Breast Imaging and Intervention during Pregnancy and Lactation

Abstract

Physiologic changes that occur in the breast during pregnancy and lactation create challenges for breast cancer screening and diagnosis. Despite these challenges, imaging evaluation should not be deferred, because delayed diagnosis of pregnancy-associated breast cancer contributes to poor outcomes. Both screening and diagnostic imaging can be safely performed using protocols based on age, breast cancer risk, and whether the patient is pregnant or lactating. US is the preferred initial imaging modality for the evaluation of clinical symptoms in pregnant women, followed by mammography if the US findings are suspicious for malignancy or do not show the cause of the clinical symptom. Breast MRI is not recommended during pregnancy because of the use of intravenous gadolinium-based contrast agents. Diagnostic imaging for lactating women is the same as that for nonpregnant nonlactating individuals, beginning with US for patients younger than 30 years old and mammography followed by US for patients aged 30 years and older. MRI can be performed for high-risk screening and local-regional staging in lactating women. The radiologist may encounter a wide variety of breast abnormalities, some specific to pregnancy and lactation, including normal physiologic changes, benign disorders, and malignant neoplasms. Although most masses encountered are benign, biopsy should be performed if the imaging characteristics are suspicious for cancer or if the finding does not resolve after a short period of clinical follow-up. Knowledge of the expected imaging appearance of physiologic changes and common benign conditions of pregnancy and lactation is critical for differentiating these findings from pregnancy-associated breast cancer.

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Introduction

Breast imaging during pregnancy and lactation is a common diagnostic challenge. The expected hormonal effects on the breast tissue result in increased parenchymal density and breast size, which can limit the accuracy of the clinical examination, mimic abnormalities, and obscure mammographic findings. Discussion with patients about the safety and importance of breast imaging can help to reassure them and prevent potential delays in the diagnosis and treatment of pregnancy-associated breast cancer (PABC). Breast cancer is the most common type of invasive cancer diagnosed in pregnant and postpartum women, with an incidence of one in 3000 pregnant and postpartum women in the United States, and the incidence is increasing as more women postpone childbearing until a later age (1,2). In this article, we review the normal physiologic changes of the breasts during pregnancy and lactation, discuss recommended screening and diagnostic guidelines, and describe imaging features of common benign and malignant entities.

Physiologic Characteristics

During pregnancy, the breasts undergo physiologic changes in response to changes in hormones (eg, estrogen, progesterone, prolactin, placental hormones, and cortisol) to prepare for lactation. In the first trimester, elevated levels of estrogen contribute to rapid enlargement of terminal duct lobular units, resulting in lobular enlargement, depletion of fibrofatty stroma, and increased stromal vascularity. The second and third trimesters of pregnancy are characterized by progressive lobular growth and greater proliferation and differentiation of luminal epithelial cells into specialized colostrum cell epithelium. This process is predominantly mediated by progesterone. Increased estrogen levels also stimulate the anterior pituitary gland to produce prolactin, which initiates milk production. However, high progesterone levels inhibit full milk production and only colostrum is produced (3). Estrogen and progesterone levels decrease in the postpartum period, leading to decreased inhibition of prolactin, resulting in full milk production. Milk release is mediated by oxytocin, which is produced by the posterior pituitary gland in response to breastfeeding and causes myoepithelial cell contraction (4). Postlactational involution occurs after the cessation of lactation when prolactin levels decrease.

Imaging Recommendations and Expected Appearance by Modality

Mammography and Digital Breast Tomosynthesis

The American College of Radiology (ACR) Appropriateness Criteria (5) emphasize that mammography is safe during pregnancy and lactation for both screening and diagnostic indications. Mammography is not contraindicated during pregnancy because the radiation dose to the fetus is negligible. For mammography, the fetus is indirectly exposed to scattered radiation. For a four-view mammographic examination, the fetal radiation dose is less than 0.03 mGy (5). Radiation effects can be categorized as (a) stochastic effects that have no threshold level, with dose-independent severity, and (b) deterministic effects, which have a threshold level with dose-dependent severity. The ACR and the Society for Pediatric Radiology state that there are no demonstrated deterministic effects, such as teratogenesis, below a threshold of 50 mGy and that doses up to 100 mGy are likely to be “too subtle to be clinically detectable” (6). Because the negligible dose to the uterus is primarily from internally scattered radiation, abdominal shielding is not necessary but can be used if the patient prefers.

Physiologic changes that are seen at mammography include diffuse increased breast density and increased breast size (Fig 1). These findings are typically bilateral and symmetric, unless there is a history of exclusive unilateral breastfeeding or prior unilateral whole-breast radiation therapy. When they presented for breast imaging, 88% of pregnant, lactating, and postpartum women were found to have heterogeneously dense or extremely dense breasts (7). Despite high breast density, the sensitivity of mammography has been reported to range from 74% to 100% during pregnancy and lactation (7–14). Breastfeeding or pumping 30 minutes before imaging to decrease the volume of stored milk is encouraged to decrease breast density and increase patient comfort. Calcifications related to lactational changes may also be present and are most commonly diffuse and bilateral, with a typically benign appearance. However, calcifications may occasionally show morphology and distribution suspicious for malignancy in cases of biopsy-proven benign lactational changes (Fig 2) (15). The postlactating breast is characterized by lobular atrophy and a return to the prepregnancy state approximately 3 months after the cessation of lactation (16). Normal breast parenchymal histologic results are illustrated in Figure S1, for reference.

