Neuroendocrine Breast Cancer (NECB)

Neuroendocrine breast cancer (NECB), also known as mammary neuroendocrine tumours (NETs), are a very rare type of cancer that develops in the breast, a glandular organ situated over the ribcage. While men and women both have breasts, the anatomy of the breast is slightly different between the sexes.

Breasts in females are functional organs that are used to produce milk during and after pregnancy. Female breasts are primarily made up of lobes, lobules, and ducts, which are surrounded by fatty and connective tissue. Each breast is divided into 12-20 sections called lobes.  Each lobe is made up of lobules that produce breast milk, which is then sent to the ducts. The ducts in the breasts carry milk to the nipple to be fed to babies.

In males, the breast is a non-functional organ that cannot produce milk. Unlike female breasts, male breasts do not generally contain lobes and lobules. Ducts are present in male breasts, however they do not have a function.

Neuroendocrine cancers are a complex group of tumours that develop in the neuroendocrine system, which is responsible for regulating important bodily functions such as heart rate, blood pressure and metabolism. They most commonly develop in the gastro-intestinal tract, pancreas, and the lungs; however, they can develop anywhere in the body. These tumours develop from neuroendocrine cells, which are responsible for receiving signals from the nervous system and producing hormones and peptides (small proteins) in response.

NECBs are more common in women, and tend to be diagnosed over the age of 50. However, anyone can develop this disease.

Types of Neuroendocrine Breast Cancer

NECB can be categorised into three main subtypes based on cell type and behaviour.

Well-Differentiated Neuroendocrine Tumour of the Breast

Well-differentiated neuroendocrine tumours of the breast are a rare type of cancer that are characterised by relatively ‘normal looking’ cells under the microscope. These tumours are often categorised as low-grade (slow growing), however can metastasise if left untreated.

Neuroendocrine Carcinomas of the Breast

Neuroendocrine carcinomas of the breast are a rare type of cancer that are characterised by abnormal looking cancer cells under the microscope. There are two primary subtypes of this disease.

Small Cell Carcinoma of the Breast

Small cell carcinoma of the breast is a very rare form of cancer that is often classified as a type of extrapulmonary small cell lung cancer, as the cells present are identical under a microscope. Unfortunately, small cell carcinomas of the breast are often aggressive, and may not have as good of a prognosis as other types of breast cancers.

Large Cell Carcinoma of the Breast

Large cell carcinomas of the breast are a very rare form of cancer that is often associated with large cell undifferentiated carcinoma of the lungs. Unfortunately, large cell carcinomas of the breast are often aggressive, and may not have as good of a prognosis as other types of breast cancers.

Invasive Breast Cancers of No Special Type (IBC-NST) with Neuroendocrine Differentiation

Invasive breast cancers of no special type (IBC-NST) with neuroendocrine differentiation are a rare subtype of breast cancer that encompasses various types of invasive breast cancers that have features of neuroendocrine tumours. Because of how rare this subtype is, there has been limited research done into the behaviour and prognosis of this disease.

Treatment

If a NECB is detected, it will be staged and graded based on size, metastasis, and how the cancer cells look under the microscope. Staging and grading helps your doctors determine the best treatment for you.

Cancers can be staged using the TNM staging system:

  • T (tumour) indicates the size and depth of the tumour.
  • N (node) indicates whether the cancer has spread to nearby lymph nodes.
  • M (metastasis) indicates whether the cancer has spread to other parts of the body.

This system can also be used in combination with a numerical value, from stage 0-IV:

  • Stage 0: this stage describes cancer cells in the place of origin (or ‘in situ’) that have not spread to nearby tissue.
  • Stage I: cancer cells have begun to spread to nearby tissue. It is not deeply embedded into nearby tissue and had not spread to lymph nodes. This stage is also known as early-stage cancer.
  • Stage II: cancer cells have grown deeper into nearby tissue. Lymph nodes may or may not be affected. This is also known as localised cancer.
  • Stage III: the cancer has become larger and has grown deeper into nearby tissue. Lymph nodes are generally affected at this stage. This is also known as localised cancer.
  • Stage IV: the cancer has spread to other tissues and organs in the body. This is also known as advanced or metastatic cancer.

Cancers can also be graded based on the rate of growth and how likely they are to spread:

  • Grade I: cancer cells present as slightly abnormal and are usually slow growing. This is also known as a low-grade tumour.
  • Grade II: cancer cells present as abnormal and grow faster than grade-I tumours. This is also known as an intermediate-grade tumour.
  • Grade III: cancer cells present as very abnormal and grow quickly. This is also known as a high-grade tumour.

Once your tumour has been staged and graded, your doctor may recommend genetic testing, which analyses your tumour DNA and can help determine which treatment has the greatest chance of success. This is often performed after a biopsy, and can help guide treatment options for you.

Treatment is dependent on several factors, including location, stage of disease and overall health.

Treatment options for NECB may include:

  • Surgery, potentially including:
    • Lumpectomy, also known as breast-conserving surgery.
    • Unilateral or bilateral mastectomy.
    • Breast reconstruction.
    • Lymphadenectomy.
  • Radiation therapy, potentially including peptide receptor radionuclide therapy (PRRT).
  • Chemotherapy.
  • Hormone therapy.
  • Somatostatin analogues (SSAs).
  • Clinical trials.
  • Palliative care.

Breastfeeding and Breast Cancer Treatment

Treatment for NECB may affect your ability to breastfeed. If this is a concern to you, discuss your options with your doctor prior to the commencement of treatment.

Risk factors

Because of how rare NECBs are, there has been little research done into the risk factors of this disease.

Symptoms

Some patients with NECB will appear asymptomatic in the early stages of disease. As the tumour progresses, some of the following symptoms may appear:

  • A lump or lumpiness in the breast(s).
  • A change in the size and/or shape of the breast.
  • Swollen breasts.
  • Changes to the nipple, potentially including:
    • Changes in shape.
    • Crusting, sores and/or ulcers.
    • Unusual redness.
    • Pain.
    • Clear or bloody discharge.
    • Inverted nipple (nipple turns inward when it used to face outward).
  • Dimpling or indentation on the skin of the breast.
  • A rash and/or itchiness of the breast.
  • A scaly appearance and/or changes in the colour of the breast.
  • Swelling or discomfort in the armpit or near the collarbone.
  • Persistent, unusual pain not associated with the menstrual cycle.
  • Carcinoid syndrome (rare), which carries its own set of symptoms:
    • Facial flushing (usually red or purple in the face, neck, and/or upper chest).
    • Diarrhoea.
    • Wheezing.
    • Abdominal pain.
    • Carcinoid heart disease (plaques on the heart muscle caused by excess hormone production).
    • Faecal urgency.
    • Fatigue.
    • Skin changes, such as red or purple spots on the face, neck, and/or upper chest.
  • Paraneoplastic syndromes (rare).
  • Hypercalcaemia (rare).

Not everyone with the symptoms above will have cancer, but see your general practitioner (GP) if you are concerned.

Diagnosis

If your doctor suspects you have a NECB, they may order the following tests to confirm the diagnosis and refer you to a specialist for treatment:

  • Physical examination.
  • Imaging tests, potentially including:
    • Mammogram.
    • Ultrasound.
    • MRI (magnetic resonance imaging).
    • CT (computed tomography) scan.
  • Blood tests.
  • Biopsy.

References

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