Walter P. Weber
Monica Morrow
Presentation
A 49-year-old woman, G2 P2, age 30 at first birth with no family history of breast cancer, presents with a 1-month history of increasing redness, heaviness, and swelling of her right breast (Figure 1). There was no antecedent history of trauma. Two weeks ago, she saw her primary care physician who made the diagnosis of breast infection and gave her a 10-day course of a cephalosporin. Her symptoms have not improved, and she was referred for surgical evaluation. On physical examination, there is diffuse erythema and edema of the right breast. The breast is diffusely firm compared to the left, but no discrete mass is palpable. There are no palpable supraclavicular or left axillary nodes. A firm, mobile, nontender 1-cm right axillary node is present.
FIGURE 1 • The findings of diffuse erythema and edema of the enlarged right breast with adenocarcinoma on biopsy are diagnostic for IBC.
Differential Diagnosis
In a nonlactating woman, erythema and edema over more than one-third of the breast that does not significantly improve with antibiotic treatment is inflammatory breast cancer (IBC) until proven otherwise. Bacterial infection, including mastitis and abscess, is the most common misdiagnosis. These infections, however, are rare in nonlactating women, and treatment with antibiotics tends to be of immediate benefit. Because IBC is not a true inflammatory process, it is not associated with symptoms such as fever, localized pain, or leukocytosis.
Workup
The patient undergoes bilateral mammography, which reveals only skin thickening and diffusely increased breast density on the right side (Figure 2). Ultrasonography demonstrates increased vascularity and minor architectural distortions in the right breast, and confirms the presence of an enlarged 1.2-cm right axillary node with abnormal architecture. A punch biopsy of the skin, ultrasound-guided core biopsy of the architectural distortion in the breast, and fine needle aspiration cytology of the right axillary node demonstrate adenocarcinoma, thereby confirming the clinical diagnosis of node-positive IBC. The estrogen receptor (ER), progesterone receptor (PR), and HER2 are negative. Laboratory studies show that liver enzymes and lactate dehydrogenase are within normal limits. Further staging with a PET-CT scan reveals no signs of distant metastases.
FIGURE 2 • Mediolateral oblique view of mammogram showing inferior skin thickening and diffuse increase in density from IBC.
Diagnosis and Treatment
IBC is a clinical diagnosis defined by the American Joint Committee on Cancer (AJCC) as “a diffuse brawny induration of the skin of the breast with an erysipeloid edge” and is designated T4d, Stage IIIB in the absence of distant metastases. Patients present with rapid enlargement of the breast, erythema and skin edema, often with an orange-peel appearance (peau d’ orange), and induration or ridging over more than one-third of the breast. On palpation, the breast is warm and diffusely firm, although a discrete mass is often not palpable. In addition, physical exam often reveals palpable lymph nodes as more than 50% of IBC patients have nodal involvement at the time of diagnosis. Mammography with or without ultrasound is standard of care, even though imaging studies may be inconclusive. Classic mammographic features include skin thickening and increased breast density, and a discrete mass is evident in as many as 80% of cases in some reports. Ultrasonography demonstrates increased vascularity and architectural distortion in addition to mass lesions. Distant metastases are present in approximately 25% of patients at the time of diagnosis, and staging investigations should be performed on a routine basis. PET-CT is the imaging test of choice for the detection of distant metastases.
The inflammatory appearance of the breast is due to tumor emboli within the dermal lymphatics (Figure 3). This finding can often be demonstrated on a full-thickness skin biopsy but is not necessary to make the diagnosis of IBC when the clinical signs are present and a biopsy reveals adenocarcinoma of any subtype. Core needle biopsy of any breast mass is the preferred method of diagnosis. In the absence of a discrete mass, core biopsy of any area of architectural distortion on ultrasound is usually diagnostic. The biopsy material should be sent for hormone receptor and HER2 determination.
FIGURE 3 • Photomicrograph showing tumor in the dermal lymphatic spaces (arrow). This finding supports the diagnosis of inflammatory cancer, but tumor in dermal lymphatic spaces without clinical inflammatory changes is not IBC.
IBC is rare, accounting for <3% of breast cancer cases in the United States, but it is the most lethal form of primary breast cancer. Historically, mastectomy with or without radiotherapy was standard management, resulting on average 5-year overall survival rates of <5%. By the 1970s, the treatment paradigm for IBC had shifted to one involving chemotherapy followed by radiotherapy, which improved average 5-year overall survival rates to 30% or more. The use of surgery for IBC has increased again over the last two decades, but the timing of mastectomy has changed from initial cancer management to a postchemotherapy intervention, followed by radiotherapy in all cases and hormonal therapy in hormone receptor-positive disease. The advent of multimodality therapy has significantly improved survival, with 5-year survival rates of over 40% being reported. Hence, women diagnosed with IBC should be managed in a setting where such a specialized approach can be adequately provided.
