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Simple Summary: Germline mutation rates and spectra across three cohorts of Chinese patients: a high-risk breast cancer cohort, an unselected breast cancer cohort, and a benign breast lesion cohort were compared. The high-risk cohort had the highest mutation rate at 11.9%, while the unselected cancer and benign lesion cohorts had rates of 6.5% and 8.1%, respectively. Notably, 29.3% of the unselected breast cancer patients met genetic testing criteria, and this subgroup had a mutation rate similar to the high-risk cohort. High-penetrance gene mutations were only found in the high-risk and unselected cancer cohorts. Unexpectedly, a 2% mutation rate was observed in the benign lesion cohort. These findings highlight the need for broader genetic testing of all breast cancer patients, not just those deemed high-risk, to identify more individuals harboring clinically relevant germline mutations. Mutation study for high-risk breast and ovarian cancer (HBOC) has been extensively studied in patients of different ethnicities. Here we compared the germline mutation rate and mutation spectrum of patients (n = 4341) with benign breast diseases or breast cancers, with and without other risk factors. Three cohorts of Chinese patients were recruited. The first cohort, high-risk cohort (HR, n = 3935) included high-risk breast cancer patients fulfilling high-risk HBOC criteria and who are recruited at our genetics clinic. The second cohort, unselected cancer cohort (CC, n = 307) was from general recruitment of patients with breast cancer at breast surgery clinics. The third cohort, benign breast lesion cohort (NC, n = 99) comprised 99 patients with benign breast diseases such as fibroadenoma, fibroadenomatoid hyperplasia, and intraductal papilloma. Thirty HBOC related genes were sequenced on the above-mentioned patient cohorts. The germline mutation rates of HR, CC, and NC cohort were 11.9%, 6.5%, and 8.1%, respectively. In the CC cohort, 29.3% (90/307) of patients fulfilled the National Comprehensive Cancer Network (NCCN) high-risk genetic test criteria 2022 v.2. The mutation rate for this group of patients was 11.1%, similar to that of the HR cohort, while the mutation rate for those not fulfilling testing criteria was 4.6%, like that of the NC cohort. High penetrance genes (BRCA1/2, CDH1, PALB2, PTEN, and TP53) mutations were only found in the HR (10.6%) and CC (3.3%) cohorts but were not found in the NC cohort. ATM, BRIP1, RAD51C, and RAD51D mutations were identified in all cohorts. RAD51C and RAD51D mutations showed conflicting penetrance. An unexpectedly high mutation rate of total 2% was found in the NC cohort but it was only 0.3% and 0.5% in the HR cohort and CC cohort, respectively. Our results show a clinical need to enhance genetic testing of unselected breast cancer patients to identify the high-risk patients. [ABSTRACT FROM AUTHOR]

Background: Mastalgia, or breast pain (or mastodynia), is globally a common symptom experienced by women of reproductive age; treatment for these conditions is not yet standardized. Most of the drugs used for mastalgia are expensive and have side effects, so, the aim of this study was to compare different agents for reducing mastalgia in fibrocystic disease of women in outpatient clinics at Zagazig University. Methods: this prospective random comparative study has been carried out in Zagazig University out patients clinics specifically in breast clinic subjects in period between May-2019 to March -2020 on 68 patients enrolled with 3 months period of follow up. Results: In EPO group 30% of patients showed complete resolution and 61% showed partial response. The danazol group received, 58% of patients showed complete resolution and 41% showed partial improvement. In Tamoxifen group 47% of patients showed complete resolution while 52 % showed partial improvement. In the cabergoline group 14% of patient showed complete resolution and 42% showed partial improvement. Conclusions: Evening prime rose oil is effective in reducing the severity of mastalgia with minor tolerable side effects and should be used as first line of management. Danazol is the most effective agent but its side effects make it less favorable agent. Tamoxifen is the second most effective agent among the other agents with reversible tolerable side effects. Cabergoline is significantly decrease breast pain especially cyclic mastalgia, with notable side effects. [ABSTRACT FROM AUTHOR]

Benign breast diseases (BBDs) are the most common group of diseases among women that negatively affect their quality of life. In fact, these pathological conditions are diagnosed at least 10 times more often than breast cancer. Up to 30% of women with BBDs will need treatment at some point in their lives. A triple assessment which is performed using imaging methods of clinical examination (ultrasound examination, mammography) and histopathological examination after a puncture biopsy during the initial consultation allows to exclude breast cancer in the majority of patients. ` The main clinical manifestation of BBDs is mastalgia. In recent years, a variety of natural herbal remedies have played a significant role in the symptom-modifying therapy of mastalgia. The objective: to study the possibility of using an innovative phytocomplex as a symptom-modifying agent in the presence of BBDs, which is manifested by mastalgia. Materials and methods. Clinical monitoring of 60 patients between the ages of 22 and 46 years old with BBDs of various genesis was carried out. The study group included 30 women who used a phytocomplex containing 3,3`-diindolylmethane (200 mg), vitex extract (100 mg), epigallocatechin (45 mg), broccoli extract (0.4 mg), 1 tablet twice daily for 90 days. The reference group included 30 women who used a dietary supplement with indole-3-carbinol (200 mg) according to a similar scheme. Assessment of clinical symptoms of BBDs, measurement of interleukin-6 level in blood serum, fine-needle aspiration biopsy of pathological foci and immunocytochemical analysis of biopsies, assessment of patients’ quality of life were performed before and after treatment Results. The innovative phytocomplex (diindolylmethane – DIM, Agni casti fructus) compared to the indole-3-carbinol monopreparation demonstrated a higher efficiency in creating conditions for the elimination of clinical manifestations of BBDs: discomfort, swelling, pain at rest and during palpation. A pronounced regression of clinical symptoms was observed in the study group: a decreased frequency of patients with chest discomfort from 100 to 36.7%, a decrease in pain at rest and during pressure – from 53.3 to 13.3% and from 33.3 to 13.3%, respectively, swelling – from 46.7 to 16.7%. The index of the quality of life of patients, which was determined by the sum of the scores of the questionnaire filled out by the patients themselves, showed a more pronounced tendency to increase in the study group. Conclusions. The innovative phytocomplex can be recommended as a preparation for phytotherapeutic correction in order to help reduce the intensity and eliminate mastalgia and other symptoms of BBDs. [ABSTRACT FROM AUTHOR]

