Introduction
Definition and Overview
Metaplastic carcinoma, also known as metaplastic breast cancer, is a rare and serious form of breast cancer that affects less than 1% of all females assigned at birth (FAAB).1 Inside the tumour, the presence of both glandular (ductal or lobular) and non-glandular (metaplastic) components differentiates it.1 Huvos et al. characterized metaplastic carcinoma of the breast (MCB) as mammary cancer with mixed epithelial and sarcomatoid components in 1973.2
The presence of cells that have converted from their normal glandular shape to a non-glandular form is referred to as the metaplastic component of metaplastic carcinoma. Non-glandular cells may resemble squamous cells (those found on the skin's surface) or mesenchymal cells (those that give rise to connective tissue).1
Importance of radiation therapy
Because of the disease's rarity, treatment for metaplastic breast carcinoma is somewhat unclear, however, studies show that excision of the tumor plus adjuvant radiation therapy provides the most effect.2
Understanding metaplastic carcinoma
Definition and characteristics
Metaplastic carcinoma of the breast is a rare but aggressive kind of breast cancer recognised by the World Health Organization as a distinct pathologic entity. It is distinguished morphologically by the development of neoplastic epithelium into squamous cells and/or mesenchymal-looking features (squamous cells, spindle cells, cartilage or bone, and so on).2
On mammography, it looks a lot like invasive ductal carcinoma and benign lesions, which confuses the diagnosis even more.2 Breast metaplastic carcinomas are distinguished by enormous tumour size and fast development, and they are often oestrogen receptor, progesterone receptor, and HER2/neu negative. Axillary lymph node involvement ranges from 8% to 40% of patients.2,3
Types and prevalence
Pure metaplastic carcinoma and mixed metaplastic carcinoma are two kinds of metaplastic carcinoma. Pure metaplastic carcinoma is made up solely of metaplastic components and lacks invasive ductal or lobular carcinoma. Mixed metaplastic carcinoma, on the other hand, consists of both metaplastic and conventional invasive carcinoma components.3,4
Metaplastic carcinoma has a low prevalence, accounting for fewer than 1% of all diagnosed breast malignancies. Pure metaplastic carcinoma is less common than mixed metaplastic carcinoma among the various subtypes. MBC is an uncommon kind of breast cancer that accounts for around 0.25%1.00% of all breast cancers.3
Risk factors
The greatest major risk factor for breast cancer, including metaplastic carcinoma, is FAAB. Breast cancer risk, particularly metaplastic carcinoma, rises with age, especially after menopause. A family history of breast cancer, particularly with mutations in the BRCA1 or BRCA2 genes, raises the risk. The majority of occurrences of metaplastic carcinoma, however, are not connected to specific inherited genetic abnormalities.
Certain benign breast disorders, such as atypical hyperplasia or lobular carcinoma in situ (LCIS), might increase the risk.
Factors that enhance lifelong oestrogen exposure, such as early menstruation, late menopause, and never having children or having them at an advanced age, have been linked to an increased risk of breast cancer.4
Radiation therapy in cancer treatment
Explanation and objectives
Radiation is a physical agent used to kill cancer cells.1,3 Ionising radiation is employed because it produces ions (electrically charged particles) and deposits energy in the cells of the tissues it passes through. This deposited energy has the potential to damage cancer cells or create genetic alterations that result in cancer cell death. High-energy radiation destroys cells' genetic material (deoxyribonucleic acid, DNA), preventing them from dividing and proliferating further.1,3
Although radiation causes harm to both normal and cancer cells, radiation treatment tries to increase radiation dosage to aberrant cancer cells while reducing exposure to normal cells close to or in the path of radiation. Typical cells can generally mend themselves faster and maintain their regular function better than malignant cells. Cancer cells in general are less effective than normal cells at repairing radiation-induced damage, resulting in differential cancer cell death.5
Types and mechanisms
There are two methods for delivering radiation to the site of the tumour: external and internal radiation.
