Introduction to metaplastic carcinoma

Metaplastic breast cancer (MpBC or MBC) is a rare and advanced form of breast cancer. It is usually seen as a mass or lump of cells multiplying quickly in the breast. It is therapeutically challenging and aggressive. It is characterised by the presence of glandular and non-glandular tissue within the tumour. This type of breast cancer carries the worst prognosis with a high risk of recurrence.³

Metaplastic carcinoma is a type of breast cancer that is typically rare and marked for less than 5%. It occurs in people more than 50 years of age and is most commonly seen in Hispanic or black people assigned female at birth.1 In 2019, around 9,525 deaths were recorded in England due to breast cancer, and the majority of the cases were metastatic.²

Subtypes of metaplastic carcinoma

There is minimal to no relation between the subtype to the prognosis of the metaplastic carcinoma. WHO classification of Breast tumours has classified MBC as Low-grade and High-Grade carcinomas.⁴

Low Grade Carcinoma:

1. Adenosquamous carcinoma
2. Fibromatosis like MBC

High Grade Carcinoma:

1. Squamous cell carcinoma
2. Spindle cell carcinoma
3. MBC with heterologous mesenchymal differentiation

In addition, a mixed subtype is a combination of more than one subtype.

Due to low incidence and huge pathological variation, optimal treatment strategies are unknown. 

This type of cancer is so rare that there were very few clinical trials conducted for the disease. Based on the current treatment guidelines, MBC is treated similarly to Breast cancer. Most of the metaplastic breast carcinomas are triple negative (TNBC), which means that the tumour cells don’t have receptors for estrogen, progesterone or HER2. Due to the absence of these receptors, drugs targeting these features, like hormonal therapy or targeted therapy, are not helpful. Other treatments like surgery, radiotherapy or chemotherapy are recommended based on the metastasis (spread) of the cancer cells to the adjacent organs.⁵

Surgical approaches

Principles of surgical management

Surgical treatment for MBC  is similar to the most common form of breast cancer, invasive ductal carcinoma (IDC). IDC treatment shifted to breast conservation therapy for some patients after a clinical trial. However, due to larger tumour sizes, many MBC patients still get a mastectomy instead of a lumpectomy.

Despite the tumour size, some MBC patients can still receive breast conservation therapy. Studies found no difference in overall survival whether MBC patients got a mastectomy or lumpectomy.

Lymph node staging for MBC is changing, similar to IDC. A less invasive method called sentinel lymph node biopsy is commonly used. But whether completion lymph node removal is needed for MBC patients with sentinel lymph node involvement is still uncertain.

Patient selection and assessment

When diagnosing metaplastic carcinoma, doctors need to confirm the type of breast cancer accurately. They look at the size, location and extent of the tumour to determine the best treatment approach. Checking the lymph nodes is also crucial to understanding the stage of the cancer. Knowing the hormone receptor and HER2 status helps doctors choose the right therapies. Sometimes, patients might need chemotherapy before surgery to shrink the tumour. The patient's overall health and preferences are important factors in deciding the treatment plan. A team of specialists, including surgeons, oncologists, and pathologists, works together to provide the best care. If available, participating in clinical trials can offer access to new treatments. The patient should be well-informed and involved in decision-making throughout the process.

Primary tumour resection techniques

Lumpectomy (Breast-conserving surgery)

Breast-conserving surgery is a treatment performed in cases with early cancer or for women with a lump.^20,21,22 It is a procedure where only part of the breast that has cancer is removed, and most of the breast or healthy tissue is saved. Depending on the location, size and other breast factors, how much of the breast can be removed is determined. It is also called lumpectomy or partial mastectomy. Usually, the surgery is combined with radiation. Radiation therapy after surgery destroys cancer cells that may still be in the breast. If no cancer cells are found near the surgical tissue, the pathologist denotes a negative/clear margin. If cancer cells are found at the edges, it is a positive margin or close margin, where the patient might undergo a second surgery or mastectomy.^{15,17,18,19,20,21}

