Benign breast dysplasia: clinical guidelines

List of Abbreviations

VAS – visual analog scale

BBD – benign breast dysplasia

CI – confidence interval

Malignant neoplasm – malignant neoplasm

IHC – immunohistochemical study

BMI – body mass index

COC – combined oral contraceptives (ATC – Progestogens and estrogens, fixed combinations)

MHT – menopausal hormone therapy

ICD-10 – International Classification of Diseases, Tenth Revision

MMG – mammography

INR – international normalized ratio

MRI – magnetic resonance imaging

NSAIDs – non-steroidal anti-inflammatory drugs from the ATC group of non-steroidal anti-inflammatory and antirheumatic products

FNAB – fine-needle aspiration biopsy

BC – breast cancer

US – ultrasound examination

ABUE – automated breast ultrasound elastography

FCC – fibrocystic condition

CDI – color Doppler imaging

PCD – power Doppler color mapping

ADH – atypical ductal hyperplasia

ALH – atypical lobular hyperplasia

BI-RADS – Breast Imaging Reporting and Data System

FEA – flat epithelial atypia

LCIS – lobular carcinoma in situ

MD – mammographic density

Terms and Definitions

Benign breast disease (BBD) is a group of conditions characterized by a wide spectrum of proliferative and regressive changes in breast tissue with an imbalance between the epithelial and connective tissue components [1].

1. Brief information on the disease or condition

1.1 Definition of the disease or condition

Benign breast disease (BBD) is a heterogeneous group of conditions characterized by a wide spectrum of proliferative and regressive changes in breast tissue with an imbalance between the epithelial and connective tissue components [1].

Comments: Synonyms for BBD include: "mastopathy", "fibrocystic mastopathy", "fibrocystic disease", "dyshormonal mammary hyperplasia", "fibroadenomatosis"

1.2 Etiology and pathogenesis of the disease or condition (group of diseases or conditions)

Risk factors for BBD include: high socioeconomic status, low body mass index in childhood and adolescence, rapid growth rate during adolescence, obesity, excessive intake of animal fats and meat (more than 3 servings per day during adolescence), alcohol consumption (between 16 and 23 years of age), caffeine intake, deficiency of vegetables, fruits, nuts (peanuts), and dietary fiber (during adolescence), sedentary lifestyle, prolonged combined menopausal hormone therapy (MHT) for more than 8 years, congenital and acquired genetic alterations, and high mammographic density [2], [3], [4], [5], [6], [7], [8], [9], [10], [11], [12], [13].

BBD is a hormone-dependent condition caused by an imbalance in the hypothalamo-pituitary-ovarian axis. Among all reproductive organs at risk for hormone-dependent hyperplastic processes, the breasts are affected most frequently, acting as the first indicator of neurohumoral homeostasis disorders [14]. The pathogenesis of BBD is based on chronic hyperestrogenism. Estrogens induce proliferation of the ductal alveolar epithelium and stroma, which, among other effects, leads to duct obstruction and cyst formation. Progesterone, conversely, counteracts these processes, promoting epithelial differentiation and the cessation of mitotic activity. Factors such as ovarian insufficiency (anovulation, luteal phase defect, relative estradiol predominance and progesterone deficiency), altered receptor sensitivity to sex steroid hormones, epithelial proliferation and apoptosis activity, and altered breast tissue vascularization play a significant role in the pathogenesis of BBD [15]. Furthermore, a link has been established between the development of BBD and hyperprolactinemia, which is attributed to the ability of prolactin to sensitize breast tissue to estrogens and increase the number of estradiol receptors therein (Table 1).

1.3 Epidemiology of the Disease or Condition

Benign breast disease (BBD) is the most common breast condition. Although statistical records for BBD are not maintained, various authors estimate its prevalence in the female population to be 50% or higher. The peak incidence of BBD occurs at 40-44 years of age, reaching 200-400 per 100,000 population per year, followed by a gradual decline by age 65 [16]. Certain forms of BBD are associated with an increased future risk of breast cancer (BC) [17], [18].

1.4 Features of Coding the Disease or Condition

N60: Benign mammary dysplasia:

N60.0 Solitary breast cyst

N60.1 Diffuse cystic mastopathy

Excludes: with epithelial proliferation (N60.3)

N60.2 Fibroadenosis of breast

Excludes: fibroadenoma of breast (D24)

N60.3 Fibrosclerosis of breast (cystic mastopathy with epithelial proliferation)

N60.4 Mammary duct ectasia

N60.8 Other benign mammary dysplasias

N60.9 Benign mammary dysplasia, unspecified

N62 Hypertrophy of breast

N63 Unspecified lump in breast

N64.4 Mastodynia

1.5 Classification of the disease or condition

Clinical and radiological classification of mastopathy

The severity of dysplasia is designated as mammographic density (MD), which is subdivided into 4 groups depending on the ratio of fibroglandular and adipose components. Quantitative assessment of MD was first described in 1976 by Dr. John N. Wolfe. Wolfe used an MD classification based on four grades – NI, P1, P2, and DY, ranging from the lowest adipose density and lowest risk of breast cancer to the densest structure with the highest risk, which corresponds to the modern American College of Radiology (ACR) classification – density types A, B, C, D, and N.I. Rozhkova's classification based on the percentage ratio of fibroglandular to adipose components:

Mild - MD <25%> ACR-A (N1)

Moderate - MD <50%> ACR-B (P1)

Pronounced - MD <75%> ACR-C (P2)

Severe - MD >75%-100% ACR-D (DY)

The degree of breast mammographic density correlates directly with the risk of developing breast cancer (the higher the mammographic density, the greater the risk of breast cancer) [19], [20], [21], [22], [23].

Classification of BBD according to the severity of proliferative processes in breast tissue (College of American Pathologists) [24].

• without epithelial proliferation (non-proliferative form);

• with epithelial proliferation (proliferative form);

• with atypical epithelial proliferation.

The relative risk of developing breast cancer is 1.17 (95% CI 0.94-1.47) for non-proliferative BBD, 2.07 (95% CI 1.58-1.95) for proliferative FCC without atypia, and 3.93 (95% CI 3.24-4.76) for proliferative FCC with atypia (Table 2) [17].

1.6 Clinical presentation of the disease or condition

BBD may have an asymptomatic or symptomatic course. Clinical manifestations of BBD include mastalgia, palpable lumps in the breast, and nipple discharge.

Mastalgia is characterized by subjective breast pain of varying intensity and occurs in the majority of patients with BBD. It is subdivided into cyclic and non-cyclic mastalgia. Cyclic mastalgia is a functional condition manifested by breast tenderness and swelling in the premenstrual period that resolves spontaneously with the onset of menstruation. Typically, the pain is a dull ache. True mastalgia is usually bilateral. The pain may be asymmetric and more pronounced in quadrants with well-developed glandular breast tissue (the upper outer quadrants). Non-cyclic mastalgia is unrelated to the menstrual cycle and is more frequently unilateral and localized. Causes of non-cyclic mastalgia include mastitis, trauma, thrombophlebitis (Mondor's disease), cysts, and tumors. Extramammary mastalgia occurs in costochondral syndrome (Tietze's syndrome), chest wall trauma, cervical and thoracic radiculopathy, and shingles. In some cases, breast pain can be caused by certain medications: hormonal agents, antidepressants, antihypertensive drugs, and cardiac medications.