Non-malignant breast diseases (NMBD) may increase the risk of developing a malignant neoplasm. Therefore, it seems relevant to search for criteria for cell malignancy in NMBD. Aim of the study was to investigate the relationship between expression of proliferation and epithelial-mesenchymal transition (EMT) markers and histidine-rich glycoprotein (HRG) mRNA in breast diseases. Material and methods. In breast biopsy specimens of 37 patients with invasive carcinoma of a non-specific type (ICNT) and 17 patients with NMBD expression of proliferation markers (Ki-67, cyclin D1 (CCND1)) and EMT markers (E-cadherin (CDH1), type II collagen (CII) and β1-integrin (CD29)) was determined immunohistochemically. HRG mRNA expression was estimated using real time PCR. Results. HRG mRNA expression was detected in 91.9 % cases (34 of 37) in ICNT, 82.4 % (14 of 17) in NMBD and in the latter case was inversely related to the expression of CDH1, CD29 and Ki-67. A direct relationship has been established between the presence of Ki-67 and CCND1, CII, between CCND1 and CD29 in NMBD. In patients with ICNT, a direct correlation was found between the HRG mRNA expression and the presence of CII, and an inverse correlation between the number of cells containing CII and CD29. It was found that in ICNT and NMBD with the presence of HRG mRNA expression, the CDH1 expression is less than in its absence. Conclusions. Indicators of HRG mRNA expression in NMBD, combined with the assessment of proliferation and EMT markers, can be useful in developing criteria for cell malignancy in benign breast diseases.

Background and Aims: Standard treatment regimens for fibrocystic breast disease (FBD) do not provide a permanent cure and have undesirable side effects. This study aims to investigate the therapeutic potential of different honey and propolis, as well as some important polyphenols, on breast epithelial cells (MCF-10A). Materials and Methods: The effects of five honey, two propolis extracts and seven polyphenol samples on the cell viability were assessed theWST-1 assay. Content analysis of the propolis samples was performed using high performance liquid chromatography (HPLC). Results: Chestnut and cedar honey had antiproliferative effects on MCF-10A cells at all doses (1-10 µg/mL), as well as pine honey at the highest dose. However, multifloral honey had no similar effect. Chinese propolis had significant antiproliferative effects on MCF-10A cells at doses of 50-250 µg/mL and on the human periodontal ligament (hPDL) control cells at a dose of 5 µg/mL. Türkiye propolis only had an antiproliferative effect on MCF-10A cells at the highest dose (p = 0.0013). Higher levels of ferulic acid, kaempferol, caffeic acid, pinocembrin and quercetin were detected in Türkiye propolis, while Chinese propolis was rich in pinostrobin. Ferulic acid, pinostrobin and galangin showed antiproliferative properties on MCF-10A cells (p < 0.0001), whereas the remaining four polyphenols had no significant effect on cell viability (p > 0.05). Conclusion: The findings of the study highlight the antiproliferative effects of pinostrobin, ferulic acid and galangin on MCF-10A cells and has also confirmed the antiproliferative effects of honey and propolis samples to be due to their polyphenolic properties. Therefore, this study suggests that polyphenolic substances may have both preventive and therapeutic potential in FBD. [ABSTRACT FROM AUTHOR]

In the Ukrainian-language medical literature there is very little correct information about benign changes in the mammary glands, publications mostly date from the eighties of the last century – the beginning of the current one. This article is a review of modern scientific domestic and foreign sources, which are devoted to the problem of benign changes of the mammary glands and recommendations for their treatment, which are based on the evidence base. The article analyzes 40 publications, mostly by foreign scientists. The prevalence of non-neoplastic changes in the mammary glands, which in most cases in Ukraine are interpreted as “mastopathy”, require a revision of the concept of the problem. Non-neoplastic changes in the mammary glands are most often represented by different variants of the so-called aberration of normal development and involution, which are not pathological, but, according to some signs, are those that are close to pathology, but are considered as a variant of the norm. The diagnosis should be changed to a specified variant of the aberration. The article raises problems about the difficulty of distinguishing between normal and pathological condition, considers the main positions of diagnosis and treatment of fibrocystic changes of the mammary glands, gynecological diseases that are accompanied by this pathology, and genetic prerequisites. Detailed characteristics of the main components of herbal preparations used for the treatment of mammary gland hyperplasia are also presented. Changing the interpretation of the term “fibrocystic mastopathy” to the term “fibro-cystic changes” helps to revise views on the need for therapeutic measures, since the diagnosis “mastopathy” automatically prompts therapy, while the term “changes” primarily indicates the need drawing attention to the problem, correction of lifestyle, nutrition, etc., dynamic supervision and only for diagnosing fibrocystic disease – resolving the issue of treatment. [ABSTRACT FROM AUTHOR]

