Introduction to metaplastic breast carcinoma

Definition and characteristics

Metaplastic breast carcinoma (MpBC) is the medical term for a fast-growing breast cancer in the epithelium. The World Health Organization Classification (WHO) grades tumours low-grade, intermediate or high grade, depending on their cellular characteristics. Low-grade tumours are cancer cells that grow at a slower rate and look similar to normal cells under the microscope, or high-grade tumours with cells that appear very different to normal cells and grow at a quicker rate.

High-grade tumours are invasive cancers that have the potential to invade other parts of the body.⁷ Compared to other breast cancers, MpBC is more likely to spread or metastasize aggressively, frequently moving to the lungs, bone and liver. Many breast cancer cells have receptors for hormones like oestrogen, progesterone, or human epidermal growth factor receptor 2 (HER2) that can signal for cell growth.

However, metaplastic breast cancer is triple negative; it does not have these receptors making it difficult to detect them early on⁴ and treat due to a lack of response to hormonal therapies. 

Prevalence and incidence

MpBC is a rare type of cancer that accounts for less than 1% of breast cancers and plays a significant role in the global breast cancer death rate. Due to its rarity, the data and research are quite limited. The American Cancer Research Publication estimated that incidence rates for metaplastic breast cancer have been rising by roughly 0.5% annually.

This increase is most likely caused by declining fertility rate and the rising age of those assigned female at birth (AFAB) having their first child. As it mostly originates from breast tissues, it is more common in those AFAB than in those assigned male at birth (AMAB). 

97,790 AFAB and 2,800 AMAB in the United States have been diagnosed with invasive breast cancer. In the UK, there has been 8,000 new cases in 2023 alone. Including skin cancer, breast cancer is the most prevalent cancer in those AFAB in the US. In 2020, there were 2,261,419 new cases of breast cancer among people AFAB worldwide.¹

Understanding chemotherapy

Definition and purpose

Chemotherapy is a cancer treatment that uses drugs to reduce or stop the growth of cancer cells. It is regarded as a systemic therapy as it travels through the bloodstream, across the whole body. Chemotherapy is a key form of treatment administered for many types of cancers.

Many chemotherapy drugs target mechanisms of cell replication making them effective as cancer cells multiply and proliferate quicker than normal and healthy cells.⁶ These drugs, however, are potent and harm healthy cells as well, particularly cells that grow and divide quickly. The main purpose of chemotherapy is to treat and manage cancer, and in rare cases, cure cancer.

This includes controlling the growth and spread of cancer cells, alleviating symptoms associated with cancer (such as pain and bleeding), and decreasing the likelihood of a relapse after initial treatment.⁶

Role of chemotherapy in cancer treatment

The roles of chemotherapy in cancer treatment include:

• Neoadjuvant chemotherapy - initial form of treatment to reduce the size of tumours before surgery or radiation therapy
• Adjuvant chemotherapy - eliminate any cancer cells that could still be present after radiation treatment or surgery
• Palliative chemotherapy - no longer a cure, but to alleviate pain and improve quality of life
• Make other therapies more effective
• Rid your body of cancer cells that have returned or expanded (metastasised) to other areas²

Chemotherapy approaches

Chemotherapy is used to treat breast cancer in all stages in a variety of ways. The characteristics of breast cancer, your medical history, and your personal preferences all play a role in whether or not the doctor advises chemotherapy. The approaches are divided mainly into neoadjuvant chemotherapy, adjuvant chemotherapy and palliative chemotherapy. During the course of treatment, patients mostly undergo a combination of chemotherapy approaches.

Neoadjuvant chemotherapy

This is chemotherapy given before surgery for early-stage MpBC metaplastic breast cancer.

Chemotherapy is used prior to surgery to reduce big tumours, giving the surgeon the best opportunity of entirely eliminate them. It helps to make the surgery less invasive. Early-stage MpBC includes Ductal Carcinoma in Situ (stage 0), stage I, stages IIA and IIB, and stage IIIA. Using neoadjuvant chemotherapy across these stages is helpful as it allows the doctor to see if the breast cancer responds to the chemotherapy medicines or if a change in medication is required.³

Adjuvant chemotherapy

This is chemotherapy given after surgery for early-stage MpBC. It is administered to eliminate any cancer cells that may have been left behind or that have spread to other parts of the body. These single cells, or groupings of two or three cells, are so tiny that they do not show up on imaging tests. Chemotherapy following surgery lowers the likelihood of the cancer returning, also known as recurrence.³

Palliative chemotherapy

This chemotherapy approach is commonly seen in advanced-stage MpBC. At this stage, the likelihood of recovery can be low. A combination of chemotherapy is given to help improve the patient’s quality of life by relieving the symptoms or side effects of chemotherapeutic drugs. They also help to manage the spread of the disease. However, it is not a treatment for long-term benefits.³

Chemotherapeutic agents 

These drugs are able to target and kill cancer cells and are classified based on their mechanism of action. There are 10 types of chemotherapeutic agents such as anthracyclines, taxanes and alkylating agents.

