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Breast Cancer Practice Essentials

Worldwide, breast cancer is the most frequently diagnosed life-threatening cancer in women and the leading cause of cancer death among women.

Essential update: Integrated 2D and 3D mammography achieves better detection of breast cancer
In a study of 7292 women older than 48 years who were screened with both conventional 2D mammography and integrated 2D and 3D mammography, integrated 2D-3D mammography showed improved breast-cancer detection with a decrease in false-positive results.[1] A total of 59 cancers were detected in 57 women. Of the cancers found, 39 cancers were detected by both 2D and integrated 2D-3D screening, and an additional 20 were detected only by the integrated screening. Of 395 falsepositive results, 181 resulted from both screenings, 141 were from 2D screening only, and 73 were from integrated 2D-3D screening.

Signs and symptoms


Early breast cancers may be asymptomatic, and pain and discomfort are typically not present. If a lump is discovered, the following may indicate the possible presence of breast cancer: Change in breast size or shape Skin dimpling or skin changes Recent nipple inversion or skin change, or nipple abnormalities Single-duct discharge, particularly if blood-stained Axillary lump See Clinical Presentation for more detail.

Diagnosis
Breast cancer is often first detected as an abnormality on a mammogram before it is felt by the patient or health care provider. Evaluation of breast cancer includes the following: Clinical examination Imaging Needle biopsy Physical examination The following physical findings should raise concern: Lump or contour change Skin tethering Nipple inversion Dilated veins Ulceration Paget disease Edema or peau dorange If a palpable lump is found and possesses any of the following features, breast cancer may be present: Hardness Irregularity Focal nodularity Fixation to skin or muscle Screening Early detection remains the primary defense in preventing breast cancer. Screening modalities include the following:

Breast self-examination Clinical breast examination Mammography Ultrasonography Magnetic resonance imaging Ultrasonography and MRI are more sensitive than mammography for invasive cancer in nonfatty breasts. Combined mammography, clinical examination, and MRI are more sensitive than any other individual test or combination of tests. Biopsy Core biopsy with image guidance is the recommended diagnostic approach for newly diagnosed breast cancers. This is a method for obtaining breast tissue without surgery and can eliminate the need for additional surgeries. Open excisional biopsy is the surgical removal of the entire lump. See Workup for more detail.

Management
Surgery Surgery is the primary treatment for breast cancer. Lumpectomy or total mastectomy may be indicated. Radiation therapy may follow surgery in an effort to eradicate residual disease while reducing recurrence rates. Adjuvant treatment for breast cancer involves radiation therapy and a variety of chemotherapeutic and biologic agents. There are 2 general approaches for delivering radiation therapy: External-beam radiotherapy (EBRT) Partial-breast irradiation (PBI) Surgical resection with or without radiation is the standard treatment for DCIS. Pharmacologic agents Hormone therapy and chemotherapy are the 2 main interventions for treating metastatic breast cancer. Common chemotherapeutic regimens include the following: Docetaxel Cyclophosphamide Doxorubicin Carboplatin Methotrexate Trastuzumab Two selective estrogen receptor modulators (SERMs), tamoxifen and raloxifene (Evista), are approved for reduction of breast cancer risk in high-risk women. The 2011 National Comprehensive Cancer Network (NCCN) guidelines include recommendations for the use of denosumab and eribulin, both of which received FDA approval in 2010. The 2011 guidelines support the use of biologic denosumab for the prevention of skeletal events. See Treatment and Medication for more detail. Image library

Anatomy of the breast.

Background
Worldwide, breast cancer is the most frequently diagnosed life-threatening cancer in women and the leading cause of cancer death among women. Many early breast carcinomas may be asymptomatic; pain or discomfort is not usually a symptom of breast cancer. Breast cancer is often first detected as an abnormality on a mammogram before it is felt by the patient or healthcare provider. The general approach to evaluation of breast cancer has become formalized as triple assessment: clinical examination, imaging (usually mammography and/or ultrasonography), and needle biopsy. (See Workup.) Increased public awareness and improved screening have led to earlier diagnosis, at stages amenable to complete surgical resection and curative therapies. Consequently, survival rates for breast cancer have improved significantly, particularly in younger women. Surgery is considered primary treatment for breast cancer. Many patients with early-stage breast cancer are cured with surgery alone. (See Treatment and Management.) Adjuvant treatment of breast cancer is designed to treat micrometastatic disease, or breast cancer cells that have escaped the breast and regional lymph nodes but which have not yet had an established identifiable metastasis. Depending on the model of risk reduction, adjuvant therapy has been estimated to be responsible for 35-72% of the reduction in mortality rate. Over the last 2 decades, breast cancer research has led to extraordinary progress in our understanding of the disease, resulting in more efficient and less toxic treatments. (See Treatment and Management.)

