In women, breast cancer is number one in incidence and mortality when compared to all cancers.[1] It is the most common non-skin cancer and second deadliest cancer in women than for any other cancer. In theory, diagnosing early-stage tumors should reduce mortality; however, it is critical to incorporate lead-time bias. The issue of concern is to determine who should be screened. There could be some slow-growing tumors that do not become clinically evident during the patient's life. Therefore, risk stratification, the age to begin screening, the age to stop screening are critical for the apt screening of breast cancer. More recently, rather than focusing on the size and extent of a tumor to guide therapy, the focus has been on determining biologic characteristics that can help guide the prognosis and plan.[2]
The methods of screening are :
Breast palpation- Clinical breast examination and breast self-examination.
Breast imaging techniques - mammography, ultrasonography, magnetic resonance imaging (MRI), and digital breast tomosynthesis (DBT)
Many multiple randomized trials have come to the consensus that routine screening mammography should be offered to women ages 50 to 69 rather than that for women of the age group 40 to 49 or women over 70 years of age. Genetic mutations have been discovered, and an increase in the risk of breast cancer and the development of breast cancer risk prediction models have stimulated rigorous efforts to develop screening methods for risk stratification. For high-risk women, in addition to mammography, ultrasonography & breast Magnetic resonance imaging (MRI) has been studied as a screening method.[3] The discussion will include patient risk stratification and management options for women with a genetic predisposition to breast cancer. Surveillance in women with a personal history of breast cancer is discussed in detail separately.
The mature adult breast comprises of skin, subcutaneous tissue, epithelial, and stromal components. The epithelial component comprises of branching ducts that connect the structural and functional units of breasts, known as lobules to the nipple. The stromal component comprises the majority of the breast volume in a non-lactating breast and is composes of fibrous and adipose tissue. The breast tissue extends from the 2 and 6 ribs vertically and sternal edge to midaxillary line horizontally. A part of breast tissue projects into the axilla and is known as the axillary tail of Spence. The skin of the breast is thin and contains sebaceous glands, exocrine sweat glands, and hair follicles. The nipple is devoid of hair follicles and contains abundant sensory nerve endings and sebaceous and apocrine glands. The areola, measures about 16 to 60 mm, is nearly circular and has higher pigmentation. There are elevations near the periphery of the areola, which form due to the opening of ducts of Montgomery glands, which are large sebaceous glands and are known as Morgagni tubercles. The Montgomery glands represent a stage between sweat and mammary glands. The breast is covered with the superficial pectoral fascia, which continues with the superficial abdominal fascia of Camper. The breast is covered from the underside with deep pectoral fascia, which covers the muscles – pectoralis major and serratus anterior. The two fascial layers covering the breast tissue are connected by fibrous bands – Cooper suspensory ligaments that provide natural support to the breasts. The majority of total breast blood supply comes from internal mammary vessels. Sensory innervations are mainly from anterolateral and anteromedial branches of thoracic intercostal nerves T3 to T5. It is also supplied by lower fibers from supraclavicular nerves of cervical plexus.
In 2015, the guideline update from the American Cancer Society (ACS) recommended that for patients with breast cancer: women with an average risk should undergo regular screening mammography starting at age 45 (strong recommendation). Women who are between 45 to 54 years should undergo screening annually, and women 55 years and older can undergo biennial or annual screening.[4] It recommends that women age 40 to 44 are to be given a choice to start annual mammography. Routine screening strategies are not strongly advised for women in age groups of 40 to 49 or those above the age of 70.[5] However, in collaboration with mammography, breast MRI has been studied as an important screening method for high-risk females and those with dense breasts.[3] Women are advised to continue screening mammography who have until ten years of life expectancy and good health in general.
United States Preventive Services Task Force (USPSTF) recommends biennial mammography in women of age group 50 to 74. For the women age group, 40 to 49 age, group screening can be considered after discussing and evaluating the risks and benefits of this test with their physician.[6]
WHO based strategy includes biennial mammography screening for women aged 50 to 69 years in well-resourced settings.
