#Breast Cancer and Rehabilitation

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Breast Cancer and Rehabilitation

Breast cancer can occur in any adult. Incidences have been increasing over the last decades for both premenopausal and postmenopausal women. Although the incidence of breast cancer increases during postmenopausal years, it is the leading cause of cancer death in women younger than 50 years. Age is not a predictor of complications, but it may affect the patient’s outcome, ability to cope, and extent of psychological distress. Breast cancer is the most frequent cancer in women, and more than 85% of patients are alive 5 years after diagnosis. For these reasons, more than 700,000 survivors of breast cancer in the United States are alive within 5 years of diagnosis; their total prevalence is over 2 million. [17, 18, 19, 20]
Burstein and Winer wrote an excellent review of survivorship issues for women with breast cancer. [21]
Treatment Options

On initial presentation, clinical and pathologic staging is performed to identify prognostic factors and to determine treatment options.
Surgery and/or radiation therapy is used for local control and often successful in early-stage breast cancer. If they are smaller than 5 cm and limited to the breast and axillary nodes, most such cancers may be treated surgically with modified radical mastectomy or breast-conserving surgery. In both cases, the axilla is usually dissected. Disease-free survival rates are equal in patients undergoing mastectomy and breast-conservation surgery. Locally advanced breast cancers are treated with modified radical mastectomy, preceded or followed by chemotherapy. Irradiation of the chest wall is often considered when the risk of chest-wall or nodal recurrence is high, when primary tumors are large or multicentric, or when 4 or more axillary nodes contain metastatic cancer.
Systemic therapy (ie, chemotherapy and/or hormonal therapy) is recommended for patients who present with metastatic disease or who have risk factors for metastases. Risk factors for metastatic cancer include age younger than 35 years, positive involvement of the lymph nodes, high-grade histologies, negative estrogen receptors, large tumor, high growth fraction, aneuploid DNA content, and other biologic markers. Chemotherapy may be administered before, during, or after irradiation with parameters of timing and duration depending on the type of chemotherapy.
Estrogen and progesterone receptors can be assessed to predict the patient’s response to hormonal manipulation. Tamoxifen had been the first-line adjunct hormonal therapy and was started during or after radiation therapy. Hormonal manipulation for the treatment of metastatic breast cancer may include the administration of tamoxifen. However, results of the Arimidex, Tamoxifen, Alone or in Combination (ATAC) trial suggested that an aromatase inhibitor is therapeutically superior and better tolerated than tamoxifen in postmenopausal women with primary breast cancer. Aromatase is expressed in nonovarian tissues, such as muscle and fat in both premenopausal and postmenopausal women. These nonovarian tissues become the dominant sources of estrogen in postmenopausal women.
At present, the available aromatase inhibitors belong to 1 of 2 classes. Class I inhibitors irreversibly bind aromatase and have a steroidal structure (eg, exemestane). Class II agents reversibly bind aromatase and are nonsteroidal (eg, anastrozole and letrozole). Because of the specificity of its mode of action, this class of compound is well tolerated and thus lends itself to the management of both early- and advanced-stage disease.

In metastatic breast cancer, radiation therapy is often successful in palliating symptoms from painful bony sites, brain metastases, or other metastatic sites causing symptoms or obstruction. Metastatic breast cancer rarely is curable; however, studies are underway investigating efficacy of high-dose chemotherapy followed by peripheral stem-cell rescue of bone marrow to eradicate metastatic cancer.
Current issues in breast-cancer management
Current issues in breast-cancer management include the following:
Necessity for axillary-node dissection and/or breast irradiation after wide excision of breast cancer in patients with a good prognosis (eg, those with small tubular, colloid, or mucinous tumors)
Necessity for whole-breast treatment for intraductal carcinoma
Timing and type of chemotherapy with surgery and radiation
Utility of high-dose chemotherapy with stem-cell rescue in poor-prognosis breast cancer
Treatment of young and old women with breast cancer
Role of estrogen replacement in breast cancer
Surgery and Its Acute and Chronic Morbidity

