Breast Cancer Stages And Types
Breast Cancer Staging System
Once breast cancer is diagnosed, tests are performed to determine the cancer stage, which will influence which type of treatment patients receive.
The TNM cancer staging system, used by the American Joint Commission on Cancer (AJCC), is widely accepted and has used a combination of T- tumor size and features, N- lymph node involvement and M- presence or absence of distant metastases to stage cancer. However, there is increasing recognition that the prognosis of breast cancers is determined by not only anatomical presentation, like tumor size and lymph node involvement, but also by biology. Estimates of tumor grade, hormone and HER2 receptors, and multigene assays such as Oncotype, PAM 50 EndoPredict, Mammoprint or Breast Cancer Index also help to determine to the aggressiveness and chance of recurrence of breast cancers. These features have been incorporated into a new version of the AJCC staging system, Version 8, on January 1, 2018. It is felt that combining both the anatomic data and the biologic features of a cancer will give a more accurate picture of the cancer and its chance of recurrence.
Stages of Breast Cancer
Carcinoma in situ (DCIS) is considered Stage 0, since invasive cancer has not yet formed.
Stage I means that cancer has formed. In stage IA, cancer has not yet spread outside the breast, and the tumor is 2 centimeters or smaller. In stage IB, small clusters of breast cancer cells are found in the lymph nodes, and either no tumor is present, or the tumor is 2 centimeters or smaller.
Stage IIA is defined as either: a tumor between 2 and 5 centimeters without any cells having spread to the lymph nodes; or, no tumor is present in the breast, or the tumor is 2 centimeters or smaller, but there are cancer cells in 1 to 3 axillary lymph nodes or in the lymph nodes near the breastbone. (Axillary lymph nodes are in the armpit region and drain lymph from the breast and nearby areas.)
In stage IIB, the tumor is either: between 2 and 5 centimeters in size, and small clusters of breast cancer cells are found in the lymph nodes; the tumor is between 2 and 5 centimeters in size, and cancer has spread to 1 to 3 axillary lymph nodes or to the lymph nodes near the breastbone; or the tumor is larger than 5 centimeters, and cancer has not spread to the lymph nodes.
In stage IIIA, the tumor is either: larger than 5 centimeters, and small clusters of breast cells are found in the lymph nodes; larger than 5 centimeters, and cancer has spread to 1 to 3 axillary lymph nodes or to the lymph nodes near the breastbone; or, no tumor is present in the breast, or the tumor may be any size, and cancer cells are found in 4 to 9 axillary lymph nodes or in the lymph nodes near the breastbone.
In stage IIIB, the tumor may be any size and cancer has spread to the chest wall and/or to the skin of the breast and caused swelling or an ulcer. Cancer that has spread to the skin may be considered inflammatory breast cancer. In addition, cancer may have spread to up to 9 axillary lymph nodes or the lymph nodes near the breastbone.
In stage IIIC, the tumor may be any size. Cancer may have spread to the skin of the breast and caused swelling or an ulcer and/or has spread to the chest wall. Also, cancer has spread to 10 or more axillary lymph nodes, lymph nodes above or below the collarbone, or axillary lymph nodes and lymph nodes near the breastbone. Cancers with these features in the nodes or chest wall without a breast mass are also considered IIIC.
Any spread of breast cancer outside of the breast and draining lymph node regions is considered Stage IV. For more information on Stage IV breast cancer, click here.
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Types of Breast Cancer
Lobular breast cancer is a distinct subtype of breast cancer.
Invasive Lobular cancer (ILC) has specific molecular features distinct from ductal breast cancer. with its own uniques subtypes and variants. Lobular presents differently in the breast.
Invasive ductal carcinoma (IDC) begins in the milk ducts whereas invasive locular begins in lobules (the milk producing glands of the breast).
A hallmark feature of classical invasive lobular breast cancers is that tumors form in single-file strands rather than the more common “lump” seen in invasive ductile breast cancers.
ILC has differences in presentation and behavior symptoms that can include hardening of the breast, swelling, changes in the appearance of the breast, nipple skin changes or breast pain.
How Is Lobular Breast cancer diagnosed?
Current imaging tools are less reliable for early detection of lobular disease and detection of distance recurrence. ILC is often not seen in routine mammogram or other screening.
ILC tumors can be more difficult to identify on imaging studies and by physical exam because many lack the protein called e-cadherin, which causes an unusual linear growth pattern and not lumps.
If it’s found by palpating the breast, it is more likely to resemble a fullness or thickening in one area. On a mammogram, ILS often appears as an area of distortion.
The diagnosis is confirmed by extracting a small piece of the abnormal tissue with a needle and existing it under a microscope.
ILC has generally been treated like HR-positive invasive ductal carcinoma. Treatments may include: surgery, radiation therapy, chemotherapy or hormonal therapy.
