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.

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

• 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.