Breast-conserving surgery is increasingly used for many breast cancers because disease-free survival rates are equal for women undergoing either this procedure or non–breast-conserving surgery. Breast-conserving surgery is associated with improved body image and, perhaps, hastened psychological recovery.
Breast-conserving surgery refers to removal of the cancer along with a margin of normal breast tissue and axillary dissection. In breast-preservation surgery, wide excision implies the removal of a 1- 2-cm margin of normal tissue, whereas in segmental mastectomy, even more normal breast tissue than this is removed.
A relatively uncommon surgical procedure is quadrantectomy. This is a procedure to remove the quadrant of the breast that contains the tumor plus the underlying pectoral fascia. Any increase in the extent of surgery is associated with increased risk of both early and late complications. Most reported surgical complications are associated with axillary dissection. Debate still surrounds issues of whether axillary dissection is necessary and, if so, which parameters should be used to determine its extent.
Principles of wound healing directly affect the initiation and appropriate intensity of any rehabilitation program. Wound healing is a dynamic process that lasts months to years. Wounds initially produce inflammation that lasts a few days unless necrosis, infection, or foreign bodies are present. At the edge of an epithelial wound, basal epithelial cells migrate across the defect on fibrin strands. Epithelial cells cover the wound within 48 hours and thereafter begin to differentiate and keratinize.
Fibroblasts, from the adventitia of blood vessels, migrate into the wound on fibrin strands on day 3 and begin to synthesize collagen fibers, which begin to appear on day 4. Wound strength is related to the rate of collagen formation. By 3 weeks, most wounds achieve 15% of their ultimate strength. Strength increases at a constant rate for 4 months and then at a lower rate thereafter for more than a year. Pain at the wound site generally limits the amount of stress an individual can place on the wound.
Changes in sensation are common; therefore, wounds should be treated gingerly. Because external skin sutures may provide a nidus for infection and cause extra scarring, remove them early. Factors that may impede healing include malnutrition (more common in elderly individuals than in younger patients); deficiencies of vitamin A, vitamin C, and zinc; cigarette smoking; and any conditions that decrease tissue oxygenation. Steroid use, radiation therapy, and some chemotherapy agents impede healing. The administration of doxorubicin (Adriamycin), which commonly used in adjunct chemotherapy programs, should be delayed until 4 weeks after surgery.
Early complications after mastectomy include seroma formation (10%), wound infection (7%), and skin-flap necrosis (5%). The fewest wound infections are seen when diagnoses are made by means of fine-needle aspiration. Immediate reconstruction is not associated with an increased rate of complications. Most surgeons agree that a drain must be placed after axillary dissection. The duration of drainage is not standard, but most surgeons agree that the drain can be removed when the volume of fluid draining from the wound decreases to less than 20 mL/day. The presence of a drain or a seroma can lead to infection. If seroma develops after the drain is removed, most surgeons aspirate the seroma only if the patient is uncomfortable. Do not place a drain in a lumpectomy site because cosmesis diminishes.
Complications associated with axillary dissection are secondary to nerve, vascular, and lymphatic injury. The most common complaints after axillary dissection are reduced sensation under the right arm and decreased ROM of the shoulder. Sensory deficit improves with time but may never return to normal. No known treatment exists for this adverse effect. Lymphedema can be seen immediately after surgery and results in a small increase in diameter in the upper arm only. Collateral circulation should resolve the edema within several weeks.
Chronic lymphedema and its treatment are discussed elsewhere (see the section Management of Lymphedema, below). Injury to the long thoracic nerve results in winging of the scapula. About 30% of patients develop serratus anterior muscle palsy secondary to injury to the long thoracic nerve but appear to recover by 6 months. Injury to the thoracodorsal nerve causes slight weakness in internal rotation and abduction of the shoulder from weakness of the latissimus dorsi muscle. Injury of the medial pectoral nerve results in atrophy of the lateral portion of the pectoralis major muscle. Injury to the intercostobrachial nerve results in reduced sensation along the medial aspect of the arm, and, in some patients, subsequent disabling neuralgia develops.
Breast Reconstruction

Intuition suggests that breast reconstruction offers a woman the opportunity to retain a positive self image, mitigating concern about breast cancer treatment significantly and perhaps even encouraging women to seek earlier diagnosis of breast cancer. However, the psychosocial benefit of reconstruction is only slight when patients who have undergone surgical reconstruction are compared with patients treated with mastectomy alone. Breast-preserving surgery affects body image less than mastectomy and breast reconstructive procedures do. Studies show lower scores for body image in women who have undergone breast reconstruction than in patients who have undergone breast-preserving surgery. This phenomenon may be related to the complicated nature of reconstructive surgery.
A cohort analysis of 13,388 women confirmed findings from numerous studies in that breast-augmentation surgery does not increase the risk of breast cancer and does not delay diagnosis.
Although breast-reduction surgery is never performed as cancer prophylaxis, it appears to reduce the risk of breast cancer proportionate to the amount of tissue removed. Prophylactic mastectomy has a proven role in reducing the incidence of breast cancer, both among women with a moderate or high-risk family history and among those with proven mutations of BRCA1 or BRCA2.
Methods of reconstruction

