How is Breast Cancer in Men Classified?

After you have a biopsy, the samples of breast tissue are looked at in the lab to determine whether breast cancer is present and if so, what type it is. Certain lab tests may be done that can help determine how quickly a cancer is likely to grow and (to some extent) what treatments are likely to be effective. Sometimes these tests aren’t done until either breast-conserving surgery or mastectomy.

If a benign condition is diagnosed, you will need no further treatment. Still, it is important to find out from your doctor if you need special follow-up.

If the diagnosis is cancer, there should be time for you to learn about the disease and to discuss treatment options with your cancer care team, friends, and family. It is usually not necessary to rush into treatment. You might want to get a second opinion before deciding what treatment is best for you.

Breast cancer type

The tissue removed during the biopsy (or during surgery) is first looked at under a microscope to see if cancer is present and whether it is a carcinoma or some other type of cancer (like a sarcoma). If there is enough tissue, the pathologist may be able to determine if the cancer is in situ (not invasive) or invasive. The biopsy is also used to determine the cancer's type, such as invasive ductal carcinoma or invasive lobular carcinoma. 

With an FNA biopsy, not as many cells are removed and they often become separated from the rest of the breast tissue, so it is often only possible to say that cancer cells are present without being able to say if the cancer is in situ or invasive.

The most common types of breast cancer, invasive ductal and invasive lobular cancer, generally are treated in the same way.

Breast cancer grade

A pathologist (a doctor who specializes in diagnosing disease in tissue samples) also assigns a histologic grade to the cancer (known as grading). The grade is a measure of how closely the cancer in the biopsy sample looks like normal breast tissue and how fast the cancer cells are dividing. It is based on the arrangement of the cells in relation to each other, as well as features of individual cells. The grade helps predict the patient's prognosis (outlook). In general, a lower grade number indicates a slower-growing cancer that is less likely to spread, while a higher number indicates a faster-growing cancer that is more likely to spread.

  • Grade 1 (well differentiated) cancers have relatively normal-looking cells that do not appear to be growing rapidly and are arranged in small tubules.
  • Grade 2 (moderately differentiated) cancers have features between grades 1 and 3.
  • Grade 3 (poorly differentiated) cancers have cells that appear very abnormal, grow rapidly, and rarely form tubules.

This system of grading is used for invasive cancers. Ductal carcinoma in situ is also graded, but the grade is based only on the features of the cancer cells.

Tests to classify breast cancers

Estrogen receptor (ER) and progesterone receptor (PR)

Receptors are cell proteins that can attach to certain substances, such as hormones, that circulate in the blood. Normal breast cells and some breast cancer cells have receptors that attach to estrogen and progesterone. These 2 hormones often fuel the growth of breast cancer cells.

An important step in evaluating a breast cancer is to test a portion of the cancer removed during the biopsy (or surgery) for estrogen and progesterone receptors. Cancer cells may contain neither, one, or both of these receptors. Breast cancers that contain estrogen receptors are often referred to as ER-positive cancers, while those containing progesterone receptors are called PR-positive cancers.

HER2/neu testing

In a small number of breast cancers in men, the cells have too much of a growth-promoting protein called HER2/neu (often just shortened to HER2). Tumors with increased levels of HER2/neu are referred to as HER2-positive.

The HER2/neu gene instructs cells to make this protein, and cells can become HER2-positive breast cancers by having too many copies of the HER2/neu gene (known as gene amplification). Cancer cells with greater than normal amounts of the HER2/neu protein tend to grow and spread more aggressively than other breast cancers.

All newly diagnosed breast cancers should be tested for HER2/neu because the outlook for HER2-positive cancers is improved if drugs that target the HER2/neu protein, such as trastuzumab (Herceptin®) and lapatinib (Tykerb®) are used as part of treatment. See the section " Targeted therapy for breast cancer in men" for more information on drugs that target this protein.

The biopsy or surgery sample is usually tested in 1 of 2 ways:

  • Immunohistochemistry (IHC): In this test, special antibodies that identify the HER2/neu protein are applied to the sample, which cause it to change color if abnormally high levels are present. The test results are reported as 0, 1+, 2+, or 3+.
  • Fluorescent in situ hybridization (FISH): This test uses fluorescent pieces of DNA that specifically stick to copies of the HER2/neu gene in cells, which can then be counted under a special microscope.

Many breast cancer specialists think the FISH test gives more accurate results than IHC, but it is more expensive and takes longer to get the results. Often the IHC test is used first. If the results are 1+ (or 0), the cancer is considered HER2-negative. People with HER2-negative tumors are not treated with drugs that target HER2.

