Pregnancy And Metaplastic Carcinoma

Introduction

Breast cancer 

Breast cancer is a complex disease where abnormal cell growth leads to the formation of lumps or masses in the breast, known as tumours. If untreated, these tumours can spread from the breast to the lymph nodes or other parts of the body and become life-threatening. Sometimes, women can develop breast cancer during pregnancy or after giving birth, which adds extra difficulties.

Metaplastic carcinoma in pregnancy

Metaplastic breast cancer (MpBC) is a rare form of breast cancer characterised by distinct features that require specialised treatment approaches. Metaplasia, or "change in form" in Greek, underlies the development of MpBC when cells or tissues transform after their formation. Dealing with this cancer is already challenging, and when it's diagnosed during pregnancy, it becomes even more complicated to manage.¹   

Breast cancer in pregnancy

Incidence and diagnosis challenges

Breast cancer during pregnancy, although rare in general (1 in 3,000), is the most commonly diagnosed cancer during this critical time. It typically affects women between the ages of 32 to 38 years, making those diagnosed notably younger than non-pregnant women with the condition. Breast cancer is frequently detected during the second and third trimesters.

Diagnosing breast cancer during pregnancy poses significant obstacles for both the patient and the medical team involved. Often, the diagnosis is delayed due to physiological changes and other minor pregnancy-related conditions that can mask symptoms or signs of breast cancer.

Hormonal fluctuations during pregnancy, nursing, or shortly after giving birth can lead to changes in the breasts. These changes may include enlargement, increased tenderness, and the formation of lumps. Hormonal changes may make it difficult for you or your doctor to detect small lumps until they have significantly grown in size. Additionally, the breast tissue may become denser, further complicating the detection of breast cancer through mammography.

Impact of pregnancy on prognosis and treatment

There is still no definite answer on how breast cancer affects women during and after pregnancy. Some studies show similar survival rates to non-pregnant women, while others suggest a potentially worse prognosis for pregnant women with breast cancer.^2,3 The different conclusions in the studies may be because there is no agreement among experts on how long the postpartum period should be, and this can affect the results they find.

Breast cancer during pregnancy can complicate treatment decisions, but there are safe and effective options available. A study conducted by the International Network on Cancer, Infertility, and Pregnancy (INCIP) involving 1,170 patients over 20 years showed that 67% of patients received cancer treatment during pregnancy.⁴

Careful planning with the medical team is essential to balance cancer treatment and protect the baby. Factors can influence timing and type of treatment, like

• Tumour size
• Pregnancy stage
• Overall health
• Personal preferences

Metaplastic carcinoma overview

Definition and classification

MpBC is a rare and aggressive form of cancer, making up about 0.2% to 5% of all breast cancers. This type of carcinoma is categorised into two main groups based on the tumour's characteristics: pure epithelial and mixed epithelial and mesenchymal groups.

Unique features and subtypes

This unique subtype of cancer is classified by the World Health Organization (WHO) under various subtypes, including:

• Mixed metaplastic carcinoma
• Low-grade adenosquamous carcinoma
• Squamous cell carcinoma
• Fibromatosis-like carcinoma
• Spindle cell carcinoma  
• Metaplastic carcinoma with mesenchymal differentiation

Except for fibromatosis-like carcinoma and low-grade adenosquamous carcinoma, all other metaplastic variants show aggressive behaviour, are resistant to chemotherapy, and have a high chance of spreading to other parts of the body.⁵   

Metaplastic tumours tend to be larger and have a higher grade (tumour cells appear more abnormal under a microscope and have a greater tendency to grow and spread rapidly) compared to other types of breast tumours that are more commonly seen. It is usually a triple-negative breast cancer, which means that the cancer cells do not have receptors for estrogen (ER), progesterone (PR), and human epidermal growth factor 2 (HER2).

Hormone therapy and anti-HER2 drugs are not effective treatments for these women. A study showed that patients diagnosed with stage I-III MpBC had lower survival rates after five years compared to patients with invasive ductal carcinoma (IDC) of the breast (78% vs 93%). Hence, women with MpBC may encounter obstacles in terms of long-term survival.⁶   

Diagnosis and characteristics

MpBC is difficult to treat due to its aggressive behaviour and the presence of various cell types in the tumour. Doctors use imaging techniques like mammography, ultrasound, and magnetic resonance imaging (MRI) to assess the size, location, and characteristics of breast lesions.

