HYMAN B. MUSS, MD, is Professor of Medicine and Director of the Geriatric Oncology Program at the University of North Carolina Lineberger Comprehensive Cancer Center.
Breast cancer, like most solid tumors, is a disease of aging, with an incidence that dramatically rises with increasing age. As the population ages, more and more older women with breast cancer will require oncology services that will pose challenges for surgical, medical, and radiation oncologists. What’s different about older women with breast cancer is that they frequently have major comorbidity, and breast cancer is not always their most important medical problem.
The first thing I do when seeing an older breast cancer patient is take a detailed social history so I get a feel of what the patient’s life is like, her social support system, and what’s important to her. After that I usually take a few moments and calculate her life expectancy -- exclusive of her breast cancer. I use www.eprognosis.org for this. It has several scales that give reasonable estimates of survival for community-dwelling elders. You should select a scale to use in your practice because some of the questions in the various scales relate to geriatric issues that most of us don’t incorporate (or ask about) in the usual history and physical examination (like how far can you walk?). Once you know your patient’s life expectancy, the next order of business is to define the goals of therapy. For older women with metastatic disease, the goals of treatment are ameliorating cancer-related symptoms while maintaining the highest quality of life. The best approach for almost all these older women with metastases is to use endocrine therapy for those with hormone-receptor positive tumors until it is clear that the tumor is refractory to endocrine treatment, and then consider sequential single-agent chemotherapy.
For those with earlier-stage disease, the goal of therapy -- as in younger patients -- is increasing the chances for cure. Unless older women have a very short estimated survival, definitive surgery with either lumpectomy or mastectomy should be considered. Older women with hormone-receptor positive tumors can be managed with primary endocrine therapy, but unless they have very short estimated survival, the majority will have tumor progression by five years, and initial surgery is a better option for most. In addition, older women with hormone-receptor positive tumors less than or equal to 2 cm treated with lumpectomy, and who are willing to take endocrine therapy, can be spared breast irradiation without any adverse influence on survival. Women who elect this path of treatment will have a higher rate of in-breast recurrence at 10 years -- about 10 percent compared with two to three percent for patients who receive breast irradiation – but if they relapse they can be treated again with surgery and then if needed, radiation.
For older women with hormone-receptor positive tumors, endocrine therapy is the mainstay of systemic treatment, and the decision as to whether to also suggest chemotherapy should be based on its potential added value to endocrine therapy. For most node-negative patients, and many with one to three positive nodes, genomic assays (Oncotype DX and others) can be helpful in estimating the potential benefits of chemotherapy. In addition, it always pays to remember that the bulk of relapses in women with hormone-receptor positive tumors treated with an adjuvant endocrine therapy occur after five years. This is why it’s so important to calculate the non-breast cancer related estimated survival as even older hormone-receptor positive patients with extensive nodal involvement will rarely benefit from chemotherapy if their estimated survivals are less than five to 10 years.
For those with early-stage hormone-receptor negative and HER-2 negative (“triple-negative”) tumors and estimated survivals exceeding five years, chemotherapy is the treatment of choice and should be considered for most patients. Those with small tumors less than 1 cm should be considered for chemotherapy on an individual basis. Online programs such as www.adjuvantonline.com and www.predict.nhs.uk/predict.shtml can help greatly in the selection of treatment. Unless there is a major benefit from more intensive anthracycline- and taxane-based therapy in these patients -- I like to see at least a 3% improvement in overall survival for the more aggressive, toxic, treatment -- I favor non-anthracycline regimens such as docetaxel and cyclophosphamide (TC). Cyclophosphamide, methotrexate, and fluorouracil can also be considered in this setting, although it is not as effective and takes longer to complete treatment than TC does. I use white blood cell growth factors in all older patients I treat with TC as in community settings the risk of neutropenic fever can exceed 20 percent.
What about older patients with HER2-positive breast cancer? For those with early-stage potentially curable cancers and reasonable life expectancy, I recommend chemotherapy and anti-HER2 directed treatment. It’s important to factor into your treatment decision that women with hormone-receptor positive, HER2-positive tumors (HR+/HER2+) have less aggressive clinical courses than those who present with hormone-receptor negative and HER2-positive phenotypes. I use www.predict.nhs.uk/predict.shtml to calculate the added value of chemotherapy and anti-HER2 based therapy in HER2-positive patients as HER2 status can be incorporated into the model. For those for whom I recommend chemotherapy and anti-HER2 directed treatment, I tend to use non-anthracycline combinations such at docetaxel, carboplatin, and trastuzumab. Trials of anti-HER2 based adjuvant therapy without chemotherapy are in progress. In addition, new agents such as ado-trastuzumab emtansine may prove to be ideal treatments in this setting. For those with metastatic HER2-positive breast cancer there are numerous choices, and such treatment decisions should be individualized and based on the tempo of the disease, the extent of the metastases, anticipated toxicity, and symptom burden.
A comprehensive geriatric assessment can play a major role in optimizing the management of older patients with cancer, regardless of type. Screening instruments and short versions of such assessments are gaining popularity and likely to be helpful in suggesting interventions that improve function and quality of life prior to and during treatment. In addition models that use a combination of clinical and geriatric assessment variables may prove to be extremely helpful in predicting chemotherapy toxicity. Consider also the frail elderly; here the overriding goals of care are maintenance of function and quality of life and any treatment that does not support these goals should be discouraged.
My hope is that this discussion will be helpful to you for treating the older woman with breast cancer. Expected survival, which is dependent on so much more than age, and the goals of treatment, are the prime considerations when approaching the older breast cancer patient. In addition, and most important, is asking the patient and family what their expectations of treatment are, and tailoring treatment options to their wishes. Providing the best options and making the right treatment decision for an older patient frequently is a major challenge but is always worth your time and effort.