Stages and Types of Breast Cancer

Stages-and-Types

Once breast cancer is diagnosed, tests are performed to determine the stage of the disease, which will influence which type of treatment patients receive.

Stage 0

Carcinoma in situ (DCIS or LCIS) is considered Stage 0, since invasive cancer has not yet formed.

Stage I

Stage I signifies 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 II

Stage IIA is defined as either: a tumor between 2 and 5 centimeters without cancer having spread to the lymph nodes; or, no tumor is present in the breast, or the tumor is 2 centimeters or smaller, but there is cancer 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.

The prognosis of breast cancers is not only determined by anatomical presentation like tumor size and lymph node involvement, but by biology.”

Stage III

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 is 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 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, 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 presenting with these features in the nodes or chest wall without a breast mass are also IIC

Stage IV

Any spread of breast cancer outside of the breast and draining lymph node regions.

Types of Breast Cancer

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.

HER2-positive breast cancer refers to the presence of a high amount of human epidermal growth factor receptor 2 genes and HER2 proteins on cancer cells.

How is HER2-positive breast cancer diagnosed?

A laboratory test will measure the presence of HER2 receptor proteins on the cancer cells and how much HER2 protein is made in a tissue sample. If the level of genes and proteins are higher than normal, the cancer is considered HER2 positive. This lab test helps determine treatment options. 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 account for 15-20% of all breast cancers. The cells may also be ER or PR positive ,or they may be negative for hormone receptors. HER2 positive breast cancer have a higher chance or recurrence and tend to do so earlier than other breast cancers.

How is HER2-positive breast cancer treated?

Treatment for HER2 positive breast cancer is aimed at interrupting the stimulation of cell growth that occurs through the HER2 receptor on the cell surface. This can be done with antibody drugs that bind to the receptor or small molecule oral drugs that interrupt the HER2 mediated signal inside the cell.

The first antibody drug trastuzumab binds to HER2 on the surface of HER2-positive cancer cells, and may kill the cells. In combination with chemotherapy, it has had dramatic effects in metastatic disease, as well when used for prevention in the adjuvant (post-surgica) setting. Pertuzumab is another antibody that binds to a different part of the HER 2 receptor, and in combination with trastuzumab, is used in patients with locally advanced or metastatic breast cancer. Infrequently, some women may develop heart damage from treatment with trastuzumab and /or pertuzumab, and the risk of heart damage is higher when these drugs are taken with certain chemotherapy drugs, especially doxorubicin. Doctors will often check patients’ heart function before and during treatment with these drugs.

Small molecule drugs known as tyrosine kinase inhibtors can also block the HER 2 pathway. They include lapatinib and neratinib, which may also be used in metastatic disease. Neratinib was recently approved for use in prevention once patients completed their chemotherapy and antibody treatment. The most common side effects of these oral agents are diarrhea or skin rash.

Hormone receptors are proteins on the surface of all cells, including normal breast cells and some breast cancer cells, that help to mediate how hormones such as estrogen interact with cells; they may also stimulate cell growth.

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 Abation

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.

SERMs

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.

Aromatase Inhibitors

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.

Inflammatory breast cancer is a type of disease in which cancer cells block lymph vessels in the skin of the breast, causing it to become red and swollen.

How is inflammatory breast cancer diagnosed?

Inflammatory breast cancer progresses very quickly, and at diagnosis, is either stage III or IV disease. 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.

The affected breast will also be examined to determine whether the cancer is hormone receptor positive or HER2 positive. Testing for inflammatory breast cancer includes a diagnostic mammogram of the 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 for patients.

How is inflammatory breast cancer treated?

Inflammatory breast cancer is typically treated with a multimodal approach: 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 cells are HER2 positive, therapy can be used to specifically target this protein with drugs like trastuzumab and pertuzumab. This type of treatment can be administered as part of neoadjuvant (pre-surgery) therapy and after surgery. If cancer cells are hormone receptor positive, hormone therapy with drugs that either block hormones from binding to their receptors, or block the production of that hormone, can cause 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, radiation therapy is used targeting 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 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.