Figure 1.

Normal mammographic appearance of the breasts in a 33-year-old lactating woman who presented with a palpable abnormality in the left breast. Bilateral craniocaudal (A) and mediolateral oblique (B) mammograms show symmetric increased parenchymal density (breast composition category D, extremely dense). No underlying mammographic abnormality is identified. The palpable area of concern corresponded with normal breast tissue on US images (not shown).

Figure 2.

Lactational changes in a 47-year-old lactating woman with screening-detected calcifications in the right breast. (A) Diagnostic magnification craniocaudal (left) and mediolateral (right) mammographic views of the right breast show grouped amorphous calcifications at 7 o'clock (oval outlined areas). (B) US image of the right breast shows corresponding calcifications with punctate echogenic foci (arrowheads). The calcifications were categorized as Breast Imaging Reporting and Data System (BI-RADS) 4B. Because the patient was lactating and there was concern for formation of a milk fistula with stereotactic-guided biopsy, US-guided biopsy of the suspicious calcifications in the right breast was performed. (C) Specimen radiograph of the cores obtained from the right breast US-guided biopsy show representative calcifications (arrowhead). Pathologic examination showed benign breast tissue with lactational changes associated with calcifications.

Digital breast tomosynthesis (DBT) may provide added benefit for detection of cancer in pregnant and lactating women by overcoming the masking effect of dense breast tissue seen with mammography. However, to our knowledge, there are currently no published studies in which the authors specifically focused on DBT for this patient population. Thus, the ACR Appropriateness Criteria for DBT are the same as those for mammography during pregnancy and lactation (5).

Breast US

US is the preferred initial breast imaging modality during pregnancy because it has greater sensitivity than mammography and confers no radiation exposure to the fetus and expectant mother (5). Authors of most studies (7,8,10–14) report the sensitivity of US for the detection of PABC as nearly 100%. However, authors of a large single-institution study (9) of 117 cases of PABC found lower sensitivity (77%) with US. The authors explained that the lower sensitivity of US in their study was due to incorrect classification of masses with a falsely reassuring US appearance (ie, resembling fibroadenoma) as probably benign and due to cases of ductal carcinoma in situ for which the US examination was negative (9). The US appearance of breast tissue during pregnancy is diffusely hypoechoic and heterogeneous due to the proliferation of fibroglandular elements (Fig 3A). During lactation, the echotexture becomes diffusely echogenic, with prominent ducts and increased vascularity (Fig 3B). Occasionally, lactational change can manifest as a hypoechoic vascular mass or a complex cystic and solid mass due to variable lobular and ductal hyperplasia (Fig 4) (17).

Figure 3.

Normal US appearance of the breasts during pregnancy and lactation in two patients. (A) US image in a 30-year-old pregnant patient at 15 weeks gestation shows diffusely hypoechoic and heterogeneous fibroglandular tissue. (B) US image in a lactating patient shows that the fibroglandular tissue is diffusely echogenic, with prominent ducts.

Figure 4.

Lactational changes in a 33-year-old lactating woman who presented with a palpable abnormality in the left breast. Mammogram (not shown) showed no underlying abnormality. (A) US image shows an oval hypoechoic mass with indistinct margins (arrows), which correlated with the palpable mass reported by the patient. The mass was categorized as BI-RADS 4A, and US-guided biopsy was subsequently performed. (B) Photomicrographs show cores with variably sized acini (left) and variably dilated acinar units (★, right) in lobules containing intraluminal secretions consistent with lactational changes. Note preservation of outer myoepithelial layers (arrowheads, right). (Hematoxylin-eosin stain; original magnification, left, ×4; right, ×200.)

Breast MRI

Breast MRI can be safely performed during lactation but not during pregnancy (5). Contrast-enhanced MRI is contraindicated in pregnancy due to the unknown risks associated with exposure to gadolinium-based contrast agents (U.S. Food and Drug Administration [FDA] pregnancy class C). Gadolinium chelates cross the placenta and have the potential for dissociation into toxic free gadolinium ions. Safety data are limited in this patient population, and there are no well-controlled studies regarding the teratogenic risks of contrast-enhanced MRI in pregnant women (18). Thus, the ACR Committee on Drugs and Contrast Media recommends that a gadolinium-based contrast agent “should be administered only when there is a potentially significant benefit to the patient or fetus that outweighs the possible but unknown risk of fetal exposure to free gadolinium ions” (18). The use of noncontrast sequences such as diffusion-weighted imaging as an alternative to contrast-enhanced breast MRI for pregnant women is an area of ongoing research (19,20).

For MRI of lactating women, as with mammography, breastfeeding or pumping 30 minutes before imaging is typically performed. The ACR does not recommend cessation of breastfeeding after the use of gadolinium-based contrast agents because neonates absorb less than 1% of the dose, although patients may pump and discard milk for 12–24 hours if they prefer (18). Physiologic changes seen at breast MRI in lactating patients include marked background parenchymal enhancement, increased vascularity, increased T2 signal intensity due to increased fluid content, and increased fibroglandular tissue volume (Fig 5). These normal changes in the breast related to lactation were initially hypothesized to limit the sensitivity of MRI for breast cancer detection (21). Contrary to this hypothesis, authors of several studies have shown that the sensitivity of breast MRI for detecting breast cancer during lactation is very high (98%–100%) despite high background parenchymal enhancement (12,13,19,22–24).

Figure 5.