Fibrocystic breast disease is the most common benign breast disease in women, and it is necessary to investigate the most effective treatment method to reduce its symptoms. Therefore, the study was conducted to investigate the effect of melatonin supplementation on clinical symptoms and paraclinical outcomes in women diagnosed with fibrocystic breast disease. Investigating the Effects of melatonin supplementation on clinical symptoms and paraclinical outcomes in women diagnosed with fibrocystic breast disease. The present study is a controlled intervention-placebo treatment conducted on women suffering from fibrocystic breast disease aged 18-40. This interventional study was conducted on 66 patients (33 in the intervention group and 33 in the control group). Melatonin supplement of 3 mg was administered to the intervention group and a placebo to the control group for 12 weeks. Patient information, symptoms, and paraclinical outcomes were recorded at the beginning of the study before the intervention and 12 weeks after the intervention. After collecting the data, we analyzed it using SPSS version 16 software and appropriate statistical tests. The findings of this study showed that melatonin administration in patients with fibrocystic breast disease reduced anxiety, depression, improved sleep quality, increased TAC (Total Antioxidant Capacity), and decreased MDA (Malondialdehyde). However, both study groups did not have statistically significant differences in the average pain and hs-CRP before and after the intervention. According to the findings of the study and the identification of the positive effect of melatonin on laboratory indicators and symptoms in patients with fibrocystic breast disease, it is recommended to prescribe melatonin in addition to standard treatment to witness a better and faster recovery, and in this way, the quality of life of patients can be increased.

Diabetic mastopathy is a rare fibro-inflammatory breast disease that closely mimics breast carcinoma. The disease predominantly affects insulin-dependent diabetics, and the etiology is still unclear. A proper physical examination, imaging, and core-needle biopsy usually lead to a diagnosis. Management is conservative and revolves around counseling the patient to allay fears and regular follow-up. In this review, we highlight the recent information on diabetic mastopathy with emphasis on historical background, epidemiology, etiopathogenesis, diagnostic approaches, and treatment choices. [ABSTRACT FROM AUTHOR]

Fibrocystic breast disease is the most common benign breast disease in women, and it is necessary to investigate the most effective treatment method to reduce its symptoms. Therefore, the study was conducted to investigate the effect of melatonin supplementation on clinical symptoms and paraclinical outcomes in women diagnosed with fibrocystic breast disease. Investigating the Effects of melatonin supplementation on clinical symptoms and paraclinical outcomes in women diagnosed with fibrocystic breast disease. The present study is a controlled intervention-placebo treatment conducted on women suffering from fibrocystic breast disease aged 18-40. This interventional study was conducted on 66 patients (33 in the intervention group and 33 in the control group). Melatonin supplement of 3 mg was administered to the intervention group and a placebo to the control group for 12 weeks. Patient information, symptoms, and paraclinical outcomes were recorded at the beginning of the study before the intervention and 12 weeks after the intervention. After collecting the data, we analyzed it using SPSS version 16 software and appropriate statistical tests. The findings of this study showed that melatonin administration in patients with fibrocystic breast disease reduced anxiety, depression, improved sleep quality, increased TAC (Total Antioxidant Capacity), and decreased MDA (Malondialdehyde). However, both study groups did not have statistically significant differences in the average pain and hs-CRP before and after the intervention. According to the findings of the study and the identification of the positive effect of melatonin on laboratory indicators and symptoms in patients with fibrocystic breast disease, it is recommended to prescribe melatonin in addition to standard treatment to witness a better and faster recovery, and in this way, the quality of life of patients can be increased. [ABSTRACT FROM AUTHOR]

Background: Fibroadenosis, popularly termed aberrations of normal development and involution (ANDI), is by far the most common female breast presentation to a surgeon. ANDI accounts for the most common breast lumps in women