Reconstruction of the breast can be accomplished in several ways at any time after surgery. The type and timing of reconstruction do not affect biologic processes or the detection of breast cancer. For advanced cancers for which irradiation of the chest wall and regional nodes is planned, breast reconstruction should be delayed, but the intention to perform reconstructive surgery does not prevent radiation therapy if unexpected pathologic findings are discovered.
The simplest reconstruction consists of placing an expandable saline implant under the pectoralis muscle in the musculofascial layer and stretching the tissues of the chest wall to reduce tightness and firmness of the chest wall. The implant is then replaced with a permanent implant. Saline is instilled into a fill valve at regular intervals over several weeks until the expander is overfilled to 200 mL beyond the volume of the contralateral breast. After the chest wall is stretched to allow for a normal breast contour, a second operation is performed to replace the implant with a shaped prosthesis or to remove the excess fluid and fill valve. Complications include extrusion of the expander, infection, and deflation. Patients complain of chest-wall tightness and asymmetry.
The 3 most common of the autologous procedures are the latissimus dorsi muscle flap procedure (performed by using muscles taken from the back), the procedure involving a pedicular transverse rectus abdominis muscle (TRAM flap, sometimes called conventional flap), and the free TRAM flap procedure (sometimes called the microsurgical flap). Both TRAM procedures are performed by using muscle taken from the abdomen. The deep inferior epigastric perforator (DIEP) procedure and the superior gluteal artery perforator (SGAP) flap procedure are relatively new techniques in which fat and skin without muscle are used for reconstruction. See the images below.


http://img.medscapestatic.com/pi/meds/ckb/16/ cancer. Transverse rectus abdominis muscle (TRAM) flap.
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Breast cancer. Transverse rectus abdominis muscle (TRAM) flap.
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Flap procedures are used to transfer distant tissue with its own blood supply. Muscle and skin can be transplanted from the back (latissimus dorsi flap), abdomen (transabdominal rectus or TRAM flap), or buttocks (gluteus flap), and a microvasculature anastomosis is performed. The TRAM flap has become the flap of choice because of the volume of tissue that can be moved. However, cigarette smoking, diabetes mellitus, and obesity are relative contraindications because of decreased microcirculation. When the irradiated chest wall is reconstructed, the TRAM flap is preferred because of its vascularization.
The pedicle TRAM flap procedure requires the entire rectus abdominis muscle for construction of a new breast. The surgeon rotates the muscle, pulls it up through a previously constructed tunnel in the chest, pockets it out, and molds it into a breast. Blood supply from the superior epigastric artery and vein remain intact at their source, and they are pulled up with the muscle.
The free TRAM flap procedure requires only a portion of the rectus abdominis muscle. The surgeon fully removes a portion of the muscle from the donor site, with blood supply intact from the deep inferior epigastric vein and artery, and reattaches it to the chest wall to reconstruct the breast. The surgeon then connects the tiny vessels to recipient vessels, most often the thoracodorsal artery and vein in the axilla near the new breast, in a separate microvascular procedure.
The free TRAM flap surgery is not performed as often as other procedures in women who choose breast reconstruction after mastectomy (only 5% of reconstructions involve this procedure). However, it is a highly satisfactory option for the right candidates, and, in some cases, it may be the most logical choice.
Postprocedural care

