Rare Type of Breast Cancer

Learn about rare types of breast cancer, including inflammatory, metaplastic, Paget’s disease, phyllodes tumors, and angiosarcoma.

1. Based on gene expression and receptors

In breast cancer, estrogen and progesterone signaling play a major role in driving the growth of certain tumors, particularly those that express hormone receptors.

Breast cancer is classified into four major subtypes based on gene expression patterns and the status of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). These are:

Triple negative breast cancer (ER⁻/PR⁻/HER2⁻)
Luminal A (ER⁺/PR⁺, HER2⁻, low Ki-67)
Luminal B (ER⁺/PR⁺, HER2⁻, high Ki-67; ER⁺/PR⁺, HER2⁺)
HER2-positive (ER⁻/PR⁻, HER2⁺)

1a. Triple-Negative Breast Cancer

Triple-negative breast cancer (TNBC) grows and spreads more rapidly compared with other types of invasive breast cancer. It is an aggressive subtype of invasive breast cancer and is associated with limited treatment options.

In most other invasive breast cancers, tumor cells express estrogen receptors (ER), progesterone receptors (PR), and/or human epidermal growth factor receptor 2 (HER2). In contrast, TNBC is defined by the absence of ER and PR expression and the lack of HER2 overexpression.

TNBC is more commonly diagnosed in younger women, particularly those under 40 years of age, and in individuals with BRCA1 mutations. It accounts for approximately 10–15% of all breast cancer cases.

1b. Luminal Breast Cancer

Luminal breast cancer is the most common subtype of breast cancer, accounting for approximately 70% of all cases. This subtype is hormone receptor–positive and depends on the presence of estrogen receptors (ER) and/or progesterone receptors (PR) for tumor growth.

Luminal breast cancer is further classified into luminal A and luminal B subtypes based on hormone receptor expression, the proliferation marker Ki-67, and HER2 status. Luminal A tumors typically have lower Ki-67 levels and a better prognosis, whereas luminal B tumors show higher proliferative activity and are generally more aggressive.

1c. HER2-Positive Breast Cancer

HER2-positive breast cancer is characterized by overexpression or amplification of the human epidermal growth factor receptor 2 (HER2/ERBB2) and typically lacks estrogen and progesterone receptor expression. The HER2-enriched subtype accounts for approximately 10–15% of all breast cancers.

Additionally, HER2-enriched tumors frequently exhibit a high mutational burden associated with the activity of the APOBEC3B enzyme. APOBEC3B belongs to a family of cytidine deaminases that induce cytosine-to-uracil alterations in DNA, leading to clusters of mutations that contribute to tumor initiation and progression.
Unlike luminal or basal-like breast cancers, HER2-enriched tumors are primarily driven by genes involved in rapid cell proliferation and signaling pathways, including ERBB2 (HER2) and GRB7.
Clinically, HER2-enriched breast cancers tend to grow more rapidly and display more aggressive behavior than luminal breast tumors. Prior to the introduction of HER2-targeted therapies such as trastuzumab, this subtype was associated with a poor prognosis; however, targeted treatments have significantly improved patient outcomes.

2. Inflammatory Breast Cancer

Inflammatory breast cancer is a rare and aggressive type of breast cancer that grows rapidly. It is called inflammatory breast cancer because it causes redness, swelling, and a warm, inflamed appearance of the breast skin.

Unlike many other breast cancers, inflammatory breast cancer typically originates in the ducts or lobules and spreads quickly to surrounding breast tissue and other parts of the body.

It is sometimes misinterpreted as a common breast infection, such as mastitis.

These cancers cause inflammation by blocking the dermal lymphatic vessels in the skin of the breast.

3. Paget’s disease of the Breast

Paget’s disease is a rare form of breast cancer, accounting for less than 5% of breast cancer cases in women. Although uncommon, Paget’s disease can also affect men.

The most common sign of Paget’s disease is a scaly, red rash on the nipple. In individuals with darker skin tones, redness may be more difficult to recognize. The rash may be accompanied by itching or a burning sensation. The darker area of skin surrounding the nipple (the areola) may also become involved.

This condition is also referred to as Paget’s disease of the nipple. It originates in the skin of the nipple and areola and is characterized by the presence of distinctive malignant cells known as Paget cells.

Paget’s disease can resemble eczema or other benign skin conditions; however, there are important differences.

