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Breast cancer screening

Worldwide the most common cancer in women with approximately 1.3 million new cases an estimated 458,000 deaths and 2008.

Mammography accounts for almost $8 billion in annual healthcare expenditures in the US.

In the United States many groups encourage annual screening starting at age 40, while in most other countries recommendation begins screening at age 50 and less frequent intervals of every 2-3 years.

Clinical breast exam has a sensitivity of 54% and a specificity of 94% and should be done for women age 40 years and older.

Can prevent some breast cancer deaths but not breast cancer.

Most cases are diagnosed between ages 55 and 64 years.
Routine screening should not be started before age 50, and should be performed from ages 50-74 and continue therrafter, but not when expected survival is less than 10 years.

Breast screening prevents death in a minority of women with breast cancer, and the effect size maybe smaller in the current era of effective adjuvant therapy (Miller AB et al).

Primary benefit of breast cancer screening is a reduction in breast cancer mortality, estimated to be between 14 and 33% for women age 52-74 years.

The process of greater awareness of breast cancer is associated with small average size of breast lesions diagnosed outside of mammography use.

Most women diagnosed with breast cancer do not die of the disease, even if it tumors of detected without mammography.

Many women diagnosed with late breast-cancer who were not screened, wrongly blame themselves and encourage others not to make the same mistake.

Other patients attribute their survival to screening mammography, when it is unlikely that this may be the case.

Breast cancer occurs almost 3 times more often in advanced stage in women who did not attend a screening program compared with those who do so (de Munck L).

Breast clinical examination recommended to be performed annually.

Handbook Working Group concluded the efficacy of screening by mammography is sufficient in reducing mortality from breast cancer for women 50-69 years of age, limited for women 40 to 49 years of age, and inadequate for women younger than 40 or older than 69 years of age.

In a British study of 160,921 women yearly mammogram before age 50, commencing at age 40 or 41 years, was associated with a relative reduction in breast cancer mortality (DuffySW).

No specific upper age at which mammography screening should be discontinued, and should be based on individual benefits and risks of screening in the overall context of the patients health status and estimated longevity.

As long as a woman is in good health and can benefit from the treatment of breast cancer, screening with mammography should be done.

Since the lifetime risk of dying from breast cancer is 2.3-2.9% more than 97% of women will not die from breast cancer, the absolute benefit or increase in survival over a decade from screening mammography is only .05% (NCI).

For women in their 80’s to prevent one death from breast cancer would require 2131 screening mammograms, in patients 75 years of age 330 screening mammograms, and 133 pateints 50 years of age (Walter LC).

Furthermore, 73.6% of non-Hispanic white women in their 40s have an absolute risk of breast cancer that is greater than that of a 50-year-old woman without risk factors.

One in six breast-cancer deaths is attributable to a diagnosis that was made when the woman was in her 40s, and breast cancer is a leading cause of premature death among women.

One third of all the years of life lost as a result of breast cancer are due to diagnoses that were made when the women were in their 40s.

Breast cancer among women in their 40s is a considerable, not small, fraction of the overall burden of this disease.

Meta-analysis of randomized, controlled trials showed a 15% reduction in mortality among women who undergo screening mammography in their 40s.

A Swedish study showed that among women who underwent screeningin their 40s, there were 29% fewer deaths from breast cancer after 16 years in counties that offered mammography than in those that did not.

The risk of a false positive finding is greater than 50% during a decade of regular mammographic screening.

False positive mammographic findings are associated with temporary anxiety.

Most women accept the trade-off of false positives in favor of finding breast cancer early.

Women whose breast cancer was not diagnosed by mammography were more likely to be diagnosed with a stage II or higher tumor than were women in whom breast cancer was diagnosed by mammography (66% vs. 27%) and were more likely to have a mastectomy (47% vs. 25%); undergo surgery, radiation therapy, and chemotherapy (59% vs. 31%); and have poorer 5-year survival rates.

American Cancer Society breast cancer screening guidelines emphasize his annual screening for women under age 55 and among postmenopausal women 55 years and older biennial screening is recommended.

Ten times more women will receive overdiagnosis, over treatment, and radiation induced coronary artery disease from mammography than benefit (Moss).

Screening mammography can trigger calls for more testing, biopsies, mastectomies, radiation therapy, systemic chemotherapy, days off work, and financial consequences.