Women with mild, short-lived mastalgia and no physical breast abnormalities have the same risk of breast cancer (1.2%-6.7%) as women without mastalgia. With more severe and prolonged pain, the risk of developing breast cancer increases [25], [26], [27], [28].

Breast tissue heterogeneity in BBD may be associated with various areas of induration. In the diffuse form of BBD, indurations lack distinct borders and present as fibrous strands and fine granularity. Nodular forms of BBD are characterized by indurations with clear contours and a nodular surface.

Nipple discharge may be unilateral or bilateral, originates from multiple ducts, and varies in color from colostrum-like to dark yellow, green, brown, or bright red.

2. Diagnostics, medical indications and contraindications for diagnostic methods

The diagnosis of BBD is established based on complaints, medical history, physical examination, breast ultrasound, and mammography.

2.1 Complaints and Anamnesis

Comments: When analyzing complaints and medical history, it is necessary to pay attention to symptoms such as pain, presence of masses and lumps in the breast, their location, duration and dynamics over time, as well as the presence and color of spontaneous nipple discharge.

The taking of medical history should include the following patient data: age, presence of bad habits (smoking, alcohol), family history, menstrual character (age at menarche and menopause, duration and regularity of the menstrual cycle), obstetric history (number of previous pregnancies and childbirths and their outcomes, age at first childbirth, duration of breastfeeding), past and current gynecological diseases, surgical interventions on the pelvic organs and mammary glands, past and current somatic diseases (in particular, thyroid diseases, hepatobiliary system disorders, etc.), allergic reactions, and medications taken.

• When taking the medical history, it is recommended to pay special attention to the presence of high-risk factors for breast cancer in patients with benign breast diseases [30].

Level CLevel 5Level of recommendation evidence C (reliability level of evidence – 5).

Comments: These factors include [30]:

1) The presence in close relatives (1st–2nd degree) of such diseases as breast cancer (including in men), ovarian cancer, pancreatic cancer, prostate cancer, and their age at the time of diagnosis.

2) Carriage of pathogenic variants in the BRCA1/2, PALB2, TP53, CDH1, and PTEN genes in the women with benign breast diseases themselves or in their close relatives.

3) History of chest radiation therapy (medical or technogenic).

4) History of breast biopsy or surgery for atypical breast hyperplasia.

Patients with high-risk factors for breast cancer must be referred for a consultation with an oncologist for further evaluation, selection of an individual (selective) cancer screening program, and implementation of preventive measures [1].

Mastalgia is the most frequent symptom of benign breast diseases, occurring in 45–70% of cases. During clinical examination, the intensity of pain is assessed using the visual analogue scale (VAS) [31], [33].

[1] ^{Order No. 168n dated March 15, 2022, "On Approval of the Procedure for Dispensary Observation of Adults" by the Russian Ministry of Health.}

2.2 Physical Examination

Comments: The method of objective breast examination has a low sensitivity (54%), but its specificity is 94% [35], [36]. Although objective breast examination during screening does not ensure a reduction in breast cancer mortality, it has nevertheless been proven that its use allows for the diagnosis of breast cancer at earlier stages [37].

The direct duties of an obstetrician-gynecologist include risk assessment and early detection of both benign and malignant breast diseases, as well as the provision of specialized care for benign breast diseases, including therapeutic and preventive approaches.

The optimal period for a physical breast examination in menstruating women is considered to be days 5–16 of the menstrual cycle (preferably by day 10 of the menstrual cycle if possible). Non-menstruating women can be examined at any time.

The examination should be performed in a standing position, first with arms lowered and then raised behind the head. The symmetry and shape of the mammary glands, the condition of the nipples, and the skin are assessed. Palpation is performed in the vertical position of the patient; for additional information, it is desirable to also examine the patient in the horizontal position on a couch, lying on the back and on the side. Palpation determines the localization, dimensions, contours of indurations, their surface and consistency, as well as mobility and relationship with surrounding tissues. Palpation covers the entire mammary gland—around the nipple and sequentially by quadrants down to the inframammary fold.

Nodular formations are more clearly defined during clinical examination of patients in a standing position. In the supine position, indurations may lose their outlines and merge with the surrounding adipose tissue. When pressing the induration with the palm against the chest wall, it ceases to be palpable (negative Koenig's sign).

In medical documentation, it is necessary to indicate the location, size, and consistency of detected formations and indurations, their relationship with the skin and surrounding tissues, and the distance from the edge of the areola (Figure 8).

During the objective examination, the presence of signs characteristic of breast cancer is assessed for differential diagnosis with benign breast diseases (Table 3).

The presence of scanty, clear nipple discharge is a physiological norm [28].

Spontaneous, unilateral discharge from a single duct of a serous, serous-hemorrhagic, or hemorrhagic nature may be a clinical manifestation of both benign intraductal proliferation and a malignant neoplasm, and requires a more thorough evaluation.

2.3 Laboratory Diagnostics

Comments: The cause of milk-like discharge can be the use of medications such as antidepressants, domperidone, metoclopramide**, methyldopa**, verapamil**, and combined oral contraceptives (according to the Anatomical Therapeutic Chemical (ATC) classification – Progestogens and estrogens, fixed combinations) [38], [40].

2.4 Instrumental Diagnostics

• In hyperprolactinemia, it is recommended to perform a brain MRI to rule out a pituitary adenoma [178].

GCR CLOE 4Grade of Recommendation C (Level of Evidence – 4).

Comments: Mammography, which allows for the timely recognition of pathological changes in 92–95% of cases, is recommended for the objective assessment of the condition of the mammary glands [32], [42]. The diagnostic value of mammography depends on compliance with X-ray imaging standards for the breast. Mandatory conditions for performing mammography are: standard examination of both breasts in two projections (craniocaudal and mediolateral oblique at 45 degrees); breast compression; examination of both breasts. The sensitivity of the method is 85–87%, and specificity is 91–92%. With increased mammographic density, the sensitivity of mammography is significantly reduced.

Comment: High mammographic density (ACR density categories C and D) is an independent risk factor for breast cancer, which can reduce the sensitivity of mammography to 48%. The breast density category according to the ACR classification is indicated in the mammography report for both diagnostic and screening studies; in case of asymmetric density, the category is indicated separately for each breast [32], [46].

Comments: Suspicious changes in the breast on mammography may be visualized as a mass or nodular formation, an area of architectural distortion (including radial scar), grouped microcalcifications, focal asymmetry, or changes in the nipple and skin. Not all types of calcifications are suspicious for breast cancer. Microcalcifications suspicious for breast cancer include: ductal segmental and linear distribution, clustered acinar, with architectural distortion [32], [46]. According to international guidelines, for newly detected palpable breast masses, mammography is recommended in women over 30 years of age, although in some cases this study may be performed even in women under 30. Thus, the NCCN guidelines (2023) consider the possibility of using diagnostic mammography and digital breast tomosynthesis in women under 30 with newly identified palpable breast masses in the absence of ultrasound findings [32].