The patient or her caregiver at home must be able to empty any remaining surgical drains and record amounts of drainage. The surgeon usually orders removal of a drain when it has less than 25 mL of output in 24 hours. Drainage from the incisions should be absent or minimal. However, for the first 2-3 days after drain removal, a small amount of serosanguineous drainage from the exit sites is normal. Abnormal drainage is foul smelling and saturates a 4 X 4-in gauze. After the drain is removed, a small piece of gauze may be placed over the drain exit, but the supportive bra should hold it in place. Tape should not be used on the reconstructed breast. For the first few weeks, showering should replace bathing in a tub.
Binding: Instruct patients in the use of a supportive bra without underwires in the hospital, usually a day after surgery. Some patients may desire an abdominal binder in addition to the supportive bra.
Smoking: Avoidance of smoking is especially important during the first few weeks of vascular and tissue healing. Also, avoidance of smoking at least 4 weeks before surgery reduces complications, such as flap necrosis and hernia after surgery.
Exercise: Encourage women after mastectomy to perform arm abduction and reaching exercises; however, advise patients to avoid these exercises after free TRAM flap surgery. The patient may be limited to lifting no more than 10-lbs. for 4-6 weeks, and the patient should keep her affected arm below the height of her shoulder for 2 weeks. However, encourage use of the arm in front of the body (as in washing the face or eating) to prevent stiffening of the joints. Some patients benefit from physical therapy (PT) to strengthen the abdominal muscle after TRAM flap surgery.
If a TRAM flap reconstruction is planned, address rehabilitation issues, and preoperatively counsel the patient about the need for a program to address back and shoulder strengthening. Decreased trunk flexion and extension strength also result from the surgery. PT focuses on strengthening exercises and compensatory movements for most patients, particularly for individuals with chronic spinal pain.
Other types of reconstruction are associated with discomfort related both to loss of tissue from their respective areas and to the actual surgical procedure. The latissimus dorsi flap procedure is less complicated than other reconstructive procedures, but an implant is required for adequate cosmesis. The most common complication is seroma formation. No functional loss of shoulder strength is observed. A gluteus maximus flap is both less painful and less morbid than a TRAM flap, but it is more technically demanding. A nipple can be constructed in all types of reconstruction by puckering skin and tattooing an areola, or by grafting skin into a nipple site and tattooing. Avoid grafts on irradiated skin.
Shoulder and Arm Rehabilitation

The goal of arm and shoulder exercises is to enable the patient to return to normal activity after axillary dissection. At 3 or 15 months after surgery, approximately 80% of patients continue to report at least 1 problem. Problems may include swelling (25%), weakness (25%), limited ROM (30%), stiffness (40%), pain (50%), and/or numbness (55%). Increasing numbers of complaints are associated with high levels of psychological distress. In the optimal situation, preoperatively evaluate the patient for strength, ROM, sensation, posture, endurance, and general functional ability. Instruct the patient regarding ROM exercises, postoperative breathing, and initial mobility after surgery. Start shoulder and arm rehabilitation as soon as the surgical incision appears healed and recurrent seroma or infection is absent; remember the principles of wound healing.
Early PT to the shoulder after axillary dissection does not increase the incidence of lymphedema. The development of seromas is most prevalent with extensive surgeries. Encourage the patient to begin gradual stretching exercises for all degrees of motion within a few days of surgery. The optimal program starts postoperatively with gentle ROM exercises of the shoulder from 45-90° in patients without reconstruction. PROM should start to 90° of flexion and abduction with external and internal rotation as tolerated. Early mobilization of the glenohumeral joint improves shoulder ROM. Recovery was faster in patients who began shoulder flexion to 40° on day 1 and 90° on day 4 than in those who had a delayed start of ROM exercises. Methods to compensate for nerve injury improve muscle strength and prevent shoulder tightness and discomfort.
Patients should begin full shoulder and arm ROM exercises as soon as the surgeon deems them safe, often after the drains are removed. Active and active-assistive exercises can be increased at this stage. Exercises, such as wall climbing, and use of pulley or wand, should be added. After all sutures are removed, exercises more aggressive than these can be incorporated.
Physical modalities may be helpful. Use ultrasound with caution, given its potential risks of promoting residual tumor cell growth or metastasis. Include stretching exercises and electrical stimulation as part of the rehabilitation program. Patients treated with mastectomy are more likely than patients receiving breast-conserving surgery to have impaired mobility. Prospective studies demonstrate that patients who receive structured PT achieve arm and shoulder function better than the function of those who do not receive such PT.
A home exercise program should be implemented, and follow-up PT assessment should be included. Massaging of scars is usually incorporated into this program around 1 month after surgery. With radiation treatment, ongoing ROM exercises are particularly important to prevent contracture formation.
Discuss lymphedema precautions with the patient before surgery, and review her condition within several days of surgery. When resting, the patient should elevate her arm higher than her heart but not over her head. Exercises using the forearm and hand should be performed immediately to help muscular propulsion of blood and lymph fluid from the lower arm. Encourage the patient to squeeze a tennis ball or other soft ball when resting. Advise the patient not to lie on her arm in the ipsilateral decubitus position and to avoid a prone position.
Discuss the effects of skin or soft tissue infections on the development of arm edema, the effect of gravity on lymph drainage, the importance of avoiding procedures on the arm that may break the skin, and the type of exercises that can improve muscle tone in the arm. Encourage the patient to be aware of the importance of weight management because edema of the arm is associated with weight gain. Advise the patient to seek medical help immediately if signs of erythema or swelling occur. Many physicians prescribe antibiotics for acute edema.
Radiation Therapy and Its Consequences

