Published: November 2019
Breast health is an important health care concerns in the United States and worldwide. Health care services for women are often fragmented across multiple providers. Misunderstandings about breast health are common in the general population and even among health providers. Providers are often overwhelmed by complex insurance requirements and time constraints, thus it is imperative that primary care providers (PCPs), obstetricians/gynecologists (OB/GYNs), and other frontline providers have the tools and knowledge to accurately evaluate and diagnose breast disorders.
Breast cancer is the most common cancer in women and second only to lung cancer in cancer mortality among women in the United States with an estimated 268,600 new cases and 41,760 deaths in 2019.1 Breast cancer also occurs in men at a much lower incidence than women with an estimated 2,670 new cases and 500 deaths in men in 2019.1
Women in the U.S. have a 12.4 % (1 in 8) estimated lifetime risk for developing breast cancer, with a median age at diagnosis of 62 years.2 Breast cancer screening and treatment with hormonal therapy, chemotherapy, radiation therapy, and more recently, targeted therapy are increasing the survival rate of patients with breast cancer since 1990.1
Most breast health concerns are caused by benign breast disease (BBD). About 25% of women will present with a breast complaint during their lifetime. Among patients presenting with BBD, the majority (67%) were age 21 to 40.3 Pain, lump, and nipple discharge are common symptoms of BBD.
Most breast complaints are due to BBD or noncancerous disorders of the breast. Though not life threatening, some BBDs may increase the risk of breast cancer. BBD constitutes a diverse spectrum of lesions including developmental lesions, inflammatory lesions, neoplasms, and epithelial and stromal proliferative as well as nonproliferative disorders.
Histologically, BBD can be divided into 3 groups based on a classification system proposed by Dupont and Page:
Fibrocystic changes (FCC) are the most common BBD and patients often present with pain, lumpiness, and nodularity. Over 50% of women will develop symptomatic FCC at some point in their lifetime. FCC appear to be hormonal in etiology. FCC is most prevalent in women age 20 to 59. Seldom do postmenopausal women experience symptomatic FCC unless they are on postmenopausal hormone replacement therapy.
Breast cysts range in size from 1 mm to several centimeters and are a common form of benign FCC and are usually unilocular within the breast. They are thought to arise as lobular lesions in which the terminal ductules dilate and unfold to enlarge as a cyst.
Ectopic breast or supernumerary breast tissue is the most common congenital/developmental abnormality of the breast.
A variety of inflammatory conditions can affect the breast. Some of these are from an infection, while others do not have a known etiology and may represent autoimmune processes and are classified as idiopathic.
Fibroadenoma is the most common benign breast neoplasm with a peak incidence at age 15 to 35. Lipoma of the breast is another typically solitary benign tumor composed of mature fat cells. Lactating adenoma is the most prevalent breast mass during pregnancy and puerperium. Hamartoma of the breast, also called fibroadenolipoma, is an uncommon benign tumor. Some cases have been related to a germline genetic mutation in patients with PTEN hamartoma tumor syndrome.
|Factors with a relative risk greater than 4.0
|Factors with a relative risk 2.1 to 4.0
|Factors with a relative risk 1.1 to 2.0
Data from reference 5
A hereditary predisposition to breast cancer also increases the risk of developing breast cancer at a younger age. Early identification of patients with a hereditary predisposition is imperative to take advantage of enhanced surveillance, chemoprevention, and risk reducing surgery. All women, especially black women and those of Ashkenazi Jewish descent, should be evaluated for the risk of breast cancer no later than age 30. Hallmark features of hereditary cancer are multiple cancers in an individual of family member(s), cancer at a young age, and rare cancers. Factors to identify individuals who should get tested for hereditary breast cancer are presented in Table 2.
|1 relativea: Diagnosis of 1 of the following in a patient, or a first- or second-degree relative:
|2 member(s)a: Diagnosis of 2 cancers in a patient of a family member(s):
|3 ageb: Diagnosis of 3 of these cancers in any combination on the same side of the family at any age:
Adapted from the National Comprehensive Cancer Network6, American College of Obstetricians and Gynecologists7, U.S. Preventive Services Task Force8 and American Society of Breast Surgeons.9
aFirst-degree relatives include: parents, siblings and children; second-degree relatives include half-siblings, grandparents, aunts/uncles, nieces/nephews, and grandchildren
bIn this category only, third-degree relatives may be considered, which include first cousins, great-grandparents, great aunts/uncles, and great grandchildren
Mathematical models have been developed to quantitate the risk of breast cancer in women with no genetic predisposition. The most comprehensive model, which includes breast density, is the Tyrer – Cuzick model, or IBIS Breast Cancer Risk Evaluation Tool (http://www.ems-trials.org/riskevaluator/).