Comments: Ultrasound is an indispensable instrumental diagnostic method in mammology and complements both mammography and magnetic resonance imaging. As additional options for expert ultrasound, Doppler mapping (breast ultrasound with Doppler study) and breast elastography (US elastography) [50], [51], [52] can be used.

• Contrast-enhanced breast MRI at the initial stage of benign breast disease diagnosis is not recommended [54], [55].

Level CLevel 5Level of recommendation evidence C (reliability level of evidence – 5).

Comments: Contrast-enhanced breast MRI has high sensitivity but low specificity, which leads to a high number of false-positive results. However, this imaging method provides additional information in complex clinical and diagnostic situations (young age, high mammographic density, "suspicious" nipple discharge, presence of breast implants, in cases of identified BRCA 1 or 2 gene mutations) [56], [57].

Comments: The BI-RADS category is uniform for all breast imaging methods; it is indicated separately for the right and left breasts in the study report (Appendix G1, Table 4) [32], [46], [58], [59], [60].

Obstetrician-gynecologists must receive the BI-RADS report:

0 - Inconclusive imaging results (poor quality study, incorrect positioning, insufficient projections). Additional images or prior examination data are required.

1 – Negative. Probability of malignancy: 0%

2 – Benign findings. Probability of malignancy: 0%

3 – Probably benign findings. Additional imaging is indicated (targeted mammography, tomosynthesis, breast ultrasound). Follow-up in 6 months. Probability of malignancy: 0–2%.

4 - Findings requiring morphological verification (fine-needle aspiration biopsy for fluid collections and core needle biopsy for solid masses)

4A - Probability of malignancy: 2–10%,

4B - Probability of malignancy: 10–50%,

4C - Highly suspicious findings, probability of malignancy: 50–95%.

5 – Assigned when findings have all features of malignancy. Probability of malignancy greater than 95%.

6 - Morphologically verified breast cancer.

With BI-RADS 1 and 2 results, the patient is monitored by an obstetrician-gynecologist; for all other BI-RADS categories (0, 3, 4, and 5), an initial appointment (examination, consultation) with an oncologist is necessary to rule out or verify the diagnosis and determine further management. Patients with BI-RADS 6 findings undergo treatment and follow-up by an oncologist.

2.5 Other Procedures

(performed upon recommendation and are the responsibility of the oncologist).

Women with identified complex cystic and nodular breast lesions are referred to an oncologist for diagnosis verification. Indications and contraindications for invasive diagnostic methods are determined by the oncologist, and the interventions themselves are performed in medical organizations licensed in the field of "Oncology".

A wide range of additional technologies is used for further diagnostic clarification, including fine-needle aspiration biopsy, core needle biopsy (targeted percutaneous puncture of a breast neoplasm under ultrasound guidance), vacuum-assisted biopsy under X-ray guidance (per NMU - targeted percutaneous biopsy of a breast neoplasm under X-ray guidance), ultrasound guidance (per NMU - targeted percutaneous puncture of a breast neoplasm under ultrasound guidance), or MRI guidance, as well as excisional biopsy and ductography. After ruling out malignant neoplasms, women with benign breast diseases are kept under dispensary observation by an obstetrician-gynecologist [1], [59], [61].

Comments: Follow-up monitoring implies physical examination with mammography and ultrasound every 6 months for 1–2 years. If negative dynamics—changes in the mass characteristics—are noted during follow-up, the patient is re-referred for a consultation with an oncologist [59], [64], [65].

Comments: According to ultrasound, a simple cyst presents as a round or oval anechoic mass with clear, smooth margins, homogeneous structure, with a capsule, usually showing posterior acoustic enhancement on grayscale, and without vascularity on color Doppler [66].

Comments: According to ultrasound, a complicated cyst shares most characteristics of a simple cyst, but with possible visualization of hyperechoic inclusions of various shapes, sizes, and structures (septa, tissue component, debris, etc.) without signs of vascularity on color-coded modes [66], [67].

Comments: According to ultrasound, a complex (atypical, complicated) cyst simultaneously has anechoic (fluid) and hyperechoic (less often hypoechoic) components, which may be represented by thick walls or septa and/or mural tissue proliferations with signs of vascularity [70], [71], [72], [73].

• In the presence of palpable breast masses suspicious for malignant neoplasms, but without signs of a malignant process on ultrasound or mammography, contrast-enhanced breast MRI is recommended for differential diagnosis [74], [179], [180].

Level CLevel 5Level of recommendation evidence C (reliability level of evidence – 5).

For adults: Level of recommendation validity B (level of evidence – 3).

For children: Level of recommendation validity C (level of evidence – 5).

Comments: Core needle biopsy is the method of choice for obtaining tissue samples for histological and immunohistochemical examinations.

Comments: These diagnostic methods are performed in clinical situations where the results of the pathomorphological examination of samples obtained via core needle biopsy do not match imaging findings, as well as in cases of technical difficulties during core needle biopsy (sometimes in the presence of breast implants) [84], [85]. Performing an excisional biopsy for non-palpable breast lesions requires prior placement of localization needles under imaging guidance [40].

[1] ^{Order of the Russian Ministry of Health No. 1130n dated October 20, 2020, “On Approval of the Procedure for Providing Medical Care in the Field of ‘Obstetrics and Gynecology’}

[2] ^{Order of the Ministry of Labor and Social Protection of the Russian Federation No. 360n dated June 2, 2021, “On Approval of the Professional Standard ‘Oncologist’}

3. Treatment, including drug and non-drug therapies, diet therapy, and pain management

3.1 Non-drug treatment

Comments: Observation alone and reassuring the patient that there is no threat to her health help relieve pain in 86% of women with moderate pain intensity and in 22% with acute pain. Approximately 61% of women who listened to relaxation audio cassettes daily for 4 weeks reported a reduction in mastalgia compared to 25% of women in the control group [86], [88].

Comments: A sports bra provides the most effective breast support and helps reduce breast pain [83].

Comments: Among women who restricted caffeine intake for a year, 61% experienced a reduction or complete disappearance of breast pain [90].

Comments: Restricting the intake of foods containing animal fats helps reduce mammographic density [92].

3.2 Pharmacotherapy

The obstetrician-gynecologist prescribes therapy only to patients with diffuse forms of benign breast disease (BBD).

Comments: Clinical studies of the transdermal route of administration of micronized progesterone (ATC - Progestogens) have demonstrated a reduction in breast tension and tenderness, regression of cysts according to breast ultrasound and mammography, and a decrease in mammographic density [82], [94], [95], [100], [101], [99], [102], [103].

Comments: These medications lead to the regression of pathological processes in the breast tissue [104], [114].

Comments: Treatment with indole-3-carbinol is accompanied by a reduction in breast pain and swelling, as well as a decrease in the number and/or size of breast cysts [110], [111], [112], [113], [177].