There is increasing evidence that standard of care chemotherapy and endocrine therapies currently equally applied to breast cancer patients may have different effectiveness as applied to ILC and IDC (Invasive Ductal Carcinoma).
DCIS is a noninvasive condition referring to abnormal cells in the lining of the breast duct that have not spread to other tissues. It is possible for DCIS to become invasive cancer and spread to other parts of the body, so treatment can reduce the likelihood of recurrence. DCIS is considered Stage 0, since it is noninvasive.
How is DCIS diagnosed?
DCIS can be diagnosed starting with a physical examination, though more often a lump may not be present with DCIS. The abnormal cells can also be detected with a mammogram, which shows the calcifications from old cancer cells dying off and piling up. If a patient has an abnormal mammogram, the doctor will perform a biopsy in which tissue is extracted and examined.
How is DCIS treated?
DCIS may be treated with breast-conserving surgery, which is often followed by radiation therapy. With breast-conserving surgery, only the DCIS and some normal tissue around it is removed, and this type of surgery often does not alter the appearance of the breast significantly. Breast-conserving surgery may also be called a lumpectomy, a partial mastectomy, breast-sparing surgery, or segmental mastectomy.
DCIS can also be treated with single or double mastectomy, another type of surgery in which the whole breast is removed.
The goal of radiation therapy is to keep the DCIS from returning to the same breast, and research has shown that the risk of recurrence is substantially reduced by radiation therapy in some patients. Your radiation oncologist will take into account age, size of tumor, other medical problems and degree of differentiation in the cells (microscopic appearance) before making a recommendation.. For patients with DCIS, radiation therapy would follow surgery. Radiation therapy can cause changes in the skin and increases the risk of developing secondary cancers in the future.
Patients may also have a recommendation for hormonal therapy. The goal is to decrease the likelihood of developing either further DCIS in or an invasive cancer.
How is HER2-positive breast cancer diagnosed?
A lab test will measure the presence of HER2 receptor proteins on the cancer cells and how much HER2 protein is being made in a tissue sample. If the amount of genes and proteins reach a certain level, the cancer is considered HER2 positive. This is measured by the pathologist using special stains on the slides of the tumor specimen. In certain cases, a more precise test called FISH (in situ fluorescent hypbridization) may be used.
HER2 positive breast cancer accounts for 15-20% of all breast cancers. The cancer cells may also be hormone receptor positive (HR positive, or ER or PR positive) or HR negative. HER2 positive breast cancers have a higher chance or recurrence and tend to do so earlier than other breast cancers. Knowing your HER2 status will help your doctor determine your treatment options.
How is HER2-positive breast cancer treated?
Treatment for HER2 positive breast cancer is aimed at blocking the HER2 protein receptor's ability to stimulate cell growth. This can be done with targeted therapy, drugs that bind to the HER2 protein receptor, interrupt the cells' ability to receive signals that encourage cells to grow, or that stop cancer cells from dividing and growing. These therapies do less damage to normal, healthy cells than chemotherapy.
In particular, the drugs trastuzumab/pertuzumab and palbociclib have had success in treating women with HER2 positive metastatic breast cancer. Trastuzumab binds to HER2 receptors on the surface of cancer cells, blocking the cells' ability to receive growth signals. It is used in combination with chemotherapy, and for prevention of recurrence post-surgery. Pertuzumab works similarly. Palbociclib stops the cells from growing and dividing. However, there are other targeted therapies available to women with metastatic disease or to women with early-stage HER2 positive disease.
Breast cancer cells can overexpress (be positive for) either estrogen receptors (ER+), progesterone receptors (PR+), or both. Hormone receptor positive tumors can occur over several years after an initial diagnosis.
How is hormone receptor–positive breast cancer diagnosed?
A pathologist will test the breast cancer cells for estrogen or progesterone receptors using special stains on the tumor specimen called immunohistochemistry or IHC. One type of multigene test, the Oncotype DX, may also provide information about the hormone receptor status by measuring the RNA (genetic material in the tumor) that codes for the development of these receptors on the cell surface.
How is hormone receptor–positive breast cancer treated?
Hormone therapy either blocks the body’s ability to produce estrogen or progesterone, or interferes with the effects of hormones on breast cancer cells, which helps to slow or stop the growth of hormone-sensitive tumors.
Ovarian ablation, or treatment that stops or lowers the amount of estrogen made by the ovaries, can be done surgically, through radiation, or using drugs. With surgical treatment (removal of the ovaries) or radiation, the ovarian ablation is typically permanent. Suppressing ovarian function with drugs is temporary, and this group of medicines functions by interfering with signals from the pituitary gland stimulating the ovaries to produce estrogen. Side effects of ovarian suppression may include bone loss, mood swings, depression, and loss of libido.
