Secretory Carcinoma of the Breast: Understanding Your Pathology Report

by Jason Wasserman MD PhD FRCPC and Sarah Strickland MD FRCPC
July 2, 2026

Secretory carcinoma is a rare type of breast cancer that usually grows slowly and has a favorable outlook. It is called secretory carcinoma because the tumor cells produce secretions, which can be seen inside the cells and in the spaces between them under the microscope. Almost all secretory carcinomas are driven by a single genetic change, the ETV6::NTRK3 gene fusion, which is important both for confirming the diagnosis and for treatment.

Secretory carcinoma can occur at any age, including in children, but it is most often diagnosed in adults. It usually appears as a painless lump, often near the nipple or in the upper-outer part of the breast, and can occur in both women and men. This article will help you understand the findings in your pathology report, what each term means, and why it matters for your care.

What causes secretory carcinoma?

Most cases of secretory carcinoma are caused by a genetic change called the ETV6::NTRK3 gene fusion. This change joins two genes, ETV6 and NTRK3, into a single abnormal gene that continuously signals the cancer cells to grow. This fusion is found only in the tumor cells and is not inherited, so it cannot be passed on to family members. It is considered the defining feature of secretory carcinoma and can be confirmed with molecular tests.

What are the symptoms of secretory carcinoma?

Secretory carcinoma usually appears as a firm, painless lump in the breast. When the tumor is located near the nipple, there may be nipple discharge. Because secretory carcinoma tends to grow slowly, some patients do not notice symptoms for a long time, and the tumor is often discovered during routine breast imaging.

How is the diagnosis made?

The diagnosis of secretory carcinoma is usually made after a core needle biopsy or after the tumor is removed by surgery. A pathologist examines the tissue under the microscope. Secretory carcinoma is composed of uniform, round cells that often contain small bubbles or droplets of secretory material. The cells may be arranged in solid, tubular, papillary, or microcystic (with many small spaces) patterns, and the secretions within and around the cells have a characteristic bubbly appearance.

To confirm the diagnosis, the pathologist usually performs immunohistochemistry (IHC), a test that highlights specific proteins in the tumor cells. Secretory carcinoma is typically positive for S100, mammaglobin, SOX10, and MUC4 and is characteristically negative for the estrogen receptor, progesterone receptor, and HER2 (as discussed in the biomarker section below). The diagnosis is confirmed by detecting the ETV6::NTRK3 gene fusion using fluorescence in situ hybridization (FISH) or next-generation sequencing (NGS). Because this same fusion also guides treatment, it is described in more detail in the biomarker section. After the diagnosis is made, imaging of the breast is used to measure the size and extent of the tumor and to plan treatment.

Histologic grade

Breast cancers, including secretory carcinoma, are given a histologic grade using the Nottingham grading system (also called the modified Scarff-Bloom-Richardson grade), which describes how closely the cancer cells resemble normal breast tissue and how quickly they are growing. The pathologist scores three features, each from 1 to 3:

Tubule formation — How much of the tumor forms normal-looking gland-like structures. More tubule formation is scored lower.
Nuclear pleomorphism — How abnormal and variable the cell nuclei (the part of the cell that holds the DNA) look compared with normal cells. More abnormal nuclei are scored higher.
Mitotic count — How many cells are actively dividing, seen as mitotic figures. A higher count is scored higher.

The three scores are added together (total 3 to 9) to give grade 1 (score 3 to 5, low grade), grade 2 (score 6 or 7, intermediate grade), or grade 3 (score 8 or 9, high grade). Secretory carcinoma is usually low-grade (grades 1 or 2). Unlike most other breast cancers, secretory carcinoma tends to behave in a slow-growing, favorable way regardless of its grade, so the grade is a less powerful predictor of outcome for this tumor than it is for common breast cancers.

Tumor size

The size of a secretory carcinoma is used to determine the pathologic tumor stage (pT, described in the staging section below), and larger tumors are more likely to metastasize (spread) to lymph nodes and other parts of the body. The final size can only be measured after the entire tumor has been removed at surgery, so it does not appear in a biopsy report.

Tumor extension

Secretory carcinoma begins in the breast, but in some cases, the tumor can invade the overlying skin or the muscles of the chest wall. This is called tumor extension. Although uncommon in this slow-growing tumor, its presence is associated with a higher risk of local recurrence and distant spread, and it raises the pathologic tumor stage to pT4.

Lymphovascular invasion

Lymphovascular invasion (LVI) means cancer cells have entered small blood vessels or lymphatic channels near the tumor. These vessels can serve as pathways for cancer cells to travel to nearby lymph nodes or other parts of the body. The pathologist examines the specimen under the microscope and reports lymphovascular invasion as “present” (or “positive”) or “absent” (or “negative”). When present, it raises the chance that the cancer could spread or return, and the team may discuss additional treatment such as chemotherapy or radiation therapy.

Margins

A margin is the edge of the tissue removed during surgery. The pathologist examines the margins under the microscope to determine whether the entire tumor was removed. Margins are assessed only after surgery that removes the whole tumor, not after a biopsy.

Negative margin — No cancer cells at the cut edge. The report may also state how close the nearest cancer cells came to the edge; a wider clear margin lowers the risk of local recurrence.
Positive margin — Cancer cells present at the cut edge, meaning some cancer may remain. Additional surgery or radiation may be considered.

Lymph nodes

Lymph nodes are small immune organs that filter fluid and can trap cancer cells. When breast cancer spreads, it often travels first to the lymph nodes under the arm (the axillary lymph nodes). During surgery, some of these nodes may be removed and examined. The report includes the number of nodes examined, the number that contain cancer, and the size of the largest cancer deposit. It may also mention extranodal extension, meaning cancer has broken through the outer capsule of a node into the surrounding tissue.

