Breast Cancer: Staging and Survival Rate

When diagnosed with breast cancer, most patients are naturally anxious to learn the severity of their disease – the stage of breast cancer they have. The cancer stage gives them an idea of their prognosis and the types of treatment that may be needed to recover from the disease. Being well-informed about the stages of breast cancer can help patients prepare for what’s to come physically, mentally and emotionally.

The most common staging system for breast cancer follows the American Joint Committee of Cancer (AJCC) staging manual. The 8th edition, which is the latest edition of the staging manual, has both clinical and pathological staging systems for breast cancer.

The clinical prognostic stage is the stage given regardless of the type of treatment. It is based on physical examinations, imaging tests, diagnostic tests, biopsies and your medical history.

The pathological prognosis stage is the stage given after surgery or resection of the tumor. It is based on information obtained from the surgery as well as from any tests done before surgery. The pathological prognosis stage tends to be more reflective of the patient’s outlook than the clinical prognosis stage as it is based on more accurate information on the size and spread of cancer.

Both the clinical prognostic stage and pathological prognosis stage are based on:

• Size of primary tumor
• Nodal involvement
• Presence of distant metastases
• Tumor grade (how different tumor cells look compared to normal cells)
• Estrogen-Receptor (ER) status
• Progesterone-Receptor (PR) status
• HER2 status
• Multi-gene expression assay score (e.g. Oncotype DX® recurrence score)

The size of the primary tumor, nodal involvement and presence of distant metastases are described using the AJCC TNM system.

Primary tumor (T)

This category is based on the size of the tumor and whether or not the cancer has spread to the skin of the breast or the chest wall behind the breast. It is described with the letter ‘T’ followed by ‘X’, ‘is’, 0, 1, 2, 3 or 4.

TX: Size of the tumor cannot be measured.

T0: No tumor is present.

Tis: Carcinoma in situ (precancerous cells, e.g., DCIS or Paget’s disease of the breast)

T1: Tumor is smaller than 3/4 of an inch.

T2: Tumor is larger than 3/4 of an inch but not over 2 inches.

T3: Tumor is larger than 2 inches.

T4: Any size of tumor growing into the chest wall or skin.

Nodal involvement (N)

This category looks at how many lymph nodes the cancer has spread to, if any. It is described with the letter ‘N’ followed by ‘X’, 0, 1, 2 or 3. This is a brief and simplified description of nodal involvement:

NX: The lymph nodes cannot be checked.

N0: No cancer has advanced to the neighboring lymph nodes.

N0(i+): Few cancer cells, referred to as isolated tumor cells, were observed in routine stains or when utilizing a specific staining technique known as immunohistochemistry.

N0(mol+): Cancer cells were not found in the underarm lymph nodes, even with the application of specialized stains; however, small amounts of cancer cells were identified through a method called RT-PCR. RT-PCR is a molecular test capable of detecting extremely small quantities of cancer cells.

N1: Cancer has advanced to 1 to 3 underarm lymph node(s), or has been discovered in lymph nodes near the breast bone

N2: Cancer has advanced to 4 to 9 underarm lymph nodes or caused swollen lymph nodes near the breast bone

N3: Cancer has spread to the lymph nodes below the collarbone, around the armpit and behind the breast bone, or above the collarbone.

Distant metastases (M)

This category determines if the cancer has spread to a more distant part of the body like the lungs, bones, or liver, after imaging tests, physical examination or biopsy. It is described with the letter ‘M’ followed by 0 or 1.

M0: Cancer has not advanced to other parts of the body. cM0(i+): No sign of cancer advancing to other parts of the body but cancer cells are detected in the blood or bone marrow, or lymph nodes far from the breasts, in laboratory tests.

M1: Cancer has advanced to distant organs (common sites include the bones, lungs, brain or liver).

In addition, the 8th edition staging manual looks at the tumor grade and breast biomarkers (ER, PR, HER2).

In pathology, tumor grading compares the appearance of the breast cancer cells to the appearance of normal breast tissue under a microscope. Pathologists look for certain features that help to predict whether the cancer will spread.

Systems used to describe tumor grade can differ depending on the cancer type. Generally, most breast tumors are graded as 1, 2, or 3:

• Grade 1: Well differentiated (low grade)
• Grade 2: Moderately differentiated (intermediate grade)
• Grade 3: Poorly differentiated (high grade)

High-grade tumors look the most different from normal breast cells and these tend to have the worst prognosis.

Learn more: Understanding your Histopathology Report: Classification of Breast Cancer

The biopsied tissue will also be tested for breast cancer biomarkers, mainly estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). This is done to establish the hormone receptor and HER2 receptor status, which provide both prognostic and predictive value.

• ER

Breast cancers with estrogen receptors are known as ER-positive breast cancers, while those without ER are known as ER-negative breast cancers.

• PR

Breast cancers with progesterone receptors are known as PR-positive breast cancers, while those without PR are known as PR-negative breast cancers.

• HER2

Some cancerous tumors have cancer cells that make too much of a protein called HER2. These cancers are known as HER2-positive breast cancer.

Receptors are cell surface proteins that receive stimulants from the surroundings of cells. In response to certain stimulants, the receptors relay signaling messages to the cells, which can affect cellular appearance, behavior, or function. Depending on the presence of these receptors, specific anticancer drugs are available for treating different molecular subtypes. Cancers that do not have any of these receptors are known as triple-negative breast cancers. These can be harder to treat due to their limited treatment options.

A multi-gene expression assay is a diagnostic test used to determine a breast cancer’s gene expression profile. It analyzes the levels of different cancer-causing oncogenes to determine the aggressiveness of the cancer. It helps to determine the likelihood of the cancer to spread and/or recur in the future and whether or not chemotherapy would be beneficial. Oncotype DX® is one such test that may be used. The results obtained from such a test may influence the staging of the cancer.

With all this information, breast cancer is staged from stage 0 to IV (with sub-categories for each type). This determines the patient’s clinical prognostic stage. If the patient undergoes resection of their primary tumor, the T and N sections of the TNM staging will be re-evaluated according to the resection outcome. This updated information, together with the preoperative tumor grade and biomarker information, is used to determine the pathologic prognostic stage.

The outlook for early-stage breast cancer is generally positive. Stage 0 and stage I have close to 100% 5-year survival rate. For stage II and stage III breast cancer, the 5-year survival rates are approximately 93% and 72%, respectively. However, when the disease metastasizes, the prognosis takes a significant downturn. Merely 22% of individuals with stage IV breast cancer are expected to survive the following 5 years.

While learning your breast cancer stage can be a stressful experience, it is an important step in the cancer journey. Being informed about the stages of breast cancer can help you feel more in control and better prepared for the future. It is normal to experience a myriad of emotions after receiving a breast cancer diagnosis and relying on a strong support system to help you through each step of the process is crucial. Be assured that at every step of the way, your healthcare team will be there for you to answer your queries and help you along the way.