Anatomy
The breasts of an adult woman are milk-producing glands situated on the front of the chest wall. They rest on the pectoralis major muscle and are supported by and attached to the front of the chest wall on either side of the sternum by ligaments. Each breast contains 15-20 lobes arranged in a circular fashion. The fat that covers the lobes gives the breast its size and shape. Each lobe comprises many lobules, at the end of which are glands where milk is produced in response to hormones (see the image below).

Anatomy of the breast.

Pathophysiology

The current understanding of breast tumorigenesis is that invasive cancers arise through a series of molecular alterations at the cellular level, resulting in the outgrowth and spread of breast epithelial cells with immortal features and uncontrolled growth. Genomic profiling has demonstrated the presence of discrete breast tumor subtypes with distinct clinical behavior (eg, 4 subclasses: luminal A, luminal B, basal, and human epidermal growth factor receptor 2 [HER2]-positive). The exact number of disease subtypes and molecular alterations from which these subtypes derive remains to be fully elucidated, but they generally align closely with the presence or absence of hormone receptor and mammary epithelial cell type (luminal or basal). Evidence from the Cancer Genome Atlas Network showed that the 4 main breast tumor subtypes are caused by different subsets of genetic and epigenetic aberrations. [2] Interestingly, basal-like tumors shared a number of molecular characteristics common to serous ovarian tumors such as the types and frequencies of genomic mutations, suggesting that breast and ovarian cancer have a related etiology and potentially similar responsiveness to some of the same therapies. The figure below summarizes the current general understanding of breast tumor subtypes, prevalence, and the major associated molecular alterations. This view of breast cancer--not as a set of stochastic molecular events, but as a limited set of separable diseases of distinct molecular and cellular origins--has altered thinking about breast cancer etiology, type-specific risk factors, prevention, and treatment strategies.

Intrinsic subtypes of breast cancer.

Etiology
Epidemiologic studies have identified many risk factors that increase the chance of a woman developing breast cancer. Go to Breast Cancer Risk Factors for more information on this topic.

Epidemiology
Over the past 25 years, breast cancer incidence rates have risen globally, with the highest rates in Westernized countries. Reasons for this trend include change in reproductive patterns, increased screening, dietary changes, and decreased activity. Although breast cancer incidence is on the rise globally, breast cancer mortality has been decreasing, especially in industrialized countries. The 2002 international female breast cancer incidence rates varied by more than 25-fold, ranging from 3.9 cases per 100,000 in Mozambique to 101.1 cases per 100,000 in the United States. In 2008, the American Cancer Society (ACS) estimated there were nearly 1.4 million new cases of invasive breast cancer worldwide. In the US, approximately 207,090 new cases of female invasive breast cancer were predicted to occur in 2010, along with 1,970 cases in men.[3] In addition to invasive breast cancer, 54,010 new cases of in situ breast cancer were expected to occur among women, of which approximately 85% were expected to be ductal carcinoma in situ (DCIS). After 2 decades of increasing incidence rates, the number of new female breast cancers decreased by 2.2% per year from 1999 to 2005. This decrease is thought to reflect reduced use of HRT following the publication of the WHI findings in 2002, which linked HRT use to an increased risk of heart disease and breast cancer. Rates of DCIS have stabilized since 2000.[4]