Selective estrogen receptor modulators (SERMs) bind to estrogen receptors, preventing estrogen from binding. In addition to blocking estrogen activity, SERMs can also mimic estrogen effects because of their ability to bind. A SERM called tamoxifen, for example, blocks the effects of estrogen in breast tissue but acts like estrogen in the uterus and bone. Tamoxifen is effective in treating early-stage breast cancer after surgery. Some SERMs can treat advanced or metastatic breast cancer. Side effects of tamoxifen may include risk of blood clots, stroke, cataracts, endometrial and uterine cancers, bone loss in premenopausal women, mood swings, depression, and loss of libido.
Other types of drugs called aromatase inhibitors block the activity of an enzyme called aromatase, which the body uses to make estrogen in the ovaries and in other tissues. These are most effective in postmenopausal women, since premenopausal women produce more aromatase than can be blocked effectively. However, certain aromatase inhibitors can treat early-stage breast cancer in pre and postmenopausal women. Others can treat metastatic cancer (cancer that has spread) in postmenopausal women. Aromatase inhibitors can also be effective in neoadjuvant (pre-surgery) (pre-surgery) treatment of breast cancer in postmenopausal women. Side effects of aromatase inhibitors may include risk of heart attack, angina, heart failure, and hypocholesterolemia, bone loss, joint pain, mood swings, and depression. The aromatase inhibitors used in clinical practice include anastrazole, letrazole and exemestane.
Other antiestrogen drugs, such as fulvestrant, bind to and disrupt the estrogen receptor, preventing estrogen stimulation of the cells. Unlike the SERMS they do not mimic estrogen function in other tissues. These drugs function solely as estrogen antagonists. Side effects of fulvestrant include gastrointestinal symptoms, loss of strength, and pain.
Side effects of hormone therapy vary based on the type of drug or treatment used, and the risks and benefits should be assessed for each patient.
Resistance to hormone therapy
Sometimes, despite the presence of the estrogen receptor or progesterone receptor, cells do not respond to hormone therapy, or they respond initially and become resistant. Laboratory investigation has identified biochemical pathways of resistance. Combinations of drugs to block these resistance pathways, along with hormonal therapy, have been effective against ER positive tumors. Two examples include a drug call everolimus that blocks the MTOR resistance pathways, and a family of drugs called CDK 4-6 inhibitors that block a different resistant pathway. These have shown excellent results in metastatic ER positive breast cancer and are being tested in adjuvant prevention setting in combination with other hormonal therapy. Current examples include palbociclib, ribociclib and abemaciclib.
How is inflammatory breast cancer diagnosed?
Inflammatory breast cancer progresses very quickly, and at diagnosis, is considered either stage III or IV. Because there is often no lump present in the breast, this type of cancer can be difficult to diagnose through a physical examination or mammogram. Often, it is initially misdiagnosed as an infection of the breast or the overlying skin, like mastititis or cellulitis. The following symptoms are the minimum criteria for diagnosing inflammatory breast cancer: erythema (redness), edema (swelling), peau d'orange (ridged or pitted skin) in the affected breast, and/or abnormal breast warmth; the symptoms have been present for less than 6 months; the erythema covers at least a third of the breast; and initial biopsy samples from the affected breast show invasive carcinoma.
A doctor will perform a diagnostic mammogram of the affected breast and nearby lymph nodes, as well as a PET or CT scan and a bone scan, to determine if the cancer has spread to other parts of the body. Determining the stage of inflammatory breast cancer helps doctors determine the best possible treatment plan. Biopsied cells will be tested to determine whether the cancer is hormone receptor positive or HER2 positive.
How is inflammatory breast cancer treated?
Inflammatory breast cancer is typically treated with systemic chemotherapy to help shrink the tumor, then surgery to remove the tumor, then radiation therapy.
Neoadjuvant (pre-surgery) chemotherapy is given generally for six cycles over the course of 4–6 months. If the cancer is HER2 positive, a targeted therapy can be used to specifically target its cells with drugs like trastuzumab and pertuzumab. This type of treatment can be given as part of neoadjuvant (pre-surgery) therapy and after surgery. If cancer cells are hormone receptor positive, hormone therapy will be used; hormone therapies either block hormones from binding to their receptors, or block the production of that hormone, which causes the cancer cells to stop growing and die.
The type of surgery used to treat inflammatory breast cancer is typically a modified radical mastectomy. This surgery involves the removal of the entire breast, most or all of the lymph nodes under the adjacent arm, and sometimes the lining over the underlying chest muscles or the smaller chest muscle.
After surgery, doctors may radiate the chest wall under the removed breast. While breast reconstruction is an option post-surgery, many doctors recommend delaying reconstruction because of the importance of radiation therapy in treating inflammatory breast cancer.
Adjuvant (post-surgery) therapy, including chemotherapy, hormone therapy, targeted therapy, or some combination of those treatments, may be administered after surgery to reduce the chance of cancer recurrence.
Written by: Anna Szilagyi. Reviewed by: Dr. James Speyer, NYU Langone.