WEEK+13+oncology

4. Identify and differentiate among types of cancers based on cell type, such as adenocarcinoma, lymphoma, or sarcoma.

5. Identify the two mutational routes resulting in uncontrolled cellular proliferation.

6. Describe viral causes of cancer.

7. Discuss the factors implicated in metastasis of tumors: rate of growth, angiogenesis, lack of cellular adhesion, and absence of cellular barriers.

8. Discuss mechanisms that favor or inhibit the metastasis of cancer cells.

9. Describe the clinical manifestations of cancer.


 * 10. Describe the treatment strategies and related side effects associated with cancer treatment. (patho p257-262)**


 * Chemotherapy(mod 7 part II-3m)**Tumors are derived from rapidly replicating cells, and so chemotherapeutic agents are designed to block cell division or some of the vital metabolic pathways that allow division to occur. As the last screen implied, therapy that does not rid the body of most (if not all) of the cancer cells might not eliminate the cancer. The remaining cancer cells could replicate and form another tumor (//recurrence//). To combat recurrence, highly effective drugs must be used in relatively high doses.

Most chemotherapeutic agents target all rapidly dividing cells and therefore have significant toxicity to all tissues, especially healthy tissues that also have high replication rates, such as the gastrointestinal tract, bone marrow, hair, skin, and reproductive tract. Two approaches to reduce the toxicity in healthy cells include: Because surgery remains the best way to achieve cure for solid tumors, chemotherapy can be used after (//adjuvant//) or before (//neoadjuvant//) surgery to maximize surgical success and reduce the likelihood of recurrence.
 * Combination chemotherapy that uses combinations of drugs that increase effectiveness without compounding toxicity; and
 * Seeking the most favorable therapeutic index,which means choosing the least amount of drug necessary to kill the cancer cells while limiting toxicity to normal cells.


 * Radiation(3n)**The administration of ionizing radiation to a tumor results in damage to and death of the DNA of the cancer cells. Although the beam of radiation can be focused on the tumor by using sophisticated imaging techniques, there is almost always some collateral damage to surrounding healthy tissues. There are few cancers for which radiation is considered curative; it is most often used for adjuvant, neoadjuvant, or palliative purposes.

Surgery remains the most likely modality to result in cure of a solid tumor. If the tumor has already spread or cannot be removed in its entirety, surgery may still be indicated to //debulk// (or lessen the size of) the primary tumor to reduce local complications. Deciding what type of surgery might be most helpful to an individual with cancer requires careful staging of the tumor.
 * Surgery(3o)**

As described in Module 07: Biology of Cancer and Tumor Spread Part 1, some cancer cells have receptors for hormones that act as growth factors for the tumor and so stimulate cell division. The growth of these tumors can often be slowed or even reversed by blocking this effect with hormonal therapies, such as antiestrogens for breast cancer and antiandrogens for prostate cancer.
 * Hormonal Therapy(3p)**


 * Immunotherapy(3q)**For a tumor to develop and spread, it must avoid detection and destruction by the immune system. Cancer cells do this by many mechanisms, such as by not expressing their tumor-specific antigens. Efforts at stimulating an immune response that can effectively kill cancer cells are focused on making the cancer more immunogenic. This is accomplished through techniques such as tumor vaccination (e.g., vaccines that stimulate the body to attack melanoma cells) and the production of monoclonal antibodies.

Monoclonal antibodies can also block cancer cell growth factor receptors (e.g., Herceptin for breast cancer) or carry toxins directly to the cancer cells (//conjugated antibodies//). Biologic response modifiers work by stimulating the immune system or by making the cancer cells more vulnerable to immune and inflammatory attack (e.g., Bacillus Calmette-Guérin for bladder cancer).


 * Anti-angiogenesis agents(3r)**The ability to provide itself with an increased oxygen and nutrient supply via the process of angiogenesis is an important feature of tumor growth. Drugs that block this ability can limit the size of primary tumors.


 * Complementary and alternative therapies(3s)**Studies indicate that the majority of individuals with cancer use alternative therapies such as herbals, homeopathics, and stress-reduction interventions. These modalities are used to increase the individual’s immune competence and overall health, although some are reported to have direct effects on some cancer cells. While the efficacy of these modalities continues to be explored, knowledge of these therapies is essential for the care of those who are using these techniques.


