Lymphovenous Canada: Lymphedema - the Secret Epidemic of Breast Cancer Survivors

Abstract - Nearly 180,000 women in the United States are newly diagnosed with breast cancer each year. The two million breast cancer survivors comprise the largest single group of cancer survivors in this country. During their lifetimes, some 20-40% of these survivors likely will develop lymphedema, a condition in which significant and persistent swelling occurs in the affected area. The physiological and psychosocial changes associated, with post-breast cancer treatment lymphedema significantly impact function and quality of life, potentially adversely affecting interpersonal relationships, occupational and family roles, and activities of daily living. Fundamental to improving care and outcomes for women experiencing post-treatment lymphedema are more accurate estimates of the extent of the problem, early and continuing valid and reliable assessment of physiological and psychosocial status targeting early intervention, and rigorous evaluation of alternative physiological and psychosocial interventions and management protocols. WOMEN AND CANCER, 3 (1), 15-33, 2001

Extent of the Problem of Lymphedema among Women Treated for Breast Cancer

The Secret Epidemic - The American Cancer Society reports that nearly 180,000 women in the U.S. develop breast cancer annually. Although typically less than half of the two million breast cancer survivors develop lymphedema, all survivors are at risk for developing symptoms. Lymphedema occurs as both an acute and chronic condition in which significant and persistent swelling develops as the result of an abnormal accumulation of protein-rich fluid in the affected area (8)(22) which for breast cancer patients is generally the arm on the same side as the affected breast. In addition, the swelling often causes discomfort and disability; later, cellulitis and lymphangitis often occur, predisposing the patient to infection.

Symptoms experienced most commonly among a group of breast cancer survivors with measurable lymphedema were limb swelling, heaviness, tenderness, and numbness (Armer & Whitman) (4). Breast cancer survivors with lymphedema, compared to those without, reported more signs and symptoms. Hull (12) noted a wide impact of lymphedema on womens daily lives, such as the following: a) sleeping becomes difficult as women try to position their arms; b) carrying items, even heavy pots or groceries, becomes difficult; c) many forms of exercise, even walking, become difficult; and d) fit and comfort of clothing become problematic (e.g., blouses need to be larger, long sleeves are worn even in the summer to covet the swelling or pressure garment). Thus, the physical impact of lymphedema is significant on a wide range of daily activities. Despite the widespread impact of lymphedema on women's lives, it is under-recognized and under-treated.

Quantification of lymphedema has been problematic, despite the fact that various methods have been used to measure the lymphedematous arm (28). Perhaps the most common criterion for diagnosis has been a finding of 2 centimeters or more difference in arm circumference (or 200 ml difference in limb volume) between affected and non-affected limb (20). Lymphedema can be categorized as mild, moderate, or severe. Three stages are identified: Grade I, in which pitting occurs upon application of pressure and edema reverses with limb elevation; Grade 11, in which edema becomes larger and harder and no longer pits under pressure; and Grade 111, in which swelling worsens and skin changes occurthe skin may become very thick and develop huge folds associated with elephantiasis (8).

Another inhibiting factor in the recognition of the extent of the problem of lymphedema in terms of numbers affected and the extent of the impact on lives, is the apparent under-diagnosis and recognition by health care providers. As noted earlier, it is conservatively estimated that 20 to 40 of every 100 women treated for breast cancer with contemporary treatment modalities will experience lymphedema in their lifetimes. Indeed, Armer found 39% of 103 women returning for follow-up after breast cancer treatment (mean time since diagnosis = 36 months) had _> 2 cm difference in circumference between the affected and non-affected limbs at one or more points (4-5). However, among the 99 reviewed medical records, only 21 charts (21%), just over half; were found to have a medical diagnosis of lymphedema.

In addition, although oncology physicians might be aware of the general risk for lymphedema, Armer's early findings indicate that oncology physicians might not always be aware of the existing condition of lymphedema. For example, in one case, a lymphedema patient reported that the referring physician informed her about the lymphedema study and suggested she consider participating, because even though she did not have lymphedema, she was at risk of someday developing lymphedema. In fact, circumferential arm measurements revealed _> 2 cm difference between the affected and nonaffected arms at two of five measurement sites, sufficient for a diagnosis of lymphedema. Upon questioning, the patient reported several signs and symptoms of lymphedema, including nonreversing swelling of the affected hand and wrist.

