The influences of age and co-morbidities on treatment decisions for patients with HER2-positive early breast cancer

doi:10.1016/j.critrevonc.2010.01.002

Critical Reviews in Oncology/Hematology

Volume 76, Issue 2, November 2010, Pages 127-132

https://doi.org/10.1016/j.critrevonc.2010.01.002 Get rights and content

Abstract

Objective

To investigate the influences of age and co-morbidities on the use of adjuvant chemotherapy and trastuzumab in patients with HER2-positive early breast cancer.

Methods

Thirty surgeons and 101 oncologists reviewed the profiles of 16 hypothetical patients which included details of age, tumour size/grade, nodal/ER status, and co-morbidities. Respondents viewed different patient profiles. Oncologists were asked how likely they would be to prescribe chemotherapy ±trastuzumab. Surgeons were asked whether they would refer to an oncologist.

Results

Oncologists’ treatment decisions were most affected by age and co-morbidities: 81% would prescribe chemotherapy for a high-risk patient aged 68 years, but only 47% for an otherwise identical patient aged 73 years. The majority of surgeons (84%) would still refer older patients.

Conclusions

National variation in the use of adjuvant chemotherapy in women aged ≥70 years with high-risk breast cancer is substantial. Practice audits or clinical trials addressing the outcomes of systemic adjuvant therapy are needed for this ever-increasing population of patients.

Introduction

Life expectancy is improving, and it is anticipated that the number of people aged 65 years or over in the UK will increase from 9.2 million in 1996 to 14.5 million in 2061 [1]. The incidence of breast cancer increases with age, and in the USA between 2000 and 2003, 43% of women were aged 65 years or over at the time of diagnosis of breast cancer [2]; with a mean age at diagnosis of 61 years. Over the forthcoming decades, this ageing of our population will lead to a significant increase in the number of older women diagnosed with breast cancer.

The benefits of post-operative adjuvant chemotherapy in older women diagnosed with breast cancer are uncertain. It is clear from the Oxford overview published in 2005 that the benefits of chemotherapy diminish with age, but the absolute benefits in older patients are unknown: only 4% of the women accrued to the clinical trials analysed were aged 70 years or over [3]. The International Society of Geriatric Oncology (SIOG) recommends that treatment with adjuvant chemotherapy should not be an age-based decision, but instead, should take into account individual patient's estimated absolute benefit, life expectancy, treatment tolerance, and preference [4]. This issue was due to be addressed by the National Cancer Research Network ACTION trial, randomising women aged 70 years or over with high risk of relapse to adjuvant chemotherapy or observation. Unfortunately, the trial closed owing to poor recruitment. Epidemiological analyses of the SEER (Surveillance Epidemiology and End Results) database in women aged 65 years or over with breast cancer suggest a benefit from adjuvant chemotherapy, but that these benefits appear to be restricted to women with poor prognostic features such as ER-negative, lymph-node-positive tumours [5]. The over-expression of the HER2 oncogene is also associated with a poor prognosis; one might therefore expect older patients with this tumour characteristic also to benefit from adjuvant chemotherapy [6]. The issue of adjuvant chemotherapy in this older HER2-positive high-risk population assumes greater significance because adjuvant trastuzumab has only been shown to be of benefit in those who have received adjuvant (or neoadjuvant) chemotherapy.

This survey's purpose was to investigate what factors influence surgeons and oncologists when making treatment decisions about the use of chemotherapy (with or without trastuzumab) in patients with HER2-positive early breast cancer.

