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• W4220669603 abstract "Breast cancer is the most common cancer worldwide, with 2.3 million new diagnoses and 685 000 associated deaths globally in 2020 [[1]World Health OrganisationBreast cancer fact sheet.2021https://www.who.int/news-room/fact-sheets/detail/breast-cancerDate accessed: January 21, 2022Google Scholar]. Life expectancy has increased and there are 703 million people aged >65 years old, accounting for 9.1% of the world's population [[2]United Nations World population ageing 2019.2019https://www.un.org/en/development/desa/population/publications/pdf/ageing/WorldPopulationAgeing2019-Highlights.pdfaccessedDate accessed: January 21, 2022Google Scholar]. As the risk of breast cancer increases with age, breast cancer in the older patient is going to become an increasingly common occurrence.Here we aim to provide an overview of the current issues that arise when caring for older people with breast cancer:(i)Patient-related factors, such as comorbidities and frailty, and the importance of assessing these with patient-centred approaches and validated screening tools(ii)Tumour-related factors, including the biology of the tumours themselves(iii)Treatment-related challenges specific to breast cancer(iv)Discrepancies in survival and the reasons behind this.Older patients often have multiple concurrent health problems, including comorbidities, polypharmacy, frailty, depression, cognitive impairment and physical limitations, as well as a broad range of socioeconomic complexities. Comorbidities and their impact on life expectancy are particularly important in making oncological treatment decisions. Breast cancer-specific mortality decreases with age [[3]van de Water W. Markopoulos C. van de Velde C.J.H. Seynaeve C. Hasenburg A. Rea D. et al.Association between age at diagnosis and disease-specific mortality among postmenopausal women with hormone receptor-positive breast cancer.JAMA. 2012; 307: 590-597Crossref PubMed Scopus (155) Google Scholar] and most older patients with early disease die from non-breast cancer causes [[4]Schonberg M.A. Marcantonio E.R. Li D. Silliman R.A. Ngo L. McCarthy E.P. Breast cancer among the oldest old: tumor characteristics, treatment choices, and survival.J Clin Oncol. 2010; 28: 2038-2045Crossref PubMed Scopus (305) Google Scholar]. Certainly, the findings of Jobsen et al. [[5]Jobsen J.J. van der Palen J. Siemerink E. Struikmans H. Limited impact of breast cancer and non-breast malignancies on survival in older patients with early-stage breast cancer: results of a large, single-centre, population-based study.Clin Oncol. 2022; (S0936-6555(21)00424-6)Abstract Full Text Full Text PDF Scopus (1) Google Scholar] reflect this, with 9.1% of the patients in their study dying from breast cancer, 24.6% from non-malignant causes and 6.1% from a secondary non-breast cancer malignancy. Oncologists must evaluate wider concurrent health problems to guestimate their impact on life expectancy, the scope for optimisation to mitigate against treatment toxicity and to aid cancer treatment decision-making. Assessment of the level of frailty is critical to identifying vulnerability to cancer treatments as well as part of life expectancy guestimation. Frailty is ‘a condition characterised by loss of biological reserves across multiple organ systems and increasing vulnerability to physiological decompensation after a stressor event’ [[6]NHS England Why is diagnosing frailty important? - professor Martin Vernon.2016https://www.england.nhs.uk/gp-old/2016/09/19/martin-vernon-2/Date accessed: January 21, 2022Google Scholar]. Identifying cancer patients as fit, vulnerable or frail [[7]Fried L.P. Tangen C.M. Walston J. Newman A.B. Hirsch C. Gottdiener J. et al.Frailty in older adults: evidence for a phenotype.J Gerontol A Biol Sci Med Sci. 2001; 56: M146-M156Crossref PubMed Google Scholar] can be a helpful way of quickly identifying risk groups to aid treatment decisions and/or support needs. Evidence would suggest frailer patients have poorer outcomes than fit patients [[8]Handforth C. Clegg A. Young C. Simpkins S. Seymour M.T. Selby P.J. et al.The prevalence and outcomes of frailty in older cancer patients: a systematic review.Ann Oncol. 2015; 26: 1091-1101Abstract Full Text Full Text PDF PubMed Scopus (423) Google Scholar].Evaluation of patients at the outset minimises the risks of planning overly aggressive or insufficient treatment. The Comprehensive Geriatric Assessment (CGA) is a clinical process that identifies (by screening and assessment) and manages reversible conditions (through goal-directed intervention). The CGA addresses comorbidities, medications, geriatric syndromes (e.g. falls), mental health, nutrition, function and social support [[9]Rubenstein L.Z. Stuck A.E. Siu A.L. Wieland D. Impacts of geriatric evaluation and management programs on defined outcomes: overview of the evidence.J Am Geriatr Soc. 1991; 39 (8S–16S; discussion 7S–8S)Google Scholar]. It is a multi-component complex intervention with a robust evidence base for positive outcomes in a number of non-cancer settings [[10]Ellis G. Whitehead M.A. Robinson D. O’Neill D. Langhorne P. Comprehensive geriatric assessment for older adults admitted to hospital: meta-analysis of randomised controlled trials.BMJ. 2011; 343: d6553Crossref PubMed Scopus (636) Google Scholar]. Evidence is building to support its role in improving tolerance to cancer treatments [11Kalsi T. Babic-Illman G. Ross P.J. Maisey N.R. Hughes S. Fields P. et al.The impact of comprehensive geriatric assessment interventions on tolerance to chemotherapy in older people.Br J Cancer. 