“We are in the midst of a steep increase” in the incidence of breast cancer among women aged 65 years and older, Arti Hurria, MD, reported at the 19th Annual Lynn Sage Breast Cancer Symposium, Chicago.1 “Are we prepared as a health-care system and as providers to address this burgeoning need?” she asked.
According to Dr. Hurria, several factors indicate that more preparation is needed. The underrepresentation of older Americans in clinical trials “highlights that we study a younger population while we treat an older population,” she noted. Evidence-based information about the efficacy and toxicity of newer drugs function in older adults is very limited, she said, although representatives of ASCO, the U.S. Food and Drug Administration (FDA), and the pharmaceutical industry are meeting to address this issue at an ASCO-FDA symposium.
Dr. Hurria is Vice Provost of Clinical Faculty, Director of the Center for Cancer and Aging, and the George Tsai Family Chair in Geriatric Oncology, City of Hope, Duarte, California.
“The challenge we face is that we work in the ultimately efficient clinic, designed to see more patients in less time,” Dr. Hurria noted, “and we need to find a way to integrate geriatric assessment into our workflow.” Often the clinician first sees a patient already in a gown on an examination table, losing cues of functional age, such as the patient’s ability to walk or get up onto the examining table. A geriatric assessment can provide this critical information which predicts the risk of morbidity and mortality in older adults and guides interventions to address these vulnerabilities. The assessment includes an evaluation of functional status, comorbid medical conditions, cognition, nutritional status, psychological state, social support, and the number and type of medications the patient is taking.
The challenge we face is that we work in the ultimately efficient clinic, designed to see more patients in less time, and we need to find a way to integrate geriatric assessment into our workflow.— Arti Hurria, MD
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A study in 500 patients at least 65 years old with several different types of cancer who had geriatric assessments identified 11 variables that independently predict chemotherapy toxicity,2 and the predictive model was externally validated in an independent cohort of 250 patients.3 The patient’s age was only one out of 11 predictors of chemotherapy toxicity. Of the remaining 10 predictors, 4 were tumor and treatment variables, and 5 were geriatric assessment variables: fall(s) in the past 6 months, hearing impairment, limited walking ability, assistance needed to take medication, and decreased social activity.
The results of the study were used to create a predictive model, available at the website of the Cancer and Aging Research Group (www.mycarg.org). Other similar models are also available. Dr. Hurria and colleagues at 16 institutions are completing a study in 500 older adults to develop a breast cancer–specific model for adjuvant therapy.
Selecting Patients for Adjuvant Therapy
The value of a geriatric assessment was seconded by Hyman B. Muss, MD, Mary Jones Hudson Distinguished Professor in Geriatric Oncology and Director of Geriatric Oncology at the University of North Carolina at Chapel Hill School of Medicine.4 The assessment can reveal factors useful in selecting cancer treatment in older patients.
In general, if older patients are in good condition, they can receive the same treatments as younger patients, Dr. Muss said. If patients are vulnerable and “you can do interventions to get them in better condition, certainly do so. It may delay treatment a little bit but can be very helpful. It is questionable whether frail people should get any of these therapies, because frequently they are going to be people with very short survivals. If they are too sick, they need palliative care.”
Defining Treatment Goals
“In early-stage breast cancer, our goals are to use adjuvant therapy to increase cure,” Dr. Muss said, “but patients also want to maintain function and independence as long as possible. They want a good quality of life, they want to minimize toxicity, and they want to have a meaningful survivorship.”
As time goes on with older people, they are always going to have a poorer survival than younger patients … [but it is] not necessarily due to their breast cancer or another malignancy.— Hyman B. Muss, MD
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The majority of patients with hormone receptor–positive disease irrespective of HER2 status relapse after the 5-year mark, Dr. Muss noted. Treatment for these patients is endocrine therapy and perhaps chemotherapy for some, and those who have HER2-positive tumors may also benefit by chemotherapy and anti-HER2 therapy. Patients with HER2-positive and hormone receptor–negative breast cancer, as well as those with triple-negative disease, frequently relapse within a 5-year period and should be treated with chemotherapy, with many also receiving anti-HER2 therapy. Most patients with triple-negative breast cancer, except those with the smallest tumors, are treated with chemotherapy.