Normal MRI appearance of the breasts in a high-risk 36-year-old lactating woman with a family history of breast cancer. (A) Axial maximum intensity projection MR image shows marked bilateral background parenchymal enhancement and increased vascularity. (B) Axial fat-saturated T2-weighted MR image shows diffuse increased signal intensity. (C) Axial fat-saturated early phase contrast-enhanced MR image shows an increased amount of fibroglandular tissue. (D) Maximum intensity projection MR image acquired in the patient before pregnancy and lactation shows only mild background parenchymal enhancement.

Other Imaging Modalities

Contrast-enhanced mammography is not discussed in the ACR Appropriateness Criteria (5). It seems reasonable to consider the use of contrast-enhanced mammography for lactating patients who have an indication for but are unable to undergo breast MRI. However, to our knowledge, there are currently no published studies on contrast-enhanced mammography for this patient population.

Molecular breast imaging is not performed during pregnancy due to potential fetal radiation exposure from the radiopharmaceutical technetium 99m (^99mTc) sestamibi, which crosses the placenta (25). Molecular breast imaging can be performed during lactation without necessitating any interruption of breastfeeding (25). Authors of a case report (26) demonstrated significant diffuse bilateral breast uptake of ^99mTc sestamibi in a postpartum woman undergoing myocardial perfusion imaging. Thus, it is possible that high background parenchymal uptake during lactation could reduce lesion conspicuity. However, to our knowledge, there are currently no published studies of molecular breast imaging for this patient population. Given the lack of data, the ACR Appropriateness Criteria indicate that “there is no role for molecular breast imaging in breast cancer screening during lactation” (5).

Imaging Recommendations by Clinical Scenario

Screening

The ACR Appropriateness Criteria (5) indicate that breast cancer screening is appropriate in both pregnant and lactating women, with recommendations based on age and breast cancer risk status. Table 1 summarizes the recommended screening guidelines.

Table 1:

ACR Breast Cancer Screening Guidelines in Pregnant and Lactating Women

In pregnant and lactating women aged 40 years or older at average risk, mammography with DBT is recommended (5). In women with dense breasts, supplemental screening with whole-breast US may be considered, with recognition of the increased false-positive rates of this modality (27). MRI may be considered for supplemental screening in lactating women only. MRI is not recommended for women who are pregnant or are at average risk.

In patients at high risk aged 30 years and older, mammography with DBT is recommended for pregnant and lactating women (5). This recommendation pertains to women with genetic mutations associated with an increased risk of breast cancer (and their untested first-degree relatives) and women with a lifetime risk of at least 20% (28). The recommendation for women with a history of undergoing mantle chest radiation therapy (cumulative dose of ≥10 Gy) administered before the age of 30 years is to start screening mammography at age 25 or 8 years after therapy, whichever is later (28). US may be considered for supplemental screening during pregnancy when MRI is contraindicated. Breast MRI is recommended in lactating women but may be delayed until 3 months after the cessation of breastfeeding if the total planned time period for breastfeeding is not prolonged.

Diagnostic Imaging

Pregnant and lactating women with clinical symptoms such as a palpable mass, focal pain, or suspicious unilateral nipple discharge should undergo diagnostic imaging to exclude underlying malignancy (Fig 6). During pregnancy, workup of new clinical breast symptoms should begin with US for patients of all ages (5). If the US findings are suspicious for malignancy or fail to show the cause of the clinical symptoms, diagnostic mammography is recommended. Palpation-guided biopsy should be considered for patients with clinical symptoms suspicious for cancer and a negative imaging workup (5). The diagnostic workup for women during lactation is the same as that for nonpregnant nonlactating individuals, beginning with US in patients younger than 30 years and beginning with mammography followed by US for patients aged 30 years or older.

Figure 6.

Diagnostic imaging algorithm for pregnant and lactating women with a new clinical concern. For pregnant patients or patients younger than age 30 who are breastfeeding with a BI-RADS category 4C or 5 abnormality, mammography ideally should be performed before biopsy.

Staging of Known Breast Cancer

Local-regional staging of newly diagnosed breast cancer is important for treatment planning. The ACR Appropriateness Criteria highlight that bilateral diagnostic mammography is indicated in pregnant women once breast cancer is diagnosed to evaluate for suspicious calcifications that may increase the extent of disease, to assess for multifocal and/or multicentric disease, and to screen the contralateral breast (5). Whole-breast US is not recommended due to a lack of supportive evidence (5). Ipsilateral axillary US may be considered for nodal staging on the basis of surgeon preference. Breast MRI may be performed in lactating patients to evaluate the extent of disease but is contraindicated during pregnancy. In a retrospective study (12) of 53 women with PABC, postpartum preoperative breast MRI changed surgical treatment in 28% (15 of 53) of patients.

Neoadjuvant Therapy

The ACR Appropriateness Criteria (5) do not provide specific guidelines for assessing response to neoadjuvant therapy during pregnancy or lactation, given the limited data available in this area. It is reasonable to use a similar approach to the imaging algorithms used to evaluate nonpregnant nonlactating patients (29), with the exception of not performing breast MRI during pregnancy. US has been used to evaluate the response to neoadjuvant chemotherapy in the breast and regional lymph nodes in women with breast cancer that was diagnosed during pregnancy (11). Breast MRI has been used to assess the response after neoadjuvant chemotherapy for patients with breast cancer that was diagnosed during lactation (23).