Many risk factors affect the lifetime exposure of breast tissue to hormones (early menarche, late menopause, obesity, and hormone use). Although exposures that influence risk accumulate throughout a woman’s life, research suggests that the time between menarche and first pregnancy may be particularly critical.10,11 About a third of post-menopausal breast cancers are thought to be caused by behavioral factors that are modifiable, such as postmenopausal obesity, physical inactivity, use of combined postmenopausal hormone therapy, alcohol consumption and not breastfeeding.12
Breast pain, lumps, and nipple discharge are the most common symptoms of BBD and breast cancer. Other possible symptoms include nipple inversion, skin changes (peau d’orange, ulcers, nipple excoriation, erythema, and scaling), swollen lymph nodes, and asymmetric thickening/nodularity.
Breast pain (ie, mastalgia or mastodynia) is any discomfort or tenderness in the breast or underarm region. Onset, duration, relation to the menstrual cycle, current medications, and caffeine intake should be obtained.
Breast pain can be classified as cyclic or noncyclic. Cyclic pain is due to monthly hormonal changes and mostly occurs reproductive-age females. It generally ceases with pregnancy and menopause. Noncyclic pain is often isolated to 1 specific area of the breast and is the result of changes that occur in the milk ducts or milk glands, which can result in development of breast cysts.
Women can experience pain after breast injury, breast biopsy, or scar formation from prior breast surgery. Large pendulous breasts can also cause pain and so can a poorly fitted bra. FCC can cause pain and tenderness in the upper and outer quadrants of the breasts usually right before menses.
Some medications like oral birth control pills, postmenopausal hormone therapies, and infertility treatments may be associated with breast pain and tenderness.
Mastitis is an infection of the breast tissue that manifests as sudden onset of pain with local inflammation. Hidradentis suppurativa can manifest as painful breast nodules.
Chest wall pain, also known as extramammary breast pain, refers to pain that feels like it is coming from the breast, but actually is referred from elsewhere. It can be musculoskeletal pain or pain due to another medical condition like gallstones or cardiac ischemia. Costcohondritis or Tietze syndrome is an arthritic pain in the middle of the chest between the ribs and sternum. Patients are often very tender over the costochondral junctions on physical exam.
Pain can be the only presenting symptom of breast cancer in a small number of patients. Typically it is focal and sometimes there is an underlying mass or overlying skin erythema.
Most breast lumps result from benign conditions such as cysts or fibroadenomas. A breast lump can be a sign of breast cancer when it is firm or hard. Cancerous lumps can be irregular. Fixation to the chest wall or skin is a late finding of breast cancer. Cysts may be smooth and tender and fibroadenomas are often oval and slippery. Lumps cannot be accurately classified clinically. Discrete breast lumps warrant diagnostic evaluation. Nodularity related to FCC may be reported as a lump and may vary with the menstrual cycle. Any reported focal breast symptom should be thoroughly evaluated.
Lumps associated with nipple changes such as nipple inversion or nipple discharge are more suspicious for malignancy.
Abnormal nipple discharge may be described as any discharge not associated with lactation and pregnancy.
Purulent discharge may be caused by mastitis or breast abscess. Milky discharge can occur with certain psychotropic medications and endocrine disorders such as hypothyroidism or prolactinoma. Milky discharge after breast-feeding can continue for up to 2 to 3 years after stopping nursing. Non-milky nipple discharge may be thick, sticky, greenish/black, clear, colorless, serous, sanguineous, serosanguineous, or bloody.
Pathologic discharge requiring diagnostic evaluation (diagnostic imaging and retroareolar ultrasound) is that which is spontaneous, bloody, clear or serosanguinous. It is most often unilateral and elicited from one duct. Pathologic nipple discharge is most commonly caused by a benign intraductal papilloma, but can also be a sign of ductal carcinoma in situ (DCIS) or invasive cancer.
