New Palpable Breast Mass

Etiology

Breast Anatomy

The breast, or mammary gland, is a modified sweat gland containing various fibrous, glandular, and adipose tissue. Each breast has 15 to 20 lobes drained by lactiferous ducts that converge beneath the nipple in the subareolar region. The lobes are supported by fibrous stroma and fatty stroma. Lymphatic drainage is primarily through the axillary lymph nodes and involves the pectoral, subscapular, and internal mammary nodes.[6] (See Image. Breast Sagittal View). Breast tissue is present in children and males but is more developed in females of reproductive age due to hormonal surges that arise at puberty. Breast tissues involute significantly following menopause; the glandular tissue atrophies due to reduced circulating estrogen levels and is largely replaced by fatty tissue. Breast tissues and most breast pathologies are responsive to changes in hormone levels.[6]

Breast Mass Etiologies

The underlying etiology of a palpable breast mass includes a wide array of differential diagnoses. (Please refer to the Differential Diagnoses section for more information). Breast masses have various causes that differ based on age group and clinical presentation. In women younger than 25, the most common cause of a breast mass is a fibroadenoma; other causes in this population include giant juvenile fibroadenomas, cysts, hamartomas, fat necrosis, and inflammatory breast conditions (eg, abscesses). Breast carcinomas are a rare cause of a palpable breast lesion. For those 25 years and older, common causes of palpable breast masses include fibroadenomas and benign cysts, and the risk of a malignant condition increases as age increases.[7][8] 

Benign and Malignant Breast Mass Risk Factors

Although the majority of these masses are associated with benign breast conditions, patients with palpable breast masses have an increased likelihood of having a breast malignancy.[2] Therefore, risk factors that increase a patient's chances for breast cancer should be considered when assessing the differential diagnoses of breast symptoms.

The primary risk factor for developing breast cancer is excess exposure to estrogens. Therefore, clinicians should inquire about lifetime estrogen exposure in all patients presenting a new breast mass. Early age of menarche, late age of first pregnancy, nulliparity, oral contraceptive or hormone replacement therapy, and late menopause increase estrogen exposure, while breastfeeding is a protective factor.[9] Male patients should be asked about previous hormonal treatments for prostate cancer, the use of finasteride or testosterone, episodes of orchitis/epididymitis, or previously diagnosed Klinefelter syndrome.[10] Other risk factors, eg, excess alcohol intake and obesity, are thought to increase endogenous estrogens.[11] Please see StatPearls' companion resource, "Breast Cancer," for further information on breast cancer risk factors.

Risk factors for benign breast disorders are not well studied. However, a recent study found age, family history, and hormonal factors appear to influence the risk of benign breast lesions in a similar fashion as observed with breast malignancy. A family history of breast cancer significantly increases the risk for all types of benign breast conditions.[12]

Women of reproductive age with regular cycles, who were of older age at first childbirth, breastfed longer, or who currently use or have used oral contraceptives for ≥8 years appeared to have a high risk of fibroadenoma, while postmenopausal women have an increased risk of epithelial proliferation with atypia.[12] Additionally, hormone replacement therapy raises postmenopausal risks for epithelial proliferation with atypia, fibrocystic change, breast cysts, and fibroadenoma. Nulliparity increases the risk of breast cysts compared to multiples who have had 3 or more children but decreases the risk when compared to women who have only had 1 child. Obesity did not appear to increase the risk of benign breast disorders, according to this study, and in some instances, had a reduced risk.[12]

Epidemiology

According to recent studies, breast cancer is the leading cause of cancer in women.[13] A palpable breast mass is the most common presenting symptom of breast cancer. However, of the 3% of general practitioners' encounters with female patients that are due to breast complaints, benign breast disease is a more common cause of breast symptoms (eg, palpable masses and pain), with malignancy accounting for <10% of these cases.[14][1] 

The incidence of benign breast conditions varies based on age and type of lesion. Fibroadenomas account for 95% of palpable breast masses in adolescent girls and 12% of menopausal women.[8][7] A recent study found fibroadenomas, epithelial proliferation, and fibrocystic changes are most common in women aged 25, with incidence rates of 45, 32, and 42 per 100,000 person-years, which increases to 81, 55, and 140 per 100,000, respectively, at age 40, and declines after age 55.[12]

Pathophysiology

The pathophysiology of palpable breast masses varies depending on the underlying etiology. Please see StatPearls' companion resources, "Breast Cancer," "Breast Cyst," "Breast Fibroadenoma," "Fibrocystic Breast Disease," and "Breast Fat Necrosis," for further information on the pathophysiology of these breast disorders.