The Predict model provides survival estimates with and without adjuvant therapy for 5 and 10 years following surgery for breast cancer. Dr. Muss noted that the model uses average life-expectancy data for the United Kingdom, “which is probably similar to most, but not all, of North America.” The Predict model can be accessed at www.predict.nhs.uk/technical.html.
Based on Oxford Criteria, if the 10-year overall survival benefit with chemotherapy is < 3%, chemotherapy is not recommended. If 10-year overall survival benefit with chemotherapy is 3% to 5%, treatment should be discussed, and if it exceeds 5%, chemotherapy is recommended.
For more on the Predict model, designed to help patients and physicians decide on a course of treatment following breast cancer surgery, visit www.predict.nhs.uk.
Anti-HER2 therapy alone is administered “only on the rarest of occasions,” Dr. Muss said. Updated data from a trial of adjuvant paclitaxel and trastuzumab (Herceptin) among 410 women with small node-negative HER2-positive breast cancer (including 96 patients aged 60 to 70 and 41 patients over age 70)5 showed that at 6.5 years, only 4 patients had distant metastases.
These results are “almost hard to believe,” Dr. Muss remarked. “This is a very appropriate regimen for older people. But if you are considering neoadjuvant therapy, especially in someone with a HER2-positive, node-negative tumor that is not that big, perhaps a surgical procedure first … would be appropriate, so you can minimize the amount of chemotherapy and anti-HER2 therapy that you give later.”
Toxicities and Hospitalizations
“Chemotherapy-induced peripheral neuropathy is becoming one of the most important long-term toxicities of chemotherapy,” Dr. Muss noted. Even grade 2 neuropathy “might take someone from independent living to assisted living.
“Another major issue is hospitalization,” Dr. Muss said. “With virtually all adjuvant chemotherapy regimens, there is a substantial risk of hospitalization, and hospitalization is the worst thing for an older person in the United States, because frequently that 3- to 5-day hospitalization for neutropenic fever or other toxicity is the beginning downhill trajectory compromising survival and quality of life.” Dr. Muss and Dr. Hurria are working together on a trial to determine if a walking intervention can ameliorate some of the toxicities of chemotherapy.
When More Chemotherapy Is Better
The biology of triple-negative breast cancer is similar irrespective of age, Dr. Muss said, and “more chemotherapy is better, but it is more toxic. Most of the meta-analyses looking at these patients show that anthracyclines and taxanes are more effective than nonanthracycline regimens. Estimating life expectancy is key, because this is going to be very aggressive chemotherapy.”
A meta-analysis of four trials showed that adjuvant chemotherapy improved disease-free survival as much for older as for younger patients, but overall survival was significantly worse for patients 65 and older.6 “As time goes on with older people, they are always going to have a poorer survival than younger patients due to their higher likelihood of comorbidities,” Dr. Muss said, “and not necessarily due to their breast cancer or another malignancy.” ■
DISCLOSURE: Drs. Hurria and Muss reported no conflicts of interest.
2. Hurria A, Togawa K, Mohile SG, et al: Predicting chemotherapy toxicity in older adults with cancer: A prospective multicenter study. J Clin Oncol 29:3457-3465, 2011.
3. Hurria A, Mohile S, Gajra A, et al: Validation of a prediction tool for chemotherapy toxicity in older adults with cancer. J Clin Oncol 34:2366-2371, 2016.
5. Tolaney SM, Barry WT, Dang CT, et al: Adjuvant paclitaxel and trastuzumab for node-negative, HER2-positive breast cancer. N Engl J Med 372:134-141, 2015.
6. Muss HB, Woolf S, Berry D, et al: Adjuvant chemotherapy in older and younger women with lymph node-positive breast cancer. JAMA 293:1073-1081, 2005.