What is Inflammatory Breast Cancer? What Are Its Symptoms? How Is It Diagnosed and Treated?

Inflammatory breast cancer, an inflammatory disorder of the breast, is a very rare but extremely dangerous type of breast cancer. Although it accounts for only 1% to 5% of all breast cancer cases, it is responsible for 8% to 10% of breast cancer-related deaths.

This aggressive type of cancer progresses rapidly and typically manifests with symptoms such as redness, swelling, and a feeling of warmth in the breast. Ranking among the inflammatory disorders of the breast, this disease can frequently be confused with a breast infection. Therefore, early diagnosis can be difficult, and careful evaluation is of great importance.

In our article, we will answer the question of what inflammatory disorders of the breast are, and share the symptoms, diagnostic methods, and treatment options for inflammatory breast cancer with you. Prepared in a clear and understandable language, this information contains important clues for your health.

What is Inflammatory Breast Cancer?

Inflammatory breast cancer is, as the name suggests, a type of breast cancer that presents with inflammation-like findings in the breast tissue. Although this type of cancer is rare, it is extremely dangerous and rapidly progressive. Accounting for approximately 1% to 5% of all breast cancers, this disease is responsible for 8% to 10% of breast cancer-related deaths. In inflammatory breast cancer, cancer cells clog the lymphatic vessels of the breast, causing symptoms such as redness, swelling, and increased warmth in the skin.

What do inflammatory disorders of the breast mean?

Inflammatory disorders of the breast are conditions characterized by inflammation and swelling in the breast tissue. The breast consists of adipose tissue, connective tissue, and the mammary gland. When inflammatory disorders of the breast occur, the skin over the mammary gland may be red and warm. Severe pain and swelling in the mammary gland can often be felt.

However, the breast is not an organ frequently affected by systemic inflammatory reactions, and clinical findings of systemic chronic diseases are not commonly seen in the breast. For this reason, reactive inflammatory diseases of the breast appear extremely rarely in clinical practice.

The difference between inflammatory breast cancer and other breast cancers

Inflammatory breast cancer differs from other breast types because a distinct palpable lump is usually not detected. While normal breast cancers typically present with the formation of a mass first, in inflammatory breast cancer, the characteristic red, swollen appearance of the breast occurs as a result of cancer cells blocking the lymphatic vessels in the breast skin.

Additionally, inflammatory breast cancer progresses more rapidly, and the presence of axillary lymph node metastasis upon diagnosis is a finding encountered in almost all patients. Furthermore, approximately one-third of patients present with distant organ metastasis.

Which age groups are more frequently affected?

Inflammatory breast cancer occurs at a younger age than other breast cancers. Although it frequently occurs between the ages of 40 and 59, the age preference is much less pronounced compared to non-inflammatory breast cancer. The overall rate is 1.3 cases per 100,000 people. Black women (1.6) have the highest rate, while Asian and Pacific Islander women have the lowest rate (0.7).

It tends to appear at younger ages, particularly in Black women, and is observed more frequently in obese women.

Rapid progression feature of the disease

Inflammatory breast cancer is the most rapidly progressing type of breast cancer. It generally progresses quickly within a few weeks to months. From the appearance of the initial symptoms, it can spread aggressively within a few weeks or months.

Due to this rapid progression feature, early diagnosis is difficult, and there is a high risk of delayed treatment. The rapid onset of symptoms is typical; the breast often appears swollen and red or 'inflamed', sometimes changing appearance seemingly overnight.

The rapid course of the disease necessitates a comprehensive and urgent treatment plan. Therefore, every new condition occurring in the breast must be proven not to be breast cancer, and it is necessary to consult an expert breast surgeon or general surgery specialist.

Causes of Inflammatory Breast Cancer

The exact cause of inflammatory breast cancer is not yet fully known. However, scientists have identified various factors that may play a role in the development of this aggressive cancer type. These factors influence the rapid progression and aggressive nature of the disease.

Genetic mutations and molecular mechanisms

Various genetic alterations play a role in inflammatory breast cancer. In this type of cancer, the E-cadherin protein is particularly overexpressed, and paradoxically, this situation is associated with especially aggressive subtypes. Furthermore, the RhoC GTPase gene is also overexpressed, likely in association with the overexpression of Caveolin 1 and 2.

On the other hand, the hyperactivation of the NF-κB pathway may contribute to the inflammatory phenotype. Some studies have shown that particularly aggressive phenotypes of inflammatory breast cancer are characterized by high levels of NF kappaB gene expression.