Use of radiation therapy after breast-preserving surgery is common to reduce the probability of recurrence in the breast and after mastectomy, when the risk of recurrence in the chest wall is high. The breast is treated with tangential techniques that also include irradiation of the underlying muscle, rib, and anterior surface of the lung. After mastectomy, the chest wall is treated with similar techniques, but radiation is delivered after subcutaneous tissue is damaged by production of skin flaps. The supraclavicular, axillary, and sometimes internal mammary nodes are irradiated when the risk of nodal recurrence is high. Direct anterior fields are used to treat increased volumes of rib and lung tissue. The brachial plexus is often in the node fields, but damage is uncommon with standard doses. Irradiation of the axillary nodes is associated with an increased risk of lymphedema; avoid it unless the risk of recurrence in the axillary nodes is clinically significant.
Irradiation exaggerates the effects of surgery. Fibrosis secondary to radiation in the treatment field may cause the following effects:
Increased obstruction of arm lymphatics (if in the radiation field)
Increased tightness of the chest wall and pectoralis decreasing shoulder mobility (most prevalent in patients undergoing mastectomy)
Pain in subcutaneous tissues, intercostal muscles, or ribs
Decreased pulmonary reserve (rare unless more than 10% of the lung volume is treated)
Rib fractures (1% risk)
Soft tissue infections, cigarette smoking, and diseases that may impair microcirculation (eg, diabetes, arteriosclerotic vessel disease) increase the probability of fibrosis. Exercise and manual massage may decrease pain and discomfort associated with fibrosis. Ointments to treat dry skin may relieve dryness and itching. Breast edema is an adverse effect unique to breast preservation and related to the extent of axillary dissection, the location and extent of breast surgery, and the size of the breast. Weight gain may aggravate breast edema. Breast edema resolves with time, but weight loss, proper breast support, and avoidance of prone sleeping position may help. Development of late breast edema is uncommon and may represent infection or recurrent cancer.
If volumes of lung tissue greater than 10% are included in the radiation fields, the patient may develop cough, shortness of breath, and low-grade fever 4-12 weeks after radiation. The physician must rule out an infectious source. Chemotherapy increases the risk of pneumonitis. Temporary, low-dose steroids may relieve symptoms of radiation pneumonitis, and antibiotics are often added empirically. Acute radiation pneumonitis resolves in 2-3 months and is not predictive of long-term pulmonary insufficiency. About 10% of lung volume must be treated to observe pneumonitis. Always compare chest radiographs with radiation portal images to confirm the etiology of the disease process.
Most patients have subclinical effects of the lung. In most patients, the diffusing capacity of carbon monoxide decreases but returns to normal levels by 24 months. However, patients who smoke cigarettes have greater deficit and less recovery than those who do not smoke. Cigarette smoking affects the tolerance of the lung to radiation; therefore, encourage patients to stop smoking. Permanent injury to the lung because of interstitial fibrosis is localized to only the radiation field and can be identified on lung radiographs. Long-term effects of lung fibrosis are related to the volume of irradiated lung and to the patient’s pulmonary status before irradiation.
Radiation-induced brachial plexopathy is characterized by shoulder discomfort and progressive paresthesias and weakness in the arm and hand. About 1% of patients who receive nodal irradiation with doses greater than 50 Gy and who are usually treated with chemotherapy develop problems. If doses are limited to 50 Gy, symptoms are generally transient. Symptoms develop 3-14 months after irradiation and commonly affect the distribution of the lower plexus. Progressive neurologic dysfunction of the brachial plexus is associated with radiation fibrosis because of large fractions. The prevalence of pain, in addition to paresthesias of the hand and proximal arm weakness, may be increased. Weakness in the distribution of the upper plexus is most common. Associated arm edema secondary to irradiation is often noted. No treatment, other than symptomatic management, is known. However, cancerous infiltration of the brachial plexus can mimic these symptoms and must be ruled out.
Women treated with direct fields to the left side of the chest may have increased incidence of arteriosclerotic heart disease and, consequently, of myocardial infarctions. Women often become menopausal as a result of estrogen deprivation; this development may add to incidence of cardiovascular disease. Discuss the benefits of diet, exercise, hypertension treatment, and treatment of cholesterolemia with any patient with breast cancer, but the importance of this step is most obvious in patients treated with irradiation and chemotherapy.
Hormonal Treatment

