future directions in the field. With the exception of Oncotype Dx, which has also been licensed for prediction of response from adjuvant chemotherapy, these tools have been licensed for use as prognostic tools only, mainly in the setting of adjuvant therapy following surgery. The evidence base for use in older women is strongest for Mammostrat and PAM50, although overall the evidence is much weaker than that in younger women. Where older women have been included in validation studies, this is often in small numbers, or the exact proportion of older women is unknown. In practice, all six of the tools are recommended to be utilised on surgical excision specimens, as well as in core needle biopsy (CNB) specimens in all of the tools except Mammostrat. This is extremely important in the setting of older women, of whom a large proportion do not undergo surgery. The suggested nature of the sample is formalin-fixed paraffin-embedded in all the tools except MammaPrint, which can also be performed on fresh-frozen samples. Future development of prognostic tools in older women with breast cancer should focus on treatment dilemmas specific to this population. This includes the decision of primary treatment between surgery or endocrine therapy and decisions regarding adjuvant therapy, in particular, chemotherapy.

19.
Oncol Ther ; 8(1): 1-11, 2020 Jun.
Article in English | MEDLINE | ID: mdl-32700069

ABSTRACT

Invasive lobular carcinoma comprises 10-15% of all breast cancers and is increasingly recognised as a distinct and understudied disease compared with the predominant histological subtype, invasive ductal carcinoma. Hallmarks of invasive lobular carcinoma include E-cadherin loss, leading to discohesive morphology with cells proliferating in single-file strands and oestrogen receptor positivity, with favourable response to endocrine therapy. This review summarises the distinct histological and molecular features of invasive lobular carcinoma with focus on diagnostic challenges and the impact on surgical management and medical therapy. Emphasis is placed on recent advances in our understanding of the unique molecular biology of lobular breast cancer and how this is optimising our therapy approach in the clinic.

20.
Cancers (Basel) ; 12(6)2020 Jun 12.
Article in English | MEDLINE | ID: mdl-32545448

ABSTRACT

Endocrine therapy is the mainstay of adjuvant treatment for patients with luminal breast cancer. Despite ongoing advances in endocrine therapy to date, a proportion of patients ultimately develop endocrine resistance, resulting in failure of therapy and poor prognosis. Therefore, as part of the growing concept of personalised medicine, the need for identification of predictive markers of endocrine therapy response at an early stage, is recognised. The METABRIC series was used to identify differentially expressed genes (DEGs) in term of response to adjuvant endocrine therapy. Drebrin 1 (DBN1) was identified as a key DEG associated with response to hormone treatment. Next, large, well-characterised cohorts of primary luminal breast cancer with long-term follow-up were assessed at the mRNA and protein levels for the value of DBN1 as a prognostic marker in luminal breast cancer, as well as its potential for predicting the benefit of endocrine therapy. DBN1 positivity was associated with aggressive clinicopathological variables and poor patient outcomes. Importantly, high DBN1 expression predicted relapse patients who were subject to adjuvant endocrine treatment. Our results further demonstrate that DBN1 is an independent prognostic marker in luminal breast cancer. Its association with the response to endocrine therapy and outcome provides evidence for DBN1 as a potential biomarker in luminal breast cancer, particularly for the benefit of endocrine treatment. Further functional investigations into the mechanisms underlying sensitivity to endocrine therapy is required.

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