Rowa’ Al-Ramahi 1.  The strongest risk factors for breast cancer are female gender and increasing age.  Additional risk factors include endocrine factors

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Text of Rowa’ Al-Ramahi 1.  The strongest risk factors for breast cancer are female gender and...

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  • Rowa Al-Ramahi 1
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  • The strongest risk factors for breast cancer are female gender and increasing age. Additional risk factors include endocrine factors (e.g., early menarche, nulliparity, late age at first birth, hormone replacement therapy), genetic factors (e.g., personal and family history, mutations of tumor suppresser genes [BRCA1 and BRCA2]), and environmental and lifestyle factors (e.g., radiation exposure). 2
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  • Breast cancer cells often spread undetected by contiguity, lymph channels, and through the blood early in the course of the disease, resulting in metastatic disease after local therapy. The most common metastatic sites are lymph nodes, skin, bone, liver, lungs, and brain. 3
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  • The initial sign in more than 90% of women with breast cancer is a painless lump that is typically solitary, unilateral, solid, hard, irregular, and nonmobile. Less common initial signs are pain and nipple changes. More advanced cases present with prominent skin edema, redness, warmth, and induration. 4
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  • Symptoms of MBC depend on the site of metastases, but may include bone pain, difficulty breathing, abdominal pain or enlargement, jaundice, and mental status changes. Many women first detect some breast abnormalities themselves, but it is increasingly common for breast cancer to be detected during routine screening mammography in asymptomatic women. 5
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  • Initial workup for a woman presenting with a localized lesion or suggestive symptoms should include a careful history, physical examination of the breast, three-dimensional mammography, and, possibly, other breast imaging techniques such as ultrasound & MRI. Breast biopsy is indicated for a mammographic abnormality that suggests malignancy or for a palpable mass on physical examination. 6
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  • Stage is based on the size of the primary tumor extent & size (T14), presence and extent of lymph node involvement (N13), and presence or absence of distant metastases (M01). Simplistically stated, these stages may be represented as follows: Early Breast Cancer Stage 0: Carcinoma in situ or disease that has not invaded the basement membrane. Stage I: Small primary tumor without lymph node involvement. Stage II: Involvement of regional lymph nodes. 7
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  • Locally Advanced Breast Cancer Stage III: Usually a large tumor with extensive nodal involvement in which node or tumor is fixed to the chest wall; also includes inflammatory breast cancer, which is rapidly progressive. Advanced or Metastatic Breast Cancer Stage IV: Metastases in organs distant from the primary tumor. 8
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  • The development of malignancy is a multistep process with preinvasive (or noninvasive) and invasive phases. The goal of treatment for noninvasive carcinomas is to prevent the development of invasive disease. The pathologic evaluation of breast lesions establishes the histologic diagnosis and presence or absence of prognostic factors. Most breast carcinomas are adenocarcinomas and are classified as ductal or lobular. 9
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  • Tumor size and the presence and number of involved axillary lymph nodes are primary factors in assessing the risk for breast cancer recurrence and subsequent metastatic disease. Other disease characteristics that provide prognostic information include histologic subtype, nuclear or histologic grade, lymphatic and vascular invasion, and proliferation indices. 10
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  • The estrogen receptor & progesterone receptor are 2 hormone receptors used as indicators of prognosis and to predict response to hormone therapy. HER2/neu (HER2) overexpression is associated with transmission of growth signals that control aspects of normal cell growth and division. Overexpression of HER2 is associated with increased tumer aggresiveness,rates of recurrence & mortality. Genetic profiling tools provide additional prognostic information to aid in treatment decisions for subgroups of patients with otherwise favorable prognostic features. 11
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  • The goal of therapy with early and locally advanced breast cancer is cure. The goals of therapy with MBC are to improve symptoms, improve quality of life, and prolong survival. 12