Incidence and prevalence - Perhaps in part because of difficulties in measurement and diagnosis, the reported incidence of lymphedema varies greatly among women treated with surgery and radiation for breast cancer. The most recent reviews of the literature have estimated the incidence of lymphedema from 6 to 30%28 and from 6 to 62.5%.(25_

Petrek and Heelan (28) noted that the study with the shortest follow-up (12 months) reported the lowest incidence (6%); likewise, one of the studies with the longest follow-up (11 years) reported the highest incidence. This broad statistical range of findings probably reflects major breakthroughs in breast cancer treatment, including progress in breast conservation and therapeutic combinations leading to increased survivorship (20) (32). Methodological weaknesses include: inconsistent criteria for defining lymphedema in the literature; (25) and small samples, retrospective analyses, and the psychometric difficulties (particularly reliability) in assessing lymphedema. The incidence of lymphedema among breast cancer patients, even using the lowest estimates for this country alone, affects hundreds of thousands of women and represents a major societal need. Management of the physical and psychosocial aspects of lymphedema is a major largely-unrecognized need in the health care community.

Impact of current cancer treatments - Over the past decade, breast conservation techniques, most often coupled with radiotherapy, have been used widely in an effort to diminish unpleasant, lasting side effects (such as lymphedema) long associated with more radical treatments (30). Similar medical optimism regarding reduction in lymphedema has been associated in recent years with the advent of sentinel lymph node biopsy procedures that spare the breast cancer patient the more invasive and traumatic axillary lymph node dissection (30). However, preliminary observations indicate that the incidence of lymphedema following breast conservation surgical methods, such as lumpectomy and partial mastectomy combined with radiotherapy, may be equal to or in fact greater than the incidence following traditional surgical treatment (mastectomy with or without radiation) (30) (32).

  Armer et al (6) recently completed preliminary analysis of data in a convenience sample of women returning for follow-up after surgical intervention for breast cancer. Among 23 participants who underwent attempted sentinel node biopsy (SLNB) procedure (which is considered more conservative than the traditional axillary lymph node dissection procedure), 6 (over 25%) of 23 had measurable lymphedema (6). Indeed, one patient who underwent SLNB, lumpectomy, and no radiation presented with lymphedema.

Clearly, sentinel node procedures alone are not sufficient to eliminate lymphedema as a treatment consequence. The impact of sentinel lymph node biopsy on lymphedema occurrence is not yet known because too little time has elapsed to observe lymphedema, which may occur up to 20 years after treatment (28).

Both breast conservation techniques and sentinel lymph node biopsies are generally components of a program of treatment including radiotherapy to the breast and/or axilly (30). Since radiation exposure is associated with trauma to the lymphatic system, risk for lymphedema likely continues for women treated with state-of-the-art treatment modalities. Through increased measurement accuracy, incidence and prevalence of lymphedema following current therapeutic approaches for treatment of breast cancer will be better understood, and more informed decisions about risk factors, treatment interventions, and recovery will be made. In addition, appropriate sampling decisions can be made for the next stage of intervention research.

Interventions for Lymphedema

Certain less-studied approaches, such as complete decongestive physiotherapy (including a program of manual lymph drainage, bandaging, exercise, and meticulous skin care) and directional-flog gradient-foam devices, show promise in reducing lymphedema (6) (9) (14). Early detection and intervention hold the greatest promise of reducing this widespread condition (29) (32). Identification of epidemiological and clinical factors associated with risk and incidence will provide the necessary foundation for preventive intervention. Research more rigorously examining type and frequency of treatments and optimal outcomes is needed.

Self-management - Although personal and historical characteristics such as age, weight, infection, and axillary dissection are believed to affect women's risk for onset of lymphedema, patient compliance has been identified as the most important factor in treating lymphedema (29)(34). Even so, little is known about factors influencing patient compliance and the factors that promote effective self-management strategies for lymphedema symptoms. For example, many of the most promising lymphedema management techniques are time-consuming, very difficult to accomplish by the patient herself, and may be vulnerable to incomplete patient compliance without strong support and practical assistance from family or friends.

In one recent study, the most frequently reported lymphedema selfmanagement strategy was no action (Armer & Whitman) (4). In the author's clinical experience, a breast cancer survivor with moderately severe lymphedema in her dominant limb reported she was unable to comply with the bandaging regime when her husband traveled or was too tired to assist her. It was evident that the patient experienced difficulties with both social support and problem-solving which negatively influenced her lymphedema symptom management and ultimately, limb fluid volume and functional health status.