Procedural Considerations

Core needle biopsy is the standard of care for tissue diagnosis and is safe during pregnancy and lactation. Fine-needle aspiration is not generally performed for breast biopsy because the cellular changes that normally occur during pregnancy and lactation have histologic features that can overlap with those of neoplasia and may contribute to a false-positive diagnosis of malignancy (30). Core biopsies are also preferred to obtain sufficient tissue for analysis of tumor biomarkers including estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (HER2) (also known as Erb-B2 receptor tyrosine kinase 2 or ERBB2). Although blood and lidocaine may be present in breast milk after biopsy, it is considered safe to continue breastfeeding after the procedure. Complications of biopsy to discuss as part of the informed consent process include increased risk of bleeding due to increased vascularity, increased risk of infection due to ductal dilatation and milk production, and formation of milk fistulas (if the patient is lactating). Concern for a milk fistula should not deter biopsy, and the risk may be reduced by using a smaller-gauge needle and fewer passes, breastfeeding or pumping immediately before the procedure, decreasing milk production with ice packs or breast binding, and using a pressure dressing after biopsy (31,32). Milk fistulas may spontaneously close while lactation continues. However, the only reliable means of stopping milk leakage is to suppress lactation. Surgical closure of the tract may be required in refractory cases (31,32).

Stereotactically guided and US-guided breast biopsies can be safely performed in patients who are pregnant or breastfeeding. However, US guidance is generally preferred over stereotactic guidance, because a smaller-gauge biopsy device, which reduces the risk of a milk fistula in patients who are breastfeeding, can be used. If US-guided biopsy is performed for calcifications, radiography of the specimen is recommended to confirm the presence of calcifications in the cores. MRI-guided biopsy should not be performed in pregnant patients due to the use of a gadolinium contrast agent and the inability to place the patient in a prone position later in pregnancy. Postprocedural mammography, with craniocaudal and 90-degree lateral views, is performed if preprocedural mammography was previously performed as part of the diagnostic workup. This is particularly relevant for pregnant patients or patients younger than 30 years old who are breastfeeding and have Breast Imaging Reporting and Data System (BI-RADS) category 4C or 5 disease to confirm appropriate placement of biopsy clips and planning for subsequent localization.

Image-guided preoperative localization procedures are similar for pregnant and lactating patients to those for nonpregnant and nonlactating patients. However, MRI-guided localization should not be performed in pregnant patients due to the use of a gadolinium contrast agent and the inability to place the patient in a prone position later in pregnancy.

Pathologic Evaluation

The breasts may be affected by a variety of benign and malignant entities during pregnancy and lactation. Although most breast abnormalities that affect pregnant and lactating patients are benign, breast cancer during pregnancy and lactation is more likely to manifest as advanced disease at initial presentation and to result in worse outcomes than those in patients who are not pregnant and not lactating. This highlights the importance of understanding the radiologic presentation of various breast abnormalities. Some disorders are specific to pregnancy and lactation, while most are the same as those observed in nonpregnant nonlactating women, although the imaging appearance may differ. Table 2 lists benign and malignant entities that may be encountered during pregnancy and lactation. Management depends on the imaging evaluation and BI-RADS assessment.

Table 2:

Breast Abnormalities Related to Pregnancy and Lactation

Benign Disorders

Galactocele

A galactocele is the most common benign breast mass in lactating women, who usually present clinically with a palpable mass (33,34). Galactoceles can occur in women who have recently stopped breastfeeding. Galactoceles are milk-containing retention cysts from an occluded mammary duct. The pathognomonic imaging appearance of a galactocele is a round or oval circumscribed mass with a fat-fluid level (Fig 7). The fat-fluid level is best visualized on a 90-degree lateral mammographic view (35). Peripheral rim calcifications may also be present (36). On US images, an antidependent layer of fat (hypoechoic or hyperechoic) is often seen in a complicated cyst with no internal vascularity (37). The pathognomonic fat-fluid level can be identified using non–fat-saturated T1-weighted MR images to demonstrate the fat component and T2-weighted fat-saturated MR images for the fluid component (36,38). In the prone position for breast MRI, the fat component rises toward the chest wall (Fig 8). The classic imaging appearance of galactoceles occurs when there are variable proportions of fat and water and the milk content is fresh. However, atypical appearances may occur, depending on the amount and viscosity of fat and protein (34,35). A high fat content may appear as a completely radiolucent mass mimicking a lipoma or oil cyst on mammograms, while variable proportions of old milk and water may create a pseudohamartoma appearance. If the imaging appearance is characteristic of a galactocele, a BI-RADS 2 categorization is appropriate.

Figure 7.

Galactocele in a 30-year-old lactating woman who presented with a palpable lump in her right breast. (A) Mediolateral mammogram shows an oval circumscribed mass with a fat-fluid level (arrow). (B) US image also shows the fat-fluid level (arrow), with echogenic fat occupying the nondependent portion of the cyst. The imaging features are characteristic of a galactocele (BI-RADS 2). US-guided aspiration for symptomatic relief yielded milky fluid.

Figure 8.

Incidental galactocele in a 34-year-old lactating woman at high risk (BRCA2 mutation). Axial fat-saturated T2-weighted (A) and precontrast non–fat-saturated T1-weighted (B) MR images show a complicated cyst in the left breast, with a fat-fluid level (arrow) consistent with that of a galactocele (BI-RADS 2). Note that the fat component is posterior because the patient was imaged in the prone position.

