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Incidence- Breast carcinoma has increased in frequency over the last decade. As many as one in nine women will develop breast cancer during her lifetime.
Risk factors Breast Cancer Symptoms and Signs
1. Family history. There are at least two hereditary patterns to breast cancer.
Familial aggregation is associated with a modest increase in risk and is relatively common. The risk is markedly increased among first-degree relatives.
True genetic pattern. Linkage to a specific gene with high penetrance accounts for less than 5% of all cases of breast cancer. Cancer tends to occur at a younger age and is more likely to be bilateral. Multiple family members three or more generations are affected.
p53 is a tumor suppressor gene that appears in carriers and patients in Fraumeni families. The gene is located on chromosome 17.
BRCAI gene, located on chromosome 17q, is seen in patients with a familyy history of breast and ovarian cancer.
Early menarche
Late menopause
Nulliparity or a first pregnancy after age 30 years
Fibrocystic breast disease
Prior history of invasive or noninvasive breast cancers (intraductal or lobular carcinoma in situ)
Age
Estrogen replacement therapy (ERT) is associated with a modest relative risk breast cancer.
Prolonged use of oral contraceptives before the first pregnancy
Dietary factors [e.g., high-fat diet (unproven), alcohol consumption]
Pathology. Breast cancers are adenocarcinomas.
1. Classification
Papillary carcinomas (1 % of breast cancers) are low-grade, non invasive int ductal lesions.
Medullary carcinomas (5%-10% of breast cancers) are large bulky tumors have a low-grade infiltrating tendency and are surrounded by lymphocytes.
Inflammatory carcinomas (5% of breast cancers) invade the dermal lymphi and cause skin redness, induration, warmth, and an erysipeloid margin.
Infiltrating ductal scirrhous carcinomas (70% of breast cancers) are charac ized by nests and cords of tumor cells surrounded by a dense collagenous stroma.
2. Estrogen receptor (ER) status. Breast cancer can be classified according to the presence or absence of ERs, cellular proteins found in hormone-responsive tissues. Receptor status can change over the course of the disease. The 20%-309 of breast cancer patients with erbB-2 oncogene expression have more aggressil cancers and may have greater drug resistance.
ER-positive tumors are more common in postmenopausal patients. Approximately 60% of primary breast cancers have detectable ERs.
ER-negative tumors are common in premenopausal patients. One third of p tients with ER-negative primary breast cancers develop recurrent tumors tha are ER-positive.
Diagnosis Of Breast Cancer
1. Early detection. Routine breast self-examination and screening mammograpl have led to earlier detection of curable breast cancers.
Breast self-examination All women should be taught the technique of br self-examination. Such examinations are best performed monthly after the strual period, when breast swelling and fibrocystic changes are less likely terfere with the detection of a lump or mass. More than 80% of breast ca occur as a painless mass.
Mammography. All women between 35 and 40 years old should have a line mammogram.
(1) Depending on the presence of known risk factors, patients should urn mammography either yearly or every other year between age 40 and years, and yearly after age 50 years.
Women with risk factors for breast carcinoma should have a yearly mammogram at an earlier age.
Most breast cancers are irregular masses or areas associated with microcalcifications.
2. Pretreament evaluation of Breast cancer
In addition to a medical history, physical examination, chest radiograph, and routine laboratory tests (e.g., blood count, liver and renal function values, and serum calcium), all patients with newly diagnosed breast cancer should have a mammogram to detect multicentricity or bilateral involvement.
Radiologic tests include a bone scan and in advanced breast cancer, a CT or MRI scan of the liver. If the bone scan shows evidence of metastatic disease and radiographs are negative a CT scan or MRI scan of the bone or a bone biopsy should be performed to determine the correct therapy.
Excisional biopsy is indicated for patients who are good candidates for lumpectomy and breast preservation. Needle biopsy may also be helpful for diagnostic purposes before excisional biopsy.
Tumor markers. Patients with metastatic disease may have elevation in CA-153 or carcinoembryonic antigen (CEA) tumor markers.
Staging gives the currently used staging system for breast cancer.