Unfortunately, support groups and training in practical problem-solving seem to be rarely available to patients. For example, only one support group was listed in 1999 by the National Lymphedema Network (23) for the home state of the authors. In total, there were only 111 lymphedema support groups listed for all 50 states (www.lymphnet.org/support.html).

Psychosocial issues -As limited as are the proven-effective physiological interventions in lymphedema management, testing of psychosocial interventions has been even more limited. Preliminary research suggests that lack of social support and avoidant coping is related to psychosocial and functional morbidity in lymphedema patients. In one recent study; women who had poor social support, pain, and/or passive and avoidant coping styles reported the highest levels of disabilities (27). Thus, psychosocial factors such as social support and problem solving style may serve as personal and environmental resources. If available, these resources may allow women to successfully manage lymphedema and its emotional and psychological impact; if lacking, they may exacerbate the functional impact of their condition. These findings suggest further study is needed of psychosocial factors, especially problem solving capacity style and social support, in relationship to the progression of lymphedema.

Issues in Psychosocial Factors Influencing Adaptation to Breast Cancer Lymphedema

In addition, Tobin et al.(35) observed that some patients reported complete loss of interest in dress and appearance, difficulties in sexual and interpersonal relations, and loss of occupational aspirations, with subsequent loss in self-esteem and depression. One 88-year old breast cancer survivor who has lived 41 years with post-treatment lymphedema reports that her extended experience living with lymphedema was far more life-changing than her treatment for breast cancer itself (3). In short, coping with lymphedema is not only stressful, but potentially results in serious psychosocial problems that directly influence the quality of life of breast cancer survivors.

Family impact - In a qualitative study examining the impact of lymphedema on womens family roles, Radina and Armer (31) carried out face-to-face ethnographic-style interviews to elicit data regarding ways women coped with the chronic condition of post-breast cancer lymphedema and the perceived impact on their family roles. The Family Adjustment and Adaptation Response Model was used to interpret data regarding how lymphedema affected the women and their families in terms of task completion and family functioning. Findings indicate that families who are more flexible in modification for completing daily tasks and who have pre-existing resources for coping with stressors have more positive outcomes than those families who are more rigid and cope with stressors poorly. Further work in this area has potential to provide the foundation for family-level interventions in dealing with chronic illness such as lymphedema.

State of the science - Whereas the psychological sequelae of the treatment of breast cancer have been documented (35), the examination of psychosocial adjustment related to lymphedema is in its infancy (25)(35-36). Two studies provided some evidence that lymphedema is associated with psychosocial distress (24)(26). These investigations employed uncontrolled case studies, however, and thus do not provide strong empirical support for the link between lymphedema and psychosocial adjustment. Tobin et al.(35) provided some support for a link between lymphedema and psychosocial adjustment in an English sample, but their findings were not consistent across measures, and they employed a pre-experimental design that greatly limited their conclusions.

Maunsell, Brisson, and Deschene(18) also reported a link between lymphedema and psychosocial distress in a Canadian sample, but their outcome measures assessed distress in a global manner. Moreover, their measures were developed two decades ago and are not typically employed in the psychosocial adjustment literature today. Another study by Passik, et al.(27) also suggested a link between lymphedema and psychosocial adjustment, and particularly pointed to social support deficits and avoidant coping as being significantly related to psychological and functional morbidity of lymphedema patients. This study offers the strongest support linking psychosocial distress to lymphedema, although it utilized patients seeking physical rehabilitation for lymphedema, thus limiting the generalizability of the findings.

Uncharted territory - As is often the case, the initial studies investigating a particular problem are not theory driven, but descriptive. While descriptive studies can be informative, the lack of theory-driven research can inhibit more complete understanding of an area. Moreover, the initial studies examining the link between lymphedema and psychosocial adjustment are limited by measurement problems of both lymphedema and psychosocial adjustment, as well as by several research design issues that limit experimental rigor.