American College of Obstetricians and Gynecologists recommend twice-annual screening mammography after age 55 years of age, which prevents harm as long as the patient is informed.
The USPSTF and ACS differ markedly for recommendations for clinical breast examinations (CBE). ACS does not recommend them, while the USPSTF recommends a Clinical Breast Examination with mammography in women with an average risk of developing breast cancer.
The panel of National Comprehensive Cancer Network (NCCN) recommends Women with average risk in the age group of 25 to 39 years to have a clinical assessment, risk reduction counseling & Clinical Breast Examination every 1 to 3 years. They should also be recommended to inform any changes in their breast to their health care provider immediately.[6]
Certain precautions are to be taken for breast screening considering the age of a woman. New guidelines by the American College of Physicians suggest that it is cautioned that beginning at the age of 40, average-risk women with no symptoms should discuss with their physician benefits, their personal preferences, and potential harms of breast cancer screening with mammography before the age of 50.
Clinical breast examinations screening is not recommended no matter what age for average-risk women. Recommendations about ceasing the screening for those women age 75 years or older or with a life expectancy of 10 years or less were made.[5]
Mammography is a low-dose x-ray modality for detailed imaging of the breast. It is the best population-based method for screening. It can demonstrate micro-calcifications less the 100 micrometers, which makes it capable of detecting lesions before they become palpable. Mammography can be done in two forms: screening and diagnostic. Those with family or personal history of breast cancer require additional views in diagnostic/screening mammography.[7]
Breast Imaging Reporting and Data System is used to guide the breast cancer diagnostic rule. It involves levels of categorization to interpret breast lesions in standardized format amongst radiologists. However, the majority of screening mammograms show the absence of evidence of cancer on subsequent testing, 1% to 2% show abnormality requiring biopsy. Also of which majority (80%) are benign lesions.
BI-RADS scoring[8]:
Digital mammography can be applied better to diagnose breast cancer in dense breasts. Tomosynthesis or 3D mammography may also be used, which improves the ability to find minutely sized cancers and decrease probabilities of false-positives.
Magnetic resonance imaging (MRI) cost is higher than for mammography worldwide.
Thermography use is based on the fact of elevated breast skin temperatures overlying breast cancers, which are supposed to detect occult malignancies, show inconclusive results.[9]
Ultrasound is usually used to know more about the positive clinical examination or screening mammography on diagnostic fronts. It has limited use as a screening device due to various factors, including the inability to find micro-calcification and poor specificity.
Screening MRI is considered less specific, but more sensitive than mammography in high-risk women for detection of invasive cancers.[3]
Annual mammography and MRI, and at times at 6 months duration, is needed for women with BRCA gene mutations, strong family history for breast cancer, and prior chest radiation therapy.
As a patient can herself find breast cancer at times, she should not only be informed and made aware of the breast self-awareness but also instructed to notify the health care provider if and when any change in the breast occurs.The health care providers should be affluent with screening and counseling asymptomatic patients with a family history of BRCA cancers. Genetic counselors and the team should be doing assessments to provide genetic testing after informed consent.
Patients’ history – personal as well as family is important to be assessed periodically by the health care providers. This should include risk factors, prior biopsies, and their results, radiation exposure, as well as a family history of breast cancer. The identification of women who will benefit from genetic counseling is essential. The Gail model is used to assess and stratify high-risk women.[7]
Breast self-awareness is promoted according to new studies. Breast self-awareness being different from breast self-examination by appearance and feel of the woman’s breasts and ability to notice any change in the breasts and reporting to the primary health care provider rather than a regular and systematic way to examine breasts as in self-examination.[10]
Imaging techniques for breast cancer screening are best and well accepted from sensitivity and specificity point of view, keeping into consideration the complications and harms to the screening population. Others are breast self-examination and clinical breast examination. Amongst the imaging techniques, mammography is best accepted. Other commonly used ones are Ultrasonography and MRI.
