Breast Cancer-5

TESTS FOR DISTANT METASTASES

Cancer cells have the ability to leave the original tumor site, travel to distant locations, and metastasize in organs such as the liver, lungs, or bones. The process of metastasis is dynamic and requires an optimal environment in order for a tumor cell to proliferate, invade surrounding tissues, be released into the circulation, adhere to blood vessels in the liver, invade the liver, proliferate, and establish its own blood supply (tumor angiogenesis). This complex process requires interaction of tumor cells with the microenvironment of the liver to the extent that the tumor cell can utilize the growth factors and blood vessels of the liver in order to grow.

In addition to tests for prognostic and predictive factors, women diagnosed with node-positive breast cancer will require a number of tests to confirm that the cancer has not spread to other organs, such as the lungs, liver, and bone. Only about 6% of women when first diagnosed with breast cancer have distant metastases (Ries et al. 2000). Most women found to have metastases have previously been treated for the disease and are experiencing a recurrence.

Symptoms such as shortness of breath, a chronic cough, weight loss, and bone pain may indicate distant metastases. However, only after specific tests can the occurrence of distant metastasis be confirmed or ruled out. The three primary tests performed are blood tests that check for liver and/or bones metastasis, bone scans to test for bone metastasis, and x-ray/CT scans to test for chest, abdomen, and liver metastasis. Based on the results of the primary tests and the symptoms the woman experiences, further testing may be required.

Common Tests for Distant Metastases

X-rays. An x-ray is a test in which an image is created using low doses of radiation reflected on film paper or fluorescent screens providing an image of specific areas. The films created by x-rays show different features of the body in various shades of gray. The darkest images are those areas that do not absorb x-rays well; the lighter images are dense areas (like bones) that absorb more of the x-rays. To enhance visibility, some x-ray exams will use a contrasting solution that can be swallowed, injected intravenously into the circulatory system, or given by an enema to locate or confirm possible metastases.
Computer Axial Tomography (CAT or CT) scan.
This procedure combines the use of a digital computer together with a rotating x-ray device to create detailed cross-sectional images, or "slices," of the different organs and body parts. This procedure may or may not involve injecting an intravenous contrasting solution into the circulatory system. It does, however, always involve exposure to ionizing radiation. A CAT scan has the unique ability to image a combination of soft tissue, bone, and blood vessels and can assist in locating possible metastasis.

Magnetic Resonance Imaging (MRI).
MRIs involve no ionizing radiation and can be used for precise imaging of any organ suspected of having metastases. This is a special imaging technique used to image internal structures of the body, particularly the soft tissues. An MRI image is often superior to a normal x-ray image. In an MRI exam, the patient passes through a tunnel surrounded by a magnet, which polarizes hydrogen atoms in the tissues and then monitors the summation of the energies within living cells. A computer tracks the magnetism and produces a clear picture of the tissues, particularly soft tissues. Images are very clear and are particularly good for soft tissue, brain, and spinal cord, joints, and abdomen. These scans may be used for detecting some cancers or for following their progress.

Positron Emission Tomography (PET). A highly specialized imaging technique using short lived substances such as simple sugars (glucose), which are labeled with signal emitting tracers (18-fluoro-deoxyglucose (18-FDG)) and injected into the patient. A scanner records the signals these tracers emit as they travel through the body and collect in various organs targeted for examination. Although all cells use glucose, more glucose is used by cells with increased metabolism such as tumor cells, which use more glucose than neighboring cells, and thus, they are easily seen on the PET scan. PET uses a camera that produces powerful images to reveal metastasis that other imaging techniques simply cannot detect. This technique is very sensitive in deciphering and picking up active cancer cells or tumor tissue but does not measure size. PET can follow the course of cancer through the body and accurately show the extent of the disease. PET can differentiate between normal tissue, scar tissue, and malignant cancerous tissue.

Ultrasound. Very high frequency sound waves are used to produce an image of many of the internal structures in the body without exposure to ionizing radiation. This is highly operator-dependent and is thought to be useful in diagnosis but not particularly accurate in the assessment of tumor response. For the latter, CT or MRI scans are more accurate. Intraoperative ultrasonography is useful in the detection of liver metastases.