Treatment of Breast Cancer
Therapy. The primary goal of therapy is to provide optimal control of the disease in the breast and regional tissues while providing the best possible cosmetic result. Systemic therapy should be given to patients at high risk for metastatic disease to eradicate micrometastases. Patients should be seen by a medical oncologist, radiation therapist, and surgeon to determine the best course of treatment, which may include surgery, radiation therapy, adjuvant chemotherapy, and adjuvant endocrine therapy.
Surgery
The optimal surgical approach is determined by the following factors.
Disease stage of Brest Cancer
Tumor size
Tumor location
Breast size and configuration
Number of tumors in the breast
Available surgical and radiotherapeutic techniques
Patient preference concerning breast conservation
Contraindications for Breast Conservation Surgery
Large tumor in a small breast (increases likelihood of poor cosmetic results) Subareolar primary tumors
More than one tumor in the breast
Contraindications to radiotherapy
Advanced disease (i.e., beyond stage II)
Large areas of intraductal disease or microcalcifications
Tumors with an extensive intraductal component (i.e., X25% of the primary tumor is in situ and there is at least one focus of breast cancer that is in situ in normal breast tissue and is separate from the breast primary)
Procedures of Breast Cancer
(1) Modified radical mastectomy entails removal of the breast and axillary contents with preservation of the pectoral muscles. Patients may undergo breast reconstruction during surgery or at a later time.
(2) Partial mastectomy, or lumpectomy, involves excision of the tumor and an adjacent rim of normal tissue.
A level I or 1I axillary dissection is performed for adequate staging and local control.
Level III dissection should be considered in patients with clinically positive nodes.
Three weeks after surgery, external beam radiation is used, with a boost to the local tumor site.
(3) In the past, most patients underwent modified radical mastectomy. Recent data indicate that breast conservation procedures, such as lumpectomy, allow adequate local control of the tumor and improve cosmetic outcome in selected cases; however, not all patients are suitable candidates for breast conservation.
Radiation therapy in Breast Cancer
a. Patients treated with lumpectomy and axillary dissection should receive definitive radiation therapy to the breast and lymphatics if they have positive lymph nodes.
b. Patients undergoing mastectomy should receive postoperative radiation if they have any of the following risk factors for local recurrence.
Primary tumor over 5 cm in size
More than four positive axillary nodes
Tumors involving the margin of surgical resection, invasion of pectoral fascia or muscle, or extranodal extension into the axillary fat
c. In patients at a high risk for distant metastases, radiation therapy can be given concurrently or delayed until the completion of adjuvant chemotherapy. The risk of arm edema is increased by postoperative axillary radiation.
3. Adjuvant chemotherapy delays or prevents recurrence and improves survival in patients with positive axillary nodes as well as in some patients with negative axillary nodes.
Premenopausal patients with positive axillary nodes are most likely to benefit from chemotherapy; such patients experience a 25%-30% reduction in mortality.
Combination chemotherapy is superior to single-agent therapy, especially in patients with metastatic breast cancer. Six cycles of therapy or 6 months of treatment are as effective as longer treatment periods.
Drug regimens. Maximal doses should be used unless the patient develops significant toxicity.
(1) The most popular adjuvant therapy regimen is cyclophosphamide, methotrexate, and 5-FU.
2) Patients at higher risk for developing recurrent or metastatic disease may be administered cyclophosphamide, doxorubicin, and 5-FU. Response rates for this regimen in patients with metastatic breast cancer range from 65%-80%.
3)Alternative regimens for patients with metastatic disease include doxorubicin, thiotepa, and vinblastine; high-dose cisplatin; mitomycin; intravenous vinblastine or 5-FU by continuous infusions; cyclophosphamide, methotrexate, and 5-FU; Taxol; and Navelbine.
4. Adjuvant endocrine therapy
a.Studies of ovarian ablation by radiation or oophorectomy or chemically by Lupron or Zoladex in premenopausal patients have reported mixed results, with possible long-term benefits in certain subgroups.
b.Hormonal therapy
(1) The estrogen antagonist tamoxifen is the preferred agent in postmenopausal patients with positive hormone receptors. In these patients, tamoxifen delays recurrence and improves survival; chemotherapy is about half as effective as tamoxifen.