Tamoxifen or aromatase inhibitors are commonly prescribed for women with hormone receptors positive for estrogen whose cancers are larger than 1 cm. Many premenopausal women receive tamoxifen after chemotherapy, whereas many postmenopausal women with large tumors or positive nodes receive it as single-agent adjunct therapy. Tamoxifen may be prescribed for a minimum of 5 years. In addition to the antitumoral effect, other benefits of tamoxifen may include reduced bone loss and an improved lipid profile. Tamoxifen often exaggerates symptoms of estrogen deprivation, with hot flashes (50-60%), depression (10%), weight gain, and vaginal dryness as common complaints. Examine patients annually because of a possible risk of endometrial carcinoma secondary to tamoxifen. The aromatase inhibitors have equal efficacy and a slightly improved adverse-effect profile.
Chemotherapy and Its Consequences

In the adjunct setting, chemotherapy is usually administered in 4-6 cycles of 3-4 weeks. Preconceived notions, often incorrect, can affect a woman’s attitude toward chemotherapy. The clinician must anticipate these concerns, particularly nausea, hair loss, and lifestyle changes, when introducing the topic of chemotherapy. Immediate effects of chemotherapy include general fatigue, as well as nausea and vomiting, which are effectively countered with medication, including prochlorperazine, lorazepam, ondansetron, and granisetron. Patients often gain weight because food may relieve nausea, and their basic metabolic rate may decrease. Fatigue can be overwhelming and affect exercise and activity levels. Work and family issues may be important during chemotherapy because treatment can last for many months.
During therapy, many women have a diminished immune status, which puts them at risk for infection. These periods are short, but some women require increased intervals between chemotherapy cycles or use of growth factors, which are associated with their own adverse effects. Prolongation of chemotherapy may be devastating for many women who have planned for periods of disability for a certain length, who are limited in their sick absences from work, or who must rely on childcare. In general, these women should avoid being around children with the usual childhood diseases (eg, chickenpox).
Chemotherapy may render women, generally those in their late 30s or 40s, menopausal. The incidence of premature ovarian failure is about 70%, but it is lower than this in women younger than 30 years. The most common severe late effect of doxorubicin (Adriamycin) chemotherapy is cardiomyopathy, occurring in less than 1% of women with a total cumulative dose of 300 mg/m2. A previously active young woman may become dyspneic on exertion. Appropriate consultations with a cardiologist and staff from cardiac rehabilitation programs may improve the performance status of women made symptomatic by therapy. Another serious adverse effect of chemotherapy is an increased risk of leukemia, which is related to dose and type of alkylating agent (incidence of 0.7% at 10 y); this risk may increase with adjunct radiation. Current data suggest that the risk of leukemia is minimal with regimens containing cyclophosphamide that are used today.
Nonetheless, the use of adjuvant chemotherapy clearly benefits women with early breast cancer. A meta-analysis of randomized trials of adjuvant prolonged polychemotherapy in women with early breast cancer demonstrated that, in terms of survival advantage, relatively short regimens of approximately 3-6 months were as effective as the longer chemotherapy regimens. Polychemotherapy provided an absolute improvement of 7-11% in 10-year survival among women younger than 50 years at presentation; for women 50-69 years of age, the absolute improvement in 10-year survival was 2-3%.
Anthracycline-containing regimens were slightly more active than the previous standard combination chemotherapy of cyclophosphamide, methotrexate and 5-fluorouracil (CMF), with the former producing a moderate improvement over the latter with respect to the percentage of patients surviving and being disease-free after 5 years. The benefit of anthracycline-containing regimens is particularly evident in premenopausal patients, and increasing evidence suggests that 6 or more cycles of the 3 drug regimens are more effective than the 4 cycles of doxorubicin and cyclophosphamide (ie, Adriamycin and cyclophosphamide [AC]) that has become popular.
Taxanes, such as paclitaxel, have promising activity in patients with node-positive primary breast cancer. Preliminary results from a large, multicenter study showed that patients treated with AC followed by paclitaxel had a significantly better disease-free survival and overall survival than patients treated with only AC. Moreover, the addition of paclitaxel to AC was well tolerated. Further results from this trial are awaited with interest, particularly because preliminary results from other studies have not yet confirmed these findings.
Encourage women to be active and to seek support. Evidence suggests that participating in support groups or having a confidant increase probability of survival. Continuation of regular activities during chemotherapy is beneficial. In 1 study, 41% of women found that treatment was easier than expected. By focusing on delayed benefits of chemotherapy (ie, survival issues), women can cope with short-term adverse psychological effects. In some professions, women are not allowed to continue working during therapy (eg, firefighter, airline pilot), and they are placed on medical disability. The Americans with Disabilities Act (ADA) protects women with breast cancer from workplace discrimination in most settings. The Family Medical Leave Act (FMLA) also requires flexibility in scheduling for patients and family members to accommodate treatments.