To confirm the diagnosis, a tissue sample is taken from the breast lesion using a needle biopsy. The sample is then examined to check how it looks and if contains specific markers or substances which are important for the diagnosis.

A pathologist examining metaplastic carcinoma under a microscope may observe a mixture of different cell types, including spindle cells, squamous cells, chondroid cells, or osseous (bone-like) cells and the absence of the typical glandular components found in other types of breast cancer. To confirm the diagnosis of metaplastic carcinoma and differentiate it from other types of breast cancer, doctors may also use immunohistochemical staining. This involves looking for specific markers in the tissue sample such as high-molecular-weight cytokeratins and p63 proteins.⁷ 

Epidemiology and risk factors

Incidence during pregnancy

Cancer in expectant mothers occurs in about 1 out of every 1,000 pregnancies, with breast cancer being the most common type. The reported occurrence of breast cancer during pregnancy is 1 in 3,000 pregnancies. MpBC is rare, accounting for only 0.2-5% of all breast cancer cases, but it has the poorest prognosis compared to other types. Sadly, MpBC remains a significant contributor to breast cancer-related deaths worldwide.⁵ The exact incidence of metaplastic carcinoma during pregnancy is not well-documented in the literature. The rarety of metaplastic carcinoma and the infrequency of breast cancer during pregnancy means that the possibility of suffering from metaplastic carcinoma during pregnancy is uncommon. 

Known risk factors

Pregnancy-associated breast cancer (PABC) refers to cancer diagnosed during pregnancy and/or the time after childbirth (postpartum period). There are several factors linked to the development of PABC. Some of these factors include:

• Having a history of breast cancer in the family
• Starting menstruation at an early age
• Having inherited gene mutations such as  BRCA1 and BRCA2
• Getting pregnant at an older age
• Not breastfeeding enough or not at all
• Having an abnormal body mass index (BMI)

Many studies have shown or suggested that these characteristics can increase the risk of developing PABC.⁷ 

The risk of breast cancer during the postpartum period is influenced by factors such as maternal age, family history and total number of pregnancies. Family history and advanced maternal age act synergistically to increase the risk. Women who have given birth to one child experience a temporary rise in risk that reaches its highest point five years after the first delivery. On the other hand, those who have given birth to two children experience a lesser degree of risk, which peaks at three years after childbirth. Having a family history of breast cancer exacerbates the transient increase in breast cancer incidence after childbirth.  Women aged 30 or older at the time of their first birth, with a family history, experience a three-fold increased risk of breast cancer, which persists for 20-30 years after childbirth.⁸

Clinical presentation and diagnosis

Symptoms and signs

Most people do not experience noticeable symptoms in the early stages of breast cancer. The American Cancer Society emphasizes that regular mammograms are the most effective way to detect breast cancer in its early stages, even before symptoms are noticeable. It's important to remember that although mammograms are reliable, they may not detect every single case of breast cancer. That's why it is crucial to pay attention to any changes in your breasts, as you have the best understanding of your own body.

The first symptom of breast cancer that most women notice is a new lump or mass (although most breast lumps are not cancer) or an area of thickened tissue or swelling near your breast or under your arm.  Other possible symptoms may include

• Changes in the size or shape of your breast
• Nipple or breast pain, tenderness, or aching
• Nipple discharge (often bloody) in one breast
• Nipple retraction, where the nipple turns inward or pulls back into the breast
• Changes in the texture of the skin of your breast, areola, or nipple, such as itching or scaliness (like eczema)
• Changes in the appearance of the skin of your breast, areola, or nipple, such as dimpling, puckering, or changes in colour 

While these symptoms can be caused by various health conditions if you experience any of these symptoms it is important to visit a doctor.

Imaging and biopsy techniques

The first test pregnant women have is an ultrasound scan that uses sound waves to look inside the breast. Mammograms (an X-ray picture of the breast) are generally safe and effective for detecting breast cancer during pregnancy. If a mammogram is needed, a lead shield is used to protect the baby from radiation. 

