Newsletters - February 2010
Lymphedema After Breast Cancer Surgery
by Tina W.F. Yen, MD, MS, Assistant Professor of Surgery
Lymphedema, or arm/hand swelling, is an important source of treatment-related morbidity among breast cancer survivors. Lymphedema causes physical discomfort and disability, as well as a cosmetic deformity which can result in psychosocial issues (anxiety, depression, and emotional distress) that further adversely affect activities of daily living and quality of life. Minimizing treatment-related morbidity in breast cancer survivors is important.
Despite the well-known morbidity of this chronic problem, a better understanding of lymphedema risk factors is important to moving this field ahead. Two well-established risk factors for lymphedema are the extent of axillary lymph node dissection (ALND) and the combined treatment of axillary radiation and ALND. The relative contribution of several other factors to the development of lymphedema needs to be better studied. These factors include patient age, body mass index, hand dominance, extent of disease, type of breast and axillary surgery, and various treatment modalities (modern radiotherapy, chemotherapy and hormonal therapy). Furthermore, since axillary surgery results in the iatrogenic disruption and damage of lymphatic channels, it is likely that surgeon technique plays a role in the development of lymphedema.
The current literature has two main limitations. First, there is a paucity of population-based studies. Almost all studies are retrospective, largely single-institutional with small numbers of patients. In addition, these studies are difficult to compare as patient populations were diverse, surgery and radiation treatments differed and duration of follow-up varied. There is no standard definition or measurement of lymphedema or standard time interval to assess for its development. Finally, these studies have the potential for substantial selection bias of patients and surgeons. Therefore, these study results may not be applicable to the at-large population of breast cancer patients who are operated on mostly by community surgeons who perform relatively few breast cancer operations annually.
The second limitation is that much of the literature relates to older surgical techniques. Most of the previous studies were performed 20 to 30 years ago, when more radical breast and axillary surgeries were performed and axillary radiation therapy was more frequently utilized. Now, we have improved techniques. The combined treatment of ALND and axillary radiation has not been routinely recommended since around the late 1980s. Current guidelines recommend less extensive axillary dissections (levels I and II only in most situations) and the avoidance of circumferential stripping of the axillary vein and removal/splitting of the pectoralis minor muscle. More women are candidates for less invasive breast and axillary surgery: breast-conserving surgery, or BCS (lumpectomy followed by breast radiation) and sentinel lymph node biopsy, or SLNB. SLNB has probably been the biggest technical advance in decreasing lymphedema and other arm morbidities.
Given these limitations, we evaluated potential risk factors for lymphedema in a large population-based cohort of 3,083 older women (ages 65-89) undergoing incident breast cancer surgery in 2003. These women were drawn from the Medicare population in four large, geographically diverse states (California, Florida, Illinois, New York) and completed four telephone surveys. Surveyors collected information on demographic variables, disease extent, treatments, recurrent disease and quality of life measures. State tumor registry and Medicare claims information was also collected. Our initial work in 1,338 women who reside in California and Illinois and were operated on by 707 different surgeons showed that 14 percent of these women had self-reported lymphedema at four years postoperatively. When controlling for patient age, tumor size, type of breast cancer, type of breast and axillary surgery, receipt of radiation, chemotherapy and hormonal therapy, and surgeon case volume, the only independent predictors of lymphedema were the removal of more than five lymph nodes and the presence of lymph node metastases. Of particular note, in contrast to many older studies, the receipt of radiation therapy was not associated with lymphedema development. Furthermore, the number of lymph nodes
removed was more predictive of lymphedema than whether a SLNB or more extensive ALND was performed. In subsequent analyses of more than 1,800 women in this cohort, the overall incidence of lymphedema at five years was 20 percent and the removal of more than five lymph nodes and the presence of lymph node metastases remained predictors of lymphedema. Furthermore, other potential risk factors (patient body mass index, hand dominance, surgeon volume and hospital volume) were not associated with lymphedema development.
