Primary Neuroendocrine Cancers of the breast (NECB) are rare, with an incidence of less than 5% of all breast cancers. They are usually diagnosed during tests or following surgery for breast cancer.
The breast may also be a secondary site – where Neuroendocrine Cancer has spread from somewhere else in the body.
Vital to confirming diagnosis is accurate, expert histopathology review.
World Health Organisation (2012) classifies 3 subtypes:
- Well-differentiated neuroendocrine tumour (NET)
- Poorly differentiated neuroendocrine carcinomas or small-cell carcinomas (NEC)
- Invasive breast carcinomas with neuroendocrine differentiation – this is different to both NET and NEC.
There are no current standardised guidelines for treatment, but there is an agreement that care should be individualised and specialist opinion sought.
Causes and potential risk factors for Neuroendocrine Cancer
We do not know exactly what causes Neuroendocrine Cancer – however it is important to follow advice in leading a healthy lifestyle: eat healthily, exercise and avoid smoking and too much alcohol.
Most Neuroendocrine Cancers do not run in families; however, a number of rare conditions may increase the risk of them developing. Therefore, if other members of the family have been diagnosed with cancer, or have a known genetic condition, it is important that you tell your specialist team about not only your personal medical history, but also any family medical illnesses or conditions.
Most cases of breast cancer do not run in families, but genes known as BRCA1 and BRCA2 can increase your risk of developing both breast and ovarian cancer.
The genes TP53 and CHEK2, are also associated with an increased risk of breast cancer.
We recommend speaking to your GP, and specialist team, if Breast or Ovarian Cancer runs in your family. They may refer you for an NHS genetic test, which will tell you if you have inherited one of the cancer-risk genes.
Neuroendocrine Cancer of the Breast is very rare – and may not be associated with the above mentioned genetic alterations. However, if there is a strong family history of Breast, Ovarian or Neuroendocrine Cancer or you do have a genetic alteration this may help inform your care and ensure follow up is appropriate for you.
Symptoms that may or may not include Neuroendocrine Cancer associated syndromesSymptoms that may or may not include Neuroendocrine Cancer associated syndromes(a syndrome is where 2 or more related symptoms occur).
Neuroendocrine Cancer of the breast is uncommon and usually only discovered during tests or treatments for suspected breast cancer or other condition. Therefore symptoms, if they do occur, would be similar to those for suspected breast cancer:
- A change in the size or shape of one or both breasts
- Discharge from either of your nipples, which may be streaked with blood
- A lump or swelling in either of your armpits
- Dimpling on the skin of your breasts
- A rash on or around your nipple
- A change in the appearance of your nipple, such as becoming sunken into your breast
Breast pain is not a common symptom of breast cancer.
Neuroendocrine Cancer of the Breast is rarely associated with a Neuroendocrine associated syndrome.
Other, rarer symptoms, including Paraneoplastic syndrome and oncological emergencies, (a specific set of health concerns that can occur in any cancer), such as raised calcium levels (Hypercalcaemia), may occur.
Further information about Neuroendocrine Cancer associated and Paraneoplastic Syndromes – including Oncological emergencies – can be found here.
Tests that may be used for the diagnosis and / or monitoring of Neuroendocrine Cancer of the Breast.
Blood and / or urine:
Full blood count
Liver and kidney function
Breast cancer genetics
Urinary or serum 5HiAA (serotonin).
Breast +/- axilla (armpit) ultrasound scan
CT or MRI breast
If further disease (spread) or a different primary site is suspected:
CT chest & abdomen and / or CT chest & MRI abdomen
Bone scintigraphy – if bone metastases (spread) is suspected
Octreotide (SPECT) or Gallium-Dotatate PET/CT.
Pathology (what can be seen through special tests under a microscope):
Differentiation and cellular morphology
The key aim of treatment, should be to help you have the best possible care and quality of life – by ensuring access to appropriate treatment, management of symptoms and addressing what’s most important to you
Treatment options will depend on the type, position and size of your cancer – and whether (and to where) it has spread.
It will also depend on whether you have any other health concerns and / or illnesses and your general health and fitness.
One or more of the approaches below may be suggested:
Control of your disease, by slowing or stopping further growth and / or spread
Palliation, or easing, of any symptoms you may be experiencing.
Monitoring through clinic review, bloods and scans, can be used to assess how well treatment is working or in periods between treatments (which may be months/years).
As not everyone will need to be on treatment – surveillance can be used to check your cancer and general health for any signs of change that may mean that a treatment might need to be considered. All treatments have possible side-effects, therefore, it is important to know when treatment may be helpful for you or not.
