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Sunday, 16 October 2011

Breast cancer screening


Breast cancer screening refers to testing otherwise-healthy women for breast cancer in an attempt to achieve an earlier diagnosis. The assumption is that early detection will improve outcomes. A number of screening test have been employed including: clinical and self breast exams, mammography, genetic screening, ultrasound, and magnetic resonance imaging.
A clinical or self breast exam involves feeling the breast for lumps or other abnormalities. Evidence however does not support its use. Mammographic screening for breast cancer is also controversial. The Cochrane collaboration in 2009 concluded that it is unclear whether screening does more good than harm. Many national organizations still however recommend it. If mammography is decided up it should only be done every two years in women between the ages of 50 and 74. Several tools are available to help target breast cancer screening to older women with longer life expectancies.
Abnormal findings on screening are further investigated by surgically removing a piece of the suspicious lumps (biopsy) to examine them under the microscope. Ultrasound may be used to guide the biopsy needle during the procedure. Magnetic resonance imaging is used to guide treatment, but is not an established screening method for healthy women.
Women with a family history of breast and ovarian cancer have a higher risk of mutations of the BRCA1 and BRCA2 genes. These mutations result in a higher risk of breast cancer. Testing for these genes is expensive and not done routinely. However those with this mutation should be screened more aggressively: starting at an earlier age, with greater frequency, and possibly with magnetic resonance imaging.

Breast examination,

All about: Breast cancer classification and Self-examination of Breasts



An pictorial example of breast self-examination in six steps. Steps 1-3 involve inspection of the breast with the arms hanging next to the body, behind the head and in the side. Step 4 is palpation of the breast. Step 5 is palpation of the nipple. Step 6 is palpation of the breast while lying down.
Breast examination ( either clinical breast exams (CBE) by a health care provider or by self exams ) were once widely recommended. They however are not supported by evidence and may contribute to harm. Their use in women without symptoms and at low risk is thus controversial.
A 2003 Cochrane review found no benefit in terms of mortality from screening by breast self-examination or by clinical exam, but rather that they do possible harm in terms of increased numbers of benign lesions identified and an increased number of biopsies performed. They conclude "screening by breast self-examination or physical examination cannot be recommended." 


 Mammography

Normal (left) versus cancerous (right) mammography image.
Mammography is a common screening method, since it is relatively fast and widely available in developed countries. When detected by mammography breast cancers are usually smaller (in an earlier stage) than those detected by patients or doctors as a breast lump, and presumably treatment in an earlier stage will improve outcome. This assertion however has been challenged by recent reviews.
A 2009 Cochrane review estimated that mammography in women between 50 and 75 years old results in a relative risk reduction of death from breast cancer of 15% or an absolute risk reduction of 0.05%. Those who have mammograms however end up with increased surgeries, chemotherapy, radiotherapy and other potentially procedures resulting from the over-detection of harmless lumps. Consequently, the value of routine mammography in women at low or average risk is controversial. With unnecessary treatment of ten women for every one woman whose live was prolonged, the authors concluded that routine mammography may do more harm than good..
A 2009 U.S. Preventive Services Task Force analysis come to similar conclusions: for women in their 40s 2000 would need to be screened for 10 years, resulting in 1000 people with false results and 250 unnecessary biopsies to prevent 1 breast cancer death, for women in their 50s 1339 would need to be screened for 10 years to prevent a single breast cancer related death, and for women in their 60s 377 women would need to be screened for 10 years.
An analysis of the Norwegian breast-cancer screening program published in 2010 found a 10% reduction in breast cancer mortality (2.4 deaths per 100,000 person-years) but difference was none significant.
For places that recommend screening the age at which this should begin and how frequently women differ around the world. In the UK, all women are invited for screening once every three years beginning at age 50. As of 2009 the US Preventive Services Task Force recommends that women over the age of 50 receive mammography once every two years.
Women at higher risk may benefit from earlier or more frequent screening. Women with one or more first-degree relatives (mother, sister, daughter) with premenopausal breast cancer often begin screening at an earlier age, perhaps at an age 10 years younger than the age when the relative was diagnosed with breast cancer.
Mammography is not generally considered as an effective screening technique for women less than 50 years old. A systematic review by the American College of Physicians concluded that, for women 40 to 49 years of age, the risks of mammography outweighed the benefits, and the US Preventive Services Task Force says that the evidence in favor of routine screening of women under the age of 50 is "weak". Part of the difficulty in interpreting mammograms in younger women stems from breast density. Radiographically, a dense breast has a preponderance of glandular tissue, and younger age or estrogen hormone replacement therapy contribute to mammographic breast density. After menopause, the breast glandular tissue gradually is replaced by fatty tissue, making mammographic interpretation much more accurate. Some authors speculate that part of the contribution of estrogen Hormone replacement therapy to breast cancer mortality arises from the issue of increased mammographic breast density.