Mastectomy (Breast removal surgery)

Mastectomy is a surgery for the removal of the whole breast. It is the recommended therapy when patients are sensitive to radiation therapy or if the tumour size is too large and the breast can’t be saved. Depending on the cancer, surgery could be the removal of one breast (unilateral or single mastectomy) or both breasts (bilateral or double mastectomy). Other types of Mastectomy include skin-sparing, nipple-sparing, radical or modified radical mastectomy.²³ Patients undergoing these types of surgeries are recommended for the option of Breast reconstruction after the surgery to restore the shape of the breasts. Patients who choose not to have breast reconstruction surgery can wear a breast prosthesis to have the shape of the breasts under their clothes.^{16,17,18,19,20,21,22}

Axillary lymph node evaluation

The presence of lymph node metastasis and the number of positive lymph nodes determine the stage of breast cancer and affect overall recurrence and survival rates. In all cases of invasive breast cancer, axillary surgery should be performed to evaluate the lymph nodes and remove any cancer cells. The nodal status guides the treatment of the carcinoma.

Axillary lymph node dissection

Axillary surgery, also known as axillary dissection, removes cancerous lymph nodes found in the armpit region. This type of procedure is performed less frequently as it involves complications like infection of the armpit or fluid accumulation around the armpit, or lymphedema.²⁵

Sentinel lymph node biopsy

For women with early-stage breast cancer and no clinical signs of lymph node involvement, the initial approach is to perform a sentinel lymph node biopsy (SLNB). This procedure is widely accepted as a reliable method to assess the lymph nodes and determine if cancer has spread. It is considered an accurate way of determining the stage of the disease.²⁴

Reconstruction options

Overview of reconstructive techniques

Breast reconstructive surgeries restore the shape and appearance of the breast after lumpectomy or mastectomy. These techniques aim to help women regain their self-esteem and quality of life by providing a sense of wholeness and symmetry. There are several breast reconstructive options available, and the choice of technique depends on individual preferences, medical history, and the extent of breast tissue removal.^14,15

1. Implant-Based Reconstruction: involves placing a silicone or saline breast implant under the chest muscle or skin to recreate the breast mound. Implant-based reconstruction is typically a staged procedure and may require tissue expanders to gradually stretch the skin before the final implant is inserted
2. Autologous (Flap) Reconstruction: Tissue usually from the abdomen, back, or buttocks is used to create the new breast mound
3. Mixed reconstruction: Surgery that uses both implant-based and autologous methods to build the new breast mound

Depending on the subtype of cancer, how much of the breast has been removed and if any follow-up treatment is required after surgery, reconstruction could be immediate or delayed.¹⁵

These reconstruction surgeries create a smooth breast mound with no nipple. New nipples can be created from other body tissues, like during an autologous reconstruction surgery. Alternatively, nipples can be tattooed on or tailor-made stick-on nipples can be created.

Considerations for metaplastic carcinoma

Breast reconstruction considerations are multifaceted and require a tailored approach. A team of healthcare professionals decide the optimal timing and type of reconstruction based on the patient's tumour extent, medical history, and treatment plan. Options include implant-based or autologous reconstruction. The availability of tissues for autologous reconstruction may be affected by prior treatments. Emotional support is crucial for patients facing these decisions, and the impact of reconstruction on cancer treatment effectiveness is carefully evaluated.^5,14,15

Benefits and risks of different options

Though the breast reconstruction is to make a breast similar in size and shape to your original breast, It has risks along with the benefits.^26,27

Benefits: 

• Implants offer a wide range of sizes and shapes to achieve the desired breast appearance
• Shorter surgery with less recovery time is required
• It eliminates the need for a prosthesis
• Do not require harvesting the tissue from another part of the body
• Autologous reconstruction has longer results when compared to the implants

Risks: 