A conclusion by Maunsell et al.(18) still stands: The impact of arm problems on patient quality of life has not been quantitatively assessed (p. 316). After reviewing the lymphedema literature, Petrek and Heelan (28)noted that the scanty evaluation of lymphedema may be attributed to several factors, including a history of relative neglect of women's health problems and, perhaps most importantly, the traditional view that quality of life is less important than the eradication of cancer and detection of recurrence. Unfortunately, neglect of lymphedema has not only meant that many women go undiagnosed and fail to receive basic preventive information (see Maunsell, et al.18), but has also inhibited the development of effective psychosocial interventions. As Passik and McDonald (25) concluded, what recommendations to make to women are anything but clear and well studied at this time (p. 2819). Treatment of lymphedema has been, and continues to be, a major challenge for health care professionals (12) (29).

Future directions. Although there has been mixed support for the utility of psychosocial factors in understanding cancer onset, recent methodologically sound studies have suggested that psychosocial factors may have more utility in understanding cancer progression (16) (p. 130). In particular, psychosocial factors such as problem solving and social support seem to be associated with fighting cancer (21). However, literature reviews have concluded that many studies investigating the clinical course, prognosis, and psychosocial adjustment of breast cancer patients have serious methodological flaws, and thus the major question of what constitutes effective coping with cancer is still largely unexplained.

No one can reliably identify which coping strategies are most successful and for whom, and on what basis to begin to plan programs that promote coping and adjustment. There is a need for more rigorous, prospective studies examining the role of psychosocial factors in the progression of breast cancer and particularly in the development and progression of lymphedema. Such studies would have clear implications for interventions for women at risk for lymphedema.

Proposed Model of Post-Breast Cancer Treatment Lymphedema Psychosocial Adjustment

Specifically, our conceptualization of lymphedema is guided by a biobehavioral model of cancer, stress, and disease progression proposed by Anderson, Kiecolt-Glaser, & Glaser (2), and emerging models of stress and coping (11). Research clearly indicates that stressors of both a minor and major nature can substantially affect a person's psychological and physiological well-being (15). Moreover, in the last 15 years there has been growing empirical evidence that psychosocial factors, such as problem solving and social support, play key roles in adaptive responses to stress (see Zeidner & Endler (37). In particular, individual characteristics such as problem solving, and environmental systems such as social support, can be protective mechanisms that reduce the risk due to life crises and transitions (11)(19) Thus, we conceptualize problem solving and social support as potential protective mechanisms that could reduce the progression of lymphedema; these factors are on the left of [Figure 1] below.

Figure 1 - Structural Model of Post Breast Cancer Treatment Outcomes

The center of [Figure 1] reflects our conceptualization of lymphedema in terms of both objective and subjective indicators, specifically limb fluid volume difference (LFVD) and associated signs and symptoms and coping effectiveness, respectively. Objective and subjective assessments describe different dimensions of lymphedema, which may help to further our understanding of not only the physical aspects of lymphedema but also the cognitive and affective components associated with coping with this disease.

Finally, the right side of [Figure 1] depicts multiple dimensions of post-breast cancer treatment outcomes, namely psychosocial adjustment, specifically psychosocial distress, quality of life, and adjustment to chronic illness, as well as functional health status.

Because both effective problem solving and high social support have been implicated as protective mechanisms in the progression of lymphedema (27) and because social support and problem solving style may be critical personal and environmental resources in coping with and management of the disease course (10)(21), instruments designed to provide a fine-grained assessment of problem solving and social support must be used to assess these variables. In addition, since patient compliance has been suggested as an important variable in the progression of lymphedema (34) (38), we believe we need to examine the roles of the frequency of symptoms, and lymphedema coping efficacy in predicting limb fluid volume difference and psychosocial outcomes/functional health status.

Tracking changes in these variables over time, along with changes in functional health status and psychosocial adjustment, will allow the investigation of selected variables (e.g. problem solving ability, social support, and coping effectiveness) as predictors of change in LFVD, psychosocial adjustment outcomes (e.g. quality of life), and functional health status over time. Our goal is to identify variables that influence disease progression and psychosocial outcomes/functional health status, which then can inform subsequent interventions. Although psychosocial adjustment has been linked to lymphedema in the past, a prospective design to provide both a more accurate assessment of lymphedema and a more stringent test of linkage between limb fluid volume and psychosocial outcomes/functional health status is recommended.

In short, our model or other models may help to direct future research to increase our knowledge about the progression and management of lymphedema. Over time, well-designed empirical studies will not only add to the existing knowledge base about lymphedema, but also lead to more encompassing and sophisticated conceptual models of lymphedema.

