ABSTRACT: Over the past 2 decades, breast-conservation therapy with lumpectomy and whole-breast radiotherapy has become a standard option for the majority of women with newly diagnosed breast cancer. Long-term local control is achieved in approximately 85% of patients, and the therapy is generally well tolerated. There can, however, be long-term effects on the breast and other nearby tissues that may range from asymptomatic findings on examination to severe, debilitating problems. Infection, fat necrosis, and severe musculoskeletal problems such as osteoradionecrosis or soft-tissue necrosis are uncommon, affecting less than 5% of patients. However, changes in range of motion, mild-to-moderate musculoskeletal pain, and arm and breast edema are much more common. As more women choose breast-conservation therapy for management of their breast cancer, physicians will encounter these problems, as well as in-breast tumor recurrence, with greater frequency. This review will focus on the incidence, contributing factors, and management of the late problems of infection, fat necrosis, musculoskeletal complications, and local recurrence following breast-conservation therapy.
Breast-conserving therapy with lumpectomy, axillary dissection, and radiotherapy, has been associated with a variety of side effects and complications. It is important to have a good understanding of the frequency and severity of treatment- related problems in order to adequately counsel patients about their treatment options. In addition, continual assessment of techniques and other factors that may influence the incidence of complications is necessary to develop safer treatment approaches. In general, the best way to manage a treatment-related problem is to avoid its occurrence. This is especially important in patients who undergo irradiation, because the options for treatment of late effects may be limited.
This review will focus on some of the less commonly discussed side effects and complications of breast-conserving surgery and radiotherapy for early-stage breast cancer such as infection, fat necrosis, musculoskeletal effects, and pain. In addition, the options for management of in-breast tumor recurrence will be reviewed.
The incidence of cellulitis or breast abscess after breast-conserving therapy is low, ranging from 1% to 5% in most case series, with an annual risk for the development of delayed cellulitis of 0.8%.[1-3] Patients may present with cellulitis or abscess in the perioperative period, or at any time before, during, or after radiation therapy.[2,4] The majority of cases present with pain, erythema, axillary swelling, and warmth in the involved breast, whereas a breast abscess or seroma may present as suspicious mammographic changes or a clinically palpable breast mass. The median latency period for the development of delayed cellulitis is 3 to 5 months postradiotherapy, and it may even occur many years after the completion of therapy.[1-3,6,7]
Although the clinical scenario in which delayed breast cellulitis commonly occurs points to a multifactorial etiology, specific risk factors have been evaluated. Brewer et al performed a matched case-control study to statistically associate potential risk factors with the development of breast cellulitis in a cohort of patients treated with breast-conserving therapy. Their analysis of 17 cases revealed that arm lymphedema was the most prominent risk factor for the development of delayed breast cellulitis. Other trials have also identified the potential role of clinical or subclinical lymphedema of the breast secondary to alteration of vascular and lymphatic flow from surgery and radiotherapy as a potential predisposing factor for the development of breast infection.
It is believed that lymphedema results in stasis within the lymphatic channels, serving as a medium for bacterial growth. Similarly, microvasculature injury or skin desquamation may play an etiologic role.[2,4,7] It is felt that in this anatomically altered setting, microtrauma to the breast may precipitate cellulitis. In addition, many reports have implicated posttreatment breast seroma and aspiration of seroma fluid with the development of cellulitis.[1,4]
Mertz et al found that radiographically demonstrable fluid collections at the lumpectomy site were present in 75% of a small cohort of patients treated for cellulitis after breast-conserving therapy. This finding may point to the presence of these fluid collections as a predisposing factor for the development of later infections.
As with a variety of other cellulitis syndromes, bacterial pathogens are often not recovered, and procedures such as aspiration of the leading edge of a lesion and blood cultures, in the absence of other systemic symptoms of infection, usually produce a low yield.[4,6] Hence, treatment is generally empiric, and choice of antibiotic treatment is influenced primarily by clinical presentation. The most frequently cultured organisms are Staphylococcus aureus or beta-hemolytic streptococci species.[4,6]
Initial treatment for mild cases consists of empiric therapy with oral antibiotics to cover normal skin flora. Penicillinase-resistant penicillins, including nafcillin and oxacillin(Drug information on oxacillin), and first-generation cephalosporins, including cefazolin(Drug information on cefazolin) and cephalexin, are commonly selected. If S aureus is suspected, a beta-lactamase-inhibiting penicillin such as amoxicillin(Drug information on amoxicillin)/ clavulanate (Augmentin) or ampicillin(Drug information on ampicillin)/ sulbactam(Drug information on sulbactam) (Unasyn) may be used. For persistent cases or for patients with leukocytosis and fever, hospital admission for a course of intravenous antibiotics may be warranted.
Although many patients will experience a relatively quick response to empiric therapy, clearance of breast changes may be gradual and may persist for extended periods (Figure 1). Cultures of abscesses or seroma aspirates may be obtained prior to the initiation of therapy to facilitate later revision of therapy as needed for patients without a clinical response. The recommended period of treatment is usually 10 to 14 days.
Incision and drainage should be considered for persistent abscess after completion of therapy. For nontoxic patients who do not respond to antibiotic therapy, a 7- to 14-day trial of nonsteroidal anti-inflammatory agents or topical corticosteroids may be warranted to treat potential dermatitis. Skin biopsy to rule out cancer recurrence should be considered in all patients who fail to respond to conservative therapy.
In addition to antibiotics, other preventive techniques to decrease lymphedema may be employed, such as compression therapy, skin care, and exercise. Patients with axillary or breast seromas should be counseled on the signs, symptoms, and treatment of cellulitis because they may be at higher risk of developing the problem.
Fat necrosis commonly presents as an indurated mass in the region of the lumpectomy scar, with overlying skin fixation, retraction, erythema, and tenderness. Some reports indicate an incidence of less than 1% on long-term follow-up of patients treated with standard breast radiotherapy.[9,10] Boyages and colleagues found a 4.5% 5-year actuarial risk of fat necrosis or fibrosis requiring surgery. The rate of fat necrosis may be significantly higher in patients treated with certain regimens of high-dose rate brachytherapy alone rather than standard whole-breast external-beam irradiation. Wazer et al found that 27% of 30 patients, who received irradiation twice daily at 340 cGy for 5 days to the lumpectomy cavity plus a 2-cm margin, developed symptomatic fat necrosis. In another report, 10% of patients treated with high-dose rate brachytherapy (372 cGy twice daily for 5 days) developed fat necrosis within 4 to 18 months. The average time to onset of symptoms is approximately 12 months posttherapy. In most patients, the presentation of fat necrosis clinically mimics that of recurrent tumor. Mammographic evaluation is helpful in identifying the lesion if characteristic changes such as radiolucent oil cysts are present. However, fat necrosis may also appear on mammography as round opacities, dystrophic calcifications, and clustered pleomorphic calcifications. Given the often confusing clinical presentation and inconclusive imaging, ultrasound-guided core biopsy should be performed in all patients, even those with a history of breast trauma predating the appearance of their lesion. If local symptoms of discomfort persist, excision may be considered in selected patients.