The current lifetime risk of breast cancer in the US is estimated at 12.7% for all women, 13.3% for non-Hispanic whites, and 9.98% for black women. Overall, the annual incidence rates in black women (119.4/100,000) and Hispanic/Latina women (89.9/100,000) have been stable since the early 1990s, and they are lower than the annual incidence of breast cancer in white women (141.1/100,000). However, black women are more likely than white women to be diagnosed with larger, advancedstage tumors (>5 cm). Although incidence rates among Asian and Pacific Islander women have continued to increase at 1.5% per year (89/100,000), they are still significantly lower than the rates in white women. Japanese and Taiwanese woman have one fifth the risk of US women.[5] The various types of breast cancers are listed below by percentage of cases: Infiltrating ductal carcinoma is the most commonly diagnosed breast tumor and has a tendency to metastasize via lymphatics; this lesion accounts for 75% of breast cancers Approximately 64,000 cases of DCIS are diagnosed annually in the US Over the last 25 years, lobular carcinoma in situ (LCIS) incidence has doubled and is currently 2.8 per 100,000 women; the peak incidence is in women aged 40-50 years Infiltrating lobular carcinoma comprises less than 15% of invasive breast cancers Medullary carcinoma accounts for about 5% of cases and generally occurs in younger women Mucinous (colloid) carcinoma is seen in fewer than 5% of invasive breast cancer cases. Tubular carcinoma of the breast is comprises 1-2% of all breast cancers Papillary carcinoma is usually seen in women older than 60 years and accounts for approximately 12% of all breast cancers Metaplastic breast cancer accounts for less than 1% of breast cancer cases, tends to occur in older women (average age of onset in the sixth decade), and has a higher incidence in blacks Mammary Paget disease comprises 1-4% of all breast cancers and has a peak incidence in the sixth decade of life (mean age, 57 y)

Prognosis
Death rates from breast cancer in the United States have decreased steadily in women since 1990. The breast cancer mortality rate fell 24% between the years 1990 and 2000 for women aged 30-79 years. The largest decrease in mortality has been seen in women younger than 50 years (3.3% per year) compared with those aged 50 years and older (2.0% per year). The decrease in breast cancer death rates is thought to represent progress in both earlier detection and improved treatment modalities.[3] The 2010 estimates were 40,230 expected breast cancer deaths (39,840 women, 390 men).[3]

Prognostic and Predictive Factors


Numerous prognostic and predictive factors for breast cancer have been identified by the College of American Pathologists (CAP) to guide the clinical management of women with breast cancer. Breast cancer prognostic factors include the following: Axillary lymph node status Tumor size Lymphatic/vascular invasion Patient age Histologic grade Histologic subtypes (eg, tubular, mucinous [colloid], papillary) Response to neoadjuvant therapy ER/ PR status HER2 gene amplification and/or overexpression (see below) (Also see Breast Cancer and HER2.) Breast cancer predictive factors include the following: ER/PR status HER2 gene amplification and/or overexpression

Cancerous involvement of the lymph nodes in the axilla is an indication of the likelihood that the breast cancer has spread to other organs. Survival and recurrence are independent of level of involvement but directly related to the number of involved nodes. Patients with node-negative disease have an overall 10-year survival rate of 70% and a 5-year recurrence rate of 19%. In patients with lymph nodes that are positive for cancer, the recurrence rates at 5 years are as follows: 1-3 positive nodes: 30-40% 4-9 positive nodes: 44-70% More than 10 positive nodes: 72-82% Hormone-positive tumors have a more indolent course and are responsive to hormone therapy. ER and PR assays are routinely performed on tumor material by pathologists, and immunohistochemistry (IHC) is a semiquantitative technique that is observer and antibody dependent. Five-year survival rates are highly correlated with tumor stage, as follows: Stage 0: 99-100% Stage I: 95-100% Stage II: 86% Stage III: 57% Stage IV: 20% This prognostic information can guide physicians in making therapeutic decisions. Pathologic review of the tumor tissue for histological grade along with the determination of estrogen/progesterone receptor status and HER2 status is necessary for determining prognosis. Evaluation of lymph node involvement by sentinel lymph node biopsy or axillary lymph node dissection is generally[6]necessary as well. (See Staging.)