Recommendations for Future Work

Findings from future rigorous studies have the potential to redefine measurement of lymphedema, and perhaps, in the longrange, to redefine the diagnostic criteria for lymphedema itself. Future prospective studies are essential for further systematic research to evaluate the effectiveness of interventions in preventing, controlling, and resolving lymphedema in women treated for breast cancer.

Without a valid and reliable limb fluid volume measurement protocol, accurate comparisons of treatment effectiveness across multiple sites, therapeutic modalities, and patient characteristics remain impossible. Furthermore, measurement of lymphedema as a dichotomous variable (generally > 2 cm difference between limbs) using often-imprecise and -unreliable measurement tools such as circumferential tape measures has not allowed examination of volume changes that may begin immediately after surgery and/or radiation and that are not easily detectable with current measurement strategies. Added measurement precision will provide a more stringent examination of the relationships among variables such as protective mechanisms, psychosocial adjustment and functional health outcomes, and potential mediating or moderating variables such as lymphedema coping effectiveness, limb fluid volume, or the number and intensity of lymphedema symptoms. Moreover, use of prospective longitudinal designs will allow examination of these relationships over time.

In addition to developing and refining state-of-the-art detection and measurement of limb fluid volume difference, future research must use reliable and valid multidimensional measures of psychosocial constructs. Use of extensively validated instruments or rigorously developed new instruments in lymphedema research will allow a more precise identification and understanding of constructs associated with the progression, treatment, and successful management of the disease. Moreover, such research would provide important information about what kind of interventions might be most helpful in dealing with lymphedema. For example, identification of coping assets and deficits in social support and problem solving may be a critical step in the development of psychosocial interventions which can then be administered and evaluated as part of an ongoing program of research. Ultimately, such a program of research has the potential to influence clinical practice guidelines for women undergoing treatment for breast cancer.

Future research findings could have potentially widespread clinical applications in developing and testing a protocol for consistent, accurate, noninvasive, and labor- and cost-effective measurement of the lymphedematous limb. Potential application is considerable for both upper and lower extremity lymphedema attributable to surgery, radiation, and other adjunct treatment for malignancy; including breast, melanoma, prostate, ovarian, and other cancers involving lymph node dissection and irradiation. Moreover, examining the link between variables such as protective mechanisms, limb fluid volume differences, coping effectiveness, and psychosocial outcomes/functional health status could lead to a more complete understanding of the consequences of lymphedema, and subsequently to more appropriate care. In addition, identification of potential protective mechanisms could greatly inform clinical treatment and preventive interventions.

Finally, accurate physiological measurements and multidimensional psychosocial measures are essential to sound clinical understanding and assessment of disease management and progression, as well as the scientific understanding and evaluation of the effectiveness of lymphedema treatments.

Ideally; cross-disciplinary research teams (made up of nurses, physicians, psychologists, physical therapists, social workers, and physiologists) will examine more precisely limb fluid volume measurement and psychosocial and functional correlates. To date, no reliable and valid method of assessing limb fluid volume difference is available in this country other than water displacement, which is not clinically practical and thus not used routinely for diagnosis. The result is that lymphedema in women treated for breast cancer is under-diagnosed and undertreated, leaving a large number of women with untoward outcomes and compromised quality of life and functional health. A more sophisticated continuous measurement of LFVD and its correlation with coping effectiveness and psychosocial adjustment and functional health will provide a more robust test of this association, greatly increasing our understanding of the impact of lymphedema. In addition, multidisciplinary research partners have a great deal of potential to identify more encompassing models of lymphedema that could inform treatment interventions in post-breast cancer treatment lymphedema.

The secret epidemic of post-breast cancer treatment lymphedema, affecting tens of thousands of breast cancer survivors in this country; is gradually being exposed. Increased consumer and professional awareness of the risk factors, need for early and continuing valid and reliable assessments of physiological measures of limb fluid volume and subjective signs and symptoms, and related psychosocial issues will serve as the foundation for improved patient care and outcomes. Successful clinical protocols must be built on a foundation of rigorous research aimed at better understanding the physiological and psychosocial correlates of adjustment to post-trcatment lymphedema. Only then numbers of surviving years with the high quality of life they so will breast cancer survivors be enabled to live those increasing deserve. S2

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