| Inflammatory breast cancer | |
|---|---|
| Specialty | Oncology |
Inflammatory breast cancer[1] (IBC) is one of the most aggressive types ofbreast cancer. It can occur in women of any age (and, extremely rarely, in men, seemale breast cancer[2]). It is referred to as "inflammatory" due to its frequent presentation with symptoms resembling a skin inflammation, such aserysipelas.
Inflammatory breast cancer presents with variable signs and symptoms, frequently without detectable lumps or tumors; it therefore is often not detected bymammography orultrasound.[3] Typical presentation is rapid breast swelling, sometimes associated with skin changes (peau d'orange), and nipple retraction. Other signs include redness, persistent itching, and unusually warm skin. IBC often initially resemblesmastitis. Approximately 50% to 75% of cases have the typical presentation; an atypical presentation makes diagnosis more difficult. In some cases, a sign such as acute centralvenous thrombosis may be the sole presenting indication of the disease.
IBC comprises a small proportion of breast cancer cases (1% to 6% in the USA).[4] African-Americans are usually diagnosed with IBC at younger ages than Caucasian women, and they are also at higher risk for the disease.[5] Recent advances in therapy have improved the prognosis considerably; at least one-third of women will survive with IBC for ten years or longer.[6]
Signs and symptoms are quite variable, and may not be present at all in "occult" inflammatory breast cancer. Rapid onset of symptoms is typical; the breast often looks swollen and red, or "inflamed", sometimes seemingly changing overnight. IBC is frequently misdiagnosed asmastitis. Invasion of the locallymphatic ducts, the hallmark sign of IBC, impairslymphatic drainage and causesedematous swelling of the breast. Because the skin of the breast is tethered bythe suspensory ligament of Cooper, the accumulation of fluid within the lymphatic system of the skin may cause the breast skin to assume a dimpled appearance similar to an orange peel (peau d'orange). A palpable tumor is not always found as it would be in other forms of breast cancer.
Symptoms may include:
Other symptoms may rarely include:
Most patients do not experience every known symptom of IBC. Not all symptoms need to be present to make an IBC diagnosis.[7]
The reliable method of diagnosis by imaging,Mammography, breastMRI or ultrasound, which often show suspicious signs (general skin edema, skin thickening, mass, suspected breast lesions). It is important to biopsy the suspected lesions and/or skin. However, despite significant effort, a diagnosis could be missed. Therefore, repeat imaging and biopsies are important if a diagnosis of IBC is suspected.
Clinical presentation is typical in only 50% to 75% of cases; many other conditions, such asmastitis or evencardiac insufficiency, can mimic the typical symptoms of inflammatory breast cancer.
Temporary regression or fluctuation of symptoms, spontaneously or in response to medications or hormonal events should not be considered of any significance in diagnosis. Treatment with antibiotics or progesterone have been observed to cause a temporary regression of symptoms in certain cases.[8][9][10][11][12][excessive citations]
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Inflammatory breast cancer is a high-gradeaneuploid cancer, with mutations and overexpression ofp53,[13] high levels ofE-cadherin and abnormalcadherin function. It is often regarded as a systemiccancer. A large number of IBC cases present astriple negative breast cancer (TNBC). Similar to TNBC, as opposed tohormone receptor-positive breast cancer, there is a high rate of relapse and metastasis in the first three years after presentation, with few late events (five years or later).
IBC is characterised by the presence of cancer cells in the subdermal lymphatics on skin biopsy. Consequently, IBC is always staged atstage IIIB or above, as that type oflocallyadvanced disease is a classic prognostic indicator.
Searches forbiomolecular characteristics has produced a broad range of possible biomarkers, such as loss ofLIBC andWISP3expression.[citation needed] Inflammatory breast cancer is similar in many ways, both prognostically and treatment-wise, to late-stage ormetastatic breast cancer; it can be distinguished from those cancer types both bymolecular footprint and clinical presentation. On the molecular level, some similarity exists withpancreatic cancer.[citation needed]
Estrogen and progesterone receptor status is frequently negative, corresponding with poor survival. IBC tumors are highlyangiogenic andvascular, with high levels ofVEGF andbFGF expression.
