Treatment Options For Secretory Carcinoma Of The Breast

Overview of secretory carcinoma

Secretory carcinoma is a rare type of breast cancer, accounting for less than 1% of all breast cancer cases. It is also known by several other names, including mammary analogue secretory carcinoma (MASC) and secretory breast carcinoma.¹ 

Secretory carcinoma is distinguished by the presence of secretory features, which means that the cancer cells produce and secrete a substance that can be seen under a microscope. It typically manifests as a painless breast lump or mass. In some cases, it may be associated with nipple discharge or skin changes. It is usually slow-growing and has a favourable prognosis compared to other types of breast cancer.¹ 

The diagnosis of secretory carcinoma involves a combination of clinical examination, imaging studies (such as mammography or ultrasound), and a biopsy of the suspicious breast lump. Histopathological examination of the biopsy sample is crucial for confirming the presence of secretory carcinoma and assessing its characteristics. The primary treatment for secretory carcinoma is surgery, which involves the removal of the tumour and, in some cases, lymph nodes in the surrounding area.¹

Diagnosis

Clinical presentation and symptoms

1. Age: although it can arise at any age, secretory carcinoma is more common in pediatric and young adult populations. It is uncommon in comparison to other kinds of breast cancer.²
2. Breast lump: A breast lump is a common clinical sign of secretory carcinoma. The lump is normally painless and well-defined, with a range of sizes. To the touch, it may feel stiff or rubbery. Secretory carcinoma, unlike certain other kinds of breast cancer, is frequently slow-growing.²
3. Nipple discharge: Some people with secretory carcinoma may have nipple discharge. The discharge might be clear or bloody, and it can occur spontaneously or as a result of breast or nipple manipulation.²
4. Secretory carcinoma can induce skin and nipple alterations in the affected breast. Dimpling, puckering, redness, swelling, and skin thickening are examples of these changes. The nipple may become inverted (pushed inward) or indicate changes in appearance, such as scaling, ulceration, or crusting.²
5. Uncommon symptoms: In rare cases, secretory carcinoma may present with other less common symptoms, such as breast pain or tenderness, breast enlargement, or axillary lymph node enlargement. However, these symptoms are not specific to secretory carcinoma and can be observed in other breast conditions as well.²

Diagnostic procedures and tests

The following are some frequent diagnostic techniques and tests used to detect and diagnose secretory carcinoma:³

Clinical history and physical examination: The first step is to obtain a thorough medical history, which includes any breast-related symptoms, risk factors, and a family history of breast cancer. A comprehensive physical examination of the breast is also performed to detect any palpable tumours or abnormalities.

Imaging studies: 

• Mammogram: A mammogram is an X-ray of the breast tissue and is commonly used for breast cancer screening. However, secretory carcinoma might not always appear distinct on mammograms, and other imaging techniques may be needed. 
• Ultrasound: Breast ultrasound can provide detailed images of breast tissue and can help distinguish between cystic and solid masses. 
• Magnetic Resonance Imaging (MRI): MRI can be valuable in evaluating breast lesions, especially when additional information is needed after a mammogram or ultrasound.

Different types of biopsy procedures:

• Fine-needle aspiration biopsy (FNAB): Involves extracting cells from the mass using a thin needle. 
• Core needle biopsy (CNB): Involves removing a small core of tissue with a larger needle. 
• Surgical biopsy: In some cases, if other biopsy methods are inconclusive, a surgical biopsy may be necessary to remove a larger sample of the tumour.

Immunohistochemistry (IHC): After obtaining the biopsy sample, immunohistochemistry tests are performed on the tissue to detect specific biomarkers associated with secretory carcinoma. The most common markers for secretory carcinoma include S-100 protein, mammaglobin, and GATA3.

Molecular testing: Genetic testing of the tumour tissue may be performed to identify specific genetic mutations or rearrangements that can aid in the diagnosis and treatment of secretory carcinoma. The most well-known genetic alteration associated with secretory carcinoma is the ETV6-NTRK3 fusion gene.

Treatment approaches

Surgery

Here are some surgical options commonly used for the treatment of secretory carcinoma:²

Lumpectomy: Also known as breast-conserving surgery or partial mastectomy, a lumpectomy involves the removal of the tumour along with a small margin of healthy tissue around it. This approach is typically used for small-sized tumours and when the tumour is in an accessible location. After a lumpectomy, radiation therapy is often recommended to reduce the risk of cancer recurrence.

Mastectomy: Mastectomy is the surgical removal of the entire breast. It may be recommended for larger tumours, cases where the tumour is not amenable to breast-conserving surgery, or if the patient prefers a more extensive surgical approach. There are different types of mastectomy procedures, including:

• Total or simple mastectomy: Removal of the entire breast without removing the lymph nodes under the arm (axillary lymph nodes).
• Modified radical mastectomy: Removal of the entire breast and the axillary lymph nodes.
• Skin-sparing mastectomy: Removal of the breast tissue while preserving the overlying skin to facilitate breast reconstruction.
• Nipple-sparing mastectomy: Removal of the breast tissue while preserving the nipple-areola complex, also to facilitate breast reconstruction.