 * __Side effects (mod7 part II 4b-e)__**

The gastrointestinal (GI) tract is lined with actively dividing cells that are vulnerable to the effects of chemotherapy and radiation. Infections of the mouth, esophagus, and colon can also complicate treatment. One of the most feared side effects of chemotherapy is nausea, although this can often be effectively prevented or treated, and patient education is essential to adequate control of this problem. There are many highly effective antinausea regimens, many of which can be started before chemotherapy and therefore prevent this distressing symptom from occurring.**__Bone Marrow__**As discussed previously in this module, cancer chemotherapy works by killing rapidly replicating cells. The bone marrow is a constant source of new blood cells and therefore is highly susceptible to the effects of chemotherapy. Individuals suffer from anemia, leukopenia, and thrombocytopenia and therefore are at increased risk for fatigue, infection, and bleeding. Stimulation of the marrow with erythropoietin and colony-stimulating factors may be helpful, and transfusion of blood products may be necessary in severe cases.
 * __GI__**

Alopecia and skin changes are common with chemotherapy, and radiation can cause significant burns. Although these side effects cannot always be avoided, proper care can often restore skin health once the treatment is over.
 * __Hair and skin__**


 * __Reproductive tract__**Both radiation and chemotherapy can result in germ cell death or damage, increasing the likelihood of sterility or genetic changes in offspring. In addition, hormonal changes are common in malignancies and may further reduce fertility. Individuals of reproductive age may want to explore sperm or embryo banking before pursuing treatment.


 * 11. Differentiate between fibrocystic breast disease and breast cancer in regard to risk factor detection, manifestations, treatment, and prognosis.**
 * __fibrocystic breast disease__ (MS p1346,**

Most common between ages 30-50, does not increase risk of breast cancer for majority of patients. Fibrocystic changes most commonly occur in women with premenstrual abnormalities, nulliparous women, women with a history of spontaneous abortion, nonusers of oral contraceptives, and women with early menarche and late menopause. Symptoms related to fibrocystic changes often worsen in the premenstrual phase and subside after menstruation. **manifestations** Manifestations of fibrocystic breast changes include one or more palpable lumps that are usually round, well delineated, and freely movable within the breast (see [|Table 52-1]). Some lumps are fibrous and do not contain cysts. There may be accompanying discomfort ranging from tenderness to pain. The lump is usually observed to increase in size and perhaps in tenderness before menstruation. Cysts may enlarge or shrink rapidly. Nipple discharge associated with fibrocystic breasts is often milky, watery-milky, yellow, or green. Diagnosis of benign breast conditions is done using mammography, sonography, aspiration of lumps, and surgical or needle biopsy. Treatment typically includes wearing a supportive brassiere, draining cysts, and avoiding caffeine and chocolate.
 * risk factor detection**
 * treatment**


 * prognosis(mod 14, 12c)**
 * Types of Breast Lesion || Summary ||
 * Nonproliferative || * This type is not associated with increased breast cancer risk.
 * Fibrocytic changes cause breast tenderness with menstrual cycle.
 * Risk factors are genetics, age, parity, caffeine, lactation history, exogenous hormones. ||
 * Proliferative || * Slight increase in breast cancer risk
 * Proliferation of ductal epithelium and/or stroma without malignancy
 * Subtypes:
 * Epithelial hyperplasia—More than two cell layers above the basement membrane
 * Florid hyperplasia—More than four cell layers above the basement membrane
 * Sclerosing adenosis—The number of acini per terminal duct greater than twice the number in uninvolved lobules
 * Complex sclerosing lesion—Irregular, radial proliferation of ductlike small tubules in a dense central fibrosis
 * Papillomas—Multiple, finger-like projections lined by myoepithelial and luminal cells ||
 * Proliferative with Atypia || * Moderate increase in breast cancer risk
 * Subtypes:
 * Atypical hyperplasia—Increase in number of cells and cell structure variation
 * Ductal hyperplasia—Increased number of cells within the lumen of the terminal ducts
 * Lobular hyperplasia—Proliferation of small, uniform cells in the lumen of lobular units ||
 * __breast cancer__**


 * risk factor detection (mod 14, 12e)**
 * Positive family history
 * It has long been known that breast cancer runs in families and that a family history of a first-degree relative with breast cancer confers a considerable increase in risk. Many mutations have been described in breast tumors, most of which are acquired. However, careful genetic studies conducted in families with a high incidence of breast cancer have led to the discovery of several inherited tumor suppressor gene mutations that are associated with a significant increase in risk for the development of breast cancer.
 * Hormone replacement therapy (HRT)
 * Reproductive and hormonal factors that contribute to breast cancer risk are well described. In recent years, the relationship between hormone replacement therapy and breast cancer has been explored in greater detail, although controversies still exist.
 * Environmental factors
 * Radiation, diet, exercise, chemicals, and other environmental factors have been tied to an increased risk of breast cancer.