• Implant rupture or infection
• Additional surgeries might be needed for implant replacement.
• Surgical complications

Adjuvant therapies and considerations

Role of adjuvant therapies

If the cancer has spread to other organs beyond the breast, adjuvant therapy is considered and is usually recommended after the surgery. These treatments reduce the risk of breast cancer returning in the same breasts or developing in the other breasts or spreading somewhere else in the body.^5,10

Radiation therapy considerations

Radiation therapy for the treatment of metaplastic carcinoma is not well studied. In a study, it was found that regardless of the type of surgery, adjuvant radiation therapy improved overall survival for all MBC patients. Radiation therapy for breast cancer involves different techniques to deliver the most effective and precise treatment. Your doctors and radiation oncologist work together to choose the best approach for you. Rapidly growing cells are more prone to X-rays compared to normal cells. Radiation therapy may be delivered through either external or internal radiation. External Radiation is the most common radiation therapy in which the machine delivers rays/radiation from outside your body to the breast. In Internal radiation, the surgeon inserts radioactive material into your body to target cancer cells. Brachytherapy is a type of internal radiation, a device is placed inside the body during or after the surgery.^5,9,10,11,12

Systemic therapies (chemotherapy, targeted therapy, immunotherapy)

Systemic therapy refers to cancer treatments that are administered throughout the entire body to target cancer cells that may have spread beyond the primary tumour. Unlike local treatments such as surgery and radiation, which target specific areas, systemic therapy circulates throughout the bloodstream to reach cancer cells in various parts of the body.

There are different types of systemic therapy used in cancer treatment^{5,10,11,12,13,14,15}

1. Chemotherapy: It uses drugs to kill or slow the growth of cancer cells. Anthracycline-containing combinations, such as epirubicin or doxorubicin, followed by taxanes such as paclitaxel or docetaxel often used in both early-stage and advanced breast cancer cases
2. Hormone Therapy: This treatment is used for hormone receptor-positive cancers by blocking hormones or inhibiting their effects on cancer cells. Treatment includes endocrine therapy with Tamoxifen, Aromatase inhibitors, and Ovarian suppression (reduces estrogen production)
3. Targeted Therapy: These drugs specifically target certain molecules or proteins that are involved in cancer cell growth and survival. Trastuzumab is an option for HER2-positive patients and can be used alone or with chemotherapy. However, if there is cancer progression during adjuvant therapy or while receiving a combination of trastuzumab with chemotherapy, the treatment should be stopped
4. Immunotherapy: It stimulates the body's immune system to recognise and attack cancer cells and has shown promising results in various cancer types

Neoadjuvant therapy benefits

Treatment suggested before surgery to shrink the tumour is known as neoadjuvant therapy. This can make it possible for some to have less invasive surgery instead of removing the whole breast. Besides affecting surgery, it also helps doctors to see how well the tumour responds to the treatment.⁶

It allows doctors to evaluate how well the treatment is working by looking at the complete pathologic response, which can indicate how well the patient may survive. It also helps assess new treatments quickly and stop ineffective ones early, reducing side effects for patients. If the patient doesn't respond well to the treatment, doctors can adjust the dose or try a different drug to improve outcomes and reduce toxicity. Neoadjuvant chemotherapy allows personalised treatment and gives researchers a chance to study tumour samples before, during, and after treatment to understand how tumours behave.^7,8

Recurrence and metastatic disease

Local recurrence and treatment options

Although there is a chance that the cancer may come back, having a reconstructive surgery doesn’t change the chances of detecting it. Most local recurrences, if they happen, are usually felt as lumps in the skin or the tissue just under the skin.³ 

They can often be treated by surgically removing the affected area without needing to remove the rest of the reconstructed breast. Imaging the reconstructed breast routinely is not necessary, and most local relapses can be managed successfully with surgery and, if needed, radiation therapy to the remaining breast tissue. Sometimes, additional treatments like hormonal therapy or chemotherapy may be considered based on the characteristics of the tumour. 