2015; 112: 1435-1444Crossref PubMed Scopus (167) Google Scholar, 12Mohile S.G. Mohamed M.R. Xu H. Culakova E. Loh K.P. Magnuson A. et al.Evaluation of geriatric assessment and management on the toxic effects of cancer treatment (GAP70+): a cluster-randomised study.Lancet. 2021; 398: 1894-1904Abstract Full Text Full Text PDF PubMed Scopus (77) Google Scholar, 13Lund C.M. Vistisen K.K. Olsen A.P. Bardal P. Schultz M. Dolin T.G. et al.The effect of geriatric intervention in frail older patients receiving chemotherapy for colorectal cancer: a randomised trial (GERICO).Br J Cancer. 2021; 124: 1949-1958Crossref PubMed Scopus (27) Google Scholar]. It is not often fully utilised in oncology clinics in the UK, although pockets of good practice are emerging [[14]Gomes F. Lewis A. Morris R. Parks R. Kalsi T. Babic-Illamn G. et al.The care of older cancer patients in the United Kingdom.Ecancermedicalscience. 2020; 14: 1101Crossref PubMed Google Scholar].Abbreviated screening tools are a time-efficient and user-friendly way of identifying patients who should have more in-depth CGA; Rockwood's Clinical Frailty Scale takes an average of 1 min to complete [[15]Rockwood K. Song X. MacKnight C. Bergman H. Hogan D.B. McDowell I. et al.A global clinical measure of fitness and frailty in elderly people.CMAJ. 2005; 173: 489-495Crossref PubMed Scopus (4090) Google Scholar,[16]Elliott A. Phelps K. Regen E. Conroy S.P. Identifying frailty in the Emergency Department – feasibility study.Age Ageing. 2017; 46: 840-845Crossref PubMed Scopus (44) Google Scholar], the Geriatric 8 (G8) comprises seven items together with an indicator of age [[17]Bellera C.A. Rainfray M. Mathoulin-Pélissier S. Mertens C. Delva F. Fonck M. et al.Screening older cancer patients: first evaluation of the G-8 geriatric screening tool.Ann Oncol. 2012; 23: 2166-2172Abstract Full Text Full Text PDF PubMed Scopus (485) Google Scholar] and there are a number of others, including self-administered cancer-specific questionnaires [[18]Hurria A. Gupta S. Zauderer M. Zuckerman E.L. Cohen H.J. Muss H. et al.Developing a cancer-specific geriatric assessment: a feasibility study.Cancer. 2005; 104: 1998-2005Crossref PubMed Scopus (478) Google Scholar,[19]Whittle A.K. Kalsi T. Babic-Illman G. Wang Y. Fields P. Ross P.J. et al.A comprehensive geriatric assessment screening questionnaire (CGA-GOLD) for older people undergoing treatment for cancer.Eur J Cancer Care. 2017; 26: 1-17Crossref Scopus (18) Google Scholar]. The choice of tool is not necessarily important; what is important is that screening for wider health issues occurs. International guidelines specific to older people are available to apply the results of screening and CGA and assist in breast cancer treatment decision-making [[20]Biganzoli L. Battisti N.M.L. Wildiers H. McCartney A. Colloca G. Kunkler I.H. et al.Updated recommendations regarding the management of older patients with breast cancer: a joint paper from the European Society of Breast Cancer Specialists (EUSOMA) and the International Society of Geriatric Oncology (SIOG).Lancet Oncol. 2021; 22: e327-e340Abstract Full Text Full Text PDF PubMed Scopus (41) Google Scholar]. Furthermore, understanding patient preferences is critical in creating a personalised management plan led by patients' goals and expectations of treatment, in the context of the possible effects of therapy on function and quality of life.Breast cancer has been the focus of extensive scientific research but despite this, relatively few studies have explored our understanding of the biology of this disease in older people [[21]Van Herck Y. Feyaerts A. Alibhai S. Papamichael D. Decoster L. Lambrechts Y. et al.Is cancer biology different in older patients?.Lancet Healthy Longevity. 2021; 2: e663-e677Abstract Full Text Full Text PDF Scopus (14) Google Scholar]. Favourable tumour characteristics, such as hormone receptor positivity, human epidermal growth factor-2 (HER-2) negativity and lymph node negativity are more frequently seen in this population, but aggressive forms are not uncommon, with triple-negative breast cancer reported in 15–18% [[22]Aapro M. Wildiers H. Triple-negative breast cancer in the older population.Ann Oncol. 2012; 23 (vi52–5)Abstract Full Text Full Text PDF Scopus (39) Google Scholar]. The tumour mutational profile is altered with age, with reduced numbers of some driver mutations (e.g. TP53, AKT1 and GATA3) but an increase in PIK3CA mutations, suggesting that the proportion of older patients requiring targeted treatments may differ from that in younger people [[21]Van Herck Y. Feyaerts A. Alibhai S. Papamichael D. Decoster L. Lambrechts Y. et al.Is cancer biology different in older patients?.Lancet Healthy Longevity. 2021; 2: e663-e677Abstract Full Text Full Text PDF Scopus (14) Google Scholar]. Older patients are grossly under-represented in clinical trials [[23]Murthy V.H. Krumholz H.M. Gross C.P. Participation in cancer clinical trials: race-, sex-, and age-based disparities.JAMA. 2004; 291: 2720-2726Crossref PubMed Scopus (1452) Google Scholar], often being excluded due to age or comorbidities, and selection bias may affect the minority that are recruited [[24]Markopoulos C. van de Water W. Older patients with breast cancer: is there bias in the treatment they receive?.Therapeut Adv Med Oncol. 2012; 4: 321-327Crossref PubMed Scopus (29) Google Scholar]. In the absence of older age-specific data, the standard for older patients is treatment based on trials carried out in a younger cohort. Often, ‘standard’ treatment is then modified to reduce toxicity in more vulnerable older people, with ad hoc dose reductions or inclusions of granulocyte-colony stimulating factor [[11]Kalsi T. Babic-Illman G. Ross P.J. Maisey N.R. Hughes S. Fields P. et al.The impact of comprehensive geriatric assessment interventions on tolerance to chemotherapy in older people.Br J Cancer. 