Inflammatory breast cancer
Encyclopedia
Inflammatory breast cancer is an especially aggressive type of breast cancer
that can occur in women of any age (and
extremely rarely, in men).
It is called inflammatory because it frequently presents with symptoms resembling an inflammation. However it can present with very variable signs and symptoms, frequently without detectable tumors and therefore is often not detected by mammography
or ultrasound
.
Typical presentation is rapid swelling, sometimes associated by skin changes (peau d' orange), and nipple retraction. Other symptoms include rapid increase in breast size, redness, persistent itching, skin hot to touch. IBC often initially resembles mastitis
.
Only about 50-75% cases have the typical presentation. Symptoms can be completely atypical such as acute central venous thrombosis as the sole presenting symptom.
IBC makes up only a small percentage of breast cancer cases (1-6% in the USA). IBC is often diagnosed in younger women although average age of presentation does not differ much from other kinds of breast cancer (average age 57 years). African-Americans are usually diagnosed at younger ages than Caucasian women, and also have a higher risk of getting IBC. Recent advances in therapy have improved the prognosis considerably and at least one third of women will survive the diagnosis by 10 years or longer.
tous swelling of the breast. Because the skin of the breast is tethered by the suspensory ligament of Cooper, the accumulation of fluid may cause the skin of the breast to assume a dimpled appearance similar to an orange peel (peau d'orange
). IBC is sometimes misdiagnosed as an insect bite or breast infection.
In the case of IBC, a lump is usually not present as in other forms of breast cancer.
Symptoms may include:
Other symptoms may rarely include:
Most patients do not experience all the symptoms of IBC. Not all symptoms need to be present in order to be diagnosed.
. Mammography
, MRI or ultrasound often show suspicious signs; however in a significant proportion of cases they would miss a diagnosis.
Clinical presentation is typical only in 50-75% of cases; and many other conditions such as mastitis
or even heart insufficiency can mimic the typical symptoms of Inflammatory Breast Cancer.
Temporary regression or fluctuation of symptoms, spontaneous or in response to conventional treatment or hormonal events should not be considered of any significance in diagnosis. Inflammatory breast cancer is known to respond to antibiotics and progesterone, and reaction to other medications or hormones cannot be excluded.
.
It is characterised by the presence of cancer cells in the subdermal lymphatics on skin biopsy.
Search for biomolecular characteristics produced a broad number of possible markers, such as loss of LIBC and WISP3 expression. Inflammatory breast cancer is in many ways very similar to late stage or metastatic breast cancer however it can be distinguished from those cancer types both by molecular footprint and clinical presentation. On molecular level some similarity exists with pancreatic cancer.
Estrogen and Progesterone receptor status is frequently negative, corresponding with poor survival. The tumors are highly angiogenic and vascular, with high levels of VEGF and bFGF expression.
A number of proteins and signalling pathways show behaviour that can be considered paradoxical compared to their function in normal tissue and other breast cancer types.
RhoC GTPase is overexpressed, possibly related with overexpression (hypomethylation) of Caveolin-1,-2. Caevolin is paradoxically tumour promoting. NF-kappaB pathway activation overexpression may contribute to the inflammatory phenotype.
Most known breast cancer risk predictors do not apply for inflammatory breast cancer. It maybe be slightly associated with cumulative breast-feeding duration. While there may be a slight risk correlation with breast feeding duration it must be considered that the resulting effect would be by far outweighed by the protective effect breastfeeding has against more frequent breast cancer types.
Typically IBC shows low levels of estrogen and progesterone receptor sensitivity corresponding with poor outcome. In 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 high level of NF kappaB target gene expression which can be - under laboratory conditions successfully modulated by estrogen but not tamoxifen.
better. Staging for IBC has been adapted to meet the specific characteristics of the disease. IBC is typically diagnosed in one of these stages:
with a combination of several agents, radiation therapy, hormonal therapy where appropriate and in some cases surgery.
Estrogen antagonist or aromatase inhibitors appear to improve outcome for ER positive cancer, similar for Herceptin.
Surgery was only rarely performed because inflammatory breast cancer is considered essentially a systemic cancer, however it may improve outcome and is now being reconsidered. A lumpectomy
, when only a portion of the breast is removed, is not an option for IBC patients. A lymph node dissection
is also recommended over a sentinel lymph node
biopsy. Lymphedema
, swelling of the arm and the hand on the side of the body where surgery was performed, may be a complication after a lymph node dissection. Reconstruction of the breast may be an option for healthy women after a mastectomy. However, for patients who smoke or have diabetes, complications are more common.
A number of promising new therapeutic agents exists, such as
Premenopausal cases have significantly worse prognosis. In postmenopausal cases lean women have significantly better prognosis than obese women.
that can occur in women of any age (and
extremely rarely, in men).
It is called inflammatory because it frequently presents with symptoms resembling an inflammation. However it can present with very variable signs and symptoms, frequently without detectable tumors and therefore is often not detected by mammography
or ultrasound
.
Typical presentation is rapid swelling, sometimes associated by skin changes (peau d' orange), and nipple retraction. Other symptoms include rapid increase in breast size, redness, persistent itching, skin hot to touch. IBC often initially resembles mastitis
.
Only about 50-75% cases have the typical presentation. Symptoms can be completely atypical such as acute central venous thrombosis as the sole presenting symptom.
IBC makes up only a small percentage of breast cancer cases (1-6% in the USA). IBC is often diagnosed in younger women although average age of presentation does not differ much from other kinds of breast cancer (average age 57 years). African-Americans are usually diagnosed at younger ages than Caucasian women, and also have a higher risk of getting IBC. Recent advances in therapy have improved the prognosis considerably and at least one third of women will survive the diagnosis by 10 years or longer.
tous swelling of the breast. Because the skin of the breast is tethered by the suspensory ligament of Cooper, the accumulation of fluid may cause the skin of the breast to assume a dimpled appearance similar to an orange peel (peau d'orange
). IBC is sometimes misdiagnosed as an insect bite or breast infection.