In 1984, Rosen and Scott1 first described cystic hypersecretory breast lesions. This entity has a spectrum of histologically distinct lesions ranging from cystic hypersecretory hyperplasia (CHH), CHH with atypia, cystic hypersecretory carcinoma (CHC) in situ, and invasive CHC. CHH’s macroscopic examination is distinct, which shows numerous cysts of varying sizes containing gelatinous material. The cyst lining epithelium, in CHH, consists of a single layer of flattened, columnar, or cuboidal epithelium without cytological atypia. Atypical CHH shows epithelial crowding, enlarged nuclei with loss of nuclear polarity, nuclear hyperchromasia, and mitoses. The in-situ carcinoma shows intermediate to high nuclear-grade lesions with micropapillary architecture.2 Most reported cases are of in-situ CHC. Invasive CHC shows solid nests of poorly differentiated cells with no secretory characteristics.3 This rare breast cancer subtype is not included in the 5th edition of the WHO breast tumor classification. The figure above shows the macro and microscopic examination of a lesion from a 58-year-old lady who presented with a lump in her right breast for six months. Imaging revealed a large solid tumor in the upper inner quadrant of the breast. A right mastectomy was performed for this patient. On gross inspection, the skin and nipple areola complex were unremarkable. The cut surface of the breast showed two different lesions. The first was a large, solid, well-demarcated whitish mass of 8.5x6.5x4.0 cm (Figure 1A). Additionally, an ill-defined lesion was identified in the adjacent breast parenchyma composed of clusters of multiple variable-sized yellowish nodules, ranging in size from few millimetres to 1.0 cm (Figure 1B). Figure 1A – gross examination from the first lesion reveals large, well-defined solid, greyish white firm tumour of 8.5x6.5x4.0 cm (scale bar= 3 cm); B – gross examination from the second lesion shows multiple variable-sized yellowish-white nodules of 1.0 mm to 10.0 mm (scale bar 1 cm); C – photomicrograph from the solid tumour shows a cellular invasive tumour arranged in solid trabecular and sheet-like architecture with marked nuclear anaplasia and focal necrosis (H&E 100X); D – photomicrograph from the second lesion shows multiple cystically dilated spaces lined by cuboidal epithelium and filled with homogeneous eosinophilic colloid-like material with few macrophages, indicating CHH (H&E, 40X); E – photomicrograph shows CHH with nuclear atypia and epithelial multilayering (H&E 400X).: The microscopic examination of the large solid mass showed a high-grade pleomorphic invasive tumor arranged in sheets and trabeculae of cells with marked nuclear pleomorphism (Figure 1C). Mitotic figures were frequent, and a focal area of necrosis was also identified. However, no microcystic or secretory changes could be identified even on examining multiple sections. Microscopic examination from the ill-defined nodular lesions showed numerous dilated cysts lined by cuboidal to columnar epithelial cells containing colloid-like eosinophilic cyst content admixed with a few foamy macrophages (Figure 1D). Occasional cysts showed nuclear atypia and epithelial multilayering (Figure 1E). However, definite in-situ carcinoma was not detected. IHC for hormone markers revealed ER and PR negative status with strong, complete membranous Her-2-neu expression in the tumor cells. Given the high-grade pleomorphic solid tumor con-existing with CHH and CHH with atypia, the invasive tumor was diagnosed as CHC. The diagnosis of CHH can be challenging on FNA and core needle biopsy specimens. Lesions like juvenile papillomatosis, fibrocystic change, columnar cell change with or without atypia, extravasation mucocele, mucinous carcinoma, secretory carcinoma, ‘clinging’ type DCIS, and metastatic thyroid carcinoma can mimic the morphology of CHH.4 Although CHH is considered a benign lesion, malignant transformation on long-term follow-up has been reported.2 Also, there is a chance of having an in-situ or high-grade invasive tumor component with CHH. Hence, a diagnosis of CHH should alert the physician about possible association with malignancy, and a wide local excision followed by thorough sampling should be performed to look for any invasive tumor.5 In conclusion, cystic hypersecretory lesions rarely encountered entities with a wide spectrum of lesions, from benign to overtly malignant. Pathologists should be well versed in the gross and microscopic features and consider the possible diagnostic pitfalls while dealing with this tumor. Although cystic hypersecretory carcinoma is not identified as a separate entity in the WHO 5th edition of breast tumor classification, associated CHH in the surrounding parenchyma indicates the invasive tumor as an invasive CHC. The available literature is limited; however, most cases of invasive CHC are high-grade solid tumors, as encountered in this case.

Context.--Inflammatory lesions of the breast are rare but not infrequently pose problems both clinically and morphologically, particularly on needle core biopsies. These lesions range from acute inflammatory conditions to chronic lymphoplasmacytic and lymphohistiocytic to granulomatous inflammatory diseases. Objective.--To provide a comprehensive overview of inflammatory lesions of the breast, with etiopathogenesis and clinical, radiologic, and pathologic features as well as differential diagnostic considerations, clinical management, and prognosis. Data Sources.--The existing literature in the English language, including original research articles and review articles describing inflammatory lesions of the breast. Conclusions.--Inflammatory lesions of the breast are characterized by a wide variety of clinical, radiologic, and morphologic features. The histopathologic differential diagnosis often includes a neoplastic process requiring ancillary studies and correlation with clinical and radiologic findings. Although most specimens display nonspecific findings precluding a definitive pathologic diagnosis, pathologists have a unique opportunity to play a crucial role in identifying key histologic features suggestive of certain entities, such as cystic neutrophilic granulomatous mastitis, immunoglobulin (Ig) G4 mastitis, or squamous metaplasia of lactiferous ducts, in the right clinical and radiologic context, and thereby guiding optimal and timely clinical management. The information presented herein will be helpful to practicing anatomic pathologists and pathology trainees in becoming more familiar with specific morphologic features and overcoming differential diagnostic challenges related to pathology reporting of inflammatory lesions of the breast. [ABSTRACT FROM AUTHOR]

