Inflammatory breast cancer

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Inflammatory breast cancer
Specialty Oncology

Inflammatory breast cancer [1] (IBC) is one of the most aggressive types of breast cancer. It can occur in women of any age (and, extremely rarely, in men, see male breast cancer [2] ). It is referred to as "inflammatory" due to its frequent presentation with symptoms resembling a skin inflammation, such as erysipelas.

Contents

Inflammatory breast cancer presents with variable signs and symptoms, frequently without detectable lumps or tumors; it therefore is often not detected by mammography or ultrasound. [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 resembles mastitis. 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 central venous 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]

Symptoms

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 as mastitis. Invasion of the local lymphatic ducts, the hallmark sign of IBC, impairs lymphatic drainage and causes edematous swelling of the breast. Because the skin of the breast is tethered by the 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]

Diagnosis

The reliable method of diagnosis by imaging, Mammography, breast MRI 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 as mastitis or even cardiac 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 ]

Characterization

Inflammatory breast cancer is a high-grade aneuploid cancer, with mutations and overexpression of p53, [13] high levels of E-cadherin and abnormal cadherin function. It is often regarded as a systemic cancer. A large number of IBC cases present as triple negative breast cancer (TNBC). Similar to TNBC, as opposed to hormone 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 at stage IIIB or above, as that type of locally advanced disease is a classic prognostic indicator.

Searches for biomolecular characteristics has produced a broad range of possible biomarkers, such as loss of LIBC and WISP3 expression.[ citation needed ] Inflammatory breast cancer is similar in many ways, both prognostically and treatment-wise, to late-stage or metastatic breast cancer; it can be distinguished from those cancer types both by molecular footprint and clinical presentation. On the molecular level, some similarity exists with pancreatic cancer.[ citation needed ]

Estrogen and progesterone receptor status is frequently negative, corresponding with poor survival. IBC tumors are highly angiogenic and vascular, with high levels of VEGF and bFGF expression.

A number of proteins and signalling pathways show behaviour of biochemicals which can be considered paradoxical, 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.

The epidermal growth factor receptor (EGFR) pathway is commonly active in inflammatory breast cancer; this has the clinical implication that EGFR targeting therapy may be effective in inflammatory breast cancer. [15]

Epidemiology

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]

Role of hormones

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 of estrogen and progesterone 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 that especially-aggressive phenotypes of IBC are characterised by a high level of NF kappaB target gene expression, which can be, under laboratory conditions, successfully modulated by estrogen, but not by tamoxifen.[ citation needed ]

Staging

Staging is designed to help organize the different treatment plans and to understand the prognosis better. Staging for IBC has been adapted to meet the specific characteristics of the disease. IBC is typically diagnosed in one of these stages:

Treatment

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, or skin sparing mastectomy are not recommended. Immediate reconstructive surgery is not recommended. Immediate,"upfront" surgery is contraindicated, as results are better using neoadjuvant 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 a multidisciplinary 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 novel targeted therapy in a clinical trial setting. [20] Three-modality combination therapy: surgery, chemotherapy, and radiation, 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] Pathological complete response to preoperative chemotherapy imparts a more favorable prognosis than a pathological complete response to surgery. [23] Loss of diploidy (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), the overall survival (OS) is worse in patients with IBC than in those with non-IBC breast cancers. [18]

See also

Related Research Articles

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<span class="mw-page-title-main">Mastitis</span> Medical condition

Mastitis is inflammation of the breast or udder, usually associated with breastfeeding. Symptoms typically include local pain and redness. There is often an associated fever and general soreness. Onset is typically fairly rapid and usually occurs within the first few months of delivery. Complications can include abscess formation.

<span class="mw-page-title-main">Uterine cancer</span> Medical condition

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<span class="mw-page-title-main">Endometrial cancer</span> Uterine cancer that is located in tissues lining the uterus

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<span class="mw-page-title-main">Ovarian cancer</span> Cancer originating in or on the ovary

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<span class="mw-page-title-main">Male breast cancer</span> Medical condition