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  • The treatment of breast cancer is rapidly evolving. Specific information regarding the most promising interventions can be found only in the primary literature. Treatment can cause substantial toxicity, which differs depending on the individual agent, administration method, and combination regimen. Because a comprehensive review of toxicities is beyond the scope of this chapter, appropriate references should be consulted. 13
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  • Local-Regional Therapy Surgery alone can cure most patients with in situ cancers and approximately one-half of those with stage II cancers. Breast-conserving therapy (BCT) is appropriate primary therapy for most women with stage I and II disease; it is preferable to modified radical mastectomy because it produces equivalent survival rates with cosmetically superior results. BCT consists of lumpectomy (i.e., excision of the primary tumor and adjacent breast tissue) followed by radiation therapy (RT) to prevent local recurrence. 14
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  • RT is administered to the entire breast over 4 to 6 weeks to eradicate residual disease after BCT. Reddening and erythema of the breast tissue with subsequent shrinkage of total breast mass are minor complications associated with RT. Simple or total mastectomy involves removal of the entire breast without dissection of underlying muscle or axillary nodes. This procedure is used for carcinoma in situ where the incidence of axillary node involvement is only 1% or with local recurrence following breast conservation therapy. 15
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  • Axillary lymph nodes should be sampled for staging and prognostic information. Lymphatic mapping with sentinel lymph node biopsy is a new, less invasive alternative to axillary dissection; however, the procedure is controversial because of the lack of long-term data. 16
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  • Systemic adjuvant therapy is the administration of systemic therapy following definitive local therapy (surgery, radiation, or both) when there is no evidence of metastatic disease but a high likelihood of disease recurrence. The goal of such therapy is cure. Chemotherapy, hormonal therapy, or both result in improved disease-free survival and/or overall survival (OS) for all treated patients. 17
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  • The National Comprehensive Cancer Network practice guidelines reflect the trend toward the use of chemotherapy in all women regardless of menopausal status, and the addition of hormonal therapy in all women with receptor-positive disease regardless of age or menopausal status. Genetic tests are being prospectively validated as decision-support tools for adjuvant chemotherapy in ER +, node- negative patients to identify characteristics of the primary tumor that may predict for the likelihood of distant recurrence and death. 18
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  • Early administration of effective combination chemotherapy at a time of low tumor burden should increase the likelihood of cure and minimize emergence of drug-resistant tumor cell clones. Combination regimens have historically been more effective than single agent chemotherapy 19
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  • Anthracycline-containing regimens (e.g., doxorubicin and epirubicin) significantly reduce the rate of recurrence and improve OS 5 and 10 years after treatment as compared with regimens that contain cyclophosphamide, methotrexate, and fluorouracil. Both node-negative and nodepositive patients benefit from anthracycline- containing regimens. 20
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  • The addition of taxanes, docetaxel and paclitaxel, a newer class of agents, to adjuvant regimens resulted in consistently and significantly improved disease-free survival and OS in node-positive breast cancer patients. The use of taxane containing regimens in node negative patients remains controversial. Chemotherapy should be initiated within 12 weeks of surgical removal of the primary tumor. The optimal duration of adjuvant treatment is unknown but appears to be on the order of 12 to 24 weeks depending on the regimen used. 21
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  • Dose intensity refers to the amount of drug administered per unit of time, which can be achieved by increasing dose, decreasing time, or both. Dose density is one way of achieving dose intensity by decreasing time between treatment cycles. Dose-dense regimens may be considered as options for adjuvant therapy for node- positive breast cancer. Increasing doses in standard regimens appears to not be beneficial and may be harmful. 22
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  • Decreasing doses in standard regimens should be avoided unless necessitate by severe toxicity. Short-term toxicities of adjuvant chemotherapy are generally well tolerated, especially with the availability of serotonin- antagonist and substance P/neurokinin 1- antagonist antiemetics and colony- stimulating factors. Survival benefit for adjuvant chemotherapy in stage I and II breast cancer is modest. The absolute reduction in mortality at 10 years is 5% in node negative and 10% in node-positive disease. 23
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  • Adjuvant Biologic Therapy Trastuzu