Bone Scan. A bone scan is a nuclear medicine study of the body skeleton used to look for cancer, stress fractures, and other bone or joint problems. It does not measure bone density and is not used to diagnose osteoporosis. This procedure uses a radioisotope tracer (Technetium-99m MDP or HDP) injected intravenously into the circulatory system. This radioactive compound localizes in the bone and the distribution of the radioactivity in the body is recorded by the radionuclide scanner (better known as a gamma or scintillation camera), producing an image of the tracer's distribution in the skeletal system. This recording can reveal the presence of bone metastases.

Bone Density. Since excessive bone breakdown releases tumor growth factors into the bloodstream that can fuel cancer growth, a bone density scan and a test that can be used to assess bone resorption rates should be regularly performed for cancer patients. All bone density scan measurements with the exception of ultrasound use small doses of radiation to determine the amount of bone present.

DPD. The deoxypyridinoline (DPD) cross-links urine test (Pyrilinks-D) can be used to assess bone resorption rates; this test should be done every 60-90 days to detect bone loss in patients with cancer that has a proclivity to spread to bone. A QCT bone density scan should be done annually. Every cancer patient should take a bone-protecting supplement to protect against excess bone breakdown. For information regarding maintaining bone integrity refer to the protocol Cancer Treatment: The Critical Factors.

QCT. Quantitative Computed Tomography, or QCT Densitometry (often referred to as a QCT bone density scan) is a method used to measure bone mass. The principle underlying QCT densitometry and other bone mass measurements (such as DXA) is that calcified tissue will absorb more x-rays than surrounding tissue so that the CT density measurement can be used to measure total bone mass within a sample of tissue. With proper technique, precision for the conventional (2D) method is 2-3%, and about 1% for 3D QCT, so monitoring patients at yearly intervals yields clinically useful results. Only QCT isolates the metabolically active bone for analysis. The QCT examination is performed on any modern CT scanner and takes approximately 10 minutes. Insurance companies and Medicare may reimburse for QCT examinations.

DXA. DXA stands for dual x-ray absorptiometry. It was previously known as DEXA, dual energy x-ray absorptiometry. Low dose x-rays of two different energies are used to distinguish between bone and soft tissue, giving an accurate measurement of bone density at these sites. However, DXA also includes aortic calcification and osteophytes in the calculation of bone mineral. Lateral DXA, has been shown to have a sensitivity intermediate between the high sensitivity of QCT and the somewhat lower one of conventional DXA (used for detection of osteoporosis), but it uses 4-10 times the radiation exposure, is less precise, and the study time is increased compared to conventional DXA/QDR.

Blood Tests. A variety of blood tests can assess the health of different organs and systems in your body. "Cancer marker" tests can detect possible cancer activity in the body. If cancer is present, it can produce specific protein in the blood that can serve as a "marker" for the cancer. CA 15.3 is the name of a protein used to find breast and ovarian cancers, although it is important to note that there may be insufficient quantities of this protein present in the blood to ensure early stage breast cancer detection. Creatine-kinase-BB serves as a marker for breast, ovarian, colon, and prostate cancers. CEA (carcinoembryonic antigen) is a marker for the presence of colon, lung, and liver cancers and a marker for secondary breast and ovarian cancer sites. CA125 may signal ovarian cancer and secondary breast and colorectal cancer sites. TRU-QUANT and CA 27.29 are other examples of proteins associated with the recurrence of breast cancer (more information on tumor markers will follow). Blood tests should evaluate for the presence of anemia or hepatic dysfunction, both of which can be consequences of the patient’s underlying cancer.

TREATMENT OF BREAST CANCER

a)Localized Treatment
b)Adjuvant Treatment

In the past 20 years, many strides have been made to improve the treatment of breast cancer. Some of the trauma associated with breast cancer treatment has been reduced because of increased early detection through mammography, surgery options that conserve much of the breast, and the increasing long-term survival rate. The treatment goal is to rid the body of the cancer as completely as possible and to prevent the cancer from returning. This is usually accomplished by utilizing multimodalities, including surgery, anticancer drugs (chemotherapy), irradiation, hormone therapy, nutritional supplementation, and diet modification.

Surgery and radiation therapy are considered local treatments. They focus on eliminating cancer from a limited or local area - such as the breast, chest wall, and axillary nodes. Chemotherapy, hormone therapy, nutritional supplementation, and diet modification are considered systemic therapy. In systemic therapy, the entire body is treated in order to eradicate any cancer cells that may have spread from the breast tumor to other areas of the body.

Treatment depends on many factors, such as age, tumor stage, and estrogen-receptor status. However, deciding on a particular treatment is both a personal and a medical choice. Each treatment option has risks and benefits. Therefore, the type of treatment a woman chooses should be based on an understanding of how these risks and benefits relate to one's personal values and lifestyle.


