Breast cancer

Breast cancer

BASICS

DESCRIPTION:

Malignant neoplasm in the breast. Breast cancers are classified as noninvasive (in situ) or invasive (infiltrating) with approximately 70% of all breast cancers possessing a component of invasion.Read more....

System(s) affected: Skin/Exocrine, Pulmonary, Gastrointestinal, Musculoskeletal, Nervous
Genetics:
  •Only 20% of patients have a significant family history of breast cancer. This predisposition tends to be autosomal dominant with maternal lineage.
  •Recent studies have revealed families with breast cancer susceptibility genes including BRCA1 and BRCA2. Family history suggestive of breast cancer susceptibility genes include multiple first and second degree relatives with early breast cancer diagnosis and the presence of ovarian cancer. Approximately 1 in 400 U.S. women will carry a germ-line mutation for BRCA1. BRCA1 and BRCA2 carriers have a 50 - 85 % lifetime risk of breast cancer, ovarian cancer, or both. BRCA2 carriers have a higher risk of male breast cancer.
Incidence/Prevalence in USA:
  •1 in 8 women will develop breast cancer within a lifetime
  •The American Cancer Society estimates that 182,800 new cases will be diagnosed in 2000 with 40,800 deaths (including 400 men)
Predominant age: 30-80 with peak age 45-65; 77% of cases occur in women > age 50
Predominant sex: Female > Male (1% occurs in male)

SIGNS AND SYMPTOMS:

  •Palpable mass (55%)
  •Abnormal mammogram without a palpable mass (35%)
  •Color changes
  •Lymphedema (peau d'orange)
  •Dimpling
  •Nipple retraction
  •Breast enlargement
  •Axillary mass
  •Bone pain (rare)
  •Discharge (bloody discharge is more ominous)

CAUSES:

Unknown

RISK FACTORS:

  •Increased breast cancer risk occurs in first degree relatives (relative risk [RR] = 2.3), with bilateral disease in premenopausal relatives (RR = 10.5), or bilateral disease in postmenopausal relatives (RR = 5.0)
  •Increased hormone risks include early menarche, late menopause, nulliparity or first full term pregnancy after age 30
  •Women with a prior history of breast cancer or previous breast biopsies revealing atypical changes are at increased risk (5-10 times) for subsequent cancer
  •Exogenous estrogen use, especially in conjunction with progestins increase the risk of breast cancer

DIAGNOSIS

DIFFERENTIAL DIAGNOSIS:

  •Differential diagnosis is extensive
  •Benign breast disorders such as abscesses, hematomas, or fibroadenomas
  •Proliferative breast diseases such as fibrocystic changes, ductal and lobular hyperplasia, or sclerosing adenosis
  •Malignant breast diseases including sarcomas, lymphomas, or metastatic disease to breast

LABORATORY:

Initial lab tests include CBC, LFTs, CXR, bilateral mammography +/- ultrasound, pathologic review of biopsy, estrogen and progesterone receptor determination, and S phase determination

Drugs that may alter lab results: N/A
Disorders that may alter lab results: N/A

PATHOLOGICAL FINDINGS:

  •Noninvasive cancers (carcinoma in situ)
      •The percentage of non-invasive cancers diagnosed is increasing due to increased mammography screening
      •Usually detected by abnormal mammogram
      •Noninvasive cancers are of two types: Intraductal or intralobular. Intraductal cancers are subdivided by growth patterns: Micropapillary, cribriform, solid, or comedo. The comedo growth pattern is considered more aggressive.
  •Invasive cancers
      •Tend to present with a breast lump
      •Subdivided into - not-otherwise-specified (50%), lobular (5%), Paget's disease (2%), and miscellaneous (metaplastic, neuroendocrine, or squamous cell carcinomas [1%])
      •Patients with invasive histologies with medullary 6%, colloid 7%, tubular, papillary, and adenoid cystic carcinomas 2%, have improved survival

SPECIAL TESTS:

  •Bone scan should be performed if symptoms suggest bony metastasis, if alkaline phosphatase is elevated, or if widespread disease is suspected
  •CT or US of the abdomen may be indicated if widespread or recurrent disease is suspected

IMAGING:

  •Mammography, which detects 80% of breast cancers, is the best technique for the detection of minimal (< 0.5 cm) breast cancer. The most common abnormality representing cancer is an irregular mass. Microcalcifications can occur as the only sign of malignancy in 35% of breast cancers.
  •Ultrasound may confirm whether a suspicious lump is solid or cystic and help define its size and extent

DIAGNOSTIC PROCEDURES:

  •Tissue confirmation of the suspicious mass or abnormal mammogram is essential. Biopsy may be excisional or incisional depending upon the size and location of the abnormality.
  •Biopsy of non-palpable lesions is achieved with needle localization
  •Cytologic confirmation of a palpable abnormality may be obtained by fine needle aspiration or core needle biopsy

TREATMENT

APPROPRIATE HEALTH CARE:

Patients are usually treated by a team consisting of a medical oncologist, a surgeon, and a radiation oncologist

GENERAL MEASURES:

  •Early breast cancer treatment (Stage I/II)
      •Lumpectomy (wide excision with breast conservation) and radiotherapy is the treatment of choice for early primary breast cancer.
      •Axillary node dissection is indicated with all invasive tumors and large noninvasive ones. Identification and biopsy of sentinel nodes may soon be preferred over axillary dissection because of its lower morbidity rate.
      •Most women with primary breast cancer have subclinical metastases and many will have recurrence of disease despite apparently curative surgery and the use of radiotherapy.
  •Treatment of locally advanced breast cancer (Stage III)
      •Usually multidisciplinary treatment consisting of mastectomy, axillary dissection, radiation, and chemotherapy +/- tamoxifen
      •Preoperative chemotherapy or hormonal therapy often converts inoperable tumors to operable ones
  •Treatment of advanced or recurrent disease (Stage IV)
      •Surgical resection if possible; chemotherapy, radiation, hormonal therapy.

SURGICAL MEASURES:

  •Breast conserving surgery is appropriate for most breast cancers
  •Studies comparing mastectomy to breast conserving procedures show no difference in long-term survival
  •If any axillary nodes are positive, 60-70% risk of relapse within 5 years
  •If all axillary nodes are negative, there is 70-80% chance of long-term cure

ACTIVITY:

Minimal activity restrictions exist during treatment

DIET:

No proven relationship exists between breast cancer and diet

PATIENT EDUCATION:

  •Instruct patients in monthly breast self-examination to detect lumps, skin or nipple changes and the importance of mammography
  •For a listing of sources for patient education materials, physicians may contact: American Cancer Society and the National Cancer Institute

MEDICATIONS

DRUG(S) OF CHOICE:

  •Metastatic disease is considered incurable, but treatable with remissions occurring in 30-40% of patients
  •Chemotherapy reduces the risk of recurrence 22-37% and death 14-27%
  •The process of deciding when to use chemotherapy or hormonal therapy is complex and is dependent on tumor type, size, node status, hormone receptor status and other factors; practice guidelines are available
  •Combination chemotherapy is preferred over single agents.
  •Tamoxifen reduces the risk of recurrence and death for women of all ages; treatment should be continued for five years. It should be discontinued if tumor growth continues. It probably is not of benefit to women with estrogen receptor negative tumors.

Contraindications: Strict hematologic, renal, hepatic, and cardiac guidelines need to be followed for the administration of cytotoxic chemotherapy
Precautions: Monitoring for infection is important for patients receiving chemotherapy. Tamoxifen increases the patient's risk of developing endometrial cancer and interacts with warfarin, erythromycin, cyclosporin, nifedipine, and diltiazem.
Significant possible interactions: Drug interactions are common and depend on combinations used. Refer to manufacturer's literature.

ALTERNATIVE DRUGS:

N/A

FOLLOW UP

PATIENT MONITORING:

  •Up to 60% of patients with invasive disease will relapse within five years despite initial therapy
  •The status of the axillary lymph nodes is the most important indicator for disease relapse
  •Surveillance for recurrent disease should include physical examination every 4 months for 2 years, every six months for 3 years, then yearly. Mammography and routine chemistries should be done annually. Women on tamoxifen should have annual pelvic exams.
  •Workup of suspected recurrence should include CBC, LFTs, CXR, bone scan, CT of affected area, +/- biopsy

PREVENTION/AVOIDANCE:

  •Decreasing dietary fat or alcohol has not been shown to alter breast cancer risk
  •The synthetic antiestrogen, tamoxifen, may be a useful prophylactic agent in high risk women
  •The selective estrogen receptor modulator, Evista, reduced the risk of breast cancer in short term studies and may play a role in prevention in the future
  •Mammography
      •Screening for disease: US Preventive Services Task Force recommends mammography with or without clinical breast examination every 1-2 years for ages 50-69. American Cancer Society recommends mammography and a clinical breast examination every year after age 40. They also recommend clinical breast examination every 3 years for ages 20-39 and self-breast examination starting at age 20. ACOG and AMA recommend mammogram every 1-2 years and annual clinical breast examination starting at age 40 and then annual mammograms at age 50.
      •Diagnostic mammography should be performed at the advice of the patient's physician
      •In women ages 50-69, mammography screening can reduce mortality by 30%; the reduction in mortality is less impressive for women younger than 50 or older than 70

POSSIBLE COMPLICATIONS:

  •Postoperative: lymphedema (< 5% in modified radical mastectomy), seromas, wound infection, and limited shoulder motion
  •Chemotherapy: nausea, vomiting, alopecia, leukopenia, bladder irritation, stomatitis, fatigue, and menstrual abnormalities
  •Tamoxifen: hot flushes, menstrual irregularities including menopause, vaginal discharge, hypercalcemia, skin rashes, and possible endometrial carcinoma
  •Irradiation: skin reaction, fibrosis (1%), brachial plexopathy (1%), rib fracture (1%), arm edema, pulmonary fibrosis (1%), and rarely second breast malignancy.

EXPECTED COURSE AND PROGNOSIS:

  •5 year survival
      •Stage 0 (noninvasive) 100%
      •Stage I (2 cm, no spread) 98%
      •Stage II (>2 cm, or spread to axillary lymph nodes) 76-88%
      •Stage III (>5 cm or fixed nodes, metastatic disease to the skin, inflammatory changes, chest wall extension, or supraclavicular lymph nodes) 49-56%
      •Stage IV (distant metastatic disease) 16%

MISCELLANEOUS

ASSOCIATED CONDITIONS:

Organ disease at metastatic sites

AGE-RELATED FACTORS:

Age-specific incidence of breast cancer increases sharply until menopause and continues to increase at a slower rate in the geriatric population

Pediatric: Breast cancer occurs rarely in children with the most common pathology being secretory carcinoma
Geriatric: There is a higher percentage of ER positive tumors (80%) in the geriatric population. This correlates with improved disease-free survival.
Others: N/A

PREGNANCY:

Breast cancer occurs infrequently during pregnancy (2.8%). Delay in diagnosis is common, and most series report poorer survival related to advanced stage at diagnosis.

SYNONYMS:

N/A

ICD-9-CM:

174 Malignant neoplasm of female breast
175 Malignant neoplasm of male breast

SEE ALSO:

N/A

OTHER NOTES:

N/A

ABBREVIATIONS:

  •ER = estrogen receptor
  •PgR = progesterone receptor

REFERENCES

  •Margolese RG. Surgical considerations for invasive breast cancer. Surg Clin No Amer 1999 Oct;79(5):1031-46
  •Smith RA, Mettlin C, Johnson-Davis K, et al. American Cancer Society guidelines for the early detection of cancer. CA Cancer J Clin 2000;50(1):34-49
  •Schairer C, Lubin J, Troisi R, et al. Menopausal estrogen and estrogen-progestin replacement therapy and breast cancer risk. JAMA 2000;283(4):485-91
  •Hortobagyi G Treatment of breast cancer. N Engl J Med 1998;339(14):974-984
  •Krag D, Weaver D, et al. The sentinel node in breast cancer. N Engl J Med 1998;339(14):941-946
  •Osborne C Tamoxifen in the treatment of breast cancer. N EngI J Med 1998;339(22):1609-1618.
  •Update of the NCCN guidelines for the treatment of breast cancer. Oncology 1997; I I(II A):199-220
  •US Preventive Services Task Force. Guide to Clinical Preventive Services. 2nd Ed. Baltimore, Williams & Wilkins, 1996

Web citations:

National Cancer Institute - CancerNet
American Cancer Society
Cancernet Breast cancer