Breast Cancer: Epidemiology, Risk Factors, Diagnosis, and Treatment

Posted on Jan 29, 2025 in Medicine & Health

Epidemiology: 36 cases per 100,000 inhabitants annually, with 17,000 new cases each year. Incidence increases with age, with higher rates in those aged 60-79.

Risk Factors

Multifactorial:

  • Sex (male to female ratio is 1:100)
  • Age
  • Hormonal factors:
    • Early menarche, late menopause
    • Reproductive history
    • Hormone replacement therapy (HRT)
  • Mammographic density (dense connective tissue similar to circulating estrogens)
  • Previous history of cancer
  • Alcohol consumption
  • Family history
  • Hereditary breast cancer
  • Susceptibility genes: BRCA1, BRCA2, CHK2, p53, RB1, STK11/LKB1, PTEN (Cowden syndrome), MSH2, MLH1, CDH-1

Diagnosis

Screening Programs: Campaigns start at age 50, using screening mammography. Sensitivity is >85%, and specificity is >90%.

Early Diagnosis:

  • Monthly breast self-exams are not recommended (causes anxiety, false positives, biopsies, and unnecessary expense).
  • For women 35-40 years old: annual clinical examination and bilateral mammography.
  • For women 40+ years old: annual clinical examination and mammography every 1-2 years.
  • No age limit for mammograms.

Reported Symptoms: A painless breast lump, pain, bloody discharge from the nipple, nipple retraction.

Radiological Diagnosis:

  • Clinical suspicion: palpation and inspection: finding nodes, lymph.
  • Mammography: >5 microcalcifications in <1 cm2, spiculated irregular nodular densities, architectural distortion.
  • Biopsy.

Mammography Findings: BI-RADS (same as ultrasound):

  • I. Normal, benign characteristics.
  • II. Benign characteristics.
  • III. Probably benign but ambiguous characteristics.
  • IV. Probably malignant.
  • V. Malignant.

Definitive Diagnosis: Fine needle aspiration (FNA), core needle biopsy, ultrasound-guided biopsy, stereotactic-directed biopsy.

Triple Diagnosis: Examination, mammography/breast ultrasound/MRI, and FNA/needle biopsy is more effective than each alone or any combination of two.

Immunohistochemical study of hormone receptors (estrogen and progesterone) and HER-2. Study of gene amplification of HER-2 by FISH.

Paget’s disease: Eczema of the nipple. Intraepithelial nipple duct carcinoma may or may not be related to invasive carcinoma.

Histological Diagnosis

Adenocarcinoma (85%):

  • Ductal: In situ, infiltrating
  • Lobular: In situ, invasive (Best prognosis; responsive to treatment, resistant to some therapies)

Other (15%): Mucinous, Papillary, Medullary (Best prognosis), tubular, Adenocystic.

Treatment

Locoregional Treatment: Complete local excision (lumpectomy) or mastectomy plus axillary staging (axillary dissection or sentinel lymph node biopsy). If conservative surgery, radiotherapy or radical mastectomy. For tumors >4 cm and/or >4 nodes.

Adjuvant Systemic Treatment:

  • Response to hormone therapy: High hormone sensitivity, incomplete hormone sensitivity, hormone resistance.
  • Adjuvant hormone therapy:
    • Premenopausal: tamoxifen, goserelin (LH-RH antagonist).
    • Postmenopausal: aromatase inhibitors (letrozole, anastrozole, exemestane), tamoxifen.
  • Chemotherapy: CMF, Anthracyclines, Taxanes, Anti-HER-2 therapy, Herceptin (monoclonal antibody).

Stage III Treatment

Neoadjuvant Systemic Treatment: Multimodal treatment: chemotherapy (6-8 cycles of anthracycline and taxane combinations), trastuzumab for HER-2+ cases, hormone therapy (4-6 months of aromatase inhibitor). Local treatment: surgery (modified radical mastectomy) + radiotherapy. Adjuvant systemic therapy: chemotherapy + hormone therapy.

Palliative Treatment: Prevents disease progression, reduces disease-related symptoms. Considered incurable with a median survival of 24 months. 5-year survival rate is 3-12%.

Treatment of Metastatic Breast Cancer: Systemic treatment: Hormonal therapy, chemotherapy, trastuzumab, bisphosphonates.

Decision Algorithm in Metastatic Breast Cancer

Hormone therapy:

  • Postmenopausal: Aromatase inhibitor.
  • Premenopausal: Tamoxifen and/or ovarian ablation (oophorectomy or LH-RH antagonist).
  • Response to previous hormonal therapy.
  • Indolent disease.
  • Postmenopausal antiestrogen.
  • Premenopausal: ovarian ablation.
  • Response to previous hormonal therapy (all postmenopausal).
  • Megestrol acetate.
  • Estrogen.
  • Androgens.

Chemotherapy:

  • First-line chemotherapy:
    • Interval less than 12 months from adjuvant chemotherapy: Different chemotherapy than used in the adjuvant setting.
    • Interval greater than 12 months or no adjuvant chemotherapy: FAC, AC, CMF alone or taxane (paclitaxel, docetaxel).
  • Progression after first line:
    • No taxane in 1st line: taxanes.
    • Taxane in 1st line: FAC, AC, CMF.
  • Progression after second line: Vinorelbine, Capecitabine, 5-FU/FA, liposomal Adriamycin, Gemcitabine, Etoposide.