LOCALIZED TREATMENT
Surgery
Radiation Therapy

Surgery
1)Breast-Conserving Surgery

2)Total Mastectomy

3)Luteal Phase Surgery

Breast cancer surgery strives to completely remove the tumor from the breast. However, surgery may also include the removal of one, some, or all of the axillary lymph nodes. Following surgery, both the tumor and/or lymph nodes are sent to a pathologist for examination to determine the stage of the breast cancer so the physician and patient can decide what additional treatment may be required after surgery.

There are two basic types of surgery for breast cancer: breast-conserving surgery and total mastectomy.


Breast-Conserving Surgery
Breast-conserving surgery consists of the removal of the breast tumor and some surrounding normal tissue. This procedure can be referred to as a lumpectomy, wide excision, or partial-radical mastectomy. During the operation, axillary lymph nodes may also be removed.

During breast-conserving surgery, the patient is usually given general anesthetic, causing unconsciousness. The surgeon then opens the breast and removes the tumor and a small amount of normal tissue. The surgeon then sutures together the edges of the incision, trying to keep the breast as normal looking as possible.

If axillary lymph nodes are removed, the surgeon will also open the area under the armpit on the same side as the affected breast, removing about 10-15 lymph nodes. However, if a sentinel node biopsy is performed only 1-3 lymph nodes are removed and used to assess node status.

Breast-conserving surgery can be done on palpable tumors (tumors that the physician is able to feel), as well as tumors that are not palpable but that can be located by mammography. In the case of tumors that are not palpable, a radiologist will insert a very thin wire into the area of the tumor in the breast during a mammogram. This procedure is called wire-localization or needle-localization (and was discussed earlier). The wire remains in the breast until the surgery and serves as a guide for the surgeon.

The tumor and lymph nodes removed during surgery are sent to a pathologist, who will assess the tumor margins to determine whether there is an adequate amount of normal tissue surrounding the tumor. This margin of normal tissue helps indicate whether or not the entire tumor was removed. If clean, uninvolved, or negative margins are found, this indicates that only normal tissue remains at the edges of the tissue removed and no additional surgery is needed. If normal tissue does not completely surround the tumor, the margins are considered "dirty," "involved," or "positive." Additional surgery will then be done to obtain adequate margins (Love et al. 1997).

A second breast-conserving operation is usually done if the tumor margins are found to be "dirty." This surgery is called a re-excision. If it does not achieve negative margins, a total mastectomy may be recommended.


Total Mastectomy
A total mastectomy procedure entails the removal of the entire breast. This may include an axillary dissection as well. For women who have decided to have breast reconstruction, this procedure will directly follow the mastectomy surgery.

A total mastectomy is done under general anesthetic. During the operation, all of the breast tissue is removed, including the nipple. For women considering breast reconstruction during or sometime after surgery, as much skin as possible is left intact in order to cover the implant. If a woman is not having reconstruction or is having it at a later time, the skin in the area is sewn together and a drainage tube is inserted so fluid from the healing wound can drain away.

The pathologist will evaluate the breast tissue and lymph nodes. The results of these tests will help determine which adjuvant therapy will be used.


Luteal Phase Surgery
Studies have suggested that premenopausal women who have their breast-conserving procedure or mastectomy done during the later part of their menstrual cycle (during the luteal phase) may have a better outcome after surgery. However, researchers are still assessing the benefits to "timing surgery" (Senie et al. 1997; NCI 1998).


Radiation Therapy
Radiation therapy (also known as radiotherapy) is considered a local treatment for breast cancer that uses targeted, high-energy x-rays to impede cancer cells' ability to grow and divide. The aim of radiation therapy is to rid the breast, chest, and axillary lymph nodes of cancer by using high-energy x-rays. For women with early-stage breast cancer, radiation therapy is most often performed following breast-conserving surgery. It is believed that after conserving surgery, there may still be microscopic cancer in the breast undetectable to the naked eye. Therefore, to reduce the chance of recurrence, radiation therapy is necessary to eliminate any remaining cancer.

Radiation therapy may also be used on the axillary lymph nodes and the chest wall following total mastectomy. Radiation therapy usually commences several weeks after surgery. However, it may be postponed if a patient is receiving chemotherapy first. (For more information regarding radiation therapy, please see the Cancer Radiation Therapy protocol.)