In the case of IBC, a lump is usually not present as in other forms of breast cancer.
Symptoms may include:
Other symptoms may rarely include:
Most patients do not experience all the symptoms of IBC. Not all symptoms need to be present in order to be diagnosed.
. Mammography
, MRI or ultrasound often show suspicious signs; however in a significant proportion of cases they would miss a diagnosis.
Clinical presentation is typical only in 50-75% of cases; and many other conditions such as mastitis
or even heart insufficiency can mimic the typical symptoms of Inflammatory Breast Cancer.
Temporary regression or fluctuation of symptoms, spontaneous or in response to conventional treatment or hormonal events should not be considered of any significance in diagnosis. Inflammatory breast cancer is known to respond to antibiotics and progesterone, and reaction to other medications or hormones cannot be excluded.
.
It is characterised by the presence of cancer cells in the subdermal lymphatics on skin biopsy.
Search for biomolecular characteristics produced a broad number of possible markers, such as loss of LIBC and WISP3 expression. Inflammatory breast cancer is in many ways very similar to late stage or metastatic breast cancer however it can be distinguished from those cancer types both by molecular footprint and clinical presentation. On molecular level some similarity exists with pancreatic cancer.
Estrogen and Progesterone receptor status is frequently negative, corresponding with poor survival. The tumors are highly angiogenic and vascular, with high levels of VEGF and bFGF expression.
A number of proteins and signalling pathways show behaviour that can be considered paradoxical compared to their function in normal tissue and other breast cancer types.
RhoC GTPase is overexpressed, possibly related with overexpression (hypomethylation) of Caveolin-1,-2. Caevolin is paradoxically tumour promoting. NF-kappaB pathway activation overexpression may contribute to the inflammatory phenotype.
Most known breast cancer risk predictors do not apply for inflammatory breast cancer. It maybe be slightly associated with cumulative breast-feeding duration. While there may be a slight risk correlation with breast feeding duration it must be considered that the resulting effect would be by far outweighed by the protective effect breastfeeding has against more frequent breast cancer types.
Typically IBC shows low levels of estrogen and progesterone receptor sensitivity corresponding with poor outcome. In 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 high level of NF kappaB target gene expression which can be - under laboratory conditions successfully modulated by estrogen but not tamoxifen.
better. Staging for IBC has been adapted to meet the specific characteristics of the disease. IBC is typically diagnosed in one of these stages:
with a combination of several agents, radiation therapy, hormonal therapy where appropriate and in some cases surgery.
Estrogen antagonist or aromatase inhibitors appear to improve outcome for ER positive cancer, similar for Herceptin.
Surgery was only rarely performed because inflammatory breast cancer is considered essentially a systemic cancer, however it may improve outcome and is now being reconsidered. A lumpectomy
, when only a portion of the breast is removed, is not an option for IBC patients. A lymph node dissection
is also recommended over a sentinel lymph node
biopsy. Lymphedema
, swelling of the arm and the hand on the side of the body where surgery was performed, may be a complication after a lymph node dissection. Reconstruction of the breast may be an option for healthy women after a mastectomy. However, for patients who smoke or have diabetes, complications are more common.
A number of promising new therapeutic agents exists, such as
Premenopausal cases have significantly worse prognosis. In postmenopausal cases lean women have significantly better prognosis than obese women.
that can occur in women of any age (and
extremely rarely, in men).
It is called inflammatory because it frequently presents with symptoms resembling an inflammation. However it can present with very variable signs and symptoms, frequently without detectable tumors and therefore is often not detected by mammography
or ultrasound
.
Typical presentation is rapid swelling, sometimes associated by skin changes (peau d' orange), and nipple retraction. Other symptoms include rapid increase in breast size, redness, persistent itching, skin hot to touch. IBC often initially resembles mastitis
.
Only about 50-75% cases have the typical presentation. Symptoms can be completely atypical such as acute central venous thrombosis as the sole presenting symptom.
IBC makes up only a small percentage of breast cancer cases (1-6% in the USA). IBC is often diagnosed in younger women although average age of presentation does not differ much from other kinds of breast cancer (average age 57 years). African-Americans are usually diagnosed at younger ages than Caucasian women, and also have a higher risk of getting IBC. Recent advances in therapy have improved the prognosis considerably and at least one third of women will survive the diagnosis by 10 years or longer.
tous swelling of the breast. Because the skin of the breast is tethered by the suspensory ligament of Cooper, the accumulation of fluid may cause the skin of the breast to assume a dimpled appearance similar to an orange peel (peau d'orange
). IBC is sometimes misdiagnosed as an insect bite or breast infection.
In the case of IBC, a lump is usually not present as in other forms of breast cancer.
Symptoms may include:
Other symptoms may rarely include:
Most patients do not experience all the symptoms of IBC. Not all symptoms need to be present in order to be diagnosed.
. Mammography
, MRI or ultrasound often show suspicious signs; however in a significant proportion of cases they would miss a diagnosis.
Clinical presentation is typical only in 50-75% of cases; and many other conditions such as mastitis
or even heart insufficiency can mimic the typical symptoms of Inflammatory Breast Cancer.
Temporary regression or fluctuation of symptoms, spontaneous or in response to conventional treatment or hormonal events should not be considered of any significance in diagnosis. Inflammatory breast cancer is known to respond to antibiotics and progesterone, and reaction to other medications or hormones cannot be excluded.
.
It is characterised by the presence of cancer cells in the subdermal lymphatics on skin biopsy.
Search for biomolecular characteristics produced a broad number of possible markers, such as loss of LIBC and WISP3 expression. Inflammatory breast cancer is in many ways very similar to late stage or metastatic breast cancer however it can be distinguished from those cancer types both by molecular footprint and clinical presentation. On molecular level some similarity exists with pancreatic cancer.
