OBSTETRICS & GYNECOLOGY

DANIELA CONTAGE SICCARDI, MD

Breast Cancer II



Once the diagnosis of breast cancer is made, the physician must stage the disease based on physical findings and special preoperative studies, since staging guides treatment.

I - Staging

Table 1. Clinical Staging of Breast Cancer
Primary Tumor
T1=Tumor 2 cm or less in greatest dimension
T2=Tumor greater than 2 cm but no more than 5 cm
T3=Tumor greater than 5 cm in greates dimension
T4=Tumor of any size with direct extension to chest wall(not pectoralis major) or skin.

Regional Lymph Nodes
N0=No Papable Axillary Nodes
N1=Metastases to Movable Axilary Nodes
N2=Metastases to Fixed, Matted Axillary Nodes

Distant Metastases
M0=No Distatnt Metatases
M1=Distant Metastases Including Ipsilateral Supraclavicular Nodes
Staging
5 Year Survival Rate
Clinical Sage I T1 N0 M0 93%
Clinical Stage IIA T1
T2		 N1
N0		 M0
M0		 72%
Clinical Stage IIB T2
T3		 N1
N0		 M0
M0		 72%
Clinical Stage IIIA T1
T2
T3
T3		 N2
N2
N1
N2		 M0
M0
M0
M0		 41%
Clinical Stage IIIB T4 Any N M0 41%
Clinical Stage IV Any T Any N M1 18%

As defined by Haagensen, criteria for inoperability are:

1-Extensive edema of the breast;

2-Inflamatory carcinoma;

3-Paraesternal tumor, indicating spread to the internal mammary nodes;

4-Satellite nodules of carcinoma;

5-Supraclavicular metastasis;

6-Arm edema;

7-Distant metastasis. Determination of distant metastasis:

  • liver function tests - alkaline phosphatase is the most sensitive in detecting hepatic metastasis. A liver ultrasound or CT scan may also be used.

  • chest radiograph - detects pulmonary parenchymal or bone metastasis.

  • bone scan - should always be performed when nodes are positive, or if the patient has bone pain.

  • mammogram - to determine aditional foci and the presence of metastatic or synchronous disease.

  • CT scan or radioisotope of the brain - in the presence of neurologic signs or symptons.

    A pathological sample of the suspected metastasis must be obtained to prove diagnosis.

    ** 25% of patients with no evidence of metastatic disease have had occult dissemination at the time of initial diagnosis!

    II - Treatment

    Therapeutic options include surgery, radiation therapy, chemotherapy, endocrine therapy and combinations of these methods. Options are determined based on histology and stage of disease.

    1 - Curative Treatment - For clinical stage I and II disease. Patients with stage III tumors may be cured with multimodality therapy , but in most cases palliation is all that can be expected.

    Lumpectomy ( partial or segmental mastectomy ), axillary lymphadenectomy*, and postoperative radiation therapy (4500 rads with a boost to the tumor site of 2000 rads) are combined as the treatment of choice for most stages I and II breast cancer.

    *removal of level I or II nodes in relation to the axillary vein. Complete axillary dissection is not needed because skip metastases ( level III nodes + with levels I and II - ) occur in less than 5% of cases.

    ( FIGURE 1 )

    Contraindications to this approach:

  • large tumor size (>5 cm) compared to small breast size, which compromises the cosmetic result;

  • inability to participate in needed follow-up;

  • gross, multifocal disease or diffuse malignant microcalcifications;

  • retroareolar or nipple lesions, unless the nipple-areola complex is removed , which again tends to detract from the cosmetic result.

    If one of these contraindications is present or if the patient prefers another surgical approach, modified radical mastectomy ( Patey's operation ) must be performed . It removes the skin, the entire breast and the axillary contents ( the original operation involves removing the pectoralis minor muscle, but this part is not oftten included because adequate lymph node removal does not require it ). The major advantage of modified radical mastectomy is that radiation therapy is usually not necessary. Breast reconstruction is often performed simultaneously, with either a subpectoral prothesis or autogenous tissue transfer.

    Chemotherapy or hormonal therapy is advocated for most patients with curable breast cancer. Their objective is to eliminate the occult metastases responsible for late recurrences while they are microscopic and theoretically most vulnerable to anticancer agents.

    There are numerous regimens for chemotherapy, but the most extensive and favorable clinical experience has been with cyclophosphamide, methotrexate and fluorouracil (CMF). Cyclophosphamide can be given either orally, in a dose of 100mg/m2 daily for 14 days; or intravenously, in a dose of 600mg/m2 on days 1 and 8 ; and fluorouracil is given intravenously, 600mg/m2 on days 1 and 8. This cycle is repeated every 4 weeks for 6 months.

    Hormone therapy uses tamoxifen for 2-5 years in a dosage of 1mg orally twice a day. Tamoxifen , a competitive inhibitor of endogenous estrogen, binds to estrogen receptors and achieves an antitumor effect by an unknown mechanism. It can be given with few side effects even in the elderly ( different from chemotherapy ), and appears to increase bone density and favorably affect lipid and lipoprotein profiles.