Comments: The use of selective estrogen receptor modulators (according to the Anatomical Therapeutic Chemical (ATC) classification system - antiestrogens) allows a therapeutic effect to be achieved in 75%–97% of patients with severe mastalgia. However, due to frequent side effects (hot flashes, excessive sweating, nausea, dizziness, vaginal dryness, thrombophlebitis, and endometrial hyperplasia), drugs from this group should be used as a second-line therapy for BBD [115], [116].

Comments: The main mechanism of action of dopamine receptor agonists is the suppression of prolactin secretion via stimulation of dopamine receptors without affecting the normal levels of other pituitary hormones. The administration of bromocriptine** is accompanied by a reduction/relief of pain [54], [183].

Comments: The use of NSAIDs in the treatment of various forms of mastopathy is due to the ability of drugs in this group to inhibit the synthesis of prostaglandins, which play a major role in the development of edema and venous stasis in the mammary glands. In addition, drugs from this group can be effective in the treatment of extramammary mastalgia caused by musculoskeletal disorders [117], [118]. NSAID therapy cannot be prolonged due to a high incidence of side effects affecting the gastrointestinal tract and other organs and systems.

3.3 Use of hormonal contraceptives in BBD.

Comments: The lack of randomized trials comparing different estrogen/progestogen combinations (ATC - Progestogens and estrogens, fixed combinations) makes it impossible to highlight the advantages of any specific drug regarding its effect on the risk of developing BBD. In women with an average population risk of breast cancer, a slight increase in breast cancer risk is noted with increasing duration of CHC use. Every additional 10 years of CHC use is associated with a significant 14% increase in breast cancer risk (95% CI: 1.05–1.23) [140]. In women with a family history of breast cancer and pathogenic variants in the BRCA1 and BRCA2 genes, the risk of breast cancer with CHC use corresponds to the general population risk [137], [141]. The use of progestogen-only contraceptives (ATC - Progestogens), regardless of the route of drug delivery, is associated with a slight increase in breast cancer risk comparable to that of CHCs [142].

Comments: This approach applies both to the initial choice and the continuation of contraception when an unspecified breast mass is detected [143], [144].

3.4 Use of MHT in benign breast diseases (BBD).

BBD is not a contraindication for prescribing MHT [145], [146].

For the majority of women, the risk of breast cancer is low and requires individual assessment in each specific case. Combined estrogen-progestogen MHT is associated with a small increase in breast cancer risk, which largely depends on the type of progestogens in the drug composition [149], [150], [151], [152], [153]. A number of studies have reported a lower risk of breast cancer development in patients who received dydrogesterone**, drospirenone (ATX: Drospirenone and estrogen) as the progestogen component of combined MHT with long-term use compared to patients who received MPA (ATX: Progestogens), NETA, LNG-IUS (ATX: Plastic progestogen-containing IUDs) as part of combined MHT [149], [150], [151], [152]. Estrogen monotherapy, tibolone, as well as micronized progesterone** as part of combined MHT in postmenopausal women are associated with no or a small increase in breast cancer risk [149], [152], [153].

During MHT use, the additional risk of breast cancer is low and is not cumulative with other risk factors (age, family history of breast cancer, genetic risk, BBD, personal breast cancer risk factors).

The risk of breast cancer increases with the duration of MHT use and decreases several years after its discontinuation [149], [152]. A confirmed diagnosis of breast cancer is an absolute contraindication for both the initiation and continuation of MHT.

3.3 Surgical Treatment

Determination of indications and contraindications for surgical treatment methods in BBD is the competence of an oncologist. Surgical treatment is carried out in oncological medical organizations.

4. Medical Rehabilitation and Sanatorium-Resort Treatment

Specific rehabilitation for BBD has not been developed.

5. Prevention and Dispensary Observation

5.1 Methods of general prevention of BBD

Comments: BMI ≥25 at age 18 is associated with a 33% reduction in BBD risk [171].

For adults: Recommendation grade B (Level of evidence – 3).

For children: Recommendation grade B (Level of evidence – 3).

Comments: The use of combined MHT preparations containing estrogens and synthetic progestins (ATX: Progestogens) for more than 8 years increases the risk of BBD by 74%.

5.2 Methods of breast cancer prevention in high-risk BBD patients

The prescription of prophylactic drug therapy and the determination of indications for risk-reducing interventions fall within the competence of an oncologist.

Comments: Every 12 months of breastfeeding is associated with a 4.3% reduction in the relative risk of breast cancer.

• In patients with BBD older than 35 years with atypical breast hyperplasia, it is recommended to administer risk-reducing drugs (antiestrogens) to suppress proliferative activity and prevent breast cancer [30], [40].

Level CLevel 5Level of recommendation evidence C (reliability level of evidence – 5).

Comments: In adult women with a history of atypical breast hyperplasia, the use of #tamoxifen** at a dose of 20 mg/day for 5 years is associated with an 86% reduction in the risk of developing breast cancer [174], [175]. The use of aromatase inhibitors (#exemestane at a dose of 25 mg/day or #anastrozole** 1 mg/day) for 5 years in high-risk menopausal patients reduces breast cancer risk by 65% [30], [174], [175], [176].

• Adult female carriers of pathogenic variants in the BRCA1,2 genes after discussing the benefit-risk ratio are recommended risk-reducing mastectomy (A16.20.043) with or without salpingo-oophorectomy in the presence of breast changes accompanied by pronounced hyperplasia or epithelial atypia in order to reduce breast cancer risk [30], [134], [135], [185].

GCR BLOE 2Grade of Recommendation B (Level of Evidence – 2).

Comments: Risk-reducing mastectomy reduces breast cancer risk by 93% [135].

The issue of risk-reducing salpingo-oophorectomy is decided by a medical commission.

5.3 Dispensary follow-up of patients with BBD

The scope and frequency of examination for patients with BBD are regulated by current documents (clause 6.1). With BI-RADS 1, 2 results, the patient is monitored by an obstetrician-gynecologist; with BI-RADS 4, 5, 6, the patient is monitored by an oncologist; with 0, 3 – a consultation with an oncologist is required to determine further management tactics (Table 4).

Comment: A 2-year screening interval is recommended for women in the absence of breast changes, breast cancer risk factors, patient complaints, and mammographic density types A and B. With mammographic density types C and D, a shorter screening interval (1 year) and an additional imaging method available at the specific medical facility (MRI, digital breast tomosynthesis, breast ultrasound) are advisable [32], [44].

[1] Order of the Russian Ministry of Health dated October 20, 2020, No. 1130n “On Approval of the Procedure for Providing Medical Care in the Field of Obstetrics and Gynecology”

[2] Order of the Ministry of Health of the Russian Federation No. 404n dated April 27, 2021

“On approval of the procedure for conducting preventive medical examination and clinical health assessment of certain groups of adults”

6. Organization of Medical Care

6.1. Organization of Outpatient and Inpatient Care.

Since certain forms of BBD are associated with an increased risk of developing breast cancer, optimizing the diagnosis and management tactics for women with BBD is part of the strategy to reduce breast cancer incidence.

