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.
- Hormone therapy for ER-positive tumors:
- 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.