Washington, DC—With more breast cancer survivors living longer, patients and their physicians face challenges regarding appropriate follow-up care. In addition, younger and older women have different survivorship issues as well as ones in common, such as cognitive impairment after chemotherapy and the occurrence of lymphedema. Speakers addressed approaches to these issues in a session on Challenges in Survivorship at the 2008 Breast Cancer Symposium, held in Washington, DC September 5-7.
Hyman Muss, MD, Professor of Medicine at the University of Vermont and a member of the Vermont Cancer Center in Burlington, noted that the majority of women with breast cancer will die of other causes and so general medical follow up is an essential part of patient management. Whereas patients perceive high value in blood tests and imaging to detect recurrences in the absence of symptoms, Dr Muss said such tests do not detect asymptomatic metastases and do not prolong survival or improve health related quality of life (HRQoL—see, for example, GIVIO Investigators. JAMA. 1994;271:1587-1592.)
American Society of Clinical Oncology (ASCO) guidelines recommend regular history and exams, mammography, and breast self-exam but not blood work, chemistries, assessment of tumor markers, or other imaging except as specifically indicated. Dr Muss says giving a copy of the guidelines (available at www.cancer.net/patient/ASCO+Resources/Patient+Guides/ASCO+Patient+Guide%3A+Follow-Up+Care+for+Breast+Cancer) to patients helps them to understand what should be done “because every patient asks you about follow up usually at some point in medical oncology...and that's very helpful to them.”
He also gives patients a checklist to fill out that uncovers survivorship issues that may otherwise be missed
in a busy practice. His list, which becomes part of the patient record, involves symptoms of recurrence, lymphedema, nutrition, fatigue, bone loss, and cognitive function, as well as vasomotor symptoms, sexual function, fertility issues, emotional issues, work status, and any new cancers in relatives.
Who should do cancer follow up is a troubling question. A 2007 ASCO survey estimated that by 2025 there will be a severe shortage of oncologists, resulting in a deficit of 40 million physician visits a year. One randomized trial (Grunfeld E, et al. J Clin Oncol. 2006;24:848-855) found that recurrence rates, serious clinical events, mortality, and HRQoL outcomes were the same whether primary care physicians or oncologists followed early-stage breast cancer patients. The bad news is that primary care physicians will also be in short supply.
Physician assistants, nurse practitioners, and oncology nurses may help to fill the gap. “After a year or 2 they know how I think...and they frequently come up with things I haven't thought of, but I think they're scare commodities, too,” Dr Muss said. “One strategy might be to develop survivorship clinics where you had 1 or 2 of these people working with a whole bunch of other people to address multiple issues at once.”
Survivorship Issues With Age
Younger and older women may experience different issues after treatment for cancer. Ann Partridge, MD, MPH of the Dana-Farber Cancer Institute and Assistant Professor in Medicine at Harvard Medical School in Boston said about 5% to 6% of breast cancers are diagnosed in women <40 years old, who often have more aggressive disease and therefore receive more aggressive treatment, with more late effects.
“Many of these problems are related to premature menopause, such as sexual dysfunction, possibly psychosocial distress, weight gain, possibly fatigue,” she noted. “And younger women have a much longer time to live on average...so you've got a lot more time to have problems, like potential secondary leukemia or cardiac dysfunction,” as well as osteoporosis and cognitive impairment. Late effects specifically related to hormone therapy include endometrial malignancies, cataracts, thromboembolic events, and hyperlipidemia.
Dr Partridge said that fertility and pregnancy are the major issue for many young women. “Pregnancy after breast cancer looks to be safe,” she advised, and several studies have not demonstrated any adverse effects of subsequent pregnancy on prognosis. But all the studies are limited because one can not do a randomized controlled trial for this outcome. Furthermore, she explained that timing of pregnancy can be difficult, especially for women with hormone-sensitive disease, because pregnancy planning can affect their treatment decisions and adherence to and optimal length of therapy.
More research is needed in psychosocial areas, including whether young women will still be able to care for children, work, go to school, finish a degree, build a career, and maintain a positive body image, according to Dr Partridge.
For older breast cancer survivors especially pertinent issues are treatment-related leukemia, congestive heart failure (CHF), and osteoporosis, along with emotional needs. Arti Hurria, MD, Director of the Cancer and Aging Research Program at City of Hope in Duarte, California, discussed survivorship issues in this population.
The risk of leukemia and myelodysplasia associated with adjuvant chemotherapy increases with age (incidence of 0.3% for <50 years vs. 1.8% for ≥65 years; Muss HB, et al. J Clin Oncol. 2007;25:3699-3704). While age itself is a risk factor for CHF, administering anthracycline chemotherapy and/or trastuzumab increases the risk.
Osteoporosis and fracture risk increase with age, and treatment with aromatase inhibitors (AI's) exacerbates the problem, especially for women with pre-existing osteoporosis. Results of the Arimidex, Tamoxifen, Alone or in Combination (ATAC) trial showed anastrozole treatment was associated with a 6% to 7% bone loss during about 5 years of treatment, Dr Hurria said. The risk of fracture was 11% with anastrozole versus 7.7% with tamoxifen during the treatment period (Howell A, et al. Lancet. 2005;365:60-62). Women on AI's also complained more of musculoskeletal side effects and arthralgias, she said.
