Inflammatory breast cancer

Accounts for 1-3% of breast cancers.

Approximately 5000 cases per year in the U.S.

Characterized by breast erythema and edema often without a discrete breast mass.

Often a history of recent and rapid change in clinical breast findings.

Prior to the use of systemic chemotherapy median survival was 15 months and local recurrence rates of 50% (Zucali R et l).

Often misdiagnosed as mastitis or breast infection.

Typically diagnosed in young women, who are more likely to have metastases than patients with other types of breast cancer.

Higher rates in African-American women than white women, and they are diagnosed at an earlier age as well.

Associated with higher BMI index.

African-American women have a 50% higher incidence than white women, and decreased survival times (Levine PH et al).

Higher incidence in North Africa countries.

Mean age 55 years, more than half of the patients ER-, and 33% triple negative, more than 50% have a BMI of greater than 30, more than two-thirds are postmenopausal at the time of diagnosis (Bondy M et al).

Diagnosis not made by mammography but rather by the patient with detection of a warm and tender breast with skin changes.

No pathophysiological inflammation is noted despite the name, and the changes of redness, inflammation and edema due to tumor cells in the lymphatic channels and small blood vessels of the skin.

Pathological findings of tumor emboli in dermal lymphatics.

Most inflammatory breast cancer is more high-grade double carcinomas, but there is no association with any particular histological subtype.

The tumor emboli are in the papillary and reticular dermis of the skin overlying the breast.

Dermal lymphatic dilatation is seen without red blood cells and the cells in the emboli are usually of high grade with a ductal phenotype (Rosen PP).

The tumor emboli in IBC are more numerous and often larger than in noninflammatory breast cancers.

No direct relationship exists between the number of lymphatic tumor emboli and skin manifestations of the disease.

Dermal lymphatic involvement in IBC can be demonstrated in 75% of cases by skin punch biopsies, so that absence of these findings in a patient with clinically suspicious disease does not rule the diagnosis out.

Skin thickness may measure up 8 mm, while the normal thickness of breast skin is 1-1.5 mm +/-0.2 mm -2.0 mm.

Usually there is no skin ulceration, Paget’s disease of the nipple or nipple discharge with IBC.

Because the tumor usually infiltrates the stroma diffusly assessing tumor size is difficult.

Pathologically the tumor is distributed as several foci of disease, with uninvolved adjacent parenchyma with lymphovascular tumor emboli.

Pathologically involvement of supraclavicularnand axillary lymph nodes is 60-85%.

EGFR is overexpressed that 18% of breast cancer cases and up to 50% of inflammatory breast cancer cases.

Tumor emboli in lymph vessels may be present in skin that clinical is normal.

Frequently misdiagnosed as an infective process.

Must be differentiated from locally advanced breast cancer with secondary inflammatory changes.

20-40% of patients have evidence of distant metastases at the time of diagnosis.

Women with inflammatory breast cancer have a two times greater risk of dying from breast cancer than do patients with locally advanced breast cancer.

Disease free and overall survival is lower among patients with inflammatory breast cancer than among patients with locally advanced breast cancer with a median overall survival of 3.8 years, even when the patients are treated with similar pre-operative systemic therapies (Anderson WF et al).

The age-specific rate of inflammatory breast cancer peaks and plateaus and 50 years of age, while locally advanced disease continues to increase after the age of 50.

Erythema of the breast is one of the most common chages, where the skin overlying the breast shows a pink color, which may be associated with increased temperature and size secondary to edema.

Edema is associated with exagerated hair follicle pits causing the characteristic peau d’orange (orange peel) appearance of the skin.

Rapidly progressive disease along with diffuse erythema allows for the ability to distinguish inflammatory breast cancer of neglected locally advanced breast cancer.

Lymphatic blockage may cause wheals or ridging of the skin in the breast and may be associated with generalized induration of the breast.

In African-American women IBC may occur with minimal erythematous changes, and lead to a delay in diagnosis.

Not a true inflammatory process and is not associated with fever, pain or leukocytosis.

In the majority of cases a discrete mass is not palpable.

Rapidly enlarging breast and skin changes are the usual first manifestations of the disease.

55-85% of patients present with clinically palpable lymph nodes in the axilla or supraclavicular areas (Walshe JM).

Staged as IIIB, IIIC, or even IV depending upon nodal status or evidence of distant metastases (Edge S et al).

Frequently nipples may be retracted, flattened, crusted, or blistered.

It is not a specific histological type of breast cancer.

More commonly associated with ER-negative disease, have HER-2 overexpression, present at a younger age and have a poorer median survival than patients with noninflammatory breast cancer.

Peritumoral lymphatic invasion is usually prominent histologic finding.

Epidermal growth factor receptors and p53 show more intense staining, and staining for cell adhesion molecule E-cadherin, and more commonly show cytoplasmic localization of sialomucin MUC1` than non-inflammatory breast cancer.

E-cadherin and MUC1 may contribute to the highly metastatic phenotype of IBCs.

The WISP3 (WNT-1 inducible sigmnaling pathway 3) and RhoC (Ras homolog gene family, member C), may upregulate invasion related genes in IBC.

No true family link, but a Pakistani study suggested a family history of breast cancer associated with a greater risk than four patients with non-inflammatory breast cancer (Aziz SS et al).

Mammographic findings include a mass, architectural distortion, and skin thickening.

Calcifications on mammogram seen in 41-47% of patients

Ultrasound frequently demonstrates heterogeneous infiltration of the breast parenchyma, or masses within overlying skin and subcutaneous edema.

Ultrasound allows detection of up to 93% of axillary nodal involvement and up to 50% of infraclavicular, internal mammary, or supraclavicular lymph node involvement.

MRI may be the most accurate test for diagnosis (Chow CK).

Women without known distant metastases able to receive anthracycline based chemotherapy have a reported 10-year breast cancer specific survival of 28.2%.

Today with combination modality treatment 30-40% free of disease for 5-15 years.

With multimodality therapy 5 year survival about 40% (Cristofanilli M et al).

Patients with inflammatory BC have a worse prognosis than patients with non-inflammatory locally advanced BC (Dagwood S et al).

After systemic chemotherapy many patients are operable and some may have a clinically complete remission with a normal appearing breast.

Complete pathologic remission rate for neoadjuvant chemo therapy is low at 15.2%.

Both prospective and retrospective studies support the use of preoperative anthracycline and Taxane based chemotherapy regimens.

Among patients with ER negative inflammatory breast cancer the addition of taxanes improves the median overall survival from 32 months to 54 months (Cristofanilli M et al).

In responders local therapy after systemic chemotherapy may include a mastectomy followed by radiation therapy.

Patients treated with complete pathologic response after chemoradiation have a 10 year breast cancer specific survival of 67%.

There is a direct correlation between long-term survival and achievement of pathologic complete response with preoperative chemotherapy.

20% 15 year overall survival.

Local disease control also contributes to systemic disease control indicating a role for surgery and radiation therapy.

Patients with IBC have a higher risk for contralateral breast cancer and than comparably stage patients noninflammatory breast cancer.

Median overall survival is less than 4 years even with multimodality therapy (Anderson WF et al).

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