What are the other Names for this Condition? (Also known as/Synonyms)

• Mammary Neuroendocrine Carcinoma
• NEC of Breast

What is Neuroendocrine Carcinoma of Breast? (Definition/Background Information)

• Breast cancer is the most common type of cancer diagnosed in women. It is a type of cancer in which certain cells in the breast become abnormal, grow uncontrollably, and form a malignant mass (tumor). There are various types of breast cancers
• Neuroendocrine Carcinoma of Breast is a rare subtype of invasive breast carcinoma that presents neuroendocrine differentiation when the tumor cells are observed under the microscope by a pathologist. This form of malignancy is generally observed in middle-aged and older adults
• Neuroendocrine carcinomas (NECs) are considered to be high-grade malignant tumors. Mammary NECs are histologically grouped into two subtypes:
  • Large-Cell Neuroendocrine Carcinoma (LCNEC) of Breast
  • Small-Cell Neuroendocrine Carcinoma (SCNEC) of Breast
• The cause of development of Neuroendocrine Carcinoma of Breast is not well-established. There is no association of NEC to smoking history in the individual. The signs and symptoms may include the presence of a mass in the breast, swelling or skin thickening around the region of the tumor mass, and changes in the breast profile. The complications may include the spread of cancer from the breast to other locations of the body
• The healthcare provider may use a combination of therapies that may include surgery, radiation therapy, and hormone therapy to treat Neuroendocrine Carcinoma of Breast, depending on the stage of the malignancy. The prognosis of NEC of Breast is generally guarded, since it is an aggressive type of tumor

Who gets Neuroendocrine Carcinoma of Breast? (Age and Sex Distribution)

• Neuroendocrine Carcinoma of Breast is very rare - SCNEC constitutes about 0.1% of all breast cancers, while LCNEC is extremely rare
• It is usually observed in women in the 43-70 years’ age group
• All racial and ethnic groups are affected, and no specific predilection is seen

What are the Risk Factors for Neuroendocrine Carcinoma of Breast? (Predisposing Factors)

The risk factors for Neuroendocrine Carcinoma of Breast are not well established since the condition is rare. Medical literature indicate that the malignancy is not associated with a smoking history of tobacco.

In general, the risk factors for developing breast cancer may include:

• Gender: Women have a higher risk for developing the condition than men
• Age: The risk increases for women over the age of 40 years
• History of breast cancer
• Family history of breast cancer: Women with a mother, sister, or daughter diagnosed with breast cancer have a higher risk of developing the condition
• Inherited gene mutations: Mutations in certain genes (BRCA1 or BRCA2), can lead to a much higher risk
• Radiation therapy: Receiving radiation therapy to the chest or breast area can also increase the risk
• Obesity: Being overweight or obese increases the risk after menopause
• Alcohol consumption
• Physical inactivity: A lack of physical exercise (leading a sedentary life) can increase the risk
• Breastfeeding: Not breastfeeding one's child can increase the risk for developing the condition

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Neuroendocrine Carcinoma of Breast? (Etiology)

The exact cause of development of Neuroendocrine Carcinoma of Breast is currently not well understood.

• Genetic alterations involving the TP53 and RB1 genes are reported for Small-Cell Neuroendocrine Carcinoma of Breast
• The involvement of specific genes and genetic mutations for Large-Cell Neuroendocrine Carcinoma of Breast is not established

What are the Signs and Symptoms of Neuroendocrine Carcinoma of Breast?

The signs and symptoms of Neuroendocrine Carcinoma of Breast are similar to those of invasive breast carcinomas and may include:

• Presence of a tumor mass in the breast or underarm area
• The size of the tumor may range from 1.3 to 5 cm (average size 2.6 cm)
• Thickening or swelling of part of the breast; change in the size or shape of the breast
• Inversion of the nipple (pulling-in of nipple into the breast)
• Bloody discharge from the nipple
• Changes to the skin covering the breast or nipple area, including dimpling, irritation, redness, scaling, peeling, or puckering
• In some cases, pain in the breast may be noted
• The condition can be unilateral (involving only one breast) or bilateral (affecting both the breasts)

How is Neuroendocrine Carcinoma of Breast Diagnosed?