To remove, partially remove or bypass neuroendocrine cancer and / or secondary sites of disease (metastases).
Breast conserving surgery: (also called a lumpectomy, quadrantectomy, partial or segmental mastectomy) where only the part of the breast containing the cancer is removed as well as some surrounding normal tissue. How much breast is removed depends on where and how big the tumour is, as well as other factors.
Mastectomy is a surgery in which the whole breast is removed, including all of the breast tissue and sometimes other nearby tissues. Some people may need a double mastectomy, in which both breasts are removed.
Surgery may also be done to:
- Find out whether the cancer has spread to the lymph nodes under the arm (sentinel lymph node biopsy or axillary lymph node dissection).
- Restore the breast’s shape after the cancer is removed (breast reconstruction)
- Relieve symptoms of advanced cancer.
Chemotherapy can be given orally (in tablets) or Intravenously (through a vein) to slow tumour growth or try to reduce tumour size. This may be the first line therapy in high grade disease – particularly “poorly-differentiated’ NEC or in combination with other treatments. Chemotherapy may also be used to increase tumour cell sensitivity to radiation therapies.
Targeted Molecular Therapies:
Can be given orally (in tablets) or IV (through a vein) to slow tumour growth or try to reduce tumour size
Is sometimes given to the breast / chest wall / armpit area after surgery to kill any cancer cells that might remain there. It may also be used for cancer that has spread beyond the breast in particular if disease has spread to the bones – here it is used to help control growth of any spread and alleviate bone pain
Peptide receptor radionuclide therapy (PRRT):
May also be called Radioligand Therapy – uses targeted radiation to treat neuroendocrine cancer cells. Can be used in some patients who have had a ‘positive’ Octeotide or Gallium scan (‘receptor positive’ disease).
Clinical research and safe new treatment development is essential to provide best care for those with Neuroendocrine Cancer – we need to know that treatments not only work but work safely. There are several phases of trial therapy. Each trial will have specific criteria in regards to patient suitability – this can be discussed with your clinical team. You do not have take part in a trial – participation is voluntary.
Managing symptoms, including pain, is an important part of total care – and therefore occurs throughout care, not just at ‘end-of-life’. Symptom control or ‘palliation’ refers to what is used to alleviate or reduce the impact your cancer, other health issues and /or treatments may be having on you and your physical and mental health. It can include anything from simple medication and / or a combination of some of the treatments mentioned above to counselling and practical support.
There are expert agreed guidelines regarding how and when follow up should occur, however, in practice this varies and often with good reason. Follow up should be expert informed & evidence /research based but also tailored to you and what is appropriate for your best care.
Following treatment for early breast cancer:
- Annual breast screen for 5 years after treatment – with regular breast clinic review every 3 – 4 months for first 2 years, then every 6 months for years 3 – 5
- After 5 years: if 50 or older – NHS Breast Screening Programme timings. If under 50, annual breast screening until you reach 50, then follow NHS Breast Screening programme.
- Those with early invasive breast cancer do not routinely undergo tests for cancer elsewhere in the body unless they have symptoms of possible disease spread
- Women who have a high risk of developing breast cancer due to family history (including genetic mutations) may be offered additional screening, depending on their age and level of risk.
Neuroendocrine Cancer of the breast can spread to multiple sites, even after routine follow up is completed, therefore longer-term follow up is recommended.
Advice re Neuroendocrine Cancer of the Breast: follow both NHS Breast Screening programme and Neuroendocrine Cancer surveillance as per grading and differentiation (NET or NEC) :
*Grade 1-2 (Ki67 <20%) NET:
- R0 resection – complete removal, no lymph node or distant metastases – contrast CT chest/abdo post surgery then follow NHS Breast Screening Programme.
- R1 or where there is evidence of lymph node +/- distant metastases – longer term follow up recommended, to include annual CT.
*G3 (Ki67 >20%) NET or NEC:
- R0 resection – complete removal, no lymph node or distant metastases – contrast CT chest/abdo 3 months post surgery, then follow National Breast Screening Programme.
- R1 or where there is evidence of lymph node +/- distant metastases – longer term follow up recommended, to include annual CT : n.b. every 2-3 months if on therapy.
- Biochemistry may be used as a surrogate marker in Primary Breast NEN.
- Biopsy is recommended in metachronous disease – especially if there has been a long disease-free interval.
Follow up as per guidelines – but should be guided by prognosis, expected treatment efficacy and treatment related toxicity. Your health, well-being, physical activity, informed choice and preference for ongoing care as well as aim of treatment should be reviewed and discussed to best plan care.
Secondary Breast Neuroendocrine Cancer should be followed up as per primary site guidelines.