Elsevier

The Lancet Oncology

Volume 13, Issue 4, April 2012, Pages e148-e160
The Lancet Oncology

Review
Management of elderly patients with breast cancer: updated recommendations of the International Society of Geriatric Oncology (SIOG) and European Society of Breast Cancer Specialists (EUSOMA)

https://doi.org/10.1016/S1470-2045(11)70383-7Get rights and content

Summary

As the mean age of the global population increases, breast cancer in older individuals will be increasingly encountered in clinical practice. Management decisions should not be based on age alone. Establishing recommendations for management of older individuals with breast cancer is challenging because of very limited level 1 evidence in this heterogeneous population. In 2007, the International Society of Geriatric Oncology (SIOG) created a task force to provide evidence-based recommendations for the management of breast cancer in elderly individuals. In 2010, a multidisciplinary SIOG and European Society of Breast Cancer Specialists (EUSOMA) task force gathered to expand and update the 2007 recommendations. The recommendations were expanded to include geriatric assessment, competing causes of mortality, ductal carcinoma in situ, drug safety and compliance, patient preferences, barriers to treatment, and male breast cancer. Recommendations were updated for screening, primary endocrine therapy, surgery, radiotherapy, neoadjuvant and adjuvant systemic therapy, and metastatic breast cancer.

Introduction

Recommendations for management of breast cancer in older individuals are limited by a lack of level 1 evidence. Treatment is largely based on limited retrospective subgroup analyses and extrapolation of study results from younger patients. Such extrapolation might not be valid since breast-cancer biology differs in older patients, treatment tolerance varies, and there are competing risks of non-breast-cancer mortality. Modified management strategies are often used for older individuals; however, the evidence for such approaches is poor, and resulting undertreatment is well documented.1

We present recommendations for management of older individuals with breast cancer created by a European Society of Breast Cancer Specialists (EUSOMA) and International Society of Geriatric Oncology (SIOG) multidisciplinary task force. This task force—inclusive of representative specialists from medical oncology, radiation oncology, surgery, geriatric medicine, radiology, and epidemiology—used the SIOG guidelines published in 2007 as a starting document.2 Existing guidelines for screening, primary endocrine therapy, surgery, radiotherapy, adjuvant systemic therapy, and metastatic breast cancer have been updated. The guidelines have been supplemented with recommendations for geriatric assessment and management, competing causes of mortality, ductal carcinoma in situ, male breast cancer, drug safety and compliance, patient preferences, and barriers to treatment.

The scarcity of robust data on breast cancer in older individuals—particularly on modifing management for frail patients—precludes these recommendations being based on level 1 evidence. Therefore, these recommendations are a consensus by an expert task force on available evidence and expert opinion. Table 1 presents the 2007 and current recommendations. Recommendations unchanged from 20072 because of absence of new data have not been rediscussed (ie, surgery of the primary tumour, radiotherapy after conservative surgery, post-mastectomy radiotherapy, adjuvant trastuzumab, and hormone treatment for metastatic breast cancer).

Age alone should not dictate any aspect of management for older individuals with breast cancer. All decisions should consider physiological age, estimated life expectancy, risks, benefits, treatment tolerance, patient preference, and potential treatment barriers.

Section snippets

Incidence, general characteristics, and prognosis

Breast cancer incidence varies widely between and within continents. In Europe, incidence for women 70 years or older diagnosed between 2000–04 varied from 100 to 350 per 100 000 per year.3 The incidence for this group has shown a steady increase in most European countries between 1990–2002.3

Compared with younger women, older women are more likely to have breast cancer with oestrogen receptor (ER) and progesterone receptor expression, with or without HER2 overexpression.4 Variation in receptor

Competing causes of mortality

Many older patients with operable breast cancer die of non-cancer-related causes. Relative breast-cancer survival is the preferred way to describe the prognosis of older patients with breast cancer, since it considers the risk of dying from other causes.

The benefit of cancer therapy in individuals likely to die at an early stage from non-cancer-related causes is questionable; however, it is difficult for clinicians to identify these individuals. Assessment of comorbidity and the need for

Geriatric assessment

Estimation of life expectancy and ability to undergo treatment might be improved by collaborative geriatric and oncology management, and a multidomain geriatric assessment.11, 12, 13 There is currently no standard method for geriatric assessment; however, the comprehensive geriatric assessment (CGA) includes measures of function, comorbidity, nutrition, medication, socioeconomic issues, and geriatric syndromes.12 There is strong evidence in the general elderly population that implementation of

Screening

The US Preventive Services Task Force concluded that there is insufficient data on the effect of mammographic screening on breast-cancer mortality among women 70 years or older.23 While direct evidence is lacking, modelling studies suggest that mortality reduction can be achieved on a cost-effective scale up to 74 years of age,24 and is recommended in several European countries. In the absence of an overall survival benefit, however, the decision to screen beyond 70 years should be made by the

Ductal carcinoma in situ

Variability in study design and selection criteria makes the occurrence of ductal carcinoma in situ (DCIS) in elderly women difficult to assess. A French survey done in 2003–04 reported that 13·4% of women treated for DCIS were 70 years or older.25 DCIS in elderly patients was mammographically detected in 83·8%, compared with 91·6% in younger women (p<0·0001).25

There is little outcome data for elderly women treated for DCIS. A meta-analysis confirmed significant benefit from adjuvant

Surgery

Standard of care for operable breast cancer is BCS plus whole-breast radiotherapy (WBRT), or mastectomy followed by postoperative radiotherapy in selected patients. For patients with clinically positive or highly suspected nodes, axillary lymph-node dissection (ALND) is recommended, however management of the axilla in clinically and radiologically lymph-node-negative disease is controversial. Standard of care has been sentinel lymph-node biopsy (SLNB) with completion ALND for sentinel lymph

Radiotherapy omission

Omission of WBRT after BCS in elderly patients with breast cancer is controversial. Most randomised trials assessing WBRT omission excluded patients older than 70 years. In a meta-analysis by Clarke and colleagues,32 only 9% (550 of 6097) of node-negative patients who received BCS were older than 70 years. This meta-analysis showed that a 16% reduction in LRR from radiotherapy after BCS led to a 5% reduction in breast-cancer mortality at 15 years.32 However, none of the randomised trials

Systemic treatment

Decisions about systemic treatment should reflect the breast-cancer biological subtype. Such an approach is extrapolated from data in the general breast-cancer population, since there are no subtype-specific treatment data for elderly patients.

