Breast Cancer

Etiology and Incidence

• Risk varies with age

• Major risk factors

         • Gender (female > male)

         • Age: rapid increase 40-60, then slower increased risk

         • Previous breast cancer

         • Family history (threefold excess risk of the disease in first-degree relatives

         • Atypical ductal hyperplasia (nine times risk)

         • DCIS or LN

• Models (e.g. Gail) for risk stratification

   • Formulas incorporating risk factors

   • Results in % yearly risk of breast cancer

• Genetics

    • Implicated in 5% of all breast cancers, 25% of cases in women < 30

    • BRCA1

         • Normal tumor suppressor gene

         • Abnormality in long arm of chromosome 17 (17q21)

         • Associated with breast and ovarian cancer

         • 40 - 90% risk by age 65

     • BRCA2

         • Chromosome 13 abnormality

         • Found in 30% of familial breast cancer

         • Associated with breast only

     • Her2/neu

         • Proto-oncogene over expressed in 30% of breast cancer

          • Trastuzumab (humanized monoclonal antibody with high affinity for the HER2 protein) 

           under study for HER2-overexpressing metastatic   disease

 

Histological Types

• DCIS (intraductal carcinoma)

• Origin in lactiferous ducts

• No detectable invasion of the basement membrane

• Considered potentially pre-malignant; 10-30% risk of invasive cancer over 10 yrs

• 10% lesions reclassified as malignant

• Different subtypes

   • Comedo – most virulent

   • Papillary, cribiform

 • Must evaluate multifocality (multiple sites in same lobule or quadrant), multicentricity (different lobules or quadrants), and extent of disease

 • Detectable as mammographic change or palpable mass 

• Lobular Neoplasia (LCIS)

  • Proliferation of small round epithelial cells within lumens of acini

• Discovered incidentally after biopsy; not considered pre-malignant, but increases risk of subsequent invasive cancer, usually ductal

• 90% bilateral, therefore risk factor for bilateral breast cancer

• Infiltrating Ductal

   • Most common malignant tumor

   • Originates from ductal epithelium

   • Subtypes

     • Not otherwise specified (NOS) – most common

     • Medullary – better 5-yr prognosis

     • Mucinous – elderly population

     • Papillary – indolent, slow growth

     • Tubular – 100% survival (with treatment) if > 90% tubular

• Invasive Lobular

     • 3-15% of breast cancer

     • Indian filing of small round cells

   

Breast Imaging and Diagnosis

• Mammography

    • Diagnostic

    • Density abnormalities (masses, asymmetries, and architectural distortions)

    • Microcalcifications

    • Needle (wire) directed biopsy

    • Stereotactic core-needle biopsy

• Screening

    • Baseline age 35, every other year 40-50 in women without risk factors, yearly after 50; with risk factors, yearly from 40 

• Ultrasound

    • Differentiate cysts from solid lesions

    • Ultrasound-guided core biopsy

 • FNA

     • 80 – 90% sensitivity

     • 2 – 10% false negative rate

Breast Cancer Staging

Operative Approaches

• Lumpectomy

    • Treatment for DCIS (when combined with XRT)

    • Removal of localized disease

• Breast conserving therapy (lumpectomy, AXLND, XRT)

     • Negative margins priority (1cm or more)

     • Level one and two node dissection (> 6 nodes)

     • Must leave cosmetically acceptable result

     • Postoperative breast XRT of 4500 cGy

     • As efficacious as MRM in stage I and III (NSABP B-04)

• Sentinel node biopsy

     • Indemnify draining lymph nodes (one or two usually) for diagnostic purposes

     • Combination of Tch⁹⁹ and lymphazurine blue dye

     • Multiple pathological sections and special studies (PCR) to determine metastasis

     • Verification of accuracy for centers and individual surgeons involves initial series with completion ALND at this time

 

• Modified Radical Mastectomy (MRM)

    • Total mastectomy with removal of lymph nodes in conjunction with breast

    • Several modifications:

               • Patey procedure – sacrifice pectoralis minor and remove level I, II, III lymph nodes, intact pectoralis major

              • Scanlon procedure – remove level III nodes without sacrificing pectoralis minor

             • Auchincloss procedure – level I and II dissection (most common)

• Radical Mastectomy

     • Removal of breast and underlying pectoralis muscles

      • Frequently requires skin grafts or muscle flaps for wound coverage

      • Rarely used today, mainly to treat chest wall involvement

• Breast reconstruction after MRM

          • Immediate or delayed reconstruction

          • Tissue expanders followed by saline implants

         • Transverse rectus abdominus muscle (TRAM) flaps (free or pedicle)

          • Latissimus dorsi flaps

Adjuvant Therapy

• Inflammatory breast cancer (neoadjuvant, i.e. prior to surgery)

• erythema and warmth over breast skin +/- palpable mass

• may have dermal lymphatic penetration by tumor cells

• treatment – chemotherapy followed by MRM and then radiation therapy

• Node positive breast cancer (and lesions > 1cm, indications vary locally)

• AC – doxorubicin and cyclophosphamide

• CMF – cyclophosphamide, methotrexate, 5-fluorouracil

 

Node negative breast cancer

• Same as node positive if high risk of recurrence (based upon size, lymphatic involvement, nuclear grade, oncogene expression)

• Tamoxifen for ER positive tumors with intermediate risk of recurrence

• No treatment with low risk of recurrence (i.e., tumor size < 1 cm)

• Hormonal therapy (Tamoxifen, reloxifene)

          • NSABP P-1 comparison of tamoxifen against placebo in 13,000 women who had never had breast cancer showed about 40% fewer breast cancers in the tamoxifen group

          • NSABP B-24 – Tamoxifen reduced the risk of invasive cancer (relative reduction of over 40%)

 

Complications of Surgical Therapy

• Lymphedema

• May result in late occurrence of lymphangiosarcoma

• Nerve injury

       • Long thoracic nerve – winged scapula deformity

        • Thoracodorsal nerve – innervates latissimus dorsi, results in inability to adduct humerus at the shoulder joint

• Seroma formation

      • Drains usually placed during mastectomy

      • May need multiple postoperative visits for drainage

 

References

Textbook of surgery: the biological basis of modern surgical practice. – 15^th ed. / [edited by] David C. Sabiston, Jr.; editor for basic surgical science, H. Kim Lyerly.

Surgical attending rounds/ [edited by] K. Francis Lee, Cornelius M. Dyke – 2^nd ed.

Wilcken, N., et al. Tamoxifen hits the target in situ Lancet, 06/12/99, Vol. 353 Issue 9169, p1986, 2p.

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