Estrogen and Progesterone receptor status is frequently negative, corresponding with poor survival. The tumors are highly angiogenic and vascular, with high levels of VEGF and bFGF expression.
A number of proteins and signalling pathways show behaviour that can be considered paradoxical compared to their function in normal tissue and other breast cancer types.
RhoC GTPase is overexpressed, possibly related with overexpression (hypomethylation) of Caveolin-1,-2. Caevolin is paradoxically tumour promoting. NF-kappaB pathway activation overexpression may contribute to the inflammatory phenotype.
Most known breast cancer risk predictors do not apply for inflammatory breast cancer. It maybe be slightly associated with cumulative breast-feeding duration. While there may be a slight risk correlation with breast feeding duration it must be considered that the resulting effect would be by far outweighed by the protective effect breastfeeding has against more frequent breast cancer types.
Typically IBC shows low levels of estrogen and progesterone receptor sensitivity corresponding with poor outcome. In 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 high level of NF kappaB target gene expression which can be - under laboratory conditions successfully modulated by estrogen but not tamoxifen.
better. Staging for IBC has been adapted to meet the specific characteristics of the disease. IBC is typically diagnosed in one of these stages:
with a combination of several agents, radiation therapy, hormonal therapy where appropriate and in some cases surgery.
Estrogen antagonist or aromatase inhibitors appear to improve outcome for ER positive cancer, similar for Herceptin.
Surgery was only rarely performed because inflammatory breast cancer is considered essentially a systemic cancer, however it may improve outcome and is now being reconsidered. A lumpectomy
, when only a portion of the breast is removed, is not an option for IBC patients. A lymph node dissection
is also recommended over a sentinel lymph node
biopsy. Lymphedema
, swelling of the arm and the hand on the side of the body where surgery was performed, may be a complication after a lymph node dissection. Reconstruction of the breast may be an option for healthy women after a mastectomy. However, for patients who smoke or have diabetes, complications are more common.
A number of promising new therapeutic agents exists, such as
Premenopausal cases have significantly worse prognosis. In postmenopausal cases lean women have significantly better prognosis than obese women.
Breast cancer
Breast cancer is cancer originating from breast tissue, most commonly from the inner lining of milk ducts or the lobules that supply the ducts with milk. Cancers originating from ducts are known as ductal carcinomas; those originating from lobules are known as lobular carcinomas...
that can occur in women of any age (and
extremely rarely, in men).
It is called inflammatory because it frequently presents with symptoms resembling an inflammation. However it can present with very variable signs and symptoms, frequently without detectable tumors and therefore is often not detected by mammography
Mammography
Mammography is the process of using low-energy-X-rays to examine the human breast and is used as a diagnostic and a screening tool....
or ultrasound
Ultrasound
Ultrasound is cyclic sound pressure with a frequency greater than the upper limit of human hearing. Ultrasound is thus not separated from "normal" sound based on differences in physical properties, only the fact that humans cannot hear it. Although this limit varies from person to person, it is...
.
Typical presentation is rapid swelling, sometimes associated by skin changes (peau d' orange), and nipple retraction. Other symptoms include rapid increase in breast size, redness, persistent itching, skin hot to touch. IBC often initially resembles mastitis
Mastitis
Mastitis is the inflammation of breast tissue. S. aureus is the most common etiological organism responsible, but S. epidermidis and streptococci are occasionally isolated as well.-Terminology:...
.
Only about 50-75% cases have the typical presentation. Symptoms can be completely atypical such as acute central venous thrombosis as the sole presenting symptom.
IBC makes up only a small percentage of breast cancer cases (1-6% in the USA). IBC is often diagnosed in younger women although average age of presentation does not differ much from other kinds of breast cancer (average age 57 years). African-Americans are usually diagnosed at younger ages than Caucasian women, and also have a higher risk of getting IBC. Recent advances in therapy have improved the prognosis considerably and at least one third of women will survive the diagnosis by 10 years or longer.
Symptoms
Symptoms are very variable and may not be present at all in occult inflammatory breast cancer. Quick onset of symptoms is typical, the breast often looks swollen and red, or “inflamed”, sometimes overnight, and are easy to misdiagnose as mastitis. Invasion of the local lymphatic ducts impairs drainage and causes edemaEdema
Edema or oedema ; both words from the Greek , oídēma "swelling"), formerly known as dropsy or hydropsy, is an abnormal accumulation of fluid beneath the skin or in one or more cavities of the body that produces swelling...
tous swelling of the breast. Because the skin of the breast is tethered by the suspensory ligament of Cooper, the accumulation of fluid may cause the skin of the breast to assume a dimpled appearance similar to an orange peel (peau d'orange
Peau d'orange
The French term peau d'orange means "orange peel skin", or more literally, "skin of an orange". It is used in medicine to describe anatomy with the appearance and dimpled texture of an orange peel...
). IBC is sometimes misdiagnosed as an insect bite or breast infection.
In the case of IBC, a lump is usually not present as in other forms of breast cancer.
Symptoms may include:
- Pain in the breast
- Skin changes on breast
- Reddened area with texture resembling the peel of an orange (peau d’orange)
- Sudden swelling of the breast
- Itching of breast
- Nipple retraction (flattened look) or discharge
- Swelling of lymph nodes under the arm or in the neck
- Unusual warmth of the affected breast
- Breast is harder or firmer
Other symptoms may rarely include:
- Swelling of the arm
- Breast decreases instead of increasing
- Although a dominant mass is present in many cases, most inflammatory cancers present as diffuse infiltration of the breast without a well-defined tumor.
- A lump may become present and grow rapidly
Most patients do not experience all the symptoms of IBC. Not all symptoms need to be present in order to be diagnosed.
Diagnosis
The only reliable method of diagnosis is biopsyBiopsy
A biopsy is a medical test involving sampling of cells or tissues for examination. It is the medical removal of tissue from a living subject to determine the presence or extent of a disease. The tissue is generally examined under a microscope by a pathologist, and can also be analyzed chemically...