History and Physical

The clinical assessment of palpable breast masses primarily involves a thorough and accurate history of the lesion's associated symptomatic features, breast cancer risk factors, and CBE.[15][8] The CBE is the initial component of the standard triple assessment performed to evaluate breast lesions for potential malignancy.[16]

Clinical History

Patients presenting with complaints of a new breast mass should have a thorough history performed to characterize the lesion accurately. Clinicians should inquire about the mass's onset, duration, changes in size, pain, nipple discharge, and skin changes (eg, ulceration, eczema, or tethering).[7][8] These characteristics can help suggest potential diagnoses initially. For instance, an acutely tender breast lump is more likely to be an abscess or hematoma secondary to trauma. Cancerous breast masses rarely present with pain, although the presence of pain should not exclude neoplastic lesions from the differential. A history of recent pregnancy or breastfeeding may indicate that a condition associated with lactation is more likely (eg, mastitis or galactocele).[17] Nipple changes or discharge merits attention, as these can correlate with some less common breast tumors.[18][9] A history of any associated systemic symptoms should also be obtained, including weight loss, dyspnea, and bone pain, which may suggest potential malignancy.[19]

Establishing the duration for which the mass has been present is not always possible. Patients who do not regularly perform breast self-examination may not notice a breast lump until it has reached a significant size. Indeed, a proportion of breast lumps are identified through routine screening, so this is not necessarily an accurate way of determining the acuity of such a mass.[7] Furthermore, clinicians should establish whether the mass has developed in association with trauma or other symptoms, as well as if the mass appears to be rapidly growing or changing.

Breast cancer risk factors 

Family history is a key risk factor for breast cancer. Establishing an accurate family history is crucial, including relatives diagnosed with non-breast cancers, especially at a young age. Risk calculators (eg, Tyrer–Cuzick model) can be instrumental in generating an accurate risk profile.[20][7] Additionally, a detailed understanding of the patient's medical history and medications is a crucial component of calculating a patient's breast cancer risk. The primary risk factor for developing breast cancer is excess exposure to estrogens. Therefore, clinicians should inquire about lifetime estrogen exposure in all patients presenting a new breast mass, including oral contraceptives, hormone replacement therapy, and reproductive history. A history of smoking and alcohol consumption should also be obtained.[7][12]

Clinical Breast Examination

Clinical examination of a breast lump is the first stage in the triple-assessment approach. Both breasts and axillae should be examined meticulously by the clinician, and a physical examination of other body systems should be carried out as indicated by the history. Although it can be tempting to give more importance to more targeted imaging modalities, eg, mammography or ultrasound, the findings of the physical examination are crucial for the effective diagnosis and management of breast disease.[21] Repeated studies have indicated that optimal sensitivity and specificity can be achieved only by combining all 3 assessments.[16][21]

Clinical breast examination is often conducted with a chaperone to make the patient feel more comfortable. The entire chest and abdomen should be exposed, and the exam should be conducted with the patient in the supine or both supine and seated positions.[8][7] Each breast and axilla should undergo a visual inspection, looking for skin changes, nipple discharge, visible masses or asymmetry, and tethering to underlying structure; this feature can be exaggerated by asking the patient to place their hands on their hips and lift the arms.[22][8] The breasts can most easily be palpated by asking the patient to lie back at approximately 30 degrees and rest their palm up underneath their head.

Palpation of each breast must proceed in a structured manner; generally, clinicians use a 4-quadrant approach (upper outer, upper inner, lower outer, and lower inner quadrants), followed by palpating the areola and the axillary tail. Particular attention should be paid to the inframammary fold and the axillary tail. The unaffected breast is examined first, and the tissue is assessed for consistency. Masses are most often detected in the upper outer quadrant, as most breast tissue is located here. The nipple-areola complex should also be examined.[7]

Palpable breast masses should be described in location, size, shape, tenderness, fluctuance, mobility, texture, and pulsatility. If the patient describes nipple discharge that is not immediately visualized, it is appropriate to ask the patient to express the discharge themselves before the clinician attempts to do so.[23][8] Following palpation of the breast, the clinician must always palpate the axilla and supraclavicular region for lymphadenopathy. This area may present with enlarged, tender, or firm nodes, the number and nature of which should be documented. During the examination of the axilla, the clinician should take the weight of the patient's arm to relax the pectoralis muscles.[24]

Evaluation

Breast Imaging Classification

Breast imaging findings are classified by their Breast Imaging Reporting and Data System (BI-RADS) category, which correlates imaging findings with their probability of underlying malignancy and recommends a broad treatment strategy. This standard allows breast imaging to be described according to a certain structure, including the density of breast tissue, presence and location of a mass or masses, calcifications, asymmetry, and any associated features. The BI-RADS categories range from 0 to 6.[25]