Surgical Approach
The goals of surgery in IBC are to maintain local control and to improve survival in the absence of distant metastases. The current standard protocol for patients with IBC calls for initial treatment with neoadjuvant chemotherapy. Only patients who show complete resolution of all evidence of skin inflammation should undergo surgery. Surgery in the setting of residual inflammatory changes is associated with poor local control and survival.
The standard procedure in patients with IBC is modified radical mastectomy, which by definition includes total mastectomy with ipsilateral level I/II axillary lymph node dissection. Breast conservation is contraindicated in IBC. Skin-sparing and nipple-sparing mastectomies are contraindicated as well due to the diffuse nature of the tumor and the inability to reliably identify patients with pathologic complete response preoperatively. Moreover, sentinel lymph node biopsy is also contraindicated in patients with IBC. Even though increasing clinical experience suggests that sentinel node biopsy reliably stages the axilla after neoadjuvant therapy, the limited experience with sentinel node biopsy in IBC demonstrates that the false-negative rate of sentinel node biopsy in this setting is unacceptably high. Since many of the advantages of immediate reconstruction, such as the skin-sparing approach, are lost, and because postmastectomy radiotherapy is indicated for all patients, delayed reconstruction is generally preferred.
Mastectomy
The patient is placed supine, with the arm extended on a padded arm board. The arm should be prepped and draped separately to allow free rotation. The skin resection should encompass the nipple and areola, the surgical biopsy site (if present), and the excess skin of the breast. Skin flaps are then created with electrocautery or by sharp dissection with the scalpel or curved scissors. The skin flaps are raised in the plane between the subcutaneous fat and the breast tissue, and extend superiorly to the clavicle, medially to the sternal edge, laterally to the latissimus dorsi, and inferiorly to the rectus sheath. The next step is to remove the breast, which is most easily done from superior to inferior with the fascia of the pectoralis major as the deep margin of the resection. The internal mammary perforators should be ligated with clips or ties to avoid postoperative hemorrhage. The dissection is extended to the lateral aspect of the pectoralis major muscle, which is retracted, and the fascia overlying the pectoralis minor muscle is opened to allow placement of a retractor beneath the muscle. The axillary lymph node dissection is then carried out as described in detail below.
Lymph Node Dissection
Standard axillary dissection clears levels I and II (nodes lateral to the lateral border and posterior to the pectoralis minor muscle). A full level III dissection above the pectoralis minor muscle is carried out when there is gross nodal disease as described in this case. After the breast has been taken off the chest wall as described above, the latissimus dorsi muscle is followed proximally along its anterior surface until it turns tendinous, at which time it is crossed by the axillary vein. No important structures cross this plane of dissection, making it the safest approach to the axillary vein. The anterior surface of the axillary vein is then cleared of overlying fat from lateral to medial, with care being taken not to dissect superior to the vein or to strip the vein in the vascular plane, both of which promote lymphedema. When the vein is well visualized, dissection inferior to the vein is carried out, again working from lateral to medial, dividing the fat and controlling the branches of the axillary vein entering the specimen. The thoracodorsal neurovascular bundle is usually the first deep lateral branch identified after the superficial fat and the vessels have been divided. Once the thoracodorsal bundle is identified, the pectoralis minor is retracted and the level 3 nodes are dissected from the space below the axillary vein and against the chest wall. The axillary specimen is then retracted laterally; the long thoracic nerve is identified against the chest wall and dissected free from the specimen. The fat between the thoracodorsal and long thoracic nerves is then encircled with a clamp, divided, and bluntly swept inferiorly. Branches of the thoracodorsal vessels entering the specimen are controlled with clips, and the specimen is freed from its remaining attachments to the inferior chest wall. After hemostasis is obtained, two closed suction drains are inserted, one beneath the inferior flap and one in the apex of the axilla. The deep dermis is reapproximated with absorbable sutures, and the skin is closed with a running subcuticular stitch.
