This summary discusses primary epithelial breast cancers in women. The breast is rarely affected by other tumors such as lymphomas, sarcomas, or melanomas. Refer to the following PDQ summaries for more information on these cancer types:
Estimated new cases and deaths from breast cancer (women only) in the United States in 2016:
New cases: 246,660.
Breast cancer is the most common noncutaneous cancer in U.S. women, with an estimated 61,000 cases of in situ disease, 246,660 cases of invasive disease, and 40,450 deaths expected in 2016. Thus, fewer than one of six women diagnosed with breast cancer die of the disease. By comparison, it is estimated that about 72,160 American women will die of lung cancer in 2016. Men account for 1% of breast cancer cases and breast cancer deaths (refer to the Special Populations section in the PDQ summary on Breast Cancer Screening for more information).
Widespread adoption of screening increases breast cancer incidence in a given population and changes the characteristics of cancers detected, with increased incidence of lower-risk cancers, premalignant lesions, and ductal carcinoma in situ (DCIS). (Refer to the Ductal Carcinoma In Situ section in the Breast Cancer Diagnosis and Pathology section in the PDQ summary on Breast Cancer Screening for more information.) Population studies from the United States  and the United Kingdom  demonstrate an increase in DCIS and invasive breast cancer incidence since the 1970s, attributable to the widespread adoption of both postmenopausal hormone therapy and screening mammography. In the last decade, women have refrained from using postmenopausal hormones, and breast cancer incidence has declined, but not to the levels seen before the widespread use of screening mammography.
Risk and Protective Factors
Increasing age is the most important risk factor for breast cancer. Other risk factors for breast cancer include the following:
Age-specific risk estimates are available to help counsel and design screening strategies for women with a family history of breast cancer.[43,44]
Of all women with breast cancer, 5% to 10% may have a germline mutation of the genesBRCA1 and BRCA2. Specific mutations of BRCA1 and BRCA2 are more common in women of Jewish ancestry. The estimated lifetime risk of developing breast cancer for women with BRCA1 and BRCA2 mutations is 40% to 85%. Carriers with a history of breast cancer have an increased risk of contralateral disease that may be as high as 5% per year. Male BRCA2 mutation carriers also have an increased risk of breast cancer.
Risk-reducing oophorectomy or ovarian ablation.[67-70]
(Refer to the PDQ summary on Breast Cancer Prevention for more information about factors that decrease the risk of breast cancer.)
Clinical trials have established that screening asymptomatic women using mammography, with or without clinical breast examination, decreases breast cancer mortality. (Refer to the PDQ summary on Breast Cancer Screening for more information.)
When breast cancer is suspected, patient management generally includes the following:
Confirmation of the diagnosis.
Evaluation of the stage of disease.
Selection of therapy.
The following tests and procedures are used to diagnose breast cancer:
Breast magnetic resonance imaging (MRI), if clinically indicated.
Pathologically, breast cancer can be a multicentric and bilateral disease. Bilateral disease is somewhat more common in patients with infiltrating lobular carcinoma. At 10 years after diagnosis, the risk of a primary breast cancer in the contralateral breast ranges from 3% to 10%, although endocrine therapy decreases that risk.[71-73] The development of a contralateral breast cancer is associated with an increased risk of distant recurrence. When BRCA1/BRCA2 mutation carriers were diagnosed before age 40 years, the risk of a contralateral breast cancer reached nearly 50% in the ensuing 25 years.[75,76]
Patients who have breast cancer will undergo bilateral mammography at the time of diagnosis to rule out synchronous disease. To detect either recurrence in the ipsilateral breast in patients treated with breast-conserving surgery or a second primary cancer in the contralateral breast, patients will continue to have regular breast physical examinations and mammograms.
The role of MRI in screening the contralateral breast and monitoring women treated with breast-conserving therapy continues to evolve. Because an increased detection rate of mammographically occult disease has been demonstrated, the selective use of MRI for additional screening is occurring more frequently despite the absence of randomized, controlled data. Because only 25% of MRI-positive findings represent malignancy, pathologic confirmation before treatment is recommended. Whether this increased detection rate will translate into improved treatment outcome is unknown.[77-79]
Prognostic and Predictive Factors
Breast cancer is commonly treated by various combinations of surgery, radiation therapy, chemotherapy, and hormone therapy. Prognosis and selection of therapy may be influenced by the following clinical and pathology features (based on conventional histology and immunohistochemistry):
Menopausal status of the patient.
Stage of the disease.
Grade of the primary tumor.
Estrogen receptor (ER) and progesterone receptor (PR) status of the tumor.
Human epidermal growth factor type 2 receptor (HER2/neu) overexpression and/or amplification.
Histologic type. Breast cancer is classified into a variety of histologic types, some of which have prognostic importance. Favorable histologic types include mucinous, medullary, and tubular carcinomas.[81-83]
The use of molecular profiling in breast cancer includes the following:
ER and PR status testing.