Aspiration may be performed for symptomatic relief and characteristically yields milky fluid. A galactocele may become infected and may mimic an abscess at imaging, yielding milk and purulent material when aspirated. Galactoceles may rupture, yielding an imaging appearance suspicious for cancer due to surrounding inflammation and fat necrosis. If imaging features are not characteristic (eg, a complex cystic and solid mass), the radiologist should categorize the finding as BI-RADS 4 and recommend diagnostic aspiration and/or core needle biopsy (Fig 9) (39–41). Careful evaluation is warranted because PABC can manifest as a circumscribed mass with posterior acoustic enhancement and can contain cystic components (10), potentially mimicking a galactocele. Most galactoceles spontaneously resolve without treatment after cessation of lactation.

Figure 9.

Atypical appearance of a galactocele in a 30-year-old lactating woman 6 months after giving birth who presented with a palpable lump in her right breast. Craniocaudal (A) and mediolateral (B) mammograms of the right breast show an oval mass with obscured margins (arrow). (C) Color Doppler US image at the site of the palpable lump shows a mass with a heterogeneous echotexture, indistinct margins, and posterior acoustic shadowing (*), without internal vascularity (BI-RADS 4A). US-guided aspiration yielded milky fluid diagnostic of a galactocele. Subsequent core biopsy due to persistence of a palpable mass after repeated aspirations showed benign lactational changes.

Lactating Adenoma

Lactating adenomas are benign breast tumors that develop during pregnancy and lactation and often manifest as a painless palpable mass (33). Lactating adenomas occur in response to the hormonal changes of pregnancy and lactation; however, their exact histologic origin remains controversial (ie, a distinct tumor vs a hyperplastic fibroadenoma or a tubular adenoma-like lesion with superimposed physiologic lactational changes). Lactating adenomas often regress spontaneously after cessation of lactation but may recur during subsequent pregnancies (42). Imaging features may be indistinguishable from those of a classic fibroadenoma. Lactating adenomas often appear as an oval mass with circumscribed margins on mammograms and as an oval circumscribed homogeneous hypoechoic mass with parallel orientation, internal vascularity, and posterior enhancement on US images (Fig 10) (42–44). Calcifications are uncommon. On MR images, lactating adenomas typically appear as an oval enhancing mass with circumscribed margins and dark internal septa (38,43,45).

Figure 10.

Lactating adenoma in a 26-year-old pregnant woman at 28-weeks gestation who presented with a palpable lump in the subareolar region of her right breast. (A) US image shows an oval hypoechoic mass with microlobulated margins (arrow) and posterior acoustic enhancement. This was categorized as BI-RADS 4A, and US-guided biopsy was subsequently performed. (B) Photomicrographs show markedly hypercellular cores (left) and marked hyperplasia of normal-appearing lactational tissue (right), consistent with a lactating adenoma. Note minimal intervening stroma due to marked acinar expansion. However, the basement membrane remains visible (arrows, right). A myoepithelial cell layer is present but inconspicuous (arrowheads, right) due to the increase in the size and volume of epithelial cells, with finely vacuolated cytoplasms. (Hematoxylin-eosin stain; original magnification, left, ×4; right, ×200.)

Although these imaging features support a probably benign cause, biopsy is typically recommended because PABC can manifest with a similar, falsely reassuring appearance. There is limited evidence regarding the use of the BI-RADS 3 assessment category for oval, circumscribed, hypoechoic masses for women who are pregnant or lactating because the data were established from the general patient population; thus, recommendations for short-interval follow-up imaging should be used with caution in this clinical scenario. Patients with infarcted lactating adenomas may present with a painful enlarging palpable mass that has a heterogeneous echotexture and internal cystic areas on US images (46). This clinical history and associated imaging findings should prompt a recommendation for biopsy. Most lactating adenomas spontaneously regress after cessation of lactation (44). Surgical consultation can be considered if the mass is large or shows rapid growth (43).

Fibroadenoma

Fibroadenomas are hormonally sensitive benign tumors that are usually present before pregnancy but may become clinically apparent during pregnancy and lactation due to hormonally induced growth. The most common imaging appearance of a fibroadenoma is an oval mass with circumscribed margins on mammograms and an oval hypoechoic mass with circumscribed margins and parallel orientation on US images, and these appearances are similar in pregnant and nonpregnant women. Rapid growth may cause infarction, in rare cases. Patients with infarcted fibroadenomas may present with a tender nonmobile mass, with US features suspicious for abnormalities including lobulated margins, heterogeneous echotexture, and posterior shadowing (47,48). Fibroadenomas with secretory hyperplasia (during pregnancy) or postpartum lactational changes can demonstrate features mimicking a complex fibroadenoma, including heterogeneous echotexture, dilated ducts, and internal cystic spaces resembling a complex cystic and solid mass (Figs 11, 12) (34). Core biopsy should be considered for any new or growing solid mass in a pregnant or lactating patient.

Figure 11.

Fibroadenoma with lactational changes in a 32-year-old woman who presented with a lump in her left breast. (A) US image acquired at 15 weeks gestation shows an oval hypoechoic mass with circumscribed margins (arrow) and posterior acoustic enhancement, which was categorized as BI-RADS 3, with short-interval follow-up recommended. (B) Follow-up postpartum US image acquired while the patient was breastfeeding shows an interval increase in the size and heterogeneity of the mass (arrows). The mass was recategorized as BI-RADS 4A, and subsequent US-guided biopsy results confirmed the diagnosis of a fibroadenoma with lactational changes.

Figure 12.