Medical care for women aimed at detecting breast diseases is provided by an obstetriciangynaecologist. The direct responsibilities of an obstetriciangynaecologist include risk assessment and early detection of both benign and malignant breast diseases, as well as the provision of specialized care for benign breast diseases (BBD), including therapeutic and preventive approaches [1]. Following breast cancer risk assessment, physical examination, and instrumental workup, further routing of the patient is determined based on the risk category and the findings of imaging techniques according to the BI-RADS classification [59, 61]. Women with identified cystic and nodular breast changes are referred to an oncological dispensary for diagnosis verification.

Invasive diagnostic procedures are performed by an oncologist [2]. An indication for hospitalization is the impossibility of treatment and examination in an outpatient setting.

When benign breast diseases are detected, women are under dispensary observation (clinical follow-up) by an obstetriciangynaecologist, who provides treatment taking into account concomitant gynaecological pathology.

[1] Order of the Russian Ministry of Health dated October 20, 2020, No. 1130n “On Approval of the Procedure for Providing Medical Care in the Field of Obstetrics and Gynecology”

[2] Order of the Ministry of Labour and Social Protection of the Russian Federation No. 360n dated June 2, 2021, "On Approval of the Professional Standard 'Oncologist'"

Criteria for Evaluating the Quality of Medical Care

References

Appendix A1. Working Group Composition

Leyla V. Adamyan – Academician of the Russian Academy of Sciences, Doctor of Medical Sciences, Professor, Deputy Director of the V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology of the Russian Ministry of Health, Honored Worker of Science of Russia, Head of the Department of Obstetrics, Gynecology and Reproductive Medicine at the Russian University of Medicine, Chief Gynecologist of the Russian Ministry of Health, member of the Society for Reproductive Medicine and Surgery, Russian Association of Endoscopic Gynecologists, Russian Association for Endometriosis, Russian Society of Obstetricians and Gynecologists.

Andreeva Elena Nikolaevna – Doctor of Medical Sciences, Professor, Deputy Director - Director of the Institute of Reproductive Medicine, Head of the Department of Endocrine Gynecology, Professor at the Department of Endocrinology of the National Medical Research Center for Endocrinology of the Russian Ministry of Health, Professor at the Department of Obstetrics, Gynecology and Reproductive Medicine of the Russian University of Medicine, President of the International Association of Obstetricians, Gynecologists and Endocrinologists, member of the Russian Association of Endocrine Gynecologists, the Russian Association for Endometriosis, the Russian Society of Obstetricians and Gynecologists, ROSEGM.

Anisimkova Alla Alexandrovna – Radiologist at the Breast Pathology Department of the Institute of Oncogynecology and Mammology, National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov of the Ministry of Health of the Russian Federation

Artymuk Natalya Vladimirovna – Head of the Department of Obstetrics and Gynecology No. 2, Kemerovo State Medical University of the Ministry of Health of the Russian Federation, Chief freelance specialist in obstetrics and gynecology of the Russian Ministry of Health in the Siberian Federal District, Doctor of Medical Sciences, Professor, member ofROAG.

Ashrafyan Levon Andreevich – Deputy Director and Director of the Institute of Oncogynecology and Mammology, National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov of the Ministry of Health of the Russian Federation, Academician of the Russian Academy of Sciences, Doctor of Medical Sciences, Professor, President of ROSORS.

Belokrinitskaya Tatyana Evgenyevna – MD, PhD, Professor, Head of the Department of Obstetrics and Gynecology at the Faculty of Continuing Professional Education, Chita State Medical Academy of the Russian Ministry of Health, Honored Doctor of the Russian Federation, Chief freelance specialist in obstetrics and gynecology of the Russian Ministry of Health in the Far Eastern Federal District (Chita), member of the Russian Society of Obstetricians and Gynecologists, President of the Trans-Baikal Society of Obstetricians and Gynecologists.

Dolgushina Natalia Vitalievna – MD, PhD, Professor, Deputy Director for Research, National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov of the Russian Ministry of Health, Chief freelance specialist in women's reproductive health of the Russian Ministry of Health, Member of the Presidium of the Board of the Russian Society of Obstetricians and Gynecologists.

Kiselev Vladislav Ivanovich – Deputy Director of the Institute of Oncogynecology and Mammology, National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov of the Ministry of Health of the Russian Federation, Corresponding Member of the Russian Academy of Sciences, DSc (Biology), Professor, Board Member of the Russian Society of Oncoreproducers (ROSORS).

Kolyadina Irina Vladimirovna – Professor of the Department of Oncology and Palliative Medicine, Russian Medical Academy of Continuous Professional Education (RMAPO) of the Russian Ministry of Health; Leading Researcher, Oncologist at the Breast Pathology Department and Antineoplastic Drug Therapy Department, RMAPO of the Russian Ministry of Health, MD, PhD.

Kometova Vlada Vladimirovna – Head of the Oncopathology Department, National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov of the Ministry of Health of the Russian Federation, PhD, Board Member of the Russian Association of Mammology Specialists (ROOM).

Ovsiannikova Tamara Viktorovna – MD, PhD, Professor, Professor of the Department of Obstetrics and Gynecology at the Institute of Postgraduate Education, Peoples' Friendship University of Russia (RUDN University).

Protasova Anna Eduardovna – MD, PhD, Professor of the Department of Oncology, North-Western State Medical University named after I.I. Mechnikov; Professor of the Department of Oncology, St. Petersburg State University; Professor of the Department of Obstetrics and Gynecology, National Medical Research Center named after V.A. Almazov.

Rodionov Valery Vitalievich – Head of the Breast Pathology Department, Institute of Oncogynecology and Mammology, National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov of the Ministry of Health of the Russian Federation, MD, PhD, Board Member of the Russian Association of Mammology Specialists (ROOM), member of ROSORS.

Rozhkova Nadezhda Ivanovna – Professor, MD, PhD, Honored Scientist of the RF, Head of the National Center of Oncology of Reproductive Organs at the P.A. Herzen Moscow Oncology Research Institute – branch of the National Medical Research Radiological Center of the Ministry of Health of the RF, Professor of the Department of Clinical Mammology, Diagnostic Radiology and Radiation Therapy at the Faculty of Continuous Medical Education, RUDN University; President of the Russian Association of Mammologists; member of the Russian Society of Roentgenologists and Radiologists; member of the Association of Oncologists of Russia; member of ADIOR CIS and EA (Association of Directors of Centers and Institutes of Oncology and X-ray Radiology of the CIS and Eurasian countries); member of the non-profit organization "Association of Healthcare Organizers in Oncology"; member of the European Society of Radiology.

Semiglazov Vladimir Fedorovich – Head of the Scientific Department of Tumors of the Reproductive System, Head of Scientific Department – Chief Researcher of the Scientific Department of Breast Tumors, N.N. Petrov National Medical Research Center of Oncology of the Ministry of Health of the Russian Federation, Corresponding Member of the Russian Academy of Sciences, MD, PhD, Professor, President of ROOM.

Sencha Alexander Nikolaevich – Head of the Medical Imaging Department, National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov of the Ministry of Health of the Russian Federation, MD, PhD, member of the Russian Society of Roentgenologists and Radiologists (RORR).

