Introduction to Breast Cancer: Biology, Pathology, and the Latest in Screening and Diagnostic Tools

Objectives

• Understand the epidemiology of breast cancer.
• Understand the risk factors, natural history, and histopathology of breast cancer.
• Learn the current guidelines for breast cancer screening.
• Understand mammographic findings significant for breast cancer.
• Understand when a Breast MRI is indicated.

Epidemiology of Breast Cancer

• Most common cancer in women.
• 2nd leading cause of cancer death in women.
• Incidence rates increased from 1980-2000 due to increased use of screening mammography.
• Incidence rates decreased by 3.5% per year between 2001-2004 due to reduced use of hormone replacement therapy (HRT).
• Death rates from breast cancer have decreased since the 1990’s due to early detection and improved treatment.

Risk Factors for Breast Cancer

• Female gender
• Increasing age
• Alcohol consumption
• Early menarche
• Nulliparity
• Late age at first live birth
• Late menopause
• Prior breast biopsy
• Personal history of invasive breast cancer
• Obesity
• Use of Hormone Replacement Therapy (HRT)
• Family history
• Dense breast tissue

Genetics and Familial Factors

• Familial breast cancer accounts for 10% of patients.
• Germline mutations in tumor suppressor genes (p53, BRCA1, BRCA2) are associated with familial breast cancer.
• BRCA1 and BRCA2 mutations increase the risk of breast and ovarian cancer.

Signs and Symptoms of Breast Cancer

• Often found as an abnormality on mammogram.
• Painless firm mass.
• Persistent changes to the breast (thickening, swelling, dimpling).
• Nipple changes (ulceration, retraction, inversion, spontaneous discharge).

Natural History of Breast Cancer

• Slow-growing tumors, with an average of 5 years before a tumor becomes palpable.
• Most common sites of origin: upper outer quadrant (UOQ), central area, upper inner quadrant (UIQ), lower outer quadrant (LOQ), lower inner quadrant (LIQ).
• Spread of disease includes lymphatic and blood vessel involvement.
• Lymph node spread usually goes to axillary lymph nodes before supraclavicular or internal mammary lymph nodes.
• Distant spread most commonly involves bones, lungs, liver, and brain/CNS.

Workup for Breast Cancer

• Complete clinical and family history.
• Physical exam.
• Bilateral diagnostic mammogram.
• +/- MRI, ultrasound with biopsy.
• Estrogen & progesterone receptor status, Her2/neu status.
• CXR, labs (complete blood cell count, general chemistries, LFTs), +/- bone scan, +/- CT chest/abdomen/pelvis.

Breast Cancer Histology

• In situ carcinomas (DCIS, LCIS, Paget’s disease).
• Invasive carcinomas (IDC, ILC, inflammatory carcinoma).
• Other invasive carcinomas (medullary, mucinous, tubular, papillary, undifferentiated, squamous cell, adenoid cystic, secretory, cribriform).
• Bloom-Richardson histologic grading system for invasive carcinomas (Grade 1, Grade 2, Grade 3).

Hormone Receptor Status Testing

• Receptors are proteins on the surface of cells that can attach to hormones.
• ER+ and PR+ cancer cells can be targeted with hormone therapy.

HER-2/neu Testing

• HER-2/neu gene codes for a growth-promoting protein.
• Over-expression is associated with tumor aggressiveness and decreased disease-free survival.
• HER2-positive cancers benefit from treatment with drugs that target the HER2/neu protein.

Staging of Breast Cancer

• American Joint Committee on Cancer (AJCC) staging system for primary tumor, regional lymph nodes, and distant metastasis.
• Stage grouping includes stages 0 through IV.

Breast Cancer Screening

• American Cancer Society guidelines recommend annual mammogram screening starting at age 40 for women of average risk.
• Women at moderate risk should start annual mammograms at age 40 and discuss the benefits and limitations of adding annual screening MRI.
• Women at high risk should begin screening at age 30 with annual mammogram, MRI, and clinical breast exam.

Mammography

• Associated with detection of earlier stage breast cancers and reduction in breast cancer mortality rates.
• Sensitivity: ~90%, Specificity: ~94%.
• Positive Predictive Value: 8-14% for all screened patients.

Magnetic Resonance Imaging (MRI)

• More sensitive than mammogram and clinical breast exams in detecting invasive breast cancer in high-risk women.
• Sensitivity: 77-100%, Specificity: 81-99%.
• Limitations include higher cost, higher recall rates, and higher false positive rates.

Indications for Breast MRI

• Screening for breast cancer in moderate to high risk patient populations.
• Evaluation of breasts with increased density.
• Monitoring treatment response to neoadjuvant chemotherapy.
• Evaluation of extent of disease in women with a personal history of breast cancer.
• Aid in surgical planning for breast cancer treatment.

Summary

• Breast cancer is a highly prevalent disease with improved detection and treatment options.
• Screening mammography and MRI play important roles in early detection and management of breast cancer.
• Genetic factors and family history are significant in assessing risk and determining screening strategies.