4. Phyllodes Tumors

Phyllodes tumors are uncommon and most often affect women in their 40s, although they can occur at any age. They account for approximately 1% of all breast tumors and arise primarily from the connective (stromal) tissue of the breast.

Phyllodes tumors are classified into three categories based on their microscopic appearance: benign, borderline, and malignant.

A phyllodes tumor typically presents as a painless breast mass that grows rapidly and may stretch the overlying skin.

Phyllodes tumors are more likely to occur in women with Li-Fraumeni syndrome, a rare inherited genetic condition associated with an increased risk of multiple cancers.

5. Tubular Carcinoma

Tubular carcinoma is a subtype of invasive ductal carcinoma, meaning the cancer cells have the potential to spread to other parts of the body. It is a well-differentiated form of invasive ductal carcinoma that begins in the milk ducts and can spread to the surrounding breast tissue.

Tubular carcinoma primarily affects women over the age of 50 and accounts for approximately 1–2% of all invasive breast cancers. It frequently coexists with other types of breast cancer.

This subtype is characterized by well-formed, tube-like structures seen in the cancer cells under microscopic examination. Compared with other forms of breast cancer, tubular carcinoma generally grows slowly and has a favourable prognosis, making it relatively easier to treat.

6. Mucinous (Colloid) Carcinoma

Mucinous carcinoma is a rare type of breast cancer, accounting for approximately 1–2% of all breast cancers.

It originates from cancer cells that produce mucin (mucus). Although this type of cancer most commonly develops in the breast, it can also arise in other organs. Compared with many other forms of breast cancer, mucinous carcinoma is generally less aggressive and responds well to treatment.

This slow-growing subtype is more commonly diagnosed in postmenopausal women. Overall, mucinous carcinoma is uncommon and is typically associated with a favorable prognosis compared with other breast cancer types.

Although mucinous carcinoma can also occur in organs such as the colon, lung, and ovary, it is most frequently found in the breast.

7. Angiosarcoma of the Breast

Angiosarcoma is a rare type of breast cancer that arises from the lining of blood vessels or lymphatic vessels. It accounts for approximately 1–2% of all sarcomas, including those occurring in other parts of the body. This cancer is more commonly diagnosed in individuals over 70 years of age.

Angiosarcoma originates in the blood or lymphatic vessels of the breast and can spread to the overlying skin and surrounding tissues, including the arm. It has the potential to grow rapidly and metastasize to other parts of the body.

There are two types of breast angiosarcoma:

Primary angiosarcoma: This type occurs in individuals with no prior history of breast cancer or radiation therapy.

Secondary angiosarcoma: This type develops in patients who have previously been treated for breast cancer. It is most commonly associated with prior radiation therapy to the breast and may also be linked to chronic lymphedema of the breast or arm.

8. Metaplastic breast cancer

Metaplastic breast cancer (MBC) is a rare form of breast cancer, accounting for approximately 1% of all breast cancers diagnosed each year. It is characterized by the presence of diverse cell types within the tumor, including both epithelial and mesenchymal components, which can make MBC challenging to diagnose.

MBC is often more aggressive than other types of breast cancer and is commonly diagnosed at a higher grade and larger tumor size.

It is frequently triple-negative, meaning it lacks estrogen receptors, progesterone receptors, and HER2 expression, which limits the availability of targeted treatment options. As a result, metaplastic breast cancer may have a poorer prognosis and requires ongoing research to improve therapeutic strategies.

9. Medullary Carcinoma

The term medullary carcinoma (MC) is most commonly used to describe medullary thyroid carcinoma (MTC), a rare thyroid cancer that arises from parafollicular C cells, which produce calcitonin.

MTC is generally more aggressive than other thyroid cancers and may be treated with surgery, targeted therapy, and, in selected cases, chemotherapy. It is more aggressive than papillary or follicular thyroid carcinomas; however, early detection significantly improves prognosis.

In contrast, medullary carcinoma of the breast is a distinct and rare subtype of invasive breast cancer. These tumors are typically soft and fleshy in appearance, frequently triple-negative, and often associated with BRCA1 mutations.

Despite their high-grade histological features, medullary breast carcinomas are generally associated with a relatively favorable prognosis compared with other triple-negative breast cancers.

Related Article: Invasive Breast Cancer

Rare Type of Breast Cancer

Learn about rare types of breast cancer, including inflammatory, metaplastic, Paget’s disease, phyllodes tumors, and angiosarcoma.