. Mammography
Mammography
Mammography is the process of using low-energy-X-rays to examine the human breast and is used as a diagnostic and a screening tool....
, MRI or ultrasound often show suspicious signs; however in a significant proportion of cases they would miss a diagnosis.
Clinical presentation is typical only in 50-75% of cases; and many other conditions such as mastitis
Mastitis
Mastitis is the inflammation of breast tissue. S. aureus is the most common etiological organism responsible, but S. epidermidis and streptococci are occasionally isolated as well.-Terminology:...
or even heart insufficiency can mimic the typical symptoms of Inflammatory Breast Cancer.
Temporary regression or fluctuation of symptoms, spontaneous or in response to conventional treatment or hormonal events should not be considered of any significance in diagnosis. Inflammatory breast cancer is known to respond to antibiotics and progesterone, and reaction to other medications or hormones cannot be excluded.
Characterization
Inflammatory breast cancer is high grade aneuploid cancer, with mutations and overexpression of p53, high levels of E-cadherin and abnormal cadherin function. It is often regarded as a systemic cancer. Large part of IBC cases present as triple negative breast cancerTriple Negative Breast Cancer
Triple-negative breast cancer refers to any breast cancer that does not express the genes for estrogen receptor , progesterone receptor or Her2/neu. Triple negative is sometimes used as a surrogate term for basal-like, however more detailed classification is possible providing better guidance for...
.
It is characterised by the presence of cancer cells in the subdermal lymphatics on skin biopsy.
Search for biomolecular characteristics produced a broad number of possible markers, such as loss of LIBC and WISP3 expression. Inflammatory breast cancer is in many ways very similar to late stage or metastatic breast cancer however it can be distinguished from those cancer types both by molecular footprint and clinical presentation. On molecular level some similarity exists with pancreatic cancer.
Estrogen and Progesterone receptor status is frequently negative, corresponding with poor survival. The tumors are highly angiogenic and vascular, with high levels of VEGF and bFGF expression.
A number of proteins and signalling pathways show behaviour that can be considered paradoxical compared to their function in normal tissue and other breast cancer types.
- caveolin-1 and -2 are overexpressed and may contribute to tumour tumour cell motility
- E-cadherin is overexpressed and paradoxically associated with especially aggressive type.
RhoC GTPase is overexpressed, possibly related with overexpression (hypomethylation) of Caveolin-1,-2. Caevolin is paradoxically tumour promoting. NF-kappaB pathway activation overexpression may contribute to the inflammatory phenotype.
Epidemiology
Occurs in all adult age groups. While the majority of patients are between 40–59 years old, age predilection is much less pronounced than in noninflammatory breast cancer. 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.Most known breast cancer risk predictors do not apply for inflammatory breast cancer. It maybe be slightly associated with cumulative breast-feeding duration. While there may be a slight risk correlation with breast feeding duration it must be considered that the resulting effect would be by far outweighed by the protective effect breastfeeding has against more frequent breast cancer types.
Role of hormones
Age distribution and relation to breastfeeding duration is suggestive of some sort of involvement of hormones in the aetiology, however significant differences exist compared to normal breast cancer.Typically IBC shows low levels of estrogen and progesterone receptor sensitivity corresponding with poor outcome. In 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 high level of NF kappaB target gene expression which can be - under laboratory conditions successfully modulated by estrogen but not tamoxifen.
Staging
Staging is designed to help organize the different treatment plans and to understand the prognosisPrognosis
Prognosis is a medical term to describe the likely outcome of an illness.When applied to large statistical populations, prognostic estimates can be very accurate: for example the statement "45% of patients with severe septic shock will die within 28 days" can be made with some confidence, because...
better. Staging for IBC has been adapted to meet the specific characteristics of the disease. IBC is typically diagnosed in one of these stages:
- Stage IIIA - less than one complete breast is affected
- Stage IIIB - the whole breast is affected, might have spread to issues near the breast, such as the skin or chest wall, including the ribs and muscles in the chest. The cancer may have spread to lymph nodes within the breast or under the arm.
- Stage IV means that the cancer has spread to other organs. These can include the bones, lungs, liver, and/or brain, as well as the lymph nodes in the neck.
Treatment
Multimodal therapy including chemotherapyChemotherapy
Chemotherapy is the treatment of cancer with an antineoplastic drug or with a combination of such drugs into a standardized treatment regimen....
with a combination of several agents, radiation therapy, hormonal therapy where appropriate and in some cases surgery.
Estrogen antagonist or aromatase inhibitors appear to improve outcome for ER positive cancer, similar for Herceptin.
Surgery was only rarely performed because inflammatory breast cancer is considered essentially a systemic cancer, however it may improve outcome and is now being reconsidered. A lumpectomy
Lumpectomy
Lumpectomy is a common surgical procedure designed to remove a discrete lump, usually a benign tumor or breast cancer, from an affected man or woman's breast...
, when only a portion of the breast is removed, is not an option for IBC patients. A lymph node dissection
Lymph node dissection
Lymph node dissection, also lymphadenectomy is a surgical procedure in which the lymph nodes are removed and examined to see whether they contain cancer. For a regional lymph node dissection, some of the lymph nodes in the tumor area are removed; for a radical lymph node dissection, most or all of...
is also recommended over a sentinel lymph node
Sentinel lymph node
The sentinel lymph node is the hypothetical first lymph node or group of nodes reached by metastasizing cancer cells from a primary tumor.-Physiology:...
biopsy. Lymphedema
Lymphedema
Lymphedema , also known as lymphatic obstruction, is a condition of localized fluid retention and tissue swelling caused by a compromised lymphatic system....
, swelling of the arm and the hand on the side of the body where surgery was performed, may be a complication after a lymph node dissection. Reconstruction of the breast may be an option for healthy women after a mastectomy. However, for patients who smoke or have diabetes, complications are more common.