Mutations in the P53 tumor suppressor gene are also common in inflammatory breast cancer and are associated with a poor prognosis. Additionally, loss of heterozygosity is present in at least half of inflammatory breast cancers.

Hormone receptor status and effects

Hormone receptor status is critically important in determining treatment response and the course of the disease in inflammatory breast cancer. In this cancer type, the rates of having a hormone-negative (45%), HER2-positive (45%), and triple-negative (25-30%) molecular profile are higher compared to other breast cancers.

In cases of triple-negative inflammatory breast cancer, high rates of recurrence and metastasis are observed within the first three years after diagnosis. Often, the hormone receptor is negative, indicating a poor prognosis.

According to molecular classification, inflammatory breast cancer is divided into four main groups:

Luminal A (20%): HR (ER and/or PR) +, HER2 –

Luminal B (35%): HR+, HER2+/-

HER2-enriched (non-luminal HER2 positive) (20%)

Basal-like (Triple negative/TNBC) (25-30%)

Environmental and inflammatory factors

Obesity plays a significant role among environmental factors increasing the risk of inflammatory breast cancer. This type of cancer is seen more frequently in obese women. Additionally, women of Black race have a higher risk compared to white women.

Chronic inflammation is also thought to be effective in the development of inflammatory breast cancer, although the clarity of this relationship has not yet been fully established. Inflammatory breast cancer is actually a misnomer, because it involves negligible production of most inflammatory cytokines such as interleukin-12, interleukin-1, and interferon-gamma.

Relationship with inflammatory disorders of the breast

Inflammatory disorders of the breast do not frequently involve the clinical manifestations of systemic chronic diseases appearing in the breast. The breast is not an organ frequently affected by systemic inflammatory reactions.

However, some systemic diseases, albeit rarely, can cause certain clinical findings in the breast. This is usually a reactive and inflammatory process. Benign lesions of the breast characterized by localized inflammation are relatively more frequent, but their histopathological differential diagnosis is not always very easy.

Systemic diseases such as sarcoidosis, amyloidosis, and diabetes can rarely cause certain clinical findings in the breast. However, it has not yet been proven that these conditions have a direct relationship with inflammatory breast cancer.

Symptoms and Early Warning Signs

Symptoms of inflammatory breast cancer usually develop very rapidly and occur together. Unlike typical breast cancer, the disease generally appears without a palpable lump. Recognizing these symptoms can be life-saving.

Redness and orange peel appearance on the breast skin

One of the most prominent features of inflammatory breast cancer is redness covering at least one-third of the breast. This redness can be in the form of color changes including pink, purple, or bruised-like appearances. As a result of cancer cells blocking the lymphatic channels in the breast skin, the breast skin becomes edematous and an orange peel appearance (peau d'orange) emerges. This appearance is characterized by the formation of distinct indentations and protrusions on the skin.

Inversion and tenderness of the nipple

With the progression of the disease, inversion or flattening of the nipple may be observed. A newly developed unilateral nipple retraction must be investigated. Additionally, dimpling, discharge, and tenderness can be felt in the nipple. These symptoms can sometimes be the first clues of a breast cancer diagnosis.

Lymph node swellings and underarm symptoms

Inflammatory breast cancer tends to spread rapidly. The cancer may have spread to the lymph nodes near the breast, and this spread can cause swelling under the arm or above the collarbone. The presence of enlarged lymph nodes under the arm or below/above the collarbone is an important warning sign. In some cases, these symptoms may be accompanied by swelling of the arm.

Sudden swelling and increased warmth in the breast

Rapid swelling and pain in the breast are typical symptoms of inflammatory breast cancer. The rapid changes occurring in the breast tissue within a few weeks are notable. An unusual increase in warmth can be felt in the affected breast. The breast tissue may also take on a firmer or tighter structure. Rarely, the breast may appear to shrink instead of increasing in size.

Similarity with symptoms of inflammatory disorders of the breast

Symptoms of inflammatory breast cancer can show similarities to other inflammatory disorders of the breast. It can easily be confused especially with mastitis (breast infection). Tenderness, redness, warmth, and itching can be symptoms of both breast infection and inflammation. In this case, antibiotic therapy under doctor supervision can be administered initially for infection. However, if symptoms do not resolve within 7-10 days or worsen, further tests should be performed for the possibility of cancer.

In cases where the distinction between inflammatory disorders of the breast and inflammatory breast cancer cannot be made, a breast biopsy is required for definitive diagnosis.

Diagnostic Process and Methods Used

The diagnosis of inflammatory breast cancer is of life-saving importance. Early diagnosis increases treatment success. During the diagnostic process, a careful evaluation is required because symptoms show similarities with other diseases.