The finding that the risk of lymphedema is substantial with the removal of more than five lymph nodes is of significant clinical importance for patients undergoing SLNB alone, as the actual number of lymph nodes removed is a modifiable factor that is controlled by the surgeon. We advocate that a sufficient number of lymph nodes need to be removed to accurately determine nodal status. However, among women who undergo SLNB and are found to have a positive/metastatic sentinel lymph node, the metastatic sentinel lymph node is identified in the first three sentinel nodes in 97 percent to 100 percent of patients. For patients who undergo SLNB alone, the increased morbidity of removing more than five sentinel lymph nodes may need to be weighed against the possible additional information gained (if a positive node is identified after the fourth or higher sentinel node) that may alter treatment for a small number of patients.
Finally, our initial work demonstrates no association between surgeon and hospital volume and lymphedema development. Although surgeon volume is one surrogate for surgical technique, we believe surgeon experience and expertise with breast cancer care may also be important features in defining a high-quality breast cancer surgeon. Compared to surgeon case volume, we therefore propose that other surgeon-specific characteristics (for example, number of years in practice, percent of practice focused on breast cancer and membership in the Society of Surgical Oncology) might serve as more sensitive measures of surgeon technique, experience and expertise. In addition to surgeon expertise in breast cancer care, we hypothesize that hospital expertise and commitment to cancer care are important factors in determining a woman’s risk of developing lymphedema. Certain hospital characteristics (hospital breast cancer case volume, the presence of an American Cancer Society-approved cancer program, availability of oncology, radiation therapy and physical/occupational therapy programs) might serve as measures of hospital expertise and interest in quality breast cancer care.
We will further explore the relationship between surgeon and hospital characteristics, including volume, and the development of lymphedema after breast cancer surgery. If a relationship exists and can be explained by hospital-specific characteristics, the care for women with breast cancer may be improved with regionalization or by introducing better programs/systems to more reliably ensure appropriate care. If a relationship exists and
can be explained by surgeon-specific factors, regionalization of surgical treatment may be the preferred strategy to improve the quality of care of breast cancer survivors in the United States. Given the potential cost and inconvenience of regionalizing care for such a common disease, making the distinction is critical from a health policy perspective.
Dr. Yen can be reached at 414-805-5495 or firstname.lastname@example.org.
The above work is funded by Dr. Yen’s National Institutes of Health grant (NIH K07CA125586), as well as her recently awarded two year administrative supplement (NIH K07CA125586-03S1).
Petrek JA, Pressman PI, Smith RA. Lymphedema: current issues in research and management. CA Cancer J Clin 2000;50:292-307.
Sparaco A, Fentiman IS. Arm lymphoedema following breast cancer treatment. Int J Clin Pract 2002;56:107-10.
Erickson VS, Pearson ML, Ganz PA, Adams J, Kahn KL. Arm edema in breast cancer patients. J Natl Cancer Inst 2001;93:96-111.
Paskett ED, Naughton MJ, McCoy TP, Case LD, Abbott JM. The epidemiology of arm and hand swelling in premenopausal breast cancer survivors. Cancer Epidemiol Biomarkers Prev 2007;16:775-82.
Neuner JM, Gilligan MA, Sparapani R, Laud PW, Haggstrom D, Nattinger AB. Decentralization of breast cancer surgery in the United States. Cancer 2004;101:1323-9.
Edge SB, Niland JC, Bookman MA, et al. Emergence of sentinel node biopsy in breast cancer as standard-of-care in academic comprehensive cancer centers. J Natl Cancer Inst 2003;95:1514-21.
Fleissig A, Fallowfield LJ, Langridge CI, et al. Post-operative arm morbidity and quality of life. Results of the ALMANAC randomized trial comparing sentinel node biopsy with standard axillary treatment in the management of patients with early breast cancer. Breast Cancer Res Treat 2006;95:279-93.
Yen TW, Fan X, Sparapani R, et al. A contemporary, population-based study of lymphedema risk factors in older women with breast cancer. Ann Surg Oncol 2009;16:979-88.