A number of promising new therapeutic agents exists, such as
- lapatinibLapatinibLapatinib , used in the form of lapatinib ditosylate, is an orally active drug for breast cancer and other solid tumours. It is a dual tyrosine kinase inhibitor which interrupts the HER2 growth receptor pathway. It is used in combination therapy for HER2-positive breast cancer...
- a Her2neu receptor antagonist - various VEGF receptor antagonists
- tipifarnibTipifarnibTipifarnib is a farnesyltransferase inhibitor that is being investigated in patients 65 years of age and older with newly diagnosed acute myeloid leukemia . It inhibits the Ras kinase in a post translational modification step before the kinase pathway becomes hyperactive...
- a farnesyltransferaseFarnesyltransferaseFarnesyltransferase is one of the three enzymes in the prenyltransferase group. Farnesyltransferase adds a 15-carbon isoprenoid called a farnesyl group to proteins bearing a CaaX motif: a four-amino acid sequence at the carboxyl terminus of a protein...
inhibitor
Prognosis factors
Estrogen and Progesterone receptor positive cases have better prognosis. Loss of heterozygosity, stage IV disease and appearance of symptoms resembling extensive inflammation are markers of poor prognosis.Premenopausal cases have significantly worse prognosis. In postmenopausal cases lean women have significantly better prognosis than obese women.
External links
Inflammatory breast cancer is an especially aggressive type of breast cancerBreast cancer
Breast cancer is cancer originating from breast tissue, most commonly from the inner lining of milk ducts or the lobules that supply the ducts with milk. Cancers originating from ducts are known as ductal carcinomas; those originating from lobules are known as lobular carcinomas...
that can occur in women of any age (and
extremely rarely, in men).
It is called inflammatory because it frequently presents with symptoms resembling an inflammation. However it can present with very variable signs and symptoms, frequently without detectable tumors and therefore is often not detected by mammography
Mammography
Mammography is the process of using low-energy-X-rays to examine the human breast and is used as a diagnostic and a screening tool....
or ultrasound
Ultrasound
Ultrasound is cyclic sound pressure with a frequency greater than the upper limit of human hearing. Ultrasound is thus not separated from "normal" sound based on differences in physical properties, only the fact that humans cannot hear it. Although this limit varies from person to person, it is...
.
Typical presentation is rapid swelling, sometimes associated by skin changes (peau d' orange), and nipple retraction. Other symptoms include rapid increase in breast size, redness, persistent itching, skin hot to touch. IBC often initially resembles mastitis
Mastitis
Mastitis is the inflammation of breast tissue. S. aureus is the most common etiological organism responsible, but S. epidermidis and streptococci are occasionally isolated as well.-Terminology:...
.
Only about 50-75% cases have the typical presentation. Symptoms can be completely atypical such as acute central venous thrombosis as the sole presenting symptom.
IBC makes up only a small percentage of breast cancer cases (1-6% in the USA). IBC is often diagnosed in younger women although average age of presentation does not differ much from other kinds of breast cancer (average age 57 years). African-Americans are usually diagnosed at younger ages than Caucasian women, and also have a higher risk of getting IBC. Recent advances in therapy have improved the prognosis considerably and at least one third of women will survive the diagnosis by 10 years or longer.
Symptoms
Symptoms are very variable and may not be present at all in occult inflammatory breast cancer. Quick onset of symptoms is typical, the breast often looks swollen and red, or “inflamed”, sometimes overnight, and are easy to misdiagnose as mastitis. Invasion of the local lymphatic ducts impairs drainage and causes edemaEdema
Edema or oedema ; both words from the Greek , oídēma "swelling"), formerly known as dropsy or hydropsy, is an abnormal accumulation of fluid beneath the skin or in one or more cavities of the body that produces swelling...
tous swelling of the breast. Because the skin of the breast is tethered by the suspensory ligament of Cooper, the accumulation of fluid may cause the skin of the breast to assume a dimpled appearance similar to an orange peel (peau d'orange
Peau d'orange
The French term peau d'orange means "orange peel skin", or more literally, "skin of an orange". It is used in medicine to describe anatomy with the appearance and dimpled texture of an orange peel...
). IBC is sometimes misdiagnosed as an insect bite or breast infection.
In the case of IBC, a lump is usually not present as in other forms of breast cancer.
Symptoms may include:
- Pain in the breast
- Skin changes on breast
- Reddened area with texture resembling the peel of an orange (peau d’orange)
- Sudden swelling of the breast
- Itching of breast
- Nipple retraction (flattened look) or discharge
- Swelling of lymph nodes under the arm or in the neck
- Unusual warmth of the affected breast
- Breast is harder or firmer
Other symptoms may rarely include:
- Swelling of the arm
- Breast decreases instead of increasing
- Although a dominant mass is present in many cases, most inflammatory cancers present as diffuse infiltration of the breast without a well-defined tumor.
- A lump may become present and grow rapidly
Most patients do not experience all the symptoms of IBC. Not all symptoms need to be present in order to be diagnosed.
Diagnosis
The only reliable method of diagnosis is biopsyBiopsy
A biopsy is a medical test involving sampling of cells or tissues for examination. It is the medical removal of tissue from a living subject to determine the presence or extent of a disease. The tissue is generally examined under a microscope by a pathologist, and can also be analyzed chemically...
. Mammography
Mammography
Mammography is the process of using low-energy-X-rays to examine the human breast and is used as a diagnostic and a screening tool....
, MRI or ultrasound often show suspicious signs; however in a significant proportion of cases they would miss a diagnosis.
Clinical presentation is typical only in 50-75% of cases; and many other conditions such as mastitis
Mastitis
Mastitis is the inflammation of breast tissue. S. aureus is the most common etiological organism responsible, but S. epidermidis and streptococci are occasionally isolated as well.-Terminology:...
or even heart insufficiency can mimic the typical symptoms of Inflammatory Breast Cancer.
