Currently MMG is accepted as a “gold standard” in the evaluation of breast diseases in patients older than 40. The ultrasound technique is widely used in young women for examination of the breast structure. ABVS opens a new approach to assessment of breast anatomy, with visualization of the whole gland at once allowing analysis of all observed changes in relation to other X-ray and MR modalities and good reproducibility of the corresponding images during follow-up.

Normal breast structure varies over time in the same women, during the menstrual cycle, pregnancy, after weaning, and during menopause [1–3]. This variability is also reflected in the ABVS images.

The female breast is composed of glandular, fatty tissue interspersed with fibrous or connective tissue. The distribution and prevalence of the fatty or glandular tissue depends on age and hormonal changes [4–8]. Thick fascia covering the pectoralis major and serratus anterior muscles make up the bed of the breast. Layers of premammary superficial and retromammary deep fatty tissue surround the gland. Chest and intercostal muscles are located posterior to the pectoral fascia. Fibrous septa extend from the dermis into the breast parenchyma to create the Cooper suspensory ligaments. They divide the gland into 15–25 cone-shaped functional lobes which are distributed in the fibrofatty stroma in multiple lobules. The lobes are arranged radially around the nipple with apices turned to it. The lobes drain into multiple ducts which coalesce and subsequently drain into lactiferous ducts which terminate at the nipple. The breast lobule consists of 20–40 acini or alveoli which are the main secretory unit of the breast tissue. The lobule and the first terminal duct arising from it constitute the terminal duct-lobular unit (TDLU). The TDLU is an important site for the development of cancer and benign proliferations of the breast [1].

The breast fibroglandular stroma is a clinically important structure consisting of supporting stroma and periglandular stroma. The supporting stroma is formed from processes of the superficial fascia and interlobular layers consisting of coarse connective tissue from collagen fibers, relatively poor in cells. The periglandular stroma immediately surrounds the ducts and has a loose soft fibrous structure, with abundant fibroblasts and several macrophages, lymphocytes, and plasma cells. The expression of the periglandular stroma is proportional to the development of the glandular tissue. The supporting stroma and periglandular stroma absorb X-rays equally and therefore they cannot be differentiated mammographically, appearing as continuous glandular tissue. The mammographic density of the breast depends on the amount of these stromal and epithelial elements. Increased MMG density is more apparent in young women than postmenopausal women.

In young women, the differences between supporting and periglandular stromata can be seen with the help of ultrasound. The supporting stroma appears on sonograms as areas of increased echogenicity. On the contrary, periglandular stroma is seen as low echogenicity areas. These two structures should be considered as glandular tissue during ultrasound imaging analysis to enable comparisons between MMG and US. Thus, breasts in the early reproductive period (at the age of 15–25) have a cellular structure with alternating zones of low and high echogenicity. This variability of the echostructure is provided by the periglandular stroma. The structure of the glandular tissue varies from reticular to cellular in young women with a regular menstrual cycle. Edema and hyperemia of the periglandular stroma decrease echogenicity and provide a reticular pattern in the secretory phase. The periglandular stroma narrows, and the echogenicity of the glandular tissue increases with less expressed nodularity in the proliferation phase. The echostructure becomes cellular. The additional hypoechoic masses are identified more easily against this background in the proliferation phase (Figs. 4.1 and 4.2). Therefore, the proliferative phase of the menstrual cycle also is preferable for examining the breast with 3DUS in the reproductive period, as in conventional 2D ultrasound. Collapsed ducts are not clearly visible in the proliferative phase against a background of echogenic glandular tissue. They can sometimes be seen in the secretory phase of MC as hyperechoic dots or lines.

Glandular tissue occupies practically all areas of the gland in the early reproductive period and can be clearly seen in the anterior and posterior slices of a full-sized image (Fig. 4.3). Adipose tissue is expressed minimally. Cooper’s ligaments cannot be clearly visualized on the background of this high echogenic glandular tissue. The nipple is represented as a hyperechoic ovoid structure with a minimal hypoechoic distal shadow.

The structure of the right and left breasts is basically quite symmetrical. If any asymmetry is present, pathology should be excluded [3]. This was stated in relation to MMG but can be applied to ABVS as well. Computer workstations allow assessing the right and left breast by matching slices. These images and saved clips from the whole array of ultrasound data facilitate identification of developmental abnormalities, the preferential location of the glandular tissue, its distribution per quadrants, its structural features, and pathological masses (Fig. 4.4). The adaptive mode offered by ABVS—nipple shadow reduction tool—improves visualization of the retroareolar structures. 3D data should be acquired using the nipple maximum lateralization technique; it helps to reduce the “no-show” areas under the nipple and retroareolar region on LAT (latero-medial oblique) and SUP (superior craniocaudal) views. With a conventional 2D US technique, the visualization of retroareolar regions without informational and quality loss usually requires the additional use of a water paddle.

