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![[SYMPOSIUM]](../../../graphics/sym_logo.gif){kind=logo} After breast cancerImplications for long-term primary careNathan Ritter, MD Neil Love, MD Daniel Osman, MD VOL 105 / NO 6 / MAY 15, 1999 / POSTGRADUATE MEDICINE CME learning objectives
This is the third of four articles on breast cancer This page is best viewed with a browser that supports tables Preview: Fear of recurrence is a constant, nagging companion for many of the more than 2 million American women who have survived breast cancer. Primary care physicians are in an ideal position to help many of these women, not only through regular examinations and reassurance, but also through comprehensive primary and secondary prevention strategies. In this article, Drs Ritter, Love, and Osman discuss cancer surveillance, delayed adjuvant therapy, sexual function, fertility, pregnancy, menopause, and lymphedema management in breast cancer survivors.
Three years ago, a screening mammogram detected a lesion in the right breast of Mary Smith, a 42-year-old married, premenopausal, nulliparous woman, who has been in your care for 20 years. A 1.2-cm estrogen-receptor-positive infiltrating ductal carcinoma was found, for which Mrs Smith elected lumpectomy and axillary node dissection. Two nodes showed tumor invasion. Mrs Smith was treated with breast radiotherapy and a regimen of cyclophosphamide, methotrexate, and fluorouracil, during which her menstrual periods ceased. Now at age 45, she is back for a routine follow-up visit and mentions that she is troubled by vaginal dryness and dyspareunia. Physical examination reveals minimal swelling in the right arm and moderate vaginal atrophy but no evidence of tumor recurrence. What special considerations are appropriate in caring for this patient? Life during and after cancer therapy can be physically difficult and emotionally draining for patients, their families, and their healthcare providers. Of the more than 2 million women in the United States who have been treated for breast malignancy, many rely on primary care physicians for long-term follow-up and support. In caring for these women, the following key issues are of primary concern:
RecurrenceThe anxious patient, having survived the initial threat of cancer, is challenged by reentry into a "normal life." As with most breast cancer survivors, the primary concern of Mrs Smith during her visit is reassurance that the cancer has not recurred. The well-known propensity for delayed onset of metastatic disease with breast cancer makes this a lifelong issue for many women. The primary care physician often assumes responsibility for screening for recurrent or new cancers. Although patient visits can be used to provide reassurance and encouragement, they also may cause great anxiety and therefore should not be scheduled more often than medically necessary. Because about 50% of breast cancer recurrences develop in the first 3 years after diagnosis, patients should be seen more often during these years. Recent guidelines call for careful history taking and physical examination every 3 to 6 months for the first 3 years after primary therapy. Examinations can then be decreased to every 6 to 12 months for the next 2 years and annually after 5 years (1). At each appointment, the patient should be asked about bone pain, skin rash, dyspnea, cough, persistent fatigue, anorexia, weight loss, and mastectomy or lumpectomy scar changes. The patient must understand that if any of these symptoms develop, she should not wait for her scheduled visit but should see her physician promptly. Instruction in breast self-examination is also important. The physician's examination should focus on a search for breast, chest wall, and lymph node recurrence. Findings such as bone tenderness, hepatomegaly, and neurologic abnormalities may suggest systemic recurrence. Tumor may recur locally in the breast, chest wall, and axilla or in a distant site, particularly bone, lung, and liver. While early detection of recurrence does not definitively offer longer life, short-term clinical outcomes and quality of life may improve if treatment is started when invasion is minimal. Local recurrence in the breast after lumpectomy is usually managed with mastectomy. The mainstay of management of distant recurrence is systemic endocrine treatment and chemotherapy, often administered by a medical oncologist. Annual mammography is the only screening test recommended, and women treated with lumpectomy should have a mammogram 6 months after completion of radiotherapy. Screening of asymptomatic patients with chest radiography and bone and liver scans is of unproven value and is not recommended. Routine measurements of serum chemistries, blood counts, or tumor markers are not helpful (1). Gynecologic follow-up for breast cancer patients is the same as for other women. However, women receiving tamoxifen should be asked about and encouraged to report abnormal vaginal bleeding because of the known increase in risk for endometrial cancer associated with this therapy. Screening with vaginal ultrasound or endometrial biopsy is not recommended (1).