Temporary regression or fluctuation of symptoms, spontaneous or in response to conventional treatment or hormonal events should not be considered of any significance in diagnosis. Inflammatory breast cancer is known to respond to antibiotics and progesterone, and reaction to other medications or hormones cannot be excluded.
Characterization
Inflammatory breast cancer is high grade aneuploid cancer, with mutations and overexpression of p53, high levels of E-cadherin and abnormal cadherin function. It is often regarded as a systemic cancer. Large part of IBC cases present as triple negative breast cancerTriple Negative Breast Cancer
Triple-negative breast cancer refers to any breast cancer that does not express the genes for estrogen receptor , progesterone receptor or Her2/neu. Triple negative is sometimes used as a surrogate term for basal-like, however more detailed classification is possible providing better guidance for...
.
It is characterised by the presence of cancer cells in the subdermal lymphatics on skin biopsy.
Search for biomolecular characteristics produced a broad number of possible markers, such as loss of LIBC and WISP3 expression. Inflammatory breast cancer is in many ways very similar to late stage or metastatic breast cancer however it can be distinguished from those cancer types both by molecular footprint and clinical presentation. On molecular level some similarity exists with pancreatic cancer.
Estrogen and Progesterone receptor status is frequently negative, corresponding with poor survival. The tumors are highly angiogenic and vascular, with high levels of VEGF and bFGF expression.
A number of proteins and signalling pathways show behaviour that can be considered paradoxical compared to their function in normal tissue and other breast cancer types.
- caveolin-1 and -2 are overexpressed and may contribute to tumour tumour cell motility
- E-cadherin is overexpressed and paradoxically associated with especially aggressive type.
RhoC GTPase is overexpressed, possibly related with overexpression (hypomethylation) of Caveolin-1,-2. Caevolin is paradoxically tumour promoting. NF-kappaB pathway activation overexpression may contribute to the inflammatory phenotype.
Epidemiology
Occurs in all adult age groups. While the majority of patients are between 40–59 years old, age predilection is much less pronounced than in noninflammatory breast cancer. 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.Most known breast cancer risk predictors do not apply for inflammatory breast cancer. It maybe be slightly associated with cumulative breast-feeding duration. While there may be a slight risk correlation with breast feeding duration it must be considered that the resulting effect would be by far outweighed by the protective effect breastfeeding has against more frequent breast cancer types.
Role of hormones
Age distribution and relation to breastfeeding duration is suggestive of some sort of involvement of hormones in the aetiology, however significant differences exist compared to normal breast cancer.Typically IBC shows low levels of estrogen and progesterone receptor sensitivity corresponding with poor outcome. In 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 high level of NF kappaB target gene expression which can be - under laboratory conditions successfully modulated by estrogen but not tamoxifen.
Staging
Staging is designed to help organize the different treatment plans and to understand the prognosisPrognosis
Prognosis is a medical term to describe the likely outcome of an illness.When applied to large statistical populations, prognostic estimates can be very accurate: for example the statement "45% of patients with severe septic shock will die within 28 days" can be made with some confidence, because...
better. Staging for IBC has been adapted to meet the specific characteristics of the disease. IBC is typically diagnosed in one of these stages:
- Stage IIIA - less than one complete breast is affected
- Stage IIIB - the whole breast is affected, might have spread to issues near the breast, such as the skin or chest wall, including the ribs and muscles in the chest. The cancer may have spread to lymph nodes within the breast or under the arm.
- Stage IV means that the cancer has spread to other organs. These can include the bones, lungs, liver, and/or brain, as well as the lymph nodes in the neck.
Treatment
Multimodal therapy including chemotherapyChemotherapy
Chemotherapy is the treatment of cancer with an antineoplastic drug or with a combination of such drugs into a standardized treatment regimen....
with a combination of several agents, radiation therapy, hormonal therapy where appropriate and in some cases surgery.
Estrogen antagonist or aromatase inhibitors appear to improve outcome for ER positive cancer, similar for Herceptin.
Surgery was only rarely performed because inflammatory breast cancer is considered essentially a systemic cancer, however it may improve outcome and is now being reconsidered. A lumpectomy
Lumpectomy
Lumpectomy is a common surgical procedure designed to remove a discrete lump, usually a benign tumor or breast cancer, from an affected man or woman's breast...
, when only a portion of the breast is removed, is not an option for IBC patients. A lymph node dissection
Lymph node dissection
Lymph node dissection, also lymphadenectomy is a surgical procedure in which the lymph nodes are removed and examined to see whether they contain cancer. For a regional lymph node dissection, some of the lymph nodes in the tumor area are removed; for a radical lymph node dissection, most or all of...
is also recommended over a sentinel lymph node
Sentinel lymph node
The sentinel lymph node is the hypothetical first lymph node or group of nodes reached by metastasizing cancer cells from a primary tumor.-Physiology:...
biopsy. Lymphedema
Lymphedema
Lymphedema , also known as lymphatic obstruction, is a condition of localized fluid retention and tissue swelling caused by a compromised lymphatic system....
, swelling of the arm and the hand on the side of the body where surgery was performed, may be a complication after a lymph node dissection. Reconstruction of the breast may be an option for healthy women after a mastectomy. However, for patients who smoke or have diabetes, complications are more common.
A number of promising new therapeutic agents exists, such as
- lapatinibLapatinibLapatinib , used in the form of lapatinib ditosylate, is an orally active drug for breast cancer and other solid tumours. It is a dual tyrosine kinase inhibitor which interrupts the HER2 growth receptor pathway. It is used in combination therapy for HER2-positive breast cancer...
- a Her2neu receptor antagonist - various VEGF receptor antagonists
- tipifarnibTipifarnibTipifarnib is a farnesyltransferase inhibitor that is being investigated in patients 65 years of age and older with newly diagnosed acute myeloid leukemia . It inhibits the Ras kinase in a post translational modification step before the kinase pathway becomes hyperactive...
