Breast Cancer – Causes, Symptoms, Diagnosis, Treatment and Ongoing care

Basics

Description

Common malignant tumor that originates from epithelial cells of breast tissue

Epidemiology

Incidence

  • 123 cases per 100,000 women per year in 2006 (1)
  • Invasive cancer new cases in 2009: Women: 194,280
  • In situ cancer new cases in 2009: 62,280 (85% ductal carcinoma in situ)
  • Breast cancer (BC) deaths: 40,480
  • Lifetime risk BC: 1 in 8 (12%)
  • Lifetime risk BC death: 1 in 35
  • Most common malignancy in women in US, second only to lung cancer as cause of cancer death (2)

Prevalence

2.5 million women in the US

Risk Factors

  • Female, family history, nulliparity and/or older age at first live birth, early menarche, delayed menopause, increasing patient age, personal history of BC
  • Prior chest radiation (lymphoma), DES
  • Prolonged hormone replacement therapy (HRT), high ethyl alcohol (ETOH) use, high body mass index (BMI), physical inactivity

Genetics

  • BRCA1 and BRCA2
  • Other genes: ATM, CHEK2, p53
  • Cowden syndrome (PTEN): Hamartomas skin, mucosa, bones, central nervous system (CNS), thyroid (benign and malignant)
  • Li-Fraumeni syndrome (TP53): Autosomal dominance, Ca in CNS, leukemia, sarcoma, adrenal cortex
  • Criteria for additional risk evaluation/gene testing:
    • BC at age ≤50 years
    • 2 breast primaries of breast/ovary cancer in single patient or ≥2 breast primary cancers or breast + ovary cancer same side of family
    • Clustering of BC with thyroid Ca, sarcoma, adrenal cortex, endometrial, pancreas, CNS, leukemia/lymphoma same side of family
    • FH BC susceptibility gene
    • Ashkenazi Jewish with breast/ovary cancer at any age
    • Any male breast cancer
    • Ovarian cancer in family

General Prevention

  • Avoid risk factors when possible.
  • Selective estrogen receptor modulators
  • For hereditary breast and/or ovarian cancer (3):
    • Begin at age 18–25: BSE (beginning at 18 years), clinical breast exam, yearly mammogram and breast magnetic resonance imaging (MRI) (at 25)
    • Discuss risk-reducing mastectomy. Counsel, suggest risk-reducing salpingo-oophorectomy ideally between 35 and 40 or after completion of child-bearing.

Pathophysiology

  • Estrogen/progesterone induce cyclin D1 and c-myc expression
  • Bcl-2 commonly overexpressed
  • Estrogen receptor (ER) not expressed in 1/3 BC:
    • Mutations of cell adhesion molecules
    • Epidermal growth factors (EGF, c-erb-B2 [HER2])
    • IGF family
    • TGF-β family
    • BRCA1 and BRCA2 may function in cell cycle progression and in DNA repair.

Breast cancer, Ovarian cancer, HER2/neu, Ashkenazi Jewish, clinical breast exam, estrogen receptor modulators, selective estrogen receptor modulators, male breast cancer, ductal carcinoma, breast magnetic resonance,

Diagnosis

History

  • Mass, pain, redness, nipple retraction, nipple discharge
  • Symptoms of metastatic disease
  • Family history

Physical Exam

  • Careful clinician breast exam:
    • Evidence suggests that clinical exam of breast produces a reduction in breast cancer mortality.
  • Regional lymph node exam
  • Evaluate possible metastatic disease.
  • Psychosocial evaluation

Diagnostic Tests & Interpretation

Lab

Initial lab tests

New BC:

  • Complete blood count, liver function tests/alkaline phosphatase
  • Chest imaging
  • Optional bone scan, computed tomography (CT) abdomen/pelvis
  • Tumor markers usually not indicated for early BC

Imaging

Initial approach

  • Screening for BC:
    • X-ray mammography decreases BC mortality
    • Digital mammography may benefit. Computer-aided detection (CAD) increases sensitivity and decreases specificity.
    • MRI: BRCA1 or 2, lifetime breast cancer risk of ≥20%, prior chest radiation, other factors increasing risk
    • Ultrasound: Limited data in women with dense breasts
  • Diagnosis of BC:
    • X-ray, ultrasound-guided biopsy/aspirate
    • MRI commonly used to define disease in breast and presence of multifocal/multicentric ipsilateral disease

Follow-Up & Special Considerations

Staging of BC:

  • CT, bone scan (back pain)
  • MRI especially if CNS/spinal cord symptoms

Diagnostic Procedures/Surgery

  • Primary tumor: Fine-needle aspiration, biopsy
  • Genomic assay on formalin-fixed tissue for select ER-positive/node-negative (Oncotype DX)

Pathological Findings

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  • Histology:
    • Ductal/lobular/other
    • Benign/malignant
    • Tumor size
    • Inflammatory component
    • Invasive/noninvasive
    • Margins
    • Nodal involvement
    • Nodal micrometastases: Increased risk of disease recurrence
  • Estrogen receptor
  • Progesterone receptor
  • HER-2 assay