2015; 112: 1435-1444Crossref PubMed Scopus (167) Google Scholar,[25]Kotsori A.A. Noble J.L. Ashley S. Johnston S. Smith I.E. Moderate dose capecitabine in older patients with metastatic breast cancer: a standard option for first line treatment?.Breast. 2010; 19: 377-381Abstract Full Text Full Text PDF PubMed Scopus (12) Google Scholar,[26]Brugger W. Bacon P. Lawrinson S. Romieu G. Neutrophil recovery in elderly breast cancer patients receiving adjuvant anthracycline-containing chemotherapy with pegfilgrastim support.Crit Rev Oncol Hematol. 2009; 72: 265-269Crossref PubMed Scopus (9) Google Scholar], resulting in further disparity of treatment received [[27]Lavelle K. Todd C. Moran A. Howell A. Bundred N. Campbell M. Non-standard management of breast cancer increases with age in the UK: a population based cohort of women ≥65 years.Br J Cancer. 2007; 96: 1197-1203Crossref PubMed Scopus (97) Google Scholar].Although all patients with a malignancy require carefully considered management plans, breast cancer care in older patients carries some specific therapeutic challenges. Several of the treatments commonly used for breast cancer have toxicities that unfortunately overlap with comorbidities more commonly found in older people. Anthracyclines and HER-2-targeted therapies, with their associated cardiotoxicity, may need to be closely monitored or avoided altogether in patients with pre-existing heart failure [[28]Reddy P. Shenoy C. Blaes A.H. Cardio-oncology in the older adult.J Geriatr Oncol. 2017; 8: 308-314Abstract Full Text Full Text PDF PubMed Scopus (11) Google Scholar]. Similarly, in older patients with higher rates of osteoporosis, oestrogen-reducing therapies, such as aromatase inhibitors, may exacerbate this further [[29]Hadji P. Aapro M.S. Body J.J. Gnant M. Brandi M.L. Reginster J.Y. et al.Management of aromatase inhibitor-associated bone loss (AIBL) in postmenopausal women with hormone sensitive breast cancer: joint position statement of the IOF, CABS, ECTS, IEG, ESCEO IMS, and SIOG.J Bone Oncol. 2017; 7: 1-12Crossref PubMed Scopus (135) Google Scholar]. The multimodal management of breast cancer, often combining surgery, radiotherapy and systemic therapies, also results in increased potential for one or all of these stressors to result in decompensation and or accelerate frailty in someone who was not previously vulnerable or frail. Patients with breast cancer can be burdened with frequent hospital attendances; outpatient reviews with surgical and oncological teams, radiotherapy, bone-modifying therapies and the increased risk of emergency presentations associated with myelosuppressive regimens. Additional difficulties encountered by some older patients with mobility, transport, socioeconomic issues and now fears of exposure to COVID-19 may affect attendances and jeopardise optimal results.Survival is another important area where there is also a discrepancy in outcomes for older people with breast cancer, relative to their younger peers. Age is associated with increased mortality secondary to breast cancer, irrespective of stage [[24]Markopoulos C. van de Water W. Older patients with breast cancer: is there bias in the treatment they receive?.Therapeut Adv Med Oncol. 2012; 4: 321-327Crossref PubMed Scopus (29) Google Scholar,[30]Gosain R. Pollock Y. Jain D. Age-related disparity: breast cancer in the elderly.Curr Oncol Rep. 2016; 18: 69Crossref PubMed Scopus (26) Google Scholar] and even after adjusting for comorbidities [[4]Schonberg M.A. Marcantonio E.R. Li D. Silliman R.A. Ngo L. McCarthy E.P. Breast cancer among the oldest old: tumor characteristics, treatment choices, and survival.J Clin Oncol. 2010; 28: 2038-2045Crossref PubMed Scopus (305) Google Scholar]. Variation in treatments offered and decreased tolerance to these may be contributory [[30]Gosain R. Pollock Y. Jain D. Age-related disparity: breast cancer in the elderly.Curr Oncol Rep. 2016; 18: 69Crossref PubMed Scopus (26) Google Scholar] but age has also been shown to be independently linked to therapy offered [[31]Bouchardy C. Rapiti E. Fioretta G. Laissue P. Neyroud-Caspar I. Schäfer P. et al.Undertreatment strongly decreases prognosis of breast cancer in elderly women.J Clin Oncol. 2003; 21: 3580-3587Crossref PubMed Scopus (444) Google Scholar,[32]Ring A. The influences of age and co-morbidities on treatment decisions for patients with HER2-positive early breast cancer.Crit Rev Oncol Hematol. 2010; 76: 127-132Crossref PubMed Scopus (25) Google Scholar]. Survival of younger patients with breast cancer has improved in recent years, but disappointingly this has not been the case in the older population [[33]Bastiaannet E. Portielje J.E.A. van de Velde C.J.H. de Craen A.J.M. van der Velde S. Kuppen P.J.K. et al.Lack of survival gain for elderly women with breast cancer.Oncologist. 2011; 16: 415-423Crossref PubMed Scopus (63) Google Scholar]. The improved survival of younger patients has been attributed to advances in screening and treatments, which may explain some of the discrepancy [[34]Smith B.D. Jiang J. McLaughlin S.S. Hurria A. Smith G.L. Giordano S.H. et al.Improvement in breast cancer outcomes over time: are older women missing out?.J Clin Oncol. 2011; 29: 4647-4653Crossref PubMed Scopus (119) Google Scholar]. Older people do not routinely receive screening in the UK beyond the age of 70 years and younger patients are more likely to receive standard [[35]Lyman G.H. Dale D.C. Crawford J. Incidence and predictors of low dose-intensity in adjuvant breast cancer chemotherapy: a nationwide study of community practices.J Clin Oncol. 