Serova Olga Fedorovna – Chief freelance specialist of the Ministry of Health of the Moscow Region in obstetrics and gynecology, Chief Physician of the Moscow Regional Perinatal Center, MD, PhD, Professor.

Smetnik Antonina Alexandrovna – Head of the Gynecological Endocrinology Department, PhD, member of the Russian Society of Obstetricians and Gynecologists, President of the Russian Society of Gynecological Endocrinologists and Menopause Specialists.

Suturina Larisa Viktorovna – Chief Researcher, Head of the Department of Reproductive Health Protection, Scientific Centre for Family Health and Human Reproduction Problems (Irkutsk), MD, PhD, Professor.

Uvarova Elena Vitalievna – MD, PhD, Professor, Head of the 2nd Gynecological Department (Children and Adolescents), National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov of the Ministry of Health of the RF.

Khaschenko Elena Petrovna – PhD, Leading Researcher at the 2nd Gynecological Department, National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov of the Russian Ministry of Health.

Filippov Oleg Semenovich – MD, PhD, Professor, Honored Doctor of the RF, Chief freelance obstetrician-gynecologist of the Federal Medical-Biological Agency (FMBA) of Russia, Deputy Director of the Federal Research and Clinical Center of Children and Adolescents of the FMBA of Russia, Professor of the Department of Obstetrics, Gynecology and Reproductive Medicine at the Russian University of Medicine.

Khaschenko Elena Petrovna – PhD, Leading Researcher at the 2nd Gynecological Department, National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov of the Russian Ministry of Health.

Yureneva Svetlana Vladimirovna – Deputy Director for Research at the Institute of Oncogynecology and Mammology, Professor of the Department of Postgraduate Obstetrics and Gynecology, National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov of the Ministry of Health of the Russian Federation, MD, PhD, Professor, member of the Russian Society of Obstetricians and Gynecologists (ROAG).

Conflict of interest: none declared

Appendix A2. Methodology for Developing Clinical Guidelines

1. Obstetrician-gynecologist.

2. Oncologist.

3. Surgeon.

4. Radiologist.

5. Ultrasound diagnostics physician.

6. Pathologist.

Table 1. Level of Evidence (LoE) grading scale for diagnostic methods (diagnostic interventions)

Table 2. Level of Evidence (LoE) grading scale for prevention, treatment, and rehabilitation methods (preventive, therapeutic, and rehabilitative interventions)

Table 3. Grade of Recommendation (GoR) scale for prevention, diagnostic, treatment, and rehabilitation methods (preventive, diagnostic, therapeutic, and rehabilitative interventions)

Procedure for updating clinical guidelines.

The clinical guideline update mechanism provides for their systematic revision at least once every three years, as well as upon the emergence of new evidence-based medicine data regarding diagnosis, treatment, prevention, and rehabilitation, or when justified additions/comments to previously approved clinical guidelines become available, but no more frequently than once every 6 months.

Appendix A3. Reference Materials

Provision of medical care is currently regulated by the following valid documents:

Order of the Russian Ministry of Health No. 1130n dated October 20, 2020, “On Approval of the Procedure for Providing Medical Care in the Field of Obstetrics and Gynecology”

Order of the Ministry of Health of the Russian Federation No. 404n dated April 27, 2021, “On approval of the procedure for conducting routine medical check-ups and health screenings for certain groups of adults”

Note: The use of dietary supplements in the treatment of benign breast diseases is not recommended.

Appendix B. Physician Action Algorithms

Appendix B. Physician Action Algorithms

Appendix B-1. Algorithm for examining patients under 30 years of age with a palpable breast mass

Appendix B. Physician Action Algorithms

Appendix B-1. Algorithm for examining patients under 30 years of age with a palpable breast mass

Appendix B-2. Algorithm for examining patients aged 30 years and older with a palpable breast mass

Appendix B-3. Algorithm for examining patients with nipple discharge

Appendix B-4

Options for sequential breast palpation.

Established risk factors for benign breast diseases [2], [3], [4], [8], [154], [155], [156].

Relative risk of breast cancer depending on the severity of proliferative processes in breast tissue [16]

Differential diagnosis of breast masses [128]

Established risk factors for breast cancer [17], [132], [128], [157], [158], [159], [160], [161], [162], [163], [164], [165], [166], [167], [168], [169].

Appendix C. Patient Information

Breast self-examination.

It is best to perform the examination on the same day of the menstrual cycle, as breast size and structure change throughout the month. The most appropriate time is on the 5th–6th day from the start of menstruation, and after the onset of menopause – on the same day of each calendar month. Perform the examination monthly, but not more often – otherwise, changes may be too subtle each time for you to notice. Perform the examination in good lighting.

When starting the self-examination, try to calm down and relax. Treat it as a routine hygienic procedure. Remember that most changes found in the breast are benign.

The examination consists of 6 steps, but with proper and consistent organization, it takes very little time.

Step one: inspection of underwear

Minor nipple discharge may go unnoticed on its surface but leave traces on the bra. Therefore, it is necessary to thoroughly inspect the bra: check for any traces of nipple discharge in the form of bloody, brown, greenish, or yellowish spots and crusts.

Step two: general appearance of the breasts

1. Strip to the waist and stand in front of a mirror. Let your arms hang loosely. Carefully examine each breast in the mirror. Check for any changes in the size, shape, and contours of the breast (one breast may be slightly larger, which is normal). Pay attention to the symmetry of both breasts, whether they are at the same level, and whether they move evenly when you raise your arms behind your head, lean forward, or turn right and left. Check for any fixation or displacement of either breast to the side (Fig. 1).

2. Raise your arms up in front of the mirror. Examine the breasts again one by one, paying attention to their upward, lateral, or downward displacement; changes in shape with localized bulging or retraction of the skin or nipple; and the appearance of fluid droplets from the nipple when squeezed with two fingers (Fig. 2).

Step three: skin condition

Is the skin elastic? Does it gather into a fold easily?

Note any color changes, redness of the entire surface or specific areas, rashes, diaper dermatitis, or changes resembling "peau d'orange". Check for any lumps, bulges, dimples or bumps, skin retraction, ulceration, and puckering.

Do not pinch breast tissue into a fold between your fingers, as its lobular structure may create a false impression of a tumor lump.

Step four: palpation in the standing position

This step is conveniently performed in the shower with soapy fingers. Examine your left breast with your right hand, and your right breast with your left hand. Palpation is performed with the pads, not the tips of the fingers, using three or four closed fingers in circular, penetrating, springy motions. The thumb does not participate in palpation. For large breasts, the opposite hand supports it.

First, a superficial exploratory palpation is performed, where the finger pads do not penetrate deep into the breast tissue, which helps detect small formations located directly under the skin. Then, deep palpation is performed, where the finger pads gradually and sequentially reach the ribs. Palpation should be carried out from the clavicle to the lower edge of the ribs and from the sternum to the axillary line, including the axillary region, where enlarged lymph nodes may be found (Fig. 3).

Step 5: Palpation in the supine position

This is the most important part of self-examination, as it is the only way to thoroughly palpate all breast tissue. Note how the breasts feel beneath your fingers and memorize these sensations.