Differential Diagnosis

  • Benign breast disease
  • Infection

Treatment

Medication

  • Prevention:
    • Risk assessment tool at http://www.cancer.gov/bcrisktool/
    • Assertive screening/surveillance
    • Risk-reducing mastectomy
    • Risk-reducing bilateral salpingo-oophorectomy for breast and ovary cancer
    • Surgery
    • Chemoprevention/hormone therapy:
      • Risk reduction for ER-positive tumors
      • No demonstration of increased survival
  • Hormone therapy for ER-positive tumors:
    • Tamoxifen
    • Ovarian ablation
    • Aromatase inhibitors
  • Adjuvant:
    • Hormone therapy for ER-positive tumors:
      • Tamoxifen
      • Ovarian ablation with surgery or gonadotropin-releasing hormone agonists/antagonism
      • Aromatase inhibitors
    • Cytotoxic therapy:
      • Anthracyclines, alkylating agents, taxanes, antimetabolites
      • Pre-op (neoadjuvant) vs post-op (adjuvant)
      • Combinations of above
      • Dose-dense versus non–dose-dense
    • Anti-HER2/neu antibody in select HER2/neu-positive patients:
      • Monitor cardiac toxicity, especially with anthracycline.
  • Advanced disease:
    • Hormone therapy
    • Cytotoxic therapy
    • Bisphosphonates to decrease skeletal complications
    • Antivascular endothelial growth factor (VEGF) antibody
    • Anti-HER2/neu antibody in select HER2/neu-positive patients

Additional Treatment

Additional Therapies

Prevention therapy discussed in Treatment section

Complementary and Alternative Medicine

Research before prescribing

Surgery/Other Procedures

  • Breast-conserving partial mastectomy/lumpectomy therapy if possible:
    • Negative margins
    • Tumor usually <5 cm
    • No prior breast radiation
  • Mastectomy:
    • Large tumors
    • Young women with known BRCA
    • Consider immediate or delayed reconstruction.
  • Radiation therapy should be initiated without delay:
    • After breast-conserving therapy
    • Postmastectomy in select high-risk patients
    • Palliation of metastatic disease

Ongoing Care

Follow-Up Recommendations

  • Interval history/physical every 4–6 months for 1st year and while receiving adjuvant therapy, then yearly (4):
    • Recognize increased risk of ovarian cancer
    • Rare: AML (therapy-induced), angiosarcoma (radiation), endometrial cancer (tamoxifen/postmenopause)
  • Other signs/symptoms to monitor/manage related to chemo, hormone, radiation:
    • Hot flashes
    • Sexual dysfunction
    • Arthralgias (aromatase)
    • Cognitive dysfunction
    • Depression
    • Fatigue
    • BMI
    • Osteopenia or osteoporosis
    • Cardiovascular disease, congestive heart failure
    • Deep vein thrombosis
    • No evidence to support the use of “tumor markers” for BC/routine bone scan, CT scans, MRI, positron emission tomography (PET), ultrasound in the symptomatic patient
  • Mammogram/imaging every 12 months (and 6–12 months postradiation therapy if breast conserved)
  • Assess bone health.
  • Gynecologic exam for women on tamoxifen every 12 months

Patient Monitoring

  • Continue screening mammograms.
  • Bone density
  • Annual gynecologic exam if uterus present and on tamoxifen

Diet

  • Evidence that certain lifestyle characteristics are risk factors for BC (obesity, increased alcohol consumption)
  • No evidence that lifestyle modification changes BC risk

Prognosis

  • Influenced by age, menopausal status, stage of disease, ER and PR status, many other characteristics
  • Risk of BC recurrences are maintained for life and are not limited by number of years postdiagnosis/therapy.
  • Some patients with limited metastatic disease have a better prognosis.

Complications

  • Spinal cord compression
  • Hypercalcemia
  • Visceral metastatic disease
  • Emotional issues, especially depression and body-image alteration
  • Postoperative lymphedema
  • Therapy-induced toxicity

References

1. National Cancer Institute, US National institutes of Health. 2009/2010 Update http://progressreport.cancer.gov/doc_detail.asp?pid = 1&did = 2009&chid = 93&coid = 920&mid.

2. The NCCN Practice Guidelines in Oncology (Version 1. 2009) © 2009 Breast Cancer National Comprehensive Cancer Network, Inc. Accessed 6/14/2009 at http://www.nccn.org.

3. Robson M, Offit K. Clinical practice. Management of an inherited predisposition to breast cancer. N Engl J Med. 2007;357:154–62.

4. Hayes DF. Clinical practice. Follow-up of patients with early breast cancer. N Engl J Med. 2007;356:2505–13.

Additional Reading

Pruthi S, Brandt KR, Degnim AC, et al. A multidisciplinary approach to the management of breast cancer, part 1: prevention and diagnosis. Mayo Clin Proc. 2007;82:999–1012.

Codes

ICD9

  • 174.0 Malignant neoplasm of nipple and areola of female breast
  • 174.1 Malignant neoplasm of central portion of female breast
  • 174.9 Malignant neoplasm of breast (female), unspecified site
  • 174.2 Malignant neoplasm of upper-inner quadrant of female breast
  • 174.3 Malignant neoplasm of lower-inner quadrant of female breast
  • 174.4 Malignant neoplasm of upper-outer quadrant of female breast
  • 174.5 Malignant neoplasm of lower-outer quadrant of female breast
  • 174.6 Malignant neoplasm of axillary tail of female breast
  • 174.8 Malignant neoplasm of other specified sites of female breast
  • V76.10 Breast screening, unspecified

Snomed

  • 254837009 Malignant tumor of breast (disorder)
  • 188147009 malignant neoplasm of nipple and areola of female breast (disorder)
  • 188151006 malignant neoplasm of central part of female breast (disorder)
  • 188152004 malignant neoplasm of upper-inner quadrant of female breast (disorder)
  • 188153009 malignant neoplasm of lower-inner quadrant of female breast (disorder)
  • 188154003 malignant neoplasm of upper-outer quadrant of female breast (disorder)
  • 188155002 malignant neoplasm of lower-outer quadrant of female breast (disorder)
  • 188156001 malignant neoplasm of axillary tail of female breast (disorder)
  • 268547008 screening for malignant neoplasm of breast (procedure)

Clinical Pearls

  • Pursue/refer all abnormal breast PE/imaging findings.
  • Normal mammography does not exclude possibility of cancer with a palpable mass.

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