While, CT (Computerized Tomography) scans,  bone scans, and PET (Positron Emission Tomography) scans are not recommended for pregnant patients due to radiation exposure. MRI (Magnetic resonance imaging), a radiation-free imaging technique, is also not recommended during pregnancy due to the potentially harmful effects of the contrast material used (gadolinium). Gadolinium can cross the placenta and cause fetal abnormalities in lab animals, posing a potential risk to the developing baby.

A biopsy is the definitive diagnostic procedure used to ascertain whether the suspicious area is cancerous or not. There are different types of biopsis.  The core-needle biopsy is the most commonly performed biopsy during pregnancy. It uses a slightly wider needle (compared to fine needle aspiration) to remove a small amount of suspicious breast tissue. Local anaesthesia is given to numb the breast during the procedure.

In cases where core biopsy results are inconclusive, a surgical biopsy is done to remove a tissue sample or the entire lump under local or general anaesthesia. Surgical biopsy is particularly useful for deep-seated lumps Waiting for biopsy results can be an emotionally difficult time.  However, pregnant women can take comfort in knowing their doctor will be there to provide support and guidance.

Treatment considerations

Multidisciplinary approach

Breast cancer treatment is possible during pregnancy and should be carefully planned and discussed by a team of medical experts to determine the optimal treatment approach.

This team of healthcare professionals typically includes a surgeon, an oncologist (cancer doctor), an obstetrician, specialized nurses, a midwife, a neonatal doctor (specialist in newborn care) and other professionals such as psychologists and dieticians. Together, they will create a treatment plan to prioritise the best and safest care for both the pregnant patients and the baby.

Surgical and adjuvant therapy options

Surgery to treat breast cancer is possible during all stages of pregnancy, and it is generally  safe.⁹  No evidence suggests that the anaesthesia used during surgery causes birth defects in humans. However, it's important to note that surgery during pregnancy does carry some risks, such as the possibility of preterm delivery, miscarriage, or fetal distress. These risks are typically low for non-abdominal surgeries. The most important factor for ensuring the well-being of the baby is providing proper care to the mother throughout the entire surgical process.¹⁰ 

The need for additional treatments like chemotherapy, radiation therapy, hormone therapy, immunotherapy and targeted therapy after surgery may vary depending on the stage of the cancer. These treatments, known as adjuvant treatment, are given to keep cancer from returning. In certain situations, these treatments are postponed until after delivery.

Chemotherapy is typically avoided during the first trimester of pregnancy due to limited safety data and the increased risk of miscarriage. Instead, in most cases, chemotherapy administration is delayed until the second trimester, as certain chemodrugs are safer for the baby's health during this stage of pregnancy. Additionally, chemotherapy is avoided in the last 3-4 weeks before delivery to reduce the risks of bleeding and infection during childbirth.

Radiotherapy is generally not recommended during pregnancy, as the high doses used can harm the baby. If required, utmost care is taken to protect the child’s well-being. Otherwise, is postponed until after giving birth.

Hormone therapy, immunotherapy, and targeted treatments are not recommended during pregnancy as they can potentially affect the baby. These treatments are also postponed until after the woman has given birth. Immunotherapy and targeted therapies are newer treatments and evidence on how they might affect the developing baby is lacking.

Balancing maternal and fetal well being

When the health of the pregnant woman and the well-being of the baby conflict with each other, finding a balanced approach between maternal and baby well-being becomes a complex decision. The medical team determines the best solution for the health of both the mother and the baby by carefully evaluating the risks and benefits, the stage and aggressiveness of cancer and how far along the pregnancy is. It is usually not recommended to end the pregnancy if breast cancer is found unless delaying therapy poses significant risks to the mother’s health.¹¹

Summary

Breast cancer is a disease where cells in the breast undergo uncontrolled growth.  When breast cancer happens during pregnancy or shortly after giving birth, it presents additional challenges. Its diagnosis is often delayed due to pregnancy-related changes that can mask symptoms. Factors such as the stage of pregnancy, tumour characteristics, and patient preferences are thoroughly evaluated. In making decisions, the well-being of both the mother and the baby remains the primary concern. Surgery is generally considered safe, while chemotherapy is typically delayed until the second trimester. Radiation and other therapies are postponed until after birth. An expert team will work together to secure the best outcomes for both the pregnant patient and their baby in managing breast cancer during your pregnancy.