2003; 21: 4524-4531Crossref PubMed Scopus (383) Google Scholar] and adjuvant treatment [[3]van de Water W. Markopoulos C. van de Velde C.J.H. Seynaeve C. Hasenburg A. Rea D. et al.Association between age at diagnosis and disease-specific mortality among postmenopausal women with hormone receptor-positive breast cancer.JAMA. 2012; 307: 590-597Crossref PubMed Scopus (155) Google Scholar] than older patients.Both under- and overtreatment have been implicated in poorer survival in older breast cancer patients [[30]Gosain R. Pollock Y. Jain D. Age-related disparity: breast cancer in the elderly.Curr Oncol Rep. 2016; 18: 69Crossref PubMed Scopus (26) Google Scholar]. Patients are less likely to receive breast conserving surgery (BCS) [[27]Lavelle K. Todd C. Moran A. Howell A. Bundred N. Campbell M. Non-standard management of breast cancer increases with age in the UK: a population based cohort of women ≥65 years.Br J Cancer. 2007; 96: 1197-1203Crossref PubMed Scopus (97) Google Scholar], adjuvant radiotherapy [[3]van de Water W. Markopoulos C. van de Velde C.J.H. Seynaeve C. Hasenburg A. Rea D. et al.Association between age at diagnosis and disease-specific mortality among postmenopausal women with hormone receptor-positive breast cancer.JAMA. 2012; 307: 590-597Crossref PubMed Scopus (155) Google Scholar] and adjuvant chemotherapy [[3]van de Water W. Markopoulos C. van de Velde C.J.H. Seynaeve C. Hasenburg A. Rea D. et al.Association between age at diagnosis and disease-specific mortality among postmenopausal women with hormone receptor-positive breast cancer.JAMA. 2012; 307: 590-597Crossref PubMed Scopus (155) Google Scholar,[36]Bouchardy C. Rapiti E. Blagojevic S. Vlastos A.T. Vlastos G. Older female cancer patients: importance, causes, and consequences of undertreatment.J Clin Oncol. 2007; 25: 1858-1869Crossref PubMed Scopus (251) Google Scholar] than their younger counterparts. The rationale behind this is probably multifactorial; Harder et al. [[37]Harder H. Ballinger R. Langridge C. Ring A. Fallowfield L.J. Adjuvant chemotherapy in elderly women with breast cancer: patients' perspectives on information giving and decision making.Psychooncology. 2013; 22: 2729-2735Crossref PubMed Scopus (31) Google Scholar] report that chemotherapy has been declined on the basis of side-effects, minimal increase in survival advantage, duration of therapy and clinical advice. However, as Jobsen et al. [[5]Jobsen J.J. van der Palen J. Siemerink E. Struikmans H. Limited impact of breast cancer and non-breast malignancies on survival in older patients with early-stage breast cancer: results of a large, single-centre, population-based study.Clin Oncol. 2022; (S0936-6555(21)00424-6)Abstract Full Text Full Text PDF Scopus (1) Google Scholar] have shown, outcomes after BCS can be excellent, with a 12-year disease-free survival of 84.4% for patients ≥65 years. Overtreatment is a less well documented phenomenon. Studies, including CALGB 9343 and PRIME II, have shown that adjuvant radiotherapy following BCS modestly reduces local recurrence risk (PRIME II reported that 5-year ipsilateral breast cancer recurrence fell from 4.1% to 1.3%) but has no impact on overall survival in older people; the risks of toxicity need to be balanced carefully with this [[38]Hughes K.S. Schnaper L.A. Bellon J.R. Cirrincione C.T. Berry D.A. McCormick B. et al.Lumpectomy plus tamoxifen with or without irradiation in women age 70 years or older with early breast cancer: long-term follow-up of CALGB 9343.J Clin Oncol. 2013; 31: 2382-2387Crossref PubMed Scopus (738) Google Scholar,[39]Kunkler I.H. Williams L.J. Jack W.J.L. Cameron D.A. Dixon J.M. Breast-conserving surgery with or without irradiation in women aged 65 years or older with early breast cancer (PRIME II): a randomised controlled trial.Lancet Oncol. 2015; 16: 266-273Abstract Full Text Full Text PDF PubMed Scopus (536) Google Scholar]. Decision-making in this setting may be aided by the findings of a phase III trial, PRIMETIME, which is currently exploring the effect of omitting adjuvant radiotherapy in patients ≥60 years, who are stratified as low risk for recurrence based on biomarker status [[40]Kirwan C.C. Coles C.E. Bliss J. Kirwan C. Kilburn L. Fox L. et al.It's PRIMETIME. Postoperative avoidance of radiotherapy: biomarker selection of women at very low risk of local recurrence.Clin Oncol. 2016; 28: 594-596Abstract Full Text Full Text PDF PubMed Scopus (45) Google Scholar].A myriad of factors, that we have classified as patient-, tumour- or treatment-related, must be considered for this heterogenous population, which can make treatment decisions complex (Figure 1). Identifying the vulnerable and frail prior to planning treatment not only enables modifications to be made to oncological therapies but also facilitates concurrent optimisation of comorbidities and function. A multidisciplinary approach has clear benefits here, with close collaboration between oncologists, geriatricians, primary care and allied health professionals. Undoubtedly though, a paucity of evidence complicates treatment decision-making for these patients and is the biggest limitation in this field currently. Jobsen et al. [[5]Jobsen J.J. van der Palen J. Siemerink E. Struikmans H. Limited impact of breast cancer and non-breast malignancies on survival in older patients with early-stage breast cancer: results of a large, single-centre, population-based study.Clin Oncol. 