Breast Cancer, Inflammatory

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Diagnosis and reasoning

This young lady has presented with pain, erythema, and swelling of her right breast, i.e. features suggestive of an inflammatory condition. Given that she is lactating, key possibilities include lactational mastitis, cellulitis of the breast, or a breast abscess. However, examination reveals several disconcerting findings: diffuse enlargement and erythema of the breast, thickening of the overlying skin, and a single non-tender lymph node in the ipsilateral axilla. Note that both lactational mastitis and breast abscesses usually involve only a single quadrant of the breast, although cellulitis may span several quadrants. In addition, while any infectious process can result in loco-regional lymphadenopathy, this is typically tender in nature. Furthermore, the above etiologies are frequently accompanied by fever, while a leukocytosis and elevated C-reactive protein (CRP) levels are usually seen; however this patient's complete blood count and CRP assay are completely normal. Last but not least, note that she has been through a full course of antibiotics; one would expect both lactational mastitis and cellulitis to demonstrate some degree of improvement, although a breast abscess is unlikely to resolve without drainage. Thus, none of these diagnoses properly fit the clinical findings and basic investigations; this forces us to consider a far more unpleasant possibility: Inflammatory Breast Cancer (IBC), an uncommon (but highly aggressive) malignancy which can mimic an inflamed breast. The short duration of symptoms, diffuse breast enlargement, and skin thickening seen here is typical of IBC, as is the presence of painless lymphadenopathy; in fact, these findings are sufficient to clinically diagnose the condition. However, histopathologic confirmation should be obtained later on. An urgent ultrasound scan of the breasts is a good next step; this further confirms the clinical findings, while also definitively excluding a breast abscess. She should be referred to an oncologist as soon as possible. Note that there is no point in administering intravenous (IV) antibiotics; nor is breastfeeding counseling required. Surgical drainage would have been indicated in the event of an abscess.