Enhancements

In general, digital mammography and computer-aided mammography have increased the sensitivity of mammograms, but this may come at the cost of more numerous false positive results..
Computer-aided diagnosis(CAD) Systems may help radiologists to evaluate X-ray images to detect breast cancer in an early stage. CAD is especially established in US and the Netherlands. It is used in addition to the human evaluation of the diagnostician.

Health programs
In 2005, 67.9% of all U.S. women age 40–64 had a mammogram in the past two years (74.5% of women with private health insurance, 56.1% of women with Medicaid insurance, 38.1% of currently uninsured women, and 32.9% of women uninsured for > 12 months). All U.S. states (except Utah) mandate that private health insurance plans and Medicaid provide some coverage for breast cancer screening. Section 4101 of the Balanced Budget Act of 1997 required that Medicare (available to those aged 65 or older or who have been on Social Security Disability Insurance for over 2 years), effective January 1, 1998, cover and waive the Part B deductible for annual screening mammography in women aged 40 or older.
All organized breast cancer screening programs in Canada offer clinical breast examinations for women aged 40 and over and screening mammography every two years for women aged 50–69. In 2003, about 61% of women aged 50–69 in Canada reported having had a mammogram within the past two years.
The NHS Breast Screening Programme, the first of its kind in the world, began in 1988 and achieved national coverage in the mid-1990s, provides free breast cancer screening mammography every three years for all women in the UK aged 50 and over. As of March 31, 2006, 75.9% of women aged 53–64 resident in England had been screened at least once in the previous three years.
The Australian national breast screening program, BreastScreen Australia, was commenced in the early 1990s and invites women aged 50–69 to screening every 2 years. No routine clinical examination is performed, and the cost of screening is free to the point of diagnosis.
The Singapore national breast screening program, BreastScreen Singapore, is the only publicly funded national breast screening program in Asia, and enrols women aged 50–64 for screening every two years. Like the Australian system, no clinical examination is performed routinely. Unlike most national screening systems however, clients have to pay half of the cost of the screening mammogram; this is in line with the Singapore health system's core principle of co-payment for all health services.



Criticisms

Some scientific groups however have expressed concern about the public's perceptions of the benefits of breast screening.
Data reported in the UK Million Woman Study indicates that if 134 mammograms are performed, 20 women will be called back for suspicious findings, and four biopsies will be necessary, to diagnose one cancer. Recall rates are higher in the U.S. than in the UK. The contribution of mammography to the early diagnosis of cancer is controversial, and for those found with benign lesions, mammography can create a high psychological and financial cost. For those diagnosed with cancer, mammography can be the difference between a lumpectomy versus metastatic disease.
Screening leads to false positive results and subsequent invasive procedures.
Nevertheless, surveys have shown that most women participating in mammography screening programs accept the risk of false positive recall and the majority do not find this highly distressing. The majority of women recalled will undergo additional imaging only, without any further intervention. There is some debate over how harmful such noninvasive recall assessment truly is.
A major effect of routine breast screening is to greatly increase the rate of early breast cancer detection, in particular for preinvasive ductal carcinoma in situ (DCIS), which is almost always impalpable and which cannot, for the most part, be detected reliably by any other test. While this ability to detect such very early breast malignancies is at the heart of claims that screening mammography can improve survival from breast cancer, it is also controversial. This is because a large percentage of such cases will almost certainly not progress to kill the patient, and thus mammography cannot be genuinely claimed to have been beneficial in such cases; in fact, it would lead to increased morbidity and unnecessary surgery for such patients.
It has thus been claimed that finding and treating many cases of DCIS represents "overdiagnosis" and "overtreatment". However, it is not possible to accurately predict which patients with DCIS will have an indolent nonfatal course, and which will inevitably progress to invasive cancer and death if left untreated. Consequently, all patients with DCIS are treated in much the same way, with at least wide local excision, and sometimes mastectomy if the DCIS is very extensive. The cure rate for DCIS if treated appropriately is extremely high. Thus, it can be argued that some women with DCIS detected by screening mammography do in fact benefit from screening, even if others do not. Any refinement of this therapeutic approach to breast malignancy requires further research and the development of methods that accurately predict the future cellular fate and biological behaviour of early cancers.
It is salient to note that the phenomenon of finding preinvasive malignancy or nonmalignant benign disease is commonplace in all forms of cancer screening, including pap smears for cervical cancer, fecal occult blood testing for colon cancer, and prostate-specific antigen testing for prostate cancer. All of these tests have the potential to detect very early malignancy before it becomes symptomatic, and to potentially lead to long term cure. All of them have false positives, and can lead to invasive procedures that may not benefit the patient.
Given current limitations in knowledge and technology, the only way to avoid "overdiagnosis" and "overtreatment", and to eliminate all harms inherent in breast cancer screening is not to screen at all, and thus to eliminate any benefit to at least some of the screened population that screening entails. In the case of breast cancer, cessation of screening would lead to an increase in the size and stage of breast cancers at diagnosis, since most cancers would only be detected when they become symptomatic.