2022; (S0936-6555(21)00424-6)Abstract Full Text Full Text PDF Scopus (1) Google Scholar] address one of the many knowledge gaps through their exploration of survival in older breast cancer patients following BCS. More research and data are needed to equip breast cancer oncologists with robust evidence to aid treatment decision-making in older people with breast cancer.Conflicts of interestThe authors declare no conflicts of interest. Breast cancer is the most common cancer worldwide, with 2.3 million new diagnoses and 685 000 associated deaths globally in 2020 [[1]World Health OrganisationBreast cancer fact sheet.2021https://www.who.int/news-room/fact-sheets/detail/breast-cancerDate accessed: January 21, 2022Google Scholar]. Life expectancy has increased and there are 703 million people aged >65 years old, accounting for 9.1% of the world's population [[2]United Nations World population ageing 2019.2019https://www.un.org/en/development/desa/population/publications/pdf/ageing/WorldPopulationAgeing2019-Highlights.pdfaccessedDate accessed: January 21, 2022Google Scholar]. As the risk of breast cancer increases with age, breast cancer in the older patient is going to become an increasingly common occurrence. Here we aim to provide an overview of the current issues that arise when caring for older people with breast cancer:(i)Patient-related factors, such as comorbidities and frailty, and the importance of assessing these with patient-centred approaches and validated screening tools(ii)Tumour-related factors, including the biology of the tumours themselves(iii)Treatment-related challenges specific to breast cancer(iv)Discrepancies in survival and the reasons behind this. Older patients often have multiple concurrent health problems, including comorbidities, polypharmacy, frailty, depression, cognitive impairment and physical limitations, as well as a broad range of socioeconomic complexities. Comorbidities and their impact on life expectancy are particularly important in making oncological treatment decisions. Breast cancer-specific mortality decreases with age [[3]van de Water W. Markopoulos C. van de Velde C.J.H. Seynaeve C. Hasenburg A. Rea D. et al.Association between age at diagnosis and disease-specific mortality among postmenopausal women with hormone receptor-positive breast cancer.JAMA. 2012; 307: 590-597Crossref PubMed Scopus (155) Google Scholar] and most older patients with early disease die from non-breast cancer causes [[4]Schonberg M.A. Marcantonio E.R. Li D. Silliman R.A. Ngo L. McCarthy E.P. Breast cancer among the oldest old: tumor characteristics, treatment choices, and survival.J Clin Oncol. 2010; 28: 2038-2045Crossref PubMed Scopus (305) Google Scholar]. Certainly, the findings of Jobsen et al. [[5]Jobsen J.J. van der Palen J. Siemerink E. Struikmans H. Limited impact of breast cancer and non-breast malignancies on survival in older patients with early-stage breast cancer: results of a large, single-centre, population-based study.Clin Oncol. 2022; (S0936-6555(21)00424-6)Abstract Full Text Full Text PDF Scopus (1) Google Scholar] reflect this, with 9.1% of the patients in their study dying from breast cancer, 24.6% from non-malignant causes and 6.1% from a secondary non-breast cancer malignancy. Oncologists must evaluate wider concurrent health problems to guestimate their impact on life expectancy, the scope for optimisation to mitigate against treatment toxicity and to aid cancer treatment decision-making. Assessment of the level of frailty is critical to identifying vulnerability to cancer treatments as well as part of life expectancy guestimation. Frailty is ‘a condition characterised by loss of biological reserves across multiple organ systems and increasing vulnerability to physiological decompensation after a stressor event’ [[6]NHS England Why is diagnosing frailty important? - professor Martin Vernon.2016https://www.england.nhs.uk/gp-old/2016/09/19/martin-vernon-2/Date accessed: January 21, 2022Google Scholar]. Identifying cancer patients as fit, vulnerable or frail [[7]Fried L.P. Tangen C.M. Walston J. Newman A.B. Hirsch C. Gottdiener J. et al.Frailty in older adults: evidence for a phenotype.J Gerontol A Biol Sci Med Sci. 2001; 56: M146-M156Crossref PubMed Google Scholar] can be a helpful way of quickly identifying risk groups to aid treatment decisions and/or support needs. Evidence would suggest frailer patients have poorer outcomes than fit patients [[8]Handforth C. Clegg A. Young C. Simpkins S. Seymour M.T. Selby P.J. et al.The prevalence and outcomes of frailty in older cancer patients: a systematic review.Ann Oncol. 2015; 26: 1091-1101Abstract Full Text Full Text PDF PubMed Scopus (423) Google Scholar]. Evaluation of patients at the outset minimises the risks of planning overly aggressive or insufficient treatment. The Comprehensive Geriatric Assessment (CGA) is a clinical process that identifies (by screening and assessment) and manages reversible conditions (through goal-directed intervention). The CGA addresses comorbidities, medications, geriatric syndromes (e.g. falls), mental health, nutrition, function and social support [[9]Rubenstein L.Z. Stuck A.E. Siu A.L. Wieland D. Impacts of geriatric evaluation and management programs on defined outcomes: overview of the evidence.J Am Geriatr Soc. 1991; 39 (8S–16S; discussion 7S–8S)Google Scholar]. It is a multi-component complex intervention with a robust evidence base for positive outcomes in a number of non-cancer settings [[10]Ellis G. Whitehead M.A. Robinson D. O’Neill D. Langhorne P. Comprehensive geriatric assessment for older adults admitted to hospital: meta-analysis of randomised controlled trials.BMJ. 2011; 343: d6553Crossref PubMed Scopus (636) Google Scholar]. Evidence is building to support its role in improving tolerance to cancer treatments [11Kalsi T. Babic-Illman G. Ross P.J. Maisey N.R. Hughes S. Fields P. et al.The impact of comprehensive geriatric assessment interventions on tolerance to chemotherapy in older people.Br J Cancer. 2015; 112: 1435-1444Crossref PubMed Scopus (167) Google Scholar, 12Mohile S.G. Mohamed M.R. Xu H. Culakova E. Loh K.P. Magnuson A. et al.Evaluation of geriatric assessment and management on the toxic effects of cancer treatment (GAP70+): a cluster-randomised study.Lancet. 