Reconstruction: Breast reconstruction is an option for some patients who undergo mastectomy and wish to restore the breast's appearance. Reconstruction can be done either during the mastectomy or at a later time. There are various techniques available for breast reconstruction, including implants and tissue flap procedures that use the patient's tissue.

Lymph node evaluation

Sentinel Lymph Node Biopsy (SLNB): This procedure involves removing and examining the first lymph node(s) from the primary tumour where cancer cells are most likely to spread. It helps in determining the extent of lymph node involvement and directs subsequent therapy selections.¹

Axillary Lymph Node Dissection (ALND): If cancer has been detected in the sentinel lymph nodes or there are signs of widespread lymph node involvement, axillary lymph node dissection may be performed. Multiple lymph nodes in the axilla are removed and analyzed during this procedure to determine the amount of cancer distribution.¹ 

Adjuvant therapies

Radiation therapy

Radiation therapy, also known as radiotherapy, is a medical treatment that uses high-energy radiation to target and destroy cancer cells or to shrink tumours. The goal of radiotherapy is to deliver a precise dose of radiation to the tumour while minimizing the radiation exposure to surrounding healthy tissues as much as possible. It is one of the primary modalities used in the management of cancer, and it can be used alone or in combination with surgery, chemotherapy, or immunotherapy, depending on the specific type and stage of cancer.¹

1. External Beam Radiation Therapy: In this procedure, a radiation machine, also known as a linear accelerator, delivers high-energy X-rays or other types of radiation beams from outside the body to the tumour. The patient is placed on a treatment table, and radiation beams are focused at the particular site of the tumour. This type of radiation therapy is often administered in multiple sessions (fractions) to allow healthy tissues to recuperate between treatments.
2. Internal Radiation Therapy (Brachytherapy): In this procedure, radioactive sources are implanted directly into or extremely close to the tumour. Brachytherapy enables a more concentrated dosage of radiation to be given to the target area while limiting exposure to neighbouring healthy tissues. 

Chemotherapy

Chemotherapy is a systemic cancer treatment that utilizes powerful drugs to kill or slow down the growth of cancer cells. Chemotherapy, unlike surgery or radiation therapy, which targets specific areas of the body, circulates throughout the entire body, targeting cancer cells wherever they may be present. ²

Hormonal therapy

Hormonal therapy is a systemic treatment used to treat certain hormone receptor-positive cancers, most commonly breast and prostate cancers. It works by interfering with the hormones or hormone receptors that fuel the growth and proliferation of cancer cells. The primary goal of hormonal therapy is to slow down or stop the growth of hormone-sensitive tumours.²

Targeted therapies and emerging treatments

Targeted therapy is a type of cancer treatment that focuses on specific molecules or pathways involved in the growth and spread of cancer cells. Unlike traditional chemotherapy, which affects both cancerous and healthy cells, targeted therapies are designed to selectively attack cancer cells while minimizing damage to normal cells.

HER2-Targeted Therapy: Approximately 20-25% of breast cancers overexpress the human epidermal growth factor receptor 2 (HER2) protein, which promotes cell growth. HER2-targeted therapies, such as trastuzumab (Herceptin), pertuzumab (Perjeta), and ado-trastuzumab emtansine (Kadcyla), work by blocking HER2 receptors or delivering chemotherapy directly to HER2-positive cancer cells.³

Management of recurrent or metastatic secretory carcinoma

Locoregional recurrence

Locoregional recurrence in cancer refers to the reappearance of cancer cells in the same general area where cancer originated or in nearby lymph nodes after the completion of initial treatment, such as surgery, radiation therapy, or a combination of both. 

In the context of breast cancer, locoregional recurrence would typically involve the reappearance of cancer cells in the breast or the surrounding tissues (chest wall) after initial treatment. It could also involve the recurrence of cancer in the nearby lymph nodes, particularly in the axillary (armpit) lymph nodes, which are common sites for the spread of breast cancer.²

Locoregional recurrence can occur for several reasons, including:

1. Incomplete tumor removal
2. If cancer cells have already spread to nearby lymph nodes at the time of the initial diagnosis or surgery
3. If the surgical margins (the edge of the tissue removed during surgery) are positive, meaning they contain cancer cells, there is a higher likelihood of recurrence in that area.

