Secretory carcinoma of the breast: A case report

Abstract

BACKGROUND

Secretory carcinoma is a rare, differentiated, distinct histologic type of invasive breast carcinoma. It is extremely rare, accounting for less than 0.02% of all breast cancer cases. Although it is the most common primary breast cancer in children, it is most often diagnosed in adults. To date, at least 642 cases of secretory carcinoma of the breast have been reported in the literature for the last 15 years.

CASE SUMMARY

A 21-year-old female, sought medical help at the Department of Oncology and Reconstructive Plastic Surgery of the Breast and Skin of the PA Herzen Moscow Oncology Research Institute with complaints of a mass in the right mammary gland. Secretory carcinoma of the mammary gland is a malignant tumor that was first described in children in 1966 by McDivitt RW and Stewart FW and named “juvenile breast carcinoma” because it was predominantly seen in children and associated with genetic mutations. Although secretory cancer is classified as a type of basal-like triple-negative cancer, it differs significantly from it in terms of pathogenesis, clinical presentation, and treatment. Overall, it usually has a good prognosis with overall survival 5 years, 10 years, and 20 years after initial treatment of 95.79%, 93.16%, and 93.16%.

CONCLUSION

We present a case report and review of the literature of secretory carcinoma of the breast with low estrogen and low progesterone immunophenotype.

Key Words: Breast cancer; Secretory carcinoma; Sentinel lymph node; Surgery; Case report

Core Tip: Secretory carcinoma is a rare, differentiated, distinct histologic type of invasive breast carcinoma. It is extremely rare, accounting for less than 0.02% of all breast cancer cases. Although it is the most common primary breast cancer in children, it is most often diagnosed in adults.

INTRODUCTION

Secretory carcinoma of the mammary gland is a malignant tumor that was first described in children in 1966 by McDivitt RW and Stewart FW and named “juvenile breast carcinoma”. Description of several similar cases in adults in the 1980s, led Tavaosoli FA and Norris HJ to a new term “secretory carcinoma of the breast”[1-3].

Secretory carcinoma is a rare, differentiated, distinct histologic type of invasive breast carcinoma. It is extremely rare, accounting for less than 0.02% of all breast cancer cases. Although it is the most common primary breast cancer in children, it is most often diagnosed in adults. To date, at least 642 cases of secretory carcinoma of the breast have been reported in the literature for the last 15 years[4,5].

A particular trait of secretory carcinoma is its t(12;15)(p13;q25) translocation, resulting in a fusion of the ETV6: NTRK3 genes. Improvements in understanding of the complexity of cancer biology have been instrumental in advancing cancer treatments. Cancer is primarily driven by oncogenic somatic and/or germline alterations in oncogenes and tumor suppressor genes[6].

We present a case description and management of a patient with secretory breast carcinoma.

CASE PRESENTATION

Chief complaints

A 21-year-old female, sought medical help at the Department of Oncology and Reconstructive Plastic Surgery of the Breast and Skin of the PA Herzen Moscow Oncology Research Institute with complaints of a mass in the right mammary gland.

History of present illness

A mass was detected in the right mammary gland on the border of the lower quadrants, about 2 cm from the nipple, measuring 14 mm × 11 mm × 13 mm in April 2024, during a routine ultrasound examination of the mammary glands.

History of past illness

She had no comorbidities, no significant medical or medication history, and her family history was unremarkable.

Personal and family history

She had no comorbidities, no significant medical or medication history, and her family history was unremarkable.

Physical examination

The patient was consulted by an oncologist. On examination and palpation, the mammary glands were relatively small in size, symmetrical, the skin was unremarkable. The nipple-areolar complexes on both sides were unchanged and there was no discharge from the nipples. On palpation in the right mammary gland, on the border of the lower quadrants, behind the areola, there was a dense, mobile nodular mass with clear contours up to 2.0 cm in diameter. On the left, no clear nodular formations were found on palpation. Regional lymph nodes on both sides were not enlarged (Figure 1).

Figure 1 Patient’s appearance before treatment. A: Anterolateral projection on the left; B: Anterior projection; C: Anterolateral projection on the right.

Laboratory examinations

Laboratory investigations were unremarkable.

Imaging examinations

The patient underwent ultrasonography of both mammary glands - against the background of developed glandular tissue of juvenile adenosis type there was a hypoechoic lobular mass with clear contours measuring 14 mm × 11 mm × 13 mm with an enveloping type of blood flow in the color Doppler imaging mode. In the axillary regions, there were lymph nodes without visible structural changes (Figure 2).

Figure 2 Ultrasound of the mammary glands. A: Axial position of th probe; B: Saggital position of the probe. A formation located subareolarly in the right mammary gland (indicated by the arrow).