2021; 398: 1894-1904Abstract Full Text Full Text PDF PubMed Scopus (77) Google Scholar, 13Lund C.M. Vistisen K.K. Olsen A.P. Bardal P. Schultz M. Dolin T.G. et al.The effect of geriatric intervention in frail older patients receiving chemotherapy for colorectal cancer: a randomised trial (GERICO).Br J Cancer. 2021; 124: 1949-1958Crossref PubMed Scopus (27) Google Scholar]. It is not often fully utilised in oncology clinics in the UK, although pockets of good practice are emerging [[14]Gomes F. Lewis A. Morris R. Parks R. Kalsi T. Babic-Illamn G. et al.The care of older cancer patients in the United Kingdom.Ecancermedicalscience. 2020; 14: 1101Crossref PubMed Google Scholar]. Abbreviated screening tools are a time-efficient and user-friendly way of identifying patients who should have more in-depth CGA; Rockwood's Clinical Frailty Scale takes an average of 1 min to complete [[15]Rockwood K. Song X. MacKnight C. Bergman H. Hogan D.B. McDowell I. et al.A global clinical measure of fitness and frailty in elderly people.CMAJ. 2005; 173: 489-495Crossref PubMed Scopus (4090) Google Scholar,[16]Elliott A. Phelps K. Regen E. Conroy S.P. Identifying frailty in the Emergency Department – feasibility study.Age Ageing. 2017; 46: 840-845Crossref PubMed Scopus (44) Google Scholar], the Geriatric 8 (G8) comprises seven items together with an indicator of age [[17]Bellera C.A. Rainfray M. Mathoulin-Pélissier S. Mertens C. Delva F. Fonck M. et al.Screening older cancer patients: first evaluation of the G-8 geriatric screening tool.Ann Oncol. 2012; 23: 2166-2172Abstract Full Text Full Text PDF PubMed Scopus (485) Google Scholar] and there are a number of others, including self-administered cancer-specific questionnaires [[18]Hurria A. Gupta S. Zauderer M. Zuckerman E.L. Cohen H.J. Muss H. et al.Developing a cancer-specific geriatric assessment: a feasibility study.Cancer. 2005; 104: 1998-2005Crossref PubMed Scopus (478) Google Scholar,[19]Whittle A.K. Kalsi T. Babic-Illman G. Wang Y. Fields P. Ross P.J. et al.A comprehensive geriatric assessment screening questionnaire (CGA-GOLD) for older people undergoing treatment for cancer.Eur J Cancer Care. 2017; 26: 1-17Crossref Scopus (18) Google Scholar]. The choice of tool is not necessarily important; what is important is that screening for wider health issues occurs. International guidelines specific to older people are available to apply the results of screening and CGA and assist in breast cancer treatment decision-making [[20]Biganzoli L. Battisti N.M.L. Wildiers H. McCartney A. Colloca G. Kunkler I.H. et al.Updated recommendations regarding the management of older patients with breast cancer: a joint paper from the European Society of Breast Cancer Specialists (EUSOMA) and the International Society of Geriatric Oncology (SIOG).Lancet Oncol. 2021; 22: e327-e340Abstract Full Text Full Text PDF PubMed Scopus (41) Google Scholar]. Furthermore, understanding patient preferences is critical in creating a personalised management plan led by patients' goals and expectations of treatment, in the context of the possible effects of therapy on function and quality of life. Breast cancer has been the focus of extensive scientific research but despite this, relatively few studies have explored our understanding of the biology of this disease in older people [[21]Van Herck Y. Feyaerts A. Alibhai S. Papamichael D. Decoster L. Lambrechts Y. et al.Is cancer biology different in older patients?.Lancet Healthy Longevity. 2021; 2: e663-e677Abstract Full Text Full Text PDF Scopus (14) Google Scholar]. Favourable tumour characteristics, such as hormone receptor positivity, human epidermal growth factor-2 (HER-2) negativity and lymph node negativity are more frequently seen in this population, but aggressive forms are not uncommon, with triple-negative breast cancer reported in 15–18% [[22]Aapro M. Wildiers H. Triple-negative breast cancer in the older population.Ann Oncol. 2012; 23 (vi52–5)Abstract Full Text Full Text PDF Scopus (39) Google Scholar]. The tumour mutational profile is altered with age, with reduced numbers of some driver mutations (e.g. TP53, AKT1 and GATA3) but an increase in PIK3CA mutations, suggesting that the proportion of older patients requiring targeted treatments may differ from that in younger people [[21]Van Herck Y. Feyaerts A. Alibhai S. Papamichael D. Decoster L. Lambrechts Y. et al.Is cancer biology different in older patients?.Lancet Healthy Longevity. 2021; 2: e663-e677Abstract Full Text Full Text PDF Scopus (14) Google Scholar]. Older patients are grossly under-represented in clinical trials [[23]Murthy V.H. Krumholz H.M. Gross C.P. Participation in cancer clinical trials: race-, sex-, and age-based disparities.JAMA. 2004; 291: 2720-2726Crossref PubMed Scopus (1452) Google Scholar], often being excluded due to age or comorbidities, and selection bias may affect the minority that are recruited [[24]Markopoulos C. van de Water W. Older patients with breast cancer: is there bias in the treatment they receive?.Therapeut Adv Med Oncol. 2012; 4: 321-327Crossref PubMed Scopus (29) Google Scholar]. In the absence of older age-specific data, the standard for older patients is treatment based on trials carried out in a younger cohort. Often, ‘standard’ treatment is then modified to reduce toxicity in more vulnerable older people, with ad hoc dose reductions or inclusions of granulocyte-colony stimulating factor [[11]Kalsi T. Babic-Illman G. Ross P.J. Maisey N.R. Hughes S. Fields P. et al.The impact of comprehensive geriatric assessment interventions on tolerance to chemotherapy in older people.Br J Cancer. 