Anthracyclines and taxanes are the most active drugs in first-line treatment, and they can be administered as single agents or as part of combination regimens. While combination therapy boosts response rates, it also increases side effects and do not give a survival benefit over single medicines. Furthermore, single-agent chemotherapy allows the administration of adjuvant chemotherapy following initial treatment to slow the progression of secondary growths or when the initial treatment no longer affects the tumour burden.

In accordance with worldwide standards, Taxanes is used as a single-agent chemotherapy being the first treatment of choice for the majority of patients. However, combinations such as anthracyclines with cyclophosphamide or platins with taxanes are viable alternatives for patients with a high disease burden or who exhibit symptoms. 

Anthracyclines

Named examples of these drugs include doxorubicin and epirubicin. They are a form of incredibly strong antibiotics derived from Streptomyces bacteria. Their mechanism of action is by interfering with the activity of topoisomerase II and stopping DNA replication within the cell. 

Taxanes

Examples of this drug type include paclitaxel and docetaxel. This chemotherapeutic agent causes cell death through the disruption of microtubule structures like mitotic spindles and prevents mitosis. 

Other drugs

Examples are Fluorouracil/capecitabine, eribulin, cisplatin/carboplatin, vinorelbine, and ixabepilone. These drugs are suitable for patients who have tumour progression during anthracycline and taxane treatment, or for those who cannot take anthracyclines or taxanes. Capecitabine is appealing to people who want to avoid numerous injections since it can be taken by mouth.

Individualised treatment

Factors influencing chemotherapy selection

There are so many factors that can influence what chemotherapeutic approach a patient needs, these factors include results of tumour genetic testing, size and stage of the cancer, patients health and medical history as well as their preferences in terms of the treatment plan and response to current treatments especially side effects.⁵ 

Multimodal therapy considerations

Chemotherapy isn’t the only option and there is the option of the multidisciplinary approach when deciding on a treatment plan. The utilisation of surgery, radiation or hormonal therapy can be considered to be used in conjunction with chemotherapy. 

Response assessment and monitoring

Imaging techniques

Imaging techniques commonly used are:

• Mammography
• CT(computed tomography) scan
• Breast ultrasound
• MRI(Magnetic Resonance Imaging)

Biomarkers

Abnormal values in biomarkers such as ER/PR Hormone Receptors, cytokeratins, ki-67, p53 and p63 help in the diagnosis of metaplastic breast cancer.

Side effects and management

Common side effects

Due to the non-selective nature of chemotherapy, there are off-target effects that can cause both long-term and short-term side effects. Short-term side effects go away once the drug is metabolised out of the body, such as fatigue, nausea, vomiting and diarrhoea. Long-term side effects, however, remain with the patients and require further treatment, if available.

Long-term side effects of chemotherapy include infertility, bone weakening, heart disease or leukaemia. 

Infertility

Some chemotherapy drugs, especially alkylating agents, affect the ovaries ability to release eggs for menstruation or produce oestrogen. This is called primary ovarian insufficiency (POI) and may be a temporary state or result in permanent infertility. Fertility treatments, such as IVF, are an option for AFAB to get pregnant.

Chemotherapy also affects sperm cells due to their ability to quickly replicate. If all of the immature sperm cells, known as spermatogonial stem cells, are destroyed and unable to produce mature sperm cells, it might result in lifelong infertility.² However, for some AMAB, their fertility returns after a couple of years with a low sperm count. 

Bone weakening and loss

Women who experience menopause prematurely as a result of chemotherapy are more likely to develop osteopenia and osteoporosis, two disorders in which bone density is lower than usual.

Heart disease

Adriamycin (doxorubicin) and Doxil (doxorubicin) are examples of anthracycline chemotherapy medications, which can have toxic effects on the heart. Doctors are likely to recommend ongoing heart monitoring for people who have received an anthracycline or other chemotherapy medicines that can damage the heart. Learn more about the heart problems chemotherapy may cause.

Leukaemia

In rare cases, chemotherapy for breast cancer can lead to secondary cancer, such as leukaemia (cancer of the blood cells), years after chemotherapy is completed.²

Supportive care

Cancer may be a major burden for the patient, family, and friends. It might lead to emotional and practical problems. It is frequently beneficial to discuss feelings or other concerns with a skilled counsellor or therapist. They can seek this type of assistance at any stage of their condition.

A counsellor might be referred by the hospital doctor, specialty nurse, or general practitioner.

It might also be beneficial if they speak with someone who has gone through the same experience. Many breast cancer charities include helplines and online forums, and staff may also refer to appropriate resources.⁶

Summary

Although it is potentially known to have toxic side effects, Chemotherapy has been the major treatment for metaplastic breast cancer for many years. However, due to its rarity, there needs to be more clinical research to develop a targeted therapy medication that is less toxic. This will improve treatment outcomes in forthcoming years.