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References

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  7. ↑ "Inflammatory Breast Cancer Help—Signs and Symptoms". Inflammatory Breast Cancer Association. 2 April 2009. Archived from the original on 6 March 2014.
  8. ↑ Kusama M, Koyanagi Y, Sekine M, Serizawa H, Ebihara Y, Hirota T, et al. (September 1994). "[A case of inflammatory breast cancer successfully treated with 5'-DFUR and MPA]". Gan to Kagaku Ryoho. Cancer & Chemotherapy. 21 (12): 2049–2052. PMID   8085857.
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  10. ↑ Van Laere SJ, Van der Auwera I, Van den Eynden GG, Elst HJ, Weyler J, Harris AL, et al. (June 2006). "Nuclear factor-kappaB signature of inflammatory breast cancer by cDNA microarray validated by quantitative real-time reverse transcription-PCR, immunohistochemistry, and nuclear factor-kappaB DNA-binding". Clinical Cancer Research. 12 (11 Pt 1): 3249–3256. doi: 10.1158/1078-0432.CCR-05-2800 . PMID   16740744.
  11. ↑ Van Laere SJ, Van der Auwera I, Van den Eynden GG, van Dam P, Van Marck EA, Vermeulen PB, Dirix LY (September 2007). "NF-kappaB activation in inflammatory breast cancer is associated with oestrogen receptor downregulation, secondary to EGFR and/or ErbB2 overexpression and MAPK hyperactivation". British Journal of Cancer. 97 (5): 659–669. doi:10.1038/sj.bjc.6603906. PMC   2360371 . PMID   17700572.
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  13. ↑ Giordano SH, Hortobagyi GN (2003). "Inflammatory breast cancer: clinical progress and the main problems that must be addressed". Breast Cancer Research. 5 (6): 284–288. doi: 10.1186/bcr608 . PMC   314400 . PMID   14580242.
  14. ↑ Van den Eynden GG, Van Laere SJ, Van der Auwera I, Merajver SD, Van Marck EA, van Dam P, et al. (February 2006). "Overexpression of caveolin-1 and -2 in cell lines and in human samples of inflammatory breast cancer". Breast Cancer Research and Treatment. 95 (3): 219–228. doi:10.1007/s10549-005-9002-1. hdl: 2027.42/44235 . PMID   16244790. S2CID   850041.
  15. ↑ Zhang D, LaFortune TA, Krishnamurthy S, Esteva FJ, Cristofanilli M, Liu P, et al. (November 2009). "Epidermal growth factor receptor tyrosine kinase inhibitor reverses mesenchymal to epithelial phenotype and inhibits metastasis in inflammatory breast cancer". Clinical Cancer Research. 15 (21): 6639–6648. doi:10.1158/1078-0432.CCR-09-0951. PMC   2783487 . PMID   19825949.
  16. ↑ Lê MG, Arriagada R, Bahi J, Pfeiffer F, Cammoun M, Tabbane F, Rubino C (June 2006). "Are risk factors for breast cancer similar in women with inflammatory breast cancer and in those with non-inflammatory breast cancer?". Breast. 15 (3): 355–362. doi:10.1016/j.breast.2005.08.018. PMID   16198566.
  17. ↑ Fouad TM, Kogawa T, Reuben JM, Ueno T (2014). "The Role of Inflammation in Inflammatory Breast Cancer". Inflammation and Cancer. Advances in Experimental Medicine and Biology. Vol. 816. pp. 53–73. doi:10.1007/978-3-0348-0837-8_3. ISBN   978-3-0348-0836-1. PMID   24818719.
  18. 1 2 Fouad TM, Kogawa T, Liu DD, Shen Y, Masuda H, El-Zein R, et al. (July 2015). "Overall survival differences between patients with inflammatory and noninflammatory breast cancer presenting with distant metastasis at diagnosis". Breast Cancer Research and Treatment. 152 (2): 407–416. doi:10.1007/s10549-015-3436-x. PMC   4492876 . PMID   26017070.
  19. ↑ Yamauchi H, Woodward WA, Valero V, Alvarez RH, Lucci A, Buchholz TA, et al. (2012). "Inflammatory breast cancer: what we know and what we need to learn". The Oncologist. 17 (7): 891–899. doi:10.1634/theoncologist.2012-0039. PMC   3399643 . PMID   22584436.
  20. ↑ Yamauchi H, Ueno NT (June 2010). "Targeted therapy in inflammatory breast cancer". Cancer. 116 (11 Suppl): 2758–2759. doi: 10.1002/cncr.25171 . PMID   20503407.
  21. ↑ Rueth NM, Lin HY, Bedrosian I, Shaitelman SF, Ueno NT, Shen Y, Babiera G (July 2014). "Underuse of trimodality treatment affects survival for patients with inflammatory breast cancer: an analysis of treatment and survival trends from the National Cancer Database". Journal of Clinical Oncology. 32 (19): 2018–2024. doi:10.1200/JCO.2014.55.1978. PMC   4067942 . PMID   24888808.
  22. ↑ Masuda H, Brewer TM, Liu DD, Iwamoto T, Shen Y, Hsu L, et al. (February 2014). "Long-term treatment efficacy in primary inflammatory breast cancer by hormonal receptor- and HER2-defined subtypes". Annals of Oncology. 25 (2): 384–391. doi:10.1093/annonc/mdt525. PMC   3905780 . PMID   24351399.
  23. ↑ Palangie T, Mosseri V, Mihura J, Campana F, Beuzeboc P, Dorval T, et al. (1994). "Prognostic factors in inflammatory breast cancer and therapeutic implications". European Journal of Cancer. 30A (7): 921–927. doi:10.1016/0959-8049(94)90115-5. PMID   7946584.
  24. ↑ Lerebours F, Bertheau P, Bieche I, Plassa LF, Champeme MH, Hacene K, et al. (September 2003). "Two prognostic groups of inflammatory breast cancer have distinct genotypes". Clinical Cancer Research. 9 (11): 4184–4189. PMID   14519644.
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