Delayed adjuvant tamoxifenRecent attention to the potential role of the anti-estrogen agent tamoxifen in reducing the risk of breast cancer in high-risk women has led to questions about use of this agent in breast cancer survivors who have not previously used it. Indications for use of adjuvant tamoxifen to treat early breast cancers have increased steadily in the last 15 years. At present, tamoxifen therapy is considered for most breast cancer patients, in some cases because of secondary benefits, such as decreasing the risk of second breast cancer. However, many breast cancer survivors, like Mrs Smith, were treated before clear-cut evidence of tamoxifen's benefit in premenopausal women was available (2). Should they be offered tamoxifen therapy now? As mentioned earlier, one hallmark of the natural history of breast cancer is the propensity for delayed metastases. At 3 years after diagnosis, Mrs Smith is still at risk for recurrence. Almost all adjuvant systemic therapy trials have evaluated use of treatment shortly after diagnosis. However, theoretically, delayed adjuvant therapy could benefit patients whose cancer was diagnosed and treated before such therapy became available. In fact, two small trials of delayed adjuvant tamoxifen (3,4) have shown benefit when therapy was started some years after diagnosis. While the question of tamoxifen's value in previously untreated breast cancer patients probably cannot be answered soon, it appears reasonable to offer this treatment option to breast cancer survivors. Breast cancer patients have also long been known to be at high risk for development of a new breast cancer. This risk continues for at least 20 years and probably indefinitely (5). Two recent analyses (2,6) confirm that the short-term risk of a second breast cancer in breast cancer patients is as high as the risk of a first breast cancer in high-risk women who participated in the National Surgical Adjuvant Breast and Bowel Project P-1 Study, more commonly known as the Breast Cancer Prevention Trial (BCPT) (7). A number of factors further increase the risk of a second breast cancer, including young age at diagnosis, family history of breast cancer, and certain histologic features. Evidence that tamoxifen substantially decreases the risk of development of a second breast cancer (2) prompted the launch of the BCPT study. In addition, data suggest that the longer the duration of tamoxifen therapy (ie, up to 5 years), the greater the effect on preventing development of new breast cancers. Also, this preventive effect continues for some time after therapy is stopped (2). While no clear-cut evidence has yet shown that delayed tamoxifen therapy reduces the risk for a second breast cancer, it seems quite feasible that this effect would occur. In menopausal breast cancer survivors, another rationale for considering tamoxifen is the potential benefit on serum lipid profiles and bone density. These short-term effects have been reproducibly demonstrated in many adjuvant trials (8). Although few tamoxifen trials were designed to evaluate clinical outcomes related to lipid and bone, several individual adjuvant trials have shown reduced cardiovascular morbidity in breast cancer patients receiving tamoxifen (8). In addition, the BCPT revealed encouraging trends toward fewer fractures (7). Many physicians are reluctant to prescribe HRT in breast cancer survivors, and while the lipid and bone effects of tamoxifen are not identical to those of HRT, the "breast protective effect" of tamoxifen makes this agent a rational consideration. Other pharmacologic and nonpharmacologic means to improve lipid profiles and bone density may be considered as an alternative or an addition to tamoxifen. Such decisions must consider the specific risk profile for the individual patient in terms of breast cancer recurrence, second breast cancer, cardiovascular disease, and osteoporosis. Another issue that makes delayed tamoxifen a consideration is evidence of vaginal dryness and dyspareunia. A documented but poorly appreciated characteristic of tamoxifen in some patients is an estrogenic effect on the vaginal mucosa (9). In fact, the vaginal discharge associated with this therapy is often normal mucus, which acts as a lubricant. While not all patients experience this effect, when it does occur, it may improve sexual function and quality of life.
Sexual functionAlthough recurrence is the primary concern of most breast cancer patients, an altered sense of femininity, feelings of decreased attractiveness, and fear of abandoning children and family are also important causes of stress. These concerns usually are greatest at diagnosis and early in treatment and tend to diminish somewhat over time. In general, patients who are free of recurrence experience a normal quality of life in long-term marital or other partner adjustment and sexual function, regardless of whether they choose modified radical mastectomy or breast-conserving therapy (10,11). Chemotherapy seems to play a more important role in sexual dysfunction and suboptimal quality of life, particularly in younger women who stop menstruating. Tamoxifen therapy has not been associated with sexual dysfunction. Women who experience sexual difficulty are often hesitant to talk about it with their physician or their sexual partner. Therefore, it is important to establish open lines of communication early in the course of treatment planning and therapy. By asking the patient simple questions about her sex life, the treatment team can encourage her to verbalize concerns. Patient and partner education should focus on the potential effects of breast cancer and its treatment on sexuality. Persistent sexual dysfunction warrants referral to a psychotherapist or sex therapist. Altered body image perception is common, particularly in women treated with modified mastectomy. Weight gain is another common concern that alters self-perception. It may be the result of decreased metabolic rate after menopause or of psychosocial factors, such as overeating as a coping mechanism. The most important factor in long-term emotional adjustment to breast cancer is the level of emotional support received, including that from friends, family, and support groups. Whether or not routine psychosocial intervention influences long-term mortality is debatable. However, psychosocial interventions promote emotional and functional adjustment and should be encouraged and implemented.
