By the year 2030 most patients with breast cancer will be aged 65 years or more and many will be frail. Frailty implies diminished physiologic reserve; contributors include diminished organ function, comorbidities, impaired physical function, and geriatric syndromes. Time-efficient tools for assessing frailty are being developed and, once validated, can be used to identify frail cancer patients and help direct therapy. Screening mammography in frail patients is questionable, and a clinical breast exam is likely to identify breast cancers that warrant intervention. Hormonal therapy may be a reasonable primary therapy in older frail women with hormone receptor–positive lesions. For estrogen receptor– and progesterone receptor–negative lesions, excision of the primary tumor may be adequate. Adjuvant hormonal therapy may be appropriate in frail elders with high-risk hormone receptor–positive breast cancer; chemotherapy is rarely indicated regardless of tumor status. The majority of frail elders with metastases will have hormone receptor–positive breast cancers, and endocrine therapy should be considered; those with receptor-negative tumors may be treated with single-agent chemotherapy or supportive care measures. Oncologists need to acquire the skills to appropriately identify frail elders so they select appropriate therapies that will minimize toxicity and maintain quality of life.
Metastatic Breast Cancer
Metastatic breast cancer is incurable, and the goals of treatment are to control symptoms and disease progression, and improve quality of life. The majority of frail elders with metastatic breast cancer will have hormone receptor–positive tumors, and the mainstay of treatment is endocrine therapy. For patients who have not had prior endocrine therapy, the initial use of an aromatase inhibitor is probably the best choice. Upon disease progression, other endocrine agents should be used, including tamoxifen, other aromatase inhibitors, or fulvestrant (Faslodex).
Megestrol acetate or high-dose estrogens are also appropriate in selected patients with slow progression of metastases who have exhausted other hormonal agents. For the frail elder with hormone receptor–positive early breast cancer who develops metastatic disease while being treated with primary endocrine therapy, a similar strategy should be used. Such a treatment plan is likely to control metastases for the lifetime of the patient.
For patients refractory to endocrine therapy or those with hormone receptor–negative breast cancer, single-agent chemotherapy can be tried. Many single agents are well tolerated and can be started in smaller does to minimize toxicity. These include the oral agent capecitabine (Xeloda), weekly low-dose anthracyclines or pegylated liposomal doxorubicin (Doxil), weekly taxanes, vinorelbine, and gemcitabine (Gemzar). For those with HER2-positive tumors, trastuzumab (Herceptin) alone can be considered and is usually well tolerated. Frail elders treated with chemotherapy need to be closely monitored for toxicity.
For patients with bone metastases, radiation administered to affected areas can be most effective. IV bisphosphonates, which can reduce pain and other skeletal events, should be considered for patients with painful lesions. Radiation should also be considered for treatment of central nervous system (CNS) metastases or other localized metastatic lesions. A major issue in many frail elders with CNS metastases is whether to treat at all, especially those with cognitive disorders. The decision to treat must include a careful discussion of the goals of treatment with the patient, her family, and her other caregivers.
At some point, treatment of metastatic cancer becomes futile and such patients should be referred for palliative and hospice care. Such care is also appropriate for frail elders with metastatic disease who decline therapy. This is likely to occur much sooner in frail elders with metastases than in their healthier counterparts.
Breast cancer has been undertreated in elderly individuals, and elders continue to be underrepresented in clinical trials,[61,62] despite data that older women with breast cancer and younger postmenopausal patients derive similar benefits from treatment.[63,64] However, some elders may be unable to tolerate the toxicity and stress associated with cancer therapy. Frail elders with breast cancer are a challenging group. Geriatric assessment can help identify frail patients and suggest useful interventions. Nevertheless, most frail patients are still likely to have a shortened survival that minimizes the benefits of standard therapies.
The increasing numbers of older adults with a cancer diagnosis demand that oncologists prepare themselves to mange the challenges of the frail older cancer patient. In particular, skills to appropriately target the intensity of interventions, to identify complicating factors, and to prevent toxicity and institute supportive care where appropriate are needed. Balducci has suggested that several questions be considered prior to making treatment decisions: Will the patient die of cancer or with cancer? Will the patient suffer the complications of cancer during his/her lifetime? Is the patient able to tolerate the treatment of cancer? Is palliation appropriate? These questions help frame a treatment approach.
The National Comprehensive Cancer Network (NCCN) has put forth a treatment guideline for senior adult oncology patients. The NCCN guideline includes the Fried criteria for assessing frailty, an example of Comprehensive Geriatric Assessment, and the VES-13 as a screen for impairment. In addition to evaluating the patient, it is important to consider the effects of the patient's illness on family and friends, and to realize that the patient may be independent at the beginning of therapy but become temporarily or permanently dependent over time. A support system is necessary to assess function, monitor side effects, and assist in emergencies.
More research is needed to define frailty, identify its contributors, and develop assessment tools for the older oncology population. It is not yet clear how an abnormal finding on screening for frailty should impact cancer therapy decision-making. Future research evaluating variations in treatment intensity and best supportive care when warranted would be enhanced by a rigorous assessment of frailty and frailty risk. Assessment of frailty needs to be integrated into evaluation of response, toxicity, survival, and quality of life among elderly cancer patients.
The authors have no significant financial interest or other relationship with the manufacturers of any products or providers of any service mentioned in this article.
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