Cancer, Breast

SOURCE

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.

DEFINITION

• Malignancy originating from breast tissue.

ETIOLOGY

• Not completely understood.

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

PATHOPHYSIOLOGY

• 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.

EPIDEMIOLOGY

• 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.

PREVENTION AND SCREENING

• 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.

RISK FACTORS

• 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.

CLINICAL PRESENTATION

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

SIGNS AND SYMPTOMS

• 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.

DIAGNOSIS

MEANS OF CONFIRMATION AND DIAGNOSIS

• Breast biopsy: core-needle biopsy offers more definitive histologic diagnosis.

LABORATORY TESTS

• Tumor markers.

  • Cancer antigen (CA 27,29)

  • Carcino-embryonic antigen (CEA)

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

IMAGING

• 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.