Neoadjuvant therapy

Patients with locally advanced disease or large tumours relative to breast size might be offered preoperative systemic therapy to render surgery feasible or to make breast conservation possible. Most elderly patients have ER-positive, HER2-negative disease, tumours which are likely to respond to neoadjuvant endocrine therapy. Neoadjuvant aromatase inhibitors are better than tamoxifen.43, 44, 45 Neoadjuvant chemotherapy alone or with HER2-targeted treatment should be considered for triple

Primary endocrine therapy

Primary endocrine therapy, by contrast with neoadjuvant treatment, refers to systemic endocrine treatment as sole treatment for early stage ER-positive breast cancer. A Cochrane review showed a decrease in local progression with surgery plus endocrine treatment compared with primary endocrine therapy alone; however, no difference was observed in overall survival.46 For optimum local control, surgery (with or without radiotherapy) plus adjuvant endocrine therapy is better than primary endocrine

Adjuvant hormonal treatment

A Danish Breast Cancer Cooperative Group study47 identified a subgroup of patients who might not benefit from adjuvant systemic treatment. In the absence of any systemic therapy, women aged 60–74 years with small (≤10 mm), node-negative, endocrine-responsive, grade 1 ductal carcinoma or grade 1 or 2 lobular carcinoma did not have increased mortality compared with age-matched women in the general population. In such patients with very low-risk tumours, or patients with life-threatening

Benefit of chemotherapy in older individuals

There is no evidence to support differential use of specific chemotherapy drugs or dose reductions in older patients compared with younger ones. A CALGB study provided important information on the value of adjuvant chemotherapy.54 Patients 65 years or older were randomised to standard chemotherapy (cyclophosphamide, methotrexate, and fluorouracil [CMF] or cyclophosphamide plus doxorubicin [AC]) or capecitabine. At 3 years, relapse-free survival (RFS) and overall survival were significantly

Adjuvant trastuzumab

Healthy patients with HER2-positive breast cancer and without cardiac disease should be offered trastuzumab in combination with chemotherapy. There is no clinical data available for treatment with trastuzumab alone in patients who are not candidates for chemotherapy; however, the 2011 St Gallen consensus states that if chemotherapy cannot be given, it might be reasonable in some settings to give trastuzumab without it.48

Metastatic breast cancer

Older women are more likely than younger women to present with more advanced breast cancer. There is a delicate balance between overtreatment and undertreatment of advanced disease, in which maintenance of QoL is a priority.

Bone health

In elderly patients, decreases in bone mineral density and osteoporosis are prevalent. Antiresorptive therapies are standard of care for maintaining bone health in patients with osteoporosis and those with cancer, particularly when receiving drugs such as aromatase inhibitors.53, 69 Several bisphosphonates and denosumab are currently approved or under evaluation in the USA or Europe, but antiresorptive therapies are underused in elderly patients.53, 69 Special considerations should be made for

Drug safety and compliance

Careful drug prescribing in elderly patients with breast cancer is essential because of physiological age-related pharmacokinetic alteration, comorbidities, and polypharmacy. Physiological ageing can be associated with altered pharmacokinetics (drug absorption, distribution, metabolism, and excretion) which can affect efficacy and toxicity. Many drugs have reduced liver metabolism in older people, attributable to decreased hepatic blood flow and liver mass rather than altered activity of

Patient preferences

Older patients generally prefer to be well informed, with no significant age-dependent information needs.75, 76 Patients might have misperceptions about breast cancer and about excessive treatment toxicity for no or limited benefit. It is necessary for clinicians to provide clear information to elderly patients and discuss the diagnosis, prognosis, expectations of treatment, and the potential negative effect of undertreatment.1

A small proportion of older patients want an active role in decision

Male breast cancer

Male breast cancer represents less than 0·5–1·0% of all breast cancers. Median age at diagnosis is 64 years.82 In Surveillance, Epidemiology and End Results (SEER) data from 2003–2004, 392 men had invasive disease: 24% aged 70–79 years and 17% aged 80 years or older.83 Elderly men with breast cancer seem to have similar survival to elderly women with breast cancer. Breast cancer in elderly men is usually self-detected and most are ER-positive.83 Rates of HER2 overexpression are reported as

Conclusions

No aspect of management of older individuals with breast cancer should be driven by chronological age alone. A multidisciplinary oncological and geriatric approach can optimise management. Patient preference, comorbidities, and potential toxicity should guide management decisions. Patients should be closely monitored, with prompt intervention for toxicity. Several breast-cancer trials in older individuals have closed prematurely because of poor accrual. In some settings, prospective subgroup

Search strategy and selection criteria

Medline was the primary information source for this task force. A search of PubMed was done for English language articles published from 2007 to June, 2010, for the updated sections, and from 1990 to June, 2010, for the new sections. The search terms used were “breast neoplasms”, “aged”, “aged 80 and over”, “frail elderly”, “survival”, “geriatric assessment”, “mammography”, “radiography”, “mastectomy”, “segmental”, “lymph node excision”, “sentinel lymph node biopsy”, “radiotherapy”,

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