HER2
Before the routine use of trastuzumab (Herceptin, a monoclonal antibody) in adjuvant therapy, HER2 overexpression was associated with a more aggressive tumor phenotype and worse prognosis (higher rate of recurrence and mortality), independent of other clinical features (eg, age, stage, tumor grade), especially in patients who did not receive adjuvant chemotherapy. Additionally, HER2 status has been shown to be predictive for response to certain chemotherapeutic agents (ie, doxorubicin [Adriamycin]; and HER2-targeted therapies trastuzumab and lapatinib [Tykerb, a small-molecule oral tyrosine kinase inhibitor directed specifically to the HER2 receptor]). Retrospectively analyzed results from clinical trials have shown that HER2-positive patients benefit from anthracycline-based regimens secondary to the coamplification of topoisomerase II with HER2. Preliminary data also suggest that HER2 may predict response to and benefit from paclitaxel in the adjuvant setting. Go to Breast Cancer and HER2 for complete information on this topic.

Ductal carcinoma in situ


DCIS is divided into comedo (ie, cribriform, micropapillary, solid) and noncomedo subtypes, which provides additional prognostic information on the likelihood of progression or local recurrence, as shown in Table 1, below. Table 1. Ductal Carcinoma in Situ Subtypes (Open Table in a new window) DCIS Characteristic Comedo Nuclear grade Estrogen receptor High Negative Noncomedo Low Positive

HER2 overexpression Present Distribution Necrosis Local recurrence Prognosis

Absent

Continuous Multifocal Present High Worse Absent Low Better

Lobular carcinoma in situ


Approximately, 10-20% of women with LCIS develop invasive breast cancer within 15 years after their LCIS diagnosis. Thus, LCIS is considered a biomarker of increased breast cancer risk.

Infiltrating ductal carcinoma


Infiltrating ductal carcinoma is the most commonly diagnosed breast tumor and has a tendency to metastasize via lymphatics.

Infiltrating lobular carcinoma


Like ductal carcinoma, infiltrating lobular carcinoma typically metastasizes to axillary lymph nodes first. However, it also has a tendency to be more multifocal. Despite this, the prognosis is comparable to that of ductal carcinoma.

Medullary carcinoma
Roughly 30% of patients have lymph node metastasis. Typical or classic medullary carcinomas are often associated with a good prognosis despite the unfavorable prognostic features associated with this type of breast cancer. However, an analysis of 609 medullary breast cancer specimens from various stage I and II National Surgical Adjuvant Breast and Bowel Project (NSABP) protocols indicates that overall survival and prognosis are not as good as previously reported.

Mucinous carcinoma
Overall, patients with mucinous carcinoma have an excellent prognosis, with a greater than 80% 10year survival.

Tubular carcinoma
This type of breast cancer has a low incidence of lymph node involvement and a very high overall survival rate. Because of its favorable prognosis, patients are often treated with only breastconserving surgery and local radiation therapy.

Papillary carcinoma
Cystic papillary carcinoma has a low mitotic activity, which results in a more indolent course and good prognosis. However, invasive micropapillary ductal carcinoma has a more aggressive phenotype, even though approximately 70% of cases are ER-positive. A retrospective review of 1,400 cases of invasive carcinoma identified 83 cases (6%) with at least one component of invasive micropapillary ductal carcinoma. Additionally, lymph node metastasis is seen frequently in this subtype (70-90% incidence), and the number of lymph nodes involved appears to correlate with survival.

Metaplastic breast cancer


The majority of published case series have demonstrated a worse prognosis for MBC as compared with infiltrating ductal carcinoma, even when adjusted for stage, with a 3-year overall survival rate of 48-71% and 3-year disease-free survival rate of 15-60%. In most case series, large tumor size and advanced stage have emerged as predictors of poor overall survival and prognosis. Nodal status does not appear to impact survival in metaplastic breast cancer.

Mammary Paget disease


MPD is associated with an underlying breast cancer in 75% of cases. Breast-conserving surgery can achieve satisfactory results, but at the risk of local recurrence. Adjuvant chemotherapy with tamoxifen may increase survival in premenopausal patients with lymph node metastasis. Poor prognostic factors include a palpable breast tumor, lymph node involvement, histologic type, and patient younger than 60 years. The overall 5-year and 10-year survival rates are 59% and 44%, respectively.

Patient Education
For patient education information, see eMedicineHealth's Cancer and Tumors Center and Women's Health Center, as well as Breast Cancer, Mastectomy,Breast Lumps and Pain, Breast SelfExam, Mammogram, and Ovarian Cancer.

Referensi
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Sumber
http://emedicine.medscape.com/article/1947145-overview#showall