LCIS is a condition in which abnormal but noncancerous cells are found in the breast lobules, which are not cancer cells. LCIS can be considered Stage 0 since it is noninvasive and has not spread outside the breast lobules.

LCIS cells seem not to directly develop into invasive cancer. Rather they indicate an increased risk of developing an invasive cancer in either breast.

How is LCIS diagnosed?

LCIS can be diagnosed from an abnormal mammogram or biopsy, though it does not always appear on a mammogram and may not show any symptoms or changes in the breast. If a patient does have an abnormal mammogram or lump, a biopsy will be done to examine tissue from the breast.

How is LCIS treated?

Treatment for LCIS focuses on risk reduction, since the condition is not considered cancer. Careful observation in the form of regular breast self-exams, clinical breast exams, mammograms, and/or magnetic resource imaging (MRI) help monitor the condition in case signs of invasive breast cancer do surface.

Other risks for developing breast cancer and the physical exam of the breast will be considered by the physicians in determining how often to recommend these tests.

Hormonal therapy has also been shown to reduce breast cancer risk in some patients. Since LCIS is typically hormone receptor–positive, hormone therapy drugs may be effective in reducing risk of developing LCIS or invasive breast cancer. Drugs such as tamoxifen or raloxifene are used to block the effects of estrogen and limit the growth of abnormal cells. Side effects of these drugs include risk of blood clots, stroke, cataracts, endometrial and uterine cancers, bone loss in premenopausal women, mood swings, depression, and loss of libido. (Note some of these side effects are occur only very infrequently).

Some women with high risk of breast cancer, such as a strong family history of breast cancer, may choose preventative surgery called prophylactic mastectomy to lower their risk of invasive breast cancer. With this type of surgery, both breasts are removed, since LCIS and other factors can increase the risk of developing cancer in both breasts.

If breast cancer cells test negative for estrogen receptors, progesterone receptors, and HER2, the cancer is called triple-negative. While there are subtypes of triple negative cancers, they tend to be more aggressive with a higher chance of systemic recurrence.

How is triple-negative breast cancer diagnosed?

Triple-negative breast cancer is diagnosed after lab tests measuring the presence of hormone receptors (estrogen and progesterone) and HER2 genes and proteins. If cancer cells test negative for all three, this determines that the cancer cells do not depend on estrogen, progesterone, or HER2 to grow.

How is triple-negative breast cancer treated?

Though hormone therapy or therapies that target HER2 receptors are not effective for treating triple-negative breast cancer, combinations of chemotherapy, surgery, and radiation are used to treat the disease. Lumpectomy is effective in triple-negative breast cancer; bilateral mastectomy, surgery that removes all breast tissue that could become cancer, is also an option to prevent recurrence. Neoadjuvant (pre-surgery) chemotherapy can be considered to target triple-negative breast cancer.

Recent studies suggest that triple-negative breast cancers may be a target for some of the new immune therapy antibody drugs that have been effective in other kinds of cancer; this still requires more investigation.

Written by: Anna Szilagyi. Reviewed by: Dr. James Speyer, NYU Langone.


1 The current staging system is based primarily on anatomy. The TNM system used by the AJCC American Joint Commission on Cancer is widely accepted and uses a combination of T- tumor size and features, N- lymph node involvement and M presence or absence of distant metastases. The current Seventh addition of this system is summarized below. Note there is increasing recognition that the prognosis of breast cancers not only are determined by anatomical presentation- tumor size and lymph node involvement but is also determined by biology. Estimates of tumor grade, hormone and HER 2 receptors and multigene assays such as Oncotype, PAM 50 EndoPredict or Mammoprint or Breast Cancer Index also help to determine to aggressiveness and chance of recurrence of breast cancers. These features have been incorporated into a new version of the AJCC staging system- Version 8 that will replace the current system 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

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