Physical examination and clinical evaluation

The first step in the diagnostic process is a comprehensive physical examination. Your doctor carefully examines the redness, swelling, and other symptoms of inflammatory breast cancer in your breast. During the physical examination, the doctor performs a visual examination, checks for the presence of a mass, and evaluates the lymph nodes.

Clinical evaluation is important to distinguish inflammatory disorders of the breast. Inflammatory breast cancer is essentially a clinical diagnosis, so the experience and observation of the physician play a critical role in the diagnostic process.

Mammography, ultrasound, and MRI

Imaging methods are an important stage in the diagnostic process. The most common findings on mammography are skin thickening at a rate of 83% and trabecular distortion at 73%. Mass imaging on mammography is approximately 16%.

Ultrasound is useful both in defining the lesion in the breast and in determining the status of regional lymph nodes. In various studies, a mass in the breast, structural distortion, and skin thickening have been observed at a rate of approximately 95%. Involvement in axillary lymph nodes could be detected at a rate of 93%.

MRI imaging has been found to be superior to mammography and ultrasonography. In a study conducted, MRI was found to be 100% successful in revealing the primary breast lesion, PET-CT 96%, ultrasound 95%, and mammography 80%.

Biopsy and histopathological examination

Biopsy is the gold standard for the definitive diagnosis of inflammatory breast cancer. Surgical skin biopsy, punch biopsy from the skin, or core biopsy if there is a palpable mass, are used in diagnosis.

The presence of tumor emboli in dermal lymphatics is considered specific for IBC, but this condition is observed in only up to 75% of cases. In other words, diagnosis can be made even without this finding.

According to biopsy results, a diagnosis of invasive ductal carcinoma is usually made. The usefulness of fine needle aspiration biopsy in diagnosis is limited.

HER2 and hormone receptor tests

Inflammatory breast cancers are usually estrogen and progesterone receptor (ER and PR) negative. However, a small number of patients may be ER or PR positive. In this case, adjuvant hormonotherapy with tamoxifen or aromatase inhibitors can be added according to the patient's menopausal status.

HER2 status is also important for treatment planning. HER2 positivity is evaluated for the applicability of targeted therapies.

Differential diagnosis: mastitis and other conditions

Mastitis, trauma, inflammatory connective tissue diseases, and some malignant diseases should be considered in the differential diagnosis of inflammatory breast cancer. In case of doubt, one should be prompt in performing a biopsy.

Infectious mastitis and breast abscess can be seen especially in nursing mothers and are associated with fever and leukocytosis. It can have similar examination and mammography findings to inflammatory breast cancer, but typically heals with antibiotics.

Ductal ectasia, on the other hand, is a benign condition usually seen in middle-aged women that often resolves spontaneously.

It should not be forgotten that if symptoms do not respond to antibiotic therapy within 7-10 days or worsen, advanced tests should be resorted to for the possibility of inflammatory breast cancer.

Treatment Methods and Application Order

The treatment of inflammatory breast cancer requires multiple methods to be applied in a specific order. The treatment plan generally involves a multi-faceted approach and is personalized according to the stage and spread of the disease.

Neoadjuvant chemotherapy

The first treatment step in inflammatory breast cancer is usually chemotherapy administered before surgery, called neoadjuvant chemotherapy. The purpose of this treatment is to shrink the tumor and reduce inflammation in the breast tissue. Anthracycline-based chemotherapy protocols are preferred first. Drugs such as taxanes, platinum agents, and cyclophosphamide may also take place in the treatment plan. Chemotherapy is usually administered in 2-3 week cycles for 3-6 months. Neoadjuvant chemotherapy increases the success of surgery and helps destroy cancer cells that may have spread to other parts of the body.

Modified radical mastectomy

Following chemotherapy, a modified radical mastectomy is generally performed. This surgical procedure involves the removal of the entire breast and most of the underarm lymph nodes. In inflammatory breast cancer, breast-conserving surgery is usually not recommended. The duration of the surgery varies between 1.5 to 4 hours depending on the approach and simultaneous procedures that can be performed. Having clean surgical margins (containing no cancer cells) is important in terms of prognosis.

Radiotherapy applications

Following surgery, radiotherapy is administered to destroy remaining microscopic cancer cells. After mastectomy, radiotherapy is delivered to the chest wall, supraclavicular region, and internal mammary lymph nodes. Treatment usually lasts for several weeks, 5 days a week. Although each session takes 3-4 minutes, it can reach 20-30 minutes with preparation and adjustment procedures.