    Table 2. Adjuvant Therapy in Pre-menopausal Women
    Axillary Nodes Estrogen Receptor Adjuvant Therapy
    Yes Yes Combined Cherotherapy
    Yes No Combined Cherotherapy
    No Yes Tamoxifen
    No No Combined Cherotherapy

    Table 3. Adjuvant Therapy in Post-menopausal Women
    Axillary Nodes Estrogen Receptor Adjuvant Therapy
    Yes Yes Tamoxifen
    Yes No Combined Chemotherapy
    No Yes Tamoxifen
    No No Combined Chemotherapy

    2 - Palliative Treatment ( Advanced Disease ) - Stage III breast cancer may be treated either with : a)systemic therapy ( either hormonal or chemotherapy ) to determine the effectiveness of the systemic treatment and to reduce the bulk of tumor; b)with local therapy, which may be either mastectomy followed by radiation therapy or radiation therapy alone. The median length of survival after effective treatment is 18 to 24 months.

    The management of stage IV ( metastatic ) breast cancer is determined in part by sites of metastases, menopausal status and hormone receptor status. There are 3 categories of systemic therapy for advanced breast cancer: hormone therapy, chemotherapy , and combination therapy. In general, only one type of systemic therapy should be given at a time. The regimen should be changed only if the disease is clearly progressing, but not if it appears to be stable.

  • Hormone therapy - It can be very effective for tumors that have high concentration of estrogen receptor protein in the cytoplasm. Tumors with progesterone receptors are also more likely to be hormonally responsive. The sites of disease most often responsive to hormones are pulmonary nodules, pleural effusions, and osseous lesions. Patients with hepatic metastases, lymphangitic pulmonary involvement, brain metastases or skin lesions have a lower responsive rate to hormones .

  • Chemotherapy - It should be considered after hormonal manipulations have failed or when they are deemed inappropriate ( eg, in receptor-negative patients ). However, the likelihood of response is reduced when the tumor has proved resistant to other forms of treatment.

  • Radiotherapy - It should be considered for locally advanced cancers with distant metastases in order to control ulceration, pain and other manifestations in the breast and regional nodes. It is also of value in the treatment of certain bone or soft tissue metastases to control pain or avoid fracture.

    III - Prognosis

    Prognosis strongly depends on a number of clinical and histologic factors at the time of diagnosis.

    1 - Histology - The carcinomas can be categorized by the ability of a cell type to metastasize.

    a) Noninvasive breast cancer - 10% of all breast cancer. Good prognosis.

  • ductal carcinoma in situ ;

  • lobular carcinoma in situ ;

  • Paget's disease .

    b) Invasive breast cancer :

  • favorable histologic types - with 85% 5-year survival rate.

    - tubular carcinoma ;

    - colloid or mucinous carcinoma ;

    - papillary carcinoma .

  • less favorable histologic types : - medullary cancer ;

    - invasive lobular cancer ;

    - invasive ductal cancer ( is the most common histologic type and constitutes over half of brest cancers ).

  • least favorable histologic types : - inflamatory breast cancer - it is associated with local inflammatory signs, including redness, localized warmth, swelling, and pain. Histollogically, tumor-plugged subdermal lymphatics are found. The prognosis is poor; the 5-year survival rate is approximately 30%.

    - invasive ductal lesions - with poor nuclear grade and vascular and lymphatic invasion have a poorer prognosis.

    2 - Stage of Disease

    ( TABLE 1 )

    3 - Other prognostic factors :

  • hormone receptor status - the presence of hormone receptors in brest tumors indicates that such a tumor is more likely to respond to hormonal manipulation, and has a better prognosis than other breast tumors.

    # DNA content analysis - tumor ploidy - diploid tumors have a better prognosis than aneuploid ones.

    - proliferation ability - the higher the S-phase fraction, the worse the prognosis.

    Other biological markers are under evaluation, including cathepsin, HER-2/neu, and p53.

    IV - Follow-up

    Follow-up care should be lifelong and has two objectives: to detect recurrence(s) and to observe the other breast for evidence of carcinoma. Every month, the patient should examine her own breast(s). Mammography should be obtained annually or when any change is detected. During the first 3 years, when metastases are most likely, physician examinations are performed every 3-4 months. Between 4-5 years, examination is performed every 6 months. After 5 years, examinations are continued at 6-12 month intervals.

    Bibliography

    1 - Jarrel, B.E.; Carabasi, R.A. III. Surgery - The National Medical Series for Independent Study. 3rd Edition. Williams & Wilkins , 1996.

    2 - Way, L.W. Current - Surgical Diagnosis & Treatment. 10th Edition. Appleton & Lange , 1994.

    3 - Benson, R.C. ; Pernoll, M.L. Handbook of Obstetrics and Gynecology. 9th Edition. McGraw-Hill, 1994.

    4 - Goroll, A.H.; May, L.A.; Mulley, A.G. Primary Care Medicine, Office Evaluation and Management of the Adult Patient. 3th Edition. Lippincot Company, 1995.


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