The most intensive breast development starts at the end of pregnancy and in lactation. During pregnancy, the breasts are influenced by hormones produced by the placenta, with hyperplasia of glandular lobes and increase development of ducts. At the end of pregnancy, the breast loses the cellular structure and appears as a uniform thickened layer of glandular tissue. In this period, TDLU transform and develop further, connective tissue septa are stretched and thinned, and edema and increased vascularity are present. Echogenic layers of supporting stroma are correspondingly thin on a sonogram. ABVS shows these changes as a loss of reticular structure, even a decrease in echogenicity of the glandular tissue, with several subtle hyperechoic linear structures (ducts), mainly in areolar areas (Fig. 4.5). After lactation, the breast lobules involute following the withdrawal of prolactin stimulation. On ABVS, cellular or reticular breast structure is restored.

At the age of 35 or sometimes earlier, fat tissue appears in between the glandular tissues, even in lean-bodied women. Areas of the breast between the fat lobes mostly still have a cellular structure. Later, at the age of 40, the proportion of fatty tissue is further increased, and the glandular tissue loses its cellular pattern due to interlobular fibrosis (Figs. 4.6, 4.7, and 4.8).

At the age of 50–60, the proportion of fatty tissue in the breast increases even more. The breast tissue on MMG shows as transparency. This transparent background on MMG allows clear visualization of microcalcification and any additional lesions. With ABVS, it is also possible to show this fatty degeneration: the gland appears evenly as a lobular structure of reduced echogenicity with several cord-like elements of high echogenicity, representing the thinned glandular tissue and fibrosis of supporting stroma. Usually the residual glandular and fibrous tissue is preserved in the upper-outer and central areas, while the structure of internal and lower quadrants is composed mostly of fatty tissue which is of reduced echogenicity (Fig. 4.9).

The most typical ABVS features of the breast structure at the age of 60–70 and above are an islet or narrow strips of fibrous tissue of high echogenicity and sparse ducts in the nipple and areolar areas with fatty lobules of lowered echogenicity constituting the prevalent part of the gland tissue (Fig. 4.10). So with ultrasound, we have similarity of representation compared to MMG of the fatty and fibrous tissues. As ABVS covers the whole gland in the same projections as in MMG, it makes the ABVS images look like mammograms. Adipose tissue is hypoechoic on the sonotomogram, similar to on a mammogram. Glandular tissue and fibrosis are hyperechoic or have a denser background, as on a mammogram.

In some cases, the cellular structure of the stromal-glandular complex is preserved significantly longer, especially in lean-bodied women with a history of a long lactation period (up to 1 year) (Fig. 4.11). About 40 % of postmenopausal women have a significantly dense breast. Hyperestrogenism forms a background for the decreasing involution changes in the glands during this period. Uterine leiomyoma and endometriosis are accompanied by hyperestrogenism and hormonal imbalance, leading eventually to the stimulation of ductal and glandular epithelial cell proliferation, thus prolonging the beginning of breast involution (Fig. 4.12). Hormone replacement therapy also slows down the processes of fatty involution (Fig. 4.13).

X-ray mammography is almost incapable of detecting cancer against the background of dense glandular tissue. Meanwhile, high-density breast does not preclude the identification of masses by ABVS but rather enhances it [9, 10]. Therefore, ultrasound, and even better ABVS, should be present in the algorithm for screening women with dense glandular tissue (types ACR III and IV according to BI-RADS classification).

The fibroadenoma (FA) is the most common benign breast tumor, occurring frequently in the second and third decades and being reported as a common breast lesion also in postmenopausal women who fall into the screening age group [11, 12]. Overall fibroadenomas comprise 50% of all breast biopsies, and the rate increases to 75 % for biopsies in women under the age of 20 [13]. FA often occurs as a reaction to hormonal changes. Hyperestrogenemia contributes to its development. Usually it presents as a palpable non-tender mobile lesion 1–2 cm in diameter or can be detected incidentally by MMG especially in postmenopausal women. In some patients (10–20 %), they can be multiple, bilateral, or unilateral. Some FAs (especially giant FAs) can demonstrate rapid growth in adolescent girls, or during pregnancy and lactation causing asymmetry and discomfort, and thus require surgery [14]. Complex FAs are associated with an increased risk of subsequent breast cancer. Observational and molecular studies suggest FAs can transform into phyllodes tumors, which are graded as benign, borderline, and malignant.

On FNAC or needle biopsy, FAs arise from terminal duct-lobular units, the same functional unit for lobular and ductal carcinoma. An FA contains benign epithelial cells (myoepithelial and luminal). As it grows older, it becomes hyalinized, associated with calcification or undergoes myxoid degeneration. Histologically, several types of FA are defined: intracanalicular, pericanalicular, and mixed. Pericanalicular fibroadenomas are predominant in women under 45 and represent an overgrowth of connective tissue around the breast duct. Intracanalicular ones are characteristic for women over 50 and are formed inside the duct gland.