2015; 112: 1435-1444Crossref PubMed Scopus (167) Google Scholar,[25]Kotsori A.A. Noble J.L. Ashley S. Johnston S. Smith I.E. Moderate dose capecitabine in older patients with metastatic breast cancer: a standard option for first line treatment?.Breast. 2010; 19: 377-381Abstract Full Text Full Text PDF PubMed Scopus (12) Google Scholar,[26]Brugger W. Bacon P. Lawrinson S. Romieu G. Neutrophil recovery in elderly breast cancer patients receiving adjuvant anthracycline-containing chemotherapy with pegfilgrastim support.Crit Rev Oncol Hematol. 2009; 72: 265-269Crossref PubMed Scopus (9) Google Scholar], resulting in further disparity of treatment received [[27]Lavelle K. Todd C. Moran A. Howell A. Bundred N. Campbell M. Non-standard management of breast cancer increases with age in the UK: a population based cohort of women ≥65 years.Br J Cancer. 2007; 96: 1197-1203Crossref PubMed Scopus (97) Google Scholar]. Although all patients with a malignancy require carefully considered management plans, breast cancer care in older patients carries some specific therapeutic challenges. Several of the treatments commonly used for breast cancer have toxicities that unfortunately overlap with comorbidities more commonly found in older people. Anthracyclines and HER-2-targeted therapies, with their associated cardiotoxicity, may need to be closely monitored or avoided altogether in patients with pre-existing heart failure [[28]Reddy P. Shenoy C. Blaes A.H. Cardio-oncology in the older adult.J Geriatr Oncol. 2017; 8: 308-314Abstract Full Text Full Text PDF PubMed Scopus (11) Google Scholar]. Similarly, in older patients with higher rates of osteoporosis, oestrogen-reducing therapies, such as aromatase inhibitors, may exacerbate this further [[29]Hadji P. Aapro M.S. Body J.J. Gnant M. Brandi M.L. Reginster J.Y. et al.Management of aromatase inhibitor-associated bone loss (AIBL) in postmenopausal women with hormone sensitive breast cancer: joint position statement of the IOF, CABS, ECTS, IEG, ESCEO IMS, and SIOG.J Bone Oncol. 2017; 7: 1-12Crossref PubMed Scopus (135) Google Scholar]. The multimodal management of breast cancer, often combining surgery, radiotherapy and systemic therapies, also results in increased potential for one or all of these stressors to result in decompensation and or accelerate frailty in someone who was not previously vulnerable or frail. Patients with breast cancer can be burdened with frequent hospital attendances; outpatient reviews with surgical and oncological teams, radiotherapy, bone-modifying therapies and the increased risk of emergency presentations associated with myelosuppressive regimens. Additional difficulties encountered by some older patients with mobility, transport, socioeconomic issues and now fears of exposure to COVID-19 may affect attendances and jeopardise optimal results. Survival is another important area where there is also a discrepancy in outcomes for older people with breast cancer, relative to their younger peers. Age is associated with increased mortality secondary to breast cancer, irrespective of stage [[24]Markopoulos C. van de Water W. Older patients with breast cancer: is there bias in the treatment they receive?.Therapeut Adv Med Oncol. 2012; 4: 321-327Crossref PubMed Scopus (29) Google Scholar,[30]Gosain R. Pollock Y. Jain D. Age-related disparity: breast cancer in the elderly.Curr Oncol Rep. 2016; 18: 69Crossref PubMed Scopus (26) Google Scholar] and even after adjusting for comorbidities [[4]Schonberg M.A. Marcantonio E.R. Li D. Silliman R.A. Ngo L. McCarthy E.P. Breast cancer among the oldest old: tumor characteristics, treatment choices, and survival.J Clin Oncol. 2010; 28: 2038-2045Crossref PubMed Scopus (305) Google Scholar]. Variation in treatments offered and decreased tolerance to these may be contributory [[30]Gosain R. Pollock Y. Jain D. Age-related disparity: breast cancer in the elderly.Curr Oncol Rep. 2016; 18: 69Crossref PubMed Scopus (26) Google Scholar] but age has also been shown to be independently linked to therapy offered [[31]Bouchardy C. Rapiti E. Fioretta G. Laissue P. Neyroud-Caspar I. Schäfer P. et al.Undertreatment strongly decreases prognosis of breast cancer in elderly women.J Clin Oncol. 2003; 21: 3580-3587Crossref PubMed Scopus (444) Google Scholar,[32]Ring A. The influences of age and co-morbidities on treatment decisions for patients with HER2-positive early breast cancer.Crit Rev Oncol Hematol. 2010; 76: 127-132Crossref PubMed Scopus (25) Google Scholar]. Survival of younger patients with breast cancer has improved in recent years, but disappointingly this has not been the case in the older population [[33]Bastiaannet E. Portielje J.E.A. van de Velde C.J.H. de Craen A.J.M. van der Velde S. Kuppen P.J.K. et al.Lack of survival gain for elderly women with breast cancer.Oncologist. 2011; 16: 415-423Crossref PubMed Scopus (63) Google Scholar]. The improved survival of younger patients has been attributed to advances in screening and treatments, which may explain some of the discrepancy [[34]Smith B.D. Jiang J. McLaughlin S.S. Hurria A. Smith G.L. Giordano S.H. et al.Improvement in breast cancer outcomes over time: are older women missing out?.J Clin Oncol. 2011; 29: 4647-4653Crossref PubMed Scopus (119) Google Scholar]. Older people do not routinely receive screening in the UK beyond the age of 70 years and younger patients are more likely to receive standard [[35]Lyman G.H. Dale D.C. Crawford J. Incidence and predictors of low dose-intensity in adjuvant breast cancer chemotherapy: a nationwide study of community practices.J Clin Oncol. 