The size of the largest deposit is described using three terms:

Isolated tumor cells — Clusters no larger than 0.2 mm. These are not counted as positive for staging and have little effect on treatment.
Micrometastasis — A deposit larger than 0.2 mm but not larger than 2 mm, reported as pN1mi.
Macrometastasis — A deposit larger than 2 mm, associated with a higher risk of spread. Even when secretory carcinoma reaches the lymph nodes, most patients do well with treatment.

Biomarker and molecular testing

Biomarker testing in secretory carcinoma differs from that in most other breast cancers. The single most important test looks for the ETV6::NTRK3 gene fusion because it both confirms the diagnosis and identifies a specific targeted treatment.

NTRK (ETV6::NTRK3 fusion)

NTRK refers to a family of genes (NTRK1, NTRK2, and NTRK3) that normally help control cell growth. In secretory carcinoma, part of the NTRK3 gene becomes fused to the ETV6 gene, producing an abnormal protein that continuously drives the cancer cells to grow. This fusion matters because tumors with an NTRK fusion often respond very well to targeted drugs called TRK inhibitors, such as larotrectinib and entrectinib. These drugs are approved to treat any cancer that carries an NTRK fusion, regardless of where in the body the cancer started, an approach called tumor-agnostic treatment.

The fusion is usually detected by FISH or NGS; a screening test using a pan-TRK antibody by immunohistochemistry may be performed first. Your report will describe the result as NTRK fusion (or ETV6::NTRK3) detected or not detected. You can read more in our article on NTRK fusions in cancer.

Estrogen receptor, progesterone receptor, and HER2

Every breast cancer is tested for the estrogen receptor (ER), the progesterone receptor (PR), and HER2, because these results usually guide treatment. Secretory carcinoma is characteristically negative for all three, a pattern called triple-negative. In most breast cancers, a triple-negative result signals a faster-growing tumor with a less favorable outlook. Secretory carcinoma is an important exception: despite being triple-negative, it usually grows slowly and has a favorable outcome. This is why the NTRK fusion, rather than the hormone receptor or HER2 result, is the key biomarker for this tumor.

For more information, visit our Biomarkers and Genetic Testing section.

Pathologic stage (pTNM)

Secretory carcinoma is staged using the TNM system of the American Joint Committee on Cancer (AJCC), 8th edition, based on the tumor (T), lymph nodes (N), and distant metastasis (M). The pathologist determines the pT and pN stages from the removed tissue; the M stage is determined by imaging.

Tumor stage (pT)

pT1 — Tumor 2 cm (20 mm) or smaller. Subdivided into pT1mi (1 mm or smaller), pT1a (more than 1 mm up to 5 mm), pT1b (more than 5 mm up to 10 mm), and pT1c (more than 10 mm up to 20 mm).
pT2 — Tumor larger than 2 cm but not larger than 5 cm.
pT3 — Tumor larger than 5 cm.
pT4 — Tumor of any size that has grown into the chest wall or skin. pT4a is growth into the chest wall; pT4b is growth into the skin causing ulcers or swelling; pT4c is both; pT4d is inflammatory breast cancer.

Nodal stage (pN)

pN0 — No cancer in the lymph nodes. Isolated tumor cells only are recorded as pN0(i+).
pN1 — Cancer in 1 to 3 axillary lymph nodes, or micrometastases only (pN1mi), or spread to internal mammary sentinel nodes.
pN2 — Cancer in 4 to 9 axillary lymph nodes, or in internal mammary nodes without axillary involvement.
pN3 — Cancer in 10 or more axillary lymph nodes, in nodes below or above the collarbone, or in a combination of internal mammary and axillary nodes.

What is the prognosis for secretory carcinoma?

Most patients with secretory carcinoma have an excellent prognosis, especially when the tumor is found early. The cancer tends to grow slowly and rarely spreads to distant parts of the body, and even when it reaches nearby lymph nodes, most patients do well with treatment. The five-year survival rate is over 90%, and many people live much longer without the cancer returning. In rare cases, particularly in older adults, the cancer can return many years after treatment, which is why long-term follow-up is important.

What happens after this diagnosis?

After a diagnosis of secretory carcinoma, care is usually coordinated by a team that may include a breast surgeon, a medical oncologist, a radiation oncologist, and a pathologist. The pathology findings guide which options the team considers, rather than dictating a single path. Surgery is the main treatment and may involve removing just the tumor (lumpectomy) or the whole breast (mastectomy), depending on the size and location of the tumor. Radiation therapy or chemotherapy may be considered when the cancer has spread to lymph nodes or has other higher-risk features.

When secretory carcinoma is advanced, has spread, or cannot be fully removed by surgery, the ETV6::NTRK3 fusion opens the option of targeted therapy with a TRK inhibitor (larotrectinib or entrectinib), which has shown strong and lasting responses in NTRK fusion-positive tumors. If treatment is given before surgery, the pathologist reports the extent of residual cancer using the residual cancer burden (RCB) index. Because secretory carcinoma can return years later, follow-up with regular examinations and imaging continues over the long term.

Questions to ask your doctor

What did my pathology report show about the type and grade of my cancer?
Was the ETV6::NTRK3 gene fusion found in my tumor?
What is the size and pathologic stage (pT and pN) of my cancer?
Was the tumor completely removed, with negative margins?
Was lymphovascular invasion present?
Did the cancer spread to any lymph nodes?
Is my cancer triple-negative, and what does that mean given that secretory carcinoma usually has a favorable outlook?
Am I a candidate for targeted therapy with a TRK inhibitor?
Will I need radiation therapy or chemotherapy?
Are there clinical trials that might be appropriate for me?
What follow-up schedule will I need, given that this cancer can return years later?