Other possible causes of benign or physiologic nipple discharge include medications, FCC, excessive breast stimulation, mammary duct ectasia and periductal mastitis. Mammary duct ectasia, common in smokers, presents with greenish-black, creamy, yellowish or oily discharge from multiple ducts that is elicitable on examination but not typically spontaneous.
Drugs that can cause nipple discharge include psychoactive drugs, opiates, antihypertensive drugs, oral contraceptives, and estrogen.
Nipple discharge in men warrants urgent evaluation as this is a common presentation of breast cancer in men.
Women should be familiar with their breast tissue (breast self-awareness) and should report any changes to their health care provider. In premenopausal women, breast self-exam is most informative when done at the end of menses.
Comprehensive clinical examination in conjunction with history, use of diagnostic imaging, targeted breast ultrasound, breast magnetic resonance imaging, and core needle biopsy (vacuum assisted) can facilitate timely diagnosis and management of breast disorders.
A detailed history is the cornerstone of diagnostic evaluation of breast symptoms. Reproductive history, results of prior biopsies, prior treatments, and a thorough family history should be ascertained.
There is overall consensus that clinical breast examination (CBE) is a useful screening tool. The rationale for recommending a clinical encounter is to maximize the earliest detection of breast cancer.
The National Comprehensive Cancer Network Breast Cancer Screening and Diagnostic Guidelines Panel has concluded that in the absence of new evidence to suggest a lack of benefit or significant harm associated with CBE, CBE should be performed every 1 to 3 years for average-risk women aged 25 to 39 years and annually beginning at age 40 years.13 A systematic review of breast cancer screening found no benefit with the addition of CBE with mammography.14
A comprehensive breast examination should include inspection and palpation of the entire chest wall in upright and supine positions, extending up to the clavicle and neck, into the axilla, over the central chest and under the breast onto the rib cage. The clinician should note any lumps, asymmetry, nipple changes, or skin erythema or dimpling. Examination of the supraclavicular, infraclavicular, and axillary lymph nodes should follow the breast inspection. The presence of lymphadenopathy should prompt referral to a breast specialist, although the significance of shotty nodes is unclear. The characteristics of any breast lump is important. The breasts should then be palpated for thickening, nodularity, and detection of masses. Hard or irregular discrete masses suggest malignancy. The patient’s ipsilateral hand should be brought up to the head level for examination of the lateral part of the breast and the elbow should be at the shoulder level for examination of the breast. Palpation under the areola and a gentle squeeze of the nipple to elicit discharge is important.
Symptomatic or positive findings on physical examination include a palpable mass in the breast, nipple discharge, asymmetric thickening or nodularity, skin changes, and breast pain. Clinical judgment should always be an important component of the optimal management of the patient.
In addition to the traditional craniocaudal and mediolateral oblique mammographic views, diagnostic imaging often includes spot tangential or magnification views per the radiologist’s recommendation, and targeted breast ultrasound. Diagnostic digital breast tomosynthesis is also sometimes employed, particularly to evaluate areas of architectural distortion.
Mammography utilizes very low-energy X-rays (around 30 kVp) to examine breast tissue and is both a diagnostic and a screening tool. Mammography has a false-negative rate of at least 10%. It is an error to rely on negative mammography results when there is a clinically suspicious mass. In such cases, negative findings should not preclude referral to a breast specialist.
A palpable mass is a discrete lesion that can be readily identified during a physical exam. For women under the age of 30, workup for a palpable mass begins with a targeted breast ultrasound; for women 30 and older, bilateral diagnostic imaging with a targeted breast ultrasound. Negative imaging results place a patient at a very low risk of malignancy (generally less than 3%); however, clinical judgment is necessary as some women with negative imaging may warrant biopsy and may have breast cancer.
Asymmetric thickening or nodularity is often vague on physical exam and imaging evaluation for it is the same as for a palpable mass.
Nipple discharge is common and often unrelated to breast pathology. Suspicion of underlying pathology (eg, papilloma or malignancy) is raised when nipple discharge is persistent and reproducible on examination, spontaneous, unilateral, from a single duct, serous, sanguineous or serosanguinous. Workup of suspected pathologic nipple discharge begins with diagnostic imaging and a targeted retroareolar ultrasound. If negative, diagnostic breast magnetic resonance imaging (MRI) is a very valuable additional diagnostic tool. A negative MRI in this symptomatic population may obviate the need for duct exploration and excision.15 Ductography is sometimes employed to localize lesions.