Screening methods like mammography are most effective when targeting screening strategies are used, keeping age into considerations and other criteria like hormonal exposure, family history, and other risk factors like radiation, obesity, and genetics.
Magnetic resonance imaging (MRI) is done by injection of intravenous contrast material, which increases the ability to delineate the normal breast from abnormal lesions.
The mammography screening method is not accurate. Data suggest that it can be less sensitive in detecting cancer in mammographically dense breast tissue. Mammography may lead to false-negative results leading to missing cancer when it is present.
Additional treatment is associated with screening, which may not be effective and needed. Those who are screened are more likely to have surgical and radiation therapy.
And the treatment may harm economically, psychologically, physically, or productively. There have been uncertainties in estimating expectancy of life along with decreased quality-adjusted life expectancy due to overdiagnosis.
Depending on the age of initiation, frequency, and cessation of screening, the overall lifetime radiation exposure increases as women have exposure of about 3.7 mGy per digital mammography. They are hence increasing radiation-induced breast cancer risk of 125 cases per 100,000 women for women aged 40 to 74 years. And thus, an increased number of deaths due to breast cancer screen. (2 for age group 50 to 59 years to 11 for the age group 40 to 59 years). Pain due to the procedure is reported, too, leading to failure of follow up for the subsequent screening.
Ultrasonography is generally considered to be a highly operator-dependent modality and supplemental screening test that requires a skilled practitioner, high-quality examination, and state-of-the-art equipment. Given the results of these studies, a prospective, multicenter study is warranted to examine the role of this modality of imaging in breast cancer screening.[11]
Age should not be the only deciding factor to discontinue or continue breast cancer screening. Combinations and a balanced overview of all risk factors and density of breasts should be considered while planning for breast screening age-wise.[12] The sensitivity and specificity of mammography are higher as age advances in comparison to young aged women.
A dense breast has a high probability of developing breast cancer. While mammography decreases the sensitivity of detecting breast cancer in women with dense breasts, other screening strategies like MRI and ultrasonography may be employed.
It has been observed that women have fast-growing breast cancers, and mammography cannot be of much help here from a screening perspective. It is advisable to discuss breast cancer screening with all women from age 40, and proper documentation should be done.[6] According to the new guidelines, age alone should not be the guiding factor to stop screening. Women having average-risk of breast cancer should continue breast screening mammography until at least age 75 years. General health and life expectancy should be considered.
Early age of initiation and use of MRI or/and ultrasound, may be considered for women with the first-degree relative with breast cancer.[3] A combination of annual breast MRI plus mammography for breast cancer is recommended in women who are BRCA mutation carriers. Chest radiation therapy during the ages of 10 to 30 years defines high-risk criteria for breast cancer, which also includes girls treated by such chest-region specific radiation in the age group of 10 to 14 years.
However, the decision to perform screening mammography should be preceded with shared decision making about the pros and cons of the procedure, result, and next steps and also by subjective patient values and risk factors.
The harm from the screening that is associated with serial follow-ups, such as psychological problems like anxiety, distress, low adherence for subsequent screening, and false-positive results, should be kept in mind.
The screening of breast cancer is a challenging and complex arena of clinical care as well as preventive health care. The domain of primary health care is realized for not only appropriate screening, apt history, but also abilities to know and find the inherent risk factors which may cause an imbalance in the benefit obtained from screening. Keeping the age and density of breasts into consideration, proper counseling for genetic and familially predisposed patients, a shared opinion approach has to be sought.[7]
From the diagnostic fronts, the knowledge, skills, and abilities of radiologists, as well as technicians
and nursing staff, are recommended to support and obtain required details to add to the process of screening, decreasing the probabilities of false-positives as well as false negatives for enhancing the way of screening approach and increasing the quality of life and care given to the patients.[3]
The coordinated and cooperative approach to the age-wise women for screening helps in the smooth and accurate process of breast cancer detection, keeping in mind the pitfalls and flaws of the screening methods employed.
