Inflammatory breast cancer: An overview
Introduction
Inflammatory breast cancer (IBC) is a rare subtype of locally advanced breast cancer according to the tumor-node-metastasis (TNM) breast cancer staging system. IBC is classified as T4d and clinically characterized by diffuse in duration of the skin with an erysipeloid edge, usually with no underlying mass (Fig. 1) [1]. The objective of the current review is to present an overview of the literature related to the biology, imaging and multidisciplinary treatment of inflammatory breast cancer.
Section snippets
Methods
The PubMed database was searched using the following terms (Fig. 2): “inflammatory breast cancer” successively complemented with “epidemiology” and “risk factors”, “MRI” and “PET/CT”, “chemotherapy”, “surgery”, “radiotherapy”, “hormone receptors”, “epidermal growth factor receptors”, “tumor suppressor genes”, “(lymph) angiogenesis” with the limits English, Publication Date from 1980/01/01, Humans, abstract available. We augmented this computerized literature search by manually reviewing the
Clinical and pathological characteristics of inflammatory breast cancer
A differentiation between primary and secondary inflammatory breast cancer has to be made. By primary inflammatory breast cancer, we refer to the development of breast carcinoma in a previously normal breast. The term secondary inflammatory breast carcinoma is given to the development of inflammatory skin changes associated with invasive breast carcinoma in a breast that already had cancer or there was carcinoma in the chest wall that developed after a mastectomy for non-inflammatory breast
Epidemiologic features
Inflammatory breast cancer is the most aggressive entity of breast cancer and comprises 2.5% of all breast cancers [5]. The median overall survival among women with IBC is less than 4 years even with multimodality treatment options. However, an increasing survival in recent years has been noted with improvement of chemotherapeutical management [6]. The incidence of IBC appears to be increasing, particularly among Caucasian women. Women with IBC typically present at a younger age than NIBC [7].
Diagnosis and staging of inflammatory breast cancer
An appropriate initial work-up of IBC should consist of history and physical examination followed by diagnostic evaluation. Patients with IBC typically present with pain and a rapidly progressing, tender, firm, and enlarged breast. The skin over the breast is reddened, warm, and thickened, termed ‘peau d’orange’. Mammography may show an obvious tumor mass, a large area of calcification, and/or parenchymal distortion. Mammography also may show skin thickening over the breast, with or without a
Systemic neoadjuvant chemotherapy
Anthracycline- and taxane-based adjuvant chemotherapy regimens are widely used for neoadjuvant chemotherapy and are particularly effective in IBC. See Table 2. Sixty-eight patients with IBC received treatment three courses of neoadjuvant chemotherapy with cyclophosphamide, doxorubicin, 5-fluorouracil (5-FU) (CAF) or cyclophosphamide, epirubicin, 5-FU (CEF) followed by surgery and six adjuvant courses of CAF or CEF alternated with cyclophosphamide, methotrexate, 5-FU. Radiation therapy was
Surgery
Historically, patients with IBC treated by surgery alone had a very poor prognosis, thus IBC was considered to be a contraindication for surgical intervention. At present, primary systemic chemotherapy is considered the first choice of treatment aiming at downsizing the tumor followed by mastectomy combined with axillary lymph node dissection when indicated. Reports on the use of sentinel lymph node biopsy in patients with IBC have demonstrated that it is not reliable in axillary staging [25].
Radiotherapy
Radiation therapy (RT) to the thoracic wall, including ipsilateral axillary, infraclavicular, and supraclavicular lymph nodes, is generally recommended for women with IBC. Although a survival benefit for postmastectomy RT has not been proven in patients with IBC, the improvement in locoregional control makes RT an important modality in the treatment protocol [18]. Radiation fractionation schedules may vary, but usually cumulative doses above 50 gray (Gy) are applied. In a dose-escalation study,
Hormone receptors
Current hormone receptors determinants available in daily practice include the estrogen – (ER) and the progestron receptor (PR). IBC is characterized by less hormone receptor expression compared to non-inflammatory breast cancer (NIBC), which has been associated with a more aggressive clinical course and decreased survival [37], [38].
Up to 83% of IBC tumors lack estrogen receptor (ER) expression compared with other forms of locally advanced breast cancers which are mostly ER positive [39].
Conclusion
This overview of the literature shows that inflammatory breast cancer has several different characteristics which determine the aggressive biology of this disease compared to non-inflammatory breast cancer. Locoregional therapies like surgery and radiation therapy have shown to improve local recurrence, without significance on overall survival. Since the consistent use of neoadjuvant chemotherapy, overall survival increased [20]. However, new and additional agents are necessary to improve the
Conflict of interest
All authors certify that they have NO affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers’ bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed
Reviewers
Giuseppe Curigliano, MD, PhD, Istituto Europeo di Oncologia, Department of Medicine, Division of Medical Oncology, Milan, Italy.
Wolfgang Janni, MD, PhD, Chair, University of Ulm, Department of Obstetrics and Gynecology, Prittwitzstr. 43, D-89075 Ulm, Germany.
Luis A.M. Costa, MD, PhD, Hospital de Santa Maria, Unidade de Oncologia, Piso 3, PT-1649-035 Lisbon, Portugal.
D.J.P. Van Uden is a surgical registrar in the Netherlands. During his training he has a special interest in surgical oncology and inflammatory breast cancer is the subject of his PhD thesis.
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D.J.P. Van Uden is a surgical registrar in the Netherlands. During his training he has a special interest in surgical oncology and inflammatory breast cancer is the subject of his PhD thesis.
H.M.W. van Laarhoven is medical oncologist and professor of translational medical oncology in the Academic Medical Center.
A.H. Westenberg is radiation oncologist at the Institute for Radiation Oncology (ARTI) Arnhem and specialized in colorectal and breast cancer.
J.H.W. de Wilt is professor of surgical oncology at the Radboud University Medical Center and is specialized in advanced colorectal cancer. He has published more than 150 peer reviewed papers on this subject, as well as melanoma and breast cancer.
C.F.J.M. Blanken-Peeters is a surgical oncologist at Rijnstate Hospital Arnhem and is specialized in breast cancer surgery and thyroid surgery.