Inflammatory Breast Cancer (IBC) is an uncommon, highly aggressive form of breast cancer which mimics an inflamed breast; it is considered a special type of Locally Advanced Breast Cancer (LABC). While only 1% to 6% of cases of breast cancer diagnosed in the United States are due to IBC, the condition causes 8% to 10% of all breast cancer related deaths. Affected patients tend to be relatively young (e.g. pre- or perimenopausal), as compared to women with non-inflammatory breast cancer; the condition may occur during pregnancy and lactation. Note that the incidence of IBC appears to be higher in women of African-American and Asian Pacific Islander ethnicities. The American Joint Committee on Cancer (AJCC) defines IBC as a composite clinicopathologic entity characterized by diffuse edema (peau d'orange) and erythema over the majority (one third or more) of the breast, often without an underlying mass. The term 'inflammatory' is in fact a misnomer; while the disease does visually mimic an acute inflammatory breast by demonstrating erythema, warmth, edema, and induration, microscopy reveals cancer cells rather than an inflammatory infiltrate. The above phenomena are a result of pathologic plugging of the dermal lymphovascular spaces by tumor emboli; this is termed "dermal lymphatic invasion", and is a histological hallmark of IBC. Note also that while the genetic basis of the condition is still poorly understood, there appear to be several key differences which differentiate it from non-inflammatory LABC. In particular, more than half of these patients exhibit estrogen receptor (ER) negative tumors, while approximately 33% manifest triple-negative tumors. Known risk factors for IBC include a family history of breast cancer, and an elevated body mass index (BMI). Note also that according to the Tumor-Node-Metastases (TNM) classification system, IBC is classified as a T4d tumor (.e.g Stage IIIb). Changes in the skin overlying the affected breast are the first sign of IBC; these can range from any degree of erythema, to an angry red or purple discoloration. As the condition advances, a peau d'orange appearance may be seen in the dependent part of breast, and later, over the entire organ. Patients may also complain of a sensation of heaviness, or 'aching' or 'burning' sensations in the affected breast; flattening, retraction, crusting or blistering of the nipple may also be seen. It should also be appreciated that up to 30% of patients with IBC may not have a palpable breast mass. Unfortunately, it is extremely easy to mistake the above changes as being due to an inflammatory etiology, resulting in delayed diagnosis. However, IBC typically involves more than a third of the breast; as a rule of thumb, most inflammatory etiologies usually involve only a segment, or specific region. In addition, the absence of systemic inflammatory features such as fever, leukocytosis, or elevated acute phase reactants (C-Reactive Protein and ESR) may provide a further clue. In certain patients, it may also be necessary to differentiate between IBC and a neglected non-inflammatory LABC presenting at a late stage. A history of rapid enlargement of the affected breast, along with the absence of an underlying mass is a strong hint towards the former diagnosis; in addition, non-inflammatory breast cancers are usually painless. Note that the International Expert Panel on Inflammatory Breast Cancer has formulated criteria for the diagnosis of IBC; these state that that IBC is a clinical diagnosis, although subsequent pathological confirmation is essential. A core needle biopsy of the breast is the preferred histopathological study, with the aim of confirming the presence of an invasive carcinoma; this will also aid in determination of hormone receptor status, and HER2 positivity. Skin punch biopsies may also be obtained, so as to demonstrate dermal lymphatic invasion; while this is pathognomonic of the condition, it can only be detected in 50% to 75% of patients. At present, imaging studies are not part of the diagnostic criteria; this is due to the lack of data on which radiological signs are most specific for IBC. That said, all patients with suspected IBC should nonetheless undergo mammography and/or an ultrasound of the breasts and regional lymph nodes. Mammography may reveal skin thickening, trabecular and stromal thickening and markedly increased breast density. However, the diagnostic yield is often poor in younger women, due to the dense breast tissue, while breast tenderness may make the procedure technically difficult. Ultrasonography may demonstrate skin thickening, and axillary lymphadenopathy; in ~95% of affected breasts, parenchymal architectural distortions can be detected. Last but not least, it is essential to perform a metastatic workup in all patients diagnosed with the disease. The treatment of IBC will vary depending on the staging of the patient and the treatment protocols of the units involved; however, there is a general consensus that the risk of loco-regional and distant recurrence is too high to justify immediate mastectomy. Thus, trimodal therapy is usually employed, e.g. initial neoadjuvant chemotherapy followed by a mastectomy with axillary clearance, and subsequent radiotherapy to the chest wall and regional lymph nodes. Some women may also receive further hormonal modulation. After the course of treatment is complete, the American Society of Clinical Oncology (ASCO) recommends a brief physical examination every 3 to 6 months, as well as an yearly mammogram of the contralateral breast. As mentioned earlier, IBC is highly aggressive; at the time of diagnosis, a significant number of patients will have local and/or distant metastases, and despite multimodal therapy, survival is poor. Overall, modern treatment techniques have resulted in a 5-year survival rate of 40%, and 10 year survival rate of 33%.

Take home messages

  1. In an inflamed breast, once infection is excluded, IBC should always be kept in mind.
  2. Features suggestive of IBC include the absence of fever, rapidly progressive symptoms, generalized involvement of the breast and palpable non-tender axillary lymphadenopathy.
  3. While IBC is a clinical diagnosis, histopathological confirmation is essential, and can be performed via a core biopsy, or a skin punch biopsy.
  4. Most units employ trimodal cancer therapy in the management of these patients.