Consequences of screening mainly the adverse effect of overdiagnosis, that is, the detection of nonlife threatening lesions, or tumors that would not shorten the woman’s life.

About one and five cancers grow slowly and may never have cause problems.

Comparison made between women with biopsy proven invasive breast cancer receiving a single mammogram between ages of 50 and 64, with a cumulative number of tumors in a group of women aged 50-64 years who had been screened on 3 occasions: the rate of tumors in the single screen group was about 22% lower, suggesting that some tumors that may have been detected at earlier ages in the single screened group spontaneously regressed (Zahl).

MRI twice as sensitive as mammography in detecting malignancies in women with a genetic susceptibility to breast cancer.

Currently a combination of mammography and MRI are used annually to screen women with a genetic risk of breast cancer since mammography adds significantly to MRI accuracy, especially for DCIS.

MRI imaging every 18 months between the ages of 35 and 60 years for women with a 20% or more familial risk of breast cancer is an optimal screening strategy.

Screening mammography has led to decreased breast cancer-specific mortality, and both digital mammography (DM) and digital breast tomosynthesis (DBT) are available modalities. 

 

 

In an evaluation of  DM and DBT performance in over 1,500,000 women age 40-79 without a prior history of breast cancer and demonstrated greater DBT benefit on initial screening exam. 

 

 

DBT benefit persisted on subsequent screening for women with heterogeneously dense breasts and scattered fibroglandular density, while no improvement in recall or cancer detection rates was seen for women with extremely dense breasts with DBT on subsequent exams. 

 

 

The  majority of breast cancers are detected by screening mammography, a significant proportion are first noticed by a patient. 

Interval breast cancers refer to in situ or invasive cancers detected following a negative mammographic screening examination and before the date of the next recommended screening mammogram.

Interval breast cancers are divided into a) true interval and b) missed interval cancers.

True interval breast cancers referred to a review of the screening mammogram before diagnosis that is truly negative.

Interval breast cancers, those detected between a normal mammogram and next scheduled mammogram, have more unfavorable features and worse survival compared with those detected by screening . 

 

 

Interval breast cancers account for approximately 20% of cases.

Missed Interval breast cancer is referred to the process whereby the screening mammogram before diagnosis reveals a mammogram abnormality that was initially falsely negative.

True interval breast cancers are associated with more adverse prognostic factors compared with screen detected cases.

Interval cancers are more likely to be greater than 1 cm in size, have lymphovascular invasion, have the grade 3 features, have lymph node involvement, exhibit triple negative features and patients with breast cancer screening detected cases (Rayson D et al).

Interval breast cancers are over 6 times more likely to be higher grade, nearly 3 times more likely to be estrogen receptor-negative, and had a hazard ratio of 3.5 for breast cancer-specific mortality compared to screening-detected breast cancers. 

Screening for women 50-69 universally recommended: reduces deaths due to breast cancer by 14% for women in their 50s and 32% for those in their 60s.

The Swiss Medical Board found the benefits of mammography screening outweighing the benefits is not obvious.

In the Swiss Medical Board review systemic mammographic screening might prevent about 1 death from breast cancer for everyone thousand screened women, even though there was no evidence to suggest overall mortality is affected.

Canadian National Breast screening study indicated after 25 years of follow-up 106 of 484 screen detected cancers, 21.9%, are overdiagnosed.

In the above study 106 healthy women in screening group were diagnosed with and treated for breast cancer unnecessarily, resulting in needless surgical interventions, radiation therapy, chemotherapy, or some combination thereof.

A Cochrane review of 10 trials involving more than 600,000 women showed no evidence of an effect of mammography screening on overall mortality (Cochrane Database).

The above study the small reduction of breast cancer deaths was attenuated by deaths from other causes and the reduction was canceled by deaths caused by coexisting conditions, or by the harms of screening and associated overtreatment.

For every breast cancer death prevented in the US over a ten-year period of annual screening beginning at age 50, 490-670 women are likely to have a false positive mammogram with repeat examinations, 72-100 an unnecessary biopsy, and 3-14 an overdiagnosed breast cancer that would never become clinically apparent (Welch HG et al).

Annual breast MRI as an adjunct to mammography is recommended for high risk patients who have a lifetime breast cancer risk of approximately 20-25% or greater.