Magnetic resonance imaging of the mammary glands with intravenous contrast was performed. In the right mammary gland in the middle sections on the border of the lower quadrants, a rounded formation with uneven edges was determined, measuring 18.5 mm × 17.5 mm; heterogeneously accumulating the contrast agent (with the effect of contrast washout) III type of signal intensity and time curve. It was located at a distance of 23 mm from the pectoralis major muscle, 12 mm from the outer surface of the gland, 11 mm from the inner surface of the gland, 10 mm from the nipple-areolar complex. Right mammary gland - BI -RADS 5. Left mammary gland - BI -RADS 1 (Figure 3).

Figure 3 Magnetic resonance imaging of the mammary glands with intravenous contrast enhancement. A: Direct projection; B: Lateral projection.

Preoperative histology and immunohistochemistry: A core-needle biopsy of the mass was performed. According to the morphological study there were columns of breast tissue with tumor growth, represented by papillary, cribriform and tubular structures of atypical epithelial cells with moderate nuclear atypia and low mitotic activity (2 + 2 + 1 = 5 points in the Elston-Ellis gradation), areas with apocrine differentiation, fibrosis of the stroma. Cancer structures in situ, lymphovascular invasion and perineural growth were not detected. Lymphoid infiltration of the tumor stroma TILs-2%. In the surrounding tissue, sclerosing lobular adenosis. Invasive ductal breast cancer, G1 (5 points). To confirm the diagnosis and determine the surrogate molecular type of the tumor, it is necessary to conduct an immunohistochemistry (IHC) study [estrogen receptors (ER), progesterone receptors (PR), Her 2 neu, Ki-67, p63, alpha-smooth muscle actin (SMA), cytokeratin (CK) 5/6].

An immunohistochemical study was performed on sections of the paraffin block using an automatic immunostainer. Ventana Benchmark Ultra with antigen imaging systems: UltraView Universal DAB Detection Kit and OptiView DAB IHC Detection Kit using antibodies: ER, PR, Her 2 neu, Ki-67, p63, SMA, CK5/6. Nuclear expression in tumor cells was detected (result of receptor status according to Allred): ER - 2 (IS) + 2 (2%) (PS) = 4 points (TS), PR - 3 (IS) + 2 (5%) (PS) = 5 points (TS). Her 2 neu status assessment according to ASCO/CAP: Her2 neu - (0) - negative. The proliferative activity index Ki-67 is expressed unevenly: On average, 5% per tumor (the assessment was carried out using the International ki-67 in Breast Cancer Working Group), p63-negative reaction in myoepithelial cells in the area suspicious for invasive growth. SMA, CK5/6 focal expression is noted in basal/myoepithelial cells in the area suspicious for invasive growth (Figures 4, 5 and 6).

Figure 4 Secretory breast cancer. A-C: Polygonal cells with eosinophilic granular or vacuolated cytoplasm, round and oval nuclei [A: Hematoxylin and eosin (H&E), ×10; B: H&E, ×20; C: H&E, ×40].

Figure 5 Secretory breast cancer, histological preparations. A: Positive reaction with estrogen receptors, ×20; B: Expression of Ki 67 in less than 18% of tumor cells, ×20.

Figure 6 Positive reaction with S 100, ×20.

In situ hybridization assay was performed using the ETV6/NTRK3 probe for the t(12;15) fusion translocation (LBP Medicine Science and Technology, Guangzhou, China). The red signal corresponds to ETV6 and the green signal to NTRK3. It was shown that tumor cells have ETV6 gene rearrangement with an increase in the amount of ETV6-NTRK3 fusion signals (32.5%) compared to the threshold value (10%) (Figure 7).

Figure 7 ETV6-NTRK3 gene fusion (marked with arrow).

MULTIDISCIPLINARY EXPERT CONSULTATION

Taking into account the clinical and immunohistochemical data, the morphological picture is of atypical proliferation of the epithelium of the mammary gland ducts with foci suspicious for invasive ductal cancer, G1. Removal of the mass was recommended, followed by a planned morphological study. The patient was discussed at an interdepartmental consultation with the participation of a surgeon, chemotherapist and radiologist. Taking into account the stage I of right breast cancer cT1cN0M0 with low ER/PR expression, surgical treatment was recommended.

FINAL DIAGNOSIS

Taking into account the clinical and immunohistochemical data, the morphological picture is of atypical proliferation of the epithelium of the mammary gland ducts with foci suspicious for invasive ductal cancer, G1. Removal of the mass was recommended, followed by a planned morphological study. The patient was discussed at an interdepartmental consultation with the participation of a surgeon, chemotherapist and radiologist. Taking into account the stage I of right breast cancer cT1cN0M0 with low ER/PR expression, surgical treatment was recommended.

TREATMENT

On May 19, 2024, surgical treatment was performed in the amount of resection of the right mammary gland with a biopsy of the “sentinel” lymph node.

According to the planned morphological study: A fragment of breast tissue measuring 4.5 cm × 1.5 cm × 4 cm, without skin and nipple. On the cut, in the glandular tissue, at a distance of 0.9 cm from the superior, 1 cm from the medial, 0.4 cm from the cutaneous, 1 cm from the inferior, 0.5 cm from the lateral, 0.1 cm from the fascial resection edges - a dense tumor node with relatively clear boundaries, measuring 1.5 cm × 1.2 cm × 1 cm. In the “sentinel” lymph node - a picture of sinus histiocytosis, foci of fat replacement, without signs of atypical cells (Figure 8).