Section snippets

Participants

Breast cancer specialists from a representative geographical spread of UK cancer networks were contacted to participate in a survey of treatment practice. Oncologists treating at least 5 patients with HER2-positive disease per month and who are responsible for treatment decisions were asked to participate in an online exercise about how they reach treatment decisions for specific patient cases; all who agreed to participate were e-mailed a link to a secure online questionnaire (30-min

Respondent demographics and characteristics

The survey took place from 29 September 2008 to 24 October 2008. A total of 101 practising oncologists from 31 cancer networks across the UK were contacted by telephone and agreed to participate. Of these, 70 were consultants and 31 were specialist registrars (40 medical oncologists and 61 clinical oncologists). A total of 30 surgeons (15 consultants and 15 specialist registrars) were contacted by telephone and agreed to participate in the study. Oncologists and surgeons had been practising for

Discussion

Patient and physician surveys, and statistical models that help predict treatment outcomes, are becoming increasingly useful to healthcare providers.

The results of this study show that age and co-morbidity are the factors most likely to affect an oncologist's treatment decisions for patients with HER2-positive breast cancer. This is not surprising: the benefits of adjuvant chemotherapy diminish with age [3], and patients with co-morbidities are likely to be at increased risk from the

Reviewers

Professor Malcolm Reed, Royal Hallamshire Hospital, Academic Surgical Oncology Unit, K Floor, Sheffield S10 2JF, United Kingdom.

Professor Hans Wildiers, University Hospital Gasthuisberg, Dept. of Medical Oncology, Herestraat 49, B-3000 Leuven, Belgium.

Funding

The market research and administrative support were funded by Roche Products Ltd. (UK). The interpretation, discussion, and publication by the author are independent of the funding organisation, which sought no control over the content of the subsequent publication.

Conflict of interest

Dr. Alistair Ring has acted as a consultant for Roche Products Ltd. (UK).

Acknowledgements

Barry Crook and Rebekah Turner of Double Helix Development were responsible for design and implementation of the survey and Gary Bennett was responsible for statistical modelling.

Sophie Berry and David Hallett are acknowledged by the author for their impartial administrative support during the preparation of this manuscript.

Alistair Ring, M.A. MRCP M.D. is senior lecturer and honorary consultant in oncology at Brighton and Sussex Medical School, UK. He has specific interests in breast cancer and the treatment of cancer in the elderly. He is a member of SIOG and the EORTC Elderly Task Force.