Management of menopauseHRT in menopausal breast cancer patients has been a topic of debate for many years. Because of the known role of estrogen in promoting breast cancer and the theoretical risk of stimulating occult metastases, many clinicians have had strong reservations about its use. On the other hand, several case series addressing the use of estrogen or estrogen-progestin combinations in breast cancer patients have failed to demonstrate an obvious increased risk of relapse (12,13). However, no prospective randomized clinical trials of HRT in breast cancer survivors have been reported, although several are being conducted. Without data from such studies, the use of HRT in these patients is an option that must be approached with caution. Cobleigh (13) and others have proposed research projects on the use of tamoxifen in combination with HRT in breast cancer patients. This therapy is common in Europe and has been reported to relieve vasomotor symptoms (14). Here again, no reliable data document the value of this combination, but it is known that tamoxifen is effective for both prevention and treatment of breast cancer in premenopausal women, who have high circulating estrogen levels (2). Use of short-term therapy with progestational agents, either alone or with tamoxifen, is another therapeutic option. However, the breast cancer effect of this approach is not known. Nonendocrine interventions to ameliorate symptoms of menopause and lower the risk of osteoporosis and heart disease are options that may be less threatening psychologically and perhaps biologically (15). Sometimes the simplest approaches are the most appropriate. For example, many vaginal lubricants are available to alleviate vaginal dryness. Intravaginal estrogens also provide relief but can lead to increases in serum estrogen levels (13).
Fertility and pregnancyAbout 25% of all breast cancers occur in premenopausal women. Unfortunately, chemotherapy, which is commonly used as adjuvant treatment, often causes amenorrhea and early menopause. The frequency of this complication varies with the type of chemotherapy used and the patient's age; older premenopausal patients more often become menopausal. Amenorrhea during or after chemotherapy is usually permanent. An amenorrheic woman who does not wish to become pregnant should continue barrier contraception for 1 year after the cessation of menses. Serum gonadotropin levels can be ascertained to document ovarian failure. Premenopausal breast cancer survivors not wishing to become pregnant are discouraged from using hormonal means of contraception. Tamoxifen generally does not induce menopause or ovarian failure. For breast cancer patients who wish to become pregnant, an important question has been whether endocrine changes in pregnancy promote tumor recurrence. This theoretical concern is based on the known hormone responsiveness of breast cancer cells. A number of studies have addressed this issue, and evidence tends to indicate that pregnancy does not increase the chance for recurrence. However, the reported series are small and must be viewed with caution (16). Most of the patients became pregnant within several years after diagnosis, and follow-up has been limited. Nonetheless, most physicians who treat breast cancer patients support attempts at pregnancy in patients who are free of recurrence 2 or more years after diagnosis. While chemotherapy is contraindicated during the first trimester of pregnancy, use of chemotherapy before pregnancy has not been shown to increase the likelihood of birth defects in offspring of breast cancer survivors. However, because relapse occurs most often during the first 2 years after diagnosis, patients are often advised to delay attempts at conception until after this period. Laboratory testing has shown that tamoxifen has adverse fetal effects in animals. No data are available on its effects on human pregnancy, but attempts at conception should be avoided during tamoxifen therapy. Patients should be advised to use barrier contraception until tamoxifen therapy is completed.