The detection, treatment, and outlook for local recurrence after breast reconstruction are similar to those following a total mastectomy without reconstruction. Aggressive treatment can lead to positive outcomes, even if the cancer spreads to other areas of the body.^5,12

Management of metastatic disease

The location and extent of metastatic breast cancer, as well as the characteristics of the tumour, play a significant role in the long-term prognosis. Some patients can achieve complete remission and remain free of progression for many years, even up to 20 years. However, most patients with distant metastases are currently considered incurable. The average survival for metastatic breast cancer patients is around 2 to 3 years, but it can vary based on factors like the number of organs involved and hormone receptor status. Patients with low-volume metastases and hormone receptor-positive tumours tend to have longer survival. Those who achieve complete remission with chemotherapy also have better survival outcomes compared to those with hormone receptor-negative tumours or those who don't respond well to treatment.^10-15

Palliative care considerations

For patients who cannot be cured, palliative care plays an essential role in the management. The ultimate goal is to improve the quality of life, provide emotional support and address their physical and psychological needs.

1. Palliative care focuses on relieving symptoms as pain, fatigue, shortness of breath, and other discomforts
2. Dealing with cancer can be emotionally challenging for patients and their families. Palliative care teams provide counselling and guidance to cope with the condition
3. Palliative care teams work closely with the oncology team to ensure coordination of care and provide comprehensive support
4. For patients nearing the end of life due to the disease, End-of-life care provides comfort in pain management, emotional support, and helps patients and their families make decisions about care
5. Support for family caregivers also plays a crucial role by providing guidance and resources to help them manage their caregiving responsibilities and cope with the challenges they may face

Palliative care does not replace other cancer treatments but complements them to improve the patient’s overall well-being and quality of life.^12-15 

Postoperative care 

Wound care and monitoring 

The care you’ll receive after surgery will depend on your kind of treatment programme. Immediately after surgery, you may feel hazy and sluggish from the anaesthetic. Nurses will monitor you to make sure that you aren’t having any side effects while also keeping track of your blood pressure as well as checking the dressing on your surgery wound. 

Most people who have either a lumpectomy or a mastectomy can go home the same day. If you have reconstructive surgery at the same time, you may need to stay in the hospital for a couple of days after surgery. However, the majority of people are discharged from the hospital within 3 days.²⁸

Follow-up appointments are necessary to check for any signs of infection or necrosis of the surgery site, removal of stitches, as well as monitoring pain and bruising that come from the surgery.²⁸

Pain management 

After the surgery, you will experience pain and stiffness in your chest and shoulder areas and numbness and pain in your armpit area, depending on whether you’ve had a lymph node removed. To help with the pain, you will be given painkillers by IV infusion immediately after the surgery, as well as painkillers to take home with you that you can take whenever you feel the need to.²⁸

Rehabilitation and psychological support

Psychological assessments will be done before and after surgery to check your mental well-being. These can help find any psychological issues that could be linked with having surgery or cancer. Support is offered to help you overcome any issues, as well as routine follow-up checks after leaving the hospital. Physiotherapy programmes are also offered after leaving the hospital, which can help reduce recovery times and help you return to a normal day-to-day life.²⁸ 

Summary

Metaplastic carcinoma is a rare and aggressive type of breast cancer. This type of cancer is more common in older women. Metaplastic carcinoma may present as a lump or mass in the breast. Treatment typically involves a combination of surgery, radiation therapy and systemic therapies like chemotherapy or targeted therapy. However, the treatment approach may vary depending on the stage and characteristics of the tumour. Emotional support and palliative care also play a crucial role in the treatment plan to improve a patient's quality of life. Patients require specialised care from healthcare providers, including surgeons, oncologists and pathologists. If you notice any changes or abnormalities in your breasts, it's essential to seek medical attention promptly for evaluation and proper management.