Inflammatory breast cancer should be considered when dermal edema (peau d’orange) and breast erythema are present. Nipple excoriation, scaling, and erythema should increase clinical suspicion for Paget’s disease. The initial evaluation begins with a bilateral diagnostic mammogram with or without ultrasound. If imaging is negative, punch biopsy should be performed. Antibiotics may or may not be given, depending on the clinical suspicion for breast infection, but should not delay diagnostic evaluation. Referral to a breast specialist should be considered early.
Breast pain is very common and is rarely the only symptom of a malignancy. If pain is focal and persistent, age appropriate diagnostic imaging (bilateral diagnostic imaging with targeted ultrasound if 30 or older and targeted ultrasound if under 30) is recommended.
Breast biopsy is routinely performed for diagnosis of suspicious areas of concern detected clinically or with mammography or sonography. A biopsy is the only diagnostic procedure that can definitely determine if the area of concern is benign or malignant. The majority of breast biopsies performed in United States are benign.
When an entire lump or suspicious area is removed, the procedure is called excisional biopsy. An incisional biopsy or core biopsy removes a portion of the abnormal tissue and is preferred over excisional biopsy.
Core biopsy is generally performed under imaging guidance (eg, stereotactic [mammographic], ultrasound or MRI) and involves a large-bore cutting needle to remove multiple cores of tissue. Punch biopsy of skin or nipple biopsy can help when there is a clinical suspicion of inflammatory breast cancer or Paget’s disease of the nipple.
Treatment for breast pain relies on an accurate diagnosis and is aimed at symptomatic relief and patient education. Most recommendations for treatment of breast pain are based on data from observational or case controlled studies, with minimal data from randomized controlled trials.
Antibiotics and surgical drainage are required for infections and some abscesses. Therapeutic aspiration can be performed for symptomatic breast cysts. Treatment of pain associated with FCC is not well studied. A well-fitted, supportive bra may be helpful. Some patients note relief with avoidance of caffeine.
Breast reduction mammoplasty may be helpful for those with large pendulous breasts and resultant pain.
Oral analgesics like acetaminophen or a nonsteroidal anti-inflammatory medications can sometimes relieve breast pain. Topical analgesics such as over the counter salicylate cream (Aspercreme) or prescription diclofenac gel (Voltarin) for local pain can be used on intact skin. Another often helpful remedy is evening primrose oil (2000 mg to 4000 mg/day in split doses).
Danazol reduces estrogen production and levels and is the only medication approved by the U.S. Food and Drug Administration for treatment of breast pain. Though effective is use is limited by androgenic side effects including weight gain, acne, hirsutism, and amenorrhea.
Tamoxifen may be beneficial for some patients with severe breast pain. Side effects including hot flashes and night sweats are relatively common, and there is an increased risk of venous thromboembolism associated with its use. Hence it is seldom used for this indication, but may be helpful in refractory cases.
Treatment depends on the diagnosis. Benign lumps should be followed clinically, for 1 to 2 years to assess for stability.13
Nipple stimulation can sometimes cause nipple discharge and cessation will relieve the symptoms. Nipple discharge due to medication use (phenothiazines, selective serotonin reuptake inhibitors, oral contraceptives) warrants consideration of change in the medication. Medical or surgical therapy may be warranted if a prolactinoma is identified. Duct exploration and excision is sometimes required for diagnosis and treatment of pathologic nipple discharge, though a negative breast MRI currently may obviate the need for surgical intervention.15
Breast screening is performed in women without any signs or symptoms of breast. Women should be counseled about the potential benefits (including mortality reduction), risks, and limitations of breast screening.
The components of a breast screening evaluation depend on factors such as age and medical and family history. Breast screening may include breast awareness (ie, patient familiarity with her breasts and family history), physical examination, risk assessment, screening mammography and in some cases, screening breast MRI.
All women should be counseled to report any breast changes to their healthcare providers. Periodic, consistent breast self-examination may facilitate breast self-awareness. Accurate, regularly updated family history information is needed to adequately assess a woman’s individual breast cancer risk and to identify families with a hereditary predisposition.