Management of lymphedemaLymphatic stasis and engorgement of the upper extremity occur in at least 20% of women who have axillary surgery or radiation therapy for breast cancer (17) and can be devastating for some women. Lymphedema is caused by the destruction of lymphatic vessels during surgical removal or by radiation therapy to the axilla. The more extensive the dissection or irradiation, the greater the likelihood of lymphatic obstruction and subsequent lymphedema. It may arise immediately after treatment or many years later. In addition to the deformity, some women have discomfort, disability, and frequent episodes of cellulitis. The emotional toll of this condition may be greater than that with mastectomy, since arm swelling is less easily hidden. About 400,000 American women are living with this problem. The physician may discover lymphedema at physical examination, or the patient may complain of arm heaviness and an increase in arm size. Symptoms range from minimal swelling in early stages to disabling, massive engorgement. Once established, lymphedema is usually permanent and almost always progressive. Over an extended course, the skin may become brawny, at which stage management is very difficult. Assessment for lymphedema begins before surgical and radiation therapy. The circumference of both upper and lower arms is measured at several locations, using the olecranon as a landmark. While no specific size increment defines the condition, minimal circumferential increases of 1 to 2 cm can be associated with symptoms. Special attention should be given to the complaints of arm heaviness or swelling. Imaging techniques, ultrasound, and volumetric measurements may also be helpful in assessing lymphedema. Because the condition has no cure and is so difficult to manage when it becomes severe, implementation of a lifetime preventive plan is necessary. Goals are to keep lymph production in check and to maintain adequate lymph flow. In the past, women who have had axillary treatment have been encouraged to avoid exertion to the ipsilateral extremity. However, more recent studies have shown that some types of exercise actually may promote lymph flow. Patients are encouraged to wear an upper extremity compression garment (30 to 50 mm Hg) during exercise. Excessive heat (ie, sunbathing, baths, saunas) and constricting clothing should be avoided. Bras with padded straps are recommended to facilitate collateral drainage. Infection or injury of even minimal degree warrants the use of antibiotics, and patients are cautioned to avoid phlebotomy and other traumatic procedures in the affected arm. Diuretics are not effective in the high-protein state of lymphedema, but benzopyrones, such as coumarin, have been reported to benefit these patients (17). A number of rehabilitative approaches to lymphedema have been used, with varying degrees of success. Elevation of the arm is often the first approach. However, prolonged periods of elevation can interfere with daily function, and elevation during sleep may be difficult. External compression is used to reduce edema formation and to remove existing fluid. Compression garments, including those with gradient formats, are often used, as are sleeves that allow manual inflatable pressure to be applied. Pneumatic compression with intermittent pumps has been an important part of lymphedema management and is reimbursed by most third-party payers. Various surgical approaches, including debulking procedures, are available for patients with severe problems that are resistant to other approaches (18). Complete decongestive physiotherapy is a complex but safe and effective option for managing lymphedema. It is based on the fact that this problem, although most apparent in the arm and hand, actually involves an entire body quadrant. A specially trained therapist massages lymph from the affected area to adjacent lymph drainage basins. Compression bandages are applied, and the patient is led through controlled exercises. After 1 to 4 weeks of daily therapy, the patient takes over, applying the same techniques learned with the therapist. This technique is becoming more popular and is available at many specialty clinics and breast cancer centers (19).
Other long-term complicationsSome women have chest-wall or arm pain as a result of cicatrix formation after breast cancer surgery, radiation therapy, or both. Fortunately, this is usually of limited duration and responds to moisturizers, skin lubrication, and massage. Reassurance is important, and severity and duration of this type of pain are usually limited. In the few women with surgical nerve damage and severe pain, more aggressive therapies may be needed (eg, neuroma excision, corticosteroid injection). Another long-term local complication is limited range of motion in the shoulder, typically caused by pain, fear of movement, and scarring. Early mobilization and postoperative range-of-motion exercises aid in prevention. If the problem exists, massage and prolonged stretching often help regain lost function and prevent further loss.
SummaryAbout 2 million American women have survived the diagnosis and therapy of breast cancer and are free of recurrence. Primary care physicians are in an ideal position to implement comprehensive primary and secondary prevention plans that meet specific biologic and psychological needs of these patients and help them face the future with confidence and optimism.
References
Dr Ritter is staff physician, Physician and Community Education Program, University of Miami-Jackson Memorial Medical Center. Dr Love, a medical oncologist, is director, Physician and Community Education Program, University of Miami-Jackson Memorial Medical Center. Dr Osman is director, Miami International Breast Cancer Conference. Correspondence: Neil Love, MD, Department of Medicine, Division of Hematology-Oncology, University of Miami School of Medicine, 1150 NW 14th St, Suite 509, Miami, FL 33136.
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