A number of proteins and signalling pathways show behaviour of biochemicals which can be consideredparadoxical, compared with their function in normal tissue as well as in other breast cancer types.
RhoC GTPase is overexpressed, possibly related to overexpression (hypomethylation) of caveolin 1 and caveolin 2. Caveolin is, paradoxically, tumour-promoting in IBC.NF-κB pathway activation overexpression may contribute to the inflammatory phenotype.
Theepidermal growth factor receptor (EGFR) pathway is commonly active in inflammatory breast cancer; this has the clinical implication thatEGFR targeting therapy may be effective in inflammatory breast cancer.[15]
IBC occurs in all adult age groups. While the majority of patients are between 40 and 59 years old, age predilection is much less pronounced than in noninflammatory breast cancer. The overall rate is 1.3 cases per 100000; black women (1.6) have the highest rate, Asian and Pacific Islander women the lowest (0.7) rates.[4]
Most known breast cancer risk predictors do not apply for inflammatory breast cancer. It may be slightly negatively associated with cumulative breast-feeding duration.[16]
Whether inflammation contributes to the development of this disease remains an area of ongoing research.[17]
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Age distribution and relation to breastfeeding duration[citation needed] is suggestive of the involvement of hormones in the causation of IBC; however, significant differences exist between IBC and other breast cancers.
Typically, IBC shows low levels ofestrogen andprogesterone receptor sensitivity, which corresponds with poor outcome. In IBC cases with positive estrogen receptor status, antihormonal treatment is believed to improve outcome.
Paradoxically, some findings suggest[which?] that especially-aggressivephenotypes of IBC are characterised by a high level ofNF kappaB target gene expression, which can be, under laboratory conditions, successfully modulated by estrogen, but not bytamoxifen.[citation needed]
Staging is designed to help organize the different treatment plans and to understand theprognosis better. Staging for IBC has been adapted to meet the specific characteristics of the disease. IBC is typically diagnosed in one of these stages:
The standard treatment for newly diagnosed inflammatory breast cancer is to receive systemic therapy prior to surgery, followed by the radiation therapy. Achieving "no disease [pathological complete response (pCR)]" in the surgical samples gives the best prognosis. Surgery is modified radical mastectomy.Lumpectomy,segmentectomy, orskin sparing mastectomy are not recommended. Immediatereconstructive surgery is not recommended. Immediate,"upfront" surgery is contraindicated, as results are better usingneoadjuvant chemotherapy first. Contralateral prophylactic mastectomy is not recommended because it can delay the other systemic adjuvant treatment or adjuvant radiation therapy. After surgery, all cases are recommended for radiation therapy unless it is contraindicated.[19]
Due to the aggressive nature of the disease, it is highly recommended that people with IBC be seen by an IBC specialist and by amultidisciplinary team of health workers. Exploring whether clinical trials are available is very important.
In patients with newly diagnosed IBC with metastatic diseases, it is essential to discuss whether palliative surgery of the breast is indicated after the systemic treatment. In the non-IBC setting, palliative surgery is not recommended; however, for IBC, palliative surgery to improve the QOL and to improve the long-term outcome is explored in certain medical conditions.
It is critical for people with IBC to seek noveltargeted therapy in a clinical trial setting.[20] Three-modality combination therapy: surgery, chemotherapy, andradiation, was, in 2014, reported as being under-utilized in the USA.[21] Estrogen and progesterone receptor-positive cases of IBC have not been shown to have a better prognosis than hormone receptor-negative cases.[22]Pathologicalcomplete response to preoperative chemotherapy imparts a more favorable prognosis than a pathological complete response to surgery.[23] Loss ofdiploidy (heterozygosity) and extensive breast inflammation upon first clinical examination are associated with a significantly worse IBC prognosis.[24] A premenopausal occurrence of IBC has a significantly worse prognosis than a postmenopausal diagnosis.[citation needed] In postmenopausal cases, lean women have a significantly better prognosis than obese women.[citation needed] Among breast cancer patients with distant metastasis at diagnosis (stage IV disease), theoverall survival (OS) is worse in patients with IBC than in those with non-IBC breast cancers.[18]