Diabetic fibrous mastopathy (DFM) is a rare benign fibrotic disease of the breast that develops in patients with longstanding and often uncontrolled diabetes mellitus. Clinically, patients may present with an irregular, firm, palpable mass, which may be solitary or multiple, occurring in one or both breasts. Diabetic fibrous mastopathy occurs most often in premenopausal women with heterogeneously or extremely dense breasts; mammography may show focal asymmetry or, less often, a noncalcified mass with indistinct or obscured margins, but there are usually no discrete findings. On US, DFM may have marked hypoechogenicity and posterior shadowing secondary to extensive fibrosis. Diabetic fibrous mastopathy features on contrast-enhanced MRI are also nonspecific, with gradual persistent nonmass enhancement reported. Because the clinical presentation and US features of DFM overlap with those of breast cancer, histopathologic correlation is needed to confirm diagnosis and exclude malignancy. These findings include collagenous stroma often with keloidal features and chronic perilobular and perivascular inflammation. Histopathologic findings of lymphocytic lobulitis and perivascular inflammation are common to other autoimmune conditions. [ABSTRACT FROM AUTHOR]

Background: Fibroadenosis, popularly termed aberrations of normal development and involution (ANDI), is by far the most common female breast presentation to a surgeon. ANDI accounts for the most common breast lumps in women <30 years of age. Mastalgia, a significant spectrum of ANDI, is usually classified as (1) cyclical mastalgia (more common) and (2) non-cyclical mastalgia. Breast nodularity, the other spectrum of ANDI may either present as a predominant feature or coexist with mastalgia. Aims and Objectives: The aims of this study were to comparatively study ormeloxifene and evening primrose oil with respect to regression of fibroadenosis and mastalgia and evaluate their side effects. Materials and Methods: This prospective study was conducted in the Department of General Surgery of Calcutta National Medical College and Hospital, Kolkata from February 15th, 2021 to February 14th, 2022, after obtaining prior Institutional Ethical Committee Clearance. Two hundred and eighty patients were equally divided into two groups of 140 in each and screened for inclusion in this study. Results: At the start of treatment, Group A (Ormeloxifene) presented with a mean visual analog scale (VAS) score value of 5.71, while patients of Group B presented with a similar mean VAS score value of 5. Group B recorded a VAS score of 4.50 at the end of the 6th month, while Group A recorded a significant downhill slope of negligible mean VAS score value of 0.80 at the of the 6th month. In breast nodularity gradings too, Group A showed significant down staging of grades returning, 95% confidence interval at the end of 6th month as 1.144, while 2.280 was recorded for Group B. Conclusion: Benign breast disease is a common presenting problem in females of reproductive age. Ormeloxifene can be a better alternative to evening primrose oil in both cyclical and non-cyclical types of mastalgia. Larger trials are however required, to finally conclude on. [ABSTRACT FROM AUTHOR]

The objective: to study the state of the immune system in women with pathology of the mammary glands and infertility, and on the background of menstrual cycle disorders. Materials and methods. The research was performed in two stages. The first (1) stage included examination of women with infertility associated with anovulation who had breast pathology. These patients were divided into three groups: 1.1 group – 44 patients with diffuse fibrocystic breast disease (FBD), 1.2 group – 4 patients with fibroadenoma of the mammary glands, 1.3 group (control one) – 37 patients without pathological changes in the mammary glands. During the second (2) stage of the study, 110 women were examined: 2.1 group – 52 patients with regular menstruations and luteal phase insufficiency (LPI) and 2.2 group – 58 patients with anovulatory cycles. During two research stages, the immune status (CD3, CD4, CD8, immunoregulatory index (CD4/CD8), CD72, CD16, circulating immune complexes) and cytokine profile (IL-1, IL-2, IL-6, TNF-α, INF) in venous blood were determined. Differences were considered statistically significant at p<0.05. Results. A significant increase in the CD8 index was found in the group of patients with normal mammary glands (34.7±6.9 pg/ ml; p<0.05) and with a diffuse form of FBD (35.13±6.9 pg/ml; p<0.05) versus its normal level in the group of patients with fibroadenoma (26.5±15.9 pg/ml; p>0.05). During the analysis of the CD16 level, it was determined its significantly increased to 18.8±3.1 pg/ml (р<0.05) in patients with LPI and regular menstrual cycle and to 26.3±4.8 pg/ml (р< 0.05) – in patients with anovulation without LPI, the difference between the groups was significant. The level of CD16 was significantly higher in anovulatory menstrual cycle disorder without LPI compared to patients with menstrual cycle disorder and LPI. The concentration of TNF-α in patients with a regular menstrual cycle (998.1±166.3 pg/ml; p<0.05) and with an anovulatory cycle without LPI (1029.3±187.1 pg/ml; p<0.05) was significantly higher compared to normal values (778.5±64.0 pg/ml). The level of IL-2 was significantly lower than normal indices. Thus, in the group of women with LPI, this indicator was 17.13±2.85 pg/ml (р<0.05), and by anovulation without LPI – 16.84±3.07 pg/ml (р<0.05) versus normal parameter 22.29±0.81 pg/ml. Conclusions. In patients with diseases of the mammary glands and infertility associated with anovulation without LPI, a significant decrease in the activity of T2-helpers (IL-2) and an increase in the activity of T1-helpers (TNF-α) were determined in cases of anovulation without LPI compared with cases of luteal phase insufficiency. [ABSTRACT FROM AUTHOR]