Distant metastasis

Distant metastasis refers to the spread of cancer cells from the primary (original) tumour to distant organs or tissues in the body. It is a stage of cancer characterized by the most advanced progression and poses significant challenges for treatment and management.²

Common sites of distant metastasis depend on the type of cancer, but some common locations include:

1. Liver
2. Lungs
3. Bones
4. Brain
5. Adrenal glands
6. Other distant lymph nodes and organs

Treatment of Distant Metastatic Secretory Carcinoma of the Breast includes:²

1. Systemic Therapy: Chemotherapy, targeted therapy (such as HER2-targeted therapies for HER2-positive breast cancer), hormonal therapy (for hormone receptor-positive breast cancer), and immunotherapy are systemic treatments that can target cancer cells throughout the body.
2. Radiation Therapy: In some cases, radiation therapy may be used to alleviate pain and control tumour growth at specific metastatic sites.
3. Surgery: Surgical removal of isolated metastatic tumours in certain cases may be considered to control symptoms or improve outcomes.
4. Clinical Trials: Participation in clinical trials can provide access to experimental treatments and new therapies that may offer additional options for patients with metastatic breast cancer.

Prognosis and follow-up

Prognosis and follow-up for secretory carcinoma of the breast can vary based on several factors, including the stage of cancer at the time of diagnosis, the size of the tumour, the presence of lymph node involvement, and the individual characteristics of the patient. Secretory carcinoma is generally considered to have a more favourable prognosis compared to other types of breast cancer.

Prognosis: The prognosis for secretory carcinoma of the breast is generally good, especially when the cancer is detected early and has not spread to nearby lymph nodes or distant organs. This type of breast cancer tends to be less aggressive and has a relatively slow growth rate. The presence of a specific genetic rearrangement called the ETV6-NTRK3 fusion is characteristic of secretory carcinoma and may influence treatment options and prognosis.³

Follow-up:  After initial treatment for secretory carcinoma of the breast, regular follow-up visits are crucial to monitor for any signs of recurrence or new cancer developments. The follow-up schedule may vary depending on the patient's specific situation and the recommendations of their healthcare team. However, typical follow-up protocols may include:³

1. Regular physical examinations
2. Imaging: Mammograms, ultrasound, or MRI scans may be recommended to monitor for any changes or abnormalities.
3. Blood Tests: for monitoring tumour markers or assessing general health status.
4. Bone Scans: Bone scans may be performed periodically to check for any signs of bone metastasis, as this is a common site of metastasis for breast cancer.
5. Hormone Receptor Testing: If the tumour is hormone receptor-positive, hormonal therapy may be part of the treatment plan. 
6. Communication: Open communication between the patient and their medical team is essential. Patients should report any new or concerning symptoms promptly.

 Additional considerations and resources

Some additional considerations and resources for individuals with secretory carcinoma of the breast.¹

1. Second Opinions: Seeking a second opinion from another breast cancer specialist can provide valuable insights and alternative perspectives on treatment options, especially for rare types of breast cancer like secretory carcinoma. 
2. Genetic Testing: Genetic counselling and testing may be considered for individuals with secretory carcinoma of the breast, especially if there is a family history of breast or other related cancers. Testing for specific genetic mutations, such as BRCA1 and BRCA2, can provide important information about cancer risk and potential treatment options.
3. Support Groups: Joining support groups for individuals with breast cancer can offer emotional support, information sharing, and a sense of community with others who may be going through similar experiences.
4. Online Resources: Reputable organizations and websites specializing in breast cancer, such as the American Cancer Society (ACS), BreastCancer.org, and the National Breast Cancer Foundation (NBCF), offer valuable information about different breast cancer subtypes, treatment options, and resources for patients and their families.
5. Research and Clinical Trials: As secretory carcinoma is a rare type of breast cancer, patients may consider exploring ongoing clinical trials and research studies that focus on this subtype. Clinical trials can offer access to novel treatments and therapies that may not yet be widely available.
6. Psychosocial Support

Summary

Secretory carcinoma of the breast is a rare subtype of breast cancer characterized by the presence of abundant intracellular and extracellular secretions. While it is less common than other types of breast cancer, it tends to have a more favourable prognosis. The main treatment options for secretory carcinoma of the breast include surgery, radiation therapy, and sometimes hormonal therapy or targeted therapy. Lymph node evaluation is essential to determine the extent of cancer spread.

For patients with secretory carcinoma, regular follow-up visits are crucial to monitor for any signs of recurrence or new cancer developments. Follow-up may include physical examinations, imaging tests, blood tests, and bone scans, depending on the patient's specific situation and treatment plan.

Additional considerations for individuals with secretory carcinoma include seeking second opinions, genetic testing and counselling, joining support groups, exploring online resources and research, accessing psychosocial support services, and considering financial assistance if needed.

Overall, staying informed, being proactive, and having a strong support system is essential for patients with secretory carcinoma of the breast to navigate their cancer journey and make informed decisions about their care.