Targeted therapies (HER2 positivity)

Approximately 45% of inflammatory breast cancers are HER2 positive. In this case, targeted drugs such as trastuzumab (Herceptin) and pertuzumab (Perjeta) are added to the treatment plan. These drugs target the HER2 protein, which helps cancer cells grow. Targeted therapies are usually used together with or after chemotherapy and are administered for a total of 1 year.

Hormone therapy options

In hormone-sensitive inflammatory breast cancer cases, hormone therapy can be started after chemotherapy and surgery. Tamoxifen is generally preferred in premenopausal women, while aromatase inhibitors (anastrozole, letrozole, exemestane) are used in postmenopausal women. Hormone therapy can last 5-10 years and plays an important role in reducing the risk of cancer recurrence.

Supportive (palliative) care

Palliative care helps alleviate the side effects of the disease and treatment at every stage of treatment. It includes issues such as pain control, fatigue management, nutritional support, and psychological support. When applied alongside other treatments, palliative care improves patients' quality of life and can help them live longer. This care is provided by a team consisting of doctors, nurses, and other healthcare professionals.

Frequently Asked Questions

Is inflammatory breast cancer contagious?

No, inflammatory breast cancer or other types of cancer are definitely not contagious. Cancer is the uncontrolled proliferation of cells as a result of genetic mutations and is not transmitted from person to person through contact, air, or other ways. The occurrence of cancer in multiple individuals of the same family may stem from genetic predisposition or environmental factors.

What is the chance of recovery?

In inflammatory breast cancer, the average progression-free survival is 24 months. The three-year survival rate is around 40%. In a large-scale study, 5-year survival was found to be 40%, and 10-year survival was found to be 10%. With developments in treatment methods in recent years, these rates are increasing.

Can this cancer be seen during pregnancy?

Yes, inflammatory breast cancer can be seen during pregnancy. Due to hormonal changes during pregnancy, breast tissue differentiates, which makes diagnosis difficult. In studies conducted, it has been determined that there is a 5-15 month delay between the onset of symptoms and diagnosis. When inflammatory breast cancer is diagnosed, termination of pregnancy may be required since chemotherapy is mandatory.

How long does the treatment duration last?

The duration of treatment varies according to the stage and type of the disease. In general, surgical intervention is completed within a few weeks. Chemotherapy usually takes 3-6 months. Radiotherapy continues for a few weeks. Hormone therapy, on the other hand, can last 5-10 years. The total treatment process can last 1-2 years depending on the patient's condition and response to treatment.

Is breast-conserving surgery possible?

Breast-conserving surgery is not recommended in inflammatory breast cancer. Standard treatment is modified radical mastectomy after anthracycline-based chemotherapy. Existing scientific evidence does not support breast-conserving surgery in inflammatory breast cancer. Positive surgical margins are associated with poor prognosis, and therefore removing the entire breast is recommended.

What is the quality of life like after treatment?

Quality of life after treatment can vary from patient to patient. Anxiety, depression, and emotional problems can be seen in some of the patients. Lymphedema, physical activity restriction, and changes in body image can affect quality of life. However, with correct rehabilitation programs and psychological support, these problems can be largely alleviated. It has been determined that the quality of life score is higher in patients with a high level of education.

In Summary, Inflammatory Breast Cancer

Inflammatory breast cancer is a rare but very dangerous disease. Due to its rapidly progressing structure, early diagnosis is of life-saving importance. When you notice redness, swelling, increased warmth, and an orange peel appearance in the breast, you should consult a doctor without wasting time.

Actually, inflammatory disorders of the breast can be confused with conditions like mastitis. However, in cases where symptoms do not respond to antibiotic therapy or last longer than a week, advanced tests must definitely be performed.

Today, treatment options are more advanced compared to the past. The multi-faceted approach applied in the form of chemotherapy first, followed by surgery and radiation therapy, prolongs life span. Targeted therapies and hormone treatments can also be added in HER2-positive or hormone-sensitive patients.

It should not be forgotten that early diagnosis and rapid intervention are our most important weapon in this disease. Regular check-ups and having knowledge about breast health can reduce risks.

In conclusion, individuals diagnosed with inflammatory breast cancer should be treated by an experienced team and receive psychological support throughout the process. Although it is a challenging process, it is possible to cope with this disease with correct treatment approaches and a strong support system.

Inflammatory breast cancer is a rare but dangerous type of breast cancer. Get detailed information about its symptoms, diagnostic methods, and treatment options.