External beam radiation is supplied from outside the body by directing high-energy rays (photons, protons, or particle radiation) at the tumour's site. In the clinical context, this is the most prevalent strategy.
Internal radiation, also known as brachytherapy, is given from within the body via radioactive sources sealed in catheters or seeds and supplied directly to the tumour location. Based on its short-term benefits, this is commonly employed in the usual treatment of gynaecological and prostate cancers, as well as in circumstances where retreatment is necessary.5
Role of radiation therapy in metaplastic carcinoma treatment
Benefits and considerations
Benefits of radiation therapy include the following:
While metaplastic carcinoma is more aggressive in general, it still responds to typical breast cancer therapies such as surgery, radiation therapy, and chemotherapy. The treatment technique is adapted to the individual's particular condition as well as the tumour's features.
Metaplastic carcinoma's histological variety allows for more accurate diagnosis and categorization, which can assist in guiding therapy options and perhaps predict prognosis.
Although metaplastic carcinoma is uncommon, improved awareness among healthcare workers can lead to early discovery and rapid beginning of appropriate therapy, boosting the odds of a positive outcome. Metaplastic carcinoma, being a less frequent subtype, provides an opportunity for research and clinical trials aimed at developing more focused and effective therapies.3
Considerations include the following:
Aggressive Behaviour: Metaplastic carcinoma is frequently more aggressive than other subtypes of breast cancer, which means it may occur at a later stage and has a higher risk of spreading. As a result, early detection and intervention are crucial.
Targeted Therapies are Limited: Because metaplastic carcinoma is frequently triple-negative, missing hormone receptors (ER, PR) and HER2 amplification, targeted therapies that are successful against other subtypes of breast cancer are limited.
Diverse Treatment Strategies: Because metaplastic carcinoma is histologically diverse, the treatment plan may necessitate a multidisciplinary approach involving surgeons, medical oncologists, radiation oncologists, and pathologists to tailor the therapy to the specific subtype and individual characteristics.4
Effectiveness and integration with other treatments
Radiation can be used to cure patients as well as as a highly effective palliative therapy to reduce cancer-related symptoms. Radiation therapy may also be used in conjunction with other treatment techniques such as surgery, chemotherapy, or immunotherapy. Radiation will seek to reduce the tumour if given before surgery (neoadjuvant treatment). Radiation, when administered after surgery (adjuvant treatment), destroys tiny tumour cells that may have been left behind. Tumours range in their sensitivity to radiation therapy, as is well documented.5
Radiation therapy techniques for metaplastic carcinoma4
Image-guided radiation therapy (IGRT)
The likelihood of missing tumours, owing to organ motion and patient setup differences, increases as treatment margins get narrower and more conformal. When essential tissues are adjacent to the tumour, a little positioning mistake may result in unintentional radiation to normal organs.
Image-guided radiation therapy (IGRT) detects such inaccuracies using information obtained from pre-radiotherapy imaging, allowing for rectification. One such example is the acquisition of daily cone-beam computed tomography (CBCT) images before each treatment. Because of the enhanced precision, dosage escalation is now possible, which has improved the therapeutic ratio for various tumour locations, including head and neck cancers and prostate cancers.4
Brachytherapy
Brachytherapy is a type of radiation therapy that involves placing a radioactive source directly inside or very close to the tumour. The term "brachy" is derived from the Greek word meaning "short," indicating the short distance between the radiation source and the target tissue. This technique allows for the delivery of a high dose of radiation to the tumour while sparing surrounding healthy tissues.
Types of brachytherapy
Intracavitary brachytherapy
In this type of brachytherapy, a radioactive source is placed inside a body cavity, such as the uterus (intracavitary brachytherapy for gynaecological cancers) or the oesophagus (intracavitary brachytherapy for esophageal cancers). This approach is commonly used for treating cancers in hollow organs.
