Introduction

The term “breast cancer” does not refer to just one disease, but is an umbrella term for multiple types of cancers of the breast.¹ Amongst these, one very rare type is known as secretory carcinoma of the breast (SBC) — defined by a specific genetic mutation fusing two genes, resulting in an abnormal protein being made. ‘Secretory’ refers to the secretions within and outside of the cancer cells that can be seen under a microscope.

SBC accounts for fewer than 0.15% of breast cancer cases. It is also worth noting that SBC can be found in both individuals assigned male at birth (AMAB) and ones assigned female at birth (AFAB).³ It has previously been referred to as “juvenile” breast carcinoma as this form of cancer can often occur in younger patients, although this term is no longer used.² This article aims to provide an overview of secretory carcinoma of the breast. 

SBC, because it is so rare, can be misdiagnosed for other types of breast cancer. It is important to understand SBC for the sake of awareness and also for correct diagnosis and treatment outcomes. Understanding the pathology can help to aid research and development of treatment options also.³ 

Clinical presentation

Signs and symptoms

Most cases of SBC are unilateral but in rare cases they are bilateral.¹ The most common presentation for SBC is a painless, firm, slow-growing mass in the breast. In some cases, the axillary (underarm) lymph nodes were also enlarged and palpable.³

Diagnostic methods

Actual diagnosis of cancer is confirmed by taking a biopsy, which is a small sample of the affected tissue and examining it under a microscope. In the case of SBC, this can be done by a fine needle aspirate (FNA) or a needle biopsy which is a sample taken by a syringe. The cells in the sample are then tested in a laboratory.⁴

Imaging techniques

Imaging techniques are used for determining the size, location and presence of any distant metastases of the tumour. Different types of imaging include:

• Ultrasound scans
• CT scans
• Magnetic resonance imaging MRIs 

Imaging is also an essential part of planning for surgery.⁴

Pathology and molecular features

Histopathological characteristics

SBC is characterised by specific histopathological features (i.e. features that can be seen when looking at the cells under a microscope) that differentiate it from other breast cancers. SBC exhibits a cribriform or microcystic architecture (small cyst-like bumps within the tumour), similar to secretory carcinoma of the salivary glands. A hallmark feature is the presence of intracellular and extracellular secretions, showing up as space around the cells. The cells also had small to medium-sized round nuclei, which can be seen to be slowly dividing (indicating a slow-growing tumour).⁵

Immunohistochemistry and biomarkers

Immunohistochemistry (i.e using different stains and chemicals on the cell sample in a lab to determine whether certain proteins or other biomarkers are present) plays a crucial role as part of the diagnosis of SBC - the main biomarkers being S-100 and EMA (epithelial membrane antigen) Both of which are commonly found in SBC. Importantly, the identification of the ETV6-NTRK3 fusion gene through molecular testing is a key diagnostic marker, distinguishing SBC from other breast cancer subtypes.⁵

Genetic mutations and alterations

The characterising feature of SBC is a particular genetic mutation on chromosomes 12 and 15 which results in a fusion between the ETV6 and NTRK3 proteins. This particular genetic mutation is present in a pathologically similar secretory carcinoma of the salivary gland. The ETV6-NTRK3 protein is involved with activating a pathway that causes cell proliferation (at an abnormally high rate) and also allows cancer to escape the immune system response.⁵ 

Treatment options

Treatment options will vary from case to case and will be dependent on multiple factors. However, most treatment options will include one or more of the following modalities.

Surgery

Surgery is the mainstay of treatment. The type of surgery will be determined by the size of the tumour. This can be a:

• Lumpectomy (i.e removing just the tumour, conserving the breast) in the case of a well-defined tumour
• Simple mastectomy (removal of the affected breast)
• Radical mastectomy (removal of the affected breast plus the axillary (underarm) lymph nodes on that side)^3,6

Axillary node clearance is recommended in those who have larger tumours- with one study noting that 30% of patients with tumours over 2cm have had cancer detected in underarm lymph nodes.¹