The BIRADS system includes different mass classifications depending on the imaging modality. In mammography, to be considered a mass, the lesion must be visible in 2 different projections, have convex outer borders, and be denser in the center than on the periphery.[26][25] In ultrasound, a mass requires visualization in 2 different planes. Masses are defined according to their shape, margin, and density. In terms of shape, a mass can be categorized as round, oval, or irregular. Circumscribed margins are more apt to be benign, whereas microlobulated, indistinct, or spiculated margins are more likely malignant. The margin may also appear obscured. Mass density is compared to surrounding normal tissues - higher, equal, or lower - or may reflect fat within the mass.[27][25]

Table. Breast Imaging Reporting and Data System

Radiological Assessment

The most common radiological modalities for imaging breast tissue are mammography, ultrasound, and magnetic resonance imaging (MRI) (see Image. Superficial Vein With an Area of Intraluminal Thrombus, Ultrasound). Age-specific recommendations have been established to optimize the effectiveness of these diagnostic studies. The following imaging guidelines have been proposed by the American College of Radiology Appropriateness Criteria for the evaluation of new palpable breast masses based on the patient's age:

• For women 40 years and older: Either diagnostic mammography or digital breast tomosynthesis (DBT) is recommended as the initial imaging modality. Mammography alone has been found to identify abnormalities with a sensitivity of 86% to 91% (see Image. Breast Mammogram).[28] If initial imaging has BI-RADS 1 to 3 findings, ultrasound is recommended to characterize a palpable mass further. Ultrasound is also recommended if mammogram imaging is unable to visualize a palpable mass, as 40% of benign palpable masses are only seen on ultrasound.[8][28]
• Women younger than 30: For palpable masses in these women with low clinical suspicion, follow-up over 1 to 2 menstrual cycles is appropriate. Ultrasound imaging should be performed if the mass remains after the observation period. However, ultrasound imaging should be performed initially in those with abnormal findings on CBE (eg, enlarged, fixed, hard, and heterogeneous texture).[1] Ultrasound is preferred for women younger than 30 due to denser breast tissue and lower cancer incidence in this group.[8][28] If ultrasound results show BI-RADS 1, a diagnostic mammogram is appropriate for high clinical suspicion.[28] 
• Women aged between 30 and 39: Ultrasound, DBT, and mammography may be considered for initial imaging of a palpable mass. However, diagnostic mammography is preferred in high-risk patients or those with suspicious findings on CBE, as mammogram facilitates clinical assessment of the disease extent in women older than 30. Concordance between imaging findings and clinical examination is essential for accurate diagnosis.[8][28]

Ultrasound imaging is preferred to mammography in younger women and men as their breast tissue tends to be denser, with a much lower proportion of fatty tissue. This dense tissue impedes the accuracy of mammography and makes it more challenging to detect microcalcifications.[29] Magnetic resonance imaging is not typically recommended due to high costs, false-positive rates, and lower specificity. It may be reserved for specific cases, such as distinguishing scar tissue from recurrence in post-lumpectomy patients or screening high-risk individuals (eg, those with known underlying BRCA mutations).[5] 

Pathology Analysis

The third aspect of triple assessment requires an invasive procedure to allow pathological diagnosis. Pathology analysis involves either fine-needle aspiration biopsy (FNAB) or core biopsy.[16] Cytology allows an analysis of cells in isolation, while histological examination of a biopsy can provide more detail about the architecture of tissues. These invasive procedures involve risks to the patient and should, therefore, only occur when the index of suspicion is present. Whether to perform FNAB or core biopsy depends on several factors, including the expertise of the clinician, available diagnostic equipment, and the site of the lesion. However, core biopsy is generally preferred over FNAB due to its decreased incidence of insufficient tissue collection and higher sensitivity and specificity than FNAB.[30][8] Breast cancers diagnosed with an FNAB require core needle biopsy confirmation with immunohistochemical evaluation before treatment is initiated.[7] Please see StatPearls' companion resources, "Fine Needle Aspiration of Breast Masses" and "Stereotactic and Needle Breast Biopsy," for more information on these procedures.