Interstitial brachytherapy
Interstitial brachytherapy involves placing radioactive sources directly into the tumour tissue, typically using needles, catheters, or seeds. It is frequently used for the treatment of prostate cancer, breast cancer, and other solid tumours.
Intraluminal brachytherapy
Intraluminal brachytherapy is used for treating cancers within the body's hollow structures, such as the bronchi (intraluminal brachytherapy for lung cancer) or the bile ducts (intraluminal brachytherapy for bile duct cancer).
Surface brachytherapy
In surface brachytherapy, the radioactive source is applied directly to the skin or mucosal surface to treat skin cancers or cancers of the oral cavity, vagina, or rectum.5
Dosimetry and planning techniques in brachytherapy
Dosimetry in brachytherapy involves determining the optimal distribution of radiation dose within the target volume while minimising radiation exposure to nearby healthy tissues. The goal is to deliver a high dose to the tumour while sparing surrounding organs and structures.6
Treatment planning
Treatment planning for brachytherapy is a complex process that requires specialised software and expertise. It begins with obtaining detailed imaging, such as MRI, CT scans, or ultrasound, to visualise the tumour and surrounding structures. These images are used to create a three-dimensional (3D) model of the patient's anatomy.
Dose optimisation
The radiation oncologist, medical physicist, and dosimetrist work together to design a treatment plan that optimises the dose distribution. They consider factors such as tumour size, shape, and location, as well as the type and strength of the radioactive source.
Dose prescription
The prescription dose is the target radiation dose that needs to be delivered to the tumour. It is based on the tumour type, stage, and treatment goals. The prescription dose and the dose constraints for nearby critical structures are determined during treatment planning.
Applicator placement
For certain types of brachytherapy, applicators (catheters, needles, or other devices) are placed precisely into or near the tumour using imaging guidance. The radioactive sources are then inserted into these applicators to deliver the prescribed dose.
Treatment delivery
Brachytherapy treatments can be delivered in various ways, depending on the technique used. Some treatments may involve a one-time procedure, while others may require multiple sessions over several days.6
Safety and side effects of radiation therapy
Overview of potential side effects
Side effects of radiotherapy are classified as acute (early), consequential, or late effects on normal tissues over time. Acute radiation toxicity is seen within a few weeks after treatment and usually involves intermitotic cells in the skin and mucosa. Consequential effects are seen when acute complications are not treated and cause persistent damage. Late complications emerge months to years after exposure and usually involve postmitotic cells (liver, kidney, heart, muscle, and bone).6
Management and long-term effects
The management of long-term effects of radiation therapy is crucial to ensure the best possible quality of life for cancer survivors. While many side effects of radiation therapy resolve shortly after treatment, some can persist or develop years later. Here are some common long-term side effects and strategies for their management:
Skin changes
Long-term skin changes, such as increased pigmentation, skin thinning, or fibrosis, may occur in the treated area. Regular skin care with mild soaps and moisturisers can help keep the skin hydrated and reduce discomfort. Avoiding sun exposure and using sunscreen are also essential to protect sensitive skin.
Lymphedema
Radiation therapy can damage the lymphatic system, leading to swelling (lymphedema) in the affected limb, particularly after treatment for breast or head and neck cancer. Managing lymphedema involves specialised therapies, such as manual lymph drainage, compression garments, exercise, and skincare. Physical therapy and regular monitoring can help prevent and manage lymphedema.
Fatigue
Cancer survivors may experience persistent fatigue even after completing radiation therapy. Maintaining a balanced lifestyle, including regular physical activity, proper nutrition, and adequate rest, can help manage fatigue. Discussing ongoing fatigue with healthcare providers may also lead to identifying and addressing any underlying issues.
Bone health
Radiation therapy can weaken bones in the treated area, increasing the risk of fractures. Adequate calcium and vitamin D intake, weight-bearing exercises, and avoiding smoking and excessive alcohol consumption can promote bone health. Bone density tests and medication may be recommended if bone health is a concern.