Background: Breast pain is a very common complaint in women and it can negatively affect daily life. Breast pain treatment ranges from massage and simple pain relievers to psychotherapy sessions and use of drugs with serious side effects. One of the methods to prevent breast pain is to provide external breast support with the use of appropriate bra. This need is especially evident in female athletes. In our study, we aimed to investigate breast pain frequency and the effects of bra usage habits. Material and Methods: Aged 18 years and older premenopausal female athletes and volunteer women in the community were included in the study. Participation was ensured by an on-line survey consisting of 20 questions. Results: A total of 54 athletes and 191 women in control group were included in our study. Among the participants, breast pain complaints were found to be high in both athletes (61.11%) and the control group (69.63%). In total, breast pain was associated with the menstrual cycle mostly (95.03%). Having breast ultrasound previously and diagnosis of fibrocystic disease were significantly higher in patients with breast pain (p<0.05). Breast pain was less in the lean-normal weight group (p=0.035). Breast pain increased with exercise in 38.88% of athletes. Breast pain had a negative effect on exercise performance in 27.77% of athletes. The use of bra was more common all day long in the control group, on the other hand, the use of sports bra in daily life was more common in female athletes (p<0.05). Conclusion: Breast pain is an important public health problem in women. External breast support is important for breast pain control. It is important to choose a suitable bra for individual needs. [ABSTRACT FROM AUTHOR]

Background: Fibrocystic change (FCC) of the breast is one of the most common benign breast diseases commonly observed between 20-50 years, with a peak in the perimenopausal age group. Patients present with various symptoms such as lump in the breast, mastalgia (commonly related to the menstrual cycles) or nipple discharge. Materials and Methods: In our retrospective study, which included 172 patients, the imaging findings were observed by ultrasound and X-ray mammogram. Based on the Breast Imaging Reporting and Data System (BI-RADS) guidelines given by the American College of Radiology (ACR), our imaging findings were classified as BI-RADS 2 in benign lesions, an d complicated cysts were classified as probably benign - BI-RADS 3. Indeterminate findings were classified as suspicious lesions and BI-RADS 4a/b/c. Imaging and histopathological correlation was performed. Results: Ultrasound findings revealed diffuse/bilateral abnormalities with the most common finding being simple cysts followed in descending order by complicated cysts, clustered cysts, complex solid cystic masses, solid lesions, duct ectasia, and intraductal lesions. Mammogram showed dense (type C or D) fibro glandular pattern obscuring the lesions, followed by well-defined/partly obscured opacities. Simple cysts and complicated cysts showed predominant features of cyst formation on HPE. Atypical hyperplasia was seen in ductal and complex solid cystic mass lesions. Conclusion: It is essential for radiologists to be familiar with imaging and pathological findings of fibrocystic disease of the breast for further workup and management. [ABSTRACT FROM AUTHOR]

Abstract This meta-analysis aimed to determine the pooled association between polycystic ovary syndrome (PCOS), hypothyroidism, and fibrocystic breast changes. We searched important databases, including PubMed (Medline), Scopus, Web of Science, and Embase to retrieve all relevant studies published from 1990 to April 2021. The bias risk of selected articles was assessed based on the JBI checklist. Our search strategy yielded a total of 487 articles from the international databases. After screening their full-texts, 6 articles met the inclusion criteria and were considered for meta-analysis. The effect of PCOS on the incidence of fibrocystic breast changes was 2.49 (95% CI 1.85–3.34). Also, the effect of hypothyroidism on the incidence of fibrocystic breast changes was 1.90 (95% CI 0.92–3.93). The results showed that women with PCOS were at higher risks to develop fibrocystic breast changes.

Introduction. The article presents a comparative analysis of the treatment of patients with combined estrogen-dependent pathology of female reproductive system: fibrocystic mastopathy and endometrial hyperplasia without atypia. The experience of treatment with an indole-carbinol-containing drug as monotherapy while using a levonorgestrel-releasing intrauterine system is presented.Aim. To evaluate the clinical efficacy of indolecarbinol in the treatment of patients with combined estrogen-dependent pathology of the female reproductive system.Materials and methods. The authors studied the responses to the treatment of patients with fibrocystic mastopathy and simple endometrial hyperplasia (n = 65) with the indole-carbinol-containing drug at a dose of 400 mg once daily for 12 months. All patients were divided into two groups: Group I (n = 32) – women who refused hormone therapy (indole-carbinol monotherapy); Group II (n = 33) – the use of indole-carbinol while using the levonorgestrel-releasing intrauterine system. Diagnostic methods: clinical and laboratory examination, ultrasound examination of mammary glands and pelvic organs, mammography, nipple discharge cytology at baseline and 6 and 12 months after the start of therapy. Before study group assignment to treatment, all patients underwent hysteroscopy with endometrial biopsy and histological examination. Descriptive statistics were used to evaluate the data: p-values below 0.05 were considered statistically significant.Results and discussion. The presented experience in treating women with combined pathology of the female reproductive system (fibrocystic mastopathy and endometrial hyperplasia without atypia) with the indole-carbinol-containing drug showed high clinical efficacy in mastopathy (relief of mastodynia (83.0 ± 1.6%), improvement of the ultrasound view of BI-RADS (66.1 ± 1.4%), reductions in mammographic density (66.1 ± 2.1%, p < 0.05)), high tolerability and satisfactory compliance. This drug combined with hormone therapy is recommended for the treatment of endometrial hyperplasia.Сonclusion. The use of indole-carbinol in the treatment of benign hyperplastic processes in mammary glands and endometrial hyperplasia is pathogenetically substantiated and shows high clinical efficacy