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  1. ANDERSON W. F.. Inflammatory Breast Carcinoma and Noninflammatory Locally Advanced Breast Carcinoma: Distinct Clinicopathologic Entities?. Journal of Clinical Oncology [online] 2003 May, 21(12):2254-2259 [viewed 03 May 2015] Available from: doi:10.1200/JCO.2003.07.082
  2. ANDERSON WF, SCHAIRER C, CHEN BE, HANCE KW, LEVINE PH. Epidemiology of inflammatory breast cancer (IBC). Breast Dis [online] 2005-2006:9-23 [viewed 02 May 2015] Available from:
  3. BONEV V, EVANGELISTA M, CHEN JH, SU MY, LANE K, MEHTA R, BUTLER J, HSIANG D. Long-term follow-up of breast-conserving therapy in patients with inflammatory breast cancer treated with neoadjuvant chemotherapy. Am Surg [online] 2014 Oct, 80(10):940-3 [viewed 02 May 2015] Available from:
  4. CHIA S., SWAIN S. M., BYRD D. R., MANKOFF D. A.. Locally Advanced and Inflammatory Breast Cancer. Journal of Clinical Oncology [online] 2008 February, 26(5):786-790 [viewed 04 May 2015] Available from: doi:10.1200/JCO.2008.15.0243
  5. CRISTOFANILLI M, BUZDAR AU, HORTOBáGYI GN. Update on the management of inflammatory breast cancer. Oncologist [online] 2003, 8(2):141-8 [viewed 01 May 2015] Available from:
  6. DAWOOD S., MERAJVER S. D., VIENS P., VERMEULEN P. B., SWAIN S. M., BUCHHOLZ T. A., DIRIX L. Y., LEVINE P. H., LUCCI A., KRISHNAMURTHY S., ROBERTSON F. M., WOODWARD W. A., YANG W. T., UENO N. T., CRISTOFANILLI M.. International expert panel on inflammatory breast cancer: consensus statement for standardized diagnosis and treatment. Annals of Oncology [online] December, 22(3):515-523 [viewed 03 May 2015] Available from: doi:10.1093/annonc/mdq345
  7. GONZALEZ-ANGULO AM, HENNESSY BT, BROGLIO K, MERIC-BERNSTAM F, CRISTOFANILLI M, GIORDANO SH, BUCHHOLZ TA, SAHIN A, SINGLETARY SE, BUZDAR AU, HORTOBáGYI GN. Trends for inflammatory breast cancer: is survival improving? Oncologist [online] 2007 Aug, 12(8):904-12 [viewed 04 May 2015] Available from: doi:10.1634/theoncologist.12-8-904
  8. GüNHAN-BILGEN I, USTüN EE, MEMIş A. Inflammatory breast carcinoma: mammographic, ultrasonographic, clinical, and pathologic findings in 142 cases. Radiology [online] 2002 Jun, 223(3):829-38 [viewed 04 May 2015] Available from: doi:10.1148/radiol.2233010198
  9. MOLCKOVSKY A, FITZGERALD B, FREEDMAN O, HEISEY R, CLEMONS M. Approach to inflammatory breast cancer Can Fam Physician [online] 2009/01/01 00:00, 55(1):25-31 [viewed 04 May 2015] Available from:
  10. ROBERTSON FREDIKA M., BONDY MELISSA, YANG WEI, YAMAUCHI HIDEKO, WIGGINS SHANNON, KAMRUDIN SAMIRA, KRISHNAMURTHY SAVITRI, LE-PETROSS HUONG, BIDAUT LUC, PLAYER AUDREY N., BARSKY SANFORD H., WOODWARD WENDY A., BUCHHOLZ THOMAS, LUCCI ANTHONY, UENO NAOTO, CRISTOFANILLI MASSIMO. Inflammatory Breast Cancer: The Disease, the Biology, the Treatment. CA: A Cancer Journal for Clinicians [online] December, 60(6):351-375 [viewed 04 May 2015] Available from: doi:10.3322/caac.20082
  12. WALSHE JM, SWAIN SM. Clinical aspects of inflammatory breast cancer. Breast Dis [online] 2005-2006:35-44 [viewed 03 May 2015] Available from:
  13. WANG LIJUN, WANG DENGBIN, FEI XIAOCHUN, RUAN MEI, CHAI WEIMIN, XU LIN, LI XIAOXIAO, HOFFMANN ANDREAS-CLAUDIUS. A Rim-Enhanced Mass with Central Cystic Changes on MR Imaging: How to Distinguish Breast Cancer from Inflammatory Breast Diseases?. PLoS ONE [online] 2014 March [viewed 03 May 2015] Available from: doi:10.1371/journal.pone.0090355