Cardiovascular issues
In cases where radiation therapy involves the chest region, there is a risk of long-term cardiovascular effects, such as coronary artery disease or heart valve problems. Regular cardiovascular check-ups and adopting a heart-healthy lifestyle can help mitigate these risks.
Secondary cancers
While radiation therapy is aimed at treating the primary cancer, there is a small risk of developing secondary cancers in the long term. Regular cancer screenings and discussions with healthcare providers about potential risks and benefits of follow-up care are essential for early detection and appropriate management.
Emotional and psychological support
Living with the long-term effects of radiation therapy can have a significant emotional and psychological impact on cancer survivors. Support groups, counselling, or therapy can provide coping strategies and emotional support to address the challenges associated with long-term side effects.
Regular follow-up
Regular follow-up visits with oncologists and other healthcare providers are crucial for monitoring and managing long-term side effects. The healthcare team will tailor the follow-up schedule based on individual needs and the specific cancer treatment history.1,2
It's essential for cancer survivors to communicate openly with their healthcare providers about any ongoing side effects or concerns. A survivorship care plan, which includes a summary of treatments received and a plan for long-term follow-up care, can help guide survivors and healthcare providers in managing the potential long-term effects of radiation therapy effectively.
Summary
Radiotherapy is a vital component in the management of metaplastic carcinoma, a rare and aggressive subtype of breast cancer. Often used as an adjuvant treatment after surgery, it aims to eradicate remaining cancer cells and minimise local recurrence. The radiation oncologist carefully plans the treatment, ensuring precise targeting of the tumour while sparing healthy tissues. Commonly delivered through external beam radiation, radiotherapy may cause short-term side effects such as skin changes and fatigue. A multidisciplinary approach involving surgical and medical oncologists is crucial to tailor treatment and optimise outcomes, while regular follow-up enables monitoring for treatment efficacy and potential complications.
References
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- McKinnon E, Xiao P. Metaplastic Carcinoma of the Breast. Archives of Pathology & Laboratory Medicine. 2015 Jun 1;139(6):819–22. [accessed 18 Jul 2023] Available from: http://meridian.allenpress.com/aplm/article/139/6/819/65591/Metaplastic-Carcinoma-of-the-Breast
- Qiu Y, Chen Y, Zhu L, Chen H, Dai Y, Bao B, et al. Differences of Clinicopathological Features between Metaplastic Breast Carcinoma and Nonspecific Invasive Breast Carcinoma and Prognostic Profile of Metaplastic Breast Carcinoma. The Breast Journal. 2022 Aug 22;2022:e2500594. [accessed 18 Jul 2023] Available from: https://www.hindawi.com/journals/tbj/2022/2500594/
- Catroppo JF, Lara JF. Metastatic metaplastic carcinoma of the breast (MCB): An uncharacteristic pattern of presentation with clinicopathologic correlation. Diagn Cytopathol. 2001 Nov;25(5):285–91. [accessed 18 Jul 2023] Available from: https://onlinelibrary.wiley.com/doi/10.1002/dc.2056
- Baskar R, Lee KA, Yeo R, Yeoh K-W. Cancer and Radiation Therapy: Current Advances and Future Directions. Int J Med Sci. 2012 Feb 27;9(3):193–9. [accessed 18 Jul 2023] Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3298009/
- Wilson JM, Dearnaley DP, Syndikus I, Khoo V, Birtle A, Bloomfield D, et al. The Efficacy and Safety of Conventional and Hypofractionated High-Dose Radiation Therapy for Prostate Cancer in an Elderly Population: A Subgroup Analysis of the CHHiP Trial. International Journal of Radiation Oncology*Biology*Physics. 2018 Apr 1;100(5):1179–89. [accessed 18 Jul 2023] Available from: https://www.sciencedirect.com/science/article/pii/S0360301618300543