Fibroadenoma with lactational changes in a 34-year-old lactating woman who presented with an enlarging right breast lump at the site of biopsy-proven fibroadenoma. (A) US image acquired 4 years earlier when the patient was not lactating shows an oval hypoechoic mass with circumscribed margins (*). US-guided biopsy (not shown) showed a benign fibroadenoma. (B) US image acquired at presentation when the patient was lactating shows the substantially increased size of the mass, with new internal cystic spaces and indistinct margins. Due to the complex cystic and solid mass appearance and interval growth of the mass, excisional biopsy was ultimately performed, and the result confirmed the diagnosis of a fibroadenoma with lactational changes.

Mastitis and Abscess

Puerperal mastitis refers to breast inflammation occurring during pregnancy or lactation. Although it is rare during pregnancy, it is common in the postpartum period, with approximately one in four women affected during the first 25 weeks after delivery (49). The source of infection is usually Staphylococcus aureus or a Streptococcus species in the infant's nose and throat. During the process of breastfeeding and epithelial disruption, the infant may transfer bacteria to the nipple-areolar complex (49). Milk stasis is an important risk factor because milk is an excellent medium for bacterial growth (50). Patients typically present with pain, swelling, erythema, and warmth of the affected breast. Mammography commonly shows skin and trabecular thickening due to edema, and US shows skin thickening and subcutaneous edema with increased vascularity (Fig 13). Progression to abscess, a local collection of pus in the breast, occurs in 5%–11% of cases and may manifest as a palpable mass (33). An abscess may appear as a complicated fluid collection or an irregular or ill-defined mass on US images (Fig 14). Initial treatment of simple mastitis includes antibiotic therapy such as dicloxacillin or cephalexin. US-guided aspiration can be performed if mastitis is complicated by an abscess. Patients should undergo clinical follow-up, and biopsy should be considered for imaging findings that do not resolve after appropriate treatment.

Figure 13.

Puerperal mastitis in a 28-year-old woman who presented with skin erythema and pain after discontinuing breastfeeding 3 weeks earlier. US image shows skin thickening (double-headed arrow) and subcutaneous edema with no discrete fluid collection. Given the patient's presenting symptoms and imaging features compatible with mastitis, a BI-RADS 2 category was assigned. The patient improved with antibiotic treatment and received clinical follow-up to resolution.

Figure 14.

Acute puerperal abscess in a 26-year-old lactating woman who presented with skin erythema, warmth, and pain. (A) Gray-scale US image shows an irregular complicated fluid collection (*). (B) Color Doppler US image shows hyperemia surrounding the fluid collection (arrows). US-guided aspiration yielded purulent fluid, and cultures grew methicillin-resistant Staphylococcus aureus (MRSA).

Granulomatous Mastitis

Granulomatous mastitis is a benign idiopathic inflammatory breast condition characterized by noncaseating granulomas. It usually occurs within 5 years of pregnancy, with the typical onset 6 months to 2 years after cessation of breastfeeding (51,52). Granulomatous mastitis occurs less often in nulliparous women and in patients without an association with pregnancy or lactation. It is important to recognize that the clinical and imaging features of granulomatous mastitis can overlap with those of inflammatory breast cancer, infectious mastitis, an abscess, and other benign inflammatory conditions of the breast (eg, diabetic mastopathy, sarcoidosis, or Wegener granulomatosis) (51). Patients with granulomatous mastitis present clinically with a palpable mass, breast pain, and skin erythema. A draining sinus tract to the skin may also be present. The imaging appearance is variable, with some features similar to those of infectious mastitis or abscess that may also mimic carcinoma (Fig 15) (53). Typical mammographic findings are a focal asymmetry or indistinct masses with trabecular and skin thickening due to edema. The appearance on US images is frequently an irregular hypoechoic mass with parallel orientation and tubular extensions or a focal area of decreased echogenicity with acoustic shadowing, without a discrete mass (53). Patients often present with persistent clinical symptoms and imaging findings that are unresponsive to antibiotic treatment of presumed infection, and thus, core needle biopsy should be recommended to exclude malignancy. Special stains and cultures are also used to exclude mycobacterial, nonmycobacterial, and fungal causes. Thus, granulomatous mastitis is often considered a diagnosis of exclusion. Treatment options include conservative measures such as close surveillance, therapy with oral corticosteroids or methotrexate, and a more aggressive surgical approach of wide local excision (51,54). The natural history of granulomatous mastitis is typically persistent and recurrent, with a prolonged duration of disease (1–2 years after initial presentation) (51).

Figure 15.

Recurrent granulomatous mastitis in a 32-year-old woman with a history of biopsy-proven granulomatous mastitis, now 4 months pregnant, who presented with right breast pain and drainage. (A) Gray-scale US image shows a complicated fluid collection or phlegmon (arrows) with tubular extension to the skin (arrowhead). (B) Color Doppler US image shows increased vascularity (arrows). Clinical follow-up and management was recommended given the patient's symptoms and history supporting the diagnosis of granulomatous mastitis (BI-RADS 2).

Lymphadenopathy

Lymphadenopathy is common in lactating and nonlactating patients and may be related to a wide variety of causes including inflammatory, infectious, and neoplastic causes and recent vaccination. During lactation, axillary and/or intramammary lymph nodes may enlarge due to bacterial seeding of the nipple during breastfeeding (50). On mammograms, benign reactive lymph nodes typically maintain a normal morphology: an oval or reniform shape with circumscribed margins and a radiolucent notch. On US images, reactive lymph nodes demonstrate uniform cortical thickening with an echogenic hilum (Fig 16). Conversely, focal cortical bulging, ill-defined or spiculated margins, or intranodal microcalcifications raise suspicion for malignancy (55). Reactive lymph nodes may also demonstrate prominent hilar vascularity, whereas capsular peripheral vascularity favors malignancy. If suspicious features are present, biopsy should be considered. If imaging features support the diagnosis of benign reactive lymphadenopathy, a benign assessment or short-interval follow-up are options for management.