If the test comes back 3+, the cancer is HER2-positive. Patients with HER2-positive tumors may be treated with drugs that target HER2.

When the result is 2+, the HER2 status of the tumor is not clear and the tumor is then tested with FISH. Some institutions also use FISH to confirm HER2 status that is 3+ by IHC and some perform only FISH.

A newer type of test, known as chromogenic in situ hybridization (CISH), works similarly to FISH, by using small DNA probes to count the number of HER2 genes in breast cancer cells. But this test doesn't require a special microscope and looks for color changes (not fluorescence) which may make it less expensive. Right now, it is not being used as much as IHC or FISH.

Classifying breast cancer based on hormone receptors and HER2 status

Doctors often divide invasive breast cancers into groups based on the presence of hormone receptors (ER and PR) and whether or not the cancer has too much HER2.

Hormone receptor-positive: If the breast cancer cells contain either estrogen or progesterone receptors, they can be called hormone receptor-positive (or just hormone-positive). Breast cancers in men that are hormone receptor-positive can be treated with hormone therapy drugs that lower estrogen levels, block estrogen receptors, or affect androgen (male hormone) levels (see the section, "Hormone therapy for breast cancer in men"). This includes cancers that are ER-negative but PR-positive. Hormone receptor-positive cancers tend to grow more slowly than those that are hormone receptor-negative (and don’t have either estrogen or progesterone receptors). Patients with these cancers tend to have a better outlook in the short-term, but cancers that are hormone receptor- positive can sometimes come back many years after treatment. About 9 out of 10 male breast cancers are hormone receptor-positive.

Hormone receptor-negative: If the breast cancer cells don’t have either estrogen or progesterone receptors, they are said to be hormone receptor-negative (or just hormone-negative). Treatment with hormone therapy drugs is not helpful for these cancers. These cancers tend to grow more quickly than hormone receptor-positive cancers. If they return after treatment, it is more often in the first few years.

HER2 positive: Cancers that have too much HER2 protein or gene are called HER2 positive. These cancers can be treated with drugs that target HER2.

HER2 negative: Cancers that don’t have excess HER2 are called HER2 negative. These cancers do not respond to treatment with drugs that target HER2.

Triple-negative: If the breast cancer cells don’t have estrogen or progesterone receptors and don’t have too much HER2, they are called triple-negative. Triple-negative breast cancers tend to grow and spread more quickly than most other types of breast cancer. Because the tumor cells don’t have hormone receptors, hormone therapy is not helpful in treating these cancers. Because they don’t have too much HER2, drugs that target HER2 aren’t helpful, either. Chemotherapy can still be useful, though.

Triple-positive: This term is used to describe cancers that are ER-positive, PR-positive, and have too much HER2. These cancers can be treated with hormone drugs as well as drugs that target HER2.

Other lab tests of breast cancers

Tests of ploidy and cell proliferation rate

These tests might be done to help predict how aggressive a cancer may be. The ploidy of cancer cells refers to how much DNA they contain. If there's a normal amount of DNA in the cells, they are said to be diploid. If the amount is abnormal, then the cells are described as aneuploid. Tests of ploidy may help determine prognosis, but they rarely change treatment and are considered optional. They are not usually recommended as part of a routine breast cancer work-up.

The S-phase fraction is the percentage of cells in a sample that are replicating (copying) their DNA. DNA replication means that the cell is getting ready to divide into 2 new cells. The rate of cancer cell division can also be estimated by a Ki-67 test. If the S-phase fraction or Ki-67 labeling index is high, it means that the cancer cells are dividing more rapidly, which indicates a more aggressive cancer.

Tests of gene patterns

Researchers have found that looking at the patterns of a number of specific genes at the same time (sometimes referred to as gene expression profiling) can help predict whether or not an early-stage breast cancer is likely to come back after initial treatment. This can help when deciding whether to use additional (adjuvant) treatment such as chemotherapy after surgery. Two such tests (Oncotype DX® and MammaPrint®) look at different sets of genes.

Although many doctors use these tests (along with other information) to help make decisions about offering chemotherapy to women with breast cancer, the usefulness of these tests hasn’t really been studied well in men. Still, men may want to ask their doctors if these tests might be appropriate.

If you’d like to know more about biopsies and the ways they’re tested, see Testing Biopsy and Cytology Specimens for Cancer.

The American Cancer Society medical and editorial content team
Our team is made up of doctors and master’s-prepared nurses with deep knowledge of cancer care as well as journalists, editors, and translators with extensive experience in medical writing.

Last Medical Review: October 10, 2014 Last Revised: January 26, 2016

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