While there is not a criterion standard when prescribing exercise, an experienced rehabilitation team can prescribe an exercise regimen to optimize each patient’s health. For the general population, the benefits of exercise on weight and on the cardiovascular system are undisputed. Women with breast cancer who participated in aerobic exercise have improved QOL. Obesity is a minor risk factor for breast cancer; it is associated with additional complications of breast-cancer treatment (eg, lymphedema) and is associated with an increased risk of breast-cancer recurrences.
Exercise improves the functional capacity of patients with breast cancer who are receiving adjunct chemotherapy. Weight gain is common during chemotherapy and apparently connected with loss in muscle tissue, which may contribute to reduced functional capacity and a lowered metabolic rate during adjunct chemotherapy. Increased lean body weight is observed in patients who exercise while receiving chemotherapy.
In animal models, exercise did not induce metastases and was associated with a decreased number of metastases. Exercise also attenuates cachexia in animals.[#target3]
Management of Lymphedema

Any dissection of axillary lymphatics and nodes places a woman at risk for edema of the arm. Axillary surgery and irradiation can lead to lymphedema, which may be caused by direct damage to axillary lymphatics. Fibrosis of the axilla secondary to surgery and/or radiation causes venous and lymphatic obstruction by compressing major vascular trunks and blocking regeneration of lymphatic and venous collaterals. Additional radiation therapy, trauma, and infection are other causative factors. Increase in arm circumference immediately after surgery is common and should resolve within weeks. No standardization exists in the literature as to the type and location of measurement and the implications of such measurement. Most clinicians agree that a difference in circumference of more than 2 cm between the arms has clinical significance.
Nonetheless, lymphedema may be classified as 1 of 3 stages. The first stage is where pitting is associated with edema and temporarily reduced with elevation of the arm. In the second stage, the edema does not reverse spontaneously. Protein-rich edema persists and can lead to proliferation of connective tissue. With such changes, fibrosis occurs and brawny edema is seen on clinical evolution. In the last stage, lymphostatic elephantiasis, the patient has enormous volume with cartilage-like hardening of dermal tissue along with papillomatous outgrowths.
Late arm edema is associated with the patient’s age, the extent of cancer in the axilla, the extent of axillary dissection, and the dose and techniques for irradiation. Nearly 33% of patients older than 55 years and 25% of patients in whom more than 15 nodes are dissected develop a difference of 2 cm or greater in the circumference of their arms at 3 years. By comparison, late breast edema is less common after axillary dissection is performed in conjunction with breast-preservation surgery. Therefore, always consider the presence of an infection or recurrent cancer as a possible cause of late edema.
Perform medical assessment to determine the cause of swelling. Rule out or treat infection, venous thrombosis, or cancer recurrence. Prescribe antibiotics if the development of edema is acute. Make serial measurements of both arms with the olecranon as the reference point. Assess shoulder, arm, and hand strength; sensory changes; color; turgor; pulses; and mobility. In rare cases, long-standing lymphedema can lead to lymphangiosarcoma, a highly aggressive tumor with poor survival despite forequarter amputation.
Conservative management of lymphedema should include preventive and mechanical modalities as needed. Pharmacologic means include antibiotic prophylaxis to prevent and treat cellulitis and lymphangitis. Drugs such as anticoagulants, hyaluronidase, pyridoxine, benzopyrenes, and others have been used but have no proven therapeutic value. Preventive care should emphasize identification of patients at highest risk of lymphedema. Comorbid illnesses such as hypertension, heart disease, diabetes and kidney disease can contribute to edema also. Patients should understand lymphatic drainage, the pathology leading to lymphedema, as well as the signs, symptoms, and complications of lymphedema.
Self-care instructions include the following:
Proper nutrition with balanced nutrition and increased protein and lowered salt intake
Weight management
When possible, the arm should be elevated above the level of heart.
Home exercise program includes the following:
ROM exercises
Exercises and techniques to improve venous drainage
The importance of gravitational drainage
Static resistance exercises and positional changes need to be incorporated into daily activities, including positioning for sleep.
Traditionally, no heavy lifting with the involved arm, typically less than 15 lb – However, although weight lifting has generally has been proscribed for women with breast cancer–related lymphedema, in a randomized, controlled trial of twice-weekly progressive weight lifting in 141 breast cancer survivors with stable lymphedema of the arm, Schmitz et al found that, compared with the control group, the weight-lifting group had greater reductions in the self-reported severity of their lymphedema symptoms (P=0.03) and experienced more improvement in upper- and lower-body strength (P< 0.001 for both). [22]