TABLE 1. Key Technical Steps and Potential Pitfalls to Mastectomy
Special Intraoperative Considerations
Intraoperative findings that would change the operative strategy are rare after a patient has been adequately staged. If the cancer invades the pectoralis muscle, the involved muscle can be removed. There is no need for a classic radical mastectomy for limited muscle involvement, and extensive involvement is clinically evident preoperatively. If extensive axillary nodal metastases extending superiorly into the supraclavicular space are identified intraoperatively, they can be removed if they are mobile and this can be safely done. If residual disease is left behind, it should be marked with clips to assist in defining the radiotherapy fields.
TABLE 2. Key Technical Steps and Potential Pitfalls for Axillary Lymph Node Dissection
Postoperative Management
The patient usually requires an overnight hospital stay. The drain should be removed when the drainage is <30 mL/24 h. A single dose of antibiotic is given prior to surgery, but ongoing prophylactic antibiotics when the drains are in place are not recommended. Postoperative complications other than seroma are infrequent and include bleeding and infection. Postoperative hemorrhage can result from failure to control internal mammary perforators, axillary vein branches, or thoracodorsal branches. Bleeding from these sites usually requires reexploration. Seroma formation can be minimized by removing drains when drainage is <30 mL/24 h rather than on some arbitrary day. If a seroma is clinically detectable, it should be aspirated since the mastectomy flaps cannot adhere to the chest wall in the presence of seroma fluid. The chest wall is anesthetic in 100% of patients post mastectomy. This is a side effect, not a complication, and patients should be educated about this preoperatively. Skin flap necrosis is another potential complication that results from closure under tension, technical error in cutting the skin flaps, or infection. Postmastectomy infections usually present as cellulitis, and any erythema of the wound should lead to prompt antibiotic treatment to avoid flap necrosis. If flap necrosis is suspected, it should be observed until clear demarcation is present and necrotic tissue debrided at that time. With proper incision planning, major full-thickness necrosis is rare, and most necrosis is superficial and limited extent, and will heal without surgical intervention.
Axillary lymph node dissection is associated with long-term morbidity, including chronic lymphedema (5% to 25%), and shoulder dysmobility (5% to 15%). Injury to the motor nerves in the axilla is rare (<1%). Injury to the long thoracic nerve results in a palsy of the serratus anterior muscle and, clinically, will create a winged scapula. Injury to the thoracodorsal nerve causes a palsy of the latissimus dorsi muscle, which may be evident during athletic activity or when trying to scratch in the midline of the back.
Case Conclusion
Following neoadjuvant therapy with dose-dense doxorubicin, cyclophosphamide, and paclitaxel with complete resolution of inflammatory skin changes, the patient underwent modified radical mastectomy and was staged pT4dpN2a, Stage IIIB. Pathology demonstrated scattered residual microscopic foci of tumor throughout the breast, with evidence of treatment effect in the remaining breast tissue. Five of fourteen nodes contained metastases, and the ER, PR, and HER2 remain negative. Adjuvant radiotherapy to the chest wall and supraclavicular, axillary, and internal mammary node fields is planned. She will be followed with clinical exam every 3 months for 2 years, then every 6 months for 3 years, and yearly thereafter, and with annual mammography.
TAKE HOME POINTS
· Prompt biopsy is required for inflammatory breast changes that do not resolve with antibiotics.
· IBC is a clinical diagnosis; histologic confirmation of tumor emboli in dermal lymphatics is not mandatory.
· Multimodality treatment consists of neoadjuvant chemotherapy, surgery, radiotherapy, and hormonal therapy if indicated.
· Surgery is reserved for patients with resolution of skin erythema during neoadjuvant chemotherapy.
· Modified radical mastectomy is standard of care; breast conservation and sentinel lymph node biopsy are contraindicated.
SUGGESTED READINGS
Chia S, Swain SM, Byrd DR, et al. Locally advanced and inflammatory breast cancer. J Clin Oncol. 2008;26(5):786–790.
Hance KW, Anderson WF, Devesa SS, et al. Large population-based epidemiological study of IBC: Trends in inflammatory breast carcinoma incidence and survival: the Surveillance, Epidemiology, and End Results program at the National Cancer Institute. J Natl Cancer Inst. 2005;97(13):966–975.
Merajver S, Iniesta MD, Sabel MS. In: Harris JR, Lippman ME, Morrow M et al., eds. Inflammatory breast Cancer. In: Diseases of the Breast. 4th ed. Philadelphia, PA: Wolters Kluwer/Lippincott, 2010:762–773.
Ueno NT, Buzdar AU, Singletary SE, et al. Combined modality treatment of inflammatory breast carcinoma: twenty years of experience at M.D Anderson Center. Cancer Chemother Pharmacol. 1997;40(4):321–329.