Secretory Carcinoma of the Breast (SCB) is a relatively rarer subtype of invasive ductal carcinoma of the breast. Protheragen, a leading provider of preclinical research services, offers comprehensive diagnostics and therapeutics development services for SCB.
Overview of Secretory Carcinoma of the Breast (SCB)
Secretory carcinoma of the breast (SCB) is an uncommon and distinct subtype of breast cancer that differs from others based on its unique histopathological features as well as its molecular characteristics. Though initially identified in children, SCB has now been found across a broad age spectrum including adults. It is marked by the presence of a tumor with a dominant cell population exhibiting vacuolated cytoplasm containing abundant secretory material that is characteristically positive for periodic acid-Schiff (PAS), mucicarmine, and alcian blue stains.
Fig.1 A case analysis of secretory carcinoma with distant metastasis. (Hoda R. S.,
et al., 2019)
In addition, the diagnosis is confirmed with immunohistochemistry using alpha-lactalbumin, CEA, and S100. Notably, SCB differs from other secretory breast carcinomas by having a specific chromosomal translocation, t (12;15) (p13; q25), with ETV6-NTRK3 fusion gene, which is known to be diagnostic of the condition. Despite having a triple negative phenotype (no overexpression of estrogen receptor, progesterone receptor, and HER2), SCB is known for a relatively favorable outcome. On the contrary, some cases may demonstrate more aggressive behavior with distant metastases and poor prognoses.
Pathogenesis of Secretory Carcinoma of the Breast (SCB)
The causative mechanisms of SCB are largely associated with the chromosomal translocation t(12;15) (p13; q25) responsible for ETV6 and NTRK3 gene fusion. The resulting fusion leads to an uncontrolled form of tyrosine kinase, which stimulates signaling cascades related to cellular growth, sustenance, and differentiation. Most SCB cases harbor the ETV6-NTRK3 fusion gene, which is predominant in SCB cases and is frequently identified as a major contributor to cancer development. Besides, more advanced SCB cases have also been shown to have other molecular changes, including mutations in the TERT promoter and the loss of the 9p21.3 region, which contains the CDKN2A and CDKN2B tumor suppressor genes. Such genetic changes may help explain the more aggressive phenotypes and unfavorable outcomes in some cases.
Diagnostics Development for Secretory Carcinoma of the Breast (SCB)
Histopathological Diagnosis
Considerable emphasis is placed on histopathological examination when diagnosing SCB. Important characteristics are abundant granular cytoplasm, low-grade nuclei, and secretory material both extracellularly and intracellularly. For corroborative evidence, alpha-lactalbumin, S100, and CEA immunohistochemistry are done as routine procedures. The ETV6-NTRK3 fusion gene is identifiable with fluorescence in situ hybridization (FISH) or next generation sequencing (NGS).
Molecular Testing
Molecular analysis remains vital for the diagnosis of SCB. The ETV6-NTRK3 fusion gene is critical and represents a keystone of the disorder. It is now possible to detect this fusion by using FISH and NGS technologies. Moreover, molecular testing may also expose additional genetic changes like TERT promoter mutations and deletion at the 9p21.3 region which could be important in guiding prognosis.
Therapeutics Development for Secretory Carcinoma of the Breast (SCB)
- Targeted Therapy
The targeted therapies developed after the discovery of the ETV6-NTRK3 fusion gene, including TRK inhibitors like Larotrectinib, have proven to be effective in SCB. Such targeted therapies are showing remarkable response rates and sustained responses in advanced and metastatic SCB cases.
- Chemotherapy and Hormonal Therapy
The role of chemotherapy in the treatment of SCB is poorly defined and response rates appear to be low. In cases with estrogen receptor (ER) and/or progesterone receptor (PR) positive disease, some benefit from hormonal therapy could be provided, albeit evidence supporting this is lacking. More research is required to establish the best therapeutic approach with systemic therapies in SCB.
Table 1. Therapeutics of Secretory Carcinoma of the Breast (SCB).
| Therapeutics |
Drug Name |
Target |
Description |
Stage |
| Targeted Therapy |
Larotrectinib |
NTRK Fusion Proteins |
Selective TRK inhibitor targeting the ETV6-NTRK3 fusion protein. |
Approved |
| Targeted Therapy |
Entrectinib |
NTRK Fusion Proteins |
TRK inhibitor targeting the ETV6-NTRK3 fusion protein. |
Approved |
| Hormonal Therapy |
Tamoxifen |
Estrogen Receptor (ER) |
Blocks the effects of estrogen on cancer cells. |
Approved |
| Hormonal Therapy |
Anastrozole |
Aromatase Enzyme |
Reduces estrogen production in postmenopausal women. |
Approved |
| Chemotherapy |
Cyclophosphamide, Doxorubicin, 5-FU |
Rapidly Dividing Cancer Cells |
Combination chemotherapy to kill rapidly dividing cancer cells. |
Approved |
| Chemotherapy |
Docetaxel |
Microtubules |
Disrupts the microtubule network in cancer cells, leading to cell death. |
Approved |
Disclaimer: Protheragen focuses on providing preclinical research services. This table is for information exchange purposes only. This table is not a treatment plan recommendation. For guidance on treatment options, please visit a regular hospital.
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References
- Hoda, Raza S., et al. "Secretory carcinoma of the breast: clinicopathologic profile of 14 cases emphasising distant metastatic potential." Histopathology 75.2 (2019): 213-224.
- Horowitz, David P., et al. "Secretory carcinoma of the breast: results from the survival, epidemiology and end results database." The Breast 21.3 (2012): 350-353.
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