Palpation should be performed while lying on a relatively firm, flat surface; you can place a rolled towel or a firm pillow under the breast being examined, and either extend your arm straight down by your side or raise it above your head (Fig. 4).

Two palpation methods are recommended:

1. The grid method, in which the entire surface of the anterior chest wall from the clavicle to the costal margin and the breast itself are mentally divided into small squares. Palpation is performed sequentially in each square from top to bottom, stepping through each section (Fig. 5).

2. The spiral method, in which the breast is palpated in a spiral pattern of concentrically converging circles, starting from the armpit and moving toward the nipple. The finger pads make circular movements while moving toward the nipple (Fig. 6).

Step 6: Examination of the nipple

When inspecting the nipples, check for any changes in shape and color, retraction, weeping, ulceration, or cracks. It is necessary to palpate the nipple and the subareolar region, as a tumor can be missed beneath the nipple. This area is quite sensitive in women and may cause discomfort for some.

Finally, gently grasp the nipple between your thumb and index finger and press on it, noting the nature of any discharge or the absence thereof (Fig. 7).

If you believe that noticeable changes have occurred since your last examination, you should consult a doctor immediately. Of course, a woman should never attempt to diagnose herself, let alone prescribe treatment. Even a malignant tumor can be defeated if treatment is started at an early stage. Do not put off a doctor's visit; remember that your life may depend on it.

Dietary recommendations.

Nutrition is a vital biological factor upon which the functioning of all body systems largely depends. There is even an aphorism: "You are what you eat." Indeed, women should take a responsible approach to their health, maintaining energy and a positive psycho-emotional state to handle the vast number of daily tasks they face. A sensible attitude toward your environment will help reduce the risk of breast disease, including through the careful selection of your food. The recommendations below are suggested to reduce the risk of breast disease, including cancer.

1. Avoid excess weight. To achieve and maintain a normal weight, limit your daily calorie intake and eat smaller, more frequent meals. Physical activity is a must every day, with gymnastics or workouts at least half an hour three to four times a week.

2. Reduce total fat intake to 30% of total calories. Limit saturated fat intake by reducing portions of meat, eggs, cheese, and other animal products.

3. Include at least 5 portions of diverse fresh fruits and green and yellow vegetables in your daily diet.

4. Consume more high-fiber foods, such as whole grains, legumes, fruits, and vegetables.

5. If you consume alcoholic beverages, limit your intake to 150 g of wine, 350 g of beer, or no more than 45 g of spirits per day.

6. Minimize the consumption of smoked and salted foods, as well as foods processed with nitrites.

The principles to follow to achieve the goal of maintaining health in the simplest way are straightforward. In short, they can be stated as follows:

1. Introduce dietary changes gradually by reducing portion sizes.

2. Eat more fruits and vegetables.

3. Try cooking new recipes.

4. Learn the ingredients of the foods you eat.

5. Keep count: monitor what you eat.

6. Consume an adequate amount of vegetable and fruit fiber.

7. Find substitutes for high-fat foods.

Principle No. 1: Introduce dietary changes gradually.

The main rule for ensuring lasting dietary changes is to keep things simple and make changes step by step. This process of adapting to a new diet can be compared to gradually adding less salt to your food or less sugar to your coffee. Of course, at first, you notice the difference and probably don't like it. But eventually, you will come to consider this new flavor "normal." In fact, you may miss the old-fashioned taste of fatty foods when you begin to gradually eliminate them from your diet, but this craving will not last long and will be compensated for by becoming leaner and healthier.

Most doctors and researchers agree: if changes happen slowly, there is a better chance they will become a permanent part of a person's life. For example, it will do little good for you and your family to completely eliminate cream, butter, or cheese from your diet if you are not ready for a lifestyle change. That would be a pointless and overly drastic disruption. Everything in moderation.

How do you start eating healthier? The answer is: take small steps along the way. Introduce small amounts of new vegetables into soups, stews, salads, and stir-fries. And once you get used to this new taste, you can gradually increase the amount of these ingredients in your diet each time.

Principle No. 2: Eat more fruits and vegetables.

Every woman should strive to include five, and preferably nine, servings of fruits and vegetables daily. As many women have found, you can eat more of these protective foods without gaining weight. So, what exactly is a serving? Let's look at what experts recommend based on the average amount typically eaten at one time.

A serving of fruits and vegetables:

• 1 medium-sized fresh fruit

• 3/4 cup or about 170 g of 100% juice (e.g., tomato or orange);

• 1 cup of raw leafy vegetables;

• 1/2 cup of diced or cooked fruits;

• 1/4 cup of dried fruit.

Here are a few ways you can prepare 5–9 servings for yourself every day. Each serving of fruits and vegetables is rich in its own unique set of biochemicals and has the potential to reduce the risk of breast disease. Most of these plant compounds are vital if we want to stay healthy. Our bodies are unable to produce significant amounts of these chemicals. To have them in sufficient quantities, we must ensure a wide variety of plant-based foods in our diet.

Here are a few examples:

Breakfast. A serving may consist of:

• 1 cup of orange juice;

• 1/2 cup of sliced bananas, strawberries, or blueberries with cereal;

• a few pieces of dried apricots or 60 g of raisins;

• 1/2 grapefruit or another fruit.

If you usually rush out of the house without breakfast, you need to break this habit gradually. Studies show that those who skip breakfast usually make up for the missed calories later in the day by bingeing on high-fat foods. You need to find time in your schedule for your daily 5–9 servings of fruits and vegetables.

Snack (any time of day). A serving may consist of fruit—such as a small bunch of grapes, an apple, a pear, an orange, or a tangerine. Try carrying a small bag of raisins or 100 g of carrot sticks with you to work. This amount of fruits and vegetables can count as a serving. Or can you double the portion sometimes? If you feel like it, eat an orange or an apple. This adds only a few calories, which is nothing compared to eating two pies or two slices of fatback.

Lunch. This is a great time to have a serving of fruits and vegetables. Make it a rule to have a green salad or a fresh cabbage, carrot, and onion salad with lunch. Make a fresh vegetable salad with sliced red radishes, tomatoes, cucumbers, and julienned red, green, or yellow bell peppers. You can serve hot vegetables in any combination; for example, try stewing zucchini, corn, and tomatoes with basil. You can add various spices, herbs, fat-free dressings, and condiments to enhance the flavor of the vegetables.

Desserts. Add fresh fruit to fat-free yogurt or kefir. You can make any combination of fresh fruits mixed with a small amount of fruit juice. Prepare this fruit salad half an hour before lunch.

Juices. Any attempt to extract only the juice from a combination of fruits and/or vegetables usually leads to a significant loss of nutrients and biochemicals. Considering that plant foods possess health-promoting properties, such a loss of fiber and biochemicals is undesirable. Obviously, it is preferable to drink juices with pulp. The absence of nutritious vegetable or fruit pulp, valuable fiber, and biochemicals deprives fruits and vegetables of their value.

Principle No. 3: Try cooking new recipes.

The first step in discovering new recipes and subsequently incorporating them into your lifestyle is to understand the difference between relatively healthy and unhealthy foods. Generally, the more butter, cream, or vegetable oil a recipe requires, the more likely it is that fats constitute the bulk of the calories.