Regular follow- up, and discussions about all the doubts and concerns pertaining to breast cancer screening and procedures should be done by the team of screening, hence increasing the probability of diagnosing by the screening methods and enriching the health care support to the patients.
[1] | Barton H,Shatti D,Jones CA,Sakthithasan M,Loughborough WW, Review of radiological screening programmes for breast, lung and pancreatic malignancy. Quantitative imaging in medicine and surgery. 2018 Jun; [PubMed PMID: 30050787] |
[2] | Bodalal Z,Trebeschi S,Nguyen-Kim TDL,Schats W,Beets-Tan R, Radiogenomics: bridging imaging and genomics. Abdominal radiology (New York). 2019 May 2; [PubMed PMID: 31049614] |
[3] | Verburg E,van Gils CH,Bakker MF,Viergever MA,Pijnappel RM,Veldhuis WB,Gilhuijs KGA, Computer-Aided Diagnosis in Multiparametric Magnetic Resonance Imaging Screening of Women With Extremely Dense Breasts to Reduce False-Positive Diagnoses. Investigative radiology. 2020 Mar 6; [PubMed PMID: 32149858] |
[4] | Ma J,Jemal A,Fedewa SA,Islami F,Lichtenfeld JL,Wender RC,Cullen KJ,Brawley OW, The American Cancer Society 2035 challenge goal on cancer mortality reduction. CA: a cancer journal for clinicians. 2019 May 8; [PubMed PMID: 31066919] |
[5] | García-Albéniz X,Hernán MA,Logan RW,Price M,Armstrong K,Hsu J, Continuation of Annual Screening Mammography and Breast Cancer Mortality in Women Older Than 70 Years. Annals of internal medicine. 2020 Feb 25; [PubMed PMID: 32092767] |
[6] | Yaffe MJ,Mittmann N,Alagoz O,Trentham-Dietz A,Tosteson AN,Stout NK, The effect of mammography screening regimen on incidence-based breast cancer mortality. Journal of medical screening. 2018 Dec; [PubMed PMID: 30049249] |
[7] | Albright FS,Kohlmann W,Neumayer L,Buys SS,Matsen CB,Kaphingst KA,Cannon-Albright LA, Population-based relative risks for specific family history constellations of breast cancer. Cancer causes [PubMed PMID: 31030355] |
[8] | Xu P,Yang M,Liu Y,Li YP,Zhang H,Shao GR, Breast non-mass-like lesions on contrast-enhanced ultrasonography: Feature analysis, breast image reporting and data system classification assessment. World journal of clinical cases. 2020 Feb 26; [PubMed PMID: 32149054] |
[9] | Ismail HM,Pretty CG,Signal MK,Haggers M,Chase JG, Attributes, Performance, and Gaps in Current [PubMed PMID: 31975659] |
[10] | Albeshan SM,Hossain SZ,Mackey MG,Brennan PC, Can Breast Self-examination and Clinical Breast Examination Along With Increasing Breast Awareness Facilitate Earlier Detection of Breast Cancer in Populations With Advanced Stages at Diagnosis? Clinical breast cancer. 2020 Feb 11; [PubMed PMID: 32147405] |
[11] | Choudhery S,Patel BK,Johnson M,Geske J,Fazzio RT,Lee C,Pruthi S, Trends of Supplemental Screening in Women With Dense Breasts. Journal of the American College of Radiology : JACR. 2020 Feb 24; [PubMed PMID: 32105645] |
[12] | Weigel S,Heindel W,Dietz C,Meyer-Johann U,Graewingholt A,Hense HW, Stratification of Breast Cancer Risk in Terms of the Influence of Age and Mammographic density. RoFo : Fortschritte auf dem Gebiete der Rontgenstrahlen und der Nuklearmedizin. 2020 Feb 27; [PubMed PMID: 32106324] |