Figure 16.

Benign reactive lymph nodes in a 34-year-old lactating woman who presented with a palpable abnormality in the right axilla after recent ipsilateral COVID-19 vaccination. A mammogram was negative for abnormality (not shown). (A) Gray-scale US image shows prominent lymph nodes in the right axilla, with uniform cortical thickening measuring up to 6 mm (double-headed arrow). The morphology of the lymph nodes is otherwise normal, with preserved fatty hila. (B) Color Doppler US image shows hilar vascularity (arrow). The findings are consistent with reactive lymphadenopathy due to recent ipsilateral vaccination (BI-RADS 2). The patient received clinical follow-up, with no palpable abnormality on physical examination.

Ectopic Axillary Breast Tissue

Axillary ectopic breast tissue is present in approximately 0.2%–6% of women (56). Although it is typically asymptomatic, axillary breast tissue can undergo lactational change in response to hormonal influence and become palpable (57). Ectopic breast tissue is subject to all the pathologic changes that can occur in the normal breast, including galactoceles (58), lactating adenomas (59), and rarely, carcinoma (60). If the ectopic breast tissue does not communicate with the ductal system of the breast, it can be subject to development of mastitis. On mammograms, ectopic axillary breast tissue is often best visualized on the mediolateral oblique view as normal-appearing fibroglandular tissue with interspersed fat. The classic US appearance is a heterogeneous echogenic area of tissue similar to normal fibroglandular tissue (Fig 17). Imaging features consistent with accessory axillary breast tissue can be assigned a BI-RADS 2 assessment with clinical follow-up. If the imaging appearance is atypical (Fig 18), biopsy may be recommended because ectopic breast tissue can be a site for malignancy.

Figure 17.

Accessory axillary breast tissue in a 36-year-old pregnant woman who presented with a right axillary lump for 2 months. US image shows heterogeneous echogenic tissue (*), similar to normal fibroglandular tissue, consistent with accessory axillary breast tissue (BI-RADS 2).

Figure 18.

Incidental accessory axillary breast tissue in a 36-year-old lactating woman at high risk, with a family history of breast cancer. (A) Axial contrast-enhanced T1-weighted MR image shows an enhancing mass with irregular margins in the right axillary tail (arrow). Evaluation of the contrast-enhancement kinetics showed rapid initial phase and delayed phase washout (not shown). (B) Bilateral mediolateral oblique mammograms show an irregular mass in the right axillary tail region (arrow). (C) Targeted US image of the right axilla shows an irregular heterogeneous mass with indistinct margins (arrows), which was categorized as BI-RADS 4A. US-guided biopsy of the mass confirmed benign breast tissue with lactational change.

Malignant Tumors

Breast Carcinoma

PABC is commonly defined as breast cancer that occurs during pregnancy or within 1 year after giving birth. The incidence of PABC is one in every 3000–10 000 pregnancies, accounting for up to 3% of all breast cancer diagnoses (1,2). Tumors in patients with PABC are typically larger, with higher rates of axillary nodal disease, than those in age-matched nonpregnant women with breast cancer (61). This may be related to delayed diagnosis and increased biologic aggressiveness secondary to hormonal stimulation during pregnancy. Although there is a transient increased risk of breast cancer during pregnancy and lactation, the long-term risk of future breast cancer is lower for women who had their first pregnancy before age 30 (62). PABC can be any subtype, although high-grade invasive ductal carcinoma accounts for 75%–90% of tumors (63). Estrogen and progesterone receptor expression of tumors occurs less frequently in patients with PABC than it does in similar-aged nonpregnant patients, but HER2 amplification occurs more frequently (64).

Proposed new terminology differentiates breast cancer that occurs during pregnancy (PrBC) from breast cancer that occurs during the postpartum period (PPBC) 5–10 years after pregnancy (65). This is based on evolving evidence that supports specific biologic characteristics and prognosis for each type (65). PrBC represents an estimated 4% of breast cancer cases in women younger than 45 years (66). Large cohort studies of PrBC suggest that the tumor characteristics and prognosis are equivalent to that of age-matched stage-matched nonpregnant control subjects (67). In comparison, PPBC represents an estimated 35%–55% of breast cancer cases in women younger than 45 years and is associated with worse survival rates and increased risk of metastasis independent of age, stage, grade, and hormone receptor status (67,68). It is hypothesized that tissue remodeling pathways that occur during postpartum involution are similar to wound healing and inflammation and may promote tumor progression and metastasis (69).

PABC (which includes PrBC and PPBC) usually manifests as a painless palpable mass, but it may also manifest with unilateral breast enlargement, skin thickening, bloody nipple discharge, or axillary lymphadenopathy (9,10,14). The radiologic features of PABC are typically the same as those of cancers seen in nonpregnant women (Figs 19–21) (33,38). The most common finding on US images is a solid mass, although the mass may demonstrate posterior acoustic enhancement and contain cystic components (10,70). When breast MRI is performed for postpartum patients for high-risk screening or preoperative staging, PABC can be visualized on the maximum intensity projection and subtracted postcontrast T1-weighted images as masses enhancing greater than background parenchymal enhancement and on T2-weighted images as low signal intensity masses against the high T2 signal intensity of the background of normal lactating fibroglandular tissue (12,20,22).