Most cookbooks report the grams of fat contained in a single serving of a dish. Make it a rule to always find this information. Naturally, the lower the total fat content, the better. In recipes for a cancer-risk-reduction diet, vegetables, fruits, and grains should occupy a significant place, while meat should take up a relatively small one.

There is no need to sacrifice pleasure for good health. Food is one of life's true joys. No one wants to feel deprived or eat food that tastes like cardboard. In most vegetable-based recipes, you can easily substitute ingredients if, for example, you dislike a certain type of plant food.

Principle No. 4: Consume the right amount of fiber.

Fiber is much more than just vegetables passing undigested through the intestines. It is an active mass that eliminates active estrogen and other harmful substances from our bodies. Consuming vitamins and mineral salts may not yield the desired effect if you eat more than 35 g of fiber per day. What does consuming this amount of fiber daily mean? To answer this question, it is necessary to determine which foods contain fiber.

A few examples of high-fiber foods

If you increase your intake of fruits, vegetables, and grains, your fiber intake will also increase. For example, 5–9 daily servings of any fruits and vegetables will add several grams of fiber to your diet. In fact, any inclusion of bran bread or beans in your daily diet will easily raise your daily fiber intake to the required level of 25–30 g. However, you must be careful. It is especially important to introduce fiber into your diet gradually. Excess fiber is often combined with intestinal gas production, leading to bloating or indigestion. Constipation may also sometimes occur, especially if high-fiber foods are washed down with an inadequate amount of fluid. However, there is no need to worry. The intestinal bacteria responsible for these side effects gradually adapt to the increased amount of fiber, and the unpleasant symptoms will soon decrease or disappear entirely.

Principle No. 5: Find substitutes for fatty foods.

The substitution principle can be successfully applied in many areas. Here are some examples.

Meat. Replace meat-based dishes with vegetable-based ones, or simply reduce the amount of meat in recipes. Always choose lean cuts of meat or trim visible fat. Avoid all fried foods.

Dairy products. Whenever possible, avoid whole milk products, opting for skim or 1% fat dairy products.

Vegetables. In many recipes, fat-containing ingredients can be replaced with lightly stewed or raw vegetables. They should not be overcooked or stewed with a large amount of fat.

As already mentioned, your diet is the cornerstone of the overall strategy to reduce the risk of breast diseases, including breast cancer. No other approach offers the same benefits as self-monitoring of recommended changes. These changes are simple and undemanding. You can change your diet today to prevent not only breast cancer but also other types of cancer. Dietary changes can protect your entire family from this disease.

Physical activity recommendations

Physicians have long noted a link between being overweight and an increased risk of developing breast cancer. Scientists have conducted a series of experiments that convincingly show physical exercise reduces the risk of breast cancer, and the higher the physical activity, the stronger this correlation is. Physicians have long known that physical activity acts as a deterrent to the development of breast cancer in women, but for a long time it remained unclear how strong this link is and how long the effect of exercise lasts. The experiment showed that physical activity, even at moderate loads, begins to affect the prevention of breast cancer development fairly quickly. Nevertheless, according to researchers, the disease risk decreases in direct proportion to how often and how much a woman exercises. The most physically active women showed a 20–25% reduction in breast cancer risk compared to the least active ones.

How should you prepare for workouts?

It is important to choose appropriate underwear for workouts. It should be comfortable, not compress the mammary glands, and not chafe the skin. It is best to buy underwear by trying it on to see if it will be comfortable to train in. Despite the fact that the link between underwear type and breast cancer risk has not been established, an improperly fitted bra can cause certain health problems. For example, excessive compression can provoke mastopathy, and straps that are too narrow will provide poor support for large breasts, resulting in severe back pain.

What sport to choose and how long to train?

This is not about high-intensity loads, such as weightlifting or ultra-long-distance running. Experts advise spending about 150–300 minutes a week on sports—this can be walking, dancing, swimming, or yoga. Physical activity can also include things not classically considered sports, such as walking in the park, walking the dog, gardening, and even vigorous house cleaning. You don't have to "spend" your entire workout allowance at once; you can exercise a little bit every day. This, by the way, will help reduce the likelihood of oncological diseases in general. From a breast health perspective, sports that do not involve impacts (e.g., boxing) and strong compression of the glands are suitable. Although jolts do not provoke malignant tumors in breast tissue, such injuries can lead to the development of long-lasting, often painful lumps. It is better to prefer pilates, stretching, or yoga. Aerobic and strength exercises are also suitable, for which it is best to consult a trainer or sports physician to help determine the appropriate load.

How to prepare for a prolactin blood test

1. The prolactin level is determined by a blood test taken from a vein in the morning on an empty stomach, but at least 3 hours after waking up.

2. Women are advised to take the test in the first phase of the menstrual cycle (on days 5–7). Gynecological examination and breast palpation are excluded prior to blood collection. Also, be careful with your breasts before the prolactin test—avoid injuring them.

3. The day before the test, you must abstain from sexual intercourse, visiting saunas or bathhouses, and consuming alcohol.

4. It is not recommended to take the prolactin test after a stressful situation. Therefore, in the event of psychological stress of any nature, postpone the prolactin test for at least 3–4 days.

5. It is recommended to avoid smoking for one hour before the test and to remain in a state of rest for about 15 minutes before blood collection.

6. Physical activity must be excluded the day before the test and on the day of the blood draw.

7. If you are taking any medications, you MUST inform the doctor who ordered the prolactin test. There are a number of medications that increase blood prolactin levels (hormonal contraceptives, antiemetics, most neuroleptics and tricyclic antidepressants, etc.).

It is very important to follow all guidelines when preparing for a prolactin level test. Otherwise, improper preparation for blood collection may lead to falsely elevated prolactin results, which can mislead your attending physician.

Appendix G. Assessment Scales, Questionnaires, and Other Evaluation Tools

Table 4. Classification of examination results according to the BI-RADS system and recommended management [American College of Radiology (ACR). ACR-BI-RADS®--5th Edition. ACR Breast Imaging Reporting and Data System, Breast Imaging Atlas; BI-RADS. Reston, VA: American College of Radiology; 2014].

⃰cumulative breast cancer risk is calculated using a computer program based on the GAIL model (NCCN, 2017) (available at https://www.cancer.gov/bcrisktool/Default.aspx)

Table specifications:

Russian title: Classification of examination results according to the BI-RADS system and recommended management.

Source: American College of Radiology (ACR). ACR-BI-RADS®--5th Edition. ACR Breast Imaging Reporting and Data System, Breast Imaging Atlas; BI-RADS. Reston, VA: American College of Radiology; 2014.

Type (underline):

- rating scale

Content (template): The table consists of 3 columns: the first column contains the examination results according to the BI-RADS system, the 2nd column contains the probability of breast cancer, and the 3rd column contains the management tactics depending on the examination results (with 3 sub-items: ultrasound, mammography, MRI).

Key (interpretation): Allows determining patient management tactics based on examination results according to the BI-RADS system.

Explanations: The classification of examination results according to the BI-RADS system and recommended management are presented.