Adjuvant therapies

This refers to chemotherapy either after surgery, or potentially radiation therapy to kill any remaining cancer cells that may not have been removed by surgery. In many instances, it is not necessary especially where the tumour is well-defined and straightforward to remove, but in cases where there may be metastases, especially distant, neoadjuvant chemotherapy can be given.^7,8

Targeted therapies

A well-known example of targeted therapy for breast cancer is herceptin for HER2-positive tumours. However, as SBC is a triple negative tumour, targeted therapies are not generally part of treatment. There is some potential with immunotherapies, which could target the ETV6-NTRK3 protein, but more research needs to be done in this area before it is actually viable.⁶

Prognosis and survival rates

Prognostic factors

There are three different receptors (small proteins on the outer surface of cells) which are used to categorise malignant tumours of the breast:

• Oestrogen receptor (ER) 
• Human epidermal growth factor receptor (HER2)
• Progesterone receptor (PR) 

The term “triple positive” refers to when the cancer cells contain all three of the aforementioned receptors, and conversely “triple negative”, refers to when none of the receptors are present. SBC is triple negative, and although with other breast cancers, this would be a poor prognostic factor (as there are effective treatments which target each of the receptors).However, in the case of SBC this is not so as SBC has a very favourable prognosis and low recurrence rates, even with lymph node metastases.^1,2

Survival rates and outlook

Survival rates are over 95% for SBC over 5 years, one of the highest for breast cancers.⁵ This therefore gives a very positive outlook for those who are diagnosed. 

Follow-up and surveillance

Monitoring and check-ups

Regular follow-up is necessary for those who have undergone treatment for breast cancer, to monitor recurrence. Check-ups with the doctor for examination of the breasts and to see generally how the patient is doing can be done every few months but reduced in frequency as time goes on. Breast implants can be provided as part of post-cancer treatment to restore the appearance in the case of a mastectomy.

Imaging and lab tests

Imaging mainly involves mammography (an x-ray of the breasts) every year for 5 years after treatment and then every other afterwards (for those who have had a single mastectomy, the x-ray is of the remaining breast). MRIs and blood tests to search for any signs of recurrence are not recommended as they do not add any further value that a mammography would give.¹⁰

Managing recurrence and metastasis

SBC generally has a very low rate of recurrence. There are however very rare instances, mostly those with multiple distant metastases where SBC has proven to be fatal, despite surgery and neoadjuvant chemotherapy.⁸ 

Patient support and coping

Emotional support and counselling

The diagnosis of cancer as well as the emotional and physical toll of the treatment involved can be a very challenging time for patients. It is important to consult with the medical team involved as they may be able to signpost towards charities or services which are geared towards patients with cancer. Cancer Research UK has a page here which signposts towards mental health services and gives advice for those with cancer at all stages of the process. 

Support groups and resources

This is not an exhaustive list of resources, and each country/region will have their own groups, however, the Cancer Research UK website is one good source of information on cancer with links to resources. Some I have listed below:

• Rare Cancer Alliance which can offer support to those with rare cancers
• Cancer 52 is a group of organisations which advocate for those with rare cancers
• Macmillan is also a leading charity in the UK which provides services for those with cancer  

Lifestyle modifications

Obesity and smoking are known risk factors for breast cancer generally. However, for SBC specifically, as it is such a rare cancer, it is not actually proven as to whether or not these influence the risk. Nonetheless, ensuring a healthy body weight and not smoking are certainly beneficial.⁶

FAQs

How rare is bilateral breast cancer?

Bilateral breast cancer (BBC) is also a rare type of breast cancer and affects only between 1.2% to 12% of patients suffering from breast cancer.¹¹

What are the 4 types of breast lumps?

The lumps in the breasts are most commonly diagnosed as either fibroadenomas or cysts. Other diagnoses may include breast cancer and other benign conditions.¹²

Does carcinoma mean malignant?

Yes, carcinoma is a malignant cancer that arises from the epithelial cell layers.¹³

Summary

In summary, secretory carcinoma of the breast is a very rare type of breast cancer. In most cases, it is treated with surgery as a primary modality. It has a very good long-term prognosis with over 95% 5-year survival.