Obesity, a cause of subclinical inflammation, is a risk factor for the development of postmenopausal breast cancer and is associated with poorer cancer outcomes. Docosahexaenoic acid (DHA), an omega-3 fatty acid, possesses anti-inflammatory properties. We hypothesized that treatment with DHA would reduce the expression of proinflammatory genes and aromatase, the rate-limiting enzyme for estrogen biosynthesis, in benign breast tissue of overweight/obese women. A randomized, placebo-controlled, double-blind phase II study of DHA given for 12 weeks to overweight/obese women with a history of stage I-III breast cancer, DCIS/LCIS, Paget's disease, or proliferative benign breast disease was carried out. In this placebo controlled trial, the primary objective was to determine whether DHA (1,000 mg by mouth twice daily) reduced breast tissue levels of TNFα. Secondary objectives included evaluation of the effect of DHA on breast tissue levels of COX-2, IL1β, aromatase, white adipose tissue inflammation, and gene expression by RNA-seq. Red blood cell fatty acid levels were measured to assess compliance. From July 2013 to November 2015, 64 participants were randomized and treated on trial (32 women per arm). Increased levels of omega-3 fatty acids in red blood cells were detected following treatment with DHA (P < 0.001) but not placebo. Treatment with DHA did not alter levels of TNFα (P = 0.71), or other biomarkers including the transcriptome in breast samples. Treatment with DHA was overall well-tolerated. Although compliance was confirmed, we did not observe changes in the levels of prespecified biomarkers in the breast after treatment with DHA when compared with placebo. Cancer Prev Res; 11(4); 203-14. ©2018 AACRSee related editorial by Fabian and Kimler, p. 187.

Abstract Background Fibroadenoma (FA) is the most common benign solid breast mass in women, with no definite method of management. Because fibroadenoma is dependent on female sex hormones and comprises hypertrophic changes at cellular levels, we investigated the effects of metformin (MF), a safe hypoglycemic agent with anti-estrogenic and anti-proliferative properties, in the management of fibroadenoma. Methods In this randomized clinical trial study, eligible women with fibroadenomas were assigned randomly to the metformin (1000 mg daily for six months) or the placebo group. Breast physical and ultrasound exam was performed before and after the intervention, and the changes in the size of fibroadenomas were compared in the two groups. Results Overall, 83 patients in the treatment, and 92 in the placebo group completed the study. A statistically significant difference in changing size between the two groups was observed only in the smallest mass. In the largest FAs, the rate of size reduction was higher in the treatment group (60.2 % vs. 43.5 %); while a higher rate of enlargement was observed in the placebo group (38 % vs. 20.5 %). In the smallest FAs, the rate of the masses that got smaller or remained stable was about 90 % in the treatment group and 50 % in the placebo group. We categorized size changes of FAs into

Background/Aim: Fibrocystic breast disease (FBD) is the most frequent benign breast disease. Increased estrogen and decreased progesterone concentrations are thought to be involved in the pathogenesis of FBD. But there is insufficient data on benign breast disease and endometrial pathology. This study evaluates the association between FBD and endometrial pathology in women complaining of abnormal uterine bleeding. Methods: This study was designed as a retrospective case-control study. The medical records of women who had endometrial sampling for abnormal uterine bleeding between 2018 and 2020 were evaluated. Patients with FBD were included in the study group, while the first patients who had endometrial sampling after patients with FBD and without breast disease were recruited as the control group. Demographic, laboratory data, and endometrial histopathological results were obtained from hospital records and compared between the groups. Results: In total, 250 women (106 women with FBD and 144 without breast disease) were recruited for the study. There was no statistically significant difference in mean age, gravidity, parity, and BMI between FBD and control groups. Endometrial hyperplasia without atypia (19.8% versus 10.5%, respectively, P = 0.037) and endometrial polyp (12.2% versus 4.8%, respectively, P = 0.033) were found to be significantly increased in patients with FBD than women without the disease. There was no statistically significant difference in terms of other histopathological results between the groups. Conclusion: Evaluation of the endometrium for abnormal uterine bleeding is essential for early diagnosis and treatment of endometrial pathology, especially for endometrial cancer. In this study, we found that women with FBD have an increased risk for endometrial hyperplasia and endometrial polyp. As endometrial hyperplasia is a precursor lesion for endometrial cancer, clinicians should pay attention to and investigate menstrual bleeding abnormalities of women with FBD and should not delay the evaluation of the endometrium. [ABSTRACT FROM AUTHOR]

