Inflammatory Breast Cancer
Nour Abuhadra, MD
Assistant Professor
Breast Medicine Service
Memorial Sloan Kettering Cancer Center
Inflammatory breast cancer (IBC) is a rare and aggressive disease – while the incidence is only 2-4% of all breast cancers in the United States, it is responsible for up to 10% of breast cancer-related mortality 1. This type of breast cancer is associated with a high risk of early recurrence and very poor prognosis. The median overall survival is less than 4 years even with multimodality therapy 2. The only independent risk factor for inflammatory breast cancer is a high body mass index 3. There has been no significant association made with inherited genetic mutation; in one retrospective review of 500 IBC patients, germline mutations were noted in only 14% of patients, of which 7% were BRCA1 or BRCA2 4.
The diagnosis of IBC is made using clinical characteristics that are pathognomonic for this disease entity. The following characteristics are essential to make the diagnosis: (a) involvement of >30% of the affected breast and/or skin, (b) rapidly occurring skin changes (3-6 months) such as erythema, edema and/or peau d’orange-like changes, and (c) pathologic confirmation of invasive breast cancer. It is important to note that approximately 75% of IBC cases involve dermal-lymphatic invasion on biopsy5,6. The formation and invasion of these tumor emboli in the dermal-lymphatic vessels is not required to make the diagnosis but is thought to contribute to the rapid metastasis associated with this disease.
The majority of IBCs are hormone receptor-negative. Hormone receptor-positive IBC is relatively rare and these patients tend to have a poor response to standard endocrine therapy7. The human epidermal growth factor receptor 2 (HER2)-positive and triple-negative breast cancer (TNBC) subtypes are more common in IBC (40% and 30% respectively) which may play a role in driving the overall aggressive nature of the disease7.
IBC requires prompt diagnosis and initiation of treatment. The standard of care treatment for IBC at this time remains multimodal therapy (involving surgery, chemotherapy and radiation). This involves neoadjuvant chemotherapy, followed by locoregional treatment. Locoregional therapy includes modified radical mastectomy with axillary dissection and post-mastectomy radiation2,8. The backbone chemotherapy regimen must include anthracyclines and taxanes for all IBC patients. In patients with HER2 over-expression, anti-HER2 therapy must be integrated into the chemotherapy backbone; for hormone receptor-positive patients, endocrine therapy may also be used. It is important to note that approximately one-third of IBC patients have stage IV disease at the time of diagnosis and in these patients chemotherapy is the primary treatment offered. If patients have a significant clinical response to chemotherapy then aggressive locoregional control with surgery and radiation may be considered, however this remains controversial.
There is a growing interest in evaluating the tumor microenvironment of IBC (such as tumor-associated macrophages, dendritic cells etc.) and inflammatory pathways in order to elucidate novel therapeutic mechanisms9–11. Given the rarity of IBC, multi-institutional collaborative efforts and innovative clinical trial design (with longitudinal specimen collection) are necessary in order to improve our biological understanding of IBC and improve patient outcomes9.
In recognition of Breast Cancer Awareness month and to optimize the prevention, diagnosis, treatment and cure of Breast cancer, Health Care Practitioners (HCPs) in Qatar are encouraged to visit the Qatar cancer screening site and access the breast cancer guideline for HCPs: https://bit.ly/3a82irj
Bibliography
1 Hance KW, Anderson WF, Devesa SS, Young HA, Levine PH. 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: 966–75.
2 Matro JM, Li T, Cristofanilli M, et al. Inflammatory breast cancer management in the national comprehensive cancer network: the disease, recurrence pattern, and outcome. Clin Breast Cancer 2015; 15: 1–7.
3 Chang S, Buzdar AU, Hursting SD. Inflammatory breast cancer and body mass index. J Clin Oncol 1998; 16: 3731–5.
4 Rana HQ, Sacca R, Drogan C, et al. Prevalence of germline variants in inflammatory breast cancer. Cancer 2019; 125: 2194–202.
5 Bonnier P, Charpin C, Lejeune C, et al. Inflammatory carcinomas of the breast: a clinical, pathological, or a clinical and pathological definition? Int J Cancer 1995; 62: 382–5.
6 Manfrin E, Remo A, Pancione M, et al. Comparison between invasive breast cancer with extensive peritumoral vascular invasion and inflammatory breast carcinoma: a clinicopathologic study of 161 cases. Am J Clin Pathol 2014; 142: 299–306.
7 Chippa V, Barazi H. Inflammatory Breast Cancer. In: StatPearls. Treasure Island (FL): StatPearls Publishing, 2020.
8 Dawood S, Merajver SD, Viens P, et al. International expert panel on inflammatory breast cancer: consensus statement for standardized diagnosis and treatment. Ann Oncol 2011; 22: 515–23.
9 Lim B, Woodward WA, Wang X, Reuben JM, Ueno NT. Inflammatory breast cancer biology: the tumour microenvironment is key. Nat Rev Cancer 2018; 18: 485–99.
10 Menta A, Fouad TM, Lucci A, et al. Inflammatory breast cancer: what to know about this unique, aggressive breast cancer. Surg Clin North Am 2018; 98: 787–800.
11 Rosenbluth JM, Overmoyer BA. Inflammatory breast cancer: a separate entity. Curr Oncol Rep 2019; 21: 86.