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The Impact of Age on Assessment and Treatment of Breast Cancer in Older People: You Are Only as Old as Your Oncologist Thinks You Are …
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There are numerous reasons accounting for these disparities. Physician bias can result in over- or under-treatment of older people with cancer.5,20-22,26,32 Older adults are poorly represented in the key randomised controlled trials that inform current ‘best practice’ across all cancer types.27-33
As the global population ages, the care of older adults with cancer is increasingly recognised as a growing challenge in oncology practice worldwide. At present, outcomes for older adults with cancer are worse than younger counterparts. The need for improved clinician education around geriatric oncology is internationally recognised as being fundamental to addressing this problem. Radiation therapy represents an excellent localised treatment modality for older adults due to its limited systemic toxicity, especially in circumstances in which surgery and chemotherapy are deemed inappropriate. Thus, the education of future radiation oncologists and other radiation oncology professionals (including radiation therapists, nurses, and physicists) in geriatric oncology is crucial to ensuring the complex needs of this patient population are met. However, evidence shows that within the specialty of radiation oncology, knowledge levels around key concepts in geriatric oncology are low and there is limited educational focus on the specific issues important for the care of older adults. An evidence-based, global approach to improving radiation oncology professionals’ knowledge and clinical practice in geriatric oncology is needed to provide optimal care for older adults undergoing radiation therapy. This article provides an overview of the current status of geriatric oncology training and education in the specialty of radiation oncology and future directions to improve the knowledge and skills of radiation oncology professionals in caring for older adults.
Initiation of adjuvant chemotherapy and trastuzumab for human epidermal growth receptor 2-positive early invasive breast cancer in a population-based cohort study of older women in England
2020, Journal of Geriatric Oncology
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A recent report from Cancer Research UK highlights a need for better evidence of treatment effectiveness in older patients [11]. Outside of the trial setting, age is a well-documented risk factor for receipt of non-standard treatment and there have been differences reported in the rates of access to treatments among older patients, with subsequent poorer outcomes [12–19]. >50,000 women in England are diagnosed with breast cancer each year, with one third of cases occurring in women aged 70 and over [20].
Clinical guidance on recommended treatment for older patients with breast cancer is often ambiguous, particularly in the context of comorbidities and poor functional status. Older patients, aged 70 years and over, account for a substantial proportion of women with breast cancer yet are underrepresented in randomized controlled trials. This paper investigates the initiation of adjuvant chemotherapy and trastuzumab in older patients in routine care.
Women, aged 50 years and over, newly diagnosed with human epidermal growth receptor 2 (HER2)-positive early invasive breast cancer from January 2014 to December 2017 were identified from the England Cancer Registry. Chemotherapy and trastuzumab use was obtained from the Systemic Anti-Cancer Therapy (SACT) dataset. Patient and tumor characteristics influential in treatment decision-making were included in multilevel mixed-effects logistic regression models.
10% of women had HER2-positive tumors. Initiation of adjuvant chemotherapy and trastuzumab decreased with age from ≥70% among women aged 50–64 years to <15% among women aged 80+ years. Initiation varied additionally by tumor characteristics and number of comorbidities. Age remained a factor in treatment decisions despite favorable other factors, with lower use among women aged 70+ years. There was also marked variation across geographical regions.
In women with operable HER2-positive early invasive breast cancer, adjuvant chemotherapy plus trastuzumab was started less frequently as age increased, regardless of tumor characteristics or comorbidity burden. There was substantial variation in the proportion of women who started these treatments across the country.
Treatment recommendations for older women with breast cancer: A survey among surgical, radiation and medical oncologists
2017, European Journal of Surgical Oncology
Citation Excerpt :
Currently, it is unknown how clinicians weigh treatment options for patients aged ≥70 years. Previous surveys using hypothetical scenarios explored how patient age or health status influenced clinicians' treatment recommendations,11–19 but most only focused on adjuvant systemic therapy.11–15,18 Furthermore, their recommendations were seldom compared for scenarios only involving patients aged over 70.12–15,19
As older women with breast cancer (BC) are underrepresented in trials, it is often unclear what represents the best treatment option for this patient group. To understand how oncologists approach the management of BC in older patients, we assessed their treatment recommendations.
In an online survey, 106 surgical, 37 radiation and 31 medical oncologists provided a treatment recommendation for hypothetical patients aged >70 years. Scenarios included loco-regional therapy with patient age varying at 76 and 84 years; systemic therapy with Karnofsky performance score varying at 90 and 50%; neo-adjuvant therapy; and adjuvant chemotherapy in triple-negative BC.