Neuroendocrine Carcinoma of Breast may be diagnosed in the following manner:

• Complete physical examination with comprehensive medical and family history evaluation
• Breast exam to check for any lumps or unusual signs in the breasts
• Blood tests including complete blood count (CBC) test
• Mammogram: A mammogram uses X-rays to provide images of the breast
• Galactography: A mammography using a contrast solution, mostly used to analyze the reason behind a nipple discharge
• Breast ultrasound scan: Using high-frequency sound waves to produce images of the breast
• Computerized tomography (CT) or magnetic resonance imaging (MRI) scan of the breast
• Positron emission tomography (PET) scan to help determine, if the cancer has spread to other organ systems
• Breast biopsy:
  • A biopsy of the tumor is performed and sent to a laboratory for a pathological examination. A pathologist examines the biopsy under a microscope. After putting together clinical findings, special studies on tissues (if needed) and with microscope findings, the pathologist arrives at a definitive diagnosis. Examination of the biopsy under a microscope by a pathologist is considered to be gold standard in arriving at a conclusive diagnosis
  • Biopsy specimens are studied initially using Hematoxylin and Eosin staining. The pathologist then decides on additional studies depending on the clinical situation
  • Sometimes, the pathologist may perform additional studies, which may include immunohistochemical stains and molecular studies to assist in the diagnosis

Biopsies are the only methods used to determine whether an abnormality is benign or cancerous. These are performed by inserting a needle into a breast mass and removing cells or tissues, for further examination. There are different types of biopsies:

• Fine needle aspiration biopsy (FNAB) of breast mass: In this method, a very thin needle is used to remove a small amount of tissue
• Core needle biopsy of breast mass: A wider needle is used to withdraw a small cylinder of tissue from an abnormal area of the breast
• Open tissue biopsy of breast mass: A surgical procedure used less often than needle biopsies, it is used to remove a part or all of a breast lump for analysis

The differential diagnosis to exclude conditions with similar presentations include:

• Adenoid cystic carcinoma of breast
• Lymphoma of breast
• Malignant melanoma of breast
• Merkel cell carcinoma of breast
• Metastatic NEC from non-breast sites such as the lung

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Neuroendocrine Carcinoma of Breast?

The complications of Neuroendocrine Carcinoma of Breast may include:

• Emotional distress due to the presence of breast cancer
• Metastasis of the tumor to local and regional sites is commonly observed
• Recurrences following surgery may be observed; incompletely excised tumors may recur
• Treatment side effects

How is Neuroendocrine Carcinoma of Breast Treated?

Treatment options available for individuals with Neuroendocrine Carcinoma of Breast are dependent upon the following:

• Type of cancer
• The staging of the cancer: If a breast cancer is diagnosed, staging helps determine whether it has spread, and what treatment options are best-suited for the patient
• Whether the cancer cells are sensitive to certain particular hormones, and
• One’s personal preferences

Surgery: Surgery is generally the most common form of treatment involving the removal of the tumor. Various types of surgery to remove the malignant tumor include:

• Lumpectomy: Breast-sparing surgery (least invasive breast cancer surgery) in which the tumor, as well as a small portion of the surrounding tissue is removed
• Mastectomy: Surgery to remove all of the breast tissue; it may be simple (removal of the breast, nipple, areola, sentinel lymph nodes) or radical mastectomy (removal of the breast, nipple, areola, all axillary lymph nodes, and underlying muscle of the chest wall)
• Sentinel node biopsy: Procedure done to examine the “sentinel lymph node,” or lymph node(s) closest to the tumor, as this is the most likely location, where cancer cells may have spread to. This lymph node is removed and tested for cancerous cells
• Axillary node dissection: This procedure is performed to remove some axillary lymph nodes in the underarm area, to allow dissection and examination. This helps in establishing whether the cancer has spread to more than one lymph node

Other treatment options may include chemotherapy and radiation therapy.