The benefit of tamoxifen in premenopausal patients with ER-positive tumors is less clear,
Patients with ER-negative tumors exhibit little or no response.
2) Hormonal therapy for metastatic breast cancer
a)Hormonal therapy is appropriate for patients with subcutaneous metastases, lymph node involvement, pleural effusions, bone metastases, and nonlymphangitic lung metastases. Patients with liver metastases, lymphangitic disease of the lung, pericardial metastases, or other potentially life-threatening metastases should be treated with chemotherapy.
b)Patients with ER-positive primary tumors exhibit response rates of at least 30% to hormone therapy. If the tumor contains both positive estrogen and progesterone receptors, the response rate increases to 75%.
c)Patients whose hormone receptor status is unknown may respond to hormone therapy if the tumors are well-differentiated or if 1-2 years have elapsed between occurrence of the primary breast cancer and the development of metastatic disease.
Patients with a previous response to hormonal therapy may respond to discontinuation of the original agent and substitution of a second Other hormonal therapies include Megace, Arimidex, Halotestin, aminoglutethimide, and luteinizing hormone-releasing hormone (LH-RH) antagonists.
5. Specific treatment recommendations
a. Intraductal breast cancer has an excellent prognosis. Because the tumor is noninvasive (i.e., confined to the ducts), careful pathological review can exclude any risk of lymph node involvement or distant metastases.
Patients may be treated by total mastectomy or by lumpectomy followed by radiation, although this procedure is associated with a slightly higher incidence of second breast primaries.
Axillary node dissection is controversial; most experts believe it is unnecessary in these patients.
b. Lobular carcinoma in situ. Patients with this noninvasive lesion are at extremely high risk for development of invasive cancer in both breasts. Treatment options include bilateral mastectomy or rigorous observation and follow-up.
c. Stage I and 11 disease. Most patients with stage I and II breast cancer have the option of either a modified radical mastectomy or breast conservation with lumpectomy, axillary dissection, and postoperative radiation therapy.
d. Stage III disease. Treatment options are determined by tumor resectability.
1)Patients with operable tumors are treated with modified radical mastectomy and postoperative radiation therapy. These patients may also receive preoperative or postoperative adjuvant chemotherapy.
2)Patients with inoperable stage III disease have a high rate of local and distant recurrence and poor survival rates.
a)A combined-modality approach, using systemic chemotherapy in addition to surgery and radiation, is required.
b)In most cases, aggressive combination chemotherapy is initiated after biopsy to reduce tumor bulk, to facilitate local treatment, and to eradicate distant micrometastases.
Breast Cancer Prognosis:
Approximately 50% of patients with operable breast cancer develop recurrent disease unless they receive adjuvant chemotherapy or hormone therapy. Prognostic factors include:
1. Axillary node status. This status is the most important predictor of recurrence and
survival. Seventy percent of patients with negative nodes are disease-free at 10
years. This figure declines to 40% of patients with no more than three positive nodes and 15%-25% of patients with four or more positive nodes.
2. Histopathology. Poorly differentiated tumors with high nuclear grades have higher recurrence rates. Tumor size is an important prognostic factor independent of lymph node status. Tumors larger than 5 cm are associated with a decreased survival rate and an increased risk of recurrence.
Hormone receptor status. Of primary breast cancers, 60%-70% express ERs and 40%-50% express progesterone receptors. Patients with hormone receptor-positive tumors have lower rates of recurrence and prolonged survival rates compared with those with receptor-negative tumors.
S-phase fraction and DNA index. The S-phase fraction (i.e., the percentage of tumor cells in the S phase of the cell cycle) is proportional to the tumor growth rate. Patients with aneuploid tumors or high S-phase fractions, as determined by flow cytometry, have a poor prognosis compared with those with slow-growing diploid tumors.
Oncogenic expression. Expression of the HER-2 (c-erbB-2, neu) oncogene is associated with a poor prognosis.
Other prognostic factors. The following prognostic factors have been associated with a poorer prognosis in some studies: cathepsin-D, p53, HER-a/neu (erb-B2), epidermal growth factor receptor (EGF-R), TGF-a, PS2, and monoclonal antibody NCRC11.
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