HER2/neu receptor status testing.
Gene profile testing by microarray assay or reverse transcription-polymerase chain reaction (e.g., MammaPrint, Oncotype DX).
On the basis of ER, PR, and HER2/neu results, breast cancer is classified as one of the following types:
Triple negative (ER, PR, and HER2/neu negative).
ER, PR, and HER2 status are important in determining prognosis and in predicting response to endocrine and HER2-directed therapy. The American Society of Clinical Oncology/College of American Pathologists consensus panel has published guidelines to help standardize the performance, interpretation, and reporting of assays used to assess the ER/PR status by immunohistochemistry and HER2 status by immunohistochemistry andin situ hybridization.[85,86]
Gene profile tests include the following:
MammaPrint: The first gene profile test to be approved by the U.S. Food and Drug Administration was the MammaPrint gene signature. Its prognostic utility primarily targets adjuvant therapy−decision making in women aged 61 years and younger with stage I/II lymph node–negative breast cancer 5 cm or smaller.[87-91] The MINDACTtrial (NCT00433589) will help determine if the assay should be used to decide whether adjuvant chemotherapy may benefit a patient.
Oncotype DX: The Oncotype DX 21 gene assay is the gene profile test with the most extensive clinical validation thus far, albeit in a prospective–retrospective fashion. A 21-gene recurrence score (RS) is generated based on the level of expression of each of the 21 genes:
RS <18: low risk.
RS ≥18 and <31: intermediate-risk.
RS ≥31: high risk.
The following trials describe the prognostic and predictive value of multigene assays:
The prognostic ability of the Oncotype DX 21-gene assay was assessed in two randomized trials.
The NSABP B-14 trial randomly assigned patients to tamoxifen or placebo; the results favoring tamoxifen changed clinical practice in the late 1980s. Formalin-fixed, paraffin-embedded tissue was available for 668 patients. The 10-year distant recurrence risk for patients treated with tamoxifen was 7% for those with a low RS, 14% for those with an intermediate RS, and 31% for those with high RS (P < .001).
A community-based, case-control study examined the prognostic ability of the RS to predict breast cancer deaths after 10 years in a group of tamoxifen-treated patients and observed a similar prognostic pattern to that seen in patients from NSABP B-14.
Prediction of benefit from chemotherapy in patients with node-negative ER-positive breast cancer was assessed by the tamoxifen alone (n = 227) and the combination arms (n = 424) of the NSABP B-20 trial. Patients in the NSABP B-20 trial were randomly assigned to receive tamoxifen alone or tamoxifen concurrently with methotrexate and 5-fluorouracil (MF) or cyclophosphamide with MF (CMF).
The 10-year distant disease-free survival (DFS) improved from 60% to 88% by adding chemotherapy to tamoxifen in the high-risk group, while no benefit was observed in the low RS group.
Similar findings were reported in the prospective-retrospective evaluation of Southwestern Oncology Group trial S8814 in lymph node-positive patients treated with tamoxifen with or without cyclophosphamide, doxorubicin, and fluorouracil (CAF). However, the sample size in this analysis was small, follow-up was only 5 years, and the prognostic impact of having positive nodes needs to be taken into consideration.
Of note, both analyses (NSABP B-20 and S8814) were underpowered for any conclusive predictive analysis among patients identified as having an intermediate RS.
Results from the TAILORX trial (NCT00310180) may help provide recommendations for those with ER/PR-positive and node-negative disease with an intermediate RS. In this study, a low-risk score was defined as less than 11, intermediate score was 11 to 25, and high-risk score was greater than 25. These cut points differ from those described above.
Patients in this study with a low-risk score were found to have very low rates of recurrence at 5 years with endocrine therapy. Primary endpoint results from this study are awaited.
Rate of invasive DFS was 93.8%.
Rate of freedom from recurrence of breast cancer at a distant site was 99.3%.
Rate of freedom from recurrence of breast cancer at a distant or local-regional site was 98.7%.
Rate of overall survival was 98.0%.
Results from the RxPONDER trial (NCT01272037) will help to determine if there is a benefit from adjuvant chemotherapy in patients with ER-positive, node-positive early breast cancer treated with endocrine therapy, and a RS below 25.
Many other gene-based assays may guide treatment decisions in patients with early breast cancer (e.g., Predictor Analysis of Microarray 50 [PAM50] Risk of Recurrence [ROR] score, EndoPredict, Breast Cancer Index).
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www.proz.com/kudoz/english_to_spanish/art_literary/523942-key_factors.html - 65k - // www.llave.connmed.com.ar/portalnoticias_vernoticia.php?codigonoticia=17715 // www.frusculleda.com.ar/homepage/espanol/activities_teaching.htm // http://www.on24.com.ar/nota.aspx?idNot=36331 ||