In addition, the incidence of lymphedema exacerbations was lower in the weight-lifting group than in the control patients (14% vs 29%, P=0.04).
Injury and infection should be avoided, as follows:
No venipuncture or finger sticks on the involved side
Skin breaks should be cleaned with mild soap and water, followed by antibacterial ointment use.
Recommend long-sleeved shirts and bug-repellents for prevention of bug bites.
Use of gloves during gardening
Use of an electric razor for shaving
Good nail care, including not cutting the cuticles
Gauze wrapping instead of tape use
Physician should be notified about rashes, erythema, swelling, pain, increased warmth or localized infection. Daily cleaning and lubrication of skin is indicated.
Avoid constrictive pressure on the arm (eg, no blood pressure cuff, no constrictive bands).
Recommend follow-up with the physician on a regular basis and with any sudden change in arm circumference or evidence of infection.
Complex lymphedema therapy is used to treat peripheral lymphedema and typically has 2 phases, acute and maintenance. The acute phase of therapy consists of manual compression, external compressive bandaging, and specific therapy exercises, including manual and massage techniques. Patients and family members should be taught these techniques. The goals for the patient during the maintenance phase are to be able to wear specially fitted pressure gradient garments during the day, with compression bandaging or a compression device at night. Intermittent pneumatic pressure devices are used in the management of lymphedema. However, such devices may be most effective in low-protein venous edema in which fluid is directly forced back into the blood vessels. With lymphedema, such tissue fluid may simply be displaced into an adjacent region.
External compression can place increased proximal demands on the existing intact lymphatic system. Pressures over 45 mm Hg may further damage lymphatic structures. With increased pressures, pain and hematomas are common in the involved site. Patients with severe edema required prolonged compressive bandaging and close follow-up with therapists (typically several times a week for at least 3-4 wk). Afterward, results can be maintained with continued bandaging and use of manual techniques at home.
A nonelastic bandage may have to be left on in excess of 12 h/d. After the volume of the limb is stabilized, the use of manual techniques and compression garment (often customized) may be sufficient. With exacerbations of lymphedema, use of a nonelastic bandage may be necessary, along with outpatient PT for close supervision. Compression garments are ideally replaced every 3-4 months because they tend to lose their elasticity.
Counsel the patient regarding the permanent nature of the condition and how to prevent its progression. Remember that, with increased interstitial protein level, progressive fibrosis and chronic inflammation can ensue. Although treatment is time-consuming, particularly in its initial phases, it is associated with improved body image and function, which increase QOL. Arm swelling has been associated with increased psychiatric morbidity, as reflected by anxiety, depression, and poor adjustment to breast cancer. Consider psychological intervention when lymphedema is obvious to the casual observer.
Investigators in the Netherlands reported long-term impairments, disabilities, and QOL-related issues. Pain (60%) and reduction of grip strength (40%) were the most frequent impairments. The prevalence of impaired ROM and edema was 9-16% and 15%, respectively. Mean group scores for QOL differed significantly for physical functioning, vitality, and health perception compared with those for a healthy female group. Radiotherapy and chemotherapy were significant factors in the prediction of impaired ROM.
Another group of clinical investigators reported their findings in 105 survivors of breast cancer. The patients were interviewed to obtain data about their health and economic changes in the 5 years after diagnosis and initial treatment. An age- and work-matched group of 105 women without cancer were also interviewed. Key changes in functional status and economic outcomes (eg, changes in market earnings, household income, insurance coverage) were measured. Severity of impairment was compared between the study and control groups. Also tested was the adversity of economic outcomes in relation to the women’s impairment, regardless of their breast cancer status.
The analysis revealed statistically significant evidence with regard to each of the relationship tested. Survivors of breast cancer were more likely than control subjects to be functionally impaired at 5 years, and women with impairment were most likely to have reduced work effort and to experience downturns in market earnings, among other outcomes.
Korpan et al reviewed the effects of exercise on breast cancer treatment–related lymphedema. Weight-lifting exercise did not worsen lymphedema when individuals wore a compression garment on the affected limb. Hydrotherapy pool exercise decreased mild-to-moderate lymphedema 29% after 3 months of weekly sessions. [23]
Exercise facilitates lymph drainage via 2 mechanisms. First, exercise compresses lymph vessels with muscle contraction. Second, exercise alternates intrathoracic pressure with respiration. These 2 mechanisms assist lymph drainage from the extremities, into the thoracic duct, and back into circulation.


In Medscape


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