Figure 19.

PABC in a 36-year-old pregnant woman at 13 weeks gestation who presented with a lump in her left breast. (A) US image of the palpable area of concern shows an irregular hypoechoic mass with angular margins (arrow). (B) US image of the left axilla shows a morphologically abnormal lymph node, with cortical thickening and loss of fatty hilum (arrow). (C) Mammogram of the left breast shows an irregular mass with indistinct margins and associated fine pleomorphic calcifications (arrow) that corresponds to the mass seen on US images. The breast mass was categorized as BI-RADS 5, and US-guided biopsy results confirmed the diagnosis of grade 3 estrogen receptor–positive, progesterone receptor–positive, HER2–negative invasive ductal carcinoma,. The lymph node was also biopsied and demonstrated metastatic carcinoma. (D) Photomicrographs of the left breast mass specimen show an infiltrative hypercellular core (left) and irregular angulated nests (black arrowheads) and cords (arrows) of tumor cells infiltrating the stroma, with a desmoplastic reaction, in a haphazard arrangement (right), with a mitotic figure (red arrowheads). Note the intact myoepithelial cell layer in entrapped lobules for comparison (★, right). (Hematoxylin and eosin stain; original magnification, left, ×4; right, ×200.)

Figure 21.

PABC in a 31-year-old woman who presented with a left breast lump. (A, B) Craniocaudal (A) and mediolateral oblique (B) mammograms show an irregular mass in the left breast, with indistinct margins (arrows), that corresponds with the overlying triangular marker in A. (C) US image shows a corresponding irregular hypoechoic mass with angular margins (arrow) (BI-RADS 4C). US-guided biopsy results revealed grade 3 estrogen receptor–negative, progesterone receptor–negative, HER2–negative invasive ductal carcinoma. The patient subsequently discovered that she was pregnant but decided to terminate the pregnancy. MRI was performed after termination to evaluate for the extent of the disease. (D) Axial contrast-enhanced T1-weighted MR image shows the biopsy-proven malignant mass with a susceptibility artifact from the biopsy clip (arrow). No lymphadenopathy was seen. (E) Post–neoadjuvant chemotherapy contrast-enhanced T1-weighted MR image at the same level shows no residual mass or enhancement at the site of the biopsy-proven malignancy (arrow). The final pathologic results showed benign breast parenchyma with treatment effects and three negative sentinel lymph nodes.

Figure 20.

Pregnancy-associated breast cancer in a 32-year-old lactating woman who presented with a lump in her right breast. (A) Mammogram shows a focal asymmetry with associated architectural distortion and amorphous calcifications (arrow). (B) US image shows a corresponding irregular hypoechoic mass with angular margins (arrow), which was categorized as BI-RADS 5. US-guided biopsy results confirmed invasive ductal carcinoma, grade 3, estrogen receptor–positive, progesterone receptor–positive, HER2–positive. (C) Maximum intensity projection MR image (acquired to determine the extent of the disease) shows an irregular enhancing mass, consistent with the biopsy-proven malignancy (arrow). No lymphadenopathy was seen. Marked background parenchymal enhancement is also noted.

PABC may be treated with surgical and chemotherapeutic options similar to treatment of non-PABC, although radiation therapy is contraindicated until after delivery because of the risks associated with fetal radiation exposure (71). Surgery can be performed in all three trimesters. However, waiting until after 12 weeks gestation is often preferred to decrease the risk of spontaneous abortion (71). Surgical options include both mastectomy and breast conservation therapy. Breast conservation therapy is a reasonable option if radiation therapy can be delayed until after delivery. If radiation therapy cannot be delayed, such as in cases where the diagnosis is made early in pregnancy, mastectomy is preferred. Systemic treatment regimens are performed similar to regimens used in nonpregnant patients because a delay in treatment may worsen the patient's prognosis (72). Chemotherapy should be postponed until after the first trimester, when organogenesis is complete (71). Endocrine therapy, HER2-directed therapy, and other newer agents such as immune checkpoint inhibitors, poly adenosine diphosphate–ribose polymerase (PARP) inhibitors, and cyclin-dependent kinase (CDK) 4/6 inhibitors are not recommended during pregnancy (71).

Metastases and Lymphoma

Exceptionally rare malignant tumors in the breast during pregnancy and lactation include metastases and lymphoma. Case reports of bilateral breast metastases from gastric cancer and melanoma have been reported during pregnancy (73,74). Reproductive organ involvement was observed in 49% of patients with pregnancy-associated non-Hodgkin lymphoma (75), with bilateral breast involvement commonly reported (75).

Conclusion

Breast cancer during pregnancy and lactation is a rare but serious diagnosis that is associated with more advanced disease at initial presentation and worse outcomes. Therefore, any new or worsening clinical symptom in this patient population should be carefully assessed with prompt imaging evaluation to avoid a delay in diagnosis. Mammography is not contraindicated during pregnancy, because the radiation dose to the fetus is negligible. Although some diseases affecting the breast are specific to pregnancy and lactation, most are the same conditions as those observed in nonpregnant nonlactating women, although the imaging appearance may differ. Although most masses encountered are benign, biopsy should be performed if any features suspicious for abnormality are present or if the finding does not resolve after short clinical follow-up.