- a farnesyltransferaseFarnesyltransferaseFarnesyltransferase is one of the three enzymes in the prenyltransferase group. Farnesyltransferase adds a 15-carbon isoprenoid called a farnesyl group to proteins bearing a CaaX motif: a four-amino acid sequence at the carboxyl terminus of a protein...
inhibitor
Prognosis factors
Estrogen and Progesterone receptor positive cases have better prognosis. Loss of heterozygosity, stage IV disease and appearance of symptoms resembling extensive inflammation are markers of poor prognosis.Premenopausal cases have significantly worse prognosis. In postmenopausal cases lean women have significantly better prognosis than obese women.
External links
Inflammatory breast cancer is an especially aggressive type of breast cancerBreast cancer
Breast cancer is cancer originating from breast tissue, most commonly from the inner lining of milk ducts or the lobules that supply the ducts with milk. Cancers originating from ducts are known as ductal carcinomas; those originating from lobules are known as lobular carcinomas...
that can occur in women of any age (and
extremely rarely, in men).
It is called inflammatory because it frequently presents with symptoms resembling an inflammation. However it can present with very variable signs and symptoms, frequently without detectable tumors and therefore is often not detected by mammography
Mammography
Mammography is the process of using low-energy-X-rays to examine the human breast and is used as a diagnostic and a screening tool....
or ultrasound
Ultrasound
Ultrasound is cyclic sound pressure with a frequency greater than the upper limit of human hearing. Ultrasound is thus not separated from "normal" sound based on differences in physical properties, only the fact that humans cannot hear it. Although this limit varies from person to person, it is...
.
Typical presentation is rapid swelling, sometimes associated by skin changes (peau d' orange), and nipple retraction. Other symptoms include rapid increase in breast size, redness, persistent itching, skin hot to touch. IBC often initially resembles mastitis
Mastitis
Mastitis is the inflammation of breast tissue. S. aureus is the most common etiological organism responsible, but S. epidermidis and streptococci are occasionally isolated as well.-Terminology:...
.
Only about 50-75% cases have the typical presentation. Symptoms can be completely atypical such as acute central venous thrombosis as the sole presenting symptom.
IBC makes up only a small percentage of breast cancer cases (1-6% in the USA). IBC is often diagnosed in younger women although average age of presentation does not differ much from other kinds of breast cancer (average age 57 years). African-Americans are usually diagnosed at younger ages than Caucasian women, and also have a higher risk of getting IBC. Recent advances in therapy have improved the prognosis considerably and at least one third of women will survive the diagnosis by 10 years or longer.
Symptoms
Symptoms are very variable and may not be present at all in occult inflammatory breast cancer. Quick onset of symptoms is typical, the breast often looks swollen and red, or “inflamed”, sometimes overnight, and are easy to misdiagnose as mastitis. Invasion of the local lymphatic ducts impairs drainage and causes edemaEdema
Edema or oedema ; both words from the Greek , oídēma "swelling"), formerly known as dropsy or hydropsy, is an abnormal accumulation of fluid beneath the skin or in one or more cavities of the body that produces swelling...
tous swelling of the breast. Because the skin of the breast is tethered by the suspensory ligament of Cooper, the accumulation of fluid may cause the skin of the breast to assume a dimpled appearance similar to an orange peel (peau d'orange
Peau d'orange
The French term peau d'orange means "orange peel skin", or more literally, "skin of an orange". It is used in medicine to describe anatomy with the appearance and dimpled texture of an orange peel...
). IBC is sometimes misdiagnosed as an insect bite or breast infection.
In the case of IBC, a lump is usually not present as in other forms of breast cancer.
Symptoms may include:
- Pain in the breast
- Skin changes on breast
- Reddened area with texture resembling the peel of an orange (peau d’orange)
- Sudden swelling of the breast
- Itching of breast
- Nipple retraction (flattened look) or discharge
- Swelling of lymph nodes under the arm or in the neck
- Unusual warmth of the affected breast
- Breast is harder or firmer
Other symptoms may rarely include:
- Swelling of the arm
- Breast decreases instead of increasing
- Although a dominant mass is present in many cases, most inflammatory cancers present as diffuse infiltration of the breast without a well-defined tumor.
- A lump may become present and grow rapidly
Most patients do not experience all the symptoms of IBC. Not all symptoms need to be present in order to be diagnosed.
Diagnosis
The only reliable method of diagnosis is biopsyBiopsy
A biopsy is a medical test involving sampling of cells or tissues for examination. It is the medical removal of tissue from a living subject to determine the presence or extent of a disease. The tissue is generally examined under a microscope by a pathologist, and can also be analyzed chemically...
. Mammography
Mammography
Mammography is the process of using low-energy-X-rays to examine the human breast and is used as a diagnostic and a screening tool....
, MRI or ultrasound often show suspicious signs; however in a significant proportion of cases they would miss a diagnosis.
Clinical presentation is typical only in 50-75% of cases; and many other conditions such as mastitis
Mastitis
Mastitis is the inflammation of breast tissue. S. aureus is the most common etiological organism responsible, but S. epidermidis and streptococci are occasionally isolated as well.-Terminology:...
or even heart insufficiency can mimic the typical symptoms of Inflammatory Breast Cancer.
Temporary regression or fluctuation of symptoms, spontaneous or in response to conventional treatment or hormonal events should not be considered of any significance in diagnosis. Inflammatory breast cancer is known to respond to antibiotics and progesterone, and reaction to other medications or hormones cannot be excluded.
Characterization
Inflammatory breast cancer is high grade aneuploid cancer, with mutations and overexpression of p53, high levels of E-cadherin and abnormal cadherin function. It is often regarded as a systemic cancer. Large part of IBC cases present as triple negative breast cancerTriple Negative Breast Cancer
Triple-negative breast cancer refers to any breast cancer that does not express the genes for estrogen receptor , progesterone receptor or Her2/neu. Triple negative is sometimes used as a surrogate term for basal-like, however more detailed classification is possible providing better guidance for...
