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SOURCE

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Source: Michaud LB, Barnett CM, Boster BL. Breast cancer. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM. Pharmacotherapy: A Pathophysiologic Approach. 10th ed. New York, NY: McGraw-Hill; 2017. http://accesspharmacy.mhmedical.com/content.aspx?bookid=1861&sectionid=146074631. Accessed March 23, 2017.

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DEFINITION

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  • Malignancy originating from breast tissue.

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ETIOLOGY

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  • Not completely understood.

  • Current evidence supports concept of carcinogenesis as genetically regulated, multistage process.

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PATHOPHYSIOLOGY

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  • Carcinogenesis includes initiation, promotion, conversion, and progression.

  • Growth of normal and cancerous cells genetically controlled by balance or imbalance of oncogene, proto-oncogene, and tumor suppressor gene protein products.

    • Multiple genetic mutations required to convert normal cells to cancerous cells.

  • Breast cancer cells often spread undetected by contiguity, lymph channels, and through blood early in course of disease, resulting in metastatic disease after local therapy.

    • Most common metastatic sites:

      • Lymph nodes.

      • Skin.

      • Bone.

      • Liver.

      • Lungs.

      • Brain.

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EPIDEMIOLOGY

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  • Most common type of cancer.

  • Female gender and increasing age 2 variables most strongly associated with occurrence of breast cancer.

    • Median age at diagnosis: between 60 and 65 years of age.

    • Male gender is poor prognostic factor.

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PREVENTION AND SCREENING

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  • Screening programs to detect cancers in asymptomatic women at risk:

    • Breast self-examination.

    • Routine screening mammography.

  • Pharmacologic risk reduction of breast cancer.

    • Selective estrogen receptor modulators (SERMs)

      • Tamoxifen and raloxifene reduce rates of invasive breast cancer in women at high risk.

      • Rates of endometrial cancer and deep vein thromboses higher with tamoxifen.

      • Overall quality of life is similar between two agents.

    • Retinoids.

    • Aromatase inhibitors.

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RISK FACTORS

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  • Endocrine:

    • Early menarche.

    • Nulliparity.

    • Late age at first birth.

    • Hormone replacement therapy.

  • Genetic.

    • Personal and family history.

    • Mutations of tumor suppresser genes [BRCA1 and BRCA2]

  • Environmental (eg, radiation exposure)

  • See National Cancer Institute risk calculator for interactive risk assessment of multiple factors.

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CLINICAL PRESENTATION

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  • Patients may not have any symptoms; detected in asymptomatic patients through routine screening mammography.

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SIGNS AND SYMPTOMS
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  • Painless, palpable lump most common.

  • Less common:

    • Pain.

    • Nipple discharge, retraction, or dimpling.

    • Skin edema, redness, or warmth.

  • Palpable local-regional lymph nodes.

  • Systemic metastasis symptoms depend on site:

    • Bone pain.

    • Difficulty breathing.

    • Abdominal pain or enlargement.

    • Jaundice.

    • Mental status changes.

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DIAGNOSIS

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MEANS OF CONFIRMATION AND DIAGNOSIS
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  • Breast biopsy: core-needle biopsy offers more definitive histologic diagnosis.

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LABORATORY TESTS
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  • Tumor markers.

    • Cancer antigen (CA 27,29)

    • Carcino-embryonic antigen (CEA)

  • Alkaline phosphatase or liver function tests may be elevated in metastatic disease.

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IMAGING
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  • Mammography, with or without ultrasound, breast MRI, or both.

  • Chest x-ray, chest CT, bone scan, abdominal CT or ultrasound, or MRI for systemic staging.

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