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