* Context.--Associations between granulomatous lobular mastitis (GLM) and Corynebacterium kroppenstedtii have been reported since 2002, but large-scale studies to assess the actual prevalence of this bacterium in GLM have not been performed. Objective.--To assess the prevalence of C kroppenstedtii in GLM using real-time polymerase chain reaction and Sanger sequencing. Design.--We analyzed formalin-fixed, paraffin-embedded tissues from 67 cases of GLM by sequential DNA amplification and sequencing to assess the rate of C kroppenstedtii detection in GLM. A retrospective analysis including patient demographics, history of pregnancy and lactation, clinical signs and symptoms, radiographic findings, histologic pattern, Gram stain results, and microbial cultures was performed on 67 cases of GLM. In addition, 10 cases of nongranulomatous breast abscess were included as controls. Results.--C kroppenstedtii 16S rRNA SYBR real-time polymerase chain reaction was positive on formalin-fixed, paraffin-embedded tissues from 46 of 67 (68.7%) GLM cases, while all control cases were negative. Among the positive cases, the majority showed features of cystic neutrophilic granulomatous mastitis. Conclusions.--C kroppenstedtii was highly prevalent in GLM cases and was not found to be associated with nongranulomatous breast abscess in our study (P < .001). [ABSTRACT FROM AUTHOR]

Rationale and Objectives: According to the Breast Imaging and Reporting Data System (BI-RADS), one of the main limitations of MRI is diagnosing the non-mass enhancement (NME). The NME lesion is challenging since it is unique to the MRI lexicon. This study aims to report our experience with NME lesions diagnosed by MRI referred for MRI-guided biopsies and discuss the management and follow-up of these lesions. Materials and Methods: We retrospectively evaluated all MRI-guide breast biopsies. We included all patients referred for NME breast MRI-guided biopsy in screening settings. All patients had a negative second-look mammography or ultrasonography. We correlated the distribution and internal enhancement pattern (IEP) of the NME lesions with histology. Invasive ductal carcinomas (IDC) of no special type and ductal carcinoma in situ (DCIS) were considered malignant lesions. Results: From January-2018 to July-2021, we included 96 women with a total of 96 lesions in the study. There were 90 benign and 6 malignant lesions with DCIS prevalence (5/6 cancers). The most frequent benign lesion type was fibrocystic changes. There were no NME lesions with diffuse or multiple area distribution features referred to MRI-guided biopsy. The positive-predictive values (PPV) were respectively 0.0%, 2.5%, 9.0%, and 11.0% for linear, focal, regional, and segmental distribution describers, and 0.0, 3.0%, 7.9%, and 50% for homogenous, heterogeneous, clumped, and clustered-ring enhancement patterns. Conclusion: We observe the high potential risk for malignancy in the clustered-ring enhancement followed by the clumped pattern. Segmental distribution presented the highest predictive-positive values. [ABSTRACT FROM AUTHOR]

Study objective: to establish the clinical efficacy of 1.0% micronized progesterone gel Progestogel® at the preconception stage in order to prevent lactation disorders in women with fibrocystic breast disease (FBD). Materials and methods. The main group consisted of 30 women with diffuse forms of FBD who applied on each mammary gland 2.5 g 1.0% micronized progesterone gel Progestogel® for 6 months daily at the stage of pregnancy planning. The comparison group included 30 women with diffuse forms of FBD who did not use Progestogel® at the stage of pregnancy planning. The control group consisted of 30 healthy pregnant women without pathological changes in mammary glands. Stages of observation included preconception period, pregnancy, postpartum period, lactation period and long-term period (6 month after the end of lactation). Results. Preconception preparation with transdermal 1.0% micronized progesterone gel Progestogel® in patients with diffuse forms of FBD promoted long-term breastfeeding and a regressive course of the breast pathological process. Examination of this group of patients in the long-term period (6 month after the end of lactation) showed no clinical manifestations of the breast disease (pain syndrome and edema) in 24 (80.0%) women and regression of ultrasound signs of FBD in 21 (70.0%) patients. Manifestation of both clinical and echographic signs of the breast disease was diagnosed in 26 (86.7%) women in the comparison group. Transdermal 1.0% micronized progesterone gel in the preconception preparation associated with no complications of the early lactation period in 83.3% of patients and provided a long (12 months) lactation process in 66.7% of patients. Conclusion. Progestogel® is an effective pathogenically substantiated means of safe therapy for diffuse forms of FBD. The protective effect of 1.0% micronized progesterone gel Progestogel® associated with regression of clinical and echographic manifestations of FBD in 80.0% of women.

Introduction: Fibrocystic breast disease, commonly called fibrocystic breasts or fibrocystic change, is a benign (noncancerous) condition, which is the most common pathology in women of reproductive age. Treatment of fibrocystic breast disease and concomitant pathologies can involve using herbs. Materials and Methods: To make an analysis of literary sources on the development of fibrocystic breast disease in the pathogenesis of diseases of the female reproductive system (clinical human (75%) and animal studies (25%)) were published in the period of 2017-2021. Results and discussion: The diversity of plants in the world is a promising ground for therapeutic improvisation, allowing for an individual approach to each patient, but, most importantly, creates possibilities for maneuvering in the event of ineffectiveness of any means. In some situations, herbal medicine is not only possible or permissible, but strictly mandatory, and is essentially the only effective therapeutic method, which is relatively safe provided the correct selection of combinations and control by a doctor who applies a certain method of phytotherapy, especially given a duration of treatment. The need for a deeper study is long overdue for the pharmacological capabilities of various plant raw materials in the treatment of not only this pathology, but others as well. Conclusion: The development of phytotherapy should be based primarily on scientific developments, but this area can not be considered the prerogative of only phytotherapists, as herbal medicines should be in the arsenal of doctors of all specialties. [ABSTRACT FROM AUTHOR]