__Tests to predict reoccurance__These tests include axillary lymph node status, tumor size, estrogen and progesterone receptor status, and cell proliferative indices. Many of these diagnostic studies are useful prognostic indicators of the disease. Axillary lymph node involvement is one of the most important prognostic factors in breast cancer.An axillary lymph node dissection is often performed to determine if cancer has spread to the axilla on the side of the breast cancer. The more nodes involved, the greater the risk of recurrence. Patients with four or more positive nodes have the greatest risk of recurrence. The larger the tumor, and poorly differentiated tumors are more aggressive.
 * manifestations**Clinical manifestations associated with more advanced tumors include:
 * Pain in the breast
 * Dimpling of the skin
 * Nipple retraction or discharge
 * Edema of the arm
 * Enlargement of the axillary lymph nodes
 * Symptoms such as bone pain, dyspnea, or neurologic deficits are indicative of metastasis
 * treatment**
 * || Treatment **is almost always a combination of surgical removal of the primary tumor followed by hormonal therapy and/or chemotherapy, depending on the stage of the tumor. Other management techniques include administration of bisphosphonates to treat bone metastases and psychological intervention to improve quality of life and immune function.** ||
 * || Type of Treatment || Comments ||
 * Surgical || * Removal of the primary tumor (lumpectomy or mastectomy) ||
 * Hormonal || * For example: tamoxifen, raloxifene, or aromatase inhibitors ||
 * Immunotherapy || * For example: Herceptin
 * Indicated if cancer is vulnerable to this type of therapy ||
 * Chemotherapy || * Based on stage of tumor ||
 * Radiation || * Used for local tumor control and for treating metastases ||
 * Advanced disease combination therapy || * Controversial form of treatment that is reserved for very advanced cases
 * Ablative chemotherapy and radiation followed by bone marrow transplantation ||  ||   ||
 * prognosis(MS p1350)**
 * prognosis(MS p1350)**

~Another diagnostic test useful both for treatment decisions and prediction of prognosis is estrogen and progesterone receptor status. Receptor-positive tumors (1) commonly show histologic evidence of being well differentiated, (2) frequently have a //diploid// (more normal) DNA content and low proliferative indices, (3) have a lower chance for recurrence, and (4) are frequently hormone dependent and responsive to hormonal therapy. Receptor-negative tumors (1) are often poorly differentiated histologically, (2) have a high incidence of //aneuploidy// (abnormally high or low DNA content) and higher proliferative indices, (3) frequently recur, and (4) are usually unresponsive to hormonal therapy.

~Ploidy status correlates with tumor aggressiveness. Diploid tumors have been shown to have a significantly lower risk of recurrence than aneuploid tumors.

~Cell-proliferative indices indirectly measure the rate of tumor cell proliferation. The percent of tumor cells in the synthesis (S) phase of the cell cycle is another important prognostic indicator. Patients with cells that have high S-phase fractions have a higher risk for recurrence and earlier cancer death.

~Another prognostic indicator is the marker HER-2. Overexpression of this receptor has been associated with a greater risk for recurrence and a poorer prognosis in breast cancer. Between 25% and 30% of metastatic breast cancers produce excessive HER-2. High numbers of HER-2 receptors are associated with unusually aggressive tumor growth.The presence of this marker assists in the selection and sequence of chemotherapy and predicting a patient's response to treatment.

12. Discuss lifestyle changes that may modify a woman’s risk for developing breast cancer.

13. Examine the pathogenesis of breast cancer.

__**//14. Describe the types and sequencing of testing used to diagnose breast cancer.(Lewis 1345)//**__
 * Mammography**- visualize the internal structure using x-ray
 * yearly starting @ 40
 * ultrasound**- useful in women with dense breat tissue will not detect microcalcifications
 * MRI**- for women that are high risk or whose mammograms is suspicious
 * fine needle aspiration**(Sterotactic or ultrasound core biopsy)-inserting a needle into lesion & pulling out fluid. **DEFINITIVE DIAGNOSTIC**


 * //__1__////__5. Examine the etiology, pathophysiology, clinical manifestations, diagnostic evaluation of acute lymphocytic leukemia.(Lewis, 717-723)(Piliterri, 1696-1698)__//**
 * Etiology**-UNKNOWN possibly chemical agents, radiation, nuclear energy, virus, chemotherapy agents


 * Patho-**Environmental & hereditary mutations cause blocked differentiation of precursor lymphocytes, a distorted and uncontrolled proliferation of immature WBC's, the malignant cell is the lymphoblast (Immature lymphocyte) mostly B-cells


 * Clinical manifestations-** because WBC's are being excessivly produced other cells suffer, RBC'c & platelets decrease. Anemia(fever, fatigue, pallor) and bleeding disorders(petechiae, bruising) are most of the manifestations. Abnormal WBC's accumulate because they have mutated to never die. These cells get into the bone and joints and cause pain. they are ecessivly filtered by the liver & spleen causing hepato/splenomegaly. WBC's get into the brain causing CNS manifestations (HA, seizures, ataxia, N/V)


 * Diagnostic evaluation-** peripheral blood eval and bone marrow aspiration done at the iliac crest in kids. IF more than 25% immature cells are present than leukemia is diagnosed.