Benign fibrocystic change is a rare condition before the age of 20 and becomes more prevalent in perimenopausal women, and microscopic lesions persist in postmenopausal women [25]. Cystic formation is most common in patients with benign epithelial proliferations and also may present in “normal” breast tissue. Benign epithelial proliferations associated with fibrocystic change include intraductal papillomas, fibroadenomas, duct ectasia, radial scars, sclerosing adenosis, epithelial hyperplasia of the usual type, and many more. Large cysts, fibroadenomas, and duct ectasia are classified as local forms of benign fibrocystic change. Diffuse forms can be represented by predominant hyperplasia of glandular tissue (sclerosing adenosis or fibrosclerosis). Diffuse and local changes can combine.

Several hormonal abnormalities have been implicated in the pathogenesis of fibrocystic change, including hyperprolactinemia, increased estrogen levels, reduced progesterone levels, and excess thyroid hormone activity [26]. The most pronounced forms of epithelial hyperplasia and cystic formation occur in patients with endometriosis. Hyperandrogenism is accompanied with a predominance of stromal fibrosis.

Apocrine epithelium is an inherent feature of fibrocystic change, and the presence of apocrine cells in a breast biopsy is generally considered by pathologists to be a reassuring feature of benignity. Apocrine metaplastic change develops in the terminal duct-lobular unit. Acini dilate because of fluid production by this apocrine metaplastic epithelium. Several adjacent acini have fused to form a larger cystic space or multi-chambered ones [27]. There is molecular evidence that some benign forms of apocrine epithelium may be potentially neoplastic [28].

Fibrocystic change and simple cysts are generally not difficult to diagnose. Usually they present in association with other screen-detected lesions.

Breast cancer is common in women and a leading cause of cancer mortality in women worldwide [33]. Early preclinical diagnosis is of significant value because the sooner a tumor is detected, the longer the life expectancy of the patient. Life expectancy in breast cancer is influenced by the tumor size, presence or absence of metastases in regional lymph nodes, presence of receptors to female sex hormones in the tumor, histological type of the tumor, and many other factors. The number of such factors is growing as tumor biology is studied. Breast cancer is a heterogeneous disease with variations in morphological picture, clinical course, and sensitivity to treatment. This is due to the differences in tumor biology at the molecular level. The most aggressive are TN (triple-negative) and HER2-positive carcinomas. The most common histological type is considered to be ductal carcinoma, less common are lobular, mixed, medullary, colloid, nipple, and others. The numerous types of breast tumor cause polymorphism of their clinical, mammographic, and sonographic manifestations. The stage of the tumor is directly related to its size and spread. Therefore, any diagnostic method should not only identify the primary tumor but also assess the extent it has spread.

Therefore, the interest in developing new methods of early and specific diagnosis of non-palpable and “minimal” breast cancers of less than 1 cm is growing. X-ray mammography is established as a “gold standard” for assessing breast structure and breast density and for identifying regional axillary lymph nodes. MMG screening reduces mortality from breast cancer by more than 30 % [34]. However, the sensitivity of mammography depends on the breast density. Studies on women with dense breasts have demonstrated a sensitivity of MMG of less than 50 % [35]. More than 50 % of women younger than 50 and at least one-third aged over 50 have been found to have dense breast tissue [36]. Thus, cancer will be missed mammographically in every second woman with a dense breast. A mammogram is a summation image with all breast tissue overlapping in each view, thus resulting in missed cancer. It was found that the odds of interval cancer among women with extremely dense breasts were 17.8 times greater than among women with fatty breasts. In addition, breast density has been established as an independent risk factor for breast cancer [9].

Breast ultrasound, as currently considered among breast imaging modalities, has an essential and specific role as a complementary method to mammography for woman with dense breasts and clinically or radiologically detected suspicious breast lesions [37]. A combination of mammography with ultrasound in women after 40 with radiographically dense breasts doubles the detection of cancers [38, 39]. HHUS represents the gold standard for examination of young patients in which mammography is not indicated because of exposure of the breast to ionizing radiation and risk of induced breast cancer. However, the dependence on the operator for HHUS is a major concern with respect to the widespread use of whole-breast US.

Automated breast volume imaging has several advantages over HHUS: the technique is more reproducible, has 3D capability with multiplanar reconstruction, and allows delayed interpretation outside real time, optimizing the radiologist’s reading environment [40]. ABVS provides additional information to radiologists about breast cancer, especially in women with dense breast. A coronal view of the entire volume offers an easily understandable representation of the global breast anatomy and architecture, and also helps surgeons, giving a comprehensive sight of the breast from the skin line to the chest wall [23]. Breast cancer, especially IDC, shows a “retraction” phenomenon on ABVS coronal views, which is valuable in differentiating lesions as malignant [41, 42]. The high sensitivity of ABVS in detection of breast cancer was shown in many studies [23, 43–47].