The estimated cumulative risk of death from breast cancer due to radiation from mammography screening is 1 to 10 per hundred thousand women, dependent on age and frequency and duration of screening.

Radiation induced breast cancer rate is at least smaller by a factor of 100 in estimates of death from breast cancer prevented by mammography screening.

In a review of multiple randomized clinical trials it was found for women of all ages at average risk, screening is associated with the reduction in breast cancer mortality of approximately 20% (Myers ER at al).

Annual screening has more false positive test results resulting in more frequent biopsies and therefore the US Preventative Services Task Force services (USPSTF) recommends biennial screening for women 50 to 70 years.

USPSTF recommends initiation of breast cancer screening at age 50 years, as the average age of onset of menopause in the US is 51 years and breast density decreases after menopause.

Breast tissue density in younger women is increased and increases the likelihood of false negative findings because it is more difficult to identify small lesions in dense breasts.

Increased breast density is in independent risk factor for the development of breast cancer.

Younger women have more false positive results.

In a screening study premenopausal women undergoing biennial screening had more unfavorable tumor characteristics compared to women having annual screening (Miglioretti D et al).

Women who underwent biennial screening have higher proportions of tumors that were staged IIb or higher, is larger than 15 mm and less favorable prognostic characteristics compared with women who had annual screening (Miglioretti D et al).

In the above study of postmenopausal women tumor prognostic characteristics were similar irrespective of screening interval and menopausal status may be more important than age for determining optimal breast cancer screening intervals.

A contemporaneous comparison of women participating in breast cancer screening versus those not participating found that mammography screening reduced the rate of advanced and fatal breast cancers.

Participation in breast cancer screening substantially reduced the risk of having a fatal breast cancer.

Of 549,091 women, representing approximately 30% of the Swedish screening-eligible population, the incidence rates of 2,473 breast cancers that were fatal within 10 years after diagnosis and the incidence rates of 9,737 advanced breast cancers.

Women who participated in mammography screening were found to have a statistically significant 41% reduction in their risk of dying of breast cancer within 10 years and a 25% reduction in the rate of advanced breast cancers.

ACS guidelines for breast cancer screening 2015:

Women with an average risk of BC should undergo regular screening mammography starting at age 45 years.

Women age 45-54 years should be screened annually.

Women 55 years and older should transition to biennial screening or have the opportunity to continue annual screening.

ACS and USPSTF now recommending biennial screening for average risk women and encourage individualized, shared decisions about when to begin screening and at what frequency.

Women should continue screening mammography as long as their overall health is good and have a life expectancy of 10 years or longer.

The American Cancer Society does not recommend clinical breast exam for breast cancer screening among average risk women at any age.

Once a breast cancer is diagnosed, annual surveillance mammography is recommended for patient’s with residual breast tissue.

The risk of a second breast cancer event in survivors does not a plateau with time, suggesting that there may be an indefinite benefit of mammography.

Breast ultrasound is not adequately specific for asymptomatic patients it is more appropriate and staying wishing salad from cystic masses.
Tomosynthesis is widely used and has a higher detection rate, but whether it affects breast cancer mortality has not been established.

Women presenting for their first screening examination are particularly important to prioritize for DBT, regardless of breast density or age.

 

 

The investigators compared the performance of 1,273,492 DMs with 310,587 DBTs across the four Breast Imaging Reporting and Database System density types: almost entirely fatty, scattered fibroglandular density, heterogeneously dense, and extremely dense.

 

 

In women aged 50-59 years, screening recalls per 1,000 exams dropped from 241 with DM to 204 with DBT with a relative risk of 0.84.

 

 

Cancer detection rates per 1,000 exams in this age group increased from 5.9 with DM to 8.8 with DBT with a relative risk of 1.50.

 

 

Recall rates were lower with DBT for women with scattered fibroglandular density and heterogeneously dense breasts in all age groups, as well as in women with almost entirely fatty breasts aged 50-79 years.

 

 

There were no significant differences in recall rates in women with extremely dense breasts in any age group

 

 

Cancer detection rates are  higher with DBT than with DM in women with heterogeneously dense breasts in all age groups and in women with scattered fibroglandular density at 50-59 years of age and 60-79 years of age. 

 

 

Cancer detection rates are  not significantly different with DBT or DM for women with almost entirely fatty breasts or extremely dense breasts of any age.

 

 

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