February 2007

Fig4.

Fig.5

Fig.6

Diagnosis: Inflammatory breast cancer

Histopathology: A punch biopsy of the overlying skin reveals an adenocarcinoma with diffuse involvement of the dermis and extensive invasion of the dermal lymphatics. The adenocarcinoma is composed of irregular nests with some areas forming tubercles. Mitotic figures, including atypical forms are seen. (Figures 3 ­ 5.) The tumor was ER -, PR-, Her2 +, CK 7 +, and CK 20 -.

Imaging: Mammography showed skin thickening and edema of the left breast, consistent with inflammatory breast cancer. A CT scan of the chest, abdomen and pelvis revealed multiple indeterminate pulmonary nodules. A PET scan showed diffuse uptake in the left breast as well as increased uptake in the sacrum and axillary nodes. A bone scan showed increased uptake in the sacrum.

Treatment and Course: The patient was started on chemotherapy with taxotere-adriamycin-cyclophosphamide. She expired 2 weeks after her first dose due to sepis and bleeding from a peri-cecal mass.

Discussion: Inflammatory breast cancer is a rare and aggressive form of breast cancer. It accounts for 1-6% of all breast malignancies. It typically affects younger patients than other forms of breast cancer. It presents with the rapid onset of diffuse tenderness, erythema, edema, and warmth of the affected breast. The overlying skin often has a "peau d'orange" appearance. Other distinguishing features include the rapidity of progression, high angiogenic and angioinvasive capability, and aggressive behavior from inception.

Histologically, inflammatory breast cancer is characterized by diffuse invasion of the dermal lymphatics by carcinoma cells. Contrary to what the name suggests, there is no pathologic evidence of inflammation and the amount of inflammatory cytokines produced by the tumor is negligible.

The presence of lymph node involvement is the most significant prognostic factor for women with inflammatory breast cancer. Extensive erythema, ER negativity, and mutations in p53 have also been associated with a poorer outcome.

Neoadjuvant chemotherapy is the mainstay of treatment. Because initially undetectable disseminated microfoci of disease are often present, surgery alone has no role in the primary treatment of inflammatory breast cancer. It is best considered a systemic process from an early stage. Surgery is often only undertaken after at least a partial response to neoadjuvant chemotherapy has been achieved. Likewise, radiotherapy may also be added to enhance loco-regional disease control.

The overall prognosis is poor. Twenty percent of patients have distant metastasis at the time of diagnosis. Without chemotherapy, the mean 5-year survival rate is less than 5%. With chemotherapy, the mean 5-year survival rate is ~35%.

References:
1. Cariati M, Bennett-Britton TM, Pinder SE, Purushotham AD. "Inflammatory" breast cancer. Surg Oncol. 2005 Nov;14(3):133-43.
2. Chang S, Parker SL, Pham T, Buzdar AU, Hursting SD. Inflammatory breast carcinoma incidence and survival: the surveillance, epidemiology, and end results program of the National Cancer Institute, 1975-1992. Cancer. 1998 Jun 15;82(12):2366-72.
3. Kleer CG, van Golen KL, Merajver SD. Molecular biology of breast cancer metastasis. Inflammatory breast cancer: clinical syndrome and molecular determinants. Breast Cancer Res. 2000;2(6):423-9.

This case was presented by Drs. Julia Graves and Milan Anadkat. Histology is courtesy of Drs. Kimberly Crone and Anne Lind.