Excisional biopsy was once the standard method for diagnosing palpable breast masses and suspicious nonpalpable lesions; however, core needle biopsy is now preferred as it is less damaging to surrounding breast tissue while providing accurate histologic diagnosis. An excisional breast biopsy is now primarily reserved for specific situations, including:

• Imaging and core biopsy results that are discordant
• Nondiagnostic core biopsy specimens
• Lesions inaccessible to core biopsy due to location or patient anatomy
• Findings of atypical hyperplasia or lobular carcinoma in situ (LCIS) [8]

Treatment / Management

The following initial management recommendations for new palpable breast masses are based on BI-RADS recommendations and the patient's age:

• Women 30 years and older: No further evaluation is indicated for a diagnostic mammogram demonstrating a lesion with definitively benign findings. An ultrasound is recommended for diagnostic mammogram findings of BI-RADS 1 to 3 to characterize the breast mass further. However, if mammogram and ultrasound are unable to visualize a palpable mass (ie, BI-RADS 1) but clinical suspicion is low, follow-up for 1 to 2 years is preferred; palpable masses with high clinical suspicion should be evaluated with tissue biopsy. Clinicians should proceed to tissue biopsy if initial mammogram imaging has BI-RADS 4 to 5 findings.[8][28]
• Women younger than 30: If no lesion is identified on initial ultrasound imaging for a palpable mass with low clinical suspicion, follow-up over 1 to 2 years with repeated imaging and CBE is appropriate. However, a tissue biopsy is recommended if a size increase or other suspicious findings are noted during follow-up. A diagnostic mammogram is recommended for those with suspicious findings on CBE (eg, enlarged, fixed, hard, and heterogeneous texture) and BI-RADS 1 findings on ultrasound.[8][28]

The management recommendations for breast masses categorized as BI-RADS 2 to 5 are similar in women of all ages. BI-RADS 2 findings may be routinely followed if asymptomatic. BI-RADS 3 findings with low clinical suspicion may be monitored by CBE and diagnostic mammogram or ultrasound every 6 to 12 months for 1 to 2 years; however, tissue biopsy is recommended if clinical suspicion is high. A tissue biopsy should be performed if initial or second-line ultrasound imaging has BI-RADS 4 or 5 findings. Ultimately, the treatment of a breast lump varies depending on the condition diagnosed following appropriate follow-up and histologic assessment and may involve an interprofessional approach, with input from the oncology, radiology, pathology, surgical, specialist nursing, anesthetic teams, palliative care, social workers, and psychology teams where indicated.[8][28] 

Please see StatPearls' companion resources, "Breast Cancer," "Breast Cyst," "Breast Fibroadenoma," "Fibrocystic Breast Disease," "Phyllodes Tumor of the Breast," "Male Breast Cancer," "Inflammatory Breast Cancer," "Breast Abscess," and "Breast Fat Necrosis," for further information on the specific management of these breast disorders.

Differential Diagnosis

Breast masses have various causes that differ based on age group and clinical presentation. In women younger than 25, the most common causes for a breast mass are benign conditions, including fibroadenoma, giant juvenile fibroadenomas, cysts, hamartomas, fat necrosis, and inflammatory breast conditions (eg, abscesses). For those 25 years and older, palpable breast masses are also commonly caused by benign breast abnormalities; however, the risk of a malignant underlying condition increases as age increases.[7][8] Please see StatPearls' companion resources, "Breast Cancer," "Breast Cyst," "Breast Fibroadenoma," "Fibrocystic Breast Disease," "Breast Abscess," and "Breast Fat Necrosis," for further information on these breast disorders. Differential diagnoses that should be considered when evaluating patients with a palpable breast mass include:

• Breast cyst
• Breast abscess
• Breast carcinoma
• Fibrocystic changes
• Fibroadenomas
• Lactating adenoma
• Phlegmon
• Prominent lactiferous sinus
• Traumatic fat necrosis
• Hematoma
• Hamartoma [1][8][17]

Males presenting with breast masses must be treated with a high degree of suspicion to rule out malignant tumors.[4] Imaging male breasts should utilize ultrasound as male breast tissue is not amenable to mammography. In males, central masses located behind the nipple may be attributable to gynecomastia. Gynecomastia is abnormal breast tissue development in males, which can correlate with several causes, including chromosomal disorders, liver failure, paraneoplastic syndromes, and drugs such as spironolactone and calcium channel blockers.[31] Due to hormonal variations, physiological gynecomastia may also be present in the neonatal period, at puberty, and in older males.[32]

Prognosis

The prognosis of a palpable breast mass primarily depends on whether the underlying etiology is benign or malignant. The majority of breast masses prove to be benign and have an excellent prognosis. However, the prognosis of breast carcinoma varies based on the stage at diagnosis. Stage 0 and stage I both have a 100% 5-year survival rate. The 5-year survival rate of stage II and stage III breast cancer is about 93% and 72%, respectively. Only 22% of stage IV breast cancer patients will survive their next 5 years.[33] 

Complications

The primary risks involved in breast mass evaluation are during the biopsy procedures. Risk factors associated with both FNA and CNB include bleeding at the biopsy site, anesthesia risks, bruising, mild pain, infection, patient anxiety and discomfort, hematoma, and altered breast sensation; however, a core needle biopsy generally carries a slightly higher risk of complications due to the larger tissue sample obtained.[34]