Participants would less often recommend breast-conserving surgery plus radiotherapy for an 84 versus a 76-year-old patient (56% versus 73%, p = 0.001). They would more often accept omission of radiotherapy after breast-conserving surgery in older than in younger patients, if the patient wished to avoid this therapy (26% versus 4%, p < 0.001). All participants would propose systemic therapy for a high-recurrence risk patient with a good performance score, and 92% would still recommend therapy if the patient had a poor score (p < 0.001). Neo-adjuvant hormonal therapy followed by breast-conserving surgery for a large tumour was recommended by 27% of the participants. Adjuvant chemotherapy for an otherwise healthy woman with triple-negative BC was considered by 83% of the participants.
Patient age and performance status influenced specialists' treatment recommendations. The observed recommendations for the treatment scenarios under investigation differ from older women's actual treatment. This discrepancy highlights the need for studies specifically targeting older patients.
Consideration of comorbidity in treatment decision making in multidisciplinary cancer team meetings: A systematic review
2015, Annals of Oncology
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The evidence relating to the potential benefits and harms of cancer treatments among patients with comorbidity is scarce, not least of all because patients with comorbidity are often excluded from relevant randomized controlled trials [37, 38]. Consistent with the findings of this review, a number of vignette-based studies have found that surgeons and oncologists are less likely to refer or recommend treatment of cancer patients with comorbidity [39–41]. Clinicians may be concerned about potential toxicity or effectiveness of treatments among those with comorbidity, and/or may consider that some patients' life expectancy is too short to justify the risks of treatment.
Comorbidity is very common among patients with cancer. Multidisciplinary team meetings (MDTs) are increasingly the context within which cancer treatment decisions are made internationally. Little is known about how comorbidity is considered, or impacts decisions, in MDTs.
A systematic literature review was conducted to evaluate previous evidence on consideration, and impact, of comorbidity in cancer MDT treatment decision making. Twenty-one original studies were included.
Lack of information on comorbidity in MDTs impedes the ability of MDT members to make treatment recommendations, and for those recommendations to be implemented among patients with comorbidity. Where treatment is different from that recommended due to comorbidity, it is more conservative, despite evidence that such treatment may be tolerated and effective. MDT members are likely to be unaware of the extent to which issues such as comorbidity are ignored.
MDTs should systematically consider treatment of patients with comorbidity. Further research is needed to assist clinicians to undertake MDT decision making that appropriately addresses comorbidity. If this were to occur, it would likely contribute to improved outcomes for cancer patients with comorbidities.
Specialist breast care and research nurses' attitudes to adjuvant chemotherapy in older women with breast cancer
2012, European Journal of Oncology Nursing
Citation Excerpt :
Further, some studies have suggested that under-treatment can be explained by patient refusal of chemotherapy, but this is in fact thought to affect a low proportion of patients (Bouchardy et al., 2007). Scenario-based studies, presenting hypothetical cases where only the patient age is changed, have shown that some clinicians base their decision to offer chemotherapy on patient age alone (Kemeny et al., 2003; Protière et al., 2010; Ring, 2010). A further reason for clinicians not offering chemotherapy is that information about safety and efficacy in older women is lacking, as few older women take part in clinical trials (Kemeny et al., 2003).
Breast cancer largely affects older women (≥70 y) who have historically been excluded from clinical trials; consequently, treatment is often not evidence-based. Older women may not be offered adjuvant chemotherapy due to assumptions that they would not benefit, cannot tolerate it or do not wish to have it. Specialist breast care nurses (BCN) and research nurses (RN) play an important role influencing decisions. We report the roles, attitudes and involvement of such nurses regarding adjuvant chemotherapy in older women.
A questionnaire examined 259 UK BCN and RN’s views about efficacy and desirability of chemotherapy in older women, participation in decision-making in MDTs, and roles when chemotherapy was discussed with patients.
72% of BCN and 48% of RN agreed that age should not be a factor influencing who is offered chemotherapy. BCNs indicated involvement in decision-making with older breast cancer patients, discussing chemotherapy with patients at different points following diagnosis and during treatment, and proposing chemotherapy in MDT meetings. RNs were involved to a lesser extent. 69% of all nurses had not received specific training in the area and 70% thought training would be beneficial. Nurses disagreed that older patients would not tolerate or did not want chemotherapy but 1/3 agreed or were uncertain that burdens of chemotherapy outweighed benefits. A third felt that older women had less control over treatment decisions than younger women.
This study suggests a need to develop the role of specialist nurses to facilitate treatment decision-making relating to chemotherapy in older women.

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The influences of age and co-morbidities on treatment decisions for patients with HER2-positive early breast cancer

Abstract

Objective

Methods

Results

Conclusions

Introduction

Section snippets

Participants

Respondent demographics and characteristics

Discussion

Reviewers

Funding

Conflict of interest

Acknowledgements

Lancet Oncol.

How many, how old, how soon?

BMJ

Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15 year survival: an overview of the randomised trials

Lancet

Use and outcomes of adjuvant chemotherapy in older women with breast cancer

J Clin Oncol

Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene

Science