.
It is characterised by the presence of cancer cells in the subdermal lymphatics on skin biopsy.
Search for biomolecular characteristics produced a broad number of possible markers, such as loss of LIBC and WISP3 expression. Inflammatory breast cancer is in many ways very similar to late stage or metastatic breast cancer however it can be distinguished from those cancer types both by molecular footprint and clinical presentation. On molecular level some similarity exists with pancreatic cancer.
Estrogen and Progesterone receptor status is frequently negative, corresponding with poor survival. The tumors are highly angiogenic and vascular, with high levels of VEGF and bFGF expression.
A number of proteins and signalling pathways show behaviour that can be considered paradoxical compared to their function in normal tissue and other breast cancer types.
- caveolin-1 and -2 are overexpressed and may contribute to tumour tumour cell motility
- E-cadherin is overexpressed and paradoxically associated with especially aggressive type.
RhoC GTPase is overexpressed, possibly related with overexpression (hypomethylation) of Caveolin-1,-2. Caevolin is paradoxically tumour promoting. NF-kappaB pathway activation overexpression may contribute to the inflammatory phenotype.
Epidemiology
Occurs in all adult age groups. While the majority of patients are between 40–59 years old, age predilection is much less pronounced than in noninflammatory breast cancer. 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.Most known breast cancer risk predictors do not apply for inflammatory breast cancer. It maybe be slightly associated with cumulative breast-feeding duration. While there may be a slight risk correlation with breast feeding duration it must be considered that the resulting effect would be by far outweighed by the protective effect breastfeeding has against more frequent breast cancer types.
Role of hormones
Age distribution and relation to breastfeeding duration is suggestive of some sort of involvement of hormones in the aetiology, however significant differences exist compared to normal breast cancer.Typically IBC shows low levels of estrogen and progesterone receptor sensitivity corresponding with poor outcome. In 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 high level of NF kappaB target gene expression which can be - under laboratory conditions successfully modulated by estrogen but not tamoxifen.
Staging
Staging is designed to help organize the different treatment plans and to understand the prognosisPrognosis
Prognosis is a medical term to describe the likely outcome of an illness.When applied to large statistical populations, prognostic estimates can be very accurate: for example the statement "45% of patients with severe septic shock will die within 28 days" can be made with some confidence, because...
better. Staging for IBC has been adapted to meet the specific characteristics of the disease. IBC is typically diagnosed in one of these stages:
- Stage IIIA - less than one complete breast is affected
- Stage IIIB - the whole breast is affected, might have spread to issues near the breast, such as the skin or chest wall, including the ribs and muscles in the chest. The cancer may have spread to lymph nodes within the breast or under the arm.
- Stage IV means that the cancer has spread to other organs. These can include the bones, lungs, liver, and/or brain, as well as the lymph nodes in the neck.
Treatment
Multimodal therapy including chemotherapyChemotherapy
Chemotherapy is the treatment of cancer with an antineoplastic drug or with a combination of such drugs into a standardized treatment regimen....
with a combination of several agents, radiation therapy, hormonal therapy where appropriate and in some cases surgery.
Estrogen antagonist or aromatase inhibitors appear to improve outcome for ER positive cancer, similar for Herceptin.
Surgery was only rarely performed because inflammatory breast cancer is considered essentially a systemic cancer, however it may improve outcome and is now being reconsidered. A lumpectomy
Lumpectomy
Lumpectomy is a common surgical procedure designed to remove a discrete lump, usually a benign tumor or breast cancer, from an affected man or woman's breast...
, when only a portion of the breast is removed, is not an option for IBC patients. A lymph node dissection
Lymph node dissection
Lymph node dissection, also lymphadenectomy is a surgical procedure in which the lymph nodes are removed and examined to see whether they contain cancer. For a regional lymph node dissection, some of the lymph nodes in the tumor area are removed; for a radical lymph node dissection, most or all of...
is also recommended over a sentinel lymph node
Sentinel lymph node
The sentinel lymph node is the hypothetical first lymph node or group of nodes reached by metastasizing cancer cells from a primary tumor.-Physiology:...
biopsy. Lymphedema
Lymphedema
Lymphedema , also known as lymphatic obstruction, is a condition of localized fluid retention and tissue swelling caused by a compromised lymphatic system....
, swelling of the arm and the hand on the side of the body where surgery was performed, may be a complication after a lymph node dissection. Reconstruction of the breast may be an option for healthy women after a mastectomy. However, for patients who smoke or have diabetes, complications are more common.
A number of promising new therapeutic agents exists, such as
- lapatinibLapatinibLapatinib , used in the form of lapatinib ditosylate, is an orally active drug for breast cancer and other solid tumours. It is a dual tyrosine kinase inhibitor which interrupts the HER2 growth receptor pathway. It is used in combination therapy for HER2-positive breast cancer...
- a Her2neu receptor antagonist - various VEGF receptor antagonists
- tipifarnibTipifarnibTipifarnib is a farnesyltransferase inhibitor that is being investigated in patients 65 years of age and older with newly diagnosed acute myeloid leukemia . It inhibits the Ras kinase in a post translational modification step before the kinase pathway becomes hyperactive...
- a farnesyltransferaseFarnesyltransferaseFarnesyltransferase is one of the three enzymes in the prenyltransferase group. Farnesyltransferase adds a 15-carbon isoprenoid called a farnesyl group to proteins bearing a CaaX motif: a four-amino acid sequence at the carboxyl terminus of a protein...
inhibitor
Prognosis factors
Estrogen and Progesterone receptor positive cases have better prognosis. Loss of heterozygosity, stage IV disease and appearance of symptoms resembling extensive inflammation are markers of poor prognosis.Premenopausal cases have significantly worse prognosis. In postmenopausal cases lean women have significantly better prognosis than obese women.