The goal of screening using mammography is the early detection of breast cancer typically through detecting masses or microcalcifications. Breast cancer mortality is reduced by at least 20% by regular screening mammography as demonstrated by randomized controlled trials.16-19 The overall sensitivity of screening mammography is approximately 75%.17 A diagnostic evaluation is used to evaluate an existing symptom or a clinical finding.
|Absence of a personal history of:
|Absence of a family history of:
|Absence of Ashkenazi Jewish ancestry|
|Absence of an identified high- or moderate-penetrance genetic predisposition (eg, breast cancer gene [BRCA] 1 or BRCA2 mutation) in the patient or in a first-, second-, or third-degree relative|
Cleveland Clinic has proposed recommendation for screening of women of average risk (Table 4) (Cleveland Clinic Care Path):
|Age||Mammography||Clinical Breast Exam|
|20–39||Not recommended||Include with complete physical exam by primary care provider|
|40–44||Every woman should have opportunity for an annual screening mammogram; shared decision making with primary care provider strongly recommended||Include with complete physical exam by primary care provider|
|45–55||An annual screening mammogram recommended||Include with complete physical exam by primary care provider|
|55 and older||Screening mammograms recommended; shared decision-making with provider recommended to determine frequency (annual or every 2 years)||Include with complete physical exam by primary care provider|
|Upper age limit: Less than 10 years remaining in expected life span||If patient is in good health and is a reasonable candidate for treatment, mammogram is recommended; shared decision-making with provider recommended to determine frequency.||Include with complete physical exam by primary care provider|
The use of digital mammography (2-dimensional [2D]) in conjunction with digital breast tomosynthesis (DBT) appears to improve cancer detection and reduce false-positive call-back rates.21-24 DBT allows acquisition of three-dimensional data which are reconstructed using computer algorithms. The combined use of 2D and DBT results in double the radiation exposure compared with digital mammography alone. However, this increase in radiation dose falls below dose limits of radiation set by the U.S. Food and drug Administration for standard mammography. It adds to the sensitivity of screening mammography in women at all levels of breast density.25
The presence of dense breast tissue decreases the sensitivity of screening mammography and is increasingly recognized as an important risk factor for breast cancer.26 According to American College of Radiology Breast Imaging Reporting and Data System, breast density is categorized as fatty, scattered fibroglandular, heterogeneously dense, or extremely dense. Thirty states in the U.S. now require that breast density information be reported to patients and most states encourage patients to discuss their breast density with their health care providers.27 Dense breasts limit the sensitivity of the mammography and extremely dense breast tissue is associated with an increased risk for breast cancer.26
About half of all women of screening age have “dense” breast tissue (heterogeneously dense or extremely dense as categorized by the American College of Radiology Breast Imaging Reporting and Data System nomenclature). There is currently insufficient evidence to support routine universal supplemental screening in women with dense breasts and no other risk factors.
There is emerging evidence that breast scintigraphy (molecular breast imaging) may improve detection of early breast cancers among women with dense breasts, but is time intensive and associated with higher doses of radiation than standard digital mammography.
Mammography supplemented with breast ultrasound has been studied as a potential solution for screening of women with dense breasts as early detection of invasive cancers is improved with the 2 modalities over mammography alone. Screening breast ultrasounds are not available universally and require highly trained personnel. Breast ultrasonography does not detect microcalcifications, however, and is associated with a high false positive rate28 and is therefore not commonly recommended.
Current evidence does not support the routine use of thermography or ductal lavage as screening procedures.
Annual MRI screening by a breast specialist is recommended for individuals at high risk, which is defined as meeting any of the following criteria:
Contrast-enhanced breast MRI has shown substantial promise in the early detection of breast cancer. The available literature suggests that the sensitivity of contrast enhanced breast MRI in detection of cancer is considerably higher than that of either mammography or ultrasound and is generally reported to be in excess of 96 %.31-39 It, however is not as specific, resulting in a higher rate of false positive findings as compared to digital mammography. In all tissue densities, contrast enhanced MRI is far better than mammography in detecting breast cancer, but the use of MRI is limited by high cost, patient tolerance, and availability. Of note is that microcalcifications and architectural distortion are not detectable with MRI; thus digital mammography or digital breast tomosynthesis remains as a screening modality recommendation in conjunction with screening breast MRI for those at elevated risk.
Research is being conducted to further validate using shortened screening MRI times (so called “abbreviated” or “fast” MRI) and hence lower cost and make the test available to more patients for supplemental screening.40
Breast screening of patients over age 75 should be based on individual factors considering the benefits, risks, comorbidities, and life expectancy. Screening every other year is an option for women of average risk age 75 or older and can continue as long as expectancy is 10 years or greater.