Figure 8 Macroscopic specimen of the removed sector (the tumor node is indicated by an arrow).

The patient was discussed again at an interdepartmental consultation involving a surgeon, a chemotherapist and a radiologist; hormonal therapy with antiestrogens (tamoxifen 20 mg once a day) for 5 years was recommended, as well as radiation therapy to the area of the resected mammary gland. However, the patient abstained from radiation therapy.

OUTCOME AND FOLLOW-UP

Follow-up examination 5 months, 1 year and 2 years after surgery, there were no signs of recurrence or progression (Figure 9).

Figure 9 Patient’s appearance 5 months after surgical treatment. A: Anterolateral projection on the left; B: Anterior projection; C: Anterolateral projection on the right.

DISCUSSION

Secretory carcinoma is a rare, differentiated, distinct histologic type of invasive breast carcinoma. It is extremely rare, accounting for less than 0.02% of all breast cancer cases. Although it is the most common primary breast cancer in children, it is most often diagnosed in adults. To date, at least 642 cases of secretory carcinoma of the breast have been reported in the PubMed literature from January 2010 to January 2024. The male to female ratio was 1:8, and the mean age was 48 years (range, 3-91 years)[4,5].

Secretory carcinoma most often presents as a painless and slowly growing palpable mass, diagnosed equally in the right and left mammary glands. Multicentricity is extremely rare. In women, the tumor is most often localized in the nipple area or in the upper-outer quadrant, but can occur in any quadrant, including ectopic breast tissue. In men and children, it usually occurs in the subareolar region[5].

Although secretory carcinoma of the breast is classified as a basal-like carcinoma, it has immunohistochemical and genetic features that distinguish it from other basal-like breast tumors[7]. Recently, Jin et al[8] found that secretory breast carcinoma shares genomic mutations and biological pathways more closely associated with hormone-dependent breast cancer than with basal-like triple-negative breast cancer, by sequencing exome and proteomic analysis of secretory breast carcinoma[4,8]. Unlike the reported cases, our case represent a low estroden and low progesterone immunophenotype.

Del Castillo et al[9] noted that even in confirmed breast cancer, the histological grade and TNM stage do not affect the prognosis and treatment. The majority of secretory carcinomas have a t(12;15)( p13;q25) translocation, resulting in a fusion of the ETV6: NTRK3 genes[10].

The treatment options for secretory carcinoma are discussable. For advanced, recurrent, or metastatic tumors, targeted drugs called TRK inhibitors—such as larotrectinib and entrectinib—specifically block the ETV6-NTRK3 signal and show high response rates. Standard chemotherapy and radiation have unproven benefits for this specific subtype and are generally avoided in early-stage cases because the tumor often resists conventional chemotherapy[11-13]. Surgery remains the most effective treatment for secretory carcinoma, but there is no consensus on how extensive surgery should be[14].

The current practice is largely extrapolated from data on invasive breast cancer and believe that radiation may improve outcomes[15]. In our case the patient was recommended endocrine therapy and radiation therapy based on the local guidelines of breast cancer treatment. Based on the local guidelines breast conservative surgery is followed by radiation therapy and the entire operated breast should receive a dose of 46-50 Gy in 23-25 fractions or 40-42.5 Gy in 15-16 fractions[16]. Similarly, according to local guidelines tumors with detectable expression of ER and/or PR in ≥ 1% of invasive breast cancer cells are considered hormone-dependent[16].

Secretory carcinoma generally has a better prognosis and overall survival than invasive breast carcinoma without specific features. A good prognosis is associated with age < 20 years, tumor size < 2 cm, and ≤ 3 axillary lymph node metastases. Metastases beyond the ipsilateral axillary lymph nodes are rare, with the lungs and liver most commonly involved. The tumor cells characteristically express S100 protein, mammaglobin, and STAT5a and are either triple (estrogen receptor, progesterone receptor, and HER2) negative or only weakly ER/PR-positive. However, prognosis and long-term outcome of patients with secretory carcinoma, even in the presence of axillary lymph node metastasis, is better than that of triple-negative or basal breast cancers[15,17,18]. The reported survival of patients with secretory breast carcinoma who had not spread to distant tissues at 5 years, 10 years, and 20 years after initial treatment of 95.79%, 93.16%, and 93.16%, respectively[17,18]. The findings suggest that, despite a basal-like immunophenotype, secretory carcinomas of the breast are genetically more similar to mammary analog secretory carcinomas of the salivary gland than they are to other primary breast cancers[17,18].

CONCLUSION

Among the numerous subtypes of breast cancer, secretory breast carcinoma accounts for less than 0.02% of all breast cancer cases. Although secretory cancer is often classified as a type of basal-like triple-negative cancer, it differs significantly from it in terms of pathogenesis, clinical presentation, and treatment. It usually has a good prognosis.