2003; 21: 4524-4531Crossref PubMed Scopus (383) Google Scholar] and adjuvant treatment [[3]van de Water W. Markopoulos C. van de Velde C.J.H. Seynaeve C. Hasenburg A. Rea D. et al.Association between age at diagnosis and disease-specific mortality among postmenopausal women with hormone receptor-positive breast cancer.JAMA. 2012; 307: 590-597Crossref PubMed Scopus (155) Google Scholar] than older patients. Both under- and overtreatment have been implicated in poorer survival in older breast cancer patients [[30]Gosain R. Pollock Y. Jain D. Age-related disparity: breast cancer in the elderly.Curr Oncol Rep. 2016; 18: 69Crossref PubMed Scopus (26) Google Scholar]. Patients are less likely to receive breast conserving surgery (BCS) [[27]Lavelle K. Todd C. Moran A. Howell A. Bundred N. Campbell M. Non-standard management of breast cancer increases with age in the UK: a population based cohort of women ≥65 years.Br J Cancer. 2007; 96: 1197-1203Crossref PubMed Scopus (97) Google Scholar], adjuvant radiotherapy [[3]van de Water W. Markopoulos C. van de Velde C.J.H. Seynaeve C. Hasenburg A. Rea D. et al.Association between age at diagnosis and disease-specific mortality among postmenopausal women with hormone receptor-positive breast cancer.JAMA. 2012; 307: 590-597Crossref PubMed Scopus (155) Google Scholar] and adjuvant chemotherapy [[3]van de Water W. Markopoulos C. van de Velde C.J.H. Seynaeve C. Hasenburg A. Rea D. et al.Association between age at diagnosis and disease-specific mortality among postmenopausal women with hormone receptor-positive breast cancer.JAMA. 2012; 307: 590-597Crossref PubMed Scopus (155) Google Scholar,[36]Bouchardy C. Rapiti E. Blagojevic S. Vlastos A.T. Vlastos G. Older female cancer patients: importance, causes, and consequences of undertreatment.J Clin Oncol. 2007; 25: 1858-1869Crossref PubMed Scopus (251) Google Scholar] than their younger counterparts. The rationale behind this is probably multifactorial; Harder et al. [[37]Harder H. Ballinger R. Langridge C. Ring A. Fallowfield L.J. Adjuvant chemotherapy in elderly women with breast cancer: patients' perspectives on information giving and decision making.Psychooncology. 2013; 22: 2729-2735Crossref PubMed Scopus (31) Google Scholar] report that chemotherapy has been declined on the basis of side-effects, minimal increase in survival advantage, duration of therapy and clinical advice. However, as Jobsen et al. [[5]Jobsen J.J. van der Palen J. Siemerink E. Struikmans H. Limited impact of breast cancer and non-breast malignancies on survival in older patients with early-stage breast cancer: results of a large, single-centre, population-based study.Clin Oncol. 2022; (S0936-6555(21)00424-6)Abstract Full Text Full Text PDF Scopus (1) Google Scholar] have shown, outcomes after BCS can be excellent, with a 12-year disease-free survival of 84.4% for patients ≥65 years. Overtreatment is a less well documented phenomenon. Studies, including CALGB 9343 and PRIME II, have shown that adjuvant radiotherapy following BCS modestly reduces local recurrence risk (PRIME II reported that 5-year ipsilateral breast cancer recurrence fell from 4.1% to 1.3%) but has no impact on overall survival in older people; the risks of toxicity need to be balanced carefully with this [[38]Hughes K.S. Schnaper L.A. Bellon J.R. Cirrincione C.T. Berry D.A. McCormick B. et al.Lumpectomy plus tamoxifen with or without irradiation in women age 70 years or older with early breast cancer: long-term follow-up of CALGB 9343.J Clin Oncol. 2013; 31: 2382-2387Crossref PubMed Scopus (738) Google Scholar,[39]Kunkler I.H. Williams L.J. Jack W.J.L. Cameron D.A. Dixon J.M. Breast-conserving surgery with or without irradiation in women aged 65 years or older with early breast cancer (PRIME II): a randomised controlled trial.Lancet Oncol. 2015; 16: 266-273Abstract Full Text Full Text PDF PubMed Scopus (536) Google Scholar]. Decision-making in this setting may be aided by the findings of a phase III trial, PRIMETIME, which is currently exploring the effect of omitting adjuvant radiotherapy in patients ≥60 years, who are stratified as low risk for recurrence based on biomarker status [[40]Kirwan C.C. Coles C.E. Bliss J. Kirwan C. Kilburn L. Fox L. et al.It's PRIMETIME. Postoperative avoidance of radiotherapy: biomarker selection of women at very low risk of local recurrence.Clin Oncol. 2016; 28: 594-596Abstract Full Text Full Text PDF PubMed Scopus (45) Google Scholar]. A myriad of factors, that we have classified as patient-, tumour- or treatment-related, must be considered for this heterogenous population, which can make treatment decisions complex (Figure 1). Identifying the vulnerable and frail prior to planning treatment not only enables modifications to be made to oncological therapies but also facilitates concurrent optimisation of comorbidities and function. A multidisciplinary approach has clear benefits here, with close collaboration between oncologists, geriatricians, primary care and allied health professionals. Undoubtedly though, a paucity of evidence complicates treatment decision-making for these patients and is the biggest limitation in this field currently. Jobsen et al. [[5]Jobsen J.J. van der Palen J. Siemerink E. Struikmans H. Limited impact of breast cancer and non-breast malignancies on survival in older patients with early-stage breast cancer: results of a large, single-centre, population-based study.Clin Oncol. 2022; (S0936-6555(21)00424-6)Abstract Full Text Full Text PDF Scopus (1) Google Scholar] address one of the many knowledge gaps through their exploration of survival in older breast cancer patients following BCS. More research and data are needed to equip breast cancer oncologists with robust evidence to aid treatment decision-making in older people with breast cancer. Conflicts of interestThe authors declare no conflicts of interest. The authors declare no conflicts of interest. KB is supported by an MRC Clinical Research Training Fellowship . MR/P018521/1 ." @default.
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