Based on guidelines from the ASCO Bone Health Task Force, she recommended screening women for osteoporosis if they are >65 years; 60 to 64 years with a history of nontraumatic fracture, a family history of osteoporosis, or weight <70 kg; are postmenopausal and receiving an AI; or were premenopausal with treatment-associated menopause. Furthermore, bone mineral density should be assessed, and women should receive advice concerning adequate intake of calcium and vitamin D, weight-bearing exercise, muscle resistance training, and avoiding tobacco or excess alcohol intake.
Finally, Dr Hurria warned that CHF is the most common cause of hospitalization for patients >65 years. Predictors of CHF are diabetes mellitus, hypertension, coronary artery disease, age, black race, and treatment with trastuzumab and/or anthracycline, so modifiable risk factors should be identified and addressed.
Cognitive Concerns
Cognitive complaints relating to memory, attention, and concentration are common as people age, and similar complaints may occur with cancer and its treatment. So Patricia Ganz, MD of the University of California Los Angeles Schools of Medicine and Public Health and the Jonsson Comprehensive Cancer Center posed the question to the breast cancer symposium audience of whether “chemobrain” exists. Animal models, human performance testing, and brain imaging studies support the idea that chemotherapy may cause cognitive changes.
“The most common time that we see cognitive complaints is while people are actually on chemotherapy,” she said, when patients are anxious, distressed, and may not be sleeping well, and when treatments such as diazepam may interfere with thinking. Somewhat more concerning is when patients can not concentrate 6 to 12 months after chemotherapy. For 10% to 15% of women, therapy-associated cognitive decline may seriously impair quality of life.
Chemotherapy may induce premature menopause, with accompanying memory problems and vasomotor symptoms. So not all cognitive complaints are directly related to chemotherapy, Dr Ganz proposed.
Detailed neuropsychological (NP) testing reveals that 10% to 15% of women show subtle abnormalities before ever getting treatment, so the true incidence of treatment-associated cognitive decline is uncertain. Ironically, women who complain of memory, concentration, and multitasking problems are often different from the ones who test poorly. “The ones who test poorly, it really doesn't bother them,” Dr Ganz said.
“Many of the women who are diagnosed with breast cancer are very, very high functioning...and they are very sensitive to minor changes in their cognitive abilities, whereas somebody who is not having so many stresses and demands on their cognitive function may be less aware of those kinds of changes,” she noted.
She advised reassuring breast cancer patients that cognitive problems are infrequent and not necessarily caused by chemotherapy treatment. Nonetheless, “use chemotherapy judiciously,” she said, and only when its benefits outweigh its potential risks, especially with adjuvant therapy for early-stage tumors when one expects those women to do well.
If a woman complains of actually having trouble concentrating and remembering, Dr Ganz advises taking a careful history, using Dr Muss's checklist, and treating anxiety, depression, insomnia, and menopausal symptoms. If the patient does not improve, she recommends getting an NP consultation. Finally, teaching coping and organizational skills, such as how to manage daily activities, use an electronic or paper organizer, reduce distractions, and limit multitasking, may be useful.
Lymphedema
Posttreatment lymphedema is a major concern for breast cancer survivors. Limb volume changes >5% occur in as many as 60% of breast cancer survivors following surgical treatment. Current challenges are awareness, access to quality care, and good clinical and basic science programs to address the problem, according to Janice Cormier, MD, MPH, Associate Professor of Surgery and Biostatistics at the University of Texas MD Anderson Cancer Center in Houston and Chairperson, Medical Advisory Committee of the National Lymphedema Network.
Disruption or obstruction of lymphatic channels reduces lymph flow, increasing pressure in the remaining channels. The accumulation of protein-rich fluid in tissues causes inflammation leading to fibrosis, impaired immune responses, and fatty degeneration of connective tissue.
“Breast cancer surgery is the most common cause of secondary lymphedema in industrialized countries,” Dr Cormier said. Currently identified risk factors are older age, tumor burden, extensive surgery, radiation therapy, and increased body mass.
She related the findings of a prospective cohort study of 269 women undergoing surgery for breast cancer. “Patient-reported symptoms and quality-of-life differences were detected with limb volume changes as low as 5%, which for the most part presents with subtle medical findings that may not be detected on routine exam, indicating that symptom assessment may be a valuable screening tool for our patients,” she said.
Current standard of care is complete decongestive therapy (CDT), a multicomponent treatment regimen that includes manual lymphatic drainage, multilayer short-stretch compression bandages, remedial exercises, skin care, education in self-management, and elastic compression garments. Intermittent pneumatic compression may be an adjunct to CDT. Surgical approaches have been tried (eg, excisional operations, including debulking and liposuction; or lymphatic reconstruction with microvascular techniques such as lymphatic transplants or lymphovenous shunts), but outcomes research involving objective measures is lacking.
The American Lymphedema Framework Project was recently launched in partnership with other organizations to establish a leadership role in best practices. Headed by Jane Armer, PhD, RN, it aims to improve outcomes, establish evidence-based and expert consensuses, educate and mentor health professionals, conduct research, and participate in the International Lymphedema Framework Program.
Dr Cormier advised that CDT “involved as it is,” continues to be the primary treatment modality.
“Symptom assessment and limb volume measurements should be an integral component of posttreatment surveillance for all breast cancer survivors,” she said.