Ultrasonography

Breast MRI
Medical ultrasonography (Ultrasound) is a diagnostic aid to mammography.

Magnetic resonance imaging (MRI) has been shown to detect cancers not visible on mammograms. The chief strength of breast MRI is its very high negative predictive value. A negative MRI can rule out the presence of cancer to a high degree of certainty, making it an excellent tool for screening in patients at high genetic risk or radiographically dense breasts, and for pre-treatment staging where the extent of disease is difficult to determine on mammography and ultrasound. MRI can diagnose benign proliferative change, fibroadenomas, and other common benign findings at a glance, often eliminating the need for costly and unnecessary biopsies or surgical procedures. The spatial and temporal resolution of breast MRI has increased markedly in recent years, making it possible to detect or rule out the presence of small in situ cancers, including ductal carcinoma in situ.
However, breast MRI has long been regarded to have disadvantages. For example, although it is 27–36% more sensitive, it has been claimed to be less specific than mammography.. As a result, MRI studies may have more false positives (up to 30%), which may have undesirable financial and psychological costs. It is also a relatively expensive procedure, and one which requires the intravenous injection of gadolinium, which has been implicated in a rare reaction called nephrogenic systemic fibrosis. Although NSF is extremely uncommon, patients with a history of renal disease may not be able to undergo breast MRI. Further, an MRI may not be used for screening patients with a pacemaker or breast reconstruction patients with a tissue expander due to the presence of metal.
Proposed indications for using MRI for screening include:
Strong family history of breast cancer
Patients with BRCA-1 or BRCA-2 oncogene mutations
Evaluation of women with breast implants
History of previous lumpectomy or breast biopsy surgeries
Axillary metastasis with an unknown primary tumor
Very dense or scarred breast tissue
In addition, breast MRI may be helpful for screening in women who have had breast augmentation procedures involving intramammary injections of various foreign substances that may mask the appearances of breast cancer on mammography and/or ultrasound. These substances include:
Silicone oil
Polyacrylamide gel
Two studies published in 2007 demonstrated the strengths of MRI-based screening:
In March 2007, an article published in the New England Journal of Medicine demonstrated that in 3.1% of patients with breast cancer, whose contralateral breast was clinically and mammographically tumor-free, MRI could detect breast cancer. Sensitivity for detection of breast cancer in this study was 91%, specificity 88%.
In August 2007, an article published in The Lancet compared MRI breast cancer screening to conventional mammographic screening in 7,319 women. MRI screening was highly more sensitive (97% in the MRI group vs. 56% in the mammography group) in recognizing early high-grade Ductal Carcinoma in situ (DCIS), the most important precursor of invasive carcinoma. Despite the high sensitivity, MRI screening had a positive predictive value of 52%, which is totally accepted for cancer screening tests. The author of a comment published in the same issue of The Lancet concludes that "MRI outperforms mammography in tumour detection and diagnosis."
Based on this evidence, and the lack of effective alternative methods for screening in young women of very high genetic risk (either an extremely strong first degree family history or proven BRCA1 or BRCA2 oncogene mutation carrier status) for breast cancer, the Australian federal government decided to routinely reimburse annual breast MRI scans for such women under the age of 50 from January 2009 onwards.


BRCA testing

A clinical practice guideline by the US Preventive Services Task Force :
"recommends against routine referral for genetic counseling or routine breast cancer susceptibility gene (BRCA) testing for women whose family history is not associated with an increased risk for deleterious mutations in breast cancer susceptibility gene 1 (BRCA1) or breast cancer susceptibility gene 2 (BRCA2)" The Task Force gave a grade D recommendation.
"recommends that women whose family history is associated with an increased risk for deleterious mutations in BRCA1 or BRCA2 genes be referred for genetic counseling and evaluation for BRCA testing." The Task Force gave a grade B recommendation.
The Task Force noted that about 2% of women have family histories that indicate increased risk as defined by:
For non–Ashkenazi Jewish women, any of the following:
"2 first-degree relatives with breast cancer, 1 of whom received the diagnosis at age 50 years or younger"
"3 or more first- or second-degree relatives with breast cancer regardless of age at diagnosis"
"both breast and ovarian cancer among first- and second- degree relatives"
"a first-degree relative with bilateral breast cancer"
"a combination of 2 or more first- or second-degree relatives with ovarian cancer regardless of age at diagnosis"
"a first- or second-degree relative with both breast and ovarian cancer at any age"
"a history of breast cancer in a male relative."
"For women of Ashkenazi Jewish heritage, an increased-risk family history includes any first-degree relative (or 2 second-degree relatives on the same side of the family) with breast or ovarian cancer."


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