• Radiotherapy can be used as primary therapy in situations where the tumor cannot be removed completely, or when the tumor reappears after surgery
• Radiotherapy can also be used as additional therapy after surgery, if there is a possibility of tumor recurrence after surgery, or if there are inadequate margins (possibility of tumor left behind) following surgery. In some cases, due to location of tumor, a complete surgical removal of the tumor is difficult
• Hormone therapy is given for women with hormone receptor-positive NECs

How can Neuroendocrine Carcinoma of Breast be Prevented?

Currently, no specific preventive measures are available for Neuroendocrine Carcinoma of Breast. In general, it is important to be aware of the following:

• Learning to do regular ‘breast self-exams’ in order to help identify any unusual lumps or signs in the breast
• Maintain a healthy body weight and exercise regularly
• Implement and follow a well-balanced diet; a high intake of fiber via fresh fruits and vegetables helps in a healthy lifestyle
• If taking alcohol, only drink in moderation; limit to one or (maximum) two drinks a day
• Limit combination hormone therapy used to treat symptoms of menopause. It is advised that individuals be aware of the potential benefits and risks of such hormonal medications
• Cancer screenings can help detect any breast cancer during the early stages

What is the Prognosis of Neuroendocrine Carcinoma of Breast? (Outcomes/Resolutions)

• Neuroendocrine Carcinoma of Breast is a rare form of breast cancer. The prognosis of the condition generally depends upon the stage of the tumor. However, according to medical literature, it has a worse prognosis compared to classical invasive carcinoma of breast
• Generally, individuals with neuroendocrine carcinomas have unfavorable prognosis. It is reported that nearly 40% of SCNEC of Breast present metastasis at the time of initial diagnosis; SCNEC has worse prognosis than LCNEC
• The prognosis of breast cancer, in general, depends upon a set of several factors that include: 
  • The grade of the breast tumor such as grade1, grade2, and grade 3. Grade1 indicates a well-defined tumor, whereas grade 3 indicates a poorly-defined tumor
  • The size of the breast tumor: Individuals with small-sized tumors fare better than those with large-sized tumors
  • Stage of breast cancer: With lower-stage tumors, when the tumor is confined to site of origin, the prognosis is usually excellent with appropriate therapy. In higher-stage tumors, such as tumors with metastasis, the prognosis is poor
  • Cell growth rate
  • Overall health of the individual: Individuals with overall excellent health have better prognosis compared with those with poor health
  • Age of the individual: Older individuals generally have poorer prognosis than younger individuals
  • Individuals with bulky disease of the breast cancer have a poorer prognosis
  • Involvement of the lymph node, which can adversely affect the prognosis
  • Involvement of vital organs may complicate the condition
  • The surgical resectability of the tumor (meaning if the tumor can be removed completely)
  • Whether the tumor is occurring for the first time or is a recurrent tumor. Recurring tumors have worse prognosis compared to tumors that do not recur 
  • Response to treatment of breast cancer: Tumors that respond to treatment have better prognosis compared to tumors that do not respond to treatment
  • Progression of the condition makes the outcome worse
• An early diagnosis and prompt treatment of the tumor generally yields better outcomes than a late diagnosis and delayed treatment
• The combination chemotherapy drugs used, may have some severe side effects (like cardio-toxicity). These chiefly impacts the elderly adults, or those who are already affected by other medical conditions. Tolerance to the chemotherapy sessions is a positive influencing factor

Additional and Relevant Useful Information for Neuroendocrine Carcinoma of Breast:

The following DoveMed website links are useful